Aaron So

Subjective Effects of AMPT-induced Dopamine Depletion in Schizophrenia: Correlation between Dysphoric Responses and Striatal D2 Binding Ratios on SPECT Imaging

Approximately one third of schizophrenic patients treated with neuroleptic drugs experience unpleasant subjective responses, that are collectively known as neuroleptic dysphoria. Experimental research in animals indicates that drug induced dopaminergic blockade in mesolimbic circuits, especially the nucleus accumbens, leads to impaired pleasure responsivity and dysphoria. The present study tested this putative mechanism in drug-free schizophrenic patients (n = 12), through inducing dysphoric responses with alphamethyl paratyrosine (AMPT) and simultaneously quantifying their baseline striatal dopmine (D2) function with 123IBZM-SPECT imaging. Results showed a wide variability in the occurrence and severity of dysphoric responses, clearly distinguishing a dysphoric group from non-dysphoric responders. Severity of dysphoric responses, measured by standardized rating scales, correlated inversely with changes in D2 receptor binding ratios (r = +0.82, p < .01). These results support the notion that striatal dopaminergic activity is not uniformly elevated in all schizophrenic patients, and the sub-group of individuals with lower baseline dopamine function are at an increased risk for dysphoric responses during antipsychotic therapy with dopaminergic blocking drugs.

Prospectively ECG-triggered rapid kV-switching dual-energy CT for quantitative imaging of myocardial perfusion.

Dual-energy computed tomography (DECT) has recently been introduced for clinical use. One potential application of DECT is myocardial perfusion imaging through the significant reduction of beam-hardening artifacts by using monochromatic image reconstruction; analysis of these images can improve the accuracy of quantitative measurement of myocardial perfusion. Single-source DECT enabled by rapid switching between the low and high tube potentials (kV) can minimize misregistration of the high and low kV projection datasets from cardiac motion. We have recently implemented prospective electrocardiography-triggering capability in our rapid kV-switching computed tomography (CT) scanner to reduce the high effective dose from a quantitative CT myocardial perfusion imaging study with DECT. Our initial investigation suggests that prospectively electrocardiography-triggered rapid kV-switching DECT can eliminate beam hardening and provide a more reproducible myocardial perfusion measurement compared with the traditional single-energy CT protocol.

Quantitative myocardial perfusion imaging using rapid kVp switch dual-energy CT: Preliminary experience

BACKGROUND Quantitative myocardial CT perfusion (CTP) is susceptible to beam-hardening (BH) artifact from conventional single-energy (kVp) CT (SECT) scanning, which can mimic perfusion deficits. OBJECTIVE We evaluated the minimization of BH artifact with dual-energy (kVp) CT (DECT) generated monochromatic CT images to improve perfusion estimates. METHODS We investigated the performance of DECT with a scanner capable of rapid kVp switching with respect to (1) BH artifact in a myocardium phantom model comparing SECT with image-based DECT and projection-based DECT, (2) optimal imaging parameters for measuring iodine concentration at high contrast-to-noise ratio in a tissue characterization phantom model, and (3) the feasibility of a dynamic time-resolved scan protocol with the projection-based DECT technique to measure myocardial perfusion in normal (nonischemic) porcine. RESULTS In a myocardium phantom model, projection-based DECT 70 keV was better able to minimize the difference in the attenuation of the myocardium (19.9 HU) between having and not having contrast in the heart chambers in comparison to SECT using 80 kVp (30.4 HU) or 140 kVp ( 23.3 HU) and image-based DECT 70 keV (27.5 HU). Further, projection-based DECT 70 keV achieved the highest contrast-to-noise ratio (3.0), which exceeded that from imaged-based DECT 70 keV (2.0), 140 kVp SECT (1.3), and 80 kVp SECT (2.9). In 5 normal pigs, projection-based DECT at 70 keV provided a more uniform perfusion estimate than SECT. CONCLUSION By effectively reducing BH artifact, projection-based DECT may permit improved quantitative myocardial CTP compared with the conventional SECT technique.

Coronary Artery Imaging with Single-Source Rapid Kilovolt Peak–Switching Dual-Energy CT

PURPOSE To evaluate beam-hardening (BH) artifact reduction in coronary computed tomography (CT) angiography with dual-energy CT, to define the optimal monochromatic-energy levels for coronary and myocardial signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in dual-energy CT, and to compare these levels with single-energy CT. MATERIALS AND METHODS The study was approved by the institutional review board and/or ethics committee at each site. Patients provided informed consent. Thirty-nine patients were prospectively enrolled to undergo dual-energy CT, and 25 also underwent single-energy CT. Myocardial and coronary SNR, CNR, and iodine concentration were measured across multiple segments at varying monochromatic energy levels (40-140 keV). BH was defined as signal decrease in basal inferior wall versus midinferior wall, and signal increase in midseptum versus midinferior wall. Generalized estimating equation was used to identify optimal monochromatic-energy levels and compare them with single-energy CT. RESULTS BH was noted at single-energy CT with basal inferior wall mean reduction of 19.7 HU ± 29.2 (standard deviation) and midseptum increase of 46.3 HU ± 36.3. There was reduction in this artifact at 90 keV or greater (1.7 HU ± 18.4 in basal inferior wall and 20.1 HU ± 37.5 in midseptum at 90 keV; P < .05). SNR and CNR were higher in the myocardium and coronary arteries at 60-80 keV than single-energy CT (myocardium: SNR, 3.02 vs 2.39, and CNR, 6.73 vs 5.16; coronary arteries: SNR, 10.83 vs 7.75, and CNR, 13.31 vs 9.54; P < .01). Mean iodine concentration in resting myocardium was 2.19 mg/mL ± 0.57. CONCLUSION Rapid kilovolt peak-switching dual-energy CT resulted in significant BH reduction and improvements in SNR and CNR in the myocardium and coronary arteries.

Beam hardening correction in CT myocardial perfusion measurement

This paper presents a method for correcting beam hardening (BH) in cardiac CT perfusion imaging. The proposed algorithm works with reconstructed images instead of projection data. It applies thresholds to separate low (soft tissue) and high (bone and contrast) attenuating material in a CT image. The BH error in each projection is estimated by a polynomial function of the forward projection of the segmented image. The error image is reconstructed by back-projection of the estimated errors. A BH-corrected image is then obtained by subtracting a scaled error image from the original image. Phantoms were designed to simulate the BH artifacts encountered in cardiac CT perfusion studies of humans and animals that are most commonly used in cardiac research. These phantoms were used to investigate whether BH artifacts can be reduced with our approach and to determine the optimal settings, which depend upon the anatomy of the scanned subject, of the correction algorithm for patient and animal studies. The correction algorithm was also applied to correct BH in a clinical study to further demonstrate the effectiveness of our technique.

Dual-energy CT and its potential use for quantitative myocardial CT perfusion.

Application of quantitative myocardial CT perfusion (CTP) for the assessment of coronary artery disease may have a significant effect on patient care as the functional significance of a coronary stenosis can be evaluated through absolute measurement of the downstream myocardial perfusion (MP) both at rest and under exercise or pharmacologic stress. A main challenge of myocardial CTP is beam hardening (BH), arising from the polychromatic nature of x-rays used in CT scanning and the presence of highly attenuating contrast agent in the heart chambers during the CT acquisition. The BH effect induces significant nonuniform shifts in CT numbers which, if uncorrected, can lead to inaccurate assessment of MP. With the recent developments of dual-energy CT (DECT) scanning on clinical scanners, the BH effect on MP measurement could be reduced with the generation of monochromatic images relatively free of BH artifacts from the acquired dual-energy data. Here, we review the different techniques of acquiring dual-energy scans and generating monochromatic images, followed by discussion on the progress of developing a DECT technique with reduced radiation dose for quantitative myocardial CTP.

Imaging heart failure: current and future applications.

A variety of cardiac imaging tests are used to help manage patients with heart failure (HF). This article reviews current and future HF applications for the major noninvasive imaging modalities: transthoracic echocardiography (TTE), single-photon emission computed tomography (SPECT), positron emission tomography (PET), cardiovascular magnetic resonance (CMR), and computed tomography (CT). TTE is the primary imaging test used in the evaluation of patients with HF, given its widespread availability and reliability in assessing cardiac structure and function. Recent developments in myocardial strain, 3-dimensional TTE, and echo contrast appear to offer superior diagnostic and prognostic information. SPECT imaging is a common method employed to detect ischemia and viability in patients with HF; however, PET offers higher diagnostic accuracy for both. Ongoing study of sympathetic and molecular imaging techniques may enable early disease detection, better risk stratification, and ultimately targeted treatment interventions. CMR provides high-quality information on cardiac structure and function and allows the characterization of myocardial tissue. Myocardial late gadolinium enhancement allows the determination of HF etiology and may predict patient outcomes and treatment response. Cardiac CT has become a reliable means for detecting coronary artery disease, and recent advances have enabled concurrent myocardial function, perfusion, and scar analyses. Overall, available imaging methods provide reliable measures of cardiac performance in HF, and recent advances will allow detection of subclinical disease. More data are needed demonstrating the specific clinical value of imaging methods and particularly subclinical disease detection in large-scale, clinical settings.

Stress Hypoperfusion and Tissue Injury in Hypertrophic Cardiomyopathy: Spatial Characterization Using High-Resolution 3-Tesla Magnetic Resonance Imaging

Background— Ischemia and tissue injury are common in patients with hypertrophic cardiomyopathy. Cardiovascular magnetic resonance imaging offers combined evaluations of each phenomenon at sufficiently high resolution to examine transmural spatial distribution. In this prospective cohort study, we examine the spatial distribution of stress perfusion abnormalities and tissue injury in patients with hypertrophic cardiomyopathy. Methods and Results— One hundred consecutive patients with hypertrophic cardiomyopathy underwent cardiovascular magnetic resonance imaging. Cine, stress perfusion, late gadolinium enhancement, and T2-weighted imaging techniques were used. Each was spatially coregistered according to predefined segmental and subsegmental models and was blindly analyzed for abnormalities using validated techniques. Spatial associations among stress perfusion, late gadolinium enhancement, and T2 imaging were made at segmental and subsegmental levels. Of the 100 patients studied, the phenotype was septal in 86 and apical in 14. Late gadolinium enhancement imaging was abnormal in 79 patients (79%). Eighty-six patients met prespecified safety criteria to undergo stress perfusion, and ischemia was identified in 46 patients (57%). T2 imaging was available in 81 patients and was abnormal in 19 (29%). The dominant distribution of all 3 findings was to segment with hypertrophy. Subsegmental analysis revealed geographic dominance of ischemia within the subendocardial zones. However, this zone was most commonly spared from late gadolinium enhancement and T2 abnormalities, typically seen in midwall and subepicardial zones. Conclusions— Inducible hypoperfusion is a common finding in hypertrophic cardiomyopathy and is typically identified within segments exhibiting imaging markers of tissue injury. However, the respective transmural dominance of these phenomena seems distinct. Alternate factors contributing to a regional susceptibility to tissue injury are deserving of further study.Background— Ischemia and tissue injury are common in patients with hypertrophic cardiomyopathy. Cardiovascular magnetic resonance imaging offers combined evaluations of each phenomenon at sufficiently high resolution to examine transmural spatial distribution. In this prospective cohort study, we examine the spatial distribution of stress perfusion abnormalities and tissue injury in patients with hypertrophic cardiomyopathy. Methods and Results— One hundred consecutive patients with hypertrophic cardiomyopathy underwent cardiovascular magnetic resonance imaging. Cine, stress perfusion, late gadolinium enhancement, and T2-weighted imaging techniques were used. Each was spatially coregistered according to predefined segmental and subsegmental models and was blindly analyzed for abnormalities using validated techniques. Spatial associations among stress perfusion, late gadolinium enhancement, and T2 imaging were made at segmental and subsegmental levels. Of the 100 patients studied, the phenotype was septal in 86 and apical in 14. Late gadolinium enhancement imaging was abnormal in 79 patients (79%). Eighty-six patients met prespecified safety criteria to undergo stress perfusion, and ischemia was identified in 46 patients (57%). T2 imaging was available in 81 patients and was abnormal in 19 (29%). The dominant distribution of all 3 findings was to segment with hypertrophy. Subsegmental analysis revealed geographic dominance of ischemia within the subendocardial zones. However, this zone was most commonly spared from late gadolinium enhancement and T2 abnormalities, typically seen in midwall and subepicardial zones. Conclusions— Inducible hypoperfusion is a common finding in hypertrophic cardiomyopathy and is typically identified within segments exhibiting imaging markers of tissue injury. However, the respective transmural dominance of these phenomena seems distinct. Alternate factors contributing to a regional susceptibility to tissue injury are deserving of further study.

Functional CT assessment of extravascular contrast distribution volume and myocardial perfusion in acute myocardial infarction

PURPOSE In a pig model of acute myocardial infarction (AMI), we validated a functional computed tomography (CT) technique for concomitant assessment of myocardial edema and ischemia through extravscualar contrast distribution volume (ECDV) and myocardial perfusion (MP) measurements from a single dynamic imaging session using a single contrast bolus injection. METHODS In seven pigs, balloon catheter was used to occlude the distal left anterior descending artery for one hour followed by reperfusion. CT and cardiac magnetic resonance (CMR) imaging studies were acquired on 3 days and 12 ± 3 day post ischemic insult. In each CT study, 0.7 ml/kg of iodinated contrast was intravenously injected at 3-4 ml/s before dynamic contrast-enhanced (DCE) cardiac images were acquired with breath-hold using a 64-row CT scanner. DCE cardiac images were analyzed with a model-based deconvolution to generate ECDV and MP maps. ECDV as an imaging marker of edema was validated against CMR T2 weighted imaging in normal and infarcted myocardium delineated from ex-vivo histological staining. RESULTS ECDV in infarcted myocardium was significantly higher (p < 0.05) than that in normal myocardium on both days post AMI and was in agreement with the findings of CMR T2 weighted imaging. MP was significantly lower (p < 0.05) in the infarcted region compared to normal on both days post AMI. CONCLUSION This imaging technique can rapidly and simultaneously assess myocardial edema and ischemia through ECDV and MP measurements, and may be useful for delineation of salvageable tissue within at-risk myocardium to guide reperfusion therapy.

Technical Note: Comparison of megavoltage, dual‐energy, and single‐energy CT‐based μ‐maps for a four‐channel breast coil in PET/MRI

Purpose The purpose of this study was to describe and evaluate methods for calculating a megavoltage computed tomography (MVCT)‐derived MR hardware attenuation map (μ‐map) and dual‐energy CT (DECT) for 511 keV photons. Methods Phantom measurements were acquired on a whole‐body hybrid PET/MRI system, using a four‐channel receive‐only MR radiofrequency (RF) breast coil. Two acquisitions were performed: with the phantoms positioned in the four‐channel RF breast coil, and without the breast coil. PET attenuation from the breast coil was corrected using three different CT‐derived hardware μ‐maps: (a) Single‐energy CT (SECT), (b) DECT, and (c) MVCT. Each attenuation‐corrected (AC) PET volume was evaluated and compared with the acquisition performed without the breast coil. Results The breast coil attenuated PET photons by 10% overall. Threshold values were applied to the SECT μ‐map to reduce the effects of metal artifacts, but overcorrection occurred in more highly attenuated regions. The DECT‐derived virtual monochromatic image reduced beam‐hardening artifacts, but other metal artifacts remained. Despite the remaining metal artifacts in the DECT image, it led to an improvement in the more attenuated regions. The MVCT images appear to be free from metal artifacts leading to an artifact‐free μ‐map and a further improvement AC‐PET images. Conclusions Our MVCT‐based approach for creating μ‐maps for MR RF coils greatly reduces artifacts produced by metal in a SECT approach. This eliminates the need for other artifact reduction methods, including the application of a threshold of narrow beam attenuation coefficients, or disassembling hardware to remove high‐Z components before imaging with a kilovoltage source.