A novel MRI analysis for assessment of microvascular vasomodulation in low-perfusion skeletal muscle

Figures

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  Figure 1. Inadequate sensitivity of T1 measurements to assess vasomodulation in low perfusion rat skeletal muscle. (A) The highly perfused kidney cortex (triangle) exhibits large changes in T1 in response to hypercapnia, whereas changes in skeletal muscle are very modest (circle). (B) Similarly, changes in signal intensity on T1-weighted images are visible in the kidney but not in the leg skeletal muscle. Red circles are provided to localize the tissues of interest.

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  Figure 2. Constant renal elimination rate of contrast agent. Measurements of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\frac{\partial {T}_{1}}{\partial {\rm{t}}}$$\end{document}∂T1∂t in the absence of gas challenge (i.e. no vasomodulation) in both kidney (triangle) and skeletal muscle (circle) reveal a relatively constant rate of contrast elimination from the body. Note that this protocol is different from the gas challenge protocol used in the remainder of the study. The results shown herein support the validity of the mathematical model proposed for measuring vasomodulation in a low perfusion setting.

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  Figure 3. Sensitivity to vasomodulation in low perfusion setting via the parameter \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\frac{\partial {T}_{1}}{\partial {\rm{t}}}$$\end{document}∂T1∂t. Data for a representative rat is shown. In leg muscle (A), a decreasing \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\frac{\partial {T}_{1}}{\partial {\rm{t}}}$$\end{document}∂T1∂t in response to 20% CO2 reflects a diminishing blood volume without the rapid vasoconstriction dynamics seen in the kidney cortex (B). Upon transitioning to 5% CO2, an increasing \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\frac{\partial {T}_{1}}{\partial…

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  Figure 4. Vasomodulatory response in leg skeletal muscle across all animals. The ability to tease out vasoconstriction and vasodilation in skeletal muscle using the parameter \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\frac{\partial {T}_{1}}{\partial {\rm{t}}}$$\end{document}∂T1∂t is illustrated across all animals. Note the consistency in skeletal muscle vasoreactivity to 20% CO2 and 5% CO2. The change in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\frac{\partial {T}_{1}}{\partial {\rm{t}}}$$\end{document}∂T1∂t is significantly different from baseline normoxia for the last two timepoints on 20% CO2; \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt}…

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  Figure 5. Optical perfusion validation in leg muscle. Laser Doppler perfusion measurements over the course of hypercapnic challenge intervals are shown for a representative rat. Blood perfusion units (BPU) are relative quantities and do not indicate absolute blood flow.

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  Figure 6. Average changes in perfusion and heart rate in response to severe and mild hypercapnia. (A) The maximum perfusion change in leg skeletal muscle induced by 20% CO2 as measured on laser Doppler and the maximum vasodilation induced by 5% CO2 are averaged over all animals. (B) The average heart rates during normoxia, 20% CO2, and 5% CO2 are also shown. Shown are the median, first and third quartile values, and minima and maxima across all animals (*P < 0.05).