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Assessment of microvascular dysfunction in acute limb ischemia-reperfusion injury
Tameshwar Ganesh1,2, Eric Zakher1,3, Marvin Estrada4
1Ted Rogers Centre for Heart Research, Translational Biology & Engineering Program, Toronto, Canada.
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.
Insights
A novel MRI method reveals sustained microvascular dysfunction after ischemia-reperfusion (I/R) injury. This technique detects impaired vasodilation for at least 21 days, unlike conventional methods.
Area of Science:
- Biomedical Engineering
- Radiology
- Physiology
Background:
- Ischemia-reperfusion (I/R) injury causes microvessel damage and impaired function (vasomodulation).
- Dynamic contrast-enhanced (DCE) MRI detects microstructural damage but not functional deficits.
- A diagnostic tool for microvascular dysfunction in I/R injury is needed.
Purpose of the Study:
- To develop and apply a novel MRI method for assessing dynamic vasomodulation.
- To evaluate microvascular dysfunction in skeletal muscle following I/R injury using this new MRI technique.
Main Methods:
- A longitudinal study in 23 male Sprague-Dawley rats subjected to 3-hour hindlimb I/R.
- Dynamic T1 fast field echo imaging at 3.0T with pharmacokinetic modeling (Ktrans, ve).
- Assessment of vasomodulatory response to hypercapnia using gadofosveset and DCE-MRI, validated with histology and laser Doppler perfusion.
Main Results:
- The novel MRI technique demonstrated impaired vasodilation for up to 21 days post-I/R (P < 0.05).
- Vasoconstriction remained intact, but vasodilation was blunted.
- Conventional DCE-MRI parameters (Ktrans, ve) normalized after the acute phase, masking sustained functional impairment.
Conclusions:
- The new MRI approach reveals sustained microvascular functional impairment following I/R injury.
- Compromised vasomotor tone, specifically blunted vasodilation, persists for at least 21 days.
- This technique offers a diagnostic tool for microvascular dysfunction missed by conventional DCE-MRI.
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