Development and feasibility of quantitative dynamic cardiac imaging for mice using μSPECT

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 ^99mTc-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 ^99mTc 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 assumption R_T = 1 - FBV (fraction blood volume) does not hold in mice. Using a complete mixing matrix to fit a one-compartment model, we measured K1 of 0.57 ± 0.08 min^-1. Constraints on the extraction fraction curve for ^99mTc-sestamibi in mice for best-fit Renkin-Crone parameters were α = 0.99 and β = 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 measuring K1 and change in IMBV in mice, demonstrating non-invasive µSPECT-based quantitative imaging of mouse microvascular function.