The overall objective of this proposal is to develop a three-dimensional MR imaging protocol to investigate the phosphorus-31 metabolism in the muscle tissue in the lower extremities of diabetic patients. Fifteen million people suffer from diabetes mellitus in the United States and there are 650,000 new cases diagnosed each year. Changes in the structure of the basement membrane of capillaries and neuropathy of the autonomic nerves create an effective ischemia in localized capillary beds in the lower leg and foot. Anatomical methods exist for assessing the blood flow and nerve viability in the lower legs and feet of diabetics. However, these techniques do not provide a direct assessment of the metabolic state of the affected muscle tissue. Phosphorus magnetic resonance spectroscopy (MRS) has been used to study the metabolism of muscle tissue and assess the metabolic state of ischemic tissue in a noninvasive way in humans. The current MRS localization technique that can be used to provide a regional assessment of the lower leg and foot with the ability to identify focal areas of ischemia is chemical shift imaging (CSI). However, a scan of the lower extremities having a resolution that is high enough to identify local areas with poor blood flow using the currently available CSI technique would take more than 21 minutes making the MR examination prohibitively long. We have exploited the recent advances in high-speed magnetic resonance imaging techniques to develop a method for directly creating images of a single phosphorus metabolite (e.g. phosphocreatine) in human skeletal muscle. We have successfully acquired pure phosphocreatine images of human skeletal muscle in normal volunteers having a spatial resolution of 0.23 cm3 in 2 minutes on a whole body MR scanner. We propose to establish a protocol using a 3-dimensional technique for the study of muscle viability in the lower extremities of diabetic patients who suffer from complications resulting from polyneuropathy and localized ischemia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DK058651-01A2
Application #
6473293
Study Section
Metabolism Study Section (MET)
Program Officer
Jones, Teresa L Z
Project Start
2002-08-01
Project End
2004-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
1
Fiscal Year
2002
Total Cost
$162,735
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
Greenman, Robert L; Wang, Xiaoen; Smithline, Howard A (2011) Simultaneous acquisition of phosphocreatine and inorganic phosphate images for Pi:PCr ratio mapping using a RARE sequence with chemically selective interleaving. Magn Reson Imaging 29:1138-44
Greenman, Robert L; Smithline, Howard A (2011) The feasibility of measuring phosphocreatine recovery kinetics in muscle using a single-shot (31)P RARE MRI sequence. Acad Radiol 18:917-23
Greenman, Robert L; Wang, Xiaoen; Ngo, Long et al. (2008) An assessment of the sharpness of carotid artery tissue boundaries with acquisition voxel size and field strength. Magn Reson Imaging 26:246-53
Greenman, Robert L; Khaodhiar, Lalita; Lima, Christina et al. (2005) Foot small muscle atrophy is present before the detection of clinical neuropathy. Diabetes Care 28:1425-30
Greenman, Robert L; Rakow-Penner, Rebecca (2005) Evaluation of the RF field uniformity of a double-tuned 31P/1H birdcage RF coil for spin-echo MRI/MRS of the diabetic foot. J Magn Reson Imaging 22:427-32
Greenman, Robert L; Panasyuk, Svetlana; Wang, Xiaoen et al. (2005) Early changes in the skin microcirculation and muscle metabolism of the diabetic foot. Lancet 366:1711-7
Greenman, Robert L (2004) Quantification of the 31P metabolite concentration in human skeletal muscle from RARE image intensity. Magn Reson Med 52:1036-42