ABSTRACT: This study describes a HighlY constrained backPRojection (HYPR) image processing method for the reduction of image noise in low tube current time-resolved CT myocardial perfusion scans. The effect of this method on myocardial time-attenuation curve noise and fidelity is evaluated in an animal model, using varying levels of tube current.CT perfusion scans of four healthy pigs (42-59 kg) were acquired at 500, 250, 100, 50, 25, and 10 mA on a 64-slice scanner (4 cm axial coverage, 120 kV, 0.4 s∕rotation, 50 s scan duration). For each scan a sequence of ECG-gated images centered on 75% R-R was reconstructed using short-scan filtered back projection (FBP). HYPR processing was applied to the scans acquired at less than 500 mA using parameters designed to maintain the voxel noise level in the 500-mA FBP images. The processing method generates a series of composite images by averaging over a sliding time window and then multiplies the composite images by weighting images to restore temporal fidelity to the image sequence. HYPR voxel noise relative to FBP noise was measured in AHA myocardial segment numbers 1, 5, 6, and 7 at each mA. To quantify the agreement between HYPR and FBP time-attenuation curves (TACs), Bland-Altman analysis was performed on TACs measured in full myocardial segments. The relative degree of TAC fluctuation in smaller subvolumes was quantified by calculating the root mean square deviation of a TAC about the gamma variate curve fit to the TAC data.HYPR image sequences were produced using 2, 7, and 20 beat composite windows for the 250, 100, and 50 mA scans, respectively. At 25 and 10 mA, all available beats were used in the composite (41-60; average 50). A 7-voxel-wide 3D cubic filter kernel was used to form weighting images. The average ratio of HYPR voxel noise to 500-mA FBP voxel noise was 1.06, 1.10, 0.97, 1.11, and 2.15 for HYPR scans at 250, 100, 50, 25, and 10 mA. The average limits-of-agreement between HYPR and FBP TAC values measured 0.02+∕-0.91, 0.04+∕-1.92, 0.19+∕-1.59, 1.13+∕-4.22, and 1.07+∕-6.37 HU (mean difference +∕-1.96 SD). The HYPR image subvolume that yielded a fixed level of TAC fluctuations was smaller, on average, than the FBP subvolume determined at the same mA.HYPR processing is a feasible method for generating low noise myocardial perfusion data from a low-mA time-resolved CT myocardial perfusion scan. The method is applicable to current clinical scanners and uses conventional image reconstructions as input data.