Abstract
Hyperpolarized 129Xe magnetic resonance imaging (MRI) is capable of regional mapping of pulmonary gas-exchange and has found application in a wide range of pulmonary disorders in humans and animal model analogs. This study is the first application of 129Xe MRI to the monocrotaline rat model of pulmonary hypertension. Such models of preclinical pulmonary hypertension, a disease of the pulmonary vasculature that results in right heart failure and death, are usually assessed with invasive procedures such as right heart catheterization and histopathology. The work here adapted from protocols from clinical 129Xe MRI to enable preclinical imaging of rat models of pulmonary hypertension on a Bruker 7 T scanner. 129Xe spectroscopy and gas-exchange imaging showed reduced 129Xe uptake by red blood cells early in the progression of the disease, and at a later time point was accompanied by increased uptake by barrier tissues, edema, and ventilation defects—all of which are salient characteristics of the monocrotaline model. Imaging results were validated by H&E histology, which showed evidence of remodeling of arterioles. This proof-of-concept study has demonstrated that hyperpolarized 129Xe MRI has strong potential to be used to non-invasively monitor the progression of pulmonary hypertension in preclinical models and potentially to also assess response to therapy.
Highlights
Hyperpolarized 129Xe magnetic resonance imaging (MRI) is capable of regional mapping of pulmonary gas-exchange and has found application in a wide range of pulmonary disorders in humans and animal model analogs
This promising result suggests that 129Xe MRI, in the form of red blood cells (RBCs)-transfer imaging, exhibits sensitivity to altered pulmonary capillary hemodynamics that are a hallmark in Pulmonary arterial hypertension (PAH)
We have presented the first application of quantitative 3D 129Xe gas-exchange MRI to the well-established MCT rat model of pulmonary hypertension (PH)
Summary
Hyperpolarized 129Xe magnetic resonance imaging (MRI) is capable of regional mapping of pulmonary gas-exchange and has found application in a wide range of pulmonary disorders in humans and animal model analogs. Imaging results were validated by H&E histology, which showed evidence of remodeling of arterioles This proof-of-concept study has demonstrated that hyperpolarized 129Xe MRI has strong potential to be used to non-invasively monitor the progression of pulmonary hypertension in preclinical models and potentially to assess response to therapy. The major non-invasive tools currently available are echocardiography and cardiac magnetic resonance imaging (MRI) to assess right ventricular function[9] These technologies only provide a surrogate measure of pulmonary artery pressure, and the associated views of the right ventricle can be difficult to obtain and quantify outside of expert hands. Such imaging and spectroscopic signatures of PAH remain to be fully characterized, in patients, and in well-established animal models where imaging can be validated against ground truth histology
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