RESOURCESFACILITIES: Specify the facilities to be used for the conduct of the proposed research. Indicate the project/performance sites and describe capacities, pertinent capabilities, relative proximity, and extent of availability to the project. If research involving Select Agent(s) will occur at any performance site(s), the biocontainment resources available at each site should be described. Under “Other,” identify support services such as machine shop, electronics shop, and specify the extent to which they will be available to the project. Use continuation pages if necessary.

Laboratory:See the following pages for descriptions of the research environment and laboratories.

Clinical:The University of Wisconsin-Madison Hospital is a 450-bed tertiary care facility that provides access to a full spectrum of patients for clinical research. The Department of Radiology provides a full range of traditional and high technology imaging services. State-of-the-art imaging equipment includes: fifteen MR scanners (ranging in field strength from 1.5–3.0 Tesla, as described below), seven CT scanners, sixteen ultrasound systems, six nuclear medicine machines, sixty-six general imaging machines, 6 angiography units, 8 mammography systems, and three bone mineral scanners. Additional imaging equipment is available at a number of satellite facilities. The UW Hospital’s Department of Human Oncology is contained within the University of Wisconsin Comprehensive Cancer Center tower in the UW Hospital and Clinics and the adjacent WIMR building. Human Oncology provides a full range of radiation treatments for cancer with a staff of medical physicists, oncologists, and basic scientists, several of whom participate as mentors or collaborators on this grant. Major equipment includes 2 TomoTherapy HiArt systems, a newly installed Varian TrueBeam, a Varian Trilogy, a Varian 600CD a ViewRay 60Co MR-guided treatment system, all of which are available for student research and training under the supervision of staff and faculty physicists. Additionally, as described below, a 1.5T, 70-cm bore MRI system (1.5T GE Healthcare Signa Artist) soon will be installed in the Department of Human Oncology. Virtually all major anatomic site subspecialty areas are represented by multidisciplinary clinics and tumor boards, including breast, CNS, esophageal, GU, head and neck, hepatobiliary, lung, lymphoma and pediatrics. Specialized treatment programs include both low and high dose rate GYN, prostate brachytherapy, breast brachytherapy, stereotactic and fractionated stereotactic radiosurgery, stereotactic body radiosurgery and hepatic intravascular brachytherapy, Special techniques available include respiratory gating and image guidance using ultrasound, cone beam CT or megavoltage CT. The associated planning systems are also available: Eclipse, Pinnacle, TomoTherapy and ViewRay. In addition, the Department of Medical Physics houses a more widely available and accessible Treatment Planning Systems (TPS) Laboratory for student use. The Varian treatment machines are commissioned in the Medical Physics TPS Lab, so plans created in the student lab can be delivered on the clinical machines.

In addition to clinical treatment units and planning systems, a dedicated measurement system (including a Standard Imaging 1-D water tank, PTW farmer chamber, phantoms and cables) is available for student use. A GE CT/PET scanner and a Varian Acuity simulator are also available for student use. Animal:The Wisconsin Institutes for Medical Research (WIMR) includes both a small animal vivarium and a large animal unit. These are located in the first 2 floors of WIMR Tower II (see WIMR below). Two veterinarians and three veterinary technicians are on staff at the University of Wisconsin-School of Medicine and Public Health Division of Laboratory Animal Resources. Housing is available for laboratory animals through the Division of Laboratory Animal Resources. AAALAC-accredited facilities for the acquisition boarding, surgical manipulation, and veterinary care of animals are provided and regulated by the Research Animals Resource Center (RARC) on a fee for service basis. Animals are maintained by RARC in pressurized, climate controlled, automatic light-cycled modern facilities located in several sites around campus including the UW Comprehensive Cancer Center (UWCCC) and McArdle Laboratory for Cancer Research (MLRC) and the Keck Laboratory within the Waisman Center. In addition to these facilities, the College of Veterinary Medicine is located near the UW Hospital and Clinics, the Wisconsin Institutes for Medical Research and the Medical Physics Department.

Computer:All offices and labs in Medical Physics are connected via high-speed (GB) ethernet connections to the campus-wide computer system for internet access, including World Wide Web resources, e-mail, and library resources. Medical Physics has a network of 24 Unix/Linux workstations, 188 Windows machines, and 14 MACs. There are also two Windows servers and two Unix/Linux systems for file and archive servers (each machine has two

quad-core CPUs, 16GB of RAM and 24 Terabytes of general purpose storage space) in addition to shared 48 TB of space for processing and storage by funded research projects. Each user gets 260 GB of storage for home and data directories on these centralized shared resources that are accessible from user desktop machines and the 16-node computer cluster (eight 32-core systems with 128 GB of RAM, four 32-core systems with 64 GB of RAM, and four 4-core systems with 8GB of RAM) for image reconstruction and post-processing.  Each desktop system is equipped with a DVD writer and/or an external USB-based storage for personal backups in addition to the centralized backups. All systems have access to several black & white and color laser printers.  Raw data transfer for off-line post-processing from/to all the scanners using protocols such as scp/sftp is readily accomplished.

Software on UNIX systems includes all standard UNIX utilities, compilers (C/C++, Fortran, and Java), IDE such as Netbeans and Eclipse, analysis packages such as MATLAB, word processors such as OpenOffice, plotting programs such as Xfig, spreadsheets, drawing packages, presentation, image editing such as Photoshop/Gimp, Pdf writer/converter, typesetting programs such as LaTeX/TeX, image viewing and analysis programs such as ImageJ in addition to editors like and Emacs. Software available on each desktop system includes Microsoft Office and/or Open Office (word processor, presentation package, spreadsheet, and database), Adobe Acrobat Writer, EndNote, and image analysis programs such as Matlab, Fiji/ImageJ, etc. In addition, each desktop machine has X11 server and NFS/CIFS capability to access the Unix/Linux-based computer cluster. All Unix/Linux software is accessible from all workstations (unless otherwise dictated by the license agreement of a particular package).

Office:Offices and secretarial work areas are located near the laboratories, and general secretarial and administrative services are available to all departmental faculty and staff. Adequate office space is available to all faculty and staff through their respective departments.

Other:All UW faculty and staff members have access to UW support services, including University Stores and Purchasing Departments, the Safety Department, Radiation and Biological Safety, Animal Use, and Human Subjects committees. Other support services available on a fee-for-service basis include electronics and machine shops (beyond those already maintained in the Department of Medical Physics), medical illustration and photography services, and computer support services beyond those provided by the Department of Medical Physics, as described above). Each faculty member and trainee has physical and electronic access to the excellent library facilities located at several locations on campus. All are totally ethernet-connected, allowing direct, high-speed access, for example, to more than 16 electronic databases including Medline, Cancerlit, and Science Citation Index.

MAJOR EQUIPMENT: List the most important equipment items already available for this project, noting the location and pertinent capabilities of each.The following pages provide descriptions of the major equipment available within the various research and teaching laboratories, as well as that available as shared resources.

10.1 Research and Training Facilities

The University of Wisconsin-Madison (UW) is a premier research institution consistently ranked among the best-funded public universities in the nation. It is the 2nd largest public research university in the country. For example, in 2011-12, UW researchers attracted $1,184.9 million in extramural grants, including $698.5 million from the federal government, ranking 4th in terms of national research expenditures (all institutions, public and private) and 2nd in terms of Big 10 research expenditures. The UW faculty or alumni have received 18 Nobel Prizes, and 74 faculty members are active or emeritus members of the prestigious National Academy of Sciences. Additionally, since 1925, the UW has obtained more than 1,900 U.S. patents and more than 2,000 foreign equivalents for various discoveries made by its faculty.

The University of Wisconsin School of Medicine and Public Health (UWSMPH) is the nation's first School of Medicine and Public Health. It is committed to supporting basic and translational research in cancer, cardiovascular disease, neurosciences, women’s health, and other areas. The UWSMPH is at the vanguard of a new paradigm uniting public health and medicine. With this new model, the school addresses the evolving health care needs of Wisconsin and beyond while building on a tradition of more than 100 years of educating health professionals and expanding boundaries of science through research. This revolutionary synthesis seeks to develop new approaches for preventing, as well as diagnosing and treating illness, with a simultaneous focus on both individuals and populations.

The School of Medicine and Public Health has a long tradition of rapidly translating discovery into application, enabled through synergies in its tripartite missions of patient care, education and research. The school has strong partnerships with University of Wisconsin Hospital and Clinics, a university health center that consistently receives major national awards and recognitions, and the University of Wisconsin Medical Foundation, one of the 10 largest physician practice groups in the country.

Medical Physics Department: The hub of the Radiological Sciences Training Program is in the Medical Physics Department. Since the early 1980’s, Medical Physics has been a separate Medical School department, bridging the biological and physical sciences and working in close partnership with UWSMPH clinical departments, centers, and UW Hospital. The department has 30 faculty members with at least a partial paid department appointment, 4 joint department faculty, 14 affiliate faculty, 21 adjunct, volunteer, and/or visiting faculty, and 4 active emeritus professors. The department is rounded out with 29 academic staff, 10

postdoctoral fellows and 106 graduate students. Medical Physics offers a broad range of courses and research opportunities, and it awards masters and PhD degrees to candidates working in all areas of diagnostic imaging, radiotherapy, as well as in emerging technologies in biomedicine. Faculty, Fellows and Residents in Radiology and Oncology are actively engaged in research involving both basic science and clinical investigations. Research projects are supported by federal, state, and private grants, and there is extensive collaboration with multiple industrial partners.

The Medical Physics Department is located in the basement and first floors of Tower I of the Wisconsin Institutes for Medical Research (WIMR), a three-phase project that ultimately will consist of three towers. Located adjacent to UW Hospitals and Clinics and the UW School of Medicine and Public Health’s “Health Sciences Learning Center” (HSLC), WIMR and its immediate environment provide state-of-the-art laboratory, classroom, office, and conference room facilities. The physical location of these facilities helps to promote strong interdisciplinary activities by placing mentoring faculty members and trainees in close proximity with colleagues in Radiology, Human Oncology, the UW Carbone Cancer Center, the UW Institute for Clinical and Translational Research (ICTR), and the Ebling Library system. The first tower opened in 2008 and contains the headquarters of the UW Carbone Cancer Center. Entire floors are dedicated to prostate and breast cancer research as well as hematologic and pediatric oncology. Floors three and four are dedicated to researchers working on cancers affecting children and cancers of the blood, lungs, head and neck. Orthopedics, regenerative medicine and surgery researchers are on the fifth floor. The Second Tower of WIMR is occupied by the McArdle Laboratory for Cancer Research, bringing together 18 separate oncology department lab groups focusing their attention on cancer and new cancer therapies. The remaining floors of the second tower include research programs in neuroscience, cardiovascular science, regenerative medicine and broadly focused molecular medicine research. Additional shared Medical Physics/Radiology is also in WIMR Tower II.

Particularly significant Medical Physics resources for this training grant are the WIMR Imaging Facility, the WIMR Small Animal Imaging Facility, the University of Wisconsin Medical Radiation Research Center (UWMRRC), our close collaborations with the departments of Radiology, Human Oncology and Biomedical Engineering and the resources available through the University of Wisconsin Carbone Cancer Center (UWCCC), the UW Institute for Clinical and Translational Research (UW-ICTR), the Laboratory for Optical and Computational Instrumentation (LOCI) and the Wisconsin Institutes for Discovery (WID), as described below.

The WIMR Imaging Facility involves a close collaboration with the Department of Radiology and provides research imaging resources to the UWCCC and the UW-ICTR. This facility houses state-of-the-art facilities for all major imaging modalities (MRI, CT, PET, PET/CT, PET/MR, Ultrasound, X-ray/Fluoro/Angiography and Biomagnetism) as well as major facilities to support those efforts (radiofrequency coil development lab, cyclotrons and radiopharmaceutical production facilities, molecular imaging and nanotechnology agent development and production facilities, phantom production facilities, and a machine shop). There are also facilities for the development and testing of ablation technologies. Each of these is described below in greater detail. WIMR’s MRI, PET/CT, PET/MR, and CT scanners have attained accreditation, so they are able to provide standard-of-care imaging service for patients who also are serving as subjects for research studies.

In order to accommodate human subjects, the WIMR facility includes a reception area, a waiting room, two changing rooms, two prep rooms, two consultation rooms, and a restroom. The changing rooms provide a private space for human subjects to change from their street clothes into patient gowns. The prep rooms are equipped to accommodate blood draws and insertion of IVs for administration of contrast agents for CT and MR scans. The consult rooms allow private interactions between human subjects and research study

UWHC

Waisman

Future WIMR 3

Children’s Hospital

VA Medical Center

WIMR 2WIMR 1

HSLC

coordinators, where study coordinators can describe the research studies, screen subjects, obtain informed consent, and answer any questions posed by the human subjects.

MRI Equipment in WIMR: The WIMR Imaging Facility houses two dedicated research MRI scanners and a dedicated PET/MR scanner. A fully-redesigned, revolutionary 3T GE Healthcare Signa Premier MRI scanner was installed in June of 2018 and is available for whole-body human scanning. The peak gradient strength is 80 mT/m and the peak gradient slew rate is 200 mT/m/msec. The bore diameter is 70 cm. The system has 146 receivers. Additionally, a 3T GE Healthcare Discovery MR750 MRI scanner is available for whole-body human scanning. It was installed in February of 2009. The peak gradient strength is 87 mT/m and the peak gradient slew rate is 346 mT/m/msec. The bore diameter is 60 cm. The system is equipped with 32 receivers. Also available in WIMR is a GE Healthcare Signa PET/MR scanner, consisting of a 3T MRI system with an integrated ring of PET detectors. It was installed in 2015. The Signa PET/MR is designed to preserve exceptional 3T MRI performance while offering simultaneous PET and MR acquisition. The high sensitivity (21 kcps/MBq) of the integrated PET system offers the potential for vastly improved image quality, dose reduction, or faster PET scans for the same dose. The MR-compatible Silicon Photomultiplier (SiPM) detector technology provides exceptional PET sensitivity (22.5 cps/kBq) and fast coincidence timing resolution (<400 psec) enabling time-of-flight (TOF) reconstruction. The SiPM PET ring is integrated into the MR RF body coil at the magnet’s isocenter and offers a 25.8 cm axial Field-of-View (FOV) utilizing a lutetium-based scintillator. The Signa PET/MR is designed to include optimized reconstruction for exquisite image quality as well as list-mode access to PET data for research. The Signa PET/MR coils are designed for a low 511 keV photon attenuation. The suite includes a Head and Neck Unit (HNU), an integrated Central Molecular-imaging Array (CMA), for which attenuation correction is automatically performed. In addition, the Signa PET/MR allows automatic attenuation correction for the 8-channel high resolution brain coil, and an 8-channel breast coil. The peak gradient strength is 44 mT/m and the peak gradient slew rate is 200 mT/m/msec. The bore diameter is 60 cm. The MRI sub-system has 32 receivers.

Both MRI systems and the PET/MR system are equipped with a variety of imaging coils, including phased-array coils and specialized coils designed to image specific anatomical regions such as the head, neck, spine, shoulder, thorax, heart, breasts, abdomen, pelvis, wrist, knee, foot, and extremities. Specialized coils developed and built in-house (see Coil Development Lab, below) are also available for use. Furthermore, both MR systems and the PET/MR system are equipped with all of the latest applications for evaluating characteristics such as perfusion, diffusion, spectroscopy, blood flow, cardiac anatomy and function, brain anatomy and function, and much more. All of the latest imaging features are available on both MRI systems and the PET/MR system, including parallel imaging, localized volume shimming, rapid reconstruction, and more. Also, the Premier MRI system and the PET/MRI system are equipped with multi-nuclear capabilities for performing imaging and spectroscopy on nuclei such as 31P, 13C, 3He, 129Xe, and 23Na.

A host of anciliary equipment is available for use with the MRI scanners that are housed in WIMR. Adjacent to the MRI scanners are a Xenon-129 Polarizer (9800 Xe-129 Hyperpolarizer, Polareen, Durham, NC) and a Helium-3 Polarizer (9600 He-3 Hyperpolarizer, Polarean, Durham, NC) that are used to genearate high-purity hyperpolarized Xe-129 and He-3 for gas-phase MR research studies. MRI-Compatible Contrast Agent Injectors (Spectris Solaris EP Power Injector Systems, Medrad, Pittsburgh, PA) are available at both of the MR scanners and at the PET/MR scanner. The injectors are fully programmable to provide precise dose delivery of contrast agents and saline from two separate syringes. Each syringe can be programmed for a two-phase injection at a rate up to 10 ml/s and 120 ml total volume. MRI-Compatible Patient Monitoring Systems are available (Veris MR Vital Signs Patient Monitor, Medrad, Pitsburgh, PA and Expresion Patient Monitor (MR400), Philips Healthcare, Andover, MA) for monitoring patient vital signs (ECG, SpO2, Temperature, Non-invasive blood pressure, expired CO2, invasive blood pressure, etc.) during MR scanning procedures on both MR scanners and the PET/MR scanner. A CompuFlow 1000 MRI-safe computer-controlled pump system (Shelly Medical Imaging Technologies, London, Ontario, Canada) is available for MR phantom experiments. The positive-displacement pump is driven by a micro stepping motor under computer control resulting in accurate steady flow and highly reproducible pulsatile waveforms. The pump is programmable with a flow range of 0.1 to 35 ml/s (accuracy of ±1%). The computer is pre-programmed with waveforms to simulate carotid, femoral, sine, square, and steady state flow. Additionally, user-defined waveforms can be generated from ASCII data files and can include reverse flow. A DCE Perfusion Flow Phantom (Multimodality DCE Perfusion Phantom, Shelley Medical Imaging Technologies, London, Ontario,

Canada) is available for use in the MRI scanners (and the CT and PET scanners). This multimodality DCE perfusion phantom simulates in vitro blood flow and two-compartment contrast flow pharmacokinetics using pressure-controlled fluid exchange with either step function-based or typical clinical arterial input function (AIF) inputs. This phantom produces a wide range of predictable, reproductible and quantifiable time concentration curves (TCCs), which generate a wide range of realistic input and output functions simulating clinically relevant perfusion TCCs. The ability of this phantom to generate DCE quality assurance protocols with realistic flow provides an excellent framework for validation of perfusion and kinetic modeling, and enables DCE imaging to be utilized as a quantitative imaging tool to compare imaging scanners. An MRI Phantom Development Lab includes workspace for construction of inert static MRI phantoms; MRI flow phantom storage and testing; sample preparation for biological and animal models; and general equipment preparation prior to use in the MRI scanner suites. Assorted glassware, chemicals, MRI imaging reagents, and other equipment needed for MRI phantom construction are included. A fume hood and lab refrigerator are shared with the adjoining Acoustics Measurement Lab. A Radiofrequency Coil Development Lab is used exclusively for the development of radiofrequency (RF) coil technology for MRI. The RF coil laboratory is equipped with seven electronic workstations, a MRI scanner bore simulator, printed circuit board (PCB) prototyping machinery, power supplies and a variety of RF test and measurement instrumentation that includes network analyzers, a spectrum analyzer, an oscilloscope, RF signal sources and many other RF components that are essential for the successful conduct of research in RF coils for MRI. The RF coils laboratory is easily accessible to all faculty, staff, post-docs and students, fostering cutting-edge collaborative work.

MRI Eqipment in the Waisman Center: In the Waisman center, which is located immediately across the street from the WIMR building, is housed a GE Healthcare 3T Discovery MR750 MRI scanner. This system has all of the features desribed above for the MR750 MRI scanner located in the WIMR building. This scanner is a dedicated research resource. The focus of the research performed on this scanner is neurological imaging. The environement is fully equiped with stumulus devices and processing software to facliate funcional MR imaging (fMRI).

MRI Equipment in the UW Hospital and Clinics (UWHC) and Satellite Facilities: In the UW Hospital and Clinics and its satellite facilities, there are fifteen MRI scanners that are used mainly for clinical purposes, but are available for research purposes as well. This includes four systems housed in UWHC (1.5T GE Healthcare Signa HDxt MRI scanner, 1.5T GE Healthcare Optima MR450W MRI scanner, 1.5T GE Healthcare Signa Artist, and a 3T GE Healtchare Signa Architect MRI scanner), one system housed in a modular building located immediately adjacent to the UWHC (3T GE Healthcare Signa Premier MR scanner), one system housed in the American Family Children’s Hospital located immediately adjacent to the UWHC (3T GE Healthcare Discovery MR750W MR scanner), four systems housed in a sports medicine clinic located 4 miles from UWHC (two 1.5T GE Healtchare Signa HDxt MR scanners a 3T GE Healthcare Discovery MR750 MR scanner, and a 3T GE Healthcare Discovery MR750W MR scanner), two systems housed in The American Center located about 11 miles form UWHC (1.5T GE Healthcare Optima MR450W MR scanner and a 3T GE Healtchare Discovery MR750 MR scanner), two systems housed at the 1 South Park outpatient imaging facility located about 2 miles from UWHC in downtown Madison (1.5T GE Healthcare Signa Explorer MR scanner and a GE Healthcare MR450W MR scanner), and one system housed at the Health Emotions Research Institute (HERI) located about 5 miles from UWHC (3T GE Healthcare Discovery MR750 MR scanner). Two of the systems in UWHC have protected time for performing research scans on healthy volunteers and patients in the early afternoons, and basic science experiments and pulse sequence development during late afternoons, evenings, and weekends. One of the sysetms in UWHC is a 1.5T system with a 70 cm diameter bore (MR450w) situated adjacent to a fully-equipped neurosurgical operating suite. This “intra-operative MRI” has a sliding door between the two rooms and a surgical bed that facilitates patient transfer between the operating suite and the MR system. All MRI systems have between 8 and146 receivers and are equipped with a large inventory of imaging coils, including phased-array coils and specialized coils designed to image specific anatomical regions such as the head, neck, spine, shoulder, thorax, heart, breasts, abdomen, pelvis, wrist, knee, foot, and extremities. All MRI systems at UWHC are updated to the most recent commercial software available from GE Healthcare.

Work has begun on installing a new 1.5T, 70 cm diamter bore MRI scanner (1.5T GE Healthcare Signa Artist) in the Department of Human Oncology. It is expected that installation of this system will be completed

by May of 2019. This system will be used for clinical purposes, but will have dedicated time available for research, especially in the area of developing applications for radiation therapy treatment planning.

Computed Tomography Equipment in WIMR: The WIMR Imaging Facility houses a GE Discovery CT750 HD CT scanner dedicated for CT research. This fully-equipped 64-slice CT scanner provides capabilities for dual energy studies as well as cardiac and perfusion studies. Gemstone Spectral Imaging (GSI) quantitative dual-energy CT GSI is a unique technique that uses rapid kV switching and Gemstone Detector technology to acquire and generate material density data. This data enables clinicians to identify the chemical composition of body materials, and aids in the characterization of pathology. At temporal registration speeds of up to 165 times faster than the nearest competitor, GSI was the first quantitative dual energy system on the market utilizing a 50cm FOV. Individual spectral images can be derived from 101 user-selectable energy levels. This approach enables GSI to review different levels of monochromatic energy levels for better iodine conspicuity, image contrast optimization, accurate CT numbers, and up to a 50% reduction in common beam-hardening artifacts. Low dose CT imaging: Powered by advanced image reconstruction algorithms, such as ASiR (Advanced Statistical iterative Reconstruction) and Veo, a model-based iterative reconstruction platform, the Discovery CT750 HD provides exceptional image quality. Advanced iterative computation overcomes the limitations of the conventional CT reconstruction approach, i.e., filtered back projection, and arrives at an optimal image.

A benchtop multi-contrast cone-beam CT system designed and constructed by the UW CT group provides a platform to develop and test multi-contrast imaging techniques that allow simultaneous measurement of electron density, effective atomic number, and small-angle scattering in a single acquisition. The system includes a Varian G-1582 x-ray tube, a Rad-Icon Shad-o-Box 2048EV detector, CPI Indico 100 x-ray generator, Parker 6K8 and National Instruments ESP300 motion controllers and closed-loop servo control on each axis. Three x-ray gratings form a Talbot-Lau interferometer and enable measurement of x-ray refraction. This system provides spatial resolution equivalent to micro- CT and the modular hardware and software design allows quick system reconfiguration for new experiments.

Absorption Cone-Beam CT Simulator Benchtop: A benchtop absorption CT simulator system designed and constructed by the UW CT group provides 7 degrees of freedom to simulate data acquisition from nearly any existing or proposed absorption CT scanner. Currently, this system is configured with a Varian G-1592 x-ray tube, a CPI lndico 100 x-ray generator, a GE 20 cm x 20 cm flat-panel detector, and Parker 6K8 motion controller with closed-loop servo motor control of each axis.

CT Equipment in the UW Hospital and Clinics (UWHC) and Satellite Facilities: In the UW Hospital and Clinics and its satellite facilities, there are seven CT scanners that are used mainly for clinical purposes, but are available for research purposes as well. This includes five CT scanners in the UWHC. These scanners include a 70-cm bore 16-slice CT scanner (GE Healthcare 580W CT scanner), two 64-slice CT scanners (GE Healthcare Optima 660 CT scanner and a GE Healthcare Discovery CT750 HD/Revolution GSI CT scanner), and a 256-slice CT scanner (GE Healthcare Revolution CT scanner), all four of these scanners are located in the Department of Radiology, and an additional 64-slice CT scanner (GE Healthcare Discovery 750 HD/Revolution GSI CT scanner) is located in the Emergency Department. All five of these scanners are available for research after hours and on weekends.

PET/CT Equipment in WIMR: Two PET/CT scanners are housed in WIMR. One is a 64-Slice GE Healthcare Discovery 710 PET/CT scanner. This system is an ACR-accredited PET/CT scanner. It was installed in 2013. It acquires PET and CT images for clinical and research purposes. The gantry bore diameter is 70 cm. Simultaneous acquisition of up to 64 CT slices is achievable. The PET system utilizes lutetium-based scintillation crystals and provides a spatial resolution of approximately 4.5 mm, an axial field of view of 15.7 cm, a timing resolution of 560 picoseconds, and a system sensitivity of 7.0 cps/kBq. The PET system collects data in 3D mode and can reconstruct images with or without time-of-flight (TOF) and point-spread function modeling (SharpIR). The system has options for cardiac and respiratory (Varian RPM) gating. A CT injection system (Medrad Stellant, Bayer) is available for CT contrast injections.

The second PET/CT scanner housed in WIMR is a state-of-the-art GE Healthcare Discovery MI PET/CT scanner. The Discovery MI PET/CT scanner was installed in WIMR in May 2018. This scanner utilizes the same high-performance SiPM detector technology as the GE Signa PET/MR scanner that is installed in an adjacent suite in WIMR. The gantry bore on the Discovery MI PET/CT scanner is 70 cm. The CT component of the scanner is capable of simultaneously acquiring 64 CT slices. The Discovery MI PET/CT scanner utilizes lutetium-based scintillation crystals and provides a spatial resolution of approximately 4.0 mm, an axial field of view of 20 cm, a timing resolution of 375 picoseconds, and a system sensitivity of 13.7 cps/kBq. The PET component of the system collects data in 3D mode and can reconstruct images with or without time-of-flight (TOF) and point-spread function modeling (SharpIR).

Attached to each PET/CT scanner room is a control room that includes workstations to reconstruct, analyze, and transfer data over the network. The efficiency of PET/CT procedures is accented by the close proximity of a hot lab, five patient prep rooms, and two patient bathrooms. The prep rooms and the bathrooms are shared with the PET/MR scanning suite. In-depth analysis and interpretation of procedures is performed in the analysis room that is divided into clinical and research analysis areas. A GE ADVANTAGE workstation includes software for detailed analysis of imaging procedures.

PET/CT Equipment in the UW Hospital and Clinics (UWHC) and Satellite Facilities: A 64-slice GE Healthcare Discovery VCT PET/CT scanner is housed at the 1 South Park outpatient imaging facility, which is located about 2 miles from UWHC in downtown Madison. This system acquires 2D and 3D PET imaging procedures and is specially equipped with hardware and software for cardiac gating, respiratory gating, and oncology treatment planning. Software includes the capability of acquiring data into list mode which allows for data to be re-binned into desired time frames and sequences. 4D PET and CT imaging is performed utilizing the respiratory tracking system (RPM Respiratory Gating System, Varian, and Palo Alto CA). Oncology treatment planning procedures employ the use of a flat table top and the external laser lights (DORADO Simulation Laser System, LAP, Germany

A GE Healthcare Discovery IQ PET/CT scanner is housed in the American Family Children’s Hospital (AFCH) located immediately adjacent to UWHC. It was installed in 2015. It acquires PET and CT images primarily as a clinical resource. The gantry bore diameter is 70 cm with a spatial resolution of about 4.5 mm.   Its large axial field-of-view (25 cm) results in exceptional detection sensitivity, potentially allowing for reduced injected doses. The PET system collects data in 3D mode and can reconstruct images with or without point-spread function modeling (SharpIR). It has options for cardiac and respiratory (Varian RPM) gating. A CT injection system (Medrad Stellant, Bayer) is available for CT contrast injections.

PET Radiopharmacy / Cyclotron Facilities: The Medical Physics Department operates two compact cyclotrons for the production of a wide variety of radiotracers needed by basic and translational researchers, both on campus and at thirty labs across the US. The first CTI RDS 112 was bunkered at the Medical Science Center on the main campus, becoming operational in 1985. This 11 MeV proton accelerator has undergone a major upgrade, with a new LabView control system promising an open pathway for three more decades of service. This cyclotron, with its 4000 square feet of dedicated lab space, serves a teaching role as well as weekly production of copper-64 and zirconium-89 for national distribution. The second cyclotron is a GE PETtrace with 100-microAmpere beams of 16 MeV protons or 8 MeV deuterons. Installed in 2009 at WIMR, it has been upgraded with a beam line that now serves 10 target positions in the vertical plane. This orientation is essential for the high current irradiation of targets with low melting points, allowing a downward-directed beam to impinge on a horizontal pool of molten target material. The radioactive products are transported to one of eight shielded hot cells, each equipped with robotic synthesis “black boxes” to safely handle Curie levels of activities.

A wide variety of PET radiotracers are produced on a daily basis. Basic researchers request a dozen 11C-labeled neuro-ligands (PIB, DTBZ, …) and a similar number of 18F-labeled agents (FLT, MefWAY, …), as well as novel tracers labeled with unconventional PET radionuclides (64Cu, 89Zr, 68Ga, 44Sc, 45Ti, 72As, 86Y,…) that show diagnostic and therapeutic promise as anti-cancer agents.

Additional adjoining labs provide the deep infrastructure needed to support the cyclotron facility. A large counting lab houses two HPGe detectors for radionuclide assay. A large inventory of NIM electronics and

accompanying computers are pressed into teaching service. A Packard Cyclone phosphor plate reader is used in a wide variety of research and teaching applications. A dozen HPLC’s and four GC’s are employed for radiochemical analysis. The fully equipped radiochemistry labs are further backed up with electronic and machine shop facilities invaluable in the construction of new detectors and targets. The imaging facilities that are entirely dedicated to the Medical Physics teaching mission include two gamma cameras, as well as an HR+ ECAT scanner, providing our graduate students with unparalleled access to conventional and PET imaging.

The PET/CT laboratory is fully equipped for conducting synthetic organic chemistry, bioconjugation chemistry, tissue culture, and cell/molecular biology experiments. It has an analytical/semi-preparative HPLC with PDA detector and autosampler, an analytical/semi-preparative HPLC with UV detector and radio-detector, a rotary evaporator, gas/O2/vacuum lines, a biosafety cabinet, two chemical fume hoods, an incubator, and RT-PCR, electrophoresis, gel documentation systems.

Radiopharmaceutical Production Facility: Located adjacent to the cyclotron and the PET/CT scanners in WIMR is the Radiopharmaceutical Production Facility (RPF). The Radiopharmaceutical Production Facility Radiochemical is comprised of a multi-room suite. Hoods are available in two of the chemistry rooms. In addition to these chemistry rooms, an additional room is dedicated to radioHPLC and another room is dedicated to conducting small animal experiments. Equipment contained in these rooms include: HPLC systems with UV-Vis detectors (3), UV-Vis diode array detector (1), electrochemical (1), coincidence gamma detctor (1), flowthrough beta detector (1), evaporative light scattering detector (1); frozen microtome, in vivo microdialysis apparatus, refrigerators (2), freezer (1), 18-Megaohms water purification system, glassware drying oven, microbalance, automatic liquid scintillation counter, Hereaus ultracentrifuge, vacuum line system, rotary evaporators (3) and dose calibrators (2).

Ultrasound: Ultrasound Imaging Systems in the WIMR Imaging Facility include three Siemens Acuson S2000s, a Siemens S3000, and two (new) Siemens Sequoias clinical scanners that support all commercially-available imaging modes on this platform, including an Automated Breast Volume Scanning (ABVS) system, all forms of elasticity imaging (eSie Touch palpation elastography and, with IRB approval, all three Virtual Touch modes: Virtual Touch Imaging, Virtual Touch Quantification and Virtual Touch IQ). The Axius Direct Ultrasound Research Interface (URI) allows acquiring radiofrequency echo-signal data under practically all imaging modes. A Master Research Agreement with Siemens permits our manipulation of these systems beyond the capabilities of the URI and well beyond the normal clinical user interface controls. A GE system… A Supersonic Imagine Aixplorer ultrasound system is capable of shear wave imaging with an ultrafast data acquisition sequence (up to 10,000 Hz). The system is also equipped with ultrafast Doppler, which is up to ten times faster than conventional Doppler. The system has a research package license, which allows collection of focused transmit or plane wave (up to 5,000 Hz) radiofrequency echo-signal data. With an additional research agreement, we have the capability of exporting shear wave displacement videos, which allows us to develop novel shear wave tracking algorithms to measure shear wave speed. Two Ultrasonix SonicTOUCH research scanners have the ability to acquire radiofrequency echo-signal data. Custom beam sequences can be defined with the equipped research software, which can be used to develop shear wave imaging modalities. When combined with the SonixDAQ Parallel Data Acquisition Module that attaches to a transducer port on the system, 128 channels of pre-beamformed data at a full sampling rate of 40 and 80 MHz can be acquired, allowing for plane wave acquisitions similar to those obtained with the Aixplorer system.

Additional resources include three Mechanical Testing Systems for quantifying the viscoelastic properties of phantom materials and tissues. An EnduraTEC ELF 3200 (Bose EnduraTec, MN, USA) is used primarily for dynamic measurements on bulk samples (>1 cm3) for loading frequencies between about 0.1 and 50Hz. An MTS NanoIndentor XP (MTS Systems Corporation, MN, USA) is also available measurements of the complex Young’s/shear modulus of tissue specimens. With a Nano Dynamic Contact Module (NANO DCM), the range of load-displacement experimentation can be reached down to a surface contact level, i.e., a few nanometers with a displacement resolution of 0.0002 mm. The indenter column weighs in at a mere 100 milligrams and this instrument has a nominal resonant frequency of 180 Hz, so this system offers accurate and reliable data for low-frequency stimulations in our laboratory environment. A custom device accurately measures the complex shear modulus of thin samples from 10-300 Hz. Also available is a Mark-10 Tensile Tester, which is used for testing intermediate-sized specimens and is located in the Orthopedics Research Laboratories. The Mark-10

can perform pull-to-failure and dynamic tensile testing. It has a digital load frame with multiple load cells. System control and data acquisition are performed through a graphical user interface on a personal computer connected to the system. An MTS Bionix, also housed in the Orthopedics Research Laboratories, can be programmed with complex waveforms for more elaborate testing protocols. It has been modified for multi-degree of freedom testing and is fully equipped with load cells, extensometers, and various custom-made devices for biomechanical analyses.

Acoustical Properties Measurement facilities are dedicated to measurements of acoustic properties of tissue and tissue-mimicking materials. The laboratory is well equipped with single element ultrasound transducers, signal generators, amplifiers, oscilloscopes, pulsers, receivers and hydrophones, and other customized apparati for measuring speed of sound, attenuation, scattering and elastic/visco-elastic properties. Notably among these are several manual and motorized 3–6 axis position control systems that are specifically configured to scan tissue specimens and tissue-mimicking phantoms.

A Phantom Manufacturing Laboratory is devoted to custom phantom production and is well equipped to manufacture phantoms for ultrasound, MRI, CT, microwave, and elasticity imaging, or any combination of these. This lab has a ventilation hood, numerous custom devices, and fixtures for heating, cooling, mixing and rotating phantoms during the manufacturing process. This lab is recognized around the world for continuous pioneering work in state-of-the-art phantom development and manufacturing. To support this lab, the Medical Physics Department has its own machine shop (650ft2) with drill presses, lathes, milling machines, etc. It is a modern, fully equipped machine shop in close proximity to the phantom and ultrasound labs. Equipment includes a CNC M3X-2V programmable milling machine.

X-ray/Angio/Fluoro: The WIMR Imaging Facility has a Siemens Artis Zeego flat panel detector angiographic system. This is a single-plane, multi-axis angiography system that consists of a specialized angiography C-arm integrated with a multi-axis industrial robot. This provides the capability for the system to offer a range of image angulations that was not previously possible with conventional stand and floor-mounted C-arm systems. The Zeego system uses a flat plate detector that is 30cm x 40cm in size that allows for resolutions of up to 1920 x 2480 pixels and frame rates of up to 30 frames per second. The system hardware is capable of cine acquisitions and fluoroscopy/road mapping at frame rates of up to 30 frames per second.

In order to permit the development of 4D Fluoroscopy that requires a bi-plane fluoroscopy system, the Zeego system in the animal laboratory was recently replaced with a Siemens Artis Zee bi-plane flat detector angiographic system. This biplane angiography system combines both a floor stand C-arm and a ceiling mounted C-arm to enable simultaneous use of both imaging planes. The biplane system uses two flat plate detectors that have 30 cm x 40 cm physical dimensions and a native detector resolution of 1920 x 2480 pixels and native pixel size of 154 μm with a bit depth of 14 bits. The biplane system is capable of fluoroscopy acquisition rates of up to 30 p/s and DSA acquisition rates of up to 7.5 f/s in bi-plane mode and up to 30 f/s in single plane mode. The biplane system is also equipped with external video connections to provide direct digital feeds of the live x-ray video streams such that prototype components can receive x-ray images from both planes in real-time for online processing.

The laboratory will include an integrated large-screen display in the operating room that has 56 inch viewing area and a resolution of 3840x2160 pixels. The display accepts 24 different video inputs, and can display up to 9 of these different video inputs simultaneously. Custom image sizes can be configured by using preconfigured layouts to further optimize the in-room image visualization. Prototype images can then be displayed in real-time, side-by-side with standard angiographic acquisitions for direct pre-clinical evaluation by the operator.

The UW Hospital and Clinics has two state-of-the-art Siemens angiography systems installed in the Department of Radiology. These interventional suites house both a Siemens Artis Zee biplane system and a Siemens Artis Zeego multi-axis robotic angiography system. Both of these rooms are also equipped with the large-screen, multi-input monitor, which will enable a smooth transition from pre-clinical prototype work in the animal lab to online clinical evaluations of the prototype systems.

Additional resources in WIMR include an Accutron HP-D (Med Tron AG) with two injection units which can be controlled independently of each other. It is designed for exact delivery of injections of contrast medium and

physiological saline solution. The user can specify delay time of injection, volume of injection, concentration of contrast medium, flow rate and injection time. Up to 60 injection parameter profiles can be stored and then retrieved on demand. Each profile can consist of up to 3 individually programmable injection phases which are then performed automatically after start of the program. The injector has a wireless feature that can communicate with the acquisition program of the Artis Zeego angiography system described above. A Digital Video Image Processor (DVIP4) is an image processor that is based on NVIDIA Tesla Cards. It is being developed for reconstruction of 4D DSA time frames and real time implementation of 4D Fluoroscopy using CUDA. This system will be used for our initial experiments and supports MATLAB for further investigation of processing algorithms.

Also located in WIMR is a the Scanning-Beam Digital X-ray system (SBDX, Triple Ring Technologies, Inc.), an x-ray fluoroscopic technology that uses inverse-geometry beam scanning for dose reduction and real-time tomosynthesis in cardiac procedures. The system is located in a 550 square foot lead-shielded procedure room intended for x-ray fluoroscopic / angiographic equipment and a 144 square foot control room. The procedure room is equipped with 480V 3-phase power for a high voltage generator, a chilled water supply for cooling electronics, and medical gases. The SBDX system consists of a large area x-ray source with electromagnetically deflected focal spot, a 100 x 100 hole collimator, and a high speed CdTe photon-counting x-ray detector (781,250 frame/sec). The source and detector are mounted on a mobile C-arm gantry with on-board high voltage generator. The room has an x-ray table with adjustable panning and height, and table encoders to enable reproducible experimental setups. The control room houses two computer workstations for controlling the SBDX x-ray source and detector, FPGA-based hardware (HiTech Global Inc.) for real-time data capture, a high speed 30 TB disk array (Conduant Corp.) for real time data storage, and two workstations for offline analysis.

Biomagnetism: The WIMR Imaging Facility houses a fully equipped biomagnetism laboratory, currently used for fetal magnetocardiography research. The lab has a magnetically shielded room comprised of two separate shields, each consisting of 0.25” aluminum and 0.080” high permeability alloy. The shield separation on all sides is 6.7”, except on the side that accommodates the door, where it is greater. The nominal inner dimensions are 10’x10’x8’ (l.w.h). The room was fabricated by Lindgren RF Enclosures and incorporates several unique features, including a pneumatic sliding door with an air bladder that expands to provide a much tighter seal than a hinged door. A small aperture allows direct observation and communication with the subject. The MSR sits on shock mounts that minimize vibrations. The measured shielding performance is excellent. Magnetic field attenuation is 44 dB at 0 Hz, 56 dB at 0.1 Hz, 64 dB at 1 Hz, >85 dB at 10 Hz and above. A Magnes II biomagnetometer (4D Neuroimaging, Inc.) is a dual sensor MEG system, consisting of a 37-channel floor-standing unit and a 37-channel ceiling-mounted unit. Each unit covers a circular area of diameter 14.4 cm. The signal channels are configured as first-order gradiometers with 2.0 cm diameter, 5.0 cm baseline, and magnetic field resolution <10 fT/(Hz)1/2. Eight reference channels are available for measuring ambient noise. The system comes complete with all required accessory equipment for magnetic source imaging studies, including data acquisition hardware and software, computer display and analysis software, sensor position indicator, patient observation system, patient table, and phantom. A Vector biomagnetometer (Tristan Technologies, Inc) is a 21-channel vector MCG system that measures all 3 components of the magnetic signal at 7 locations. The channels are configured as first-order gradiometers with 2.0 cm diameter, 3 cm channel-to-channel separation, and 8 cm baseline that measure the z-gradient of the magnetic field. The magnetic field resolution is 4-6 fT/(Hz)1/2. This system is designed for simultaneous fMCG/ultrasound recording. The channels are concentrated in a smaller area to facilitate ultrasound scanning, and the transducer can be stabilized by a custom mount attached to the dewar. A Sonosite M-Turbo Echo/Doppler portable ultrasound scanner (Sonosite, Inc) is capable of pulsed Doppler and color Doppler capability, tissue harmonic imaging, OB and cardiac software analysis packages and transducers, ECG input, mini-docking station, Sony UP 895 MD Video Printer, and all necessary cabling

The WIMR Small Animal Imaging Facility includes a Varian 4.7T small animal MRI scanner (Varian Inc., Palo Alto, CA) acquired in 2007. The horizontal bore imaging/spectroscopy system allows scanning of rodents up to 600 grams with an in-plane resolution on the order of 50 microns. At 50% duty cycle, the maximum gradient strength is 68 mT/m and the time necessary to achieve this maximum strength is 110 microseconds, for a gradient slew rate of 618 mT/m/msec. The gradients are linear over 8 cm. The bore diameter is 12 cm. The system has four receivers and a variety of coils to image mice, rats, and marmosets. Second order shim

coils are installed to enhance the homogeneity of the magnetic field, and the magnet is actively shielded. The system is equipped with a rodent isoflurane gas anesthesia system and physiologic monitoring system that allows image gating. It has broadband capability allowing a variety of nuclei to be imaged including 1H, 31P, 19F and 13C. T1 and T2 anatomical scans are possible as is the creation of T1, T2 and T2* maps. The system is also capable of performing functional MRI (EPI), diffusion and diffusion tensor imaging, localized spectroscopy (STEAM and PRESS) as well as chemical-shift imaging, and perfusion imaging with Gd-based contrast agents. These specifications allow investigators to visualize and quantify a variety of moieties and processes including metabolites (NMR spectroscopy), anatomical structures, tumor morphology, blood flow/vessels, fiber pathways, drug effects, brain activity, and heart motion. Adjacent to the small animal MRI system is a Carbon-13 Polarizer (Hypersense, Oxford Instruments) that is able to polarize a 4mg C-13-containing sample dissolved in 100-200 microliters of solvent to levels of 20% to 30% in 2-4 hours. Dissolution in water or methanol produces a liquid volume of 4-5 ml, which can be studied in vitro or in vivo. This provides gains in sensitivity for a variety of biologically-relevant samples, including metabolites and vitamins.

We have a first generation microCT scanner and a large field-of-view MicroCAT-2 from Siemens. It is equipped with a large field-of-view detector, thus allowing high resolution scanning (18 micron) of rats up to 300 grams. The system is equipped with a rodent isoflurane gas anesthesia system and physiologic monitoring system which allows image gating. There is also the first Inveon microCT/microPET hybrid scanner from Siemens. This first hybrid scanner coupled with our own proprietary cell-selective imaging and contrast agents affords our investigators unique disease detection and evaluation technologies which can only be provided at UW. This new scanner provides unsurpassed PET sensitivity (>10%), resolution (1.2 mm), and axial field of view (12cm) as well as 15-micron spatial CT resolution and real time image reconstruction. This system is equipped with a built in BioVet physiologic monitoring system, which permits gated image acquisition and animal monitoring, integrated isoflurane anesthesia system, and internal infrared video camera which allows visual monitoring of animals during scan acquisition.

The IVIS Spectrum (Caliper Life Sciences) is capable of both bioluminescence and fluorescence scanning and is used for non-invasive longitudinal monitoring of cancer progression, metastatic cell trafficking, and gene expression patterns in living animals. An optimized set of high efficiency filters and spectral un-mixing algorithms affords noninvasive imaging of bioluminescent and fluorescent reporters across the blue to near infrared wavelength region. It also offers single-view 3D tomography for both fluorescent and bioluminescent reporters that can be analyzed in an anatomical context using a digital mouse atlas. The Spectrum has the capability to use either trans-illumination (from the bottom) or epi-illumination (from the top) to illuminate in vivo fluorescent sources. 3D diffuse fluorescence tomography can be performed to determine source localization and concentration using the combination of structured light and trans illumination fluorescent images. The instrument is equipped with 10 narrow band excitation filters (30nm bandwidth) and 18 narrow band emission filters (20nm bandwidth) that assist in significantly reducing autofluorescence by the spectral scanning of filters and the use of spectral unmixing algorithms. In addition, the spectral unmixing tools allow the researcher to separate signals from multiple fluorescent reporters within the same animal.

The UW small animal imaging lab was one of the first in the US to obtain the new Fluobeam™ (Fluoptics, Paris) hand-held imaging system, which detects in vivo near infrared fluorescence in 2D at 800 nm. The system is equipped with a laser able to excite the near infrared fluorophores (NIR), associated with a crown of LEDs allowing one to work under white light in open space with a direct access to the animal. Focused on cancer surgery improvement, this technology will afford oncology surgeons a radically new efficiency in tumor resection. Of course the success of this concept will depend in large part on the ability of the optical agent to selectively localize in the tumor prior to surgery. Several UW investigators are currently developing tumor-specific NIR optical probes for intravenous administration that may potentially afford real-time intraoperative tumor margin illumination. Intraoperative margin illumination, for example, could have significant impact in glioma resection and rapidly determining lymph node involvement during breast cancer resection. This newly introduced unit is designed to be used in a surgical suite and therefore offers rapid clinical translation potential.

Molecular Imaging and Nanotechnology: The University of Wisconsin In vivo Cellular and Molecular Imaging Center (WICMIC) was established to lead, coordinate, and facilitate multi-disciplinary research

focused on discovering, developing and translating molecular imaging technologies into clinical practice. WICMIC is focused on developing molecular imaging strategies as tools for guiding personalized treatment decisions. We aim to achieve this by exploring the uniqueness of molecular imaging to explain the biological basis that leads to variable treatment response and improve clinical outcomes by selecting appropriate treatments. The WICMIC efforts are integrated with the existing translational research efforts within the UW Carbone Cancer Center and its resources. We have developed a strategic plan for increased integration of physical, biological, chemical, biochemical, pharmacological, and engineering resources across the UW campus with a molecular imaging focus. This integration is summarized with the creation of a specialized Molecular Imaging Technology and Agent Development resource that provides a “pathway” resource for fast and efficient development of molecular imaging agents from its discovery to clinical use, as well as Molecular Imaging Agent Production and Molecular Imaging Informatics Resources, which provide the necessary molecular imaging agents and informatics infrastructure to support the WICMIC projects. We have developed a strategic plan for increased engagement of scientists from disciplines that are traditionally not involved in molecular imaging by creating a Molecular Imaging Career Development program, comprising of multi-disciplinary training and supervision.

Tumor Ablation: The WIMR Imaging Facility Tumor Ablation Laboratory is housed in the same hallway as the animal operation, PET/CT, CT, MRI, C-arm and angiography suites. The space is devoted to tumor ablation laboratory research and contains the following clinical ablation equipment: a RITA Model 1500 generator, numerous radiofrequency electrodes, ground pads and other disposables, two Valleylab (Boulder, CO) Cooltip™ generators, cooled-water pumps, numerous electrodes and ground pads; an Endocare cryosurgical unit with eight cryoprobes and eight thermosensor ports (Endocare, Inc., Irvine, CA), and numerous cryoprobes. The laboratory also houses two microwave generators capable of delivering up to 300 W at 2.45 GHz, an Agilent 8753E vector network analyzer, space for small-scale equipment fabrication, data collection and analysis, microwave test and measurement equipment such as power meters, oscilloscopes and power supplies, as well as supporting hardware. The Clinical Ablation Program has all the clinical imaging resources needed plus a dedicated nurse and assistant for clinical cases; they have performed >1000 ablation cases.

Machine Shop: The medical physics department has its own machine shop with drill presses, lathes, milling machines (including a CNC M3X-2V programmable milling machine) and cutting tools. It is a modern, 650 ft2, fully equipped facility, staffed by an experienced machinist/instrument maker.

Library: The Medical Physics Department has a small library in which it keeps special reports and publications of interest to medical physics and health physics, bound PhD theses, a limited journal collection, and specialized books as well as reserve books used in courses. An annual budget is allocated to purchase new books, allowing the department to be very responsive to special research and course needs of faculty and students. For research purposes, much more extensive use is given to the University of Wisconsin’s ‘electronic journal collection’ and to individual faculty member’s access to archived electronic journals. The university maintains a license to many search engines, including Medline, Pubmed, and Web of Science, readily permitting thorough literature searches on most topics. The Ebling Library, housed within the UW School of Medicine and Public Health, is adjacent to WIMR. Ebling is one of over 40 libraries on the UW-Madison campus. The Ebling Library web page is a comprehensive access point to health sciences resources. It includes links to electronic journals, books, and databases, as well as everything needed to know to use library services.

The University of Wisconsin Medical Radiation Research Center (UWMRRC) occupies approximately 8,000 square feet in the basement level of WIMR. The Center is completely self-funded through its AAPM-accredited calibration services, with private industry-funded research contracts supplementing its research program. The UWMRRC employs 12 professional staff and 12-15 research assistants. In addition to its AAPM accreditation, the UWMRRC has been accredited by the American Association for Laboratory Accreditation (A2LA) to ISO/IEC 17025:2005 and ANSI Z540-1-1994 standards since 2001.

The UWMRRC maintains a large inventory of equipment and other facilities available to support the laboratory’s and the department’s research and educational program. This includes investments in machine shop, computational hardware upgrades in the department, and investment in a state of the art non-clinical

educational Treatment Planning Laboratory. The UWMRRC maintains a number of NIST-traceable external beam irradiators, including Cobalt-60, Cs-137, constant potential x-ray and high frequency diagnostic radiographic units, as well as access to clinical linear accelerators at the UW Hospitals and Clinics and other facilities.

The lab has recently installed a Varian EX linac with cone beam CT capabilities and connection to an eclipse treatment planning system. This facility will be used for research, graduate student training and classroom laboratories. The normal limitations involved with a clinical machine are not involved here, since no patients will be treated on this machine. Thus, a research project can be set up and remain until completed, enabling work during the daytime hours.

The UWMRRC maintains a full range of brachytherapy sources and well-type ionization chambers for calibration, including some primary calibration equipment, such as the variable aperture free air chamber (VAFAC), the Attix Variable Length Free-air Chamber, and a cryogenic calorimeter.

The UWMRRC has developed a parallel processing computer cluster to provide mathematical modeling for the laboratory’s research projects. We have made the underlying infrastructure available to the rest of the Medical Physics department to enable development of individual clusters. Computing resources include an 82 node (328 cpu) parallel processing cluster running MCNP5, EGSnrc, and Penelope Monte Carlo codes. Additionally, the lab has 4 design/simulation computers running Solidworks CAD, MatLab, Comsol Multiphysics, and Eagle PCB.

Since its inception, the laboratory has maintained a complete and extensive Thermoluminescent Dosimetry (TLD) laboratory. Currently this separate 380 ft2 lab has 5 Fischer Scientific annealing ovens, and 4 Harshaw TLD read out devices, all computer controlled. The UWMRRC also has radiochromic film technology utilizing a wide variety of scanners for use with virtually any clinical application.

Radiation Therapy Physics: The Radiation Oncology department located in the hospital directly adjacent to the UWMRRC (Cal Lab) is well equipped with radiation physics equipment, including ionization chambers, water bath scanners, film dosimetry, and treatment planning capabilities. The radiation therapy physics group also has separate laboratory facilities within WIMR. These include a 1200 ft2 lab split, with the UWMRRC occupying one half and the radiation therapy physics group the other half, as well as a 280 ft2 brathytherapy vault within the secured hallway of the UWMRRC. The lab has radiation detection equipment, a Scanditronix RFA 300 3-dimensional dosimetry scanning system, and a Washington University 4D QA Phantom. In addition, the lab is developing capabilities for optical scanning equipment through Dr. Kissick’s work with oncologists studying oxygen dynamics in tumors. The Brachytherapy vault houses radioactive sources, detectors, and a robotics delivery system currently under development.

Treatment facilities include one Varian TrueBeam with On-board conebeam CT imaging and respiratory gated treatment delivery, one Clinac 21ix with a 120 MLC and the OBI system with Cone Beam CT and respiratory gated treatment delivery, a Clinac 600C with 120 leaf MLC, two Tomotherapy Hi-Art machines and simulators. An additional Clinac 2100 C with a 120 MLC is located at the UW East side clinic. Treatment planning is performed using the state of the art Pinnacle and Eclipse treatment planning software and hardware. Tomotherapy optimization is done on the Tomo cluster. Additional equipment of note includes a GE PET/CT scanner and two brachytherapy suites, each with a Nucleotron HDR remote after loader. The Department has extensive experience with Tomotherapy, given its early and continued participation in the development and testing of this treatment system at the University of Wisconsin. The Physics section is equipped with beam calibration; monitoring and patient dosimetry verification tools for stationary as well as IMRT based treatment deliveries.

Due to the specific clinical translational activity and unique needs, The Department of Human Oncology has its own team of clinical research coordinators for both translational and clinical trials that coordinate with the Carbone Cancer Center. Specifically, the Department of Human Oncology currently employs one regulatory/data manager, two full time research nurses, one full time grants manager and a full time editor. The Department coordinates all protocols through this team, aiding investigators in grant and proposal writing, protocol writing, oversight submission (IRB, FDA, and others), and data and safety monitoring.

Treatment Planning System: A unique facility in WIMR is a Research Radiation Treatment Planning (RRTP) laboratory, housed outside the clinical radiation oncology facility. The RRPT lab is equipped with Pinnacle Version 9.6 Sun Blade and 4 remote desktop licenses; Varian Eclipse Version 11 on 3 workstations; and a set of TomoTherapy – GPU computer workstations. The facility is used for research and training purposes. The lab is at the focus of a new graduate course on radiation treatment planning, delivered to Medical Physics and other basic science students.

Cardiovascular Imaging Group: The cardiovascular medical physics imaging group occupies a 550 square foot lead-shielded procedure and control room, intended for x-ray fluoroscopic / angiographic equipment. The lab is equipped with 480V 3-phase power for a high voltage generator, a chilled water supply for cooling electronics, and medical gases. The lab currently houses the Scanning-Beam Digital X-ray system (SBDX, Triple Ring Technologies, Inc.), an x-ray fluoroscopic technology that uses inverse-geometry beam scanning for dose reduction and real-time tomosynthesis in cardiac procedures. The SBDX system consists of a large area x-ray source with electromagnetically deflected focal spot, a 100 x 100 hole collimator, and a high speed CdTe photon-counting x-ray detector (781,250 frame/sec). The source and detector are mounted on a mobile C-arm gantry with on-board high voltage generator. The room has an x-ray table with adjustable panning and height, and table encoders to enable reproducible experimental setups. The control room houses two computer workstations for controlling the SBDX x-ray source and detector, FPGA-based hardware (HiTech Global Inc.) for real-time data capture, a high speed 30 TB disk array (Conduant Corp.) for real time data storage, and two workstations for offline analysis.

The University of Wisconsin Carbone Cancer Center (UWCCC) is one of only 41 cancer centers in the United States designated as "comprehensive" by the National Cancer Institute (NCI) - and the only one in Wisconsin. The UWCCC is an integral part of the UW Medical School, uniting more than 200 physicians and scientists who work together in translating discoveries from research laboratories into new treatments that benefit cancer patients. The Cancer Center's patient care and clinical research is conducted in alliance with UW Hospital and Clinics, in which almost 15,000 patients are seen annually for diagnosis, treatment, follow-up care or consultations. The UWCCC excels in basic laboratory and clinical cancer research, cancer prevention and control programs, cancer information services for the public, community outreach, and education.

The UW Carbone Cancer Center members participate in and have access to Scientific Programs, Disease-Oriented Working Groups/Clinical Research Groups, Shared Resources, and translational support services such as the Office of Translational Research Services and the Translational Imaging Research Working Group.

The UW Institute for Clinical and Translational Research (UW-ICTR) is an NCRR/NIH-funded resource center with the goal of creating an environment that transforms research into a continuum from investigation through discovery and to translation into real-life community practice, thereby linking even the most basic research to practical improvements in human health. UW ICTR is part of a national consortium of research institutes funded through NIH Clinical and Translational Science Awards (CTSA) through the National Center for Advancing Translational Sciences. There are 60 CTSA sites nationwide with the common goal of accelerating discoveries toward better health. More than 2000 investigators, staff, and community researchers are members of UW ICTR. Members receive biostatistics and biomedical informatics consultations, scientific editing, and community engagement and research services, as well as access to the Clinical Research Unit at UW Hospital and Clinics, discounted laboratory and imaging services, animal care, assay, and other laboratory support.

UW-ICTR is headquartered within the UW School of Medicine and Public Health and collaborates with its partner Marshfield Clinic and numerous other member sites across Wisconsin. The ICTR has major funding from a NCRR/NIH Clinical and Translational Science Award.

The Laboratory for Optical and Computational Instrumentation (LOCI) is equipped with an extensive range of high-performance microscopes, including a confocal laser scanning microscope, several 4D DIC microscopes, and conventional and fluorescent dissecting microscopes. Significant imaging instrumentation includes two complete laser scanning multiphoton systems, a swept-field confocal, spectral detector with 32

channel PMT, a 16 channel combined spectral/lifetime imaging system, and a time-correlated single photon lifetime imaging system. In addition, extensive molecular biology facilities are available in the Molecular Biology Department. These facilities include incubators, microinjection apparatus, centrifuges, PCR machines, and other standard molecular biology equipment. LOCI is a federally funded collaborative biophotonics instrumentation laboratory administered by the Laboratory of Molecular Biology and the Graduate School at the University of Wisconsin-Madison. The mission of LOCI is to develop advanced optical and computational techniques for imaging and experimentally manipulating living specimens. New and improved imaging instrumentation and optical-based experimental techniques are being developed. These projects are driven by demands arising from the scientific studies of external collaborators and the LOCI principal investigators and opportunities that arise with the emergence of new technology. Instrumentation development is undertaken in a form that is both accessible and beneficial to the scientific community. LOCI is actively developing new multiphoton-based instrumentation for intravital imaging, deeper imaging and simultaneous collection of additional dimensions such as spectra, lifetime and polarization. Education and outreach efforts related to live cell imaging are also an important component of the LOCI mission.

Winsconsin Institutes for Discovery is a visionary public-private partnership that is creating two world-class research institutes. Its partners include donors John and Tashia Morgridge, the state of Wisconsin, the University of Wisconsin, and the Wisconsin Alumni Research Foundation (WARF).

The Wisconsin Institutes for Discovery facility, which opened in December 2010, houses twin interdisciplinary research institutes: the Morgridge Institute for Research, a private, nonprofit research institute dedicated to improving human health by accelerating scientific discovery to patient delivery; and the public Wisconsin Institute for Discovery, which is part of UW–Madison organized under its Graduate School. The state-of-the-art facility brings together scientists and researchers from a broad spectrum of disciplines, such as the arts, humanities, social sciences, education, business and law. It also includes extensive public spaces in its Town Center intended to promote dialogue as a fertile crossroads for ideas among diverse parts of UW–Madison and the larger community.

The key objectives of the public-private partnership are to: Foster new approaches to biological and medical programs at the convergence of biotechnology,

information technology and nanotechnology; Create the potential for a fundamental transformation of human biology and medicine; Provide cutting-edge scientific advances for clinical application and translation in the UW–Madison

Medical School's new Wisconsin Institutes for Medical Research; Build on the university's Cluster Hiring Initiative by engaging and supporting the more than 100

multidisciplinary faculty hired as part of that initiative; Establish educational components that will integrate cross-disciplinary science into K-12, undergraduate

and graduate education; and Facilitate the invention of technologies that can be transferred to the marketplace and create jobs.

These programs synergistically benefit from the shared resources of animal care, imaging science and proteomics developed as part of the first tower. Taken together, the two towers of the Wisconsin Institutes for Medical Research represent an entirely new mode of scientific investigation for the University of Wisconsin School of Medicine and Public Health and related faculty. The Waisman Center for Brain Imaging and Behavior is adjacent to University of Wisconsin Hospital and Clinics. This research facility includes a 3 Tesla MRI scanner (GE SIGNA), a whole body PET scanner (GE Advance), a Concord Microsystems microPET-P4 system, a 7MeV Tandem Accelerator (National Electrostatics Corporation 9SDH-2) for short-life radionuclide production, a radiochemistry laboratory, and a 256 channel EEG system (Electric Geodesics, Inc.). The laboratory is a campus-wide research resource and the primary focus is on advanced neuroimaging research.

10.2 Administrative and Financial Support

The University of Wisconsin Graduate School provides $2,500 annually for each predoctoral trainee to help off-set the short-fall in the tuition coverage resulting from the current NIH tuition payment policy (the difference

between that allowed by this training grant and that charged by the University – more than $125,000 over the past five years.) Support provided by the Graduate School to the department that also directly benefits this training program includes: $70,000 to $80,000 annual support to help cover graduate student recruitment efforts. This includes 2 to 4 “Advanced Opportunity Fellowships” awarded each year to incoming Medical Physics minority graduate students; travel support to enable faculty to attend meetings targeting undergraduate minority students; grants to faculty in an annual “fall competition”, used to support graduate assistants. The Graduate School also returns of a portion of the F&A costs collected from research grants to provide capital equipment to enhance the research infrastructure in the department.

The School of Medicine and Public Health will continue to pay 1/3 of the cost of for an administrator to assist in managing this training grant (currently about $20,000 annually).

The Medical Physics Department supplements predoctoral trainee stipends for those trainees who are at the dissertator level. Currently this supplementation is approximately $350 per month, and makes their total compensation equal to that of the Research Assistant dissertators in the department. The department also routinely supplements post-doctoral trainee stipends a few thousand dollars above the NRSA levels in order to attract top quality applicants who are heavily recruited by industry. The Medical Physics Department will continue financial support of this training grant by providing additional support for administrative assistance, computer and network systems management, 10% salary support for the Program Director and 5% salary support for each mentor with a trainee funded by this grant.

(See Letters of Support from the Graduate School, the School of Medicine and Public Health and the Chair of the Medical Physics Department).