Background: To develop and evaluate a diffusion MRI-based apparent muscle fiber diameter (AFD) method in patients with muscle denervation. It was hypothesized that AFD differences between denervated, non-denervated and control muscles would be greater than those from standard diffusion metrics.Methods: A spin-echo diffusion acquisition with multi-b-valued diffusion sampling was used. An orientation-invariant dictionary approach utilized a cylinder-based forward model and multi-compartment model for obtaining restricted and free fractions. Simulations were performed to determine precision, bias, and optimize dictionary parameters. In all, 18 exams of patients with muscle denervation and 8 exams of healthy subjects were performed at 3T. Six regions of interests (ROIs) within separate shoulder muscles were selected, yielding three groups consisting 47 control (healthy), 36 non-denervated (patients), and 68 denervated (patients) muscle ROIs. Two-sample t-tests (α=0.05) between groups were performed with Holm-Bonferroni correction. T 2 -and fat fraction (FF)-mapping were acquired for comparison. Results: Mean AFD was 89.7±13.6 µm in control, 71.6±15.3 µm in non-denervated, and 60.7±15.9 µm in denervated muscles and were significantly different (P<0.001) in paired comparisons and in 10/12 individual muscle region comparisons. Correlation between AFD and FF (−0.331, P<0.001) was low, but correlation between FA and FF was negligible (0.197, P=0.016). Correlation was low between AFD and T 2 (−0.395, P<0.001) and between FA and T 2 (0.359, P<0.001).Conclusions: Diffusion MRI-based AFD complements T2-and FF-mapping techniques to non-invasively assess muscle denervation.

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Background Quantitative diffusion MRI is a promising technique for evaluating peripheral nerve integrity but low signal‐to‐noise ratio (SNR) can impede measurement accuracy. Purpose To evaluate principal component analysis (PCA) and generalized spherical deconvolution (genSD) denoising techniques to improve within‐subject reproducibility and peripheral nerve conspicuity. Study Type Prospective. Subjects Seven healthy volunteers and three peripheral neuropathy patients. Field Strength/Sequence 3T/multiband single‐shot echo planar diffusion sequence using multishell 55‐direction scheme. Assessment Images were processed using four methods: "original" (no denoising), "average" (10 repetitions), "PCA‐only," and "PCA + genSD." Tibial and common peroneal nerve segmentations and masks were generated from volunteer diffusion data. Quantitative (SNR and contrast‐to‐noise ratio [CNR]) values were calculated. Three radiologists qualitatively evaluated nerve conspicuity for each method. The two denoising methods were also performed in three patients with peripheral neuropathies. Statistical Tests For healthy volunteers, calculations included SNR and CNRFA (computed using FA values). Coefficient of variation (CV%) of CNRFA quantified within‐subject reproducibility. Groups were compared with two‐sample t‐tests (significance P < 0.05; two‐tailed, Bonferroni‐corrected). Odds ratios (ORs) quantified the relative rates of each of three radiologists confidently identifying a nerve, per slice, for the four methods. Results "PCA + genSD" yielded the highest SNR (meanoverall = 14.83 ± 1.99) and tibial and common peroneal nerve CNRFA (meantibial = 3.45, meanperoneal = 2.34) compared to "original" (P SNR < 0.001; P CNR = 0.011) and "PCA‐only" (P SNR < 0.001, P CNR < 0.001). "PCA + genSD" had higher within‐subject reproducibility (low CV%) for tibial (6.04 ± 1.98) and common peroneal nerves (8.27 ± 2.75) compared to "original" and "PCA‐only." The mean FA was higher for "original" than "average" (P < 0.001), but did not differ significantly between "average" and "PCA + genSD" (P = 0.14). "PCA + genSD" had higher tibial and common peroneal nerve conspicuity than "PCA‐only" (ORtibial = 2.50, P < 0.001; ORperoneal = 1.86, P < 0.001) and "original" (ORtibial = 2.73, P < 0.001; ORperoneal = 2.43, P < 0.001). Data Conclusion PCA + genSD denoising method improved SNR, CNRFA, and within‐subject reproducibility (CV%) without biasing FA and nerve conspicuity. This technique holds promise for facilitating more reliable, unbiased diffusion measurements of peripheral nerves. Level of Evidence: 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:1128–1137.