Accelerated dual-contrast first-pass perfusion MRI of the mouse heart: Development and application to diet-induced obese mice

Abstract

Background Gene-modified mice may be used to elucidate molecular mechanisms underlying abnormal myocardial blood flow (MBF). We sought to develop a quantitative myocardial perfusion imaging technique for mice and to test the hypothesis that myocardial perfusion reserve (MPR) is reduced in a mouse model of diet-induced obesity (DIO). Methods A dual-contrast saturation-recovery sequence with ky-t undersampling and a motion-compensated compressed sensing reconstruction algorithm was developed for first-pass MRI on a small-bore 7T system. Control mice were imaged at rest and with the vasodilators ATL313 and Regadenoson (n=6 each). In addition, we imaged mice fed a high-fat diet (HFD) for 24 weeks. Results In control mice, MBF was 5.7±0.8 ml/g/min at rest and it increased to 11.8±0.6 ml/g/min with ATL313 and to 10.4±0.3 ml/g/min with Regadenoson. In HFD mice we detected normal resting MBF (5.6±0.4 vs. 5.0±0.3 on control diet), low MBF at stress (7.7±0.4 vs. 10.4±0.3 on control diet, p<0.05), and reduced MPR (1.4±0.2 vs. 2.0±0.3 on control diet, p<0.05). Conclusions Accelerated dual-contrast first-pass MRI with motion-compensated compressed sensing provides spatiotemporal resolution suitable for measuring MBF in free-breathing mice, and detected reduced MPR in DIO mice. These techniques may be used to study molecular mechanisms that underlie abnormal myocardial perfusion.

Repeatability and variability of myocardial perfusion imaging techniques in mice: Comparison of arterial spin labeling and first‐pass contrast‐enhanced MRI

“…With first-pass MRI, the RC is approximately 30–35%. This is consistent with our recent study which showed that stress perfusion was reduced by almost 30% in wild type C57Bl/6 mice fed a high-fat diet as compared to wild type mice on a standard chow diet (16). …”

“…Absolute myocardial perfusion values for ASL and first-pass MRI obtained under the various conditions are shown in Figure 5, and are within the ranges of previously published measurements for MBF in mice at rest (11–13,15–18,25,26) and at stress (11,13,16,18,26,27). The MBF values obtained using first-pass MRI are lower than the values obtained using ASL at rest, stress and in the remote zone (Figure 5A, p<0.05), however there was good correlation between the two techniques over the entire range of MBF (Figure 5B).…”

“…Under each condition, mice were imaged using both a first-pass sequence (16) and a flow-sensitive alternating inversion-recovery (FAIR) Look-Locker ASL sequence. To assess repeatability, perfusion imaging for each technique was performed at two different sessions.…”

“…The AIF curve was fit using a gamma-variate function in order to denoise the data and remove effects due to the recirculation of gadolinium. Using data representing first-pass kinetics (but not recirculating gadolinium), the fitted AIF and TF were analyzed using Fermi function deconvolution (24) to estimate myocardial perfusion (16). …”

High field magnetic resonance imaging of rodents in cardiovascular research

“…They all rely on rapid acquisition of saturation recovery sequences during the passage of a contrast bolus through the heart. Parameters like myocardial blood flow (MBF), myocardial tissue function (TF) and arterial input function (AIF) could be precisely quantified using dual-bolus [9,154,155] or dual-contrast [106] strategies either by tracer kinetic modeling or Fermi function deconvolution [76]. FPP MRI has successfully been applied at HF in mouse models of myocardial infarction [9,40], cardiac hypertrophy [154] and obesity [106], with a good reproducibility of the regional quantitative perfusion estimates [155].…”