Robert L. Greenman

Early changes in the skin microcirculation and muscle metabolism of the diabetic foot.

BACKGROUND Changes in the large vessels and microcirculation of the diabetic foot are important in the development of foot ulceration and subsequent failure to heal existing ulcers. We investigated whether oxygen delivery and muscle metabolism of the lower extremity were factors in diabetic foot disease. METHODS We studied 108 patients (21 control individuals who did not have diabetes, 36 patients with diabetes who did not have neuropathy, and 51 patients with both diabetes and neuropathy). We used medical hyperspectral imaging (MHSI) to investigate the haemoglobin saturation (S(HSI)O2; % of oxyhaemoglobin in total haemoglobin [the sum of oxyhaemoglobin and deoxyhaemoglobin]) in the forearm and foot; we also used 31P-MRI scans to study the cellular metabolism of the foot muscles by measuring the concentrations of inorganic phosphate and phosphocreatine and calculating the ratio of inorganic phosphate to phosphocreatine (Pi/PCr). FINDINGS The forearm S(HSI)O2 during resting was different in all three groups, with the highest value in controls (mean 42 [SD 17]), followed by the non-neuropathic (32 [8]) and neuropathic (28 [8]) groups (p<0.0001). In the foot at resting, S(HSI)O2 was higher in the control (38 [22]) and non-neuropathic groups (37 [12]) than in the neuropathic group (30 [12]; p=0.027). The Pi/PCr ratio was higher in the non-neuropathic (0.41 [0.10]) and neuropathic groups (0.58 [0.26]) than in controls (0.20 [0.06]; p<0.0001). INTERPRETATION Our results indicate that tissue S(HSI)O2 is reduced in the skin of patients with diabetes, and that this impairment is accentuated in the presence of neuropathy in the diabetic foot. Additionally, energy reserves of the foot muscles are reduced in the presence of diabetes, suggesting that microcirculation could be a major reason for this difference.

3T MR of the prostate: reducing susceptibility gradients by inflating the endorectal coil with a barium sulfate suspension.

Most prostate MRI/MRS examinations are performed with an endorectal coil inflated with air, leading to an air–tissue interface that induces magnetic susceptibility gradients within the gland. Inflation of the coil with a barium sulfate suspension is described and compared to inflation with air or liquid perfluorocarbon (PFC). The B0 field in the prostate gland was mapped for five healthy volunteers when the endorectal coil was inflated with each of the three agents. A marked decrease in the posterior‐anterior (P‐A) field gradient and a significant improvement in field homogeneity were evident in the presence of a barium suspension and PFC relative to air. MRS data acquired from the prostate gland in the presence of air, PFC, and a barium suspension in the endorectal coil showed similar trends, demonstrating improvement in line‐widths and spectral resolution when the barium suspension or the PFC were inflating the endorectal coil. On this basis we conclude that a barium suspension provides an available, cheap, and safe alternative to PFC, and we suggest that inflating the endorectal coil with a barium suspension should be considered for prostate MR studies, especially at high field strengths (such as 3T). Magn Reson Med 57:898–904, 2007.

Strategies for shimming the breast.

There is evidence in the literature indicating a significant static field inhomogeneity in the human breast. A nonhomogenous field results in line broadening and frequency shifts in MRS and can cause intensity loss and spatial errors in MRI. Thus, there is a clear rationale for determining the regional variations in the static field homogeneity in the breast and providing strategies to correct them. Herein, the nature and extent of the static magnetic field at 3 T were measured in central planes of the human breast using both phase maps and multivoxel MRS techniques. In addition, the effect of first‐ and high‐order shimming and of spatial saturation pulses on the static field inhomogeneity was evaluated. Both the theoretical and the measured field were found to be primarily linear in nature, with a reduction of 300 Hz from the nipple to the chest wall. First‐order shimming reduced this inhomogeneity by 65%. Interestingly, the combination of spatial saturation pulses and first‐order shimming was more effective than high‐order shim alone. Since many clinical scanners do not have either higher‐order shim or automated higher shimming algorithms that work in the presence of fat, the suggested combination provides an effective means to correct inhomogeneities in the breast. Magn Reson Med, 2005.

Evaluation of skeletal muscle during calf exercise by 31-phosphorus magnetic resonance spectroscopy in patients on statin medications.

Muscle pain is a common side effect of statin medications, but the cause is poorly understood. We characterized phosphocreatine (PCr) exercise recovery kinetics in 10 patients with hypercholesterolemia before and after a 4‐week regimen of statin therapy using 31‐phosphorus magnetic resonance spectroscopy (31P‐MRS). 31P spectra were obtained before, during, and after exercise on a calf flexion pedal ergometer. Creatine kinase (CK) serum levels were drawn before and after statin therapy. The mean metabolic recovery time constant in subjects increased from 28.1 s (SE = 6.5 s) to 55.4 s (SE = 7.4 s) after statin therapy. The unweighted mean of the pre/post‐recovery time difference was −27.3 s (SE = 12.4 s; P = 0.02). Pre‐ and post‐therapy CK levels were not significantly different (P = 0.50). Metabolic recovery time in the calf is prolonged in patients after statin use. This suggests that statins impair mitochondrial oxidative function, and 31P MRS is a potential study model for statin‐associated myopathy. Muscle Nerve, 2011

Quantification of the 31P metabolite concentration in human skeletal muscle from RARE image intensity.

A method is described for quantifying the cellular phosphorus‐31 (31P) concentration in human skeletal muscle based on RARE (rapid acquisition with relaxation enhancement) image intensities. The 31P concentrations were calculated using relaxation rates, RF coil spatial characteristics, and RARE signal intensities from foot muscle and an external 31P standard. 31P RARE and 1H T2‐weighted images of the foot muscles in 11 normal subjects were acquired at 3.0 T using a double‐tuned (31P/1H) birdcage coil. 31P PRESS (point‐resolved spectroscopy) spectra were acquired to verify the measurable 31P concentrations in a multiecho acquisition. The mean measured concentration was 26.4 ± 3.1 mM (mean ± SD) from RARE signal intensities averaged over the entire imaged foot anatomy and 27.6 ± 4.1 mM for a 3 × 3 pixel region‐of‐interest measurement. The 31P RARE image acquisition time was 4 min with a 0.55 cm3 voxel size. These results demonstrate that the 31P concentration can be accurately measured noninvasively in human muscle from RARE images acquired in short scan times with relatively high spatial resolution. Magn Reson Med 52:1036–1042, 2004.

Evaluation of the RF field uniformity of a double-tuned 31P/1H birdcage RF coil for spin-echo MRI/MRS of the diabetic foot

To evaluate the B1 field uniformity of a double‐tuned birdcage coil designed for 31P/1H MRI/MRS spin‐echo (SE) imaging of the metatarsal head region of the foot in neuropathic diabetic patients.

The feasibility of measuring phosphocreatine recovery kinetics in muscle using a single-shot (31)P RARE MRI sequence

RATIONALE AND OBJECTIVES Heterogeneity of skeletal muscle structure, composition, and perfusion results in spatial differences in oxidative function between muscles and muscle regions. The simultaneous measurement of the postexercise phosphocreatine (PCr) recovery rate across all muscles of a human limb cross-section may provide new insights into normal physiology and disease states. The objective of this work was to assess the feasibility of acquiring PCr rapid acquisition with relaxation enhancement (RARE) images with sufficient temporal and spatial resolution to accurately measure PCr recovery kinetics in a cross-section of a human limb. MATERIALS AND METHODS One normal subject performed a finger exercise until fatigued. At cessation of exercise surface coil localized pulse-and-acquire phosphorus-31 MR spectra ((31)P- magnetic resonance spectroscopy [MRS]) of the forearm were acquired at 6 S intervals for 4 minutes. The exercise protocol was repeated 7 days later and axial PCr RARE images of the forearm were acquired following exercise with 5.6 cm(3) voxels at 6-second intervals for 4 minutes. RESULTS The PCr recovery time constants for the PCr RARE and (31)P-MRS measurements were 91.0 and 91.1 seconds, respectively, based on a monoexponential fit. A Pearson correlation test showed that the PCr recovery data that resulted from the RARE PCr imaging were highly correlated with the data resulting from the (31)P-MRS (r = 0.91, P < .0001). DISCUSSION Data from selected regions of RARE PCr images acquired at 6-second intervals compare well to those acquired using surface coil (31)P MR spectroscopy and can provide an accurate assessment of PCr recovery kinetics.

Simultaneous Acquisition of Phosphocreatine and Inorganic Phosphate Images for Pi:PCr Ratio Mapping Using a RARE Sequence with Chemically Selective Interleaving

The ratio of inorganic phosphate to phosphocreatine (Pi:PCr) is a validated marker of mitochondrial function in human muscle. The magnetic resonance imaging rapid acquisition with relaxation enhancement (RARE) pulse sequence can acquire phosphorus-31 ((31)P) images with higher spatial and temporal resolution than traditional spectroscopic methods, which can then be used to create Pi:PCr ratio maps of muscle regions. While the (31)P RARE method produces images that reflect the content of the (31)P metabolites, it has been limited to producing an image of only one chemical shift in a scan. This increases the scan time required to acquire images of multiple chemical shifts as well as the likelihood of generating inaccurate Pi:PCr maps due to gross motion. This work is a preliminary study to demonstrate the feasibility of acquiring Pi and PCr images in a single scan by interleaving Pi and PCr chemical shift acquisitions using a chemically selective radiofrequency excitation pulse. The chemical selectivity of the excitation pulse evaluated and the Pi:PCr maps generated using the interleaved Pi and PCr acquisition method with the subject at rest and during exercise are compared to those generated using separate Pi and PCr acquisition scans. A paired t test indicated that the resulting Pi:PCr ratios for the exercised forearm muscle regions were not significantly different between the separate Pi and PCr acquisition method (3.18±1.53) (mean±standard deviation) and the interleaved acquisition method (3.41±1.66). This work demonstrates the feasibility of creating Pi:PCr ratio maps in human muscle with Pi and PCr images acquired simultaneously by interleaving between the Pi and PCr resonances in a single scan.

Assessment OF aged mdx mice by electrical impedance myography and magnetic resonance imaging

Introduction: Similar to magnetic resonance imaging (MRI), electrical impedance myography (EIM) is dependent on the presence and location of water in muscle to assess neuromuscular diseases. We compared the 2 technologies in mdx mice to better understand their relationship. Methods: EIM and MRI, using T2 relaxation and diffusion‐weighted imaging (DWI), were performed on the gastrocnemius of 10 mdx and 10 wild‐type mice. Muscle function and tissue composition measurements were compared with the EIM and MRI data. Results: EIM reactance and T2 relaxation mapping can discriminate healthy from diseased mice (P < 0.001 for both), but DWI could not. Both T2 relaxation and EIM reactance also correlated closely with muscle function/composition and with each other. Conclusion: Given the low cost of EIM and the simplicity of application, it may be a valuable alternative to muscle MRI in Duchenne muscular dystrophy, where simple cumulative indices of muscle health are being sought. Muscle Nerve 52: 598–604, 2015

Foot Muscle Energy Reserves In Diabetic Patients Without And With Clinical Peripheral Neuropathy

OBJECTIVE To investigate changes in the foot muscle energy reserves in diabetic non-neuropathic and neuropathic patients. RESEARCH DESIGN AND METHODS We measured the phosphocreatinine (PCr)/inorganic phosphate (Pi) ratio, total 31P concentration, and the lipid/water ratio in the muscles in the metatarsal head region using MRI spectroscopy in healthy control subjects and non-neuropathic and neuropathic diabetic patients. RESULTS The PCr/Pi ratio was higher in the control subjects (3.23 ± 0.43) followed by the non-neuropathic group (2.61 ± 0.36), whereas it was lowest in the neuropathic group (0.60 ± 1.02) (P < 0.0001). There were no differences in total 31P concentration and lipid/water ratio between the control and non-neuropathic groups, but both measurements were different in the neuropathic group (P < 0.0001). CONCLUSIONS Resting foot muscle energy reserves are affected before the development of peripheral diabetic neuropathy and are associated with the endothelial dysfunction and inflammation.