Physiological measurements remained reasonably stable during the experiment. The average heart rate was 101 ± 18 and 98 ± 19 before and during adenosine infusion. The average systolic and diastolic blood pressures were 115 ± 11 mmHg and 68 ± 10 mmHg, respectively, before the adenosine infusion. Both systolic and diastolic blood pressures dropped slightly to 112 ± 14 mmHg and 61 ± 8 mmHg, respectively, during the adenosine infusion. For microsphere processing, the endocardial sectors weighed 0.41 ± 0.09 g (n=56), epicardial sectors weighed 0.58 ± 0.13 g (n=56), and transmural sectors averaged 0.99 ± 0.20 g (n=56). The median microsphere count in endocardial sectors was 2974 (range 926 to 9569) and in epicardial sectors was 4677 (range 1318 to 15811). Microsphere results showed successful vasodilation for all canines defined as at least a two-fold higher microsphere MBF in hyperemic sectors relative to remote sectors.
compares pixel-wise time-signal intensity curves for hyperemic versus remote regions. A similar time course of contrast enhancement was observed between pixels within the same region. There was a hyperemic response on the adenosine affected regions as shown by faster contrast wash-in and wash-out kinetics, and a higher overshoot in the pixel-wise time-signal intensity curves.
CMRTime-Signal Intensity Curves at a Pixel-level
For qualitative comparisons, shows colorized CMR perfusion pixel maps of all animals with corresponding microsphere MBF on the same absolute color scale. Regional differential blood flow was clearly seen in all animals. Qualitatively, the dynamic range of color perfusion maps from CMR was comparable to microsphere bull’s-eye plots in all animals. At the same time, there were also sectors which did not correspond perfectly due to spatial misregistration between CMR imaging slice versus pathological microsphere slice. Nevertheless, CMR perfusion pixel maps had a higher spatial resolution (0.033 g/voxel) than sector-wise microsphere maps (0.49 g/sector).
Qualitative Comparison of MBF by Pixel-Wise CMR and Microspheres
For quantitative comparisons, shows pixel-wise CMR MBF estimates averaged into sector-wise measures which correlate well with microsphere MBF in transmural, endocardial, and epicardial sectors (n=56; r=0.90, r=0.89 and r=0.87, respectively). However, Bland-Altman analysis shows there is a small bias suggesting CMR understimates microsphere MBF or spatial misregistration adds systematic errors to the comparisons.
Comparison of MBF by Pixel-Wise CMR and Microspheres
To reduce the probability of misregistration, further comparisons were performed by selecting one hyperemic and one remote sector from the center of each zone on both CMR perfusion images and the pathological slice for each animal. There were even tighter correlations between CMR estimates of MBF and microsphere measurements in transmural, endocardial, and epicardial sectors (n=14; r=0.98, r=0.97 and r=0.97, respectively, ). Bland-Altman analysis also showed minimal residual bias for these comparisons.
Higher Correlation and Smaller Bias After Reducing Misregistration
To address whether quantification of CMR time-signal intensity curves at a pixel level introduces biases relative to quantification of sector-wise time-signal intensity curves, additional correlation and Bland-Altman analysis were performed (). There was a strong correlation in transmural, endocardial, and epicardial comparisons (r=0.97 for all comparisons). Similarly, there was no significant bias in all Bland-Altman plots. This indicates that MBF quantified at the pixel level does not intrinsically alter the perfusion information content of the CMR images as estimated from conventional sector-wise analysis.
Comparison of MBF by Pixel-Wise and Sector-Wise CMR
To analyze transmural perfusion gradients in our animal model. endocardial MBF, epicardial MBF, and endocardial to epicardial MBF ratio were measured on CMR perfusion pixel maps and microspheres. For both hyperemic and remote regions, there were no significant blood flow differences between endocardial and epicardial MBF by CMR or microspheres measurements (, all p=NS). When comparing CMR and microspheres MBF measurements, there were also no significant differences between the two methods for endocardial hyperemic MBF, epicardial hyperemic MBF, or corresponding measurements in the remote region (, all p=NS). However, CMR perfusion pixel maps and microspheres both detected significant differences in MBF between hyperemic and remote regions (, all p<0.01).
Analysis of endocardial MBF, epicardial MBF, and endocardial to epicardial ratio in dogs CMR perfusion pixel maps and microspheres measurements. Results are expressed in mean ± standard deviation.
To study the heterogeneity of pixel-wise CMR perfusion MBF in hyperemic and remote regions, the coefficient of variation of pixel-wise MBF in transmural, endocardial, and epicardial sectors was measured (). There was less variability of pixel-wise MBF estimates in hyperemic sectors compared to the remote. This smaller variability was consistent in transmural, endocardial, and epicardial sectors.
The variability of pixel-wise CMR MBF in hyperemic and remote sectors as represented by coefficient of variation (CV).
Since the selective coronary infusion of adenosine did not create transmural perfusion gradients in the dogs, we analyzed transmural perfusion gradients in patients with significant coronary artery stenosis as determined by invasive coronary angiography. shows examples of pixel-wise MBF maps for human first-pass perfusion CMR imaging at rest and during stress. Pixel-wise perfusion maps of the healthy volunteer (subject 1) show MBF estimates in the range of 0.5 to 1.0 ml/g/min at rest, and increase to above 2.5 ml/g/min range during stress for all 3 coronary territories.
Clinical CMR Perfusion Pixel Maps
For two patients with single vessel LAD disease (subject 2 and 3), pixel-wise MBF maps of stress CMR showed transmural perfusion gradients in the LAD territory. In subject 4, stress CMR maps showed a severe LAD perfusion defect corresponding to a 70% ostial stenosis and a less severe subendocardial perfusion defects corresponding to intermediate stenoses in the RCA and circumflex coronary arteries. In subject 5, there were obvious stress induced perfusion defects in the LAD (80% stenosis) and RCA territory (collateral dependent occluded vessel), and a mild subendocardial perfusion defect associated with a terminal obtuse marginal branch with a 70% stenosis. There were reduced MBF in all myocardial regions on the stress CMR perfusion map of another patient with 3 vessel disease (subject 6). Overall, CMR perfusion maps were more homogeneous at rest compared to stress CMR maps in all patients with CAD.
To quantify transmural gradient in patients with significant coronary stenosis, endocardial MBF, epicardial MBF, and endocardial to epicardial MBF ratio of the ischemic and remote regions in CMR perfusion pixel maps were compared. shows there were no differential blood flows between endocardial to epicardial subsectors in the remote regions (p=NS). However, there were significant blood flow differences between endocardial and epicardial subsectors in the ischemic territories (p<0.001). Both endocardial and epicardial MBF estimates in the ischemic regions were also significantly lower than in the remote regions (p<0.001 for endocardial and p<0.01 for epicardial comparisons).
Analysis of endocardial MBF, epicardial MBF, and endocardial to epicardial ratio CMR perfusion pixel maps in patients. Results are expressed in mean ± standard deviation.