Introduction Nonhypoxic hypobaric (low atmospheric pressure) occupational exposure, such as experienced by U.S. Air Force U-2 pilots and safety personnel operating inside altitude chambers, is associated with increased subcortical white matter hyperintensity (WMH) burden. The pathophysiological mechanisms underlying this discrete WMH change remain unknown. The objectives of this study were to demonstrate that occupational exposure to nonhypoxic hypobaria is associated with altered white matter integrity as quantified by fractional anisotropy (FA) measured using diffusion tensor imaging and relate these findings to WMH burden and neurocognitive ability. Methods There were 102 U-2 pilots and 114 age- and gender-controlled, health-matched controls who underwent magnetic resonance imaging. All pilots performed neurocognitive assessment. Whole-brain and tract-wise average FA values were compared between pilots and controls, followed by comparison within pilots separated into high and low WMH burden groups. Neurocognitive measurements were used to help interpret group difference in FA values. Results Pilots had significantly lower average FA values than controls (0.489/0.500, respectively). Regionally, pilots had higher FA values in the fronto-occipital tract where FA values positively correlated with visual-spatial performance scores (0.603/0.586, respectively). There was a trend for high burden pilots to have lower FA values than low burden pilots. Discussion Nonhypoxic hypobaric exposure is associated with significantly lower average FA in young, healthy U-2 pilots. This suggests that recurrent hypobaric exposure causes diffuse axonal injury in addition to focal white matter changes.

Purpose: To quantify and compare the intramyocellular (IMCL), extramyocellular (EMCL) lipids and total fat fraction in human vastus lateralis muscle between lean and type 2 diabetic (T2DM) subjects using long echo time (TE) STEAM proton MR spectroscopy ( 1 H-MRS).Methods: 1 H-MRS using single voxel (15 × 15 × 15 mm 3 ) stimulated acquisition mode (STEAM) was performed in right vastus lateralis m. on 10 lean controls (age: 28.3 ± 3.94 yo, BMI: 24.25 ± 3.20 kg/m 2 ) and 7 type 2 diabetic (age: 54.28 ± 6.42 yo, BMI: 31.34 ± 3.13 kg/m 2 ) subjects with Siemens 3T MRI and a four-channel flex coil. Unsuppressed water spectra (NSA = 16) with TR/TE = 3000/30 ms, TM = 10 ms BW = 2000 Hz, and water-suppressed spectra (NSA = 128) with TR/TE = 3000/270 ms, TM = 10 ms, fixed water suppression BW = 50 Hz were acquired. Spectral intensity ratios of IMCL-CH2, EMCL-CH2 and total lipid (IMCL + EMCL) with unsuppressed water signal (W) were converted into absolute concentrations expressed in mmol/kg. Fat fraction (100 × F/(W+F)) was also calculated, where F includes the signal intensities of IMCL and EMCL methylene (CH2)n, peaks only.Results: Comparison of IMCL (controls: 11.70 ± 6.7, T2DM: 21.74 ± 10.2, p < 0.01), EMCL (controls: 22.89 ± 18.42, T2DM: 77.21 ± 33.4, p < 0.001) and total lipid (64.35 mmol/kg less in controls, p < 0.001) showed statistical significance using two-tailed student's t-test. Mean fat fraction (%) exhibited considerable inter-individual variability for controls (3.14 ± 2.09; range: 1.34 -7.04) and T2DM (9.34 ± 2.88; range: 4.15 -13.67) and deemed significant (p < 0.05).Conclusion: Single voxel STEAM 1 H-MRS at long TE provides a robust non-invasive method for characterizing lipids within localized muscle regions, with well-resolved IMCL/EMCL peak separation. Regional lipid estimate and fat fraction in vastus lateralis muscle is significantly different in T2DM compared to normal lean controls. -------------------------------------------------------------------Impact: Single-voxel proton MR spectroscopy ( 1 H-MRS) with STEAM at long echo time (TE = 270ms) provides a robust non -invasive method for characterizing muscle lipids in vivo. This method offers rapid and convenient acquisition of high -resolution spectra with improved baseline and better lipid peak separation in skeletal muscle and allows for fat quantification with superior sensitivity and dynamic range over other MR imaging methods. This study quantified IMCL, EMCL and fat fraction using 1 H-MRS from vastus lateralis m., predominantly utilized in ex vivo physiological studies for histochemical evaluation of muscle lipid metabolism in diabetes and obesity. The method described can be combined with biochemical assays to provide insights on excess skeletal muscle fat interference with insulin signaling in obese and diabetic states in longitudinal clinical research studies . Cite this article as: Valaparla SK, Boone GRE, Ripley EM, Giuseppe D, Duong TQ, Abdul-Ghani M, Clarke GD. Skeletal muscle lipid quantification in lean and diabetic subjects...

Purpose: To quantify and compare the intramyocellular (IMCL), extramyocellular (EMCL) lipids and total fat fraction in human vastus lateralis (VL) muscle between lean controls and type 2 diabetic (T2DM) subjects using long echo time in vivo proton MR spectroscopy (1H‐MRS) Methods: 1H‐MRS single voxel (15 × 15 × 15 mm3) stimulated acquisition mode (STEAM) was performed in right vastus lateralis m. on 10 lean controls (age: 28.3±3.94 yrs, BMI: 24.25±3.20 kg/m2) and 7 type 2 diabetic (age: 54.28±6.42 yrs, BMI: 31.34±3.13 kg/m2) subjects with Siemens 3T MRI and four‐channel flex coil. Unsuppressed water spectra (NSA = 16) with TR/TE = 3000/30 msec, TM = 10 msec, BW = 2000 Hz, and water‐suppressed spectra (NSA = 128) with TR/TE = 3000/270 msec, TM = 10 msec, and fixed water suppression BW = 50 Hz were acquired. Spectral intensity ratios of IMCL‐CH2, EMCL‐CH2 and total lipid (IMCL + EMCL) with unsuppressed water signal (W) were converted into absolute concentrations expressed in mmol/kg. Fat fraction (100 × F/(W+F)) was calculated, where F includes the signal intensities of IMCL and EMCL methylene (CH2)n, peaks only. Results: Comparison of IMCL (controls: 11.70 ± 6.7, T2DM: 21.74 ± 10.2, p ≤ 0.01), EMCL (controls: 22.89 ± 18.42, T2DM: 77.21 ± 33.4, p ≤ 0.001) and total lipid (64.35 mmol/kg less in controls, p ≤ 0.001) showed statistical significance using two‐tailed student t‐test. Fat fraction (%) exhibited considerable inter‐individual variability for controls (3.14 ± 2.09; range: 1.34 – 7.04) and T2DM (9.34 ± 2.88; range: 4.15 – 13.67) and deemed significant (p ≤ 0.05 Conclusion: Single voxel STEAM 1H‐MRS at long TE provides a robust non‐invasive method for characterizing lipids within localized muscle regions, with well‐resolved IMCL/EMCL peak separation. Regional lipid estimate and fat fraction in VL m. was significantly different in T2DM compared to lean controls. American Heart Association Southwest Affiliate Pre‐doctoral Fellowship