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

Compromised microvascular reactivity underlies many conditions and injuries, but its assessment remains difficult, particularly in low perfusion tissues. In this paper, we develop a new mathematical model for the assessment of vasomodulation in low perfusion settings. A first-order model was developed to approximate changes in T1 relaxation times as a result of vasomodulation. Healthy adult rats (N = 6) were imaged on a 3-Tesla clinical MRI scanner, and vasoactive response was probed on gadofosveset using hypercapnic gases at 20% and 5% CO2 to induce vasoconstriction and vasodilation, respectively. MRI included dynamic 3D T1 mapping and T1-weighted images during gas challenge; heart rate was continuously monitored. Laser Doppler perfusion measurements were performed to corroborate MRI findings. The model was able to identify hypercapnia-mediated vasoconstriction and vasodilation through the partial derivative [Formula: see text]. MRI on animals revealed gradual vasoconstriction in the skeletal muscle bed in response to 20% CO2 followed by gradual vasodilation on transitioning to 5% CO2. These trends were confirmed on laser Doppler perfusion measurements. Our new mathematical model has the potential for detecting microvascular dysfunction that manifests in the early stages across multiple metabolic and ischemic pathologies.

Assessment of microvascular dysfunction in acute limb ischemia-reperfusion injury.

BACKGROUND: Ischemia-reperfusion (I/R) injury involves damage to the microvessel structure (eg, increased permeability) and function (blunted vasomodulation). While microstructural damage can be detected with dynamic contrast-enhanced (DCE) MRI, there is no diagnostic to detect deficits in microvascular function. PURPOSE: To apply a novel MRI method for evaluating dynamic vasomodulation to assess microvascular dysfunction in skeletal muscle following I/R injury. STUDY TYPE: Prospective, longitudinal. ANIMAL MODEL: Twenty-three healthy male adult Sprague-Dawley rats. FIELD STRENGTH/SEQUENCE: Dynamic T1 fast field echo imaging at 3.0T with preinjection T1 mapping. ASSESSMENT: Injury in the left hindlimb was induced using a 3-hour I/R procedure. Longitudinal MRI scanning was performed up to 74 days, with animals completing assessment at different intervals for histological and laser Doppler perfusion validation. Pharmacokinetic parameters Ktrans and ve were determined following i.v. injection of gadovist (0.1 mmol/kg). Vasomodulatory response was probed on gadofosveset (0.3 mmol/kg) using hypercapnic gases delivered through a controlled gas-mixing circuit to induce vasoconstriction and vasodilation in ventilated rats. Heart rate and blood oxygen saturation were monitored. STATISTICAL TESTS: Two-way analysis of variance with Tukey-Kramer post-hoc analysis was used to determine significant changes in vasomodulatory response, Ktrans , and ve . RESULTS: This new MRI technique revealed impaired vasomodulation in the injured hindlimb. Vasoconstriction was maintained, but vasodilation was blunted up to 21 days postinjury (P < 0.05). However, DCE-MRI measured Ktrans and ve were significantly (P < 0.05) different from baseline only during acute inflammation (Day 3), with severe inflammation noted on histology. DATA CONCLUSION: While conventional DCE-MRI shows normalization after the acute phase, our new approach reveals sustained functional impairment in muscle microvasculature following I/R injury, with compromised response in vasomotor tone present for at least 21 days. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1174-1185.