This paper examines the spatial resolution properties of penalized-likelihood image reconstruction methods by analyzing the local impulse response. The analysis shows that standard regularization penalties induce space-variant local impulse response functions, even for space-invariant tomographic systems. Paradoxically, for emission image reconstruction, the local resolution is generally poorest in high-count regions. We show that the linearized local impulse response induced by quadratic roughness penalties depends on the object only through its projections. This analysis leads naturally to a modified regularization penalty that yields reconstructed images with nearly uniform resolution. The modified penalty also provides a very practical method for choosing the regularization parameter to obtain a specified resolution in images reconstructed by penalized-likelihood methods.

This paper examines the spatial resolution properties of penalized-likelihood image reconstruction methods by analyzing the local impulse response. The analysis shows that standard regularization penalties induce space-variant local impulse response functions, even for space-invariant tomographic systems. Paradoxically, for emission image reconstruction, the local resolution is generally poorest in high-count regions. We show that the linearized local impulse response induced by quadratic roughness penalties depends on the object only through its projections. This analysis leads naturally to a modified regularization penalty that yields reconstructed images with nearly uniform resolution. The modified penalty also provides a very practical method for choosing the regularization parameter to obtain a specified resolution in images reconstructed by penalized-likelihood methods.

A Maximum Likelihood (ML) image reconstruction technique using list-mode data has been applied to Compton scattering camera imaging. List-mode methods are appealing in Compton camera image reconstruction because the total number of data elements in the list (the number of detected photons) is significantly smaller than the number of possible combinations of position and energy measurements, leading to a much smaller problem than that faced by traditional iterative reconstruction techniques. For a realistic size device, the number of possible detector bins can be as large as 10 billion per pixel of the image space, while the number of counted photons would typically be a very small fraction of that. The primary difficulty in applying the list-mode technique is in determining the parameters which describe the response of the imaging system. In this work, a simple method for determining the required system matrix coefficients is employed, in which a back-projection is performed in list-mode, and response coefficients determined for only tallied pixels. Projection data has been generated for a representative Compton camera system by Monte Carlo simulation for disk sources with hot and cold spots and energies of 141, 364, and 511 keV, and reconstructions performed.

The design and application of alpha-hydroxy phosphonates, a new class of transition state analogs, toward the discovery of novel and potent inhibitors of the aspartyl protease renin is described. Tripeptidic alpha-hydroxy diethyl phosphonate 3, the first example in this series, was found to be a good inhibitor of human renin (IC50 = 29 nM), and preliminary studies led to the choice of alpha-hydroxy dimethyl phosphonate 15 (IC50 = 16 nM) as a base-line compound for further structure-activity relationship study. Corresponding phosphinate (28-30) and phosphine oxide (23 and 24) analogs of 15 were prepared to assess the steric and electronic requirements around the phosphorus center. Evaluation of these analogs suggested that the presence of at least one alkoxy group on phosphorus was a critical requirement for good activity. Inhibitors with leucine at P2 possessed better in vitro activity than the corresponding P2 histidine analogs (15, IC50 = 16 nM vs 37, IC50 = 220 nM; 33, IC50 = 8.5 nM vs 40, IC50 = 41 nM). Compound 34 (IC50 = 31 nM), the P3 aminocaproic analog of 15, showed complete and long-lasting inhibition of plasma renin activity while eliciting a 10-15 mmHg drop in mean arterial pressure when administered intravenously at 1 mumol/kg in conscious, sodium-depleted, cynomolgus monkeys. In summary, the alpha-hydroxy phosphonates represent a promising and structurally novel class of transition state analog inhibitors of human renin.