Aims: Our objective was to assess the qualitative soft tissue changes which occur in the diabetic neuropathic foot, which may predispose to ulceration, using a specific magnetic resonance imaging (MRI) contrast sequence, magnetization transfer (MT) which produces contrast based on exchange between water bound to macromolecules (e.g. collagen) and free water (e.g. extracellular fluid).
Methods: The first metatarsal head of 19 diabetic neuropathic subjects and 11 diabetic non-neuropathic controls was studied using a 'targeted' radiofrequency coil. Neuropathy was classified using vibration perception threshold (VPT) (< or > 25 V), cold threshold (< 1 degree C or > 4 degrees C) and Michigan neuropathy score (< 5 or > 15). Peripheral vascular disease was excluded. Results were expressed as percentage of tissue MT activity in a cross-sectional area. At autopsy full thickness biopsies were taken from the plantar fat pad of 10 unrelated subjects with diabetic neuropathy.
Results: Healthy muscle displays high MT activity, whereas adipose tissue induces little activity. Muscle MT activity was considerably reduced (75+/-20%, 30+/-24%, P<0.001) and fat pad MT activity was considerably increased in subjects with neuropathy (37+/-17% 68+/-21%, P<0.001). Muscle fibre atrophy decreases MT activity, whereas fibrous infiltration of the fat pad increases MT activity, fibro-atrophic post-mortem histological changes were found in the plantar fat pads of all neuropathic subjects examined (n = 10).
Conclusions: Changes in MT activity reflect qualitative structural changes which this study reveals are extensive in the diabetic neuropathic foot. Fibrotic atrophy of the plantar fat pad may affect its ability to dissipate the increased weight-bearing forces associated with diabetic neuropathy.