Development and feasibility of quantitative dynamic cardiac imaging for mice using mu SPECT

Background Despite growing interest in coronary microvascular disease (CMVD), there is a dearth of mechanistic understanding. Mouse models offer opportunities to understand molecular processes in CMVD. We have sought to develop quantitative mouse imaging to assess coronary microvascular function. Methods We used(99m)Tc-sestamibi to measure myocardial blood flow in mice with MILabs U-SPECT(+)system. We determined recovery and crosstalk coefficients, the influx rate constant from blood to myocardium (K1), and, using microsphere perfusion, constraints on the extraction fraction curve. We used(99m)Tc and stannous pyrophosphate for red blood cell imaging to measure intramyocardial blood volume (IMBV) as an alternate measure of microvascular function. Results The recovery coefficients for myocardial tissue (R-T) and left ventricular arterial blood (R-A) were 0.81 +/- 0.16 and 1.07 +/- 0.12, respectively. The assumptionR(T) = 1 - FBV (fraction blood volume) does not hold in mice. Using a complete mixing matrix to fit a one-compartment model, we measuredK1 of 0.57 +/- 0.08 min(-1). Constraints on the extraction fraction curve for(99m)Tc-sestamibi in mice for best-fit Renkin-Crone parameters were alpha = 0.99 and beta = 0.39. Additionally, we found that wild-type mice increase their IMBV by 22.9 +/- 3.3% under hyperemic conditions. Conclusions We have developed a framework for measuringK1 and change in IMBV in mice, demonstrating non-invasive mu SPECT-based quantitative imaging of mouse microvascular function.