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  • 2014 SNMMI Highlights Lecture: Cardiovascular Imaging

    From the Newsline Editor: The Highlights Lecture, presented at

    the closing session of each SNMMI Annual Meeting, was origi-

    nated and presented for more than 33 years by Henry N. Wagner,

    Jr., MD. Beginning in 2010, the duties of summarizing selected

    significant presentations at the meeting were divided annually

    among 4 distinguished nuclear and molecular medicine subject

    matter experts. The 2014 Highlights Lectures were delivered on

    June 11 at the SNMMI Annual Meeting in St. Louis, MO. The

    neuroscience presentation was included in the September Newsline

    issue; others will appear in later issues. In this issue we feature the

    lecture by Vasken Dilsizian, MD, who spoke on highlights in

    cardiovascular imaging. Note that in the following presentation

    summary, numerals in brackets represent abstract numbers as

    published in The Journal of Nuclear Medicine (2014;55[suppl 1]).

    It is an honor and privilege to summarize the highlights ofthe cardiovascular presentations at the 61st Annual Meet-ing of the SNMMI. This is a truly international meeting,

    with abstracts coming from across the globe. North Amer-ican presenters led in the number of presentations, followedby colleagues from Asia and Europe. The 3 leading Europeancountries represented were Germany, The Netherlands, andFrance. Asian countries were led by presenters from Japan.One trend that we noted in the Cardiovascular Council wasthat the number of clinical presentations was almost 3 timeshigher than that of basic science presentations. We alsonoted a trend toward a transition from foci on myocardialperfusion imaging to other areas of molecular imaging. PETinstrumentation continues to grow as a focus in abstractsubmissions, despite the fact that we still have many moreSPECT than PET cameras (;12,000 and 2,000, respectively)in the clinical setting in the United States. This interest inPET and associated hybrid modalities most likely reflectsthe direction of future research in cardiovascular imaging.

    PET and Myocardial Perfusion

    One such area of increased interest in cardiac PET is myo-cardial perfusion. Two PET agents, 82Rb and 13N-ammonia,are now U.S. Food and Drug Administration (FDA) andCenters for Medicare & Medicaid approved for cardiacimaging. The advantages of PET over SPECT in this settinginclude higher sensitivity and spatial resolution, reducedartifacts as a result of high photon energy, robust andwell-validated attenuation correction, and, of course, theability to quantify absolute myocardial blood flow (MBF)and coronary flow reserve (CFR). Renaud et al. from theNational Cardiac PET Centre at the University of OttawaHeart Institute (ON, Canada) reported on Rubidium-82PET versus thallium-201 SPECT for detection of coronaryartery disease in the Alternative Radiopharmaceutical forMyocardial Imaging (ARMI) trial [241]. These research-ers showed that when using an automatic scoring programwith comparisons to a normal database, 82Rb PET sensitiv-ity and specificity were 83% and 94%, respectively, for

    individuals with $50% stenosis and90% and 93%, respectively, for$70% stenosis. Corresponding 201TlSPECT values were lower, with sen-sitivity and specificity of 56% and85%, respectively, for individualswith $50% stenosis and 57% and83%, respectively, for$70% stenosis.

    Another area that has been ad-dressed with frequency in the recentliterature is that of the added prog-nostic value of absolute MBF andCFR as assessed with either 82Rb or 13N-ammonia PET. In2011, Ziadi et al., also from the group at the University ofOttawa Heart Institute, documented the added value of tra-ditional summed stress scores when patients were furtherstratified according to CFR (J Am Coll Cardiol. 2011;58:740708).

    It is my pleasure to announce that the winner of theCardiovascular Council Clinical Young Investigator Awardis Nishant Shah, MD, who, with colleagues from theBrigham and Womens Hospital (Boston, MA), reportedon Prognostic value of PET-derived CFR for survival inpatients with dialysis-dependent end-stage renal disease(ESRD) [26]. In this study, 196 patients with dialysis-dependent ESRD underwent 82Rb or 13N-ammonia rest/stress myocardial perfusion PET for evaluation of knownor suspected coronary artery disease (CAD). On the basis ofresulting CFR values, patients were classified as abnormal,normal, or intermediate. Data analysis at 3 years showed thatCFR as a continuous variable was independently associatedwith survival. Those with preserved flow reserve had muchhigher survival rates than those with abnormal flow reserve.

    Danad et al. from the VU University Medical Center,(Amsterdam, The Netherlands), Turku University Hospital(Finland), and Uppsala University (Sweden) reported onQuantitative cardiac PET imaging for diagnoses of hemo-dynamic significant epicardial disease [24]. These inves-tigators posed a key question: Do we really need to have bothstress and rest images, or can we simply look at absoluteblood flow in the hyperemic state with PET, similar to the con-cept of stress-only imaging with SPECT? Can this approachbe sufficient for detecting flow-limiting CAD? This was awell-conducted study in which optimal cutoff values of 15O-water PETdetermined hyperemic MBF and CFR were assessedin a large clinical cohort of 330 patients (990 vascular terri-tories) as a means of detecting flow-limiting coronary arterystenosis, using fractional flow reserve (FFR) as a compara-tive gold standard. The researchers showed that hyperemicMBF on PETwas more accurate than CFR in detecting flow-limiting stenosis, in both per-patient and per-vessel analyses.More important, among all patients with FFR-defined function-ally limiting stenosis, only 13% were missed by quantitative

    Vasken Dilsizian, MD

    Newsline 9N

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  • hyperemic MBF assessment with PET. 15O-water PET hy-peremic MBF .2.3 mL/g/min was found to exclude thepresence of flow-limiting stenosis with a high negative pre-dictive value (90% per patient and 95% per vessel).

    Although the identification of these and similar PET-derived cutoff values is encouraging, uncertainty remains asto how these thresholds for hyperemic flow assessed with non-FDA approved 15O-water compare to other FDA-approvedflow tracers, such as 13N-ammonia and 82Rb, for evaluationof diagnostic accuracy in CAD detection. It is important toduplicate these findings with FDA-approved tracers.

    Molecular Imaging: Beyond Perfusion

    Many new and exciting areas of cardiac molecular imagingbeyond perfusion were addressed at this meeting, includingbut not limited to vascular imaging, myocardial innervation,cardiac sarcoidosis, angiogenesis, atherosclerotic plaque im-aging, and thrombus imaging. Very high quality presenta-tions were made in each of these categories. Although thelimitations of the lecture format preclude citation of each ofthese meritorious presentations, a select few will serve asexamples of new directions in research and clinical practice.

    One such example also allows me to announce the winnerof the Cardiovascular Council Basic Young Investigator Award:Reza Golestani, MD, PhD. Golestani, from Yale University(New Haven, CT), with colleagues from Yale and LantheusMedical Imaging (North Billerica, CT), reported on Matrixmetalloproteinase (MMP) imaging to predict aortic aneurysmrupture [25]. These researchers created an angiotensin 2induced abdominal aortic aneurysm (AAA) model in miceand explored the utility of MMP imaging in predicting AAAand rupture (Fig. 1).

    Angiogenesis can also serve as a target for vascular im-aging. Shi et al. from the University of Wisconsin (Madison)reported on PETof AAAwith a 64Cu-labeled Fab fragment[465]. In a murine model of AAA, 64Cu-NOTA-TRC105-Fabwas shown to clear rapidly from the blood with very lowintestinal uptake, making it a suitable tracer for identifyingangiogenesis in the aortic wall (Fig. 2). The researchersalso performed a blocking study to verify that these findingswere specific.

    PET/MR imaging in large-vessel vasculitis is becom-ing much more clinically relevant. Einspieler et al. fromthe Technische Universitat Munchen (Germany) and theRheinische Friedrich-Wilhelms-Universitat (Bonn, Germany)reported on Imaging large-vessel vasculitis with fully in-tegrated PET/MR: a pilot study [185]. The research in-cluded 12 patients with histories of large-vessel vasculitis(2 Takayasu arteritis, 10 giant cell arteritis) who underwentPET/MR imaging after injection of 18F-FDG (Figs. 3 and4). Subsequent analyses demonstrated a much stronger andmore significant correlation between C-reactive proteinand the number of vessel segments affected by inflamma-tion as seen on hybrid PET/MR than seen on either PET orcontrast-enhanced MR angiography alone. Quantitativeevaluation revealed significantly higher standardized uptake

    values (SUVs) in patients with vasculitis than in a matchedreference group.

    Another area of research excitement and clinical rel-evance is that of cardiac innervation. Heart failure is charac-terized by increased sympathetic drive to the myocardium.Metaiodobenzylguanidine (MIBG) and hydroxyephedrine

    FIGURE 1. Matrix metalloproteinase (MMP) imaging to predictaortic aneurysm rupture in a mouse model. Uptake of the noveltracer in the suprarenal aorta at 1 week was significantly higherin animals with aortic aneurysm atherosclerosis (AAA)/rupturethan in those without AAA. In mice with AAA, tracer uptake at 4weeks was correlated with MMP CD68 expression. No corre-lation was found between uptake and AAA size.

    FIGURE 2. Angiogenesis as a target for vascular imaging.A: Aortic aneurysm (top) in a mouse model of atheroscleros

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