Objectives Our goal is to evaluate the application of multi-pinhole (MPH) SPECT for imaging plaques in ApoE-/- mice using ^99mTc-HYNIC-Annexin-V (A5).

Methods Experiments using a micro-Defrise phantom were first conducted to evaluate the performance of the standard single pinhole (SPH) and a new MPH SPECT technique based on a commercial small animal SPECT/CT. A series of 7 ApoE-/- mice (n=7) were fed with fatty diet starting from 5-week old to accelerate plaque growth. They were injected with ~4-7mCi of ^99mTc-A5 which targets apoptotic cells in plaques and imaged starting at age 19-week. Five animals were imaged with SPH and MPH collimators with 1mm diameter apertures and same acquisition protocol. Another mouse was imaged using half the number of views with MPH as compared to SPH. The last mouse was imaged using MPH with 0.5mm and SPH with 1mm aperture and the same acquisition protocol.

Results Results from the phantom studies demonstrated that MPH SPECT significantly reduced axial distortions as compared to SPH SPECT. Using the same aperture size and acquisition protocol, 4PH offered ~2 times counts compared to SPH and its reconstructed images showed improved noise level and contrast as compared to SPH in the ApoE-/- studies. Our results showed that the acquisition time can be shortened by half or spatial resolution improved by 26% using MPH while still maintaining the same detected counts as compared to SPH.

Conclusions We conclude that higher resolution and detection efficiency offered by MPH SPECT can be used to improve image quality over SPH SPECT, and it can be applied to atherosclerotic plaque imaging with ^99mTc-A5 in ApoE-/- mice for further understanding of plaque development and characterization.