Sharmila Majumdar, Ph.D. sharmila.majumdar@radiology.ucsf.edu

Vice Chair, Research, Radiology, University of California, San Francisco
Director, Musculoskeletal and Quantitative Imaging Research (MQIR) Group, University of California, San Francisco
Professor, Growth and Development, University of California, San Francisco
Professor, Orthopedic Surgery, University of California, San Francisco
Professor, Radiology, University of California, San Francisco
Professor, Bioengineering, University of California, Berkeley

http://www.radiology.ucsf.edu/mqir
Research Program
My current research program is aimed at developing fast, high resolution Magnetic Resonance (MR) imaging and x-ray based techniques, which in conjunction with image analysis and processing methods, may be used to derive quantitative information pertaining to tissue, organ morphology and function. In the area of musculoskeletal applications, imaging plays a role in diagnosis, in surgical planning, and in guided surgical applications. However, beyond anatomical and subjective depictions of anatomy, quantitative, morphological and functional musculoskeletal imaging methods are still under-utilized. Recently, there has been a focused attempt to increase collaborative efforts and to address the development of quantitative musculoskeletal imaging in the Department of Radiology at UCSF. This has led to the establishment of the Musculoskeletal and Quantitative Imaging Research (MQIR) group, which includes researchers from my group and three existing faculty in Radiology and their groups, as well as a recent radiologist recruit, Dr. Thomas Link (a past fellow with me, who is now the Clinical Director of MQIR). This consortium of individuals works with me to expand research in this area. As the Director of the MQIR, my role has evolved beyond developing my individual research projects to include a formal research mentor role, where it is my responsibility to foster the independence and growth of junior faculty and researchers.

Research Program Details
(I) Characterization of Trabecular Bone and the Study of Osteoporosis: Osteoporosis is characterized by a loss of bone mineral density and changes in trabecular bone architecture. In this area, my research program has been aimed at developing non-invasive MR, micro computed tomography techniques and image processing methods to quantify trabecular bone density and structure. Collaborative studies and clinical trials have been conducted which indicate that MR techniques may potentially provide additional information relating to bone strength. Current collaborators in this study include Dr. Dan Bikle (VAMC, UCSF), Dr. Bernard Halloran (VAMC), Tamara Alliston and Rik Duerynk (Dentistry, UCSF), Dr. Nancy Lane (Rheumatology), Dr. Jeffrey Lotz (Orthopedic Surgery), Dr. Tony Keaveny (Dept. of Mechanical Engineering, UCB), and Dr. Charles Chesnut (University of Washington).
(II) Characterizing Tissue Properties of Cartilage and Inter-vertebral Disk: In collaboration with the Dept. of Orthopedic Surgery and Dr. Jeffrey Lotz, high resolution MR imaging, PET and CT are being used to quantify the structure of the intervertebral disk. We have recently installed an infrared tissue-characterizing microscope, and also extended our research collaborations with Dr. Kurhanewicz, where high-resolution magic angle spinning (NMR spectroscopy) is being used to identify markers of disc degeneration.
(III) Osteoarthritis and Kinematics of the Knee Joint: In the area of osteoarthritis, high resolution MR imaging and quantitation of cartilage thickness, fraying, etc., is being conducted in collaboration with Drs. Steinbach, Lane (Rheumatology) and Ries (Orthopedic Surgery). In addition, Drs. Safran and Ma from Orthopedic Surgery are collaborating in developing kinematic imaging of the knee joint, and studying the complex kinematics of the knee in anterior cruciate ligament deficient knees.
(IV) Morphological and Functional Musculoskeletal Imaging: Synthesizing the overall focus of the above studies, my recent venture has been to develop a partnership to study musculoskeletal morphology and function. This five-year recently funded partnership sets the infrastructure for collaborations across different departments at UCSF, UC Berkeley, Lawrence Berkeley Labs and three industrial partners, and aims to push the envelope of quantitative imaging, and covers the entire musculoskeletal system. This is a technique development effort (rather than a disease-focused, hypothesis-driven project) that has led to several grants focusing on disease and supporting the studies above.
(V) High Field Magnetic Resonance Imaging of the Musculoskeletal System: With the installation of a 3 Tesla imaging system at the new China Basin facility and the installation of a 3 Tesla and 7 Tesla system at Mission Bay, a major focus of my research program is to develop high resolution imaging techniques and to optimize software and hardware for imaging the skeletal system at these fields. This includes developing fast, parallel imaging, image processing and analysis methodologies. This work is being done and will be expanded in collaboration with Drs. Nelson and Vigneron in Radiology.

Current Grants

R01 AG017762 (NIH)
Bioengineering Research Partnership: Morphological and Functional Musko-Skeletal Imaging

The aim of this partnership is to improve medical care through bioengineering developments, and to facilitate close interactions between bioengineers, computer scientists, clinical investigators, basic scientists and corporate partners. This effort will expedite the development of clinically relevant quantitative imaging tools and propel the technical advances from the laboratories into the operating rooms and clinics. We hypothesize that high resolution, fast magnetic resonance imaging techniques and positron emission tomography, combined with quantitative image analysis, processing and visualization, can provide new insights and clinically viable and relevant methods for objective evaluation of disorders of the musculoskeletal system. The long-term objective of this partnership is to understand the link between morphology, function, biochemical changes and clinical symptoms in the musculo-skeletal system. An immediate objective is to develop, implement and optimize novel non-invasive imaging methods (magnetic resonance imaging [MRI] and positron emission tomography [PET]) that will allow us to depict the musculo-skeletal system, quantitate morphology function, and provide unique 3D visualization and graphical representations of function and morphology, as well as correlate these with biochemistry and clinical status. The specific goals are as follows: (1) to develop quantitative morphological and functional markers for degenerative diseases of the spine; and (2) to develop quantitative morphological and functional markers for the degenerative changes in the knee and osteoarthritis.

Related Articles

Carballido-Gamio J, Belongie SJ, Majumdar S. Normalized cuts in 3-D for spinal MRI segmentation. IEEE Trans Med Imaging. 2004 Jan;23(1):36-44.

Lee KY, Dunn TC, Steinbach LS, Ozhinsky E, Ries MD, Majumdar S. Computer-aided quantification of focal cartilage lesions of osteoarthritic knee using MRI. Magn Reson Imaging. 2004 Oct;22(8):1105-15.

Newitt DC, Majumdar S. Reproducibility and dependence on diffusion weighting of line scan diffusion in the lumbar intervertebral discs. J Magn Reson Imaging. 2005 Apr;21(4):482-8.

Banerjee S, Krug R, Carballido-Gamio J, Kelley DA, Xu D, Vigneron DB, Majumdar S. Rapid in vivo musculoskeletal MR with parallel imaging at 7T. Magn Reson Med. 2008 Jan 25; [Epub ahead of print].

Krug R, Carballido-Gamio J, Banerjee S, Stahl R, Carvajal L, Xu D, Vigneron D, Kelley DA, Link TM, Majumdar S. In vivo bone and cartilage MRI using fully-balanced steady-state free-precession at 7 tesla. Magn Reson Med. 2007 Dec;58(6):1294-8.

R01 AR46905 (NIH)
Cartilage-Bone Interactions in Osteoarthritis

This project focuses on using Magnetic Resonance (MR) imaging at 3 Tesla to study joint degeneration and the manifested changes in articular cartilage, subchondral bone, peri-articular trabecular bone and bone marrow. Articular degeneration and progression of osteoarthritis (OA) may be preceded and/or accompanied by changes in subchondral and trabecular bone, and bone marrow. This project aims to utilize the strengths of our research environment and group and extend the study of OA to include trabecular bone structure measures, T1 of cartilage, and MR (proton) spectroscopy to characterize the adjoining bone marrow, in the study of OA. Using accepted parameters such as cartilage volume and T2 relaxation for comparison, we hypothesize the following: (1) that T2 and T1p are independently associated with cartilage loss and longitudinal progression of OA; (2) that changes of trabecular bone micro-architecture is associated with cartilage loss and progression of OA; (3) that MR spectroscopy (MRS) marrow fat/water contents are correlated with histological measurements and bone marrow edema characteristics are different between OA and acute injury. In addition to size of bone marrow edema, bone marrow edema fat/water and unsaturated/saturated fat composition are associated with cartilage loss and progression of OA. To address these we have the following aims: (1) to evaluate the relationship of T2 T-in relaxation times and trabecular bone structure to cartilage loss and OA progression; (2) to examine the MRS based water/fat compositions of bone marrow edema for patients with OA and acute injuries; and (3) to evaluate their relationship to cartilage loss and OA progression.

U01 AR055079 (NIH)
Instrument Development for the Osteoarthritis Initiative

The Osteoarthritis Initiative (OAI) is a national, multi-center, large cohort, natural history and prevalence study in knee OA that is an effort to set up a public database of images in -5000 subjects using 4 dedicated MR scanners (3 Tesla). The database, in addition to clinical data, serum, etc., will contain radiographs for grading of joint space and impact of alignment on knee OA, MR images that permit radiological grading of OA from MR images at 3T, cartilage volume and T2 estimation. The data will be available to the community for analysis. In OA, matching identical regions of interest, such that the exact same cartilage compartment (such as medial femur, lateral femur etc.) can be evaluated longitudinally is of utmost importance. This project proposes specific developments that will characterize the spatial heterogeneity of T2 and ensure that comparisons of MR derived cartilage morphology and T2 characteristics are made (1) in identical regions between subjects at baseline and (2) in identical regions in longitudinal follow-up scans for the same subject. Using a subset of images from the current data release (200 images of the knee) and the proposed release of 160 images from the OAI progression cohort, with close interactions with a scientific advisory board, we will develop the following: (1) a shape-based atlas of the knee; (2) a knee registration algorithm which will enable us to register all baseline and follow-up scans to the knee atlas, so that all scans are analyzed in a common coordinate system with common shape based anatomical regions; (3) define anatomical compartments such as the medial and lateral femur, patello-femoral compartment, medial and lateral tibia, and determine cartilage thickness and volume in those compartments; and (4) develop a graphical user-interface and platform for the software above for use by other researchers. We will also use the OAI images to generate T2 maps and use texture measures such as entropy to obtain measures of T2 spatial heterogeneity in the compartments. Our ultimate aim is to use the tools developed to assess longitudinal changes in cartilage morphology, T2 and determine whether baseline T2 and its heterogeneity predicts progression, as determined by changes in cartilage morphology, using a subset of images from the progression cohort. The tools developed will then be disseminate to one or two interested investigators for further testing.

BIO07-10641 (UC Discovery)
Non-Invasive Biomarkers of Disc Degeneration

Low back pain afflicts a significant number of working-aged adults. For many (estimated at 3%-4% of US population), the symptoms are temporary and resolved with conservative treatment (bed rest, physical therapy, anti-inflammatory medication). Still, by 2001 figures, there are approximately 1.5 million back pain patients that have failed conservative treatment who are awaiting more aggressive care that typically involves surgery. Surgery aimed at treating chronic discogenic pain (low back pain without sciatica) is a challenge to plan and execute since it is difficult to identify the specific disc(s) that cause pain. Magnetic Resonance Imaging is the current gold-standard for visualizing disc anatomy, but since many degenerated discs are painless, it doesn’t provide the surgeon with the required critical information. Provocative discography is an invasive procedure to identify a painful disc. It involves percutaneous placement of a needle into the disc, followed by injection of saline to pressurize the disc center. Theoretically, discs that hurt when pressurized are abnormal, and many surgeons use this procedure as an indication for surgery. However, provocative discography is a controversial, painful procedure having a positive predictive value of only 50% to 60%, and consequently many argue it is of limited clinical value. Physicians do not have a procedure to accurately identify painful discs and quantify disc pain risk. Such a tool would allow doctors to objectively locate discs that benefit from aggressive medical intervention, such as surgery. This tool would also be useful to monitor the efficacy of new therapies meant to restore disc health. Researchers at UCSF have recently identified chemical features of painful discs that are measurable using high strength magnetic resonance technology. Nocimed has licensed this technology and is developing the hardware and software to allow these chemical features to be measured painlessly in back pain patients. If successful, this technology will revolutionize the way physicians diagnosis and treat low back pain.

Itl-bio 10148/LSIT 1014 (UC Discovery)
Evaluation of non-invasive biomarkers using in vivo high field MR imaging and spectroscopy

The objective of this proposal is to support a collaborative effort between the California-based research and development group of a corporate leader in medical imaging technology (General Electric Medical Systems) and leaders in education and innovative research at the multi-campus California Institute for Quantitative Biomedical Research (QB3). The focus for the research component of the project is the 3T whole body scanners at UCSF and the 7T whole body scanner that is situated at the High Field Magnetic Resonance (MR) Center in the QB3 building at Mission Bay. The educational component of the project will involve students and postdoctoral scientists from UCSF, UC Berkeley and UC Southern California and will provide both hands-on and seminar-based training. The resources that are developed as part of the collaboration will be made available to researchers from all three of the institutions participating in QB3, as well as other academic and industrial partners in California. The project will make a major contribution to solving the engineering challenges associated with high field whole body MR scanners and to defining the most appropriate biological and medical applications. This is expected to benefit the citizens of California at large in terms of improving the diagnosis and evaluation of common diseases such as cancer, osteoarthritis and neurological disorders and to facilitate the growth of numerous small companies, particularly in the area of RF technologies, biomarker development and biopharmaceuticals.

Related Articles

Bauer JS, Banerjee S, Henning TD, Krug R, Majumdar S, Link TM. Fast high-spatial-resolution MRI of the ankle with parallel imaging using GRAPPA at 3 T. AJR Am J Roentgenol. 2007 Jul;189(1):240-5.

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