Myocardial perfusion imaging with a combined x-ray CT and SPECT system.

UNLABELLED: We evaluated a novel combined x-ray CT and SPECT medical imaging system for quantitative in vivo measurements of 99mTc-sestamibi uptake in an animal model of myocardial perfusion. METHODS: Correlated emission-transmission myocardial images were obtained from 7- to 10-kg pigs. The x-ray CT image was used to generate an object-specific attenuation map that was incorporated into an iterative ML-EM algorithm for reconstruction and attenuation correction of the coregistered SPECT images. The pixel intensities in the SPECT images were calibrated in units of radionuclide concentrations (MBq/g), then compared against in vitro 99mTc activity concentration measured from the excised myocardium. In addition, the coregistered x-ray CT image was used to determine anatomical boundaries for quantitation of myocardial regions with low perfusion. RESULTS: The accuracy of the quantitative measurement of in vivo activity concentration in the porcine myocardium was improved by object-specific attenuation correction. However, an additional correction for partial volume errors was required to retrieve the true activity concentration from the reconstructed SPECT images. CONCLUSION: Accurate absolute SPECT quantitation required object-specific correction for attenuation and partial volume effects. Additional anatomical information from the x-ray CT image was helpful in defining regions of interest for quantitation of the SPECT images.

Destabilizing effect of proline substitutions in two helical regions of T4 lysozyme: leucine 66 to proline and leucine 91 to proline.

A class of temperature-sensitive (ts) mutants of T4 lysozyme with reduced activity at 30 degrees C and no activity at 43 degrees C has been selected. These mutants, designated "tight" ts mutants, differ from most other T4 lysozyme mutants that are active at 43 degrees C, but only manifest their ts lesion by a reduced halo size around phage plaques after exposure of the growth plates to chloroform vapors. For example, in the series of T4 lysozyme mutants at position 157, the original randomly selected mutant, T1571, is the least stable of the series, yet, apart from the halo assay and subsequent in vitro protein stability measurements, this mutant is indistinguishable from wild type (WT) even at 43 degrees C. Two mutants were identified: L91P and L66P. Both insert proline residues into alpha-helical regions of the WT protein structure. The stabilities (delta delta G) as determined by urea denaturation are 8.2 kcal/mol for L91P and 7.1 kcal/mol for L66P. CD spectra indicate that no major conformational changes have occurred in the mutant structures. The structures of the mutants were modeled with a 40-ps molecular dynamics simulation using explicit solvent. For L91P, the reduction of stability appears to be due to an unsatisfied hydrogen bond in the alpha-helix and to a new buried cavity. For L66P, the reduction of stability appears to be due to a disruption of the interdomain alpha-helix, at least two unsatisfied hydrogen bonds, and a newly formed solvent-filled pocket that protrudes into the hydrophobic core, possibly reducing the stabilizing contribution of a partially buried intrachain salt bridge.

Description of a prototype emission-transmission computed tomography imaging system.

We have developed a prototype imaging system that can perform simultaneous x-ray transmission CT and SPECT phantom studies. This system employs a 23-element high-purity-germanium detector array. The detector array is coupled to a collimator with septa angled toward the focal spot of an x-ray tube. During image acquisition, the x-ray fan beam and the detector array move synchronously along an arc pivoted at the x-ray source. Multiple projections are obtained by rotating the object, which is mounted at the center of rotation of the system. The detector array and electronics can count up to 10(6) cps/element with sufficient energy-resolution to discriminate between x-rays at 100-120 kVp and gamma rays from 99mTc. We have used this device to acquire x-ray CT and SPECT images of a three-dimensional Hoffman brain phantom. The emission and transmission images may be superimposed in order to localize the emission image on the transmission map.