Longitudinal Evaluation of Fatty Acid Metabolism in Normal and Spontaneously Hypertensive Rat Hearts with Dynamic MicroSPECT Imaging

Abstract

The goal of this project is to develop radionuclide molecular imaging technologies using a clinical pinhole SPECT/CT scanner to quantify changes in cardiac metabolism using the spontaneously hypertensive rat (SHR) as a model of hypertensive-related pathophysiology. This paper quantitatively compares fatty acid metabolism in hearts of SHR and Wistar-Kyoto normal rats as a function of age and thereby tracks physiological changes associated with the onset and progression of heart failure in the SHR model. The fatty acid analog, (123)I-labeled BMIPP, was used in longitudinal metabolic pinhole SPECT imaging studies performed every seven months for 21 months. The uniqueness of this project is the development of techniques for estimating the blood input function from projection data acquired by a slowly rotating camera that is imaging fast circulation and the quantification of the kinetics of (123)I-BMIPP by fitting compartmental models to the blood and tissue time-activity curves.

Figure 1

Clinical dual-detector SPECT/CT scanner with custom pinhole collimators used for quantitative dynamic imaging of fatty acid metabolism in the rat heart.

Figure 2

Dynamic cardiac ¹²³I-BMIPP pinhole SPECT projection data acquired by one detector head during the interval 2–36 s for (a) a WKY normal rat and (b) an SHR. These early time frames show the arrival of the injected bolus at the heart, followed by initial uptake in the myocardium. The maximum numbers of counts in a detector bin are 10 and 12 for the WKY normal rat and SHR, respectively.

Figure 3

Piecewise quadratic temporal B-spline basis functions used to reconstruct dynamic data acquired during the first gantry rotation.

Figure 4

One-tissue-compartment model used for quantifying fatty acid metabolism during the first 90 s after injection of ¹²³I-BMIPP.

Figure 5

Typically, more trapping of ¹²³I-BMIPP is evident in late 3D static images of the WKY normal hearts (top two rows), compared to the SHR hearts (bottom two rows). Trapping also tends to decrease with age (left column, 7 months; middle column, 14 months; right column, 21 months). SHR B died of congestive heart failure before 21 months. These static images have been normalized to one another by normalizing by the injected dose per unit body weight.

Figure 6

Time-activity curves for the WKY normal rats (top two rows) and the SHRs (bottom two rows) capture quantitative differences between their spillover-corrected blood inputs and myocardial uptakes (triangles and circles, resp.). Compartmental models (solid lines) provide good fits to the myocardial uptake curves. Left column, 7 months; middle column, 14 months; right column, 21 months. SHR B died of congestive heart failure before 21 months.

Figure 7

Time-activity curves for SHR A at 7 months estimated (a) without and (b) with tissue spillover correction for the blood curve. Spillover correction improves contrast between the blood input and myocardial uptake (triangles and circles, resp.), improves the fit of the compartmental model (solid line), and yields a metabolic rate estimate (K _i) that nearly doubles, from 0.64 min⁻¹ to 1.12  min⁻¹.

Figure 8

Metabolic rate of ¹²³I-BMIPP in the myocardium as a function of age. SHR B died of congestive heart failure before 21 months.