Volume 8, Issue 2 2011 . 2 pet center of excellence newsletter Potential Clinical Applications of PET/MRI: On the Frontier of Structural-FunctionalMolecular Imaging President’s Report By Drew A. Torigian, MD, MA, University of Pennsylvania School of Medicine, Philadelphia, Pa. George M. Segall, MD Nuclear Medicine and Molecular Imaging in 2020 The importance of hybrid imaging and the emergence of molecular imaging have brought the specialty of nuclear medicine to a crossroads. It is time to reinvent ourselves. By 2020, we will need a cadre of physicians with robust training in anatomic and molecular imaging to do the research that will advance the field as well as teach future professionals. In the beginning, these future physicians will be dual-trained and dual-certified in nuclear medicine and radiology following traditional (separate) pathways. The 2011 report of the ACR-SNM Task Force on Nuclear Medicine Training recommended fully integrated training programs for future physicians. One pathway would consist of a clinical year followed by three years of radiology and two years of nuclear medicine. This is the pathway envisioned for physicians interested in research and academic careers. A second integrated pathway would include 16 months of nuclear medicine training within a four year radiology residency. This is the pathway envisioned for clinicians in large practices who will practice the full scope of molecular imaging, including using new radiotracers expected to be approved, hybrid imaging and non-nuclear technologies. Graduates of these integrated pathways will be eligible for certification by ABNM as well as ABR. Details of how these integrated training programs will work are the focus of a second ACR-SNM task force. It remains to be seen if these future professionals will identify themselves primarily as radiologists or nuclear medicine physicians, or will recognize themselves as molecular imag(Continued on page 6. See President.) PET/MRI instruments have recently been assembled for human use and may have diagnostic performance superior to that of PET/CT for particular clinical and research applications.1-8 This stems from the major strengths of MRI relative to CT, including superior soft tissue contrast resolution, multiplanar imaging, and functional imaging capability through specialized techniques such as diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), perfusion weighted imaging (PWI), MR elastography, and MR spectroscopy (MRS).9 In addition, the lack of ionizing radiation from MRI is highly appealing, particularly when pediatric or young adult patients are to be imaged. When combined with PET, MRI can also provide the means for partial volume correction of standardized uptake values for accurate disease quantification, improve anatomical localization of sites of radiotracer uptake, improve diagnostic performance, and provide for comprehensive regional and global structural-functional-molecular assessment of various clinical disorders.1, 10 Oncological Disease In the oncological disease setting, MRI provides useful structural and functional information about malignancy that is complementary to the molecular information provided by PET.1, 6, 11-15 In particular, MRI provides high resolution structural definition of tumor volume and extent of local disease In this Issue By George M. Segall, MD June 2009-June 2011 PCOE President (i.e., T staging). This is particularly useful in the evaluation of primary tumors that originate from anatomical sites that are suboptimally evaluated on CT (e.g., brain, head and neck, spinal cord, pelvic organs, breasts, musculoskeletal system), as PET provides improved molecular detection and characterization of lymph nodes as benign or malignant (i.e., N staging).12, 16-17 For example, PET/MRI has recently been shown to be feasible for use in patients with head and neck cancers and provided greater spatial resolution and image contrast compared to PET/CT.18 With regard to detection of distant metastases (i.e., M staging) in organs such as liver and bone marrow, PET and MRI are also complementary to varying degrees depending on the underlying tumor biology, the size of metastases, and the specific anatomical sites involved.19-21 Furthermore, the high spatial resolution data available from MRI allow for partial volume correction of PET data, which is essential for accurate disease quantification and has implications for accurate lesion characterization and response assessment.22-23 Advanced functional MRI techniques such as DWI and dynamic contrast enhanced (DCE) MRI used with PET can further enhance the detection and characterization of malignant lesions for prognosis assessment, biopsy and pretreatment planning, patient selection for certain therapeutic agents, and response prediction and assessment.1, 21, 24-25 (Continued on page 2. See PET/MRI.) View You Can Use 3 PET in the News 4 SNM Speaks Out on PET 5 New PCOE President5 (PET/MRI. Continued from page 1.) For example, addition of DWI to standard MRI technique provided detection of an additional 20 percent of metastatic melanoma lesions, with most lesions involving the bone marrow, liver, subcutaneous tissues, and peritoneum.26 PET/MRI mammography can potentially lead to an improvement in diagnostic performance for the detection, characterization and treatment response assessment of breast cancer.11 Hepatobiliary MRI contrast agents can be used to improve detection of metastatic disease to the liver, and may be useful in the pretransplant evaluation of patients with hepatocellular carcinoma.19, 27 As such, PET/MRI can potentially be useful to optimize the management of patients with various types of cancer before, during and after therapeutic intervention. Neurological Disease PET/MRI has the potential to provide integrated multidimensional and multiparametric structural and functional assessment of the brain in the setting of various neurodegenerative, ischemic/vascular, neuro-oncological, traumatic, psychiatric, behavioral, seizure-related, and age-related conditions.15, 28-29 This is, in part, related to the wide variety of available PET radiotracers that can be used to probe different biological properties of brain tissue in conjunction with the variety of available functional MRI techniques such as DWI, DTI, PWI, blood oxygenation level dependent (BOLD) functional MRI (fMRI), and MRS that provide complementary information.1, 5, 30 In addition, high degrees of spatial and temporal coregistration of PET and MRI datasets are feasible, allowing for evaluation of biologically relevant processes of interest such as metabolism, perfusion, oxygen consumption, receptor expression, and function in even the smallest of neuro-anatomical structures.31-32 This is particularly relevant in neuro-oncology, where accurate alignment of structural and functional information is essential for purposes of biopsy and treatment planning. Again, MRI data allow for partial volume correction of PET emission data, which is essential for accurate PET-based quantification of disease.10, 33 Coregistered PET and MRI are useful for the detection of seizure foci prior to surgery, and also for the identification of metabolic activity, neurotransmitter concentration, and enzyme expression in small structures of the brain.34-35 DWI with PET measurements of oxygen consumption and perfusion can be used for differentiation of intravascular perfusion, tissue blood flow, penumbra and irreversible tissue damage in ischemic/vascular disease.5 DWI can also be applied with PET to detect, characterize and monitor changes in brain tumors following therapeutic intervention.15 DTI, which provides exquisite detail of the white matter bundles, can be particularly useful for pretreatment planning of brain tumors by separation of peritumoral edema from infiltrative tumor, pretreatment assessment of white matter tract involvement by tumor, and intraoperative visualization and localization of major white matter tracts to decrease the chance of injury to normal tissues.36-37 PWI with PET may be useful to assess ischemic/ vascular and neoplastic brain disorders. BOLD fMRI can be used to preoperatively map functional cerebral cortex and to identify eloquent areas of the cerebral cortex in relation to brain neoplasms, potentially reducing the time of surgery and minimizing intraoperative cortical stimulation methods used during surgical resection.38-39 It can also be used with PET for comparative activation studies, for assessment of 2 PET Center of Excellence Newsletter/2011.2 activation effects upon transmitter release or receptor binding, and for studying the effects of drugs and withdrawal.5 MRS can quantify the type, amount, and location of various metabolites within brain tissue, providing complementary information to PET for evaluation of a variety of disease conditions affecting the brain.1 Cardiovascular Disease PET/MRI has much potential for the clinical assessment of myocardial viability and infarction, ventricular function, cardiomyopathy, myocarditis, cardiac masses, atherosclerosis, and vasculitis. This is in part due to the wide array of available MRI pulse sequences for spin echo (black blood), gradient echo (bright blood), time-of-flight, phase contrast, contrast-enhanced, and time-resolved imaging of structure and function, in conjunction with the wide variety of PET radiotracers that are available to probe molecular processes of interest. For example, myocardial perfusion imaging [11C]-hydroxyephedrine PET can image cardiac innervation in combination with high-resolution structural and wall motion imaging by MRI, which can be useful to delineate cardiac regional innervation and control mechanisms in the setting of dilated cardiomyopathy or following cardiac transplantation.40 In addition, respiratory-gated and ECG-gated MRI can also be used to improve cardiac PET quantification by correcting for errors due to the misregistration, the partial volume effect and bulk motion. MRI provides unique insight into the complex anatomy of the heart and surrounding structures such as the pericardium, coronary arteries, and great vessels; allows for accurate measurement of cardiac chambers, wall thickness, wall motion, and vessel diameters; provides quantitative measures of flow in cardiac chambers and vessels; and is useful to assess myocardial perfusion via dynamic perfusion MRI with pharmacological stress testing and to detect and quantify the presence of myocardial fibrosis using delayed post-contrast imaging.41-42 MRI is also useful to show the precise anatomic extent and location of cardiac and pericardiac tumors, and to characterize their gross composition, whereas FDG PET can be used for response assessment purposes.43 Lastly, PET/MRI of the vascular system may be useful for regional and global detection, characterization and quantification of atherosclerotic disease for purposes of risk assessment and drug response assessment, as it can simultaneously provide information about vascular wall thickness, wall inflammation, plaque vulnerability and degree of luminal narrowing.41, 44-45 Musculoskeletal Disease PET/MRI may also play a role in the assessment of non-neoplastic musculoskeletal disorders including infection, diabetic foot, metabolic bone marrow/bone disease, back pain, bone marrow disorders and arthritis, as MRI provides excellent soft tissue contrast for the structural assessment of the bone marrow, muscles, tendons, ligaments, cartilaginous structures and fat.14 For example, FDG PET and MRI have been shown to be synergistic for the detection and characterization of complications of the diabetic foot such as Charcot neuroarthropathy, osteomyelitis, and soft tissue infection.46-47 They are also complementary for the evaluation of various arthritides and for treatment monitoring.14, 48 FDG PET/MRI may also be useful to depict meniscal tears with associated synovitis and can provide for accurate (Continued on page 6. See PET/MRI.) Views You Can Use This 56-year-old man with a history of a reversed gastric bypass had an abdominal CT scan for evaluation of chronic nausea. The scan showed a 6 x 7 cm solid anterior splenic mass. A follow-up MRI confirmed the mass, which did not have clear-cut benign features. A PET/CT scan was performed for further evaluation of the mass and to assess for other lesions. The PET/CT scan showed that FDG uptake in the mass was identical to that in the remainder of the spleen, and no other lesions were identified. Based on this result, it was decided that the mass was likely benign and could be followed. A subsequent CT scan seven months later showed no change in the appearance of the mass. How did the PET/CT help?: Isolated splenic masses are uncommon, but have a high (~80 percent) incidence of malignancy—mostly lymphomas but also metastases and sarcomas. Benign lesions include hemangiomas, hamartomas and granulomas. PET/CT scans have been shown to have a high negative predictive value for evaluating splenic masses. Positive predictive value is lower due to false positive scans that may occur in cases of granulomatous disease1-3. References: (1) Surg Endosc. 2008;22:2009-2012 (2) Surg Endosc. 2008;22:2062-2066 About “Views You Can Use” Advanced Radiology at Medical Arts PET/CT, 410-918-3520, Gabriel Soudry, M.D., Medical Director, 443-777-7492 This case and previous cases can be seen at www.petcases.com www.snm.org/PET 3 PET in the News The international literature on PET and PET/CT continues to grow at a pace that challenges both researchers and clinicians. The media has recognized the value of PET and PET/CT and regularly features advances in research and technology in the news. In each issue, the PET COE Newsletter presents a tomographic slice of the breadth of PET media coverage that appears in publications around the world. Additional news articles can be found online at www.snm.org under “MI: Making a Difference.” Abnormal Metabolic Brain Networks in Tourette Syndrome YahooNews.com http://news.yahoo.com/s/prweb/20110327/bs_prweb/ prweb8235763_1 FDA Asks for Training Program on Lilly’s Amyvid BusinessWeek.com http://www.businessweek.com/ap/financialnews/D9M1MMKG0. htm PET Imaging in Adults With Down Syndrome Feasible, Revealing Medscape.com http://www.medscape.com/viewarticle/739457 NCCN and SNM Pool Expertise to Advance Oncology Imaging Research ImagingEconomics.com http://www.imagingeconomics.com/techedge/2011-03-16_01.asp Preclinical To Clinical: 18F-FLT PET Imaging Moving From Mice To Men MolecularImaging.net http://www.mydigitalpublication.com/article/ Preclinical+To+Clinical%3A+18F-FLT+PET+Imaging+Moving+ From+Mice+To+Men/660914/0/article.html PEM tops whole-body PET for assessing extent of cancer AuntMinnie.com http://www.auntminnie.com/index.aspx?d=1&sec=sup&sub=wom &pag=dis&ItemID=94432 Lung Cancer Imaging in the Era of Molecular Medicine HealthImaging.com http://www.healthimaging.com/index.php?option=com_articles& view=article&id=26653&division=hiit The Mere Sight, Smell of Food Hikes Dopamine Levels in Binge Eaters YahooNews.com http://in.news.yahoo.com/mere-sight-smell-food-hikes-dopaminelevels-binge-20110301-025900-378.html PET/MRI Works for Detecting Head and Neck Tumors AuntMinnie.com http://www.auntminnie.com/index.aspx?d=1&d=1&sec=sup&sub =mol&pag=dis&ItemID=94341&wf=4226 Cellphone Use Tied to Changes in Brain Activity NYTimes.com http://well.blogs.nytimes.com/2011/02/22/cellphone-use-tied-tochanges-in-brain-activity/?smid=tw-nytimeshealth&seid=auto FDG-PET Elucidates Link between Periodontal Disease and Carotid Plaque HealthImaging.com http://www.healthimaging.com/index.php?option=com_articles&a rticle=26368&publication=10&view=portals Why Women Get Anxious at that ‘Time of the Month’ NewScientist.com http://www.newscientist.com/article/dn20122-why-women-getanxious-at-that-time-of-the-month.html 4 PET Center of Excellence Newsletter/2011.2 FDA Clears Nanoparticle for Human Cancer Imaging MolecularImaging.com http://www.molecularimaging.net/index.php?option=com_articles &article=26092&publication=131&view=portals JNM: Preclinical Imaging of Atherosclerosis, Vulnerable Plaque Shows Promise HealthImaging.com http://www.healthimaging.com/index.php?option=com_articles& view=article&id=26872:jnm-preclinical-imaging-of-atherosclerosis-vulnerable-plaque-shows-promise&division=hiit Men with type 2 diabetes are more likely to suffer cardiovascular complications than women EndocrineWeb.com http://www.endocrineweb.com/news/type-2-diabetes/5749-mentype-2-diabetes-are-more-likely-suffer-cardiovascular-complications-wo PET-CT Scan Preferred in the Diagnosis of Mesothelioma Asbestos.com http://www.asbestos.com/news/2011/05/13/pet-ct-scan-preferredin-the-diagnosis-of-mesothelioma/ FEC-PET/CT helps direct radiation to prostate tumors AuntMinnie.com http://www.auntminnie.com/index.aspx?sec=sup&sub=mol&pag= dis&ItemID=95227 C Dots Give Doctors Eyes for Cancer The Cornell Daily Sun http://www.cornellsun.com/section/science/content/2011/05/04/cdots-give-doctors-eyes-cancer Speaks Out on PET Improved Lesion Detection with Time-of-Flight PET Scans Affirmed Greatest Gains Seen in Largest Patients and Shortest Studies For the first time, quantitative—not qualitative—data analysis has demonstrated that time-of-flight (TOF) positron emission tomography (PET) scans can improve cancer detection. Research published in the March issue of The Journal of Nuclear Medicine shows that oncologic TOF fluorodeoxyglucose (FDG) PET scans yielded significant improvements in lesion detection of lung and liver cancers over all contrasts and body mass indexes. Conventional PET scans create images by detecting gamma rays produced by radioisotopes that are injected into the body. Although these conventional scans track where the gamma rays go, they don’t consider the time it takes for each gamma ray to reach the detector. TOF PET scans do take into account the travel time, which results in improved image signal-to-noise. “We aimed to objectively quantify the improvement in lesion detection that can be achieved with whole-body TOF FDG PET,” said Joel S. Karp, one of the authors of the study “Improvement in Lesion Detection with Whole-Body Oncologic Time-of-Flight PET.” “In contrast with previously published studies that reported comparison of TOF and non-TOF PET using simulated data or measured data with physical phantoms, this study used wholebody patient data in order to encompass a large range of realistic activity distributions and patient body types.” To create a lesion-present clinical study while ensuring perfect knowledge of the presence and location of each lesion, 10-mm spheric lesions were added to disease-free bed positions, yielding fused lesion-present studies. These studies appropriately corrected for the body’s attenuation so that the presence or absence of the lesions was similar to that of actual patient studies. TOF PET scans were conducted, and researchers used a numeric observer—as opposed to a human observer—to rapidly detect a large number of conditions. The TOF PET images were compared to conventional PET images (the same data reconstructed without TOF information) to determine improvement in lesion detection as a function of lesion location, scan time, contrast and body mass index. Improved lesion detection was observed in the TOF PET scans, with the greatest gains achieved in the shortest-acquisition studies and in the subjects with a BMI of 30 or more. Also of note—the greatest gain in performance was achieved at the lowest lesion contrast and the smallest gain in performance at the highest lesion contrast. Nuclear medicine technologists and physicians may be able to take advantage of the gain achieved with TOF PET to reduce scanning time, therefore increasing patient comfort and minimizing patient motion. They may also be able to reduce the injected radiopharmaceutical dose, thereby reducing the exposure of patients and health professionals to radiation. Authors of the scientific article, “Improvement in Lesion Detection with Whole-Body Oncologic Time-of-Flight PET” include: Georges El Fakhri and Cathryn M. Trott, Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Harvard Medical School and Massachusetts General Hospital, Boston, Mass.; and Suleman Surti, Joshua Scheuermann and Joel S. Karp, Department of Radiology, University of Pennsylvania, Philadelphia, Pa. Welcome to the New PCOE President The PCOE is pleased to welcome Eric M. Rohren MD, PhD, as its 2011-12 president. Having served most recently as vicepresident and as a longtime member of the center, Rohren brings a great deal of experience to his post. Rohren is section chief of PET/CT and section chief ad interim of Clinical Nuclear Medicine at The University of Texas M. D. Anderson Cancer Center in Houston, Texas. Rohren received his medical degree from Mayo Medical School, and his doctorate degree in Immunology from Mayo Graduate School in Rochester, Minn. He completed residency training in diagnostic radiology and fellowship training in nuclear medicine and PET at Duke University. Rohren is co-chair of the Outreach Committee for SNM and chair of the Nuclear Medicine and Radiologist Working group of the SNM PET Utilization Task Force. He is a director and the secretary treasurer of the American Board of Nuclear Medicine, and is chair of the Education Committee for the ACR’s Nuclear Medicine Commission. He speaks nationally and internationally on clinical applications of PET/CT, and is a frequent instructor on CT and PET/CT interpretation at SNM workshops. Rohren has been reading nuclear medicine, PET, and PET/CT studies since 1997 and has a special interest in the complementary roles of functional and anatomic imaging in the assessment of malignancy. He has worked extensively on the issue of PET/CT reporting, and has developed guidelines for report structure and content through his work with the PET Utilization Task Force. His research activities include non-FDG imaging of cancer, such as the use of 18F-fluorothymidine to assess early treatment response. www.snm.org/PET 5 (President. Continued from page 1.) ers. Will they attend the annual meetings of SNM for continuing education and other professional activities? The answer is yes if SNM grows with the field and meets their needs. As a result of the Bench to Bedside molecular imaging campaign, SNM has been very successful in incorporating molecular imaging throughout the activities of the society. SNM members are now being asked to consider changing the name of the society to the Society of Nuclear Medicine and Molecular Imaging. The proposed name acknowledges the importance of nuclear medicine—including therapy—and indicates who we are and where we are headed. SNM has formed a 2020 Task Force to look at the challenges and opportunities that lie ahead. The task force members include nuclear medicine physicians and radiologists, as well as scientists, pharmacists, technologists and industry representatives. The task force will identify scenarios for 2020, define the actions and identity the uncontrollable external events that would increase the likelihood of each scenario, and develop a plan for SNM that would maximize the likelihood of the best scenario. Looking forward to the future in terms of the PET Center of Excellence, new tracers in development will expand clinical practice beyond FDG and myocardial perfusion imaging. The PET Center of Excellence has focused on PET/CT, but will need to broaden its goals to include PET/MR. The lead article in this newsletter by Drew A. Torigian, MD, MA, on PET/MR is a look to future. We have a lot of work to do to meet the challenges and opportunities that lie ahead. pet center of excellence newsletter The PET Center of Excellence Newsletter is a quarterly member information service published under the direction of the PET COE leadership and SNM. PCOE Newsletter Editorial Board François Bénard, MD [email protected] Hossein Jadvar, MD, PhD, MPH, MBA, Editor [email protected] Gabriel Soudry, MD [email protected] Jian (Michael) Yu, MD [email protected] PCOE Board of Directors Eric M. Rohren, MD, PhD President Hossein Jadvar, MD, PhD, MPH, MBA Vice President Heiko Schoder, MD Secretary/Treasurer George M. Segall, MD Immediate Past President Ryan Niederkohr, MD Lalitha Ramanna, MD (PET/MRI. Continued from page 2.) quantitative assessment of the bone marrow in normal and abnormal states.49, 50 Summary PET/MRI offers the potential for a powerful “one-stop shop” combination of structural, functional and molecular imaging technologies that may be superior to PET/CT, PET alone or MRI alone for certain clinical applications. Future research to evaluate the most appropriate clinical applications of PET/MRI based on diagnostic performance, technical feasibility, practicality, and cost relative to existing diagnostic techniques will therefore be required before standard clinical PET/MRI becomes a reality. For a complete listing of references, please visit http://interactive.snm.org/ index.cfm?PageID=10706. Bennett Greenspan, MD John O. Prior, PhD MD Ruth Tesar, CNMT, RT(N) Frederic H. Fahey, DSc Gary Dillehay, MD SNM Chief Executive Officer Virginia Pappas, CAE Managing Editor Susan Martonik Graphic Designer Laura Mahoney 6 PET Center of Excellence Newsletter/2011.2