Dynamic pinhole SPECT imaging and compartmental modeling of fatty acid metabolism in the rat heart

The goal of this work is to quantitatively compare fatty acid metabolism in the hearts of normal and spontaneously hypertensive rats (SHR) as a function of age, and thereby track physiological changes associated with the onset and progression of heart failure in the SHR model. We imposed a more-stringent negativity penalty for fully 4-D multiresolution B-spline SPECT image reconstruction, and applied this method to obtain weighted least-squares estimates of time-activity curves directly from projections for dynamic pinhole SPECT studies of ¹²³I-labeled BMIPP fatty acid analog in the myocardium of both a normal rat and an SHR. Dynamic projection data were acquired for 60 min in 1-sec time frames with an angular step of 4 degrees per frame on a dual-head GE Millennium VG Hawkeye SPECT/CT scanner equipped with custom pinhole collimators. The time-varying spatial distribution of ¹²³I-BMIPP was modeled with use of 4-D multiresolution B-splines that were piecewise constant in space and piecewise quadratic in time. The 4-D splines were organized on a 3-D spatial grid that provided sampling of 3.2 mm near the heart and 6.4 mm away from the heart. Temporal sampling intervals were 0–2.4, 2.4–9.4, 9.4–30, and 30–90 sec during the first gantry rotation. The use of nonuniform time sampling with B-splines that varied quadratically in time yielded smooth time-activity curves that captured the relatively fast rise and fall of ¹²³I-BMIPP in the left ventricular blood pool, as well as the uptake and trapping of the radiotracer in the left ventricular myocardium. Compartmental modeling was then applied to the time-activity curves. This yielded quantitative metabolic rate estimates (Ki) of 0.60 min⁻¹ and 0.22 min⁻¹ in the normal and SHR hearts, respectively. The slower rate of fatty acid metabolism in the SHR is what one expects as the SHR heart switches to a reliance on gl- - ycolysis as the primary pathway for energy production during the development of heart failure. This fully 4-D image reconstruction method can also be applied to dynamic PET.