# Quantitative MicroSPECT Imaging of Myocardial Blood Flow in Mice

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $482,697

## Abstract

This proposal’s objective is to develop and evaluate the microSPECT measurement of myocardial blood flow
(MBF) in mice. MBF is a measure of microvasculature health and is an independent predictor of cardiovascular
morbidity and mortality. Microvasculature dysfunction is often called coronary microvascular disease (CMVD)
and has become an increasingly well-recognized cardiac pathology. Yet, despite mounting clinical evidence of
its importance, there is a dearth of mechanistic understanding and targeted therapies for CMVD. The availability
of numerous disease-based and genetic models and the ease of genetic manipulations makes the mouse model
ideal for studying cardiovascular disease and its treatment. To develop non-invasive MBF measures in mice, we
plan to consider 99mTc-labeled sestamibi and 201Tl as tracers; each has its own flow-dependent tracer extraction
fraction (EXF), which can be species-specific. Thus, in Aim 1, we will map the relationship between radiotracer
uptake, as measured by K1, and MBF for both tracers in normal mice. We will validate the use of microspheres
as our gold-standard measure for MBF in mice by measuring the uncertainty of injections into the left-ventricle
(LV) and left atrium (LA), where the latter is desirable for the more uniform mixing with blood before the
microspheres are ejected from the LV, but is more technically challenging due to the small size of the LA and its
thin wall. Similarly, we will use a dose calibrator to measure the tracer’s uptake concentration in the excised
heart. With these gold standards for comparison, we will develop microSPECT MBF quantification on the MI
Labs U-SPECT+ using a unique phantom and targeted animal studies to develop quantitative corrections and
optimizations (Aim 2). This system can achieve resolution of ~0.35 mm with high sensitivity. The phantom will
be used for studying the crosstalk relationship between uptake in the myocardium and the input function, as
measured in the LV. We will optimize our dynamic fitting procedures using this phantom and determine
appropriate quantitative corrections that account for spillover due to the system’s spatial resolution. This will be
tested in our evaluations (Aim 3) where we will compare the longitudinal myocardial blood flow reserve (MBFR)
in wild-type mice and transgenic mice in which the degree of microvascular dysfunction can be regulated. These
longitudinal studies will be complemented with microsphere MBF and histological measures of capillary density.
We expect the project’s outcomes to be: (1) microsphere MBF validation in mice and uncertainty determination;
(2) EXF curves for sestamibi and 201Tl in normal mice; (3) determination of the better tracer for MBFR
measurements in mice; (4) validation of that tracer’s EXF curve in a transgenic model; (5) development and
validation of accurate in vivo MBF/MBFR measurements in mice; (6) validation of imaging-based MBF/MBFR
decline in transgenic mice with gene activation; and (7) corr...

## Key facts

- **NIH application ID:** 10219352
- **Project number:** 5R01HL149801-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** SCOTT DEAN METZLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $482,697
- **Award type:** 5
- **Project period:** 2020-07-17 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219352

## Citation

> US National Institutes of Health, RePORTER application 10219352, Quantitative MicroSPECT Imaging of Myocardial Blood Flow in Mice (5R01HL149801-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10219352. Licensed CC0.

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