A Quantitative Pixel-Wise Measurement of Myocardial Blood Flow by Contrast-Enhanced First-Pass CMR Perfusion Imaging: Microsphere Validation in Dogs and Feasibility Study in Humans

Abstract

The aim of this study was to evaluate fully quantitative myocardial blood flow (MBF) at a pixel level based on contrast-enhanced first-pass cardiac magnetic resonance (CMR) imaging in dogs and in patients. Microspheres can quantify MBF in subgram regions of interest, but CMR perfusion imaging may be able to quantify MBF and differentiate blood flow at a much higher resolution. First-pass CMR perfusion imaging was performed in a dog model with local hyperemia induced by intracoronary adenosine. Fluorescent microspheres were the reference standard for MBF validation. CMR perfusion imaging was also performed on patients with significant coronary artery disease (CAD) by invasive coronary angiography. Myocardial time-signal intensity curves of the images were quantified on a pixel-by-pixel basis using a model-constrained deconvolution analysis. Qualitatively, color CMR perfusion pixel maps were comparable to microsphere MBF bull's-eye plots in all animals. Pixel-wise CMR MBF estimates correlated well against subgram (0.49 ± 0.14 g) microsphere measurements (r = 0.87 to 0.90) but showed minor underestimation of MBF. To reduce bias due to misregistration and minimize issues related to repeated measures, 1 hyperemic and 1 remote sector per animal were compared with the microsphere MBF, which improved the correlation (r = 0.97 to 0.98), and the bias was close to zero. Sector-wise and pixel-wise CMR MBF estimates also correlated well (r = 0.97). In patients, color CMR stress perfusion pixel maps showed regional blood flow decreases and transmural perfusion gradients in territories served by stenotic coronary arteries. MBF estimates in endocardial versus epicardial subsectors, and ischemic versus remote sectors, were all significantly different (p < 0.001 and p < 0.01, respectively). Myocardial blood flow can be quantified at the pixel level (∼32 μl of myocardium) on CMR perfusion images, and results compared well with microsphere measurements. High-resolution pixel-wise CMR perfusion maps can quantify transmural perfusion gradients in patients with CAD.