2008 grant-and-award-booklet web

2008 Grants and Awards

RSNA RESEARCH & EDUCATION

FOUNDATION

FUNDING RADIOLOGY’S FUTURE®

Improving patient care by supporting research and education in radiology and related scientific disciplines through funding grants and awards to individuals and institutions that will advance

radiologic research, education, and practice.

Dear Colleague, Our commitment to radiology research and education is stronger than ever. This year, because of the generous support of our corporate, private practice, and individual donors, we were able to increase funding for grant programs. We know that getting the first grant can be the hardest and are proud of our 24-year history of providing these critical grants to launch successful academic careers. To date, the Foundation has awarded $28 million for radiologic research and education. The results are impressive—grant recipients have planted our seed money and turned it into over $900 million in additional funding and countless improvements in patient care. On behalf of the RSNA Research & Education Foundation, I would like to congratulate this year’s grant recipients. We look forward to your discoveries in the years ahead. I would also like to give special thanks to our Vanguard companies for their support. With the backing of the entire community we will keep radiology at the forefront of medicine. Sincerely, Anne G. Osborn, MD Chair, Board of Trustees RSNA Research & Education Foundation

Agfa HealthCare

Bayer HealthCare Pharmaceuticals

Bracco Diagnostics

Canon U.S.A.

Carestream Health

Cook Medical

Covidien

Fujifilm Medical Systems

GE Healthcare

Hitachi Medical Systems

Philips Healthcare

Siemens Healthcare USA

Toshiba America Medical

Systems

Varian Medical Systems

RSNA R&E Foundation

Vanguard Companies

2

Research Grant Programs Research Scholar Grant .....................................................................................................................3–7 To support junior faculty members who have completed the conventional resident/fellowship training programs but have not yet been recognized as independent investigators. $75,000 annually for 2 years ($150,000 total) to be used as salary support for the scholar.

Research Resident/Fellow Grant .................................................................................................7–18 To provide young investigators not yet professionally established in the radiologic sciences an opportunity to gain further insight into scientific investigation and to develop competence in research techniques and methods. $30,000 for a 1-year Research Resident project or $50,000 for a 1-year Research Fellow project to be used for salary and/or non-personnel research expenses.

Research Seed Grant .............................................................................................................................19 To enable investigators throughout the world to gain experience in defining objectives and testing hypotheses in preparation for major grant applications to corporations, foundations, and governmental agencies. Up to $30,000 for a 1-year project to support the preliminary or pilot phase of scientific projects. Research Medical Student Grant ...............................................................................................20–30 To make radiology research opportunities possible for medical students and to encourage them early in their medical careers to consider academic radiology as an option for their future. $3,000 for a 3-month research project to be matched by the sponsoring department ($6,000 total) as a stipend for the medical student.

Education Grant Programs

RSNA/AUR/APDR/SCARD Radiology Education Research Development Grant......................30 To encourage innovation and improvement in health sciences education by providing research opportunities to individuals in pursuit of advancing the science of radiology education. Up to $10,000 for a 1-year project. Education Scholar Grant......................................................................................................................31 To fund individuals in radiology or related disciplines who are seeking an opportunity to develop their expertise in radiologic education. The overall goal of this program is to develop teachers in radiology who can effectively share their knowledge with the radiology community. $75,000 annually for 2 years ($150,000 total) to be used for part-time salary support and educational purposes. Fellowship Training Grant ...................................................................................................................32 To provide specialty training to young physicians who are not yet professionally established in the radiologic sciences. $50,000 salary support for 1 year. Education Seed Grant ...........................................................................................................................33 To provide funding opportunities for individuals with an active interest in radiologic education. Up to $30,000 for a 1-year project to support the preliminary or pilot phase of education projects.

Recognition Awards

"As radiologists, our current practice is largely the result of research efforts in clinical and technological areas. For us to progress and prosper as a specialty, we need to continue to be in the forefront of radiology research. The RSNA Research Grants provide a significant means through which investigators can pursue a groundbreaking idea—whether they are medical students or junior faculty." - Steven C. Horii, MD Member, R&E Foundation Study Section

“As a residency program director, I am particularly delighted at the RSNA R&E Foundation's support of educational careers in radiology. Such a commitment is crucial to the future of our specialty which depends on educators and mentors for its continuing vitality. RSNA R&E this year continues its international outreach by extending the eligibility for the Education Scholar Grant to international applicants.” - Theresa C. McLoud, MD Member, R&E Foundation Board of Trustees

Roentgen Resident/Fellow Research Award..........................................................34–36 To recognize and encourage residents and fellows who have played an active role in radiologic research during the past year. Participating North American residency programs receive an award plaque with room for each year’s nominee. The Foundation provides a personalized, crystal award for the department to present to the selected resident or fellow. Outstanding Researcher/Educator Awards Program ...........................................37–38 To annually recognize and honor one senior individual in each category who has made original and significant contributions to the field of radiology or radiologic sciences throughout a career of research or teaching and education. Winners are honored at the opening session of the RSNA Scientific Assembly and Annual Meeting.

3

Prostate Specific Membrane Antigen (PSMA) PET Imaging for Detection of Metastatic Prostate Cancer and Solid Tumor Neovasculature Metastatic prostate cancer diagnostic imaging using traditional anatomic modalities including CT, MRI, and ultrasound, as well as [18F]-FDG PET metabolic imaging, is limited. PSMA is protein highly restricted to prostate cancer. PSMA is also found to be specifically expressed on the neovasculature of many solid tumors, but interestingly, not in prostate tumor neovasculature. ProstacintTM, a radiolabeled monoclonal antibody binding to the intracellular domain of PSMA, was developed to detect prostate cancer lymph node metastases but has limited accuracy due to antibody targeting characteristics. Tumor vascular imaging in a number of solid tumors with another PSMA monoclonal antibody, J591, has been recently demonstrated. Intact monoclonal antibodies-based tumor detection is limited because of their low permeability in solid tumors and slow clearance from the circulating blood pool. Smaller molecular weight-based radiotracers are more optimal for tumor detection because of their higher permeability into solid tumors and improved blood clearance in comparison to intact antibodies. [18F]-DCFBC is a novel, low-molecular-weight radiotracer targeting the more accessible extracellular domain of PSMA. Preclinical mouse prostate cancer tumor model imaging studies of [18F]-DCFBC demonstrate that this new ligand has high uptake in PSMA-expressing prostate cancer cells. [18F]-DCFBC is a clinically practical PET imaging agent with superior pharmacodynamic and pharmacokinetic characteristics that warrants further evaluation in clinical trials. [18F]-DCFBC PET images will be compared to conventional imaging methods and bone scan to localize tumors in patients with advanced metastatic prostate cancer. Radiation dosimetry and biodistribution of [18F]-DCFBC will be determined by PET imaging in patients with metastatic prostate cancer to calculate whole-body and organ-specific radiation dosimetry. We will also evaluate the potential of [18F]-DCFBC PET to specifically target solid tumor neovasculature, excluding prostate cancer. Tumor neovasculature PSMA expression will be obtained by tissue immunohistochemistry and compared to [18F]-DCFBC PET findings.

Steve Y. Cho, MDRadiology

Division of Nuclear Medicine/PETJohns Hopkins University

School of MedicineBaltimore, Md

Bracco Diagnostics/RSNA Research Scholar Grant

Beyond the Diffusion-Perfusion Mismatch: MR Imaging of Oxidative Metabolism in Acute Stroke Intravenous thrombolysis is the only FDA-approved treatment for acute stroke. Only 1%–7% of patients are treated, largely because most present after the currently required limit of 3 hours after symptom onset. Extending the 3-hour window could make this potentially lifesaving treatment available to far more patients. Recent studies have shown that thrombolysis indeed can be safe and effective up to 9 hours after onset, if MRI is used to select appropriate candidates. In these studies, a mismatch between lesions in diffusion-weighted images (DWI) and perfusion-weighted images (PWI) is presumed to reflect tissue that is threatened by ischemia but is still salvageable. Patients with a mismatch are deemed eligible for thrombolysis. The concept of the diffusion-perfusion mismatch is useful, but based only indirectly on pathophysiology. Imaging-based measurements of oxygen metabolism, specifically oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2), may be more accurate in delineating at-risk and irreversibly injured tissue. Novel MRI techniques are capable of measuring OEF and CMRO2 in only a few minutes. In this research, OEF and CMRO2 measurements will be added to the MRI examinations of acute stroke patients. Patients will be a subset of those participating in an ongoing randomized, placebo-controlled study of normobaric supplemental oxygen therapy (NBO), which may extend the viability of at-risk brain tissue, presumably by supporting oxidative metabolism. MR images obtained at presentation and at multiple follow-up time points will be analyzed with two goals: First, to assess the effectiveness and limitations of NBO in preserving oxidative metabolism in threatened brain tissue. Second, to assess whether MR-based measurement of OEF and CMRO2 is more accurate than DWI/PWI in identifying and distinguishing irreversibly damaged and at-risk tissue, and therefore, potentially more effective in selecting patients for thrombolysis and in extending the time window.

William Copen, MDRadiology

Massachusetts General HospitalBoston, Mass

Covidien/RSNAResearch Scholar Grant

Grant RReesseeaarrcchh SScchhoollaarr

4

Direct Imaging and Quantification of Cortical Bone on a Clinical 3 T MR Scanner Imaging of bone has been of fundamental importance to the practice of radiology. Plain radiographs and CT provide images of high spatial resolution, and bone density is readily measurable with DEXA and CT. However, the images and measurements very largely reflect the mineral content of bone, not the organic matrix or bone water that occupy a larger volume and have important mechanical and biological properties. There has been considerable interest in assessing the organic matrix and water in bone with magnetic resonance (MR) imaging. But bone has a very short T2, producing no signal with all clinical pulse sequences. Ultrashort echo time (UTE) sequences with TEs 100–1000 times shorter than these available on clinical scanners allow direct visualization of cortical bone. The objective of this proposal is to develop qualitative and quantitative techniques to image and quantify cortical bone on a 3 T clinical scanner. The research plan includes three parts: 1) Developing UTE imaging sequences. Technical issues including eddy currents, gradient non-linearity, and long T2 suppression will be addressed. 2) Developing quantitative techniques. A saturation recovery technique will be used for T1 measurement and multiecho techniques for T2* measurement. Reference standards will allow bone water to be estimated. Bone bulk susceptibility will be estimated using a novel UTE spectroscopic imaging (UTESI) technique. 3) Applying UTE imaging and quantitative techniques to normal volunteers and two groups of patients (osteoporosis and osteomalacia). Volunteer data will be correlated with age, sex, and weight and will serve as a control group. Patient population data will be compared to the control group. After the proposed project period, we will have developed UTE sequences for the first quantitative evaluation of cortical bone in normal volunteers and patients. The non-invasive characterization of cortical bone could be revolutionary if it proves to have a specific MR signature.

Jiang Du, PhDRadiology

University of CaliforniaSan Diego, Calif

Agfa HealthCare/RSNA Research Scholar Grant

Prostatic Artery Embolization as a Primary Teatment for Benign Prostatic Hyperplasia Background/significance: A third of men aged 50 years and over will develop bladder outlet obstruction/irritation from benign prostatic hyperplasia (BPH), and a quarter will require surgical intervention. The surgical standard, transurethral resection of the prostate (TURP), requires a 5-day hospital stay and has >50% incidence of complications (eg, urethral stricture, urinary incontinence, impotence) leading many to search for alternative, minimally invasive options. Selective embolization of the prostatic artery has been reported as a safe and effective treatment for prostate bleeding after TURP or biopsy. Along these lines, we generated preliminary results in six dogs with BPH and demonstrated a 40% reduction in prostate volume at 1 month following embolization with microspheres, with subjectively better results, but greater initial urinary retention, using a bilateral embolization technique. Specific aims:

1. To determine 6-month safety of prostate embolization in a canine model; 2. To assess short/mid-term effects of prostate embolization for BPH on gland volume and

perfusion, urethral obstruction, and histology; 3. To refine the technique by optimizing embolization particle size and assessing the need

for bilateral versus unilateral embolization. Method: Phase I. Dogs with BPH will undergo selective bilateral embolization of the prostatic arteries with 100–300µm, 300–500µm or 500–700µm (n=6, each) microspheres. Animals will be monitored clinically for 1 month after embolization for infectious, ischemic, or other complications. Retrograde urethrocystography and dynamic contrast-enhanced MRI will be obtained prior to embolization and after 1 month for quantitative and qualitative analysis of urethral stenosis, prostate volume, and enhancement. After 1 month, prostates will be excised for radiologic-pathologic correlation and microscopic analysis (particle distribution, necrosis, inflammation). Phase II. Unilateral versus bilateral embolization with the ideal particle size will be compared (n=6, each), with a 6-month follow-up (based on the results of Phase I – Optimal particle size). Clinical Significance: Potential revolutionary treatment analogous to uterine artery embolization. Potential to evolve into treatment for prostate cancer (radioembolization-Y90, chemo/hormonal embolization).

Salomao Faintuch, MDRadiology

Beth Israel Deaconess Medical Center

Harvard Medical SchoolBoston, Mass

GE Healthcare/RSNA Research Scholar Grant

5

Evaluation of Magnetic Nanoparticle-Enhanced Magnetic Resonance Imaging in Clinical Autoimmune Diabetes Type I diabetes mellitus (DM) is an irreversible, chronic disease causing disproportionately high per-capita healthcare expense (~5 fold greater than non-diabetics), secondary to both long-term glycemic management and occasional devastating acute and chronic complications. Although it is well established that DM results from autoimmune destruction of the insulin producing beta cells of the pancreatic islets, a true understanding of its immunopathogenesis in humans has remained elusive. Previous techniques used to quantify insulitis (to measure the degree of inflammation and islet destruction) and beta cell mass (BCM—a measure to gauge the amount of residual beta cells) are invasive and impractical for most human studies. Imaging may therefore play an important role in quantifying insulitis and BCM. Radionuclide attempts have shown initial promising results in animal models of diabetes, without successful translation into human clinical trials. As novel immunomodulatory therapies evolve in order to prevent beta cell destruction, a noninvasive, accurate means of visualizing and quantifying BCM and insulitis becomes critical. Recently, we developed a technique based on the properties of magnetic resonance imaging (MRI) enhanced with magnetic nanoparticles (MNP) to allow indirect quantification and visualization of insulitis in animal models of DM. We validated this MNP-MRI technique by correlating our findings with the standard invasive techniques used to study diabetes, including histology and flow cytometry of the pancreas and pancreatic inflammatory infiltrate samples. Initial translation of this technique has resulted in a trial to study insulitis in humans, funded by the NIAID (PI Mathis/Weissleder). Twelve patients with early onset diabetes have been enrolled with encouraging results. We are now poised to translate and optimize this technology and apply it to an extended human clinical trial.

Alexander R. Guimaraes, MD, PhDRadiology


Bayer HealthCare Pharmaceuticals/RSNA Research Scholar Grant

Assessment of Emerging Technology: Comparison of Breast Tomosynthesis and Digital Mammography in the Evaluation of Heterogeneously Dense and Extremely Dense Breasts Purpose: To assess the clinical utility of emerging digital tomosynthesis (DT) technology and improve breast cancer detection in women with heterogeneously dense (HD) and extremely dense (ED) breasts. To evaluate mass conspicuity on DT compared to digital mammography (DM) in HD and ED breasts. To assess reader preference and workflow issues of DT compared to DM. Design and Methods: 50 patients with HD and ED breasts and BI-RADS 4 or 5 interpretation will undergo two-view DT and DM prior to core needle biopsy or excisional biopsy of mass for histologic proof. Masses will be detected by imaging (ultrasound or mammography) or palpation. For patients with more than one mass per breast, each mass will be separately analyzed. 50 randomized cases, divided into 2 subsets, will be independently interpreted by 3 MQSA accredited radiologists. Readers will record mass size, location, conspicuity, and likelihood of malignancy. After a 4-week delay, readers will interpret corresponding DM or DT image sets in random order. After another 4-week delay, readers will evaluate DT and DM in side-by-side comparison and rank preference for DT or DM. Time for interpretation of each case and standard time motion analyses will be recorded. Statistical significance testing for mass conspicuity, reader preference, and interpretation time will be performed. Diagnostic confidence of malignancy will be evaluated with ROC analysis. Potential Significance of this work in Radiological Sciences: DT is a new DM method in which a series of low dose X-ray images is acquired over a range of angles relative to an imaged object. It can be used to reconstruct the 3D structure of the entire breast. If improved mass conspicuity in HD and ED breasts on DT is proven, this innovative technology could significantly impact the detection and characterization of breast masses in women with dense breasts.

Alexis V. Nees, MDRadiology

University of MichiganAnn Arbor, Mich

Agfa HealthCare/RSNA Research Scholar Grant

6

Creation of a Model for Predicting Response to Chemoradiation in Head and Neck Squamous Cell Carcinoma Chemoradiation of head and neck squamous cell carcinoma (HNSCC) is challenging due to frequent local or regional failures. Our objective is to develop a prediction model using pre-therapy demographic, pathologic, and MRI parameters to identify HNSCC patients who respond poorly to chemoradiation. Our long-term goal is application of the model prospectively in a multi-center clinical trial to identify poor responders who may benefit from escalated radiation doses, which are now feasible and safer due to advances in targeted radiation delivery and can improve disease-free survival. Among the factors influencing tumor response, we will study tumor cellularity as a key predictor. Diffusion weighted MR imaging (DWI) is a molecular imaging technique measuring apparent diffusion coefficient (ADC), which is considered a surrogate marker for tumor cellularity. The proposed study is part of an ongoing trial at the University of Michigan involving serial MRIs in HNSCC patients (baseline, during third week of therapy and at 3 months) to study the utility of serial ADC values in assessing tumor response. Patients undergo standard-of-care chemoradiation and therapeutic response is assessed after 3 months. As an additional step to this trial, we propose to use only the baseline MRI data to construct a prediction model that will provide information on the utility of pre-therapy scans alone in predicting response. Our specific aims are (1) building a prediction model using age, pathological grade, tumor volume, nodal status, whole tumor mean ADC, and fractional tumor volume below an ADC threshold as parameters influencing tumor response to chemoradiation, and (2) assessing the value of adding “fractional tumor volume below an ADC threshold” to “whole tumor mean ADC” in predicting therapeutic response. In summary, developing non-invasive imaging parameters that identify poor responders to chemoradiation is important since therapy can then be individualized to increase chances of treatment response.

Ashok Srinivasan, MDRadiology

University of Michigan Health System

Ann Arbor, Mich

Carestream Health/RSNA Research Scholar Grant

Correlation Between Perfusion Metrics Measured with Perfusion-Weighted MRI and Tissue Oxygenation Measured with BOLD MRI with VEGF Expression and Microvessel Density in Hepatocellular Carcinoma Hepatocellular carcinoma (HCC) is a typical angiogenic tumor, with a recent significant increase in incidence in the U.S. Treatment of advanced HCC is still limited and several systemic therapies are being assessed, including anti-VEGF (vascular endothelial growth factor) drugs. The objective of this proposal is to develop MRI methods for quantification of angiogenesis and oxygenation and to correlate the MR findings with histologic quantification of angiogenesis in HCC. We will use contrast-enhanced MRI to quantify tumor perfusion parameters using a first pass pharmacokinetic model and blood oxygenation level-dependent (BOLD) MRI to measure oxygen consumption in cirrhotic patients with HCC before they undergo cadaveric or living-related liver transplantation. Quantitative perfusion parameters (blood volume and Ktrans) and BOLD R2* (apparent transverse relaxation rate) values will be calculated in HCC lesions and surrounding non tumorous liver using regions of interest measuring signal intensity over time and a dual input single compartmental model integrating Gadolinium concentrations. Quantitative MR parameters will be correlated with VEGF expression and microvessel density in HCCs and surrounding liver parenchyma obtained on liver explants. With this study, we are aiming to validate functional MRI as a non-invasive tool for quantification of HCC angiogenesis. MRI could be used for predicting and monitoring response to targeted anti-VEGF drugs currently investigated in HCC and to transarterial chemoembolization. In addition, MRI could have a prognostic value by predicting the degree of HCC angiogenesis and the response to antiangiogenic drugs and chemoembolization, and could have a prognostic value. This would benefit tens of thousands of Americans over the next decade.

Bachir Taouli, MDRadiology

New York University Medical CenterNew York, NY

Siemens Healthcare USA/RSNA Research Scholar Grant

7

Advanced MR Imaging After External Beam Radiation Therapy of Prostate Cancer Biochemical failure (defined as PSA nadir value plus 2 ng/dl) following external beam radiation therapy (EBRT) of prostate cancer is a clinical dilemma for which adequate management is not well established. It may represent isolated local recurrence, systemic recurrence, both, or neither. The standard method of evaluating local control is transrectal ultrasound (TRUS) guided biopsy of the prostate, which is invasive and has limited accuracy after radiation treatment. Our goal is to determine if 3 Tesla MR spectroscopic imaging (MRSI) and diffusion tensor MR imaging (DTI-MRI) will non-invasively identify the patients who can be cured by salvage therapy, while potentially identifying other patients who require systemic treatment or who have adequate disease control and do not need additional therapy. Specific aims:

1. Determine the accuracy of 3 Tesla endorectal MRI in detecting locally recurrent prostate cancer in patients with biochemical failure after EBRT by correlating areas of low signal intensity on T2-weighted images, spectroscopic voxels showing a choline-to-creatine ratio greater than 1.5 on MRSI, and areas of decreased water diffusion on DTI-MRI with the presence or absence of cancer at post-radiation transrectal ultrasound-guided biopsy.

2. Determine the prognostic value of post-treatment 3-T endorectal MRI in men with prostate cancer treated with EBRT by correlating the volume of reduced water diffusion and the number of spectroscopic voxels showing a choline-to-creatine ratio greater than 1.5, as well as maximum and mean metabolite levels, with disease-free survival (defined as absence of local recurrence and/or metastases).

This will be a prospective cross-sectional study followed by a cohort of 36 consecutive adult patients referred for evaluation and management of biochemical failure after EBRT for prostate cancer. Prostate biopsy histopathology will be used as standard of reference in determining the presence or absence of local prostate cancer recurrence. Systemic disease will be considered present if periodical and systematic medical chart review produces evidence of such through pathology reports, imaging studies, and/or clinical notes. We expect to promote MRSI and DTI-MRI as prognostic tools to be used in the post-radiation prostate cancer patient population and to develop a new line of investigation in multiparametric MR imaging of prostate cancer patients.

Antonio Carlos Westphalen, MDRadiology

University of CaliforniaSan Francisco, Calif

GE Healthcare/RSNA Research Scholar Grant

RaceTrack: Improving Clinical Follow-up for Radiologists Using Information Technology Diligent radiologists seek follow-up information after challenging diagnostic cases, but current information systems do little to lower the barrier to finding out what happened to a patient. I propose to develop a system—dubbed “RaceTrack” for “Radiology Case Tracking”—that will integrate with existing technology in our department to allow radiologists to create and maintain personal databases of cases of interest. Within the system it will be easy for radiologists to access the electronic medical records to find relevant clinical outcomes for their patients. To assess the impact of this system, we will survey radiologists regarding their habits of obtaining clinical follow-up information before using the system and then monitor the degree to which they obtain follow-up using the system. We anticipate that radiologists using the system will obtain clinical information more frequently as the system decreases the effort required to obtain that information. Clinical follow-up is extremely important for radiologists who seek to improve quality throughout the specialty. Such feedback is critical both for self-improvement and for understanding the rapidly changing clinical context of radiology’s contributions to patient care. The RaceTrack system can serve as the basis for further work in this area, such that relevant clinical information about former patients comes to radiologists automatically, and reviewing those data is an important part of their professional duties. I anticipate that this work will serve as the foundation of a research program for an anticipated informatics fellowship and beyond.

Tarik Alkasab, MDRadiology


Fujifilm Medical Systems/RSNA Research Resident Grant

Grant RReesseeaarrcchh RReessiiddeenntt//FFeellllooww

8

Osteoarthritis: Abnormalities in Cartilage and Trabecular Bone Micro-architecture Determined by High-Resolution 7 T MRI According to the Centers for Disease Control, osteoarthritis affects 46 million Americans, resulting in $127 billion in annual costs. Joint deformity, pain, and decreased mobility are secondary to a complex interaction involving abnormal articular cartilage, subchondral bone, and mechanical loading at the joint. Great effort has been devoted to: 1) studying the pathophysiology of osteoarthritis and 2) identifying new markers to enable earlier diagnosis and monitor disease progression/response to treatment in clinical trials. High field strength, high resolution MRI (~100-200 micron) provides a means to address both of these issues. MRI can detect changes in cartilage morphology and alterations in trabecular bone micro-architecture before corresponding abnormalities are present on radiographs. In addition, post-processing techniques now permit the quantitative assessment of numerous properties of cartilage and trabecular bone. Only a few studies have quantitatively assessed both cartilage and trabecular bone micro-architecture in subjects with osteoarthritis by MRI, and these have been performed at standard clinical field strength. The goal of this study is to perform a quantitative assessment of cartilage and trabecular bone micro-architecture in subjects with osteoarthritis via 7 T MRI using 3 T MRI and radiographs as the standards of reference. The advantage of imaging at higher field strength is the increased signal-to-noise ratio, which can provide improved image contrast and higher spatial resolution. At RSNA 2007, we presented a paper describing the ability of 7 T MRI to detect changes in trabecular bone structure in the knees of elite athletes. This study will be the first to perform high resolution 7 T MR imaging of cartilage and trabecular bone micro-architecture in subjects with osteoarthritis. This study has the potential to: 1) shed light on the pathophysiology of osteoarthritis and 2) identify new imaging markers that could be used to diagnose osteoarthris earlier and more accurately monitor disease progression.

Gregory Chang, MDRadiology

New York University School of Medicine

New York, NY

Philips Healthcare/RSNA Research Resident Grant

Identification of Epithelial Ovarian Cancer Stem Cells for Radiotherapeutic Targeting Stem cells organize and populate the body through a hierarchy of proliferation and differentiation, while retaining the capacity to continuously self-renew. The insight that this physiologic order mirrors the deranged orderliness of a developing malignancy led to the cancer stem cell (CSC) hypothesis, which proposes that each tumor consists of a heterogeneous population of cells at various stages of differentiation, but all derived from the same small CSC pool; that purging tumors of this CSC pool will be sufficient to undermine their accumulated bulk and recurrence risk. Originally conclusively demonstrated for acute myelogenous leukemia (AML), this elemental population has since begun to be described in solid tumors, most prominently in breast cancer. Epithelial ovarian cancer (EOC) is the leading cause of death in patients with gynecological cancer, with 14,000 deaths annually. While EOC is thought to arise from the ovarian surface epithelium, pathogenesis is poorly understood. Therapy options are similarly limited, especially with radiotherapy hobbled by toxicity. This study proposes to begin the process of identifying the EOC stem cell pool, to allow targeting of this population by radiotherapeutic and molecular methods. Aim 1 seeks to identify cell surface markers that permit the enrichment of the tumorigenic population. We have generated a monoclonal antibody library of EOC markers for screening and segregation by a stepwise high volume strategy, with tumor propagation in vivo as the definitive assay. Aim 2 exploits known stem cell signaling pathways, using GPF reporter constructs on lentiviral vectors that target the Wnt and Hh pathways. The two aims will run in parallel initially, but are readily integratable into one sorting strategy. The CSC hypothesis has far reaching implications for both scientific understanding and therapy. An identified CSC population permits more specific screening for vulnerable molecular pathways and immunologic targets amenable to radioimmunologic therapy.

Robert Chin, MD, PhDRadiation OncologyStanford University

Medical CenterStanford, Calif

RSNA Research Resident Grant

9

Development of a Multivariable Risk Prediction Score for Contrast Media-Induced Nephropathy: A Tool for Prevention, Prognostication, and Decision Making Background: Contrast media induced nephropathy (CMIN) continues to cause acute renal failure in patients who are at risk. To support clinical decisions about patient management and preventative measures, there is a need for a tool to predict the probability of CMIN. The main objective of this proposal is to evaluate and develop a risk stratification tool, specifically a prediction score, to identify those patients undergoing contrast-enhanced CT examinations who should receive prophylactic regimens, reduced contrast doses, or who should not receive contrast media at all. A quantitative risk prediction rule would be better than existing qualitative methods of assessing risk based on known risk factors and creatinine or estimated glomerular filtration rate alone. Data Collection and Analysis: Using multivariate logistic regression analysis and in-depth retrospective data mining of our institution's electronic medical record, a prediction rule for accurately estimating the risk of contrast media induced nephropathy will be derived. The prediction rule will be tested in a retrospective manner in another sample population to assess reliability, accuracy, and precision. After developing and validating risk score, the prediction rule will be tested in a prospective manner via integration into decision support for the existing computerized order entry system at our institution. Significance: If successful, this research will develop and validate a clinical prediction rule to stratify the risk of CMIN based on known risk factors in order to aid in decision making to prevent contrast nephropathy. A risk prediction rule will serve as an important contribution to patient safety efforts in radiology. In addition, this work will also serve as a foundation of a host of other risk prediction rules for contrast related adverse events including nephrogenic systemic fibrosis. Relevance to Post-Residency/Fellowship Appointment: Long term, my goal is to become an academic radiologist actively working in research that is focused on improving quality and patient safety in radiology.

Garry Choy, MDRadiology



Functional MRI of Theory of Mind: A New Way of Imaging Autism Autism is a neurodevelopmental disorder that exhibits a broad phenotypic expression characterized by core deficiencies in social interaction and communication. Despite affecting between 0.3% and 0.7% of the U.S. population, the cause of autism remains unknown, although most hypotheses point towards a multifactorial genetic etiology. There is no cure for autism, but early intervention and well-structured behavioral treatments can have beneficial effects, with high levels of compensatory learning. To date, neuroimaging has had little role in diagnosing patients with autism or understanding the causes of autism. One of the two prevailing neuropsychological theories of autism suggests it results from a central deficiency in the “theory of mind” mechanism. Theory of mind (TOM) refers to the ability of one person to predict another person’s behavior or beliefs by attributing them to independent mental states. Functional MRI (fMRI) pilot data from my laboratory indicates that a simple manipulation of a two-player game (ie Scissors, Paper, Rock) can be used as a reliable assay for brain activation of “theory of mind” regions in normal subjects. This proposal describes how fMRI of autistic patients, using these game paradigms, can test the hypothesis that autistic patients demonstrate a central deficiency in activating brain regions associated with TOM. A recent neurophysiological theory of autism—the underconnectivity theory—hypothesizes that autism is marked by underfunctioning high-level neural connections and synchronization. This proposal also describes how a new type of brain fMRI analysis can test the degree of connectivity between the brain regions associated with subcomponents of TOM processes. In addition to the novel functional MRI paradigm and data analysis, this project gains statistical power by access to a cohort of nearly 100 autistic patients and their age-matched controls, as part of the longitudinal Utah Autism Research Project.

T. Jason Druzgal, MD, PhDRadiology

University of UtahSalt Lake City, Utah

Siemens Healthcare USA /RSNA Research Fellow Grant

10

Radiosensitization with Anti-VEGF in Glioblastoma Cells Glioblastoma is the most aggressive form of brain cancer, accounting for approximately 40% of all primary malignant brain tumors. Despite optimal treatment with surgery, radiotherapy and chemotherapy, the prognosis for these patients remains poor. Adjuvant temozolomide with radiotherapy serves as the standard of care for newly-diagnosed cases. Recently, anti-angiogenic therapy using bevacizumab (BV) in combination with irinotecan has emerged as a promising development in the treatment of recurrent glioblastoma. BV is a humanized monoclonal antibody directed against the vascular endothelial growth factor (VEGF). Besides its role in angiogenesis, VEGF may act in an autocrine manner to enhance cellular survival, providing a pro-survival feedback loop that may decrease the efficacy of temozolomide and/or radiation. BV treatment is expected to inhibit this feedback loop to increase cytoxicity. Therefore VEGF blockade may directly inhibit tumor growth in a paracrine/autocrine fashion. In our institution, we have undertaken a phase II trial that combines BV upfront with radiotherapy/temozolomide. Interim clinical observation has been accepted for publication. Our current proposal is to use the U87MG glioblastoma cell culture model to examine the mechanism by which BV may potentiate the efficacy of radiotherapy and temozolomide. Specific Aims:

1. To establish whether VEGF signaling is modulated by the administration of radiotherapy, temozolomide, and concurrent radiotherapy/temozolomide by measuring VEGF level via ELISA assay in both the conditioned media and the cell lysate.

2. To evaluate the effects of BV on the cytotoxicity of radiotherapy, temozolomide, and concurrent radiotherapy/temozolomide by quantifying cell survival using clonogenic assay; and elucidating cell death mechanism using TUNEL assay and flow cytometry.

This study will lay the groundwork for understanding the interplay among anti-VEGF, radiotherapy, and temozolomide in the treatment of glioblastoma. The long-term plan of this project is to analyze the roles of anti-VEGF as a radiosensitizer in animal models.

Diana L. Gage, MD, PhDRadiation Oncology

University of CaliforniaMedical Center

Los Angeles, Calif


Evaluation of Bicuspid Aortic Valve and Aortic Coarctation with 4D Flow MR Imaging Four-dimensional MR velocity mapping (4D Flow) is well suited for evaluation of multidirectional blood flow velocity data from the human aorta. Previous studies have employed the technique to characterize complex flow patterns in the thoracic aorta of healthy subjects and patients with aortic pathology, including ascending aortic aneurysm. This study will utilize 4D volumetric datasets to evaluate patients with history of aortic coarctation and bicuspid aortic valve (BAV). Flow analysis based on 2D phase contrast MR is the standard of care for evaluation of collateral flow associated with coarctation; the presence of collateral flow indicates a significant coarctation that may require intervention. In order for 4D Flow to be a clinically viable tool for evaluation of coarctation patients, it must be reasonably fast and generate reliable flow data, as well as offer advantages over the standard MR protocol. We will address these first two objectives using a combination of approaches for k-space subsampling in a direct comparison of 4D Flow and 2D PC data in patients. With regard to its advantages, 4D Flow allows for continuous breathing, does not require prospective placement of 2D planes for PC acquisition, and offers a unique method of analyzing dynamic flow data that is not available by traditional 2D PC imaging. By utilizing 3D visualization tools such as vector fields, streamlines, and particle traces, we can provide a 4D visual presentation of secondary flow characteristics unique to coarctation, which may be useful for better understanding and possibly predicting post-intervention complications. Additionally, as up to half of coarctation patients have BAV, we intend to use the same 4D Flow data sets to analyze abnormal blood flow patterns and parameters in this context that could help elucidate why many BAV patients develop pathology of the ascending aorta.

Michael D. Hope, MDRadiology

University of CaliforniaSan Francisco, Calif


11

Magnetic Resonance Imaging for in Vivo Cancer Antigen-Specific T Lymphocyte Tracking Cancer vaccine immunotherapy depends upon dendritic cell presentation of cancer antigen peptides on cell surface major histocompatibility molecules (MHC) to T lymphocytes, with subsequent recruitment of activated cancer antigen-specific T lymphocytes to tumor sites. The variable tumoricidal response elicited renders in vivo monitoring during therapy essential. Traditional imaging relying upon tumor volume cannot adequately distinguish inflammatory swelling from actual tumor growth. Novel labeling and cell tracking techniques using ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles and magnetic resonance imaging (MRI) allow even small populations of cells to be tracked in vivo. Previously demonstrated USPIO-based methods for T cell labeling and tracking have not been cancer antigen-specific, and therefore have limited clinical utility. We propose that USPIOs conjugated to MHC presenting relevant antigen peptides can label antigen-specific T cells in vivo. An ovalbumin (OVA)-transfected B16 melanoma expressed in C57BL/6 mice has been chosen as the model system, this tumor has been successfully targeted by adoptive transfer of OVA-specific CD8+ CTLs and CD4+ T cells from OT-I and OT-II transgenic mice, respectively. To label CTLs, USPIOs will be conjugated to murine MHC I (H-2Kb), OVA peptide and a fluorochrome. To label CD4+ T cells, USPIOs will similarly be conjugated to murine MHC class II (I-Ab), OVA peptide and a fluorochrome. These cells will be transferred into tumor-bearing mice, which will then be repeatedly imaged using a 9.4 T MRI system to observe cell trafficking to the tumor. Correlation with post-mortem microscopy will be performed. Eventually, direct in vivo methods for T cell labeling will also be tested, due to their greater clinical relevance. The method could also be applied to other cancer antigens like MUC1, or to autoimmune disorders. This study will expand the methods available for MR-based molecular imaging and be potentially useful in monitoring responses to cancer vaccines.

Ryan Hung, MD, PhDRadiology and Diagnostic Imaging

University of AlbertaEdmonton, Alberta

Canada


Strategic Design of Novel Radiation and Immunotherapeutic Combinations: Selective Targeting of Radiation-Induced Changes in Costimulatory Pathways Immunotherapy (IT) affords the promise of new treatments for cancer and there is growing interest in combining IT with radiation therapy (RT). The major goals of IT are to activate the immune system, eradicate malignant cells, and generate long-lasting anti-tumor immunological memory. Successful combinations of external beam RT and IT can be designed in such a way that RT achieves local tumor control and induces an anti-tumor immune response against distant metastasis. The formation of immunological memory requires T cell activation, a process regulated by several receptors and ligands on antigen presenting cells (APCs) and T cells, at the “immune synapse” between APCs and T cells. CD28, TIM-1, ICOS, HVEM, CD40L, CD27, 4-1BB, OX40, CD30, and SLAM are stimulatory receptors counterbalanced by four major co-inhibitory receptors: CTLA4, TIM-4, BTLA, and PD1. Biologic agents that augment or block the activities of these cells and receptors can be used to promote anti-tumor immune responses. Although RT may be a useful adjunct to such immunotherapies, our knowledge of the effects of RT on these IT targets is limited. This project will investigate the effects of RT on emerging IT targets. We will determine the effects of RT on 1) critical populations of immune cells, 2) the expression of key costimulatory and coinhibitory molecules, and 3) the efficacy of costimuation-enhancing IT. By quantifying the effects of RT on the cells and receptors that orchestrate immune responses, our results will establish a framework that will guide the development of improved IT methods and novel RT + IT strategies.

Jennifer Jones, MD, PhD

Radiation OncologyStanford University

Stanford, Calif


12

Intra-Tumoral Metabolic Heterogeneity of Cervical Cancer Positron emission tomography (PET) with [18F]-2-fluoro-2-deoxyglucose (FDG) is routinely utilized in patients with cervical cancer to determine disease extent and to aid in radiation treatment planning. Our previous research found that FDG uptake, measured as maximal standardized uptake value (SUVMax), of the primary cervical cancer is predictive of disease prognosis and outcome, irrespective of tumor stage or volume. We also noticed that the pattern of FDG uptake varies across individual cervical tumors, providing an opportunity for studying tumor heterogeneity. We developed a derivative function that reflects heterogeneity with a single numerical value (FDGhetero) and tools for creating and overlaying texture maps for qualitatively evaluating this variation in uptake pattern. In preliminary studies, we found pretreatment FDGhetero predicts disease extent, treatment response, and recurrence risk. For this project, we plan to study cervix tumor metabolic heterogeneity and changes in tumor FDG uptake during chemoradiation and whether these changes correlate with treatment response and patient outcome. Currently, cervical cancer patients routinely undergo a pretreatment FDG-PET followed by external radiation, weekly cisplatin, and six brachytherapy implants, and then an FDG-PET 3 months after therapy. In this study, 25 patients will undergo two additional FDG-PET studies during chemoradiation. From all four PET studies, primary tumor volume, SUVMax, and heterogeneity measures will be assessed. We will evaluate whether the changes in SUVMax and heterogeneity during treatment correlate with the tumor response, assessed by 3-month post-treatment FDG-PET and patient outcome, assessed by clinical follow-up. Preliminary research suggests a prognostic value for SUVMax and heterogeneity measures. This study will help further define the significance of these factors in overall treatment outcome. This research study will improve our understanding of the prognostic value of FDG-PET in patients with cervical cancer, which may lead to valuable tools for optimizing treatment in these patients.

Elizabeth Kidd, MDRadiation Oncology

Barnes-Jewish HospitalWashington University

St Louis, Mo


Non-Invasive in Vivo Imaging of Pleiotropic Statin Effects on Monocyte Trafficking to Atherosclerotic Plaques Background: Monocytes have been shown to represent key players in all phases of atherogenesis, from the development of fatty streaks to events that eventually lead to vulnerable plaques and arterial occlusion. To date, however, the data describing monocyte recruitment to atherosclerotic plaques have been derived almost exclusively from the analysis of ex vivo specimen, thus restricting the current knowledge to a static view and prohibiting the use in human subjects. We have recently established a technique that allows non-invasive in vivo imaging of monocyte trafficking to atherosclerotic plaques in live animals (Kircher et al, Circulation 2008). Using this technique, we have shown for the first time that monocyte trafficking to plaques is inhibited rapidly and efficiently by statin drug therapy. Hypothesis: On the basis of these results, we hypothesize that even low dosage and/or less frequent administration of statin drugs result in highly efficient suppression of monocyte recruitment. Methods: Monocytes will be isolated with a two-step negative isolation procedure, tagged with 111Indium-oxine and adoptively transferred into ApoE-/- double knockout mice. Recipient mice will be treated with atorvastatin and the amount of monocytes recruited to atherosclerotic lesions assessed by in vivo microSPECT/CT. Analysis of SPECT signal will be performed by region of interest analysis of 3D renderings using Amira software. In selected experiments, ex vivo corroboration using autoradiography, scintillation counting and immunohistochemistry will be performed. Statistical tests will include Student t test and one-way ANOVA with Tukey multiple comparison test. For correlation analyses, Pearson or Spearman correlation will be used. Potential Significance: Novel insights into the effect of statin drugs on monocyte recruitment have important implications for the treatment and prevention of atherosclerosis. If the data of this study corroborate our hypothesis, this could lead to a potent antiatherogenic treatment regimen with significantly lower side effects by exploiting the pleiotropic effects of statin drugs.

Moritz Kircher, MD, PhDRadiology

Beth Israel Deaconess Medical Center



13

A New Image-Guided Tumor Ablation: Percutaneous Irreversible Electroporation (PIE) on Head and Neck Squamous Cell Carcinoma in Rabbit VX2 Neck Tumor Model Head and neck cancer is the sixth most common cancer worldwide, with 11,210 deaths and 45,660 new cases expected in the United States in 2007. Despite recent improvement in treatments, mortality and incidence rates have not significantly improved in the last few decades. Therefore, it is crucial to develop novel and effective treatment options. In our proposal, we introduce a new minimally invasive method to ablate head and neck cancer using percutaneous irreversible electroporation (PIE). We have previously shown that PIE causes controllable irreversible cell death in a focused deliverable fashion under image guidance and real-time monitoring. In addition, PIE can be achieved in seconds of procedure time, substantially less than other currently available ablation techniques. As PIE is a non-thermal technique, the risk of injuring vital head and neck structures is minimized. In our investigation, we propose to translate these preliminary results into a practical treatment method in a large animal tumor model with the plan to bridge to human studies. We will evaluate the effectiveness of PIE on rabbit VX2 head and neck squamous cell carcinoma. This study will be conducted for prognostic assessment and physiological tumor burden assessment. In this study, PIE will be performed with real-time image guidance. The effectiveness of PIE will be evaluated by radiographical and immunohistological assessment.

Edward W. Lee, MD, PhDRadiology


Los Angeles, Calif


The Role of REPRIMO and REPRIMO-like Gene Silencing in the Radioresistance of GI Malignancies DNA hypermethylation is a common mechanism by which genes are silenced in cancer. REPRIMO is a radiation-inducible, p53 dependent gene that is commonly hypermethylated and silenced in GI malignancies. It causes cell cycle arrest in the G2 phase through unknown mechanisms. Recent studies demonstrate that the degree of methylation of REPRIMO predicts poor treatment response to chemotherapy and radiation in esophageal cancer, and portends to poorer prognosis in pancreatic cancer. Through database searches, I have identified a second gene that is a homologue of REPRIMO, coined REPRIMO-like (RPRML). It has an N terminus that is largely dissimilar, but a C terminal domain that is highly homologous to REPRIMO and well conserved from Xenopus to mammals. Preliminary data demonstrate that RPRML is also methylated, albeit at lower frequency (25%–50%), compared to REPRIMO (60%–80%), in various cell lines and primary tumors of GI origin but not in malignant brain tumors. Treatment with 5-azacytidine is able to reverse promoter methylation and cause gene re-expression. My hypothesis is that the two genes are functionally redundant in the cancer cell and epigenetic silencing of these genes attenuates the radiation response and confers radiation resistance. I propose to test this hypothesis by assessing radiation response with the overexpression or shRNA knock down of either or both genes in various human cancer cell lines. The consequence of the various genetic manipulations will be examined using assays to assess clonogenic survival, apoptosis, DNA damage, and cell cycle arrest. The role of epigenetic silencing in the responsiveness of these genes to radiation will also be studied. I believe the results of this study will help validate using genome approaches to discover other novel epigenetically silenced genes that may confer radiation resistance in cancer and highlight the potential role of epigenetic drugs to improve the efficacy of radiation treatment.

Steven H. Lin, MD, PhDRadiation Oncology

The Johns Hopkins University School of Medicine

Baltimore, Md


14

Molecular Targeted Radiation Therapy for Lung Cancer Individualization of radiation therapy by tailoring it to a given cancer genotype is an important goal of radiation research. Aberrant signaling pathways present in cancers but not the surrounding normal tissues offer attractive targets to selectively increase radiation-induced tumor kill. Thus, radiosensitization of tumors with molecular targeted agents in a selected subset of patients has the potential to effect cures without the side effects seen with traditional chemotherapeutics. Lung cancer is the leading cause of cancer death in the U.S. Non-small cell lung cancers (NSCLC), the most common type, are often difficult to treat due to large size and intrinsic radioresistance. Accumulating data suggest that epidermal growth factor receptor (EGFR) activation by radiation may cause treatment failure in many cases. There is a need for a better understanding of the molecular mechanisms underlying these observations and the radiosensitizing potential of EGFR inhibitors. This pre-clinical study focuses on the mechanisms by which EGFR activation protects NSCLC from radiation. The main hypothesis is that EGFR activation through mutant K-Ras induces pro-survival signaling, but not DNA repair, in irradiated cells. We will also test the hypothesis that the EGFR inhibitor cetuximab blocks this process more effectively than erlotinib. This 1-year project will initially rely on a mechanistic analysis of two NSCLC lines harboring mutant K-Ras. Subsequently, we will seek to replicate our findings in a larger panel of 40 lines. This study is integrated into a broader effort by the Massachusetts General Hospital Cancer Center and Dana-Farber/Harvard Cancer Center Lung Cancer SPORE to translate genotype-correlated treatments that are tested in a panel of >100 NSCLC lines. The rationale for this approach is to capture the genetic heterogeneity of NSCLC that is an essential determinant of treatment responses. In this environment, the applicant will refine his training as a clinician-scientist and interdisciplinary team researcher.

Akash Nanda, MD, PhDHarvard Radiation Oncology

ProgramMassachusetts General Hospital

Boston, Mass


In Vivo Validation of PET Labeling of Liposomal Particle Shells with Optical Imaging in Ultrasound-Enhanced Delivery to Prostate Cancer Activatable and molecularly-targeted vehicles have shown promise to improve local drug delivery. However, further improvements and systematic optimization and validation of these methods are required. In order to optimize targeting of individual or multiple receptors, new optical and PET probes have been designed to image lipid-shelled particles and their cargo. This study will use lipopeptides as targeting ligands and compare the dynamic biodistribution obtained with optical imaging and 64Cu methods. Results will be validated using immunohistochemistry. Ligands that bind to receptors on tumor vascular endothelium and tumors such as integrins, aminopeptidase N, and neuropilin-1 have been synthesized and will be evaluated. Successful validation of translational PET methods will allow us to investigate PET-guided ultrasound-enhanced delivery to prostate cancer in future studies. Eleanor Ormsby, MD, MPH

RadiologyUniversity of California

Davis, Calif

Hitachi Medical Systems/RSNA Research Resident Grant

15

Quantitative Estimation of Metastatic Tumor Burden in the Liver Using CT Perfusion Imaging Purpose: To develop and evaluate a quantitative means of assessing metastatic tumor burden within the liver using CT perfusion imaging. Materials and Methods: Perfusion imaging has attracted attention for its potential role in oncologic imaging. Prior work has shown that perfusion imaging demonstrates differences between normal and abnormal tissues and may provide evidence of early metastatic lesions before they are visible on routine imaging studies. This correlates well with histological findings showing altered vascularity accompanying early metastatic disease. These findings have not been translated into reliable metrics for tumor assessment, in part due to the complexity of the data. The application of statistical mixture modeling, in which complex datasets are decomposed into mixtures of basic populations, may allow quantification of tumor burden from this data. This study will be conducted under approval by the local institutional review board and radiation safety committee. Subjects will undergo perfusion imaging of the liver using a Toshiba Aquilion 320-slice CT scanner. Images spanning the full liver (up to 16 cm) will be acquired at multiple time points following the administration of intravenous contrast. A six-subject cross-sectional study will assess the reproducibility of the quantitative tumor volume estimates using mixture modeling analysis of CT perfusion imaging studies at enrollment and following 1 week. A 20-subject prospective cohort study will then compare the change in tumor volume estimates over a 4- to 8-week span versus independent Likert ratings of disease progression by masked radiologists and oncologists. Secondary analyses will identify the perfusion imaging time points that best discriminate between normal tissue, viable tumor, and necrotic tissue for use in protocol optimization and dose reduction. Significance: This work may result in a method of reliable quantification of tumor burden within the liver that could substantially improve assessment of response to antitumor therapy and early detection of metastatic disease.

Michael Rosenthal, MD, PhD

RadiologyBrigham and Women's Hospital


Toshiba America Medical Systems/RSNA

Research Resident Grant

Molecular Mechanisms for Hypoxia-Mediated Immune Suppression in Tumors Hypoxic tumors are more resistant to radiation and are associated with worse clinical prognosis. The reasons for this radioresistance include the selection for more malignant phenotypes as well as the decrease in oxygen radicals produced by radiation. To enhance effectiveness of radiotherapy, several groups have combined radiation with immunotherapy. Radiation in combination with antibodies or CpG oligonucleotides has improved responses in mouse and man. However, it remains unclear whether the hypoxic tumor environment also inhibits antitumor immune responses that can improve the effectiveness radiotherapy. Previously, I have found that hypoxia inhibits dendritic cells (DCs) from endocytosing and presenting antigen to T cells to stimulate an immune response. Furthermore, hypoxia likely inhibits endocytosis and antigen presentation likely through the glycolytic pathway. Using DNA microarray analyses of hypoxic DCs, I have identified a set of genes whose expression correlates with the loss of endocytosis. Of these genes, calmodulin is downregulated under hypoxia. Calmodulin inhibitors prevent endocytosis in DCs. Therefore, hypoxia may downregulate calmodulin expression and, thereby, inhibits endocytosis and antigen presentation in DCs. Here, I hypothesize that overexpression of calmodulin overcomes the inhibition of endocytosis and antigen presentation by hypoxia. In Aim 1, I shall confirm that hypoxia downregulates calmodulin expression via the glycolytic pathway. In Aim 2, I shall determine whether overexpression of calmodulin rescues endocytosis and antigen presentation of hypoxic DCs in vitro. In Aim 3, I shall determine whether “knock down” of calmodulin is sufficient to inhibit endocytosis. By understanding how hypoxia affects the ability of DCs to stimulate an immune response, we will learn how hypoxia enables cancer cells to evade the immune system. Furthermore, by discovering which genes are responsible for tumor induced immune evasion, we can develop immunotherapies that target the antigens expressed in these “ignored” tumor regions. Such strategies may better target the radioresistant hypoxic cancer cells.

Michael Spiotto, MD, PhDRadiation OncologyStanford University

Stanford, Calif

RSNA Presidents CircleResearch Resident Grant

16

Investigations on the Differential Oncogene-Dependency of MYC Versus K-Ras Murine Primary Lung Tumor Model Systems Non-small cell lung cancer (NSCLC) causes the most cancer mortality in the world. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) have made a major impact on the treatment of NSCLC. “Oncogene-addiction” is a biological phenomenon whereby tumors following oncogene-inactivation exhibit dramatic regression revealing tumor cells that are dependent on their initiating oncogene for survival. EGFR-mutation positive NSCLC patients treated with EGFR TKIs respond clinically with this “oncogene-addicted” phenotype. However, only a minority of NSCLCs and cancers in general demonstrate oncogene-addiction likely because multiple oncogenes are co-activated in most cancers. Elucidating and then targeting the finite number of activated oncogenes for cancers could provide large gains in cancer treatment. Our preliminary data used conditional mouse lung cancer systems recapitulating oncogene-addicted and non-oncogene-addicted human NSCLC using the oncogenes K-Ras and MYC, respectively. Our results suggested that during tumorigenesis in MYC mice, selection for mutations that phenocopy K-Ras activation occur and thus explain the non-oncogene-addicted phenotype in this model. Human studies suggest the K-Ras signaling axis is a common target during human NSCLC tumorigenesis. We have generated primary NSCLC cell lines from MYC- and K-Ras-induced tumors. The goal of Aim #1 is to test the hypothesis that the difference in oncogene-dependence between MYC- and K-Ras-induced NSCLC cell lines is determined by differences in other somatically activated oncogenes. After defining the differences between MYC and K-Ras-induced NSCLC cells, we will inhibit these oncogenic targets with inhibitors and/or siRNA. We expect that inhibiting these active signaling molecules with MYC-inactivation will result in an oncogene-addicted phenotype. Aim #2 we will examine this hypothesis in vivo using primary tumor samples and on in situ primary tumors. The ultimate goal of this proposal is to isolate the molecular differences between MYC- and K-Ras-induced lung tumors and then to force MYC-induced lung tumors to now exhibit an oncogene-addicted phenotype.

Phuoc T. Tran, MD, PhDRadiation OncologyStanford University School of Medicine

Stanford, Calif

RSNA Research Fellow Grant

Ultrasound-Mediated Suicide Gene Therapy with Molecularly Targeted Microbubbles in a Murine Model of Tumor Angiogenesis The primary objectives of this proposal are: a) to develop an ultrasound (US) contrast agent-based platform for molecularly targeted enhanced gene delivery and treatment monitoring and b) to apply this delivery platform for suicide gene therapy in a murine model of tumor angiogenesis. US microbubbles are potential intravascular vehicles for localized gene delivery. Region-specific transfection has been achieved with systemically administered gene-carrying, non-targeted microbubbles by application of focused therapeutic US (frequencies 1-3-MHz, intensities 0.5-3 W/cm2), resulting in microbubble destruction, release of genetic cargo, a temporary increase in cell wall permeability, and eventual transfection. In molecular imaging, targeted microbubbles bearing receptor-specific ligands have also been developed. US-mediated gene delivery with molecularly targeted microbubbles has not been previously explored. We hypothesize that a combination of these targeting strategies—molecular targeting and localized acoustic microbubble destruction—synergistically enhance site-specific US-mediated gene transfection. The addition of targeting ligands to carrier microbubbles should result in their close apposition to the cell membrane and molecularly specific accumulation at the site of disease. We apply this novel approach in suicide gene therapy targeted to tumor neovessels and then monitor treatment response with the same targeted microbubbles without genetic payload. This project involves three phases: First, cationic microbubbles will be conjugated with anti-VEGFR2 antibodies and complexed with plasmid DNA by electrostatic interactions. A tri-fusion reporter gene with combined multimodality molecular imaging and therapeutic functions (HSV1-thymidine kinase) will be delivered. Second, following systemic administration of the carrier complex and US-mediated transfection in a murine model of tumor angiogenesis, transfection efficiency will be assessed in vivo by serial bioluminescence imaging and ex vivo by fluorescence microscopy. Third, following in vivo transfection, ganciclovir will be administered to elicit the therapeutic effects of HSV1-thymidine kinase. Treatment response will be assessed in vivo by US with VEGFR2-targeted microbubbles and ex vivo by evaluation of microvascular density.

David Wang, MDRadiology

Stanford University School of Medicine

Stanford, Calif

Toshiba America Medical Systems/RSNA

Research Resident Grant

17

Neuroprotection via Enhanced Repair of Radiation-Induced DNA Damage by GSK3β Inhibitors Cranial irradiation as part of standard treatment of primary and metastatic brain tumors often results in long-term neurological sequelae. My mentor has previously reported that lithium significantly reduces radiation-induced apoptosis of neuronal cells and improves learning and memory in irradiated mice. My preliminary data suggest that lithium enhances the nonhomologous end-joining (NHEJ) DNA repair pathway. However, these protective effects require a 7-day prophylaxis with lithium prior to irradiation. Recent work reveals that neuroprotection by lithium may be through GSK3β inhibition. In support of this, 16-hour prophylaxis with GSK3β inhibitors attenuates radiation-induced apoptosis of neuronal cells and decreases radiation-induced γ-H2AX foci, which are well-characterized markers of DNA double strand breaks. Given lithium’s requirement for a 7-day prophylaxis, its narrow therapeutic window, and its lack of specificity, the use of GSK3β inhibitors as neuroprotectors provide clear advantages over lithium. Therefore, I will investigate the mechanisms of GSK3β inhibitors in neuroprotection, specifically its effects on NHEJ. Further understanding of these mechanisms will provide the potential for novel therapeutic strategies to alleviate the cognitive effects of cranial irradiation. Specific aim 1: To determine the effect of GSK3β inhibition on NHEJ DNA repair. NHEJ repair assays with or without GSK3β inhibitor in normal hippocampal neurons will be assessed. Validation utilizing ectopic expression of a kinase inactive GSK3β will be performed. I hypothesize that inhibiting GSK3β will result in enhanced NHEJ DNA repair. Specific aim 2: To determine the effects of inhibited NHEJ on neuroprotection by GSK3β inhibitors. Specific DNA-PK inhibitors will be used in neuron cell models and neuroprotection by GSK3β inhibitors will be assessed. Further validation will be performed utilizing animal models deficient in NHEJ such as in severe combined immune deficient (SCID) mice. I hypothesize that in these models, neuroprotection by either lithium or GSK3β inhibitors will be abrogated with inhibition/dysfunction of NHEJ.

Eddy Shih-Hsin Yang, MD, PhDRadiation Oncology

Vanderbilt University Medical CenterNashville, Tenn


The Role of TNF-Alpha Signaling in Normal Brain Tissue Response to Radiation Radiation therapy is an important treatment modality for brain tumors, but the outcome is generally dismal. Most patients with glioblastoma succumb to the disease within a year. Increasing radiation dose increases the time to recurrence for these patients, but at the cost of increased complications. Patients receiving whole brain irradiation for metastatic tumors also suffer a high rate of neurological complications, which can be severely debilitating. Therefore, an improved understanding of the normal brain tissue response to radiation is critical to increasing the therapeutic benefit of radiation therapy. Until recently, it has been thought that the late delayed effects of radiation therapy are the irreversible result of damage at the time of radiation. However, this paradigm is shifting to one in which the immediate damage at the time of radiation is only the beginning of a cascade of events which results in late radiation injury. Recent preclinical data suggest that TNFR2 plays a radioprotective role in the brain, while TNFR1 may be involved in promoting radiation-induced demyelination. Increased understanding of the mechanism of TNFR2-mediated radioprotection and the relationships between TNF-alpha signaling and the normal brain tissue response to radiation may lead to therapeutic options that can prevent or ameliorate the side effects of radiation therapy to the brain. The specific aims of this proposal are:

1. To determine whether radiation-induced acute apoptosis in the various cell compartments of the brain is mediated through TNFR1 signaling and negatively regulated through TNFR2 signaling.

2. To determine if subacute radiation-induced gliosis in the brain requires TNFR2 signaling and is regulated by TNFR1.

3. To identify downstream mediators of TNFR2-mediated radioprotection and to determine the effect of TNF-alpha signaling modulators on this pathway. The effect of TNF-alpha signaling modulation on the incidence of radiation-induced seizures and neurodegeneration will be also analyzed in a mouse model.

Brian Yeh, MDRadiation Oncology


Los Angeles, Calif


18

The Promise of Intensity Modulated Radiation Therapy for Head and Neck Cancer: Patterns of Care, Access to Treatment, and Functional Outcomes Purpose: Intensity modulated radiation therapy (IMRT) is a new and technologically intensive method of treating cancer. Head and neck cancer treatment with IMRT is more complex than conventional treatment. There is a risk of missing the tumor and possibly causing increased complications rates because of the relative precision by which radiation dose can be prescribed, if treatment is not planned or administered carefully. However, because of the lower possible dose to adjacent normal tissue and improved distribution of dose to areas at risk for cancer spread, and because of the economic advantage to the radiation oncology practice, IMRT is rapidly becoming adopted as the technique of choice for head and neck cancer radiotherapy. The goal of this study is to characterize (1) the pattern over time of IMRT adoption in the U.S., and patient-level and physician-level factors associated slow adoption of IMRT, and (2) the benefit of IMRT on functional outcomes. Design: The National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) – Medicare linked database is a large observational database that provides cancer diagnosis and treatment information on approximately 26% of the U.S. population. For patients who receive Medicare benefits, it also includes Medicare claims information for diverse medical interventions related to morbidity from head and neck radiation therapy. In addition, use of chemotherapy, type of staging studies performed, type of radiation treatment planning, and radiation techniques are recorded. Potential Clinical Significance: Through identification of patient-level and physician-level factors associated with the adoption of IMRT, we will provide insight into important factors modifying technology dissemination in radiation therapy and also identify barriers that limit patient access to new technologies. In addition, whether a functional benefit exists for IMRT treatment of head and neck cancer is a very important clinical question that has not been investigated on a national scale.

James B. Yu, MDTherapeutic Radiology

Yale School of MedicineNew Haven, Conn


Interventional Oncology and the Stromal-Derived Factor-1/CXCR4 Biological Axis: Implications for Post-Therapy Tumor Progression and a Novel Adjuvant Strategy As image-guided, minimally invasive cancer therapies continue to emerge, understanding their biological effects will become increasingly important. This proposal will attempt to define the role of the chemokine stromal-derived factor-1 (SDF-1) and its receptor CXCR4 in the biology of residual tumor cells after ablation or embolic therapy. Since the SDF-1/CXCR4 axis 1) is routinely upregulated in response to tissue stress of various causes and 2) effects angiogenesis, proliferation, invasion, and metastasis in cancer, we hypothesize that the insulted yet viable tumor scattered within in the embolized mass or around ablation margins will demonstrate elevated SDF-1 and/or CXCR4 expression and that inhibition of this interaction can be an effective adjuvant strategy. This hypothesis remains untested despite several supporting observations, such as treatment-associated stimulation of the hypoxia-inducible factor which is known to cause SDF-1 and CXCR4 induction. Interestingly, there are also scattered clinical and animal model papers documenting unusually aggressive tumor progression following ablation, radiation, and embolic treatments. Using orthotopic animal tumor models undergoing thermal ablation or transarterial embolization, we will evaluate short-term changes in the expression of SDF-1 and CXCR4, along with levels of angiogenic, proliferative, and invasive markers known to be effected by this axis. Pathological assessment will be performed by immunohistochemistry, Western blot, or cDNA analysis. Influence of inhibitor drugs against this interaction on post-treatment tumor biology will also be determined. Should the results prove promising, treat-and-follow animal models for evaluation of tumor growth and metastasis, with demonstration of SDF-1/CXCR4 inhibitor efficacy, will partly comprise my subsequent research endeavors as junior faculty. Ultimately, this work could be translated to the bedside to introduce an effective adjuvant therapy to be administered in concert with current interventional oncologic modalities, particularly in the management of large tumors for which complete necrosis is difficult to achieve.

Nam Yu, MDRadiology


Los Angeles, Calif

Cook Medical Cesare GianturcoRSNA Research Resident Grant

19

Early Detection of Locally Persistent Prostate Cancer Following Radiotherapy The great majority of new prostate cancers diagnosed each year in the Unites States are non-metastatic due to screening efforts with prostate specific antigen (PSA). While control rates following radiotherapy (RT) have improved over the last two decades, it has also become apparent that many men are at risk for the development of distant metastasis many years following treatment, with some resulting in death. Several studies suggest the cause for this late wave of metastasis is the presence of locally persistent prostate cancer, which lays undetected only to manifest itself once given the opportunity to spread. Routine methods for monitoring prostate cancer following RT are PSA, non-specific for the presence of normal prostate versus persistent disease versus distant metastasis, and digital rectal exam, which is oftentimes difficult to interpret. Prostate rebiopsy can be done but has been abandoned in routine practice because it is burdensome to the patient, especially when performed serially over time. High-resolution magnetic resonance imaging (MRI), dynamic contrast enhanced MRI, and MRI spectroscopy (MRSI) are promising techniques for monitoring patients over time. These techniques can diagnose prostate cancer. However, their ability to detect and monitor prostate cancer following radiotherapy is not well understood. This study is designed to determine the sensitivity of high-resolution MRI, DCE-MRI, and MRSI to prostate biopsy following radiotherapy. Eligible patients will have no evidence of relapsing PSA 2 to 3 years following the completion of treatment. Patients will first undergo imaging then prostate biopsy performed systematically and with additional biopsies directed toward abnormalities. The hypothesis is that MRI/DCE-MRI/MRSI will aid in the detection of locally persistent disease providing a means for monitoring patients and directing salvage therapy.

Mark Buyyounouski, MDRadiation Oncology

Fox Chase Cancer CenterPhiladelphia, Pa

Philips Healthcare/RSNA Research Seed Grant

Development and Validation of a Multitargeted Contrast Agent for Contrast-Enhanced Ultrasound Imaging of Tumor Angiogenesis in Early-Stage Pancreatic Cancer Angiogenesis, the formation and recruitment of new blood vessels from the host surrounding tissue, is an important process in early tumor progression of many tumors including pancreatic cancer. Non-invasive targeted contrast-enhanced ultrasound using microbubbles for contrast enhancement is a promising new molecular imaging tool that has the potential to identify angiogenesis at early tumor stages, soon after the “angiogenic switch” of cancer. The overall objective of our study is to develop novel ultrasonic contrast agents (microbubbles) that allow detection of early-stage pancreatic cancer-associated tumor angiogenesis at a time when the disease is localized and can still be cured. We hypothesize that early-stage pancreatic cancer can be detected with improved sensitivity by using molecularly-targeted contrast microbubbles that are engineered to recognize multiple markers of tumor angiogenesis including vascular endothelial growth factor (VEGF) receptor type 2, avß3 integrin, and endoglin. The proposed project includes two specific aims: First, we will develop and optimize novel multitargeted (dual- and triple-targeted) microbubbles designed to visualize tumor angiogenesis. Binding affinity of multitargeted microbubbles to tumor angiogenesis markers will be tested in flow chamber experiments in vitro and compared to traditional singly-targeted microbubbles. Second, we will test multitargeted microbubbles for in vivo imaging of tumor angiogenesis in subcutaneous pancreatic cancer xenografts. In addition, we will determine imaging signal and sensitivity of targeted contrast-enhanced ultrasound imaging using multitargeted microbubbles compared to singly-targeted microbubbles for early detection of pancreatic cancer in a spontaneous pancreatic cancer model in mice. This study will help achieve our long-term goal of developing an ultrasound imaging approach that is feasible as a second-line test in a multimodality screening program in a high-risk population. This research will validate our hypothesis in mice and lay the groundwork to translate this imaging approach into the clinic for patient use.

Jürgen K. Willmann, MDRadiology

Stanford UniversitySchool of Medicine

Stanford, Calif

Bayer HealthCare Pharmaceuticals/RSNA

Research Seed Grant

Grant RReesseeaarrcchh SSeeeedd

20

Role of Whole-Body CT Imaging Autopsy in the Investigation of Mechanisms of Blunt Force in Accidental Traumatic Death Introduction: Although much CT imaging data are available on survivors of accidental blunt trauma, little similar data have been gathered on decedents. Such trauma victims may undergo plain film radiography as part of a medical examiners investigation but are rarely studied with advanced imaging techniques. Purpose: To evaluate the value and potential role of whole-body CT imaging autopsy in the investigation of mechanisms of traumatic death following accidental blunt force injuries. Methods: CT imaging data, autopsy reports, and accident scene reports provided by police authorities are available on 25 decedents who were investigated following fatal road, workplace, or recreational accidents. Findings on CT were confirmed by autopsy. Initial results have shown that CT correctly identified cause of death as blunt trauma in 25/25 cases, with a sensitivity for major findings of 217/231 (93.4%). It is anticipated that an additional 15 cases will accrue before June 2008 to provide a study group of 40 decedents for evaluation. Work on this project will be performed in collaboration with the chief medical examiner of the state of Maryland and a trauma surgeon. The role of the medical student will be to organize data accruing from the CT imaging autopsy, conventional autopsy, and accident scene reports in computerized format and to assist the radiology faculty, medical examiner, and trauma surgeon in the analysis, presentation, and publication of these data. Endpoints: If whole-body CT autopsy can be shown to determine the exact mechanisms and forces that cause fatal injuries in road, workplace, or recreational accidents, this information will be valuable to physicians, road engineers, automobile designers, and others interested in developing new safety measures and improved safety standards with the overall aim of decreasing accidental deaths in such settings.

Samir Abboud, BSRadiology/Nuclear Medicine

University of MarylandBaltimore, Md

Canon U.S.A./RSNA Research Medical Student Grant

Assessment of Aneurysm Pulsatility in a Rabbit Model When an unruptured intracranial aneurysm is discovered in a patient, the question on course of treatment arises, which would depend on risk of the procedure as compared to risk of rupture. At the moment, it is not possible to non-invasively assess aneurysm wall thickness, a key factor in determining the risk of rupture of the aneurysm. We propose a method to estimate this thickness using CT to monitor pulsatility of the aneurysm. By capturing images of the aneurysm as it bulges and recedes with each pulse, we will measure the amount of distension the aneurysm experiences at each systolic phase. We expect the amount of distension will correlate with the weakness of the wall which would in turn correlate with the risk of rupture. For this experiment, we will use a rabbit model using elastase to induce the formation of an aneurysm in the carotid artery. The animals are then sacrificed and the arteries are attached to a pump. Using CT angiography, we will measure the amount of distention that occurs during simulated systole and diastole. We will then find the actual wall thickness of the aneurysm by physical dissection and measurement and determine if there is a correlation between the amount of distension and aneurysm wall thickness. The significance of our planned experiment is that it can serve as an anatomically realistic model of intracranial aneurysms and add to the understanding of aneurysm growth and rupture in humans. Nour Birouti will work closely with Dr. Shaibani to learn the basic protocols she will employ in this project. She will meet with him frequently to discuss progress, and during the course of the project, focus will shift from research design and implementation to data analysis. Dr. Shaibani will oversee the entire project and act as a mentor and guide.

Nour Birouti, BARadiology

Northwestern UniversityFeinberg School of Medicine

Chicago, Ill

RSNA Research Medical Student Grant

Grant RReesseeaarrcchh MMeeddiiccaall SSttuuddeenntt

21

Pilot Study—Relationship between Grey Matter Perfusion and Cognitive Impairment in Multiple Sclerosis Using CT Perfusion Multiple Sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system and 43%–65% of MS patients experience disabling cognitive dysfunction. There is evidence that microvascular impairment may play a role in the pathogenesis of MS and that cortical grey matter volume correlates with cognitive impairment. However, MRI studies on MS patients underestimate grey matter demyelination. Grey matter lesions are difficult to image with MRI and CT offers a cheaper and widely available alternative. This is the first CT perfusion (CTP) study proposed in MS patients and the first to correlate grey matter perfusion abnormalities with neurocognitive deficits in MS patients. MS patients will be recruited from an existing database. Patients will be scored by a neuropsychiatrist for cognition and then scanned by CT. CT images will be processed and analyzed with commercial and custom software. Thereafter, the CTP maps will be statistically correlated with cognitive impairment. All investigators will be blinded. It is anticipated that this study will advance the use of CTP as a practical longitudinal marker in MS patients and contribute to further understanding of neurocognitive impairment in MS. This project presents a meaningful subject for study and will allow me to interact with leaders in research at the University of Toronto. The study will be conducted under the mentorship of Dr. Richard Aviv. I will play a central role in the study and will be involved in all stages, especially in independent analysis. The technical and research training I receive will prepare me to succeed in residency, clinical practice, and radiological research. In turn, I hope to achieve my goal of giving back to medicine by initiating cross-disciplinary research efforts through my background in nanotechnology and by mentoring the next generation of medical students.

Tze Luck Chia, BScMedical Imaging

University of TorontoSunnybrook Health Sciences

Centre Toronto, Ontario

Canada

Tze is enrolled at Queen's University School of Medicine

RSNAResearch Medical Student Grant

Evaluation of Non-Mass Enhancement of the Breast Using 3 T Imaging and Correlating Pathology Background: Magnetic resonance imaging (MRI) has been utilized as a powerful imaging modality to detect cancers occult on mammography. Although MRI can detect occult malignancies, there are overlapping kinetic and morphological characteristics between benign and malignant lesions that neccesitate pathological diagnosis by biopsy. Of particular challenge are areas of non-mass enhancement, which have a broad differential diagnosis. Current research suggests that higher magnetic field strengths (ie 3 T) and MRI proton spectroscopy (MRS) may be important tools in improving the value of MRI. To this end, our specific aims are to prospectively assess the sensitivity and specificity of higher strength magnets (ie 3 T) with proton MR spectroscopy in distinguishing malignant versus benign non-mass enhancing lesions, with pathological diagnosis as the gold standard. Methods: This will be a prospective study on consecutive patients referred to our service for MR imaging-guided intervention (wire localization or core needle biopsy) or who were undergoing diagnostic MR imaging for a biopsy-proven breast lesion. Contrast-enhanced MRI will be used to identify breast lesion(s), and in vivo 3 T MRS will be undertaken to obtain spectra. Correlative imaging and clinical reports will be used when available. Final diagnoses on all identified areas of non-mass enhancement will be made by biopsy. Sensitivity, specificity, and confidence intervals will be computed. Conclusions: We hypothesize that 3 T MRI with MR spectroscopy may lead to more reliable lesion characterization and improved specificity in differentiating benign from malignant lesions presenting as non-mass enhancement. We believe that the increased specificity will decrease the number of unnecessary and costly biopsies in the future. Role of advisor and student: The student will be involved in all aspects of the project including patient recruitment, image acquisition, data analysis, and final reporting. The scientific advisor, as the lead breast radiologist for the project, will oversee day-to-day activities.

Sona Chikarmane, BARadiology

Brigham and Women's HospitalHarvard Medical School

Boston, Mass

Fujifilm Medical Systems/RSNA Research Medical Student Grant

22

The Spectrum of Findings Associated with Fibroid Expulsion after Uterine Artery Embolization Purpose: Uterine artery embolization (UAE) has become an increasingly popular alternative to surgery for women with symptomatic fibroids and is associated with a low complication rate (~0.5% hysterectomy rate). Many patients experience a post-embolization syndrome of fever, pain, and nausea lasting up to 1–2 weeks. One complication rarely seen is transvaginal expulsion of the fibroid. In some women who are unable to dilate enough to pass the fibroid, hysterectomy is required due to infection and pain. By reviewing the MRIs of patients at our institution who have expelled fibroids, we hope to find predictors of expulsion so that candidates for UAE can be better screened and counseled prior to the procedure about their likelihood of experiencing this complication. Hypothesis: We hypothesize that risk factors for expulsion will include greater fibroid size and greater fibroid contact area with the endometrium pre-UAE. Furthermore, we hypothesize that nulliparous patients will be at increased risk for the inability to pass expelling fibroids transvaginally, thereby requiring hysterectomy. Methods: I will review the charts of the 28 patients who have expelled fibroids post-UAE at our institution to date (and a random cohort of ~28 who did not) for data including age at expulsion, gravidity/parity, hysterectomy status, and time from UAE to expulsion symptoms. Follow-up calls will also be made to determine if the original fibroid symptoms improved post-expulsion, if a late hysterectomy was performed, etc. All of these patients’ MRIs will then be reviewed by myself and an experienced radiologist, from pre-UAE to the last follow-up post-expulsion. Uterine and fibroid dimensions will be measured in order to calculate volumes and changes in volume with subsequent MRIs. Fibroid location and the percentage of the fibroid in contact with the endometrium will be documented.

Lee Coryell, BARadiology

University of PennsylvaniaSchool of Medicine

Philadelphia, Pa


Evaluation of Hepatic Steatosis on Contrast-Enhanced Computed Tomography Scan Hepatic steatosis is a diagnosis in which clinical importance has only recently been recognized. These infiltrates are the most common cause of elevated liver function tests and in some cases may progress to cirrhosis or even hepatocellular carcinoma. Earlier studies concluded that detecting fatty infiltration on computed tomography (CT) is best accomplished by a non-contrast CT scan. However, in 1995 Heiken et al showed that an inverse linear relationship exists between maximum hepatic enhancement per gram of iodine contrast and body weight. It follows that one can predict the optimal level of hepatic enhancement in a patient with a known weight and iodine dose. Using this information, we aim to establish a diagnostic criteria for the identification of the hepatic steatosis on contrast-enhanced CT scan. We hypothesize that patients with steatosis will demonstrate decreased hepatic enhancement for the given weight and iodine dose. In order to develop these criteria, 350 consecutive patients who undergo an abdominal CT will undergo both a contrast enhanced and an unenhanced scan. The enhanced scan will then be evaluated for hepatic enhancement relative to other structures, while the unenhanced scan will serve as a control and determine whether steatosis is present. The medical student's role will involve measuring hepatic enhancement on the CT scans as well as compiling and analyzing the data. The research mentor will provide regular supervision to ensure that scans are being correctly interpreted and to offer guidance on data interpretation. The long-term goal of the project is to develop a widely applicable critera to detect hepatic steatosis on contrast-enhanced CT scans.

Guillermo Gonzalez, BARadiology

Washington UniversitySchool of Medicine

St Louis, Mo


23

Investigating the Tolerance of the Spinal Cord to CyberKnife Radiosurgery Stereotactic radiosurgery (SRS) using an image-guided robotic device known as the CyberKnife was introduced at Stanford University Medical Center in 1994, and the first patient with a spinal lesion was treated in 1997. In the intervening decade, Stanford has pioneered treatment of spinal lesions and has treated the world’s largest cohort of spinal cord arteriovenous malformation (SCAVMs) and benign spinal tumor patients. However, because radiation injury can take years to manifest, the factors that mitigate and predict injury have yet to be established. Additionally, no authoritative clinical standards exist to guide radiosurgical therapy for SCAVMs and benign tumors of the spine. A rigorous analysis of the unique cohort of patients at Stanford presents an opportunity to understand the factors that may help to govern benign tumor control and successful SCVAM obliteration. Furthermore, using this cohort, it is also possible to assess the radiation tolerance of the spinal cord by analyzing the dose–volume relationships. Our specific aims are: 1) To design an evidence-based algorithm for estimating risk of adverse events during latent period (time to radiographic disappearance); 2) To establish optimal radiosurgical dosimetry for spinal AVMs and benign tumors of the spine; 3) To develop methods for predicting time course of obliteration based on AVM and tumor type and location. The result of this analysis will be the development of radiosurgical “prescriptions” for various classes and radiographic presentations of SCAVMs as well as benign tumors of the spine. Ultimately these results may be applicable for all spinal lesions, exponentially expanding the clinical impact of this study. This work will allow the applicant to master the techniques and nuances of clinical radiosurgery research, which will be a key component of his future in academic radiation oncology.

Gaurav Gupta, BS, MSRadiation OncologyStanford UniversitySchool of Medicine

Stanford, Calif


Maturation of the Arteriovenous Fistula for Hemodialysis: Tracking the Process by Ultrasound Monitoring There is a need to monitor and quantify “fistula maturation” in order to promote greater primary patency rates through early identification of maturation failure. The study goal is to gain an understanding of the natural history of effective maturation of AV fistula and determine the parameters that define readiness for successful cannulation using high frequency ultrasound (US). Specifically, the primary goal of this research is to complete the cross-sectional component of this study. Objectives include: 1) To develop a reliable protocol for the use of the high frequency ultrasound prove, Vevo 770 Ultrasound (VisualSonics Inc), in the assessment of subject upper limb vessel parameters. 2) To quantify blood flow and vessel lumen radius to determine the role of wall shear stress using the Poiseuille Flow equation in patients with functional fistulae. 3) To compare observed wall shear stress values to expected wall shear stress values. 4) To quantify vessel wall thickness, pressure, and radius to elucidate the role of circumferential hoop stress using Laplace’s law in patients with functional fistulae. 5)To compare observed circumferential hoop stress to expected circumferential hoop stress values. Parameters to be collected include access flow, vessel wall thickness, vessel diameter, and blood pressures. Descriptive statistics will describe the mean and standard deviation of continuous variables. Comparative statistics will be t-tests for 2 group continuous variables. Kappa scores will be calculated to determine inter- and intra-observer reliability. The scientific advisor will be involved in parameter measurement and manuscript publication. The clinical significance of this work in the radiological sciences includes the potential routine use of US imaging to assess fistula maturation in a growing number of patients requiring hemodialysis due to renal failure. The medical student will be involved in patient recruitment, patient chart review, development of US machine measurement protocol, use of US machine, vascular parameter measurement, statistical analysis, and manuscript completion.

Arash Jaberi, HBScMedical Imaging

University of TorontoToronto, Ontario

Canada


24

Cost-Outcomes Analysis and Decision-Tree Modeling in the Investigational Vertebroplasty Efficacy and Safety Trial (INVEST) and the Carpal Tunnel Syndrome Diagnosis and Treatment Trial The proposed research is in the cost-outcomes analysis and decision-tree modeling for the Investigational Vertebroplasty Efficacy and Safety Trial (INVEST), and the Carpal Tunnel Syndrome Diagnosis and Treatment Trial. The INVEST trial is a randomized-controlled, blinded trial that compares percutaneous vertebroplasty with sham vertebroplasty. The Carpal Tunnel Syndrome Diagnosis and Treatment Trial is a randomized clinical trial of surgery versus conservative therapy for carpal tunnel syndrome which aims to determine if surgery compared to conservative therapy can benefit patients with mild or moderate carpal tunnel syndrome. This study also includes an analysis of the predictive value of magnetic resonance imaging (MRI) versus electrodiagnostic testing in evaluating the outcome of conservative therapy or surgery. Analysis of the INVEST trial data will involve a baseline descriptive data analysis, as well as the development of a decision analytic model for cost-effectiveness analysis. Analysis of the Carpal Tunnel Syndrome Diagnosis and Treatment Trial data will involve the analysis of the diagnostic accuracy of electrodiagnostic testing compared to MRI, as well as the evaluation of their predictive value in outcomes. Additionally, a resource utilization analysis of treatment arms of the trial will be performed in order to determine the cost-effectiveness of conservative versus surgical treatment. The clinical significance of data analysis of the INVEST study is that it will explore the cost-effectiveness of vertebroplasty in the care of patients who suffer from pain due to osteoporotic compression fractures. Similarly, constructing a formal decision analytic model will allow a better understanding of the relative cost-effectiveness of electrodiagnostic testing and MRI for the diagnosis of Carpal Tunnel Syndrome.

Aleksandrs Kalnins, BARadiology

University of WashingtonSchool of Medicine

Seattle, Wash


MRI of Borderline Fetal Ventriculomegaly: Imaging and Outcomes Objective: Fetal ventriculomegaly (VM) is a common end point of a variety of CNS pathologies with varying morbidity and mortality. Our goal is to determine if there is a subset of patients with borderline to mild VM who have near normal neurodevelopmental outcomes. We hypothesize that additional MR indices in addition to ultrasound will improve our prediction of postnatal outcomes. Improved prediction of outcomes will allow for better patient counseling with regard to pregnancy management and postnatal expectations. Methods: The study is a subproject of an NIH-funded project titled, MR of Fetal Ventriculomegaly: Morphology and Outcome. The prospectively designed study enrolls patients with a sonographic diagnosis of VM. A confirmatory ultrasound is performed and images are reviewed by three experts in obstetric ultrasound. Patients then undergo a prenatal MRI using an ultrafast MR protocol. The MR is interpreted by a radiologist with knowledge of the ultrasound results and additionally by three pediatric neuroradiologists. Disagreements in final diagnosis are decided by consensus. Pregnancy outcome and postnatal imaging findings are recorded. Standardized cognitive and motor tests are given at 6, 12, 24, and 36 months of age. Prenatal and postnatal imaging data will be compared to postnatal neurodevelopment outcomes. Statistical methods for analysis include: paired comparisons, ANOVA and kappa tests, and predictive modeling. Student/Investigator’s Role: The student will be involved in all aspects of the study, including: patient enrollment, analysis of prenatal imaging data, obtaining pregnancy outcome data, observing postnatal neurodevelopmental testing, and preparing data for data analysis. The student will participate in the statistical analysis of the data alongside the project statistician. She will write the first draft of the manuscript on this project. The scientific advisor (Dr. Levine) will serve as a mentor and will assist in all aspects of this work.

Gunjan Malik, BA

RadiologyBeth Israel Deaconess

Medical CenterBoston, Mass


25

Diagnostic Performance of FDG-PET in the Diagnosis of Acute Osteomyelitis and Evaluation of Atherosclerosis in the Diabetic Foot The ability to non-invasively detect osteomyelitis in the diabetic foot continues to remain a challenge. The currently employed imaging modalities such as planar X-ray lack the sensitivity to accurately exclude disease while MRI poses issues with its low specificity and certain contraindication with patients possessing bone stimulators. In this study, the first objective will be to examine the utility of FDG-PET in the diagnosis of acute osteomyelitis in the diabetic foot in comparison to that of MR and planar X-ray imaging. Diabetic mellitus increases and accelerates the progression of atherosclerosis in the lower extremities. FDG is predominantly taken up by macrophages and allows detection of the inflammatory component of atherosclerosis. Our second objective will be to investigate the correlation between atherosclerosis in the popliteal artery to metabolic activity and metabolic volumetric product in the diabetic foot. In our ongoing prospective study, patients meeting the requirements of diabetic foot disease are enrolled to undergo FDG-PET, MR, and planar X-ray imaging of the feet unless a particular contraindication exists. Each dedicated FDG-PET, MR, and planar X-ray film reviewer is blinding to the diagnosis of acute osteomyelitis made by both the other reviewers and follow-up data. The gold standard for the diagnosis of osteomyelitis in each patient is made on the basis of surgical findings, microbiology, and clinical follow-up. In evaluating atherosclerosis, diabetic patients diagnosed with neurodegenerative osteoarthropathy, osteomyelitis, and focal foot abnormalities will be excluded from the study. Region of interests (ROIs) will be drawn over the popliteal arteries and the adjacent background to calculate arterial/background ratios using maximal SUVs. ROIs will also be drawn over multiple slices for the entire axial foot and averaged using maximal SUVs. From such calculations, the relationship of the atherosclerotic burden and severity of ischemia in the diabetic foot will be assessed.

Asad Nawaz, BSRadiology/Nuclear Medicine

University of PennsylvaniaPhiladelphia, Pa


Assessment of Post-Prostatectomy Clinical Target Variation and Critical Structure Dosing During Intensity-Modulated Radiation Therapy Post-prostatectomy adjuvant and salvage radiotherapy are valuable therapeutic options for patients at high risk of prostate cancer progression or recurrence postoperatively. Intensity-modulated radiation therapy (IMRT) with optimal image-guidance provides the potential to maximize treatment efficacy and minimize toxicity through safer target volume dose escalation and limited adjacent tissue dosing. Conformal dose distributions with decreased volumes enable these achievements, but also increase the risk for target miss. IMRT in the post-prostatectomy setting is further complicated by altered anatomy and the lack of a primary tumor or target organ, creating a difficult to define clinical target volume. Additionally, daily changes in filling of the adjacent rectum and bladder contribute to prostate fossa displacement and protrusion of these structures into the radiation treatment field increase the risk for treatment related toxicities. These factors emphasize the need for image-guidance. The clinical use of CBCT image-guidance raises questions regarding which target should be the point of localization, to what extent this compromises neighboring organs at risk, and what level of compromise is acceptable. To begin answering these questions, we propose to evaluate the daily variation of the prostatectomy fossa, rectal, and bladder volumes and quantify their daily radiation dosing. The proposed project will retrospectively analyze CBCT imaging acquired during post- prostatectomy adjuvant and salvage IMRT. We will quantify the inter-fraction variation of a readily identifiable core CTV, defined by the location of surgical clips in the postoperative prostatectomy fossa. Core CTV, rectal and bladder dosing will also be compared at different alignment targets using CBCT based image alignment to bone anatomy or surgical clips at different levels. We hope to better quantify the daily prostate fossa variation and dosing of critical structures to determine the most appropriate treatment margins and alignment target for daily setup using CBCT image-guided IMRT.

Kristen O'Donnell, BSRadiation Oncology

Oregon Health & Science UniversityPortland, Ore


26

Directed Radiotherapy of MCF-7 Cells using 16a-[77Br]-bromo-11b-methoxyestradiol-17b 16a-[77Br]bromo-11b-methoxyestradiol-17b is a estrogen-selective Auger electron-emitting radiopharmaceutical that has been previously synthesized, and its in vivo rat biodistribution has been studied in the Katzenellenbogen and Welch groups. This compound was found to have a very high selective uptake into rat uterus. It is theorized that this compound provides an opportunity to study the feasibility of using small molecule radiopharmaceuticals not only for imaging, but also for targeted therapy. The use of 16a-[77Br]bromo-11b-methoxyestradiol-17b as a monotherapeutic radiopharmaceutical would require a very high specific activity to obtain the theoretical goal of 30–40 decays within the nucleus to initiate apoptosis. Due to the difficulty of obtaining radiolabeled material with sufficiently high effective specific activity for monotherapy, an alternative approach will be to combine 16a-[77Br]bromo-11b-methoxyestradiol-17b with a chemical radiosensitizer. Several chemotherapeutic compounds have been shown to act synergistically with radiation to kill cancerous tissues: 5-fluorouracil, cisplatin, hydroxyurea, and dexamethasone are a few that have been found to increase radiation efficacy. The ability of 16a-[77Br]bromo-11b-methoxyestradiol-17b to act as a radiotherapeutic agent, alone or combined with 5-FU or other chemotherapeutic radiosensitizers would be determined through a colony-forming assay. Growth inhibition controls for the chemotherapeutic drug would be done using the MTT assay with MCF-7 cells. Metabolism studies involving radiometric thin layer chromatography (TLC) would be performed to analyze the stability of 16a-[77Br]bromo-11b-methoxyestradiol-17b throughout the course of the experiment. The medical student will perform the required synthesis of the steroidal precursors as well as the radiosynthesis of the final product, 16a-[77Br]bromo-11b-methoxyestradiol-17b. The student will also grow and perform the cell culture experiments and analysis. The scientific advisor will provide expertise in producing the radioisotopes as well as the facilities required. Additionally, the scientific advisor will oversee the progress of the project and collaborate with other experts in the field as needed.

Ephraim Parent, PhDRadiology

Washington University School of Medicine

St Louis, M0

Dr. Parent is enrolled at the University of Illinois at Urbana-Champaign School of Medicine


The Effect of Varying Arterial Input Function on Cerebral Perfusion Assessment in Acute Ischemic Stroke The management of acute stroke requires rapid clinical assessment with immediate radiologic imaging to determine potential etiology, as well as to identify patients who could be candidates for emergency intravenous and/or intra-arterial thrombolytic therapy. A tool increasingly being used in this radiologic evaluation is computed tomography perfusion (CTP). CTP has the ability to identify the irreversibly damaged areas within an ischemic stroke (referred to as the “core”), as well as areas at risk of progressing to infarction if no therapies are initiated (referred to as the “penumbra”). The potential of CTP to identify a mismatch between penumbra and core serves as the basis for its application in the acute stroke setting. However, the calculation of cerebral perfusion parameters such as mean transit time (MTT), cerebral blood flow (CBF), and cerebral blood volume (CBV) may be altered greatly by the cerebral artery chosen as the arterial input function (AIF) in this calculation. Possible errors in these parameters may greatly impact the depiction of infarction versus at-risk brain tissue, and potentially influence clinical decisions made regarding the management of acute stroke. We plan to evaluate for any change in MTT, CBF, and CBV when the AIF is varied. Specifically, we plan to assess the possible errors introduced by choosing an anterior circulation artery for a posterior circulation stroke, or vice versa, which is something that no previous studies have addressed. The impact of varying AIF on penumbra and core will be assessed, as will the possible explanations for MTT variance.

Bippan Sangha, BSRadiology

University of British ColumbiaVancouver, British Columbia

Canada


27

TACE and Yttrium-90 Microspheres in the Treatment of Hepatocellular Carcinoma: A Cohort Comparison The purpose of this project is to investigate the differences in treatment modalities for hepatocellular carcinoma. The current worldwide standard is TACE (transarterial chemoembolization), involving injection of a high concentration of chemotherapeutics at tumoricidal doses, thereby generating cytotoxic and ischemic effects. A new therapy being investigated at Northwestern involves the injection of radioactive Yttrium-90 microspheres that do not generate an ischemic insult, but rather deliver low-dose-rate brachytherapy that also results in tumor killing. The advantage of this technique is less morbidity and mortality and better quality of life with the same presumed long-term outcomes. Differences in treatment will be investigated by performing a cohort comparison between patients treated with each modality. Comparisons will be made between 100 TACE and 100 microsphere patients. To make a fair comparison of the two treatment modalities, the two patient populations will be comparable from a baseline level, including child pugh status, presence of portal vein thrombosis, and tumor burden. A prospectively obtained dataset will be mined for the relative data. From this analysis, conclusions will be drawn with respect to relative long-term survival, tumor response, biochemical toxicity, and subjective toxicity. Current literature fails to provide direct comparison of TACE and microsphere treatment. Thus, the most important aspect of this project is to determine how the new and evolving therapy compares with the established standard of care. One major question to answer is whether a therapy with lower toxicity profile can generate similar long-term survival. If our hypothesis is correct, microspheres will be better tolerated and may allow for patients to receive cancer therapy on an outpatient basis. Throughout the course of the project, the advisor will be available for any necessary image reading, support, and feedback, while the student responsible for the majority of data collection, analysis and write up.

Seanthan Senthilnathan, BARadiology

Northwestern UniversityFeinberg School of Medicine

Chicago, Ill


Is Computed Tomography Necessary For All Patients with Suspected Pulmonary Embolism? A Retrospective Look Comparing the Mortality and Morbidity of Patients Diagnosed with PEs via CTPA and V/Q Over the past decade, computed tomography pulmonary angiography (CTPA) has replaced the nuclear ventilation perfusion (V/Q) scan as the most common imaging modality among patients with suspected pulmonary embolism (PE). Advantages of CTPA include its ability to directly demonstrate PE, as well as ancillary findings. Moreover, CT allows for improved visualization of isolated subsegmental emboli (ISSPE). However this has raised concerns about the possible “overdiagnosis” of these ISSPEs and their questionable management with anticoagulation (A/C). Furthermore, CT confers a considerably higher patient radiation dose than V/Q. Our research plan will retrospectively look at PE diagnoses within our center over the span of 10 years through either CT or V/Q. We hypothesize that if the two groups are made comparable, that there will be no significant difference in their case fatality. In addition, we’re interested in seeing if there is significant morbidity in the ISSPEs managed with A/C.

Steve How-Han Sheh, BSRadiology

Montefiore Medical CenterAlbert Einstein College of Medicine

Bronx, NY


28

Prostate Cancer Screening and Staging by Dynamic-Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) Pharmacokinetics Prostate cancer is second only to lung cancer as a cause of cancer-related death of men in the U.S. As no curative therapy for advanced stages of prostate cancer is available, early detection and treatment is necessary to reduce the burden of this disease. Serum prostate specific antigen (PSA) and digital rectal examination (DRE) lack the desired specificity for screening and staging for prostate cancer. Magnetic resonance imaging (MRI) has emerged as the best modality for soft tissue in vivo imaging. However, due to limited success of anatomical MR prostate images at field strengths used for standard clinical applications (1.5 Tesla and lower), MRI is currently used primarily to detect possible metastasis in advanced prostate cancer. Contrast-enhanced MRI is now used routinely in clinical applications, such as stroke and cardiac imaging. The information rich Dynamic contrast-enhanced (DCE) MRI, with its multiple acquisitions during the entire contrast reagent (CR) passage, can lead to insights of tumor vascular properties that are not available with conventional static MR images. Substantial improvements in image quality due to the development of high-field MRI scanners, combined with better data modeling and interpolation, uniquely available at Oregon Health and Science University, makes DCE-MRI an extremely promising tool for prostate cancer screening and staging. The goal of this project is to use DCE-MRI pharmacokinetics to differentiate normal prostate tissue from malignant lesions.

Faisal A. Siddiqui, PhDRadiation Oncology

Oregon Health & Science UniversityPortland, OR


Evaluation of a Novel Tool to Facilitate Critical Finding Communication Between Radiologists and Clinicians Objective: This study will evaluate the function of a novel informatics tool designed and implemented at our institution to facilitate communication between ordering physicians and radiologists. The objective of my quantitative and qualitative research will be to determine whether this tool provides an effective method to shorten the time in communicating critical findings that is consistent with and responsive to ACR and The Joint Commission guidelines. Research Plan and Data Collection: This application has been incorporated on the main reporting screen in our clinical PACS workstations. Data on current (pre-tool) delivery metrics also will be gathered. The three-part study will include: 1) a survey of >50 radiologists and clinicians who have used the tool on a regular basis since its implementation to determine: ease of use, ergonomic/interface issues, and suggestions for amendments; 2) an analysis of the aggregate data to determine elapsed times for delivery of critical findings, roadblocks to timely delivery, and radiology subspecialties/referring areas most prone to delayed communication; and 3) an evaluation of the effects of the new tool on clinical outcomes. Long-Term Goals: The project will evaluate the efficiency of this informatics tool in improving communication between radiologists and clinicians and enhancing patient care through more timely diagnoses. Successful metrics gathered in this project will provide detailed validation of the system and data needed to extend the program to other radiology departments. Moreover, this application is easily extensible beyond radiology to other specialties and healthcare systems. Scientific Advisor: Paul Nagy, PhD, is the project director. We will work to extract data from the program and identify potential modifications to the system. My primary involvement will be in data analysis and conducting interviews with program users.

Dina Sztein, BARadiology/Nuclear Medicine

University of Maryland School of Medicine

Baltimore, Md


29

Determination of Optimal Radiometal-Chelator Complexes for PET CT Visualization of Lewis Y+ Tumors using hu3S193 The field of nuclear medicine allows in vivo visualization of cellular function through the utilization of radiolabeled tracers. Positron emission tomography computed tomography (PET CT) scanners are currently being used to accurately quantify and anatomically pinpoint the areas of body where these tracers are concentrated in three-dimensional space. By using chelators to conjugate radiometals to monoclonal antibodies, researchers can specifically target cells for diagnostic visualization and therapeutic applications. Hu3S193 is a humanized monoclonal antibody that targets Lewis Y, a blood group antigen commonly overexpressed in epithelial tumors such as small cell lung cancer, metastatic breast cancer and hormone-refractory prostate cancer. Chelator chemistry can have detrimental consequences on antibody specificity and stability after conjugation. Previous research has led to the development of novel chelators, TAME-Hex A and TAME-Hex B. In this study, in vitro assays and in vivo imaging using microPET and microSPECT/CT will be used to evaluate the chelator’s effect on hu3S193 specificity and stability. Identification of optimal radiomedial-hu3S193 complexes will be rapidly taken forward into future Phase I human trials, resulting in this project’s significant clinical and translational impact.

James Walter, BSRadiology

University of Pennsylvania Philadelphia, Pa

James is enrolled at Creighton University School of Medicine

Philips Healthcare/RSNA Research Medical Student Grant

Magnetic Resonance Imaging (MRI) Perfusion: Validation in Swine and Correlation with MR BOLD measurements Current clinical methods of evaluating kidney function, such as estimated glomerular filtration rate, are insensitive and non-specific for disease. Biopsy is often necessary to obtain an accurate diagnosis, however biopsy is invasive and not without risks. We have developed non-invasive methods with magnetic resonance imaging (MRI) that can evaluate renal perfusion and function on a regional basis. These methods include arterial spin labeling (ASL) to measure perfusion and MRI-BOLD to measure oxygenation. Together these methods provide a regional snapshot of renal function. Neither the ASL nor the MRI-BOLD use contrast and therefore avoids the risk of nephrogenic systemic fibrosis. Others have validated the MRI-BOLD technique. The goal of this research proposal is to validate the ASL method for measuring renal perfusion in 15 swine and compare these to measurements of perfusion assessed by microspheres. After anesthetization, pigs will have a stenosis induced in one of the renal arteries. MRI will then be performed on a 1.5 T scanner. Four microsphere injections will be performed periodically during the imaging session. After imaging and euthanasia, the kidneys will be harvested and tissue samples will be excised and sent for analysis. Perfusion image analysis will be performed in MATLAB. Measurements of perfusion from ASL and microspheres will be compared with a Student t test. Evaluation of this ASL technique will provide a solid scientific basis for use of our perfusion methods in humans. This study will significantly contribute to our ongoing studies in renal transplant patients and will establish a newfound means of evaluating renal function of patients without the use of gadolinium-based contrast agents. The fellow in this study will perform and assist in all aspects of the study, including surgery, imaging, data and statistical analysis, and manuscript preparation. The scientific advisor will oversee and assist in each of these aspects of the study.

Andrew Wentland, BSRadiology and Medical Physics

University of Wisconsin School of Medicine and Public

HealthMadison, Wisc


30

Novel Radiotherapeutic Approaches to Prostate Cancer: In Vivo Biodistribution Studies of Radiolabeled Small-Molecule Ligands for Prostate-Specific Membrane Antigen Prostate cancer will be diagnosed in over 218,000 men and was the leading new cancer diagnosis for men in the United States in 2007. Due to the poor specificity of PSA testing, novel methodologies are being developed to detect prostate cancer and potential metastatic cancer burden by targeting prostate specific membrane antigen (PSMA), a highly specific prostate-restricted type II integral membrane cell-surface glycoprotein expressed in both benign and malignant prostate tissue, as a potential target. PSMA is an attractive marker for diagnostic radiologic imaging and therapy because of its transmembrane location and because it is significantly up-regulated in prostate cancer and in metastatic prostate cancer lesions. Dr Pomper and co-workers have synthesized a series of radiolabeled small-molecule ligands, which demonstrate a high affinity for PSMA as previously shown by in vivo biodistribution and imaging studies. In an extension of this work, Dr Pomper and co-workers have synthesized both 131I and 90Y derivatives of these small-molecule ligands that bind PSMA, which would allow for the implemention of a novel radiotherapeutic approach to prostate cancer. The proposed research will study the in vivo biodistribution of the imaging surrogates 125I and 111In by first generating prostate tumor xenografts in mice and then determining the biodistribution of these derivatives post-injection using an automated gamma counter. Statistical analysis will be done with the StatView package and the paired t test will be utilized to assess for differences in tumor radiopharmaceutical uptake between different tissues. Previous research has demonstrated the imaging efficacy of these small-molecule PSMA ligands and make them extremely promising for use as radiotherapeutic agents and would provide a clinically significant and novel therapeutic modality for the treatment of prostate cancer and metastatic prostate cancer lesions.

John-Paul J. Yu, PhDRussell H. Morgan Departmentof Radiology and Radiological

ScienceThe Johns Hopkins University

School of Medicine Baltimore, Md

Dr Yu is enrolled at the Universityof Illinois, Urbana-Champaign


Developing Radiology Residents as Teachers: Program Director Views and Implementation of a National Resident Teacher Development Course Residents have an important role in the education of medical students and fellow residents. Surveyed residents indicate they would benefit from training on how to teach more effectively. In order to teach effectively, residents need to be familiar with principles of adult learning and with a spectrum of teaching techniques that can be used during structured lectures, case presentations, and informal discussion. Formal instruction delivered to residents may enable them to be more effective teachers and increase their enjoyment in teaching. A survey of United States and Canadian Radiology Residency Program Directors will be performed in order to determine the prevalence of resident-teacher training programs and the factors associated with establishment of these programs. To address the need for resident-teacher training, a resident-teacher course will be designed to meet the specific needs of radiology residents to be held at a major national radiology conference, such as the RSNA annual meeting.

Andrea Donovan, MDMedical Imaging

Sunnybrook Health Sciences Centre, University of Toronto

Toronto, OntarioCanada

RSNA/AUR/APDR/SCARDRadiology Education Research

Development Grant

Grant RRSSNNAA//AAUURR//AAPPDDRR//SSCCAARRDD RRaaddiioollooggyy EEdduuccaattiioonn RReesseeaarrcchh DDeevveellooppmmeenntt

31

Technical and Professional Skill Development Within Radiation Oncology Radiation oncology combines two essential skills: the delivery of a highly technical treatment and ability of the physician to compassionately and professionally communicate the treatment plan. The professionalism and communication component will be developed through identification of communication and professionalism goals. The program involves didactic teaching, role playing, and standardized patients. Current programs will draw on but tailored to radiation oncology. The Mayo Clinic Multidisciplinary Simulation Center will be utilized to record the interactions with the standardized patients for debriefing and to evaluate development over time. Evaluation tools of this intervention will be created. The technical component of the training involves the development of two technical skills. First, the applicant will develop a programmatic approach to the use of the nasopharyngoscope. A series of dexterity skills will be developed, followed by creation of a digitally formatted interactive Web-based program. Second, the trainee’s technical skills in pelvis brachytherapy will be enhanced. This will involve the use of models and cadavers with ultrasound and fluoroscopy. An interactive Web-based program will be developed for some pelvic malignancies. The applicant will utilize the resources of the Multidisciplinary Simulation Center and other existing programs. The Section of Illustration and Design is available to create the interactive digital teaching tools. Finally, individuals in other departments who have interest in overlapping areas of research will be resources for the development of this program. The existing center and the strong education focus of Mayo will serve as tools to develop these skills that are not available through online, hands-on courses or other venues due to the relatively small size of the field of radiation oncology. The development of these programs will serve as a starting point for the creation of other simulation tools such as interactive Web-based programs for external beam irradiation treatment simulation and treatment planning modules.

Ivy Petersen, MDRadiation Oncology

Mayo Clinic Rochester, Minn

GE Healthcare/RSNA Education Scholar Grant

Developing a Curriculum for Teaching the Business of Radiology Organized academic radiology has largely ignored the needs of radiology trainees with respect to teaching them the essentials of radiology practice management and business principles. Residents and fellows enter their new careers vulnerable to and ignorant of pitfalls in establishing a radiology office, purchasing equipment, negotiating contracts, ensuring accurate billing and collection, and evading potential medicolegal entanglements. The proposed educational program is designed to provide, through RSNA, an electronic curriculum of one year's duration (24 lessons) for teaching these principles. The principal investigator, who already has an MBA degree, will use the Education Scholar Grant to develop the skills needed to design Web-based electronic interactive learning modules that 1) incorporate video and static teaching material, 2) create the most effective multiple choice questions and answers for determining the knowledge gained by the viewer, 3) input spread sheets that can be downloadable for offline use, and 4) develop tools for assessig the relevancy of the modules to clinical and academic practice. The value of the program will be tested serially as well via electronic surveys as trainees enter their careers. The grantee will spend 16% of his time taking lessons on educational techniques and Web design while using the textbook he co-edited, Radiology Business Practice: How to Succeed (2007) as a starting point for developing the curriculum. With this basis, the material for the lessons will be readily available, and is already well-organized. The main benefit to the radiology community would be the development of a practical user-friendly interactive online program that teaches business principles for a successful radiology practice whether in academia or private practice.

David Yousem, MD, MBARussell H. Morgan Departmentof Radiology and Radiological

ScienceJohns Hopkins Medical Institution

Baltimore, Md

Philips Healthcare/RSNA Education Scholar Grant

Grant EEdduuccaattiioonn SScchhoollaarr

32

Clinical Fellowship in Cardiovascular Imaging: Cardiac MR and CT Emphasis The Division of Cardiac Radiology, along with the Division of Body Imaging, would offer a qualified candidate meeting all requirements for RSNA funding eligibility a 1-year fellowship in cardiovascular imaging with significant emphasis in cardiac MR and CT. The RSNA supported fellow would have equivalent status with all fellows in the department with the added assurance of dedicated research time of up to 2 days per week. Emphasis would be in clinical training and research participation in our busy cardiac radiology program. The fellowship program was established in 2002. We have trained multiple fellows who have joined private and academic programs and trained RSNA funded fellows the past 2 years with excellent academic production from these fellows which included national and international presentations along with multiple publications. Our dedicated clinical cardiac assignment caseload continues to expand. We currently assign two attending staff per day to cardiac CT and MR to work with our cardiac radiology fellows. We also provided dedicated rotation in cardiac CT and MR for the radiology residents and cardiology fellows. We also perform a large volume of vascular imaging by MR and CT and the fellow would receive sufficient clinical experience and research opportunities if desired. Currently our equipment includes two 1.5 T magnets and two dual-source CT scanners that are under the control of the cardiac radiology division. A third dual source is shared with the Emergency Department. A CT innovation center has been recently established to compliment the MR research facility established over a decade ago. Demand for radiologists with expertise in cardiovascular CT and MR is exceeding the capability of programs to produce such individuals. RSNA funding would allow expansion of the established fellowship to help meet this demand.

Iulian Burtea, MDRadiology

Mayo ClinicRochester, Minn

GE Healthcare/RSNA Fellowship Training Grant

The Johns Hopkins University Cardiovascular Imaging Fellowship The primary goal of The Johns Hopkins Cardiovascular Imaging Fellowship is to provide comprehensive training in established protocols, practice, and recent achievements in non-invasive cardiovascular imaging, with emphasis on MRI and MDCT. The curriculum includes general cardiovascular imaging training, as well as dedicated time for concentrating on a specialty area in cardiovascular imaging. The fellowship program offers exposure to all aspects of cardiovascular imaging, including cardiac MR, MR angiography, cardiac CT and CT angiography. The cardiovascular imaging fellow is responsible for monitoring the study acquisition, post-processing of the data, interpreting the results, and communicating the findings with the clinical service. The Hopkins cardiovascular imaging fellow has access to dedicated MRI and MDCT scanners for cardiovascular imaging, including 1.5 T and 3 T MRI units, as well as 64-slice, 256-slice and dual-source MDCT units. Additional areas of training may include participation in ongoing cardiovascular multicenter clinical trials, coronary imaging research for both MDCT and MRI, high field imaging, pulse sequence evaluation and assessment of myocardial perfusion, function, and scar.

Amit Newatia, MDRadiology

The Johns Hopkins UniversityBaltimore, Md

RSNA Fellowship Training Grant

Grant FFeelllloowwsshhiipp TTrraaiinniinngg

33

Detection of Breast Cancer—Mammographic Architectural Distortion: Understanding the Perception to Develop Methods for Teaching The goal of this study is to understand how experts look at and analyze the mammographic signs of architectural distortion, with the intent to improve the education of radiology trainees, and ultimately the healthcare of all women. Architectural distortion is a radiographic sign that is highly specific for breast cancer. By understanding this perception, one would be able to teach the trainee how to see it. The problem is that it is the most difficult sign to learn, to perceive, and therefore, to teach. Studies have shown it is this radiographic sign that is most commonly missed, directly affecting a woman’s mortality. We will use an innovative approach of combining a mouse-tracking system and voice recorder to determine the search pattern used by experts vs the trainee when they analyze normal and abnormal mammograms with the features of architectural distortion. From the data gleaned, we will develop a tutorial and then we will teach the trainees to “see” this finding. The effect of the training will be measured using ROC curves before and after training and compared to those of the expert group. The support for this study will be key to producing preliminary data from which national funding will be sought. The ultimate goal of elucidating the features of architectural distortion such that it can be taught, described well in books, and from which neural networks can be developed, would impact the interpretation of mammograms and ultimately the health of women worldwide.

Dianne Georgian-Smith, MDRadiology

Brigham and Women's HospitalBoston, Mass

RSNA Education Seed Grant

Development, Implementation, and Assessment of an Inexpensive Cerebral Catheter Angiographic Training Laboratory and Curriculum This project aims at developing and implementing an interactive cerebral angiography laboratory and curriculum for educational purposes. Current neuroradiology fellowship programs require trainees to become adept at diagnostic cerebral angiography. The education of radiology residents and fellows in performing cerebral angiography has traditionally been through printed materials and graded supervision. At most academic training centers in the greater New York area, including our own, there is no formal curriculum specifically addressing cerebral angiographic technique. Because cerebral angiography requires the utmost attention to technique to avoid complications, it would be helpful for trainees to familiarize themselves with the procedure while practicing on models. Limited recent studies in the surgical literature have demonstrated improved resident performance in neuroendovascular procedures using sophisticated angiographic simulators. Simulators are, unfortunately, prohibitively expensive and not widely available at most training institutions. In addition, much of the software is designed for advanced treatment scenarios. There is no ideal interactive learning system readily available for the novice neuroangiographer. We propose to develop an inexpensive hands-on laboratory and an associated curriculum for trainees in cerebral catheter angiography. For the laboratory, we will develop simple models of the groin, vascular system, and the head. For the curriculum, we will cover basic topics in neuroangiography, integrating the use of models for an interactive trainee experience. The course will consist of 10, 1-hour sessions. The components of the laboratory, curriculum, and contact information will be made publically accessible on our departmental Web site. Details of the project will be submitted for presentation as it is our hope that this program will serve as a model for other institutions. We believe this project will not only benefit the trainees at our institution but potentially those at other institutions and will improve overall quality of patient care implemented into clinical practice.

Yvonne Lui, MDRadiology

Montefiore Medical CenterAlbert Einstein College of Medicine

of Yeshiva UniversityBronx, NY

RSNA Education Seed Grant

Grant EEdduuccaattiioonn SSeeeedd

34

Allison S. Aguado, MD Radiology Saint Barnabas Medical Center Lea M. Alhilali, MD Radiology University of Texas Southwestern Medical Center at Dallas Tarik K. Alkasab, MD, PhD Radiology Massachusetts General Hospital Srinesh Alle, MD Radiology Ochsner Health System Smith Apisarnthanarax, MD Radiation Oncology University of North Carolina at Chapel Hill Gautam Bahl, MD Diagnostic Radiology Wayne State University Detroit Medical Center Beth Beadle, MD, PhD Radiation Oncology Research University of Texas MD Anderson Cancer Center Avi Beck, MD Radiology Albany Medical Center Brian A. Bianco, DO, MBA Radiology Drexel University College of Medicine/Hahnemann University Hospital Garen Boghosian, MD Radiology Thomas Jefferson University Hospital Anthony Burgos, MD Radiology UMDNJ-Robert Wood Johnson Medical School Kevin C. Bylund, MD Radiation Oncology University of Iowa

George Cannon, MD Radiation Oncology University of Wisconsin Bethany Casagranda, DO Radiology University of Pittsburgh Medical Center Patrick C. Chang, MD Radiology David Geffen School of Medicine at UCLA Yasmin Chaudhri, MD Radiology Albert Einstein Medical Center Varghese Cherian, MD Radiology Lenox Hill Hospital James W. Clarke, MD Radiation Medicine Ohio State University College of Medicine Nick G. Costouros, MD Radiology University of California, San Francisco Courtney A. Coursey, MD Radiology Duke University Medical Center Marka Crittenden, MD, PhD Radiation Medicine Oregon Health Science University Tejas Dalal, MD Diagnostic Radiology University Hospitals Case Medical Center David J. D'Ambrosio, MD Radiation Oncology Fox Chase Cancer Center Gary H. Danton, MD, PhD Radiology University of Miami/Jackson Memorial Hospital Lucas M. DeJohn, DO Radiology Penn State Hershey Medical Center

Roberto Diaz, MD, PhD Radiation Oncology Vanderbilt University Maximilian Diehn, MD, PhD Radiation Oncology Stanford University Eric Drasin, MD Diagnostic Radiology Boston University Medial Center Jared M. Dunkin, MD Radiology Stony Brook University Brenda Farnquist, MD Diagnostic Radiology Queen's University Todd Flannery, MD Radiation Oncology University of Maryland Medical Center Reza Forghani, MD Diagnostic Radiology McGill University William C. Fox, MD Radiology Medical College of Virginia/VCU Bradley L. Fricke, MD Radiology Emory University

Clifton D. Fuller, MD Radiation Oncology University of Texas Health Science Center, San Antonio Ron Gefen, MD Diagnostic Radiology Cooper University Hospital Erik Gellella, MD Radiology Montefiore Medical Center Richard J. Gessman, MD Diagnostic Radiology St. Vincent's Medical Center Mark A. Gibson, MD Diagnostic Radiology Eastern Virginia Medical School Douglas G. Gold, MD, PhD Radiation Oncology Mayo Clinic Juan Gomez, MD Radiology Tulane University Health Sciences Center Christopher G. Guglielmo, MD Radiology University of Tennessee Medical Center

Award RRooeennttggeenn RReessiiddeenntt//FFeellllooww RReesseeaarrcchh

35

Gloria Guzman, MD Radiology West Virginia University Ahmad F. Haidary, MD Diagnostic Radiology William Beaumont Hospital Lilia Vanessa Hardin, MD Radiology Medical University of South Carolina Hayden Head, MD Radiology University of Texas Health Science Center, San Antonio Mark Henderson, MD Radiation Oncology Indiana University Robert Hong, MD Radiation Oncology Loyola University Medical Center Cheng Hong, MD, PhD Radiology University of Chicago Jeremy R. Hopkin, MD Radiology Dartmouth-Hitchcock Medical Center Bradford Hoppe, MD Radiation Oncology Memorial Sloan-Kettering Leland Hu, MD Neuroradiology Barrow Neurological Institute William D. Hwang, MD Radiology Long Island College Hospital Daniel J. Indelicato, MD Radiation Oncology University of Florida Craig M. Johnson, DO Radiology Aultman Hospital Alex Kagen, MD Radiology SUNY Downstate Medical Center Evguenia J. Karimova, MD Radiological Sciences St. Jude Children’s Research Hospital

Mustafa Khan, MD Diagnostic Radiology & Nuclear Medicine University of Western Ontario Valencia King, MD Radiology Memorial Sloan-Kettering Cancer Center Moritz F. Kircher, MD Radiology Beth Israel Deaconess Medical Center Andrew Nathan Knoll, MD Radiological Sciences University of California, Irvine Chi Wan Koo, MD Radiology St. Luke's Roosevelt Hospital Greg Kraushaar, MD Medical Imaging University of Saskatchewan Michael C. Kreeger, MD Radiology University of Cincinnati Saravanan Krishnamoorthy, MD Radiology University of Minnesota Grant Lattin, MD Radiology David Grant Medical Center Diego Lemos, MD Radiology University of Vermont Ying Li, PhD Radiation Medicine Roswell Park Cancer Institute Christopher Lightfoot, MD Radiology Dalhousie University Ke Lin, MD Radiology NYU School of Medicine I-Chun Jenna Liu, MD Radiology University of California San Diego Darren P. Lum, MD Radiology University of Wisconsin Medical School

Andrej P. Lyshchik, MD, PhD Radiology & Radiological Sciences Vanderbilt University Medical Center Mark Macedon, MD Radiation Oncology New York Methodist Hospital Jon Machayya, MD Radiology St. Joseph's Hospital and Medical Center Michael Mahlon, DO Radiology Tripler Army Medical Center Jonathan McConathy, MD, PhD Radiology Washington University Alyson McIntosh, MD Radiation Oncology University of Virginia Loren K. Mell, MD Radiation & Cellular Oncology University of Chicago Alexandre Menard, MD Medical Imaging University of Toronto Su Kyong Metcalfe, MD, MPH Radiation Oncology University of Rochester Jeffrey J. Meyer, MD Radiation Oncology Duke University Medical Center Elka Miller, MD Diagnostic Imaging Hospital For Sick Children Vladislav Miropolsky, MD Radiology University of British Columbia Kavita K. Mishra, MD Radiation Oncology University of California, San Francisco Richa Mittal, MD Diagnostic Imaging McMaster University University Medical Centre

Amir J. Momtahen, MD Radiology Saint Louis University Scott E. Moore, MD Radiology University of Massachusetts Medical School John Morgan, MD Radiology St. Vincent's Hospital, Manhattan Sirisha Nandalur, MD Radiation Oncology William Beaumont Hospital Elizabeth Ngan, MD Radiology & Diagnostic Imaging University of Alberta Christine Olsen, MD Radiation Oncology University of Colorado David Olson, MD Diagnostic Imaging University of Manitoba Eleanor Lee Ormsby, MD Radiology University of California, Davis Randy S. Parkhurst, MD Radiology Upstate Medical University, Syracuse, NY Hetal P. Patel, MD Radiology Baystate Medical Center Charles Perkins, MD, PhD Radiation Oncology Emory University Jeri Sue Plaxco, DO Diagnostic Radiology University of Kentucky Jagan Poli, MD Radiation Oncology NYHQ/Cornell Matthew M. Poppe, MD Radiation Oncology UMDNJ-Robert Wood Johnson Medical School Julia Prescott-Focht, DO Radiology University of Missouri Kansas City

36

Ethan A. Prince, MD Diagnostic Imaging Rhode Island Hospital/Brown Medical School Javier F. Quintana, MD Radiology Geisinger Medical Center Prabhakar Rajiah, MD Radiology University of Washington Geneva J. Randall, MD Diagnostic Radiology Oregon Health & Science University Nikhil Gadahad Rao, MD Radiation Oncology UTMB Galveston Daniel S. Reich, MD, PhD Radiology Johns Hopkins University Jeremy Rempel, MD Radiology Memorial University Margarita V. Revzin, MD Radiology North Shore University Hospital Andrew L. Rivard, MD, MS Radiology University of Florida Andrew B. Rosenkrantz, MD Diagnostic Radiology University of Maryland Medical Center

Adeel Sabir, MD Diagnostic Radiology Yale School of Medicine Jason Salsamendi, MD Radiology Jacobi Medical Center Jason W. Schroeder, MD Radiology National Capital Consortium Julie K. Schwarz, MD, PhD Radiation Oncology Washington University School of Medicine Eric T. Shinohara, MD Radiation Oncology Hospital of the University of Pennsylvania Farzan Siddiqui, MD, PhD Radiation Oncology Henry Ford Hospital Portia S. Silk, MD Radiology Hartford Hospital Justin S. Simonds, MD Radiology University of South Alabama Nicole Simone, MD Radiation Oncology National Cancer Institute Monica Smith-Pearl, MD Radiology McMaster University University Medical Centre

Aaron Spalding, MD, PhD Radiation Oncology University of Michigan Health Systems Jacek Strzelczyk, MD Radiology University of Michigan Health Systems Adam D. Talenfeld, MD Radiology Mount Sinai School of Medicine Rahul Tendulkar, MD Radiation Oncology Cleveland Clinic Seng Thipphavong, MD Diagnostic Radiology University of Ottawa Jonathan Tward, MD, PhD Radiation Oncoogy Huntsman Cancer Hospital, University of Utah Bryan J. Unsell, MD Radiology San Antonio Uniformed Services Health Education Consortium (SAUSHEC) Surjith Vattoth, MD Neuroradiology Fellowship Program University of Alabama at Birmingham Casey Veach, MD Diagnostic Radiology Southern Illinois University School of Medicine

Eric Wandler, MD Radiology Beth Israel Medical Center Graham Warren, MD, PhD Radiation Medicine University of Kentucky David Matthew Watkins, MD Diagnostic Radiology Texas A&M - Scott & White Hospital David F. Weeks, MD Radiology New York Medical College Stacy Wentworth, MD Radiation Oncology Wake Forest University Baptist Medical Center Christopher T. Whitlow, MD Radiology Wake Forest University Michael H. Wittmer, MD Radiology Mayo Clinic Joel A. Yalowitz, MD, PhD Diagnostic Radiology Indiana University School of Medicine Alice Yao-Lee, MD Diagnostic Radiology & Nuclear Medicine Rush University Medical Center James B. Yu, MD Theraputic Radiology Yale University

37

Ralph Weissleder, MD, PhD, is a professor of radiology and systems biology at Harvard Medical School, director of the Center for Systems Biology at Massachusetts General Hospital (MGH), director of the Center for Molecular Imaging Research in the Department of Radiology, and attending clinician in interventional radiology at MGH. Dr Weissleder is also a member of the Dana Farber Harvard Cancer Center, the Harvard Stem Cell Institute, and an associate member of the Broad Institute of Harvard and MIT. Dr Weissleder received his medical and doctorate degrees from the University of Heidelberg, Germany, and completed his radiology residency training at MGH. He has been at MGH/Harvard Medical School since 1986. Dr Weissleder’s primary research interests are in the field of in vivo molecular imaging, specifically, development of novel molecular imaging tools to the study of complex human diseases. He has made fundamental discoveries in early disease detection, development of nanomaterials for sensing and systems analysis. These basic research interests go hand in hand with his clinical interests in abdominal and interventional radiology. Specific examples of his translational research that have led to advanced clinical trials include the development of novel nanomaterials for MR detection of lymph node

metastases; development of enzyme activatable probes for the detection of early cancers by minimally invasive techniques such as laparoscopy; and clinical testing of long circulating polymers for angiogenesis imaging. Dr Weissleder has been a fully funded researcher for nearly 20 years. He is currently the principal investigator of several NIH grants, including R01, P01, U24, and U54 grants, a P50 center grant, and a U01 nanotechnology consortium grant. He has published over 400 original publications in peer-reviewed journals, over 90 review articles, has authored and co-authored several textbooks, and holds over 30 patents. As a mentor to 4–6 postdoctoral fellows per year, Dr Weissleder has produced over 150 molecular imaging experts, many of whom are already well known in the field. He is a highly coveted, world renowned keynote speaker, one of the few superstars whose presence is valued in many fields, most recently in the fields of cancer and metabolic and cardiovascular diseases. He is a founding member of the Society for Molecular Imaging Research and served as its president in 2002. He has unselfishly given his time and energy to RSNA to help launch its Molecular Imaging Committee and served as its inaugural chair. His work has been honored with numerous awards including the J. Taylor International Prize in Medicine, Millennium Pharmaceuticals Innovator Award, Association of University Radiologists (AUR) Memorial Award, American Roentgen Ray Society (ARRS) President's Award, Society for Molecular Imaging Lifetime Achievement Award and the Academy of Molecular Imaging 2006 Distinguished Basic Scientist Award. The impact of Dr Weissleder’s work is still to be felt as the field of molecular imaging is still young; however, he has taken radiology down important roads that will forever change the world of imaging sciences.

“Dr Weissleder has been working on molecular imaging way before this term entered the consciousness of radiologists.” - King C. Li, MD, MBA, M. D. Anderson Foundation Distinguished Chair in Radiology and Imaging Sciences, Professor of Radiology, Weill Cornell Medical College, Chair, Department of Radiology, Methodist Hospital Houston

“I speak from my experience as the former chief of the Molecular Imaging Branch of the Cancer Imaging Program of the National Cancer Institute (NCI) that Dr Weissleder is regarded as one of the most respected and accomplished imaging scientists in the world.” - John M. Hoffman, MD, Willard Snow Hansen Presidential Endowed Chair in Cancer Research, Professor of Radiology and Neurology, Director of Nuclear Medicine, Director: Molecular Imaging Program, Huntsman Cancer Institute, University of Utah School of Medicine

“Dr Weissleder has taught the rest of us that a radiologist can conduct world-class research, produce highly practical results, and be taken very seriously by other disciplines.” - Peter L. Choyke, MD, Chief, Molecular Imaging Program, NCI

Award OOuuttssttaannddiinngg RReesseeaarrcchheerr

38

Richard B. Gunderman, MD, PhD, is a professor and vice chairman of the department of radiology at Indiana University, with faculty positions in pediatrics, medical education, philosophy, philanthropy, and liberal arts. Dr Gunderman’s education began with a Summa Cum Laude/Phi Beta Kappa bachelor of arts degree (biology and philosophy) from Wabash College in Indiana. As a member of the Medical Scientist Training Program at the University of Chicago, he earned both his PhD in social thought and MD, graduating at the top of his class. After a year as a Federal Chancellor Scholar in Germany, he completed his radiology residency in Chicago, serving as chief resident. In addition, he holds a masters degree in public health from the Indiana University School of Medicine. While a student and resident at the University of Chicago, Dr Gunderman designed and taught 16 courses on topics related to medicine, ethics, and religion, creating the second-year elective in radiology. At Indiana University, he has designed and taught 13 different courses on radiology, medicine, philosophy, and philanthropy. As

a teacher at Indiana, he has won the Trustees Award for Teaching a record six times, as well as the highest teaching awards of the Indianapolis campus and the entire university system, one of few physicians and the first radiologist ever to do so. Dr Gunderman has served in many positions at Indiana University, including but not limited to, vice chair of radiology for education, director of pediatric radiology, and clerkship director for radiology. He has a long and successful history of mentoring medical students. In 2007 alone, he coauthored articles with eight different medical students, all of whom have gone on to radiology residencies. Dr Gunderman has published a remarkable number of articles in radiology, medical education, humanities, history of medicine, health policy, and philosophy. Thirty-seven of his over 210 refereed publications have focused specifically on radiology education. Because of his personal presence and creative thought, Dr Gunderman is a much sought after speaker. During the last 3 years alone, he has delivered seven named lectures, 21 keynote addresses, 17 grand rounds, 36 invited lectures, and has served as a visiting professor at eight different institutions. On the national level, Dr Gunderman created and chairs the educational track for the ARRS annual meeting. He is the past recipient of both an AUR-GERRAF Award and the first RSNA R&E Foundation Education Scholar Grant. He now serves on the Foundation’s Education Study Section. He is a member of 22 different societies, many with a focus on education. Dr Gunderman is the author of six books. The second edition of his Essential Radiology: Clinical Presentation, Pathophysiology, Imaging was hailed by the American Journal of Roentgenology, which wrote, “Anyone who has ever had the opportunity to hear Richard Gunderman lecture would expect only a product of exceptional quality by this erudite radiologist-educator. He delivers the goods!” His Achieving Excellence in Medical Education represents one of few books on medical education authored by a radiologist. Dr Gunderman’s most recent book, We Make a Life by What We Give, draws on his experiences as a physician and educator to build a case for giving as an essential element in a full career and life. His next book, Leadership in Medicine, will be published in January. Dr Gunderman will leave a lasting mark on countless undergraduates, medical students, residents, fellows and practicing physicians.

“Dr Richard Gunderman is an exemplary and truly outstanding radiologist educator who has made very important contributions locally and internationally to the field of radiology and to medical education in general.” - Bryan D. Berkey, MD, Chief of Ultrasound; Tripler Army Medical Center, Assistant Professor of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences, F. Edward Hebert School of Medicine

“Dr Gunderman is the owner of incredible intellect and energy. He has made a life-long commitment to use these qualities to advance thoughtful discussions in many areas, provide educational opportunities for numerous people in numerous arenas, and has done so with personal warmth and respect with every interaction that I have seen him make over the years.” - Andrew J. Taylor MD, Professor of Radiology, University of Wisconsin School of Medicine and Public Health

“Richard is clearly to be differentiated from other teachers by his unique commitment to reflection on teaching and the scholarship of teaching. He is unusual in that he is not only a good teacher, but also he has published very widely in the areas of philosophy and methodology of teaching.” - Mervyn D. Cohen, MB, ChB, MD, Eugene C. Klatte Professor of Radiology, Indiana University

Award OOuuttssttaannddiinngg EEdduuccaattoorr

2008 RSNA Research & Education Foundation Board of Trustees

Front row: Beverly B. Huckman, Secretary Hedvig Hricak, MD, PhD, Dr (hc) Anne G. Osborn, MD, Chair R. Gilbert Jost, MD

Back row: Theresa C. McLoud, MD C. Leon Partain, MD, PhD Jack E. Price, Treasurer E. Russell Ritenour, PhD Gary J. Becker, MD William T. Thorwarth, Jr, MD David H. Hussey, MD James H. Thrall, MD

RSNA Research & Education Foundation 820 Jorie Blvd

Oak Brook, IL 60523-2251

1-800-381-6660 R&[email protected]

RSNA.org/Foundation