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 T 1 fast field echo imaging at 3.0T with preinjection T 1 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 K trans and v e 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, K trans , and v e . 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 K trans and v e 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.