Massachusetts General Hospital

MGH Nuclear Medicine and Molecular Imaging (NMMI)

NNMI encompasses Clinical Service, Education and Research and the MGH PET Core. The research areas are organized into three Centers of excellence: PET Radiochemistry Discovery (CPRD); Advanced Radiological Sciences (CARS); and Translational Nuclear Medicine and Molecular Imaging (CTNMI).

The three pillars of MGH NMMI are Clinical, Education and Research.  The clinical operation provides full service nuclear medicine imaging (single photon and PET agents) using SPECT, PET, PET-CT and PET-MR and therapy services.  The Educational program includes a nuclear radiology fellowship and comprehensive graduate student and post doctoral education including an NIH T32 and graduate courses at MIT.  NMMI research encompasses three broad overlapping areas: 1) radiochemistry discovery; 2) imaging science and instrumentation; and 3) preclinical and clinical research. From 2008 to 2012, NMMI has experienced explosive growth in research personnel 25 to 110, research space (~3,000 sq. ft. to ~13,000 sq. ft.) and external funding (~$1M to ~$12M per year).

NMMI research includes single photon, PET and optical imaging. These areas explore agent discovery, validation and translational studies. As multimodal imaging is critical for molecular imaging, NMMI have research efforts in CT, MR and ultrasound. The research has evolved into three Centers, which constructively overlap. These efforts are located in research laboratories (~13,000 sq ft) in the MGH main campus and at the research campus in Charlestown.

Center for PET Radiochemistry Discovery (CPRD)
Research includes molecular discovery, novel radiolabeling including total radiosynthesis of 11C and 18 F radiopharmaceuticals, radiometals, biodistribution, metabolism and first in human studies.

Center for Advanced Radiological Sciences (CARS)
Research includes imaging science aspects as they pertain to instrumentation, quantitative imaging and analysis methods for PET, CT, MR, and SPECT simulations, kinetic modeling, image reconstruction etc. with applications in brain, cardiac and oncological imaging as well as radionuclide therapy and proton beam therapy.

Center for Translational Nuclear Medicine and Molecular Imaging (CTNMI)
Research includes designing, creating, and testing new methods for imaging and therapeutic targeting of important biological pathways in disease. The process spans imaging, creation of appropriate cell-based and animal models of pathology and the clinical translation of the optimized concepts to help detect disease and therapeutic response in people. Our imaging efforts focus on PET, optical-fluorescence, MR, and SPECT imaging in both preclinical systems.

MGH PET Core
Established in 1973, the MGH PET Core provides radiopharmaceutical syntheses, radioisotope production, quantitative imaging, data analysis and experimental design and data analysis services to investigators at the MGH and in the Boston research community. The PET Core includes the Cyclotron, the Radionuclide Production Facility, Imaging facilities and PET Data Analysis Laboratory.

History

Nuclear Medicine at MGH has a rich history beginning with Dr Saul Hertz experiments with ¹²⁸I uptake in rabbits in 1940's. Dr Gordon Brownell developed instrumentation to obtain the first positron emission images in the 1950’s that evolved into positron emission tomography. The MGH installed one of the first hospital-based cyclotrons in 1967 and established the MGH PET Core in 1973. In late 2007 the Division was renamed Nuclear Medicine and Molecular Imaging (NMMI) to reflect the growth and diversity of clinical and research activities. In 2009, the MGH installed a GMP PET radiochemistry production facility and a new 17MeV cyclotron. It is today at the forefront of molecular imaging research and discovery with state of the art imaging and radiochemistry instrumentation.

Leadership

Thomas Brady, MD, Director of MGH NMMI
Georges El-Fakhri, PhD, Director of MGH PET Core and CARS and Co-Director NMMI
Umar Mahmood, MD, PhD, Director of CTNMI and Co-Director NMMI
Ted Palmer, MD, Director of the Clinical Services
Neil Vasdev, PhD, Director of MGH Radiochemistry and CPRD

A Scientific Management Committee assists the Leadership in providing strategic direction for the Program. A PET Core Management Committee provides guidance for the operation of the cyclotron and radiochemistry production facilities.

NMMI has over 40 faculty members and over 60 postdoctoral research fellows and students. In addition, many researchers from various departments in MGH and the Boston Research community are affiliated faculty.

Faculty and Professional Staff

Post-doctoral fellows

Technical Staff and Research Assistants

Students                                           

Administrative Staffs

NNMI encompasses broad research areas that are organized into three centers of excellence:

• Center for Translational Nuclear Medicine and Molecular Imaging (CTNMI)Four imaging suites are located immediately adjacent to animal housing and surgical suites. Imaging equipment includes a GE eXplore Vista microPET scanner. This scanner is based on a dual-scintillation, depth-of-interaction technology that enables extremely high sensitivity and high spatial resolution. The scanner has an axial 4.6 cm FOV, a transverse 6.7 cm FOV, 36 depth of interaction modules, 12,168 crystals, and has 28.8M coincidence lines. The central spatial resolution is 1.2 mm using 3D OSEM reconstruction. The system has 15 ns timing resolution, and a 4% sensitivity.  For fluorescence and bioluminescence imaging, four systems are available: a Kodak FX Multispectral Imaging system (29 excitation and 4 emission wavelengths, overlay of white light and x-ray images, and bioluminescence-level sensitivity), a Maestro CRI multichannel fluorescence imaging system, a homebuilt bioluminescence imaging system based on a high sensitivity Roper Scientific CCD camera, and multiple home built fluorescence imaging minimally invasive system for murine endoscopy. For biodistribution studies, Wallac/Perkin Elmer Gamma counter and dose calibrators are available.
  
  There are four tissue culture rooms on CNY149-5.  Each room (150-250 sq. ft) is equipped with a laminar flow hood (Forma Scientific model 1132), CO₂ incubators (Forma Scientific water jacketed), a microscope (Nikon TMS), waterbaths (Labline), and benchtop centrifuges. There is a liquid nitrogen freezer (Thermoscientific CryoPlus 2) for long term storage of cell lines.  An Olympus Microscope Imaging System w/Phase contrast  & Fluorescence (IX51/DP-72) is available for publication quality micrographs. Flow cytometers (FACSCalibur, LSR II) and a fluorescence-activated cell sorter (FACSAria, all from Becton Dickinson) are available for use.
  
  The animal preparation area on CNY 149-5 consists of a separate room (150 sq. ft.), with surgical stainless steel benches for small animal surgery. This room was specifically designed for complex small animal surgery, anesthesia and monitoring, implantation of tumors, biodistribution experiments and injection of imaging agents and therapeutics. Each surgical suite has available all surgical equipment for small animal surgery, intubation, and dissection.  Warming pads are routinely used for maintaining body temperature during surgery. The rooms feature inhaled (isoflurane) anesthesia.
• Center for Advanced Radiological Sciences (CARS)
  
  
• Center for Transformative Radiochemistry Research

2012 Publications

• Abdelbaky, A., Corsini E., Figueroa AL, Fontanez S., Subramanian S., Brady, TJ, Hoffmann, U., Tawakol, A. Subsequent Arterial Calcification is preceded by Focal Inflammation: A longitudinal FDG-PET/CT Study. American College of Cardiology Scientific Sessions Chicago 2012
• Alcantara, D., Guo, Y., Yuan, H., Goergen, C. J., Chen, H. H., Cho, H., Sosnovik, D. E., and Josephson, L. (2012) Fluorochrome-Functionalized Magnetic Nanoparticles for High-Sensitivity Monitoring of the Polymerase Chain Reaction by Magnetic Resonance. Angew Chem Int Ed Engl. Epub.
• Blankstein R, Ahmed W, Bamberg F, Rogers IS, Schlett CL, Nasir K, Fontes J, Tawakol A, Brady TJ, Nagurney JT, Hoffmann U, Truong QA.Comparison of Exercise Treadmill Testing With Cardiac CT Angiography Among Patients Presenting To The Emergency Room With Chest Pain: ROMICAT Study. Circ Cardiovasc Imaging. 2012 Mar 1;5(2):233-42
• Bunschoten, A., Buckle, T., Visser, N. L., Kuil, J., Yuan, H., Josephson, L., Vahrmeijer, A. L., and van Leeuwen, F. W. (2012) Multimodal interventional molecular imaging of tumor margins and distant metastases by targeting alphavbeta3 integrin. Chembiochem : a European journal of chemical biology 13, 1039-45.
• Calias P, Papisov M, Pan J, Savioli N, Belov V, et al. CNS Penetration of Intrathecal-Lumbar Idursulfase in the Monkey, Dog and Mouse: Implications for Neurological Outcomes of Lysosomal Storage Disorder. PLoS ONE, 2012, 7(1): e30341. doi:10.1371/journal.pone.0030341.
• Chen W, GEWIRTZ H, Smith M, Dilsizian V. Animal Models in Cardiology. In: Targeted Molecular Imaging. (Ed. Welch MJ and Eckelman WC) Taylor and Francis Group, Boca Raton, FL, P. 37-70, 2012 (in press)
• Chen, H. H., Feng, Y., Zhang, M., Chao, W., Josephson, L., Shaw, S. Y., and Sosnovik, D. E. (2012) Protective effect of the apoptosis-sensing nanoparticle AnxCLIO-Cy5.5. Nanomedicine : nanotechnology, biology, and medicine 8, 291-8.
• Chen, H. H., Yuan, H., Josephson, L., and Sosnovik, D. E. (2012) Theranostic Imaging of the Kinases and Proteases that Modulate Cell Death and Survival. Theranostics 2, 148-55.
• Chun S.Y., Reese T., Guerin B., Catana C., Zhu X., Alpert N., El Fakhri G. Tagged MR-based Motion Correction in Simultaneous PET-MR. J. Nucl. Med. 2012; in press.
• Dagher J., Li Q., Du Y.P., El Fakhri G. Efficient and robust estimation of blood oxygenation levels in single cerebral veins. Medical & Biological Engineering & Computing 2012; in press.  
• Doraiswamy PM, Sperling RA, Coleman R.E., Johnson KA, Reiman EM, Davis MD, Grundman M, Sabbagh MN, Sadowsky CH, Fleisher AS, Carpenter A, Clark CM, Joshi AD, Mintun MA, Skovronsky DM, Pontecorvo MJ, for the AV45-A11 Study Group. Amyloid-β assessed by florbetapir F 18 PET and 18-month cognitive decline: a multi-center study. Neurology 2012 (in press)
• El Fakhri G., Fang D., and Alpert N. Single-scan Rest/Stress Imaging 18F-labeled flow tracers – Theory and Simulation Studies.  Med. Phys. Submitted.
• Fang D., El Fakhri G., Becker A., and Alpert N. Variance reduction of parametric images with Bayesian estimation: validation studies with ¹¹C-Altropane PET studies.  NeuroImage 2012;.  In press.
• Figueroa AL, Subramanian SS,  Cury RC,  Truong QA, Hoffmann U, Brady TJ, and Tawakol A Distribution of Inflammation within Carotid Atherosclerotic Plaques with High Risk Morphological Features: A Comparison Between PET Activity, Plaque Morphology and Histopathology. Circulation Cardiovascular Imaging 2012;5:69-77
• Fleisher AS, Chen K, Liu X, Ayutyanont N, Roontiva A, Thiyyagura P, Protas H, Joshi A, Sabbagh MN, Sadowsky CH, Sperling RA, Clark CM, Mintun MA, Pontecorvo MJ, Coleman R.E., Doraiswamy PM, Johnson KA, Carpenter A, Skovronsky DM, Reiman EM. APOE4 and Age Effects on Florbetapir PET in Healthy Aging and Alzheimer Disease. Neurobiology of Aging 2012 (in press).
• Gewirtz, H: PET Measurement of Adenosine Stimulated Absolute Myocardial Blood Flow for Physiological Assessment of the Coronary Circulation (Invited Review) – J Nuclear Cardiology 2012; 19:347-354
• Gomperts SN, Locascio JJ, Marquie-Sayagues M, Santarlasci AL, Rentz DM, Maye J, Johnson KA, Growdon JH. Brain amyloid and cognition in Lewy body diseases. Movement Disorders 2012 (in press).
• Gratkau B, Rebello G, Gupta, R, et al. “Transplantation of Stem Cells in an Experimental Perthes' Model Resulted in Maintenance of Femoral Head Sphericity.” Paper No. 364, AAOS Annual Meeting, February 09, 2012
• Graves C, Slocum AH, Gupta R, Walsh CJ.  Towards a Compact Robotically Steerable Thermal Ablation Probe. IEEE International Conference on Robotics and Automation, May 14-18, 2012, River Centre, Saint Paul, Minnesota, USA
• Grottkau B, Gupta R, Rebello G, Kim S, Shapiro F, Sabel B. Stem Cells Transplanted into Revascularized Epiphyses in a Piglet Perthes’ Model Promoted Restoration of Femoral Head Sphericity. 2012 POSNA Annual Meeting of the Pediatric Orthopaedic Society of North America on May 18, 2012.
• Gurm GS, Danik SB, Shoup TM, Weise S,Takahashi K, Laferrier S, Elmaleh DR, GEWIRTZ H. 4-[¹⁸F]-Tetraphenylphosphonium (TPP): A PET Tracer for Myocardial Mitochondrial membrane Potential. JACC:CV Imaging 2012; 5:285-292
• Gurol ME, Dierksen GA, Betensky RA, Gidicsin C, Halpin A, Becker JA, Carmasin J, Ayres A, Schwab KM, Viswanathan A, Salat DH, Rosand J, Johnson KA, Greenberg SM. Predicting Sites of New Hemorrhage with Amyloid Imaging in Cerebral Amyloid Angiopathy. Neurology 2012 (in press).
• Larvie M, Shoup TM, Chang WC, Chigweshe L, Hartshorn K, White MR, Stahl GL, Elmaleh DR,  Takahashi. K. Mannose-Binding Lectin Binds to Amyloid β Protein and Modulates Inflammation. J Biomedicine and Biotechnology 2012, 2012:1-12.
• Ouyang J., Chun S.Y., El Fakhri G. MR-based Attenuation Correction for Whole-Body PET-MR. Med. Phys. 2012; Submitted.
• Papisov M, Belov V, Fischman A.J., Belova E, Titus J, Gagne M. Delivery of proteins to CNS as seen and measured by Positron Emission Tomography. Drug Delivery and Translational Research, 2012 (in press)
• Papisov, M., V. Belov, A.J. Fischman, P. Calias, T. McCauley. PET imaging of protein delivery to the brain in non-human primates. 8^th Annual World Symposium of Lysosomal Disease Network, San Diego, CA 2012,  # 140.
• Sabel B., Phan C., Parikh A., Chaundry, Romero J., Yoo A., Gupta R. “Temporal evolution of high-density lesions on noncontrast CT obtained after intra-arterial thrombolysis in ischemic stroke patients.” ASNR 2012.
• Sepulcre, J., 1,234, Mert R. Sabuncu2,3, Keith A. Johnson. Network Assemblies in the Functional Brain. Current Opinion in Neurology 2012 (in press).
• Sepulcre J, Sabuncu MR, Johnson KA. Network Assemblies in the Functional Brain. Current Opinion in Neurology, 2012 Aug, in press.
• Sepulcre J, Sabuncu M, Yeo TB, Liu H, Johnson KA. Large-Scale Functional Connectome of the Modal Brain. J. Neuroscience 2012 (in revision)
• Sperling RA, Johnson KA. Dementia: new criteria but no new treatments. Lancet Neurol. 2012; 11(1): 4-5. 
• Vannini P, Hedden T, Huijbers W, Ward A, Johnson K.A, Sperling R.A. The ups and downs of the posteromedial cortex: age and amyloid-related functional alterations of the encoding/retrieval flip in cognitively normal older adults. Cerebral Cortex 2012 (in press)
• Villemagne VL, Klunk WE, Mathis CA, Rowe CC, Brooks DJ, Hyman BT, Ikonomovic MD, Ishii K, Jack KR, Jagust WJ, Johnson KA, Koeppe RA, Lowe VJ, Masters CL, Montine TJ, Morris JC, Nordberg A, Petersen RC, Reiman EM, Selkoe DJ, Sperling RA, Laere KV, Weiner MW, Drzezga AE. Aβ Imaging: Feasible, Pertinent and Vital to Progress in Alzheimer's Disease. Eur. J. Nucl. Med. Mol. Imaging 2012; 39(2):209-19.
• Whyte M, Greenberg C, Salman N, Bober M, McAlister W, Wenkert D, Van Sickle B, Simmons J, Edgar T, Bauer M, Hamdan M, Bishop N, Lutz R, McGinn M, Craig S, Moore J, Taylor J, Cleveland R, Cranley W, Lim R, Thacher T, Mayhew J, Millan J, Skrinar A, Crine P, Landy H. “Enzyme Replacement for Life-Threatening Hypophosphatasia.” In press, 2012 March 8, New England Journal of Medicine.

Chris Shambaugh

Phone: 617-726-8353
Fax: 617-726-6165
Email: cshambaugh@partners.org