Center for Molecular Functional Imaging (CMFI)
Ronald L. Arenson, MD, Acting Director, 415/353-9401

See also On the Forefront of Molecular Imaging.

See also CMFI web site.

Radiology has a rich history of innovation and academic leadership at the University of California San Francisco. Significant advances in research by our department over the past decade have fostered new clinical, technical, and scientific developments in medical imaging and have garnered growing national acclaim for the quality and scope of our teaching, research and patient care programs. The opening of the Center for Molecular and Functional Imaging at China Basin Landing, adjacent to the UCSF Mission Bay campus, positions the department for even greater advances over the next decade.

The Center for Molecular and Functional Imaging (CMFI) comes into being at a time when our colleagues in molecular biology have deciphered the human genome and are beginning to unravel both its biological manifestations and the exciting medical implications of this knowledge. These fundamental discoveries compel us to explore and innovate new noninvasive imaging tools that allow us to discern processes at the cellular, molecular, and genetic level, tools that use imaging to gain new insights into fundamental biological principles, as well as the disease process, and to enable and monitor new therapies. The CMFI was conceived to coordinate and integrate these activities under one umbrella.

Dr. Tom Ferree prepares to record EEG signals of a research subject during functional MRI scanning using the Maglink EEG system (Neuroscan, Inc.) Because EEG and fMRI are complimentary in their spatial and temporal resolution, their combination promises better images of functional brain activity.

Location, Location, Location

The decision to locate such a key program off-campus was made after careful and thoughtful consideration of the costs and benefits, and after much consultation with investigators and other faculty. It was driven by our need to expand and the desire to leverage the investment in the new resources and capabilities of many basic science research laboratories at the Mission Bay campus. In addition to standing at the gateway to the new Mission Bay campus, China Basin Landing offers:

Outstanding Facilities

• Ample, attractive, modern space with high ceilings and a strong utility infrastructure support the sophisticated equipment we require.
• The capacity for future renovation to accommodate the new resources needed to pursue leading-edge research.
• Excellent computer networking facilities support communication and high-speed image data transfer to other UCSF sites.
• Long-term lease rates and good tenant improvement allowances which make good financial sense.

A Vibrant Community

• Housing, restaurants, groceries and other amenities are all close by, as is SBC (a.k.a. PacBell) Park.

Convenient Transportation

• The N-Judah Muni light rail line runs from the Parnassus campus to China Basin Landing, as well as to the Caltrain depot, which is located directly across the street, providing ready access along the San Francisco peninsula.
• Shuttle bus service runs from the Mission Bay and Parnassus campuses, downtown San Francisco BART stations and the Market Street transit corridor, and the CMFI is close to the San Francisco Transbay Terminal.
• Ample parking is available in the building and there is affordable surface parking nearby.

State-of-the-Art Instrumentation

The CMFI includes 32,000 square feet of laboratory and office space for approximately 130 faculty, research scientists, post-doctoral fellows, graduate students and staff. Located on the third floor, with a view of the Mission Bay campus, the Center includes spacious physics, chemistry, nuclear medicine, tissue culture, and instrumentation development laboratories. Shared resources include state-of-the-art instrumentation including: high-resolution microCT, a high field Nuclear Magnetic Resonance (NMR) tissue scanner, a Fourier Transform Infrared (FTIR) microscope, a small-animal SPECT/CT dual-modality imaging system, specimen storage, and an animal housing and surgical suite.

On the first floor, adjacent to the new UCSF Radiology Imaging Center, a clinical outpatient imaging facility featuring two 1.5T MR GE scanners, is San Francisco’s first high-field 3 Tesla MR scanner, along with a bone densitometry scanner and a Phillips 16-slice research CT scanner. We expect to add a microPET and small bore 7T MR in the near future. With basic scientists nearby at Mission Bay, and members of the Radiology faculty representing physics, nuclear medicine, bioengineering, musculoskeletal research, informatics, and neuroradiology, the Center is well positioned to meet the molecular imaging needs of a diverse academic community at UCSF and to pursue research in all areas of radiology.

Collaboration a Key

One of the most important benefits of this new research facility is the co-location of a number of important faculty members who previously had been dispersed across the city and on the peninsula. Their easy access to each other is stimulating many new collaborations and research initiatives. The proximity to the new Institute for Quantitative Biomedical Research (QB3) on the Mission Bay campus is an exciting development that promises important new advances in medical imaging research. A 7T MR whole body system, recently installed in QB3, will be operated by several of our faculty. Collaborations among scientists already underway include:

• The Prostate Imaging Research Partnership. Research groups working on new prostate imaging techniques at different sites have formed a unified prostate imaging development program. They recently submitted a major NIH grant application to form a Bioengineering Research Partnership, whose goal would be to develop and translate new prostate cancer imaging techniques into clinical radiological tools. This academic/industrial partnership involves the MR Technique Development group led by Dan Vigneron, PhD; the SPECT/CT group directed by Bruce Hasegawa, PhD; a group working on ex vivo High Resolution Magic Angle Spectroscopy (HR MAS) and in vivo MRS led by John Kurhanewicz, PhD; the Image Analysis group overseen by Sarah Nelson, PhD, in collaboration with Henry Van Brocklin, PhD, at Lawrence Berkeley Laboratory for PET/CT development; biomolecular probe researcher Benjamin Franc, MD; the RF (radio-frequency) pulse design group at Stanford, headed by John Pauly, PhD; and industrial partners, including General Electric.
• The collaboration of the Image Analysis group, led by Dr. Nelson, and the MR Technique Development group, led by Dr. Vigneron, benefits the rapid development of new MRI/MRSI techniques at China Basin for both the 3T and 1.5T MR scanners. Examples include new radiofrequency pulse schemes for MRSI, rapid MRSI using oscillating gradient acquisitions and parallel imaging reconstructions.
• Locating Dr. Kurhanewicz’s 500 MHz NMR system for ex vivo MRS studies of tissue samples at the same facility as the 3T MR scanner made possible the first collaboration on new biomarker discovery studies of prostate cancer, and resulted in a new NIH grant beginning this fall.
• The Musculoskeletal and Quantitative Imaging Research (MQIR) group, directed by Sharmila Majumdar, PhD, is located at the CMFI, where it has collaborated with the HR MAS group to study disc degeneration. Together they have used HR MAS or NMR measures and FTIR measures to find markers of early disc degeneration a precursor of low back pain. MQIR also collaborates with Will Moss, PhD, from Lawrence Livermore National Laboratory and others to use wavelets to study bone structure and plans to submit grant applications in this area.
• Collaborations with Pratik Mukherjee, MD, of Neuroradiology and GE scientists from the GE Advance Science Laboratory–West on the 3T MR scanner have enabled extraordinary advances in diffusion imaging, allowing unprecedented visualization of neuronal pathways in the normal brain and following traumatic brain injury.
• Simultaneous EEG-fMRI recording capability has recently been installed in the 3T MRI facility at China Basin Landing. In collaboration with UC Berkeley and the Smith-Kettlewell Eye Research Institute, dynamical analysis and mathematical modeling are being used by Greg Simpson, PhD and the Dynamic Neuroimaging Lab to study the relationship between neural activity and stimulus-related changes in blood oxygenation levels.
• The new state-of-the-art 1.5T and 3T MR scanners and the necessary research space have enabled collaborations with GE Healthcare scientists on developing and testing new MR sequences for a wide variety of applications.
• Mission Bay scientists collaborating with the CMFI include Thomas James, PhD, director of the NMR center in Pharmaceutical Chemistry and Mark Kelley, PhD, working together on coil construction and MR science.

Dr. Dan Vigneron (center) and MR coil engineer Kostas Karpodonis (left) collaborate with Dr. Jim Tropp from GE Healthcare on developing a novel high-sensitivity phased-array coil for brain and musculoskeletal 3T imaging.

Research in Nuclear Medicine Expands

Several faculty have already established and are expanding research in nuclear medicine, positron emission tomography, and dual-modality imaging at CMFI. These include radiopharmaceutical chemistry, development of new biomolecular imaging probes, instrumentation and technique development in radionuclide and dual-modality imaging, and both functional and molecular imaging of cardiovascular biology and disease. Collaborations include:

• Michael Dae, MD, is conducting cardiovascular research at CMFI. His research involves use of high-resolution digital autoradiography, pinhole SPECT, x-ray fluoroscopy, and other advanced techniques to investigate fundamental biological relationships, new diagnostic techniques, and new therapeutic approaches in ischemic myocardium, cardiomyopathy, cerebral ischemia, and contrast-induced nephropathy using several mammalian models of these disorders.
• Drs. Dae and Hasegawa collaborate in the area of small animal imaging with both microSPECT and microCT, using submillimeter spatial resolution suitable for imaging murine models of mammalian biology and disease. Dr. Hasegawa’s group pioneered a new generation of SPECT/CT instrumentation, which has become available for use in clinical studies and now has been developed for research with small animals. The group also has major collaborations with scientists from Lawrence Livermore National Laboratory in the area of gamma-ray optics and with small businesses interested in developing new radiation detection techniques and biomedical imaging systems.
• Dr. Van Brocklin, an expert in radiopharmaceutical chemistry from Lawrence Berkeley Laboratory has active collaborations with Drs. Dae and Hasegawa, as well as other faculty members in Radiology and the Cancer Center at UCSF in developing new SPECT and PET radiopharmaceuticals for detecting, diagnosing, and treating heart disease, cancer, neurodegenerative disease, and other disorders.
• Dr. Franc, a new faculty member in the UCSF Nuclear Medicine Program, received a research grant from the Department of Energy to pursue development of new biomolecular probes that promise to provide a new approach for diagnostic imaging and for targeted delivery of therapeutic agents to specific receptors and molecular signatures associated with cancer and other diseases. Dr. Franc will collaborate closely with Drs. Van Brocklin, Dae, and Hasegawa from his CMFI office and laboratory.

Bruce Hasegawa, PhD (left) and Andrew Hwang (right), bioengineering graduate student, operate a high-resolution SPECT/CT system (Gamma Medica, Northridge, CA) used for biological research at the UCSF Physics Research Laboratory (PRL).

William Barber, PhD, (far right) also with the PRL, evaluates position-sensitive avalanche photodiodes for high-resolution gamma-ray imaging using a novel detector he developed that uses liquid-nitrogen cooling to maximize spatial and energy resolution performance.

Room to Grow

Given the vast amount of research already underway at CMFI and the vast potential represented by the myriad collaborations being formed, Radiology has exercised an option for an additional 22,000 square feet of space on the first floor of China Basin Landing, adjacent to the outpatient imaging center. This will be developed into laboratory and desk-based research space and will share adjacent space with the department’s new nuclear medicine facility and PET/CT scanner, the first of its kind in San Francisco. To complement our clinical expansion, we are also working on plans to place a cyclotron in the basement below the PET/CT and research labs, so we can continue our important work in PET research, target development and other molecular imaging research.

We anticipate that this new Center for Molecular and Functional Imaging will soon be regarded among the most outstanding research facilities in the country. Our very successful faculty, along with a number of new recruits, will use this new Center to propel our department in new and exciting research directions in the years to come.

Research Directions:

• Characterization of prostate cancer using in vivo MRI, DCE MRI, DTI and MRSI, and ex vivo tissue analysis using micro-array analysis, immunohistochemistry and high resolution MRS
• The cost-effective use of multiple diagnostic information, statistical methods for medical diagnosis, imaging clinical trials, osteoporosis, and cancer clinical trials
• Assessment of heart-brain interaction using high resolution scintigraphic techniques in models of sudden cardiac death, neural injury, and postnatal maturation.
• Assessment of mechanisms of cell injury in models of myocardial infarction and contrast induced nephropathy, and exploration of strategies for cell protection such as hypothermia and preconditioning
• Assessment of ventricular remodeling following experimental myocardial infarction using radionuclide ventriculography
• Development of novel high field MR morphological and metabolic imaging techniques for the study of cancer and brain disorders using a 3T MR scanner
• Diffusion tensor imaging of the brain and spine
• MRI and MR spectroscopic imaging of prostate cancer
• Quantitative X-ray absorptiometry
• Electrical impedance tomography to measure subregional body composition

Recent Key References:

Berman JI, Berger MS, Mukherjee P, Henry RG. Diffusion-tensor imaging-guided tracking of fibers of the pyramidal tract combined with intraoperative cortical stimulation mapping in patients with gliomas. J Neurosurg 2004; 101(1):66-72.

Cunningham CH, Vigneron DB, Chen AP, Xu D, Hurd RE, Sailasuta N, Pauly JM. Design of symmetric-sweep spectral-spatial RF pulses for spectral editing. Magn Reson Med 2004; 52(1):147-53.

Dae M, Gao D, Ursell P, Stillson C, Sessler D. Safety and efficacy of endovascular cooling and rewarming for induction and reversal of hypothermia in human-sized pigs. Stroke 2003; 34:734-8.

Dhingsa R, Qayyum A, Coakley FV, Lu Y, Jones KD, Swanson MG, Carroll PR, Hricak H, Kurhanewicz J. Prostate cancer localization with endorectal MR imaging and MR spectroscopic imaging: effect of clinical data on reader accuracy. Radiology 2004; 230(1):215-20.

Frelinger A, Furman M, Barnard M, Krueger L, Dae M, Michelson A. Combined effects of mild hypothermia and glycoprotein IIb/IIIa antagonists on platelet-platelet and leukocyte-platelet aggregation. Am J Cardiol 2003; 92:1099-101.

Graves EE, Pirzkall A, McKnight TR, Vigneron DB, Larson DA, Verhey LJ, McDermott M, Chang S, Nelson SJ. Use of proton magnetic resonance spectroscopic imaging data for planning focal radiation therapies. Image Analysis & Stereology 2004; 21:69-76.

Hale S, Dae M, Kloner R. Hypothermia during reperfusion limits 'no relow' injury in a rabbit model of acute myocardial infarction. Cardiovasc Res 2003; 59:715-22.

Henry RG, Berman JI, Nagarajan SS, Mukherjee P, Berger MS. Subcortical pathways serving cortical language sites: initial experience with diffusion tensor imaging fiber tracking combined with intraoperative language mapping. Neuroimage 2004; 21(2):616-22.

Henry RG, Oh J, Nelson SJ, Pelletier D. Directional diffusion in relapsing-remitting multiple sclerosis: A possible in vivo signature of Wallerian degeneration. J Magn Reson Imaging 2003; 18(4):420-6.

Hurd R, Sailasuta N, Srinivasan R, Vigneron D, Pelletier D, Nelson S. Measurement of brain glutamate using TE-averaged PRESS at 3T. Magn Reson Med 2004; 51(3):435-40.

Lee M, Pirzkall A, Akazawa P, Verhey LJ, Nelson SJ. MR spectroscopy of radiation effects in healthy brain tissue following radiotherapy. Int J Radiat Oncol Biol Phys 2003; 57(S):133-4.

Lee MC, Pirzkall A, McKnight T, Nelson SJ, 1H-MRSI of radiation effects in normal-appearing white matter: dose-dependence and impact on automated spectral classification. J Magn Reson Imag 2004; 19(4):379-88.

Li X, Jin H, Lu Y, Oh J, Chang S, Nelson SJ. Identification of MRI and 1H MRSI parameters that may predict survival for patients with malignant gliomas. NMR Biomed 2004; 17(1): 10-20.

Lu, Y, Fang JQ (eds). Advanced Medical Statistics. Singapore, World Scientific Publications, Co., 2003.

Lu Y, Jin H, Genant HK. On the equivalence of two diagnostic tests based on paired observations. Stat Med 2003; 22(10):3029-44.

Maas LC, Mukherjee P, Carballido-Gamio J, Veeraraghavan S, Miller SP, Partridge SC, Henry RG, Barkovich AJ, Vigneron DB. Early laminar organization of the human cerebrum demonstrated with diffusion tensor imaging in extremely premature infants. Neuroimage 2004; 22(3):1134-40.

Miller SP, McQuillen PS, Vigneron DB, Glidden DV, Barkovich AJ, Ferriero DM, Hamrick SE, Azakie A, Karl TR. Preoperative brain injury in newborns with transposition of the great arteries. Ann Thorac Surg 2004; 77(5):1698-706.

Mohr DC, Epstein L, Luks TL, Goodkin D, Cox D, Goldberg A, Chin C, Nelson SJ. Brain lesion volume and neuropsychological function predict efficacy of treatment for depression in multiple sclerosis. J Consult Clin Psychol 2003; 71(6):1017-24.

Nelson SJ. Multivoxel magnetic resonance spectroscopy of brain tumors. Mol Cancer Ther 2003; 2(5):497-507.

Oh J, Henry RG, Genain C, Nelson SJ, Pelletier D. Mechanisms of normal appearing corpus callosum injury related to pericallosal T1 lesions in multiple sclerosis using directional diffusion tensor and 1H MRS imaging. J Neurol Neurosurg Psychiatry 2004; 75(9):1281-6.

Oh J, Henry RG, Pirzkall A, Lu Y, Li X, Catalaa I, Chang S, Dillon WP, Nelson SJ. Survival analysis in patients with glioblastoma multiforme: predictive value of choline to N-acetylaspartate index, apparent diffusion coefficient and relative cerebral blood volume. J Magn Reson Imag 2004; 19:546-54.

Oh J, Pelletier D, Nelson SJ. Preferential corpus callosum axonal injury in multiple sclerosis measured by proton magnetic resonance spectroscopic imaging. Arch Neurol 2004; 61:1081-6.

Partridge SC, Mukherjee P, Henry RG, Miller SP, Berman JI, Jin H, Lu Y, Glenn OA, Ferriero DM, Barkovich AJ, Vigneron DB. Diffusion tensor imaging: serial quantitation of white matter tract maturity in premature newborns. Neuroimage 2004; 22(3):1302-14.

Pickett B, Ten Haken RK, Kurhanewicz J, Qayyum A, Shinohara K, Fein B, Roach M 3rd. Time to metabolic atrophy after permanent prostate seed implantation based on magnetic resonance spectroscopic imaging. Int J Radiat Oncol Biol Phys 2004; 59(3):665-73.

Pirzkall A, Li X, Oh J, Chang S, Berger MS, McDermott MW, Larson DA, Verhey LJ, Dillon WP, Nelson SJ. 3D MR-Spectroscopy for resected high-grade gliomas prior to RT: tumor extent according to metabolic activity in relation to MRI. Int J Radiat Oncol Biol Phys 2004; 59(1):126-37.

Pouliot J, Kim Y, Lessard E, Hsu IC, Vigneron DB, Kurhanewicz J. Inverse planning for HDR prostate brachytherapy used to boost dominant intraprostatic lesions defined by magnetic resonance spectroscopy imaging. Int J Radiat Oncol Biol Phys 2004; 59(4):1196-207.

Qayyum A, Coakley FV, Lu Y, Olpin JD, Wu L, Yeh BM, Carroll PR, Kurhanewicz J. Organ-confined prostate cancer: effect of prior transrectal biopsy on endorectal MRI and MR spectroscopic imaging. AJR Am J Roentgenol 2004; 183(4):1079-83.

Schneider TE, Barland C, Alex AM, Mancianti ML, Lu Y, Cleaver JE, Lawrence HJ, Ghadially R. Measuring stem cell frequency in epidermis: A quantitative in vivo functional assay for long-term repopulating cells. Proc Natl Acad Sci U S A. 2003; 100(20):11412-17.

Srinivasan R, Vigneron D, Napapon S, Hurd R, Nelson SJ. A comparative study of myo-inositol quantification using LCmodel at 1.5 T and 3.0 T with 3D 1H proton spectroscopic imaging of the human brain. Magn Reson Imaging 2004; 22(4):523-8.

Swanson MG, Vigneron DB, Tabatabai ZL, Males RG, Schmitt L, Carroll PR, James JK, Hurd RE, Kurhanewicz J. Proton HR-MAS spectroscopy and quantitative pathologic analysis of MRI/3D-MRSI-targeted postsurgical prostate tissues. Magn Reson Med 2003; 50(5):944-54.

Wu M, Gao D, Sievers R, Lee R, Hasegawa B. Pinhole single-photon emission computed tomography for myocardial perfusion imaging of mice. J Am Coll Card 2003; 42:576-82.

Xu D, Henry RG, Mukherjee P, Carvajal L, Miller SP, Barkovich AJ, Vigneron DB. Single-shot fast spin-echo diffusion tensor imaging of the brain and spine with head and phased array coils at 1.5 T and 3.0 T. Magn Reson Imaging 2004; 22(6):751-9.

Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A, 2004 Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight, J Bone Miner Res. Jun;19(6):1006-12.

Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ; PaTH Study Investigators, The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis, N Engl J Med. 2003 Sep 25;349(13):1207-15.