A non-invasive magnetic resonance imaging approach for assessment of real-time microcirculation dynamics

Abstract

We present a novel, non-invasive magnetic resonance imaging (MRI) technique to assess real-time dynamic vasomodulation of the microvascular bed. Unlike existing perfusion imaging techniques, our method is sensitive only to blood volume and not flow velocity. Using graded gas challenges and a long-life, blood-pool T 1-reducing agent gadofosveset, we can sensitively assess microvascular volume response in the liver, kidney cortex, and paraspinal muscle to vasoactive stimuli (i.e. hypercapnia, hypoxia, and hypercapnic hypoxia). Healthy adult rats were imaged on a 3 Tesla scanner and cycled through 10-minute gas intervals to elicit vasoconstriction followed by vasodilatation. Quantitative T 1 relaxation time mapping was performed dynamically; heart rate and blood oxygen saturation were continuously monitored. Laser Doppler perfusion measurements confirmed MRI findings: dynamic changes in T 1 corresponded with perfusion changes to graded gas challenges. Our new technique uncovered differential microvascular response to gas stimuli in different organs: for example, mild hypercapnia vasodilates the kidney cortex but constricts muscle vasculature. Finally, we present a gas challenge protocol that produces a consistent vasoactive response and can be used to assess vasomodulatory capacity. Our imaging approach to monitor real-time vasomodulation may be extended to other imaging modalities and is valuable for investigating diseases where microvascular health is compromised.

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

“…This paper describes a new analytical method that allows sensitive assessment of microvascular vasomodulation in low perfusion tissue. Compared to assessment of T 1 changes in response to hypercapnia, which have been shown in the literature to be insignificant in skeletal muscle 7 , changes in T t 1 ∂ ∂ are significant. In this study, we showed that the metric T t 1 ∂ ∂ was sensitive to both vasoconstriction and vasodilation in the leg skeletal muscle, and MRI results were corroborated by invasive Doppler perfusion measurements.…”

“…in leg skeletal muscle as its microvasculature responds to gas challenge. Results in the kidney are also shown to provide a reference for interpreting the evolution of muscle ∂ ∂ T t 1 , as renal response to gas challenges is well understood and significant vasoconstriction and vasodilation have been consistently observed in response to 20% CO 2 followed by 5% CO 2 7 . The results in Fig.…”

“…A controlled gas mixing circuit described previously 7 was used to deliver graded levels of CO 2 and O 2 . The gas blender consisted of a computer-controlled GSM-3 mixer (CWE Inc., Ardmore, PA, USA) and blended O 2 , CO 2 , and N 2 at a constant total flow of 2 L/min.…”

“…As such, it is very difficult to sensitively detect vasomodulation-induced dynamic changes in microvascular volume. In a recent innovation described by Ganesh et al 7 , a MRI technique was demonstrated for measuring the dynamics of microvessel modulation in deep organs. Their technique is unique compared to existing clinical methods to assess the microvasculature, because it can isolate strictly changes in microvessel volume and can, therefore, truly measure vasomodulation.…”

“…However, in its current form, the approach described in ref. 7 is relatively insensitive to vasomodulation in low perfusion tissue such as skeletal muscle; we need to use the approach as a starting point to build the desired capability.…”