Clinical Application of PET/CT Fusion Imaging for Three-Dimensional Myocardial Scar and Left Ventricular Anatomy during Ventricular Tachycardia Ablation

Background: Image integration has the potential to display three-dimensional (3D) scar anatomy and facilitate substrate characterization for ventricular tachycardia (VT) ablation. However, the current generation of clinical mapping systems cannot display 3D left ventricle (LV) anatomy with embedded 3D scar reconstructions or allow display of border zone and high-resolution anatomic scar features.
Objective: This study reports the first clinical experience with a mapping system allowing an integrated display of 3D LV anatomy with detailed 2D/3D scar and border zone reconstruction.
Methods: Ten patients scheduled for VT ablation underwent contrast-enhanced computed tomography (CT) and Rubidium-82 perfusion/F-18 Fluorodeoxyglucose metabolic Positron Emission Tomography (PET) imaging to reconstruct 3D LV and scar anatomy. LV and scar models were co-registered using a 3D mapping system and analyzed with a 17-segment model. Metabolic thresholding was used to reconstruct the 3D border zone. Real-time display of CT images was performed during ablation.
Results: Co-registration (error 4.3 ± 0.7 mm) allowed simultaneous visualization of 3D LV anatomy and embedded scar and guided additional voltage mapping. Segments containing homogenous or partial scar correlated in 94.4% and 85.7% between voltage maps and 3D PET scar reconstructions, respectively. Voltage-defined scar and normal myocardium had relative FDG uptakes of 40 ± 13% and 89 ± 30% (P < 0.05). The 3D border zone correlated best with a 46% metabolic threshold. Real-time display of registered high-resolution CT images allowed the simultaneous characterization of scar-related anatomic changes.
Conclusion: Integration of PET/CT reconstruction allows simultaneous 3D display of myocardial scar and border zone embedded into the LV anatomy as well as the display of detailed scar anatomy. Multimodality imaging may enable a new image-guided approach to substrate-guided VT ablation.     

Determination and Metabolism of Dithiol Chelating Agents. VII. Biliary Excretion of Dithiols and Their Interactions with Cadmium and Metallothionein

Determination and Metabolism of Dithiol Chelating Agents. VII.Biliary Excretion of Dithiols and Their Interactions with Cadmiumand Metallothionein. ZHENG, W., MAIORINO, R. M., BRENDEL, K.,AND APOSHIAN, H. V. (1990). Fundam. Appl. Toxicol. 14, 598–607.N-(2,3-Di-mercaptopropyl) phthalamidic acid (DMPA), meso-dimercaptosuccinicacid (DMSA), and 2,3-dimercapto-1-propanesulfonic acid (DMPS)are dithiol chelating agents with antidotal activity for lead,mercury, arsenic, and other heavy metals. The biliary excretionof these compounds was studied in male Sprague-Dawley rats.After iv administration of DM PA, 72% of the injected dose wasrecovered in the bile. Half of the recovered DMPA was in theunaltered form (parent compound) and the other half was in thealtered form (parent compound recovered after chemical reductionby DTT). An altered, presumably disulfide, form of DMPS wasfound in the bile. Neither unaltered nor altered DMSA was detectedin the bile. DMPA (0.10 mmol/kg), given to rats 3 days afterexposure to Cd, elicited within 30 min a 20-fold increase inbiliary Cd excretion. The increase of biliary Cd by DMPA wasdose-related and not due to an increase of bile flow rate. DMSAand DMPS did not significantly affect the biliary excretionof Cd. Incubation of DMPA or DMSA with Cd-saturated metallothionein(MT) resulted in the removal of Cd from MT. DMPA was more activethan DMSA in this respect. The evidence strongly supports themechanism that the increase of biliary cadmium following DMPAadministration is the result of DMPA entering cells and mobilizingand removing the cadmium from MT. The removal of cadmium frommetallothionein by dithiol chelating agents provides anotherdimension to their mechanisms of action and may provide an importantnew tool for the study of cadmium as well as metallothionein.     

Central Nervous System Toxicity of Manganese: I. Inhibition of Spontaneous Motor Activity in Rats after Intrathecal Administration of Manganese Chloride

The intrathecal administration of MnCl₂ to young male rats causeddoparnine depletion in the caudate-putamen and a decrease inspontaneous motor activity. Our experiments demonstrate thatin the young rat: (a) the lateral choroid plexus protects thecerebrospinal fluid (CSF) from high concentrations of Mn inthe blood by sequestering and thus preventing large amountsof this metal ion from entering the CSF. As blood Mn levelsrise, the lateral choroid plexus may become overwhelmed andleak an increasing amount of Mn into the CSF. (b) The lateralchoroid plexus does not remove Mn²⁺ from the CSF. (c) The injectionof MnCl² into the CSF of rats caused a rapid decrease in spontaneousmotor activity which is dose-dependent and reversible underthe present experimental conditions. Entrathecal Mn resultsin a substantial decrease in striatal dopamine but not homovanillicacid or 3,4-dihydroxyphenylacetic acid (DOPAC) concentrationsand is associated with an increase in the Mn concentration ofthe substantia nigra and caudate-putamen.