Faculty Bibliography

INTRODUCTION/BACKGROUND:The purpose of this study was to characterize using MRI the effects of a 10-week supervised exercise program on lower extremity skeletal muscle composition, nerve microarchitecture, and metabolic function in individuals with diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS/METHODS:) and once following intervention to measure relaxation times (T1, T1ρ, and T2), phosphocreatine recovery, fat fraction, and diffusion parameters. RESULTS:and postintervention MRI metrics were: calf adipose infiltration -2.6%±6.4%, GM T1ρ -4.1%±7.7%, GM T2 -3.5%±6.4%, and gastrocnemius lateral T2 -4.6±7.4%. Insignificant changes were observed in gastrocnemius phosphocreatine recovery rate constant (p>0.3) and tibial nerve fractional anisotropy (p>0.6) and apparent diffusion coefficient (p>0.4). CONCLUSIONS:The 10-week supervised exercise intervention program successfully reduced adiposity and altered resting tissue properties in the lower leg in DPN. Gastrocnemius mitochondrial oxidative capacity and tibial nerve microarchitecture changes were not observed, either due to lack of response to therapy or to lack of measurement sensitivity.

OBJECTIVES/OBJECTIVE:We describe measurement of skeletal muscle kinetics with multiple echo diffusion tensor imaging (MEDITI). This approach allows characterization of the microstructural dynamics in healthy and pathologic muscle. MATERIALS AND METHODS/METHODS:In a Siemens 3-T Skyra scanner, MEDITI was used to collect dynamic DTI with a combination of rapid diffusion encoding, radial imaging, and compressed sensing reconstruction in a multi-compartment agarose gel rotation phantom and within in vivo calf muscle. An MR-compatible ergometer (Ergospect Trispect) was employed to enable in-scanner plantar flexion exercise. In a HIPAA-compliant study with written informed consent, post-exercise recovery of DTI metrics was quantified in eight volunteers. Exercise response of DTI metrics was compared with that of T2-weighted imaging and characterized by a gamma variate model. RESULTS: = 0.303 ± 0.185). Diffusion and T2-weighted response magnitudes were correlated (e.g., r = 0.792, p = 0.019 for nMD vs. nT2w). CONCLUSION/CONCLUSIONS:We have demonstrated the feasibility of MEDITI for capturing spatially resolved diffusion tensor data in dynamic systems including post-exercise skeletal muscle recovery following in-scanner plantar flexion.

PURPOSE: To develop a high temporal resolution imaging method that measures muscle-specific phosphocreatine (PCr) resynthesis time constant (tauPCr ) and pH changes in muscles of the lower leg following exercise on a clinical 3T MRI scanner. METHODS: We developed a frequency-selective 3D non-Cartesian FLORET sequence to measure PCr with 17-mm nominal isotropic resolution (28 mm actual resolution) and 6-s temporal resolution to capture dynamic metabolic muscle activity. The sequence was designed to additionally collect inorganic phosphate spectra for pH quantification, which were localized using sensitivity profiles of individual coil elements. Nineteen healthy volunteers were scanned while performing a plantar flexion exercise on an in-house developed ergometer. Data were acquired with a dual-tuned multichannel coil array that enabled phosphorus imaging and proton localization for muscle segmentation. RESULTS: After a 90-s plantar flexion exercise at 0.66 Hz with resistance set to 40% of the maximum voluntary contraction, tauPCr was estimated at 22.9 +/- 8.8 s (mean +/- standard deviation) with statistical coefficient of determination r2 = 0.89 +/- 0.05. The corresponding pH values after exercise were in the range of 6.9-7.1 in the gastrocnemius muscle. CONCLUSION: The developed technique allows measurement of muscle-specific PCr resynthesis kinetics and pH changes following exercise, with a temporal resolution and accuracy comparable to that of single voxel 31 P-MRS sequences. Magn Reson Med, 2017. (c) 2017 International Society for Magnetic Resonance in Medicine.

OBJECTIVE: To develop a low-cost pedal ergometer compatible with ultrahigh (7 T) field MR systems to reliably quantify metabolic parameters in human lower leg muscle using phosphorus magnetic resonance spectroscopy. MATERIALS AND METHODS: We constructed an MR compatible ergometer using commercially available materials and elastic bands that provide resistance to movement. We recruited ten healthy subjects (eight men and two women, mean age +/- standard deviation: 32.8 +/- 6.0 years, BMI: 24.1 +/- 3.9 kg/m2). All subjects were scanned on a 7 T whole-body magnet. Each subject was scanned on two visits and performed a 90 s plantar flexion exercise at 40% maximum voluntary contraction during each scan. During the first visit, each subject performed the exercise twice in order for us to estimate the intra-exam repeatability, and once during the second visit in order to estimate the inter-exam repeatability of the time constant of phosphocreatine recovery kinetics. We assessed the intra and inter-exam reliability in terms of the within-subject coefficient of variation (CV). RESULTS: We acquired reliable measurements of PCr recovery kinetics with an intra- and inter-exam CV of 7.9% and 5.7%, respectively. CONCLUSION: We constructed a low-cost pedal ergometer compatible with ultrahigh (7 T) field MR systems, which allowed us to quantify reliably PCr recovery kinetics in lower leg muscle using 31P-MRS.

PURPOSE: The present review highlights current concepts regarding the effects of diabetic peripheral neuropathy (DPN) in skeletal muscle. It discusses the lack of effective pharmacologic treatments and the role of physical exercise intervention in limb protection and symptom reversal. It also highlights the importance of magnetic resonance imaging (MRI) techniques in providing a mechanistic understanding of the disease and helping develop targeted treatments. METHODS: This review provides a comprehensive reporting on the effects of DPN in the skeletal muscle of patients with diabetes. It also provides an update on the most recent trials of exercise intervention targeting DPN pathology. Lastly, we report on emerging MRI techniques that have shown promise in providing a mechanistic understanding of DPN and can help improve the design and implementation of clinical trials in the future. FINDINGS: Impairments in lower limb muscles reduce functional capacity and contribute to altered gait, increased fall risk, and impaired balance in patients with DPN. This finding is an important concern for patients with DPN because their falls are likely to be injurious and lead to bone fractures, poorly healing wounds, and chronic infections that may require amputation. Preliminary studies have shown that moderate-intensity exercise programs are well tolerated by patients with DPN. They can improve their cardiorespiratory function and partially reverse some of the symptoms of DPN. MRI has the potential to bring new mechanistic insights into the effects of DPN as well as to objectively measure small changes in DPN pathology as a result of intervention. IMPLICATIONS: Noninvasive exercise intervention is particularly valuable in DPN because of its safety, low cost, and potential to augment pharmacologic interventions. As we gain a better mechanistic understanding of the disease, more targeted and effective interventions can be designed.

Magnetic resonance imaging (MRI) provides the unique ability to study metabolic and microvasculature functions in skeletal muscle using phosphorus and proton measurements. However, the low sensitivity of these techniques can make it difficult to capture dynamic muscle activity due to the temporal resolution required for kinetic measurements during and after exercise tasks. Here, we report the design of a dual-nuclei coil array that enables proton and phosphorus MRI of the human lower extremities with high spatial and temporal resolution. We developed an array with whole-volume coverage of the calf and a phosphorus signal-to-noise ratio of more than double that of a birdcage coil in the gastrocnemius muscles. This enabled the local assessment of phosphocreatine recovery kinetics following a plantar flexion exercise using an efficient sampling scheme with a 6 s temporal resolution. The integrated proton array demonstrated image quality approximately equal to that of a clinical state-of-the-art knee coil, which enabled fat quantification and dynamic blood oxygen level-dependent measurements that reflect microvasculature function. The developed array and time-efficient pulse sequences were combined to create a localized assessment of calf metabolism using phosphorus measurements and vasculature function using proton measurements, which could provide new insights into muscle function.

A dual-nuclei radiofrequency coil array was constructed for phosphorus and proton magnetic resonance imaging and spectroscopy of the human brain at 7T. An eight-channel transceive degenerate birdcage phosphorus module was implemented to provide whole-brain coverage and significant sensitivity improvement over a standard dual-tuned loop coil. A nested eight-channel proton module provided adequate sensitivity for anatomical localization without substantially sacrificing performance on the phosphorus module. The developed array enabled phosphorus spectroscopy, a saturation transfer technique to calculate the global creatine kinase forward reaction rate, and single-metabolite whole-brain imaging with 1.4cm nominal isotropic resolution in 15min (2.3cm actual resolution), while additionally enabling 1mm isotropic proton imaging. This study demonstrates that a multi-channel array can be utilized for phosphorus and proton applications with improved coverage and/or sensitivity over traditional single-channel coils. The efficient multi-channel coil array, time-efficient pulse sequences, and the enhanced signal strength available at ultra-high fields can be combined to allow volumetric assessment of the brain and could provide new insights into the underlying energy metabolism impairment in several neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, as well as mental disorders such as schizophrenia.

Purpose: Elevated bone marrow fat content and elevated intramuscular fat content increase the risk for osteoporotic fracture, but it is unknown if such changes are associated with detrimental changes in bone microarchitecture and bone mass. Our goal was to determine the association between femoral neck bone marrow fat fraction and gluteal muscle fat fraction with: 1) femoral neck bone microarchitecture and 2) femoral neck bone mineral density (BMD). Materials and Methods: This study was HIPAA compliant and institutional review board approved. Written informed consent was obtained. Hips of forty-two consecutive patients referred from the osteoporosis clinic at our institution (mean-age 60.2 +/- 7.5 years) underwent dual-energy X-ray absorptiometry (DXA), high-spatial resolution three-dimensional 3 T MRI with volumetric topological analysis (VTA-MRI), and fat quantification with IDEAL-MRI. Femoral neck BMD T-scores (DXA) and trabecular bone microarchitecture parameters (VTA-MRI) were calculated. Proton density fat fractions (IDEAL-MRI) of the femoral neck bone marrow (FFmarrow) and the gluteus maximus muscle (FFmuscle) were measured by two independent readers. Interreader agreement was calculated using intraclass correlation coefficients (ICC). FFmarrow and FFmuscle were correlated with BMD, bone microarchitecture parameters, age, and body-massindex (BMI). Results: FFmarrow (mean from both readers 70.2 +/- 6.5 %) and FFmuscle (11.3 +/- 3.8 %) measurements showed excellent interreader agreement (ICC = 0.955/0.995; both p < 0.0005). No statistically significant correlation between FFmarrow and BMD was found (r = -0.257, p = 0.155). Age- and BMI-adjusted FFmarrow inversely correlated with trabecular plate-to-rod ratio (r = -0.335; p = 0.049) and trabecular plate-width (r = -0.345; p = 0.042), but not with bone volume fraction (r = 0.155; p = 0.374). FFmarrow correlated with age (r = 0.383; p = 0.021), but not with BMI (r = 0.132; p = 0.445). FFmuscle showed no correlation with BMD or bone microarchitecture. FFmuscle was independently correlated with BMI (r = 0.557; <0.0005) and age (r = 0.438; p = 0.008). Conclusion: Bone marrow fat content inversely correlated with trabecular plate-to-rod ratio and plate-width, but not BMD, suggesting that the increased fracture risk in the setting of elevated bone marrow fat content may in part be mediated via microarchitectural deterioration, rather than via reduced BMD. Gluteal muscle fat content did not correlate with changes in femoral neck microarchitecture or BMD, suggesting that intramuscular fat content may increase fracture risk independent of detrimental changes in bone microarchitecture and BMD. Overall, highresolution 3 T MRI of bone microarchitecture combined with IDEAL-based fat quantification can help provide insight into the relationship between adipose bone marrow, lean muscle mass, and possible mechanisms of osteoporotic fracture risk in vivo

PURPOSE: To assess the feasibility of mapping the kinetics and unidirectional fluxes of inorganic phosphate (Pi) to adenosine triphosphate (ATP) reactions in the entire volume of the lower leg muscles using a three-dimensional saturation transfer (ST) phosphorus (31 P) imaging sequence. THEORY AND METHODS: We imaged the lower leg muscles of five healthy subjects at 7.0 Tesla. The total experimental time was 45 min. We quantified muscle-specific forward reaction rate constants (k' f ) and metabolic fluxes (Vf ) of the Pi-to-ATP reaction in the tibialis anterior, the gastrocnemius, and the soleus. RESULTS: In the tibialis anterior, k' f and Vf were 0.11 s-1 +/- 0.03 (mean +/- standard deviation) and 0.34 mM s-1 +/- 0.10, respectively. In the gastrocnemius, k' f was 0.11 s-1 +/- 0.04 and Vf was 0.37 mM s-1 +/- 0.11, while in the soleus muscle k' f was 0.10 s-1 +/- 0.02 and Vf was 0.36 mM s-1 +/- 0.14. CONCLUSION: Our results suggest that mapping the kinetics and unidirectional fluxes from Pi-to-ATP in both the anterior and posterior muscles of the lower leg is feasible at ultra-high field and may provide useful insights for the study of insulin resistance, diabetes and aging. Magn Reson Med, 2014. (c) 2014 Wiley Periodicals, Inc.