Foot Small Muscle Atrophy Is Present Before the Detection of Clinical Neuropathy

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Abstract
OBJECTIVE—To characterize structural changes and the metabolic profile of foot muscles and correlate them with diabetic neuropathy measurements using phosphorus-31 (31P) rapid acquisition with relaxation enhancement (RARE) magnetic resonance imaging (MRI). RESEARCH DESIGN AND METHODS—We studied 12 control subjects, 9 nonneuropathic diabetic patients, and 12 neuropathic diabetic patients using 31P RARE and proton (1H) MRI at 3 Tesla. The ratio of the total cross-sectional area of the foot to that of the muscle tissue was calculated from transaxial 1H and 31P images. The average 31P concentration across the metatarsal head region was measured from the 31P images. RESULTS—The muscle area−to−total area ratio differed among all three groups (means ± SD): 0.55 ± 0.04 vs. 0.44 ± 0.05 vs. 0.06 ± 0.06 for control, nonneuropathic, and neuropathic subjects, respectively (P < 0.0001). The average 31P concentration also differed among all groups: 27.7 ± 3.8 vs. 21.7 ± 4.8 vs. 7.9 ± 8.8 mmol/l for control, nonneuropathic, and neuropathic subjects (P < 0.0001). The muscle area−to−total area ratio strongly correlated with clinical measurements: Neuropathy Disability Score, r = −0.83, P < 0.0001; vibration perception threshold, r = −0.79, P < 0.0001; and Semmes-Weinstein monofilaments, r = −0.87, P < 0.0001. CONCLUSIONS—Small muscle atrophy is present in diabetes before clinical peripheral neuropathy can be detected using standard clinical techniques. The 31P RARE MRI method evaluates the severity of muscle atrophy, even in the early stages when neuropathy is absent. This technique may prove to be a useful diagnostic tool in identifying early-stage diabetic foot problems.