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Background: Accurate alignment between cardiac CT angiographic studies (CTA) and nuclear perfusion images is crucial for improved diagnosis of coronary artery disease. This study evaluated in an animal model the accuracy of a CTA fully automated biventricular segmentation algorithm, a necessary step for automatic and thus efficient PET/CT alignment., Methods and Results: Twelve pigs with acute infarcts were imaged using Rb-82 PET and 64-slice CTA. Post-mortem myocardium mass measurements were obtained. Endocardial and epicardial myocardial boundaries were manually and automatically detected on the CTA and both segmentations used to perform PET/CT alignment. To assess the segmentation performance, image-based myocardial masses were compared to experimental data; the hand-traced profiles were used as a reference standard to assess the global and slice-by-slice robustness of the automated algorithm in extracting myocardium, LV, and RV. Mean distances between the automated and the manual 3D segmented surfaces were computed. Finally, differences in rotations and translations between the manual and automatic surfaces were estimated post-PET/CT alignment. The largest, smallest, and median distances between interactive and automatic surfaces averaged 1.2 ± 2.1, 0.2 ± 1.6, and 0.7 ± 1.9 mm. The average angular and translational differences in CT/PET alignments were 0.4°, -0.6°, and -2.3° about x, y, and z axes, and 1.8, -2.1, and 2.0 mm in x, y, and z directions., Conclusions: Our automatic myocardial boundary detection algorithm creates surfaces from CTA that are similar in accuracy and provide similar alignments with PET as those obtained from interactive tracing. Specific difficulties in a reliable segmentation of the apex and base regions will require further improvements in the automated technique., Competing Interests: Some of the authors (EG, RF, TF) receive royalties from the sale of the Emory Cardiac Toolbox and have equity positions with Syntermed, Inc., which markets ECTb. The terms of these arrangements have been reviewed and approved by Emory University in accordance with its conflict of interest policies. The remaining authors do not have any conflicts of interest.

Objectives: The aim of this study was to determine whether post-traumatic stress disorder (PTSD) is associated with coronary heart disease (CHD) using a prospective twin study design and objective measures of CHD., Background: It has long been hypothesized that PTSD increases the risk of CHD, but empirical evidence using objective measures is limited., Methods: We conducted a prospective study of middle-aged male twins from the Vietnam Era Twin Registry. Among twin pairs without self-reported CHD at baseline, we selected pairs discordant for a lifetime history of PTSD, pairs discordant for a lifetime history of major depression, and pairs without either condition. All underwent a clinic visit after a median follow-up of 13 years. Outcomes included clinical events (myocardial infarction, other hospitalizations for CHD and coronary revascularization) and quantitative measures of myocardial perfusion by [(13)N] ammonia positron emission tomography, including a stress total severity score and coronary flow reserve., Results: A total of 562 twins (281 pairs) with a mean age of 42.6 years at baseline were included in this study. The incidence of CHD was more than double in twins with PTSD (22.6%) than in those without PTSD (8.9%; p < 0.001). The association remained robust after adjusting for lifestyle factors, other risk factors for CHD, and major depression (odds ratio: 2.2; 95% confidence interval: 1.2 to 4.1). Stress total severity score was significantly higher (+95%, p = 0.001) and coronary flow reserve was lower (-0.21, p = 0.02) in twins with PTSD than in those without PTSD, denoting worse myocardial perfusion. Associations were only mildly attenuated in 117 twin pairs discordant for PTSD., Conclusions: Among Vietnam-era veterans, PTSD is a risk factor for CHD., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Left ventricular (LV) function and dyssynchrony parameters measured from serial gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) using blinded processing had a poorer repeatability than when manual side-by-side processing was used. The objective of this study was to validate whether an automatic alignment tool can reduce the variability of LV function and dyssynchrony parameters in serial gated SPECT MPI., Methods: Thirty patients who had undergone serial gated SPECT MPI were prospectively enrolled in this study. Thirty minutes after the first acquisition, each patient was repositioned and a gated SPECT MPI image was reacquired. The two data sets were first processed blinded from each other by the same technologist in different weeks. These processed data were then realigned by the automatic tool, and manual side-by-side processing was carried out. All processing methods used standard iterative reconstruction and Butterworth filtering. The Emory Cardiac Toolbox was used to measure the LV function and dyssynchrony parameters., Results: The automatic tool failed in one patient, who had a large, severe scar in the inferobasal wall. In the remaining 29 patients, the repeatability of the LV function and dyssynchrony parameters after automatic alignment was significantly improved from blinded processing and was comparable to manual side-by-side processing., Conclusion: The automatic alignment tool can be an alternative method to manual side-by-side processing to improve the repeatability of LV function and dyssynchrony measurements by serial gated SPECT MPI.

Background: Phase analysis has been developed and validated to measure left-ventricular dyssynchrony from gated SPECT myocardial perfusion imaging. The purpose of this study is to evaluate its performance in regions with perfusion defects., Methods: A special version of the eXtended CArdiac Torso digital phantom was developed to track B-spline points in each temporal frame. A region of 35 B-spline points in the inferior wall with normal and abnormal perfusion uptakes were simulated. Phase shifts were simulated in the same region, representing dyssynchronous contraction. Gated SPECT data were analyzed using a modified phase analysis algorithm, which tracked the same 35 B-spline points to calculate their phases., Results: Phases and phase shifts measured in the B-spline points with perfusion uptake in the range of 50%-10% did not significantly differ from those measured in the same B-spline points with normal perfusion uptake., Conclusion: Phase analysis can accurately measure phases in regions with abnormal perfusion uptake as low as 10% of the perfusion uptake in the normal regions, which corresponded to a regional signal-to-noise ratio (SNR) of 12.0 or greater. In 42 consecutive patients with myocardial infarction >20% of the left ventricle, only two patients had a SNR within the perfusion defects below that threshold.

Explicit fusion of perfusion data from Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) with coronary artery anatomy from Computed Tomographic Coronary Angiography (CTA) has been shown to improve the diagnostic yield for coronary artery disease (CAD) compared to either modality alone. However, most clinically available methods were developed for multimodal scanners or require interactive alignment prior to display and analysis. A new approach was developed to register the two distributions obtained either from a single multimodal imager or from separate scanners, and a preliminary validation was undertaken to compare the automatic alignment to interactive alignment by two experts.

Left ventricular (LV) wall thickening (WT) assessed from myocardial perfusion (MP) gated SPECT data has been reported to be a marker of functional recovery following myocardial damage. However, the accuracy of WT measurements obtained in the clinical setting rarely has been validated against an independent quantitative reference standard. The purpose of this investigation was to assess the degree to which quantified MP WT agrees with cardiac magnetic resonance (CMR) WT measurements, and to determine whether quantitation is as accurate as visual analysis in detecting abnormal regional WT. MP and ECG-gated True-FISP CMR data were analyzed for 20 patients evaluated after myocardial infarction (age 60 ± 11 years; 95% males). An experienced observer visually graded MP WT on a 5-point scale while viewing MP cines. MP WT was quantified using "Emory Cardiac Toolbox" (ECTb) algorithms. MP algorithms isolated myocardial counts and generated polar maps of WT. CMR data were analyzed by Medis "MASS" software. Manually drawn endocardial and epicardial contours were used to compute WT on CMR. CMR data also were processed for 10 age-matched normal volunteers to define the CMR WT threshold of abnormality. All computations were sampled into conventional 17 ACC/AHA LV wall segments. Receiver operating characteristics (ROC) curve analysis provided discrimination thresholds for optimal accuracy, which subsequently were used to dichotomize the MP methods. WT abnormalities also were assessed for the 3 major arterial territories, and for total numbers of abnormal segments per patient. 25% of all segments had abnormally low WT by CMR. While MP quantitation underestimated CMR WT values for segments with normal WT (26 ± 13% vs. 56 ± 28%, P < 0.0001), measurements were similar for segments with abnormal WT (4 ± 12% vs. 5 ± 9%, P = 0.45). On a segment-by-segment basis, detection of abnormal WT was more accurate by quantitative than visual analysis both for continuous variables (ROC area = 88 ± 2% vs. 80 ± 3%, P < 0.0001) and for dichotomized methods (83% vs. 76%, P = 0.04). Agreement of MP versus CMR for discriminating segments with normal from abnormal WT was significantly better for quantitative than visual analysis (κ = 0.59 vs. 0.40, P < 0.0001), with strongest agreement for left anterior descending artery territories (κ = 0.72). Total numbers of segments with abnormal WT per patient demonstrated significant correlation with CMR (r = 0.83, P < 0.0001). MP quantified LV ejection fractions and volumes also correlated well with CMR (r = 0.87 and 0.90, respectively). Quantified MP WT measurements correlated significantly with CMR values, and discriminated segments with abnormal WT from segments with normal WT more accurately than visual analysis. Therefore, quantification should be performed when analyzing regional WT by scintigraphy.

Myocardial perfusion imaging (MPI) using nuclear cardiology techniques has been widely applied in clinical practice because of its well-documented value in the diagnosis and prognosis of coronary artery disease. Industry has developed innovative designs for dedicated cardiac SPECT cameras that constrain the entire detector area to imaging just the heart. New software that recovers image resolution and limits image noise has also been implemented. These SPECT innovations are resulting in shortened study times or reduced radiation doses to patients, promoting easier scheduling, higher patient satisfaction, and, importantly, higher image quality. This article describes these cardiocentric SPECT software and hardware innovations, which provide a strong foundation for the continued success of myocardial perfusion SPECT.

Explicit fusion of perfusion data from Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) with coronary artery anatomy from Computed Tomographic Coronary Angiography (CTCA) has been shown to improve the diagnostic yield for coronary artery disease (CAD) compared to either modality alone. However, most clinically available methods were developed for multimodal scanners or require interactive alignment prior to display and analysis. A new approach was developed to register and display the two distributions obtained either from a single multimodal imager or from separate scanners, and a preliminary validation was undertaken using interactive alignment by experts.

This article describes advancements in hardware and software for myocardial perfusion imaging that are becoming commercialized today and their implication in clinical practice.

Background: We evaluated the incremental diagnostic value of fusion images of coronary computed tomography angiography (CTA) and myocardial perfusion imaging (MPI) over MPI alone or MPI and CTA side-by-side to identify obstructive coronary artery disease (CAD > 50% stenosis) using invasive coronary angiography (ICA) as the gold standard., Methods: 50 subjects (36 men; 56 +/- 11 years old) underwent rest-stress MPI and CTA within 12-26 days of each other. CTAs were performed with multi-detector CT-scanners (31 on 64-slice; and 19 on 16-slice). 37 patients underwent ICA while 13 subjects did not because of low (<5%) pre-test likelihood (LLK) of disease. Three blinded readers scored the images in sequential sessions using (1) MPI alone (2) MPI and CTA side-by-side, (3) fused CTA/MPI images., Results: One or more critical stenoses during ICA were found in 28 patients and non-critical stenoses were found in 9 patients. MPI, side-by-side MPI-CTA, and fused CTA/MPI showed the same normalcy rate (NR:13/13) in LLK subjects. The fusion technique performed better than MPI and MPI and CTA side-by-side for the presence of CAD in any vessel (overall area under the curve (AUC) for fused images: 0.89; P = .005 vs MPI, P = .04 vs side-by-side MPI-CTA) and for localization of CAD to the left anterior descending coronary artery (AUC: 0.82, P < .001 vs MPI; P = .007 vs side-by-side MPI-CTA). There was a non-significant trend for better detection of multi-vessel disease with fusion., Conclusions: Using ICA as the gold standard, fusion imaging provided incremental diagnostic information compared to MPI alone or side-by-side MPI-CTA for the diagnosis of obstructive CAD and for localization of CAD to the left anterior descending coronary artery.

Image quality is significantly degraded even by small amounts of patient motion in very high-resolution PET scanners. Existing correction methods that use known patient motion obtained from tracking devices either require multi-frame acquisitions, detailed knowledge of the scanner, or specialized reconstruction algorithms. A deconvolution algorithm has been developed that alleviates these drawbacks by using the reconstructed image to estimate the original non-blurred image using maximum likelihood estimation maximization (MLEM) techniques. A high-resolution digital phantom was created by shape-based interpolation of the digital Hoffman brain phantom. Three different sets of 20 movements were applied to the phantom. For each frame of the motion, sinograms with attenuation and three levels of noise were simulated and then reconstructed using filtered backprojection. The average of the 20 frames was considered the motion blurred image, which was restored with the deconvolution algorithm. After correction, contrast increased from a mean of 2.0, 1.8 and 1.4 in the motion blurred images, for the three increasing amounts of movement, to a mean of 2.5, 2.4 and 2.2. Mean error was reduced by an average of 55% with motion correction. In conclusion, deconvolution can be used for correction of motion blur when subject motion is known.

Image quality is significantly degraded even by small amounts of patient motion in very high-resolution PET scanners. When patient motion is known, deconvolution methods can be used to correct the reconstructed image and reduce motion blur. This paper describes the implementation and optimization of an iterative deconvolution method that uses an ordered subset approach to make it practical and clinically viable. We performed ten separate FDG PET scans using the Hoffman brain phantom and simultaneously measured its motion using the Polaris Vicra tracking system (Northern Digital Inc., Ontario, Canada). The feasibility and effectiveness of the technique was studied by performing scans with different motion and deconvolution parameters. Deconvolution resulted in visually better images and significant improvement as quantified by the Universal Quality Index (UQI) and contrast measures. Finally, the technique was applied to human studies to demonstrate marked improvement. Thus, the deconvolution technique presented here appears promising as a valid alternative to existing motion correction methods for PET. It has the potential for deblurring an image from any modality if the causative motion is known and its effect can be represented in a system matrix.

Objectives: This study was performed to determine the prognostic performance of quantitative PET tools in the stratification of patients with ischemic cardiomyopathy undergoing myocardial viability assessment., Methods: We applied four different quantitative tools to 104 consecutive patients with coronary artery disease and previous myocardial infarction who had undergone rest Rb/gated F-fluorodeoxyglucose (FDG) PET, to assess myocardial viability for potential revascularization. One of these tools was based on the FDG study alone and the other three tools assessed the extent of match/mismatch defects using FDG in comparison with a perfusion reference database. The four quantitative tools used in this research to define viability were (i) FDG alone, which calculates the percentage of left ventricular myocardium (LVM) that is above the 50% of the maximum LVM FDG counts, (ii) low flow match/mismatch, which determines the area with a 5% increase in normalized FDG counts in relation to defined resting perfusion defects as compared with a reference database, (iii) all regions match/mismatch, which computes the area with a 10% increase in normalized FDG counts in relation to the left ventricle resting perfusion distribution, and (iv) percentage max FDG match/mismatch, which defines the area with FDG uptake greater than 60% of the maximum LVM FDG counts within defined perfusion defects as determined by the reference database. The primary endpoint for this analysis was cardiac death., Results: During the follow-up period (22+/-14 months), 19 patients (18%) died; in 17 of these the cause of death was cardiac. Using univariate analysis, none of the methods were predictive of cardiac death. Receiver operating characteristic analysis defined the optimal thresholds for the extent of myocardial viability for the four tools in the prediction of cardiac death: FDG alone=20%, low flow match/mismatch=15%, all regions match/mismatch=35%, and percentage max FDG match/mismatch=20%. A censored survival analysis using a Kaplan-Meier method showed a statistically significant difference between patients with cardiac death and those with no cardiac death using only the low flow match/mismatch (hazard ratio=0.29, P=0.01) and percentage max FDG match/mismatch criteria (hazard ratio=0.23, P=0.005) tools., Conclusion: The low flow match/mismatch and percentage max FDG match/mismatch quantitative PET tools are useful for prognostic stratification of patients with ischemic cardiomyopathy undergoing myocardial viability assessment.

Background: Multiharmonic phase analysis (MHPA) was developed to assess left-ventricular dyssynchrony from gated myocardial perfusion single-photon emission computed tomography (GSPECT) studies. This study was intended to determine the temporal resolution of MHPA., Methods: A reference normal GSPECT study with 128 frames/cycle was simulated using NCAT, a nonuniform rational B-splines-based cardiac torso phantom. It was shifted in the time domain to insert phase delays. Realistic GSPECT studies (8 or 16 frames/cycle) were then obtained by down-sampling the reference and shifted studies. All GSPECT projections were generated with attenuation, scatter, collimator blurring, and Poisson noise. Seventeen regional phases were calculated from the GSPECT reconstructions (filtered back-projection without compensation for physical factors), using linear interpolation for the reference study, and MHPA for the realistic studies. Comparing the regional phases between the realistic studies without and with shifts determined whether MHPA could identify certain phase delays., Results: When there were enough counts/pixel (>10 counts/pixel), MHPA with either 1, 2, or 3 harmonics could resolve a phase difference of 5.6 degrees , corresponding to 1/64 of the cardiac cycle., Conclusions: With clinically equivalent counts, the temporal resolution of MHPA is 1/64 of a cardiac cycle. Achieving this high temporal resolution from data with low temporal resolution demonstrates the benefit of replacing discrete points with continuous harmonic functions.

In humans, the wakeful resting condition is characterized by a default mode of brain function involving high levels of activity within a functionally connected network of brain regions. This network has recently been implicated in mental self-projection into the past, the future, or another individual's perspective. Here we use [(18)F]-fluorodeoxyglucose positron emission tomography imaging to assess resting-state brain activity in our closest living relative, the chimpanzee, as a potential window onto their mental world and compare these results with those of a human sample. We find that, like humans, chimpanzees show high levels of activity within default mode areas, including medial prefrontal and medial parietal cortex. Chimpanzees differ from our human sample in showing higher levels of activity in ventromedial prefrontal cortex and lower levels of activity in left-sided cortical areas involved in language and conceptual processing in humans. Our results raise the possibility that the resting state of chimpanzees involves emotionally laden episodic memory retrieval and some level of mental self-projection, albeit in the absence of language and conceptual processing.

Single photon emission computed tomography (SPECT) myocardial perfusion imaging has attained widespread clinical acceptance as a standard of care for patients with known or suspected coronary artery disease. A significant contribution to this success has been the use of computer techniques to provide objective quantitative assessment in interpreting these studies. We have implemented the Emory Cardiac Toolbox (ECTb) as a pipeline to distribute the software tools that we and others have researched, developed, and validated to be clinically useful so that diagnosticians everywhere can benefit from our work. Our experience has demonstrated that integration of all software tools in a common platform is the optimal approach to promote both accuracy and efficiency. Important attributes of the ECTb approach are (1) our extensive number of normal perfusion databases for SPECT and positron emission tomography (PET) studies, each created with at least 150 patients; (2) our use of Fourier analysis of regional thickening to ensure proper temporal resolution and to allow accurate measurement of left ventricular function and dyssynchrony; (3) our development of PET tools to quantify myocardial hibernation and viability; (4) our development of 3-dimensional displays and the use of these displays as a platform for image fusion of perfusion and computed tomography angiography; and (5) the use of expert systems for decision support. ECTb is an important tool for extracting quantitative parameters from all types of cardiac radionuclide distributions. ECTb should continue to play an important role in establishing cardiac SPECT and PET for flow, function, metabolism, and innervation clinical applications.

Our current approach to fusion of CTCA and PET perfusion data uses the epicardial surface from the perfusion data onto which the CT coronary arteries are aligned and warped. This work was undertaken to improve the alignment and the display realism by using CT epicardial boundary information. PET and CTCA images from a combined scanner were used. Based on the location of the LV detected from PET during standard perfusion processing, the LV chamber of the CT was located. Hounsfield units were used to define an estimated endocardial surface in the CT. Based on the endocardial surface, the epicardial boundary was detected, again using Hounsfield units, or when that failed, by estimating its position based on the detected endocardium. Coronary arteries were detected using a commercial program; the epicardial surface was forced to be congruent with all detected artery points. A confidence factor in each epicardial boundary point was maintained based on how each was detected, whether through threshold, through estimation, or by using he coronary artery points. The epicardial boundary surface points were nonlinearly filtered; erroneous surface points, as defined by local properties and confidence factors, were replaced with values interpolated from the nearest points deemed more accurate. The resulting epicardial surface was linearly aligned to the epicardial boundary detected from the PET, and the CT boundaries were then color-coded based on the PET perfusion. Resulting surfaces were much more realistic than those created using PET epicardial boundaries (Fig 1.) Forcing the CT epicardial surface to lie on the detected coronary arteries eliminated problems with alignment and warping of the coronary arteries onto the PET surface.

Background: Emission-transmission misalignment with single-photon emission computed tomography (SPECT)-computed tomography (CT) systems can impair attenuation correction (AC) in myocardial perfusion imaging. This study was performed to develop automated quality control (Auto-QC) to detect critical misalignment that can significantly impact AC., Methods and Results: Auto-QC was developed to segment myocardium and mediastinum from emission and transmission reconstructions, respectively. Myocardium-mediastinum mismatch was used as the quality-control index (QCI). The QCI threshold for acceptable AC was determined with NCAT (NURBS [nonuniform rational B-spline]-based cardiac torso phantom) simulation and verified with 2 patients with minimal misalignment. Compromised data sets, generated by shifting the attenuation maps by 0.5, 1.0, 1.5, and 2.0 pixels along left-right, up-down, and head-foot directions, respectively, were qualitatively and quantitatively compared with the unshifted data sets. Auto-QC was tested with the 2 verification patients and 41 additional patients. Shifts by more than 1 pixel along any direction compromised AC. Auto-QC with the QCI threshold (3%) had highly concordant results with manual quality control in the detection of critical misalignment (sensitivity of 88% and 90% and specificity of 93% and 95% for the tests by use of the 2 verification patients and 41 additional patients, respectively)., Conclusion: QCI quantitatively represented the severity of misalignment. Auto-QC can help clinicians be aware of critical misalignment and can assist in realignment of SPECT and CT images.

Background: A count-based method using technetium-99m sestamibi electrocardiography-gated myocardial perfusion single photon emission computed tomography imaging has been developed to extract the left ventricular (LV) regional phase of contraction (onset of mechanical contraction [OMC]) throughout the cardiac cycle. This study was performed to develop OMC normal databases and dynamic OMC displays for assessment of cardiac mechanic dyssynchrony., Methods and Results: LV regional phases were extracted from 90 enrolled normal subjects (45 men and 45 women) by use of the Emory Cardiac Toolbox and then submitted to statistical analysis to generate the normal databases. The LV OMC wave was dynamically propagated over the perfusion polar map by blackening either sequential phase bins or all past phases. The developed OMC normal databases consisted of peak phase (134.5 degrees +/- 14.3 degrees for men and 140.2 degrees +/- 14.9 degrees for women), phase SD (14.2 degrees +/- 5.1 degrees for men and 11.8 degrees +/- 5.2 degrees for women), and phase histogram bandwidth (38.7 degrees +/- 11.8 degrees for men and 30.6 degrees +/- 9.6 degrees for women), skewness (4.19 +/- 0.68 for men and 4.60 +/- 0.72 for women), and kurtosis (19.72 +/- 7.68 for men and 23.21 +/- 8.16 for women). Both statistical analysis and dynamic OMC displays were incorporated into a user interface as a diagnostic tool., Conclusion: The OMC normal databases and dynamic OMC displays should help clinicians evaluate cardiac mechanic dyssynchrony. Prospective clinical trials are needed to validate whether this tool can be used to select patients with severe heart failure symptoms who might benefit from cardiac resynchronization therapy.

Background: New algorithms were evaluated for their efficacy in detecting and quantifying serial changes in myocardial perfusion from single photon emission computed tomography (SPECT)., Methods and Results: We generated 72 simulations with various left ventricular positions, sizes, count rates, and perfusion defect severities using the nonuniform rational B-splines (NURBs)-based CArdiac Torso (NCAT) phantom. Images were automatically aligned by use of both full linear and rigid transformations and quantified for perfusion by use of the CEqual program. Changes within a given perfusion defect were compared by use of a Student t test before and after registration. Registration approaches were compared by use of receiver operating characteristic analysis. Changes of 5% were not detected well in single patients with or without alignment. Changes of 10% and 15% could be detected with false-positive rates of 15% and 10%, respectively, in single studies if alignment was performed before perfusion analysis. Alignment also reduced the number of studies necessary to demonstrate a significant perfusion change (P < .05) in groups of patients by about half., Conclusion: Comparison of mean uptake by t values in SPECT perfusion defects can be used to detect 10% and greater differences in serial perfusion studies of single patients. Image alignment is necessary to optimize automatic detection of perfusion changes in both single patients and groups of patients.

Background: The purpose of this study was to determine the independent value of left ventricular (LV) functional parameters derived from gated fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to predict prognosis in patients with ischemic cardiomyopathy undergoing myocardial viability assessment., Methods and Results: We studied 90 consecutive patients with coronary artery disease and low LV ejection fraction (26% +/- 7%) undergoing gated FDG PET to assess myocardial viability for potential revascularization. The primary endpoint for this analysis was the occurrence of cardiac death, myocardial infarction, or worsening heart failure (HF) to New York Heart Association class IV. During follow-up (22 +/- 14 months), 21 patients had an event (17 died, 4 had myocardial infarctions, and 4 had worsening HF). On Cox regression analysis, the event-free survival rate at 2 years was lower for patients with an end-diastolic volume (EDV) of 260 mL or greater (relative risk, 2.7; P = .014), end-systolic volume (ESV) of 200 mL or greater (relative risk, 2.5; P = .021), and LV mass of 143 g or greater (relative risk, 1.6; P = .009). In a risk-adjusted model, EDV (chi 2 = 68, P < .0001) and ESV (chi 2 = 75, P = .035) added a significant amount in the estimation of events over the perfusion-FDG mismatch pattern (chi 2 = 40, P < .001). In a stratified Cox model, patients with PET mismatch, LV ejection fraction lower than 25%, and EDV of 260 mL or greater had the lowest survival rate (P = .006). These patients showed an apparent survival benefit with revascularization but without an improvement in HF symptoms., Conclusion: LV functional parameters determined by gated FDG PET have incremental prognostic value over viability information in patients with ischemic cardiomyopathy. Our data suggest that patients with residual viability and advanced cardiac remodeling are at high clinical risk. In these patients the apparent survival benefit of revascularization may not be associated with a measurable improvement in HF symptoms.

Unlabelled: Clinical decisions regarding diagnosis and effective treatment of coronary artery disease frequently require integration of information from various imaging modalities, which are acquired, processed, and read at different physical locations and times. We have developed methods to integrate the information in 2 cardiac imaging studies, perfusion SPECT and coronary angiography. Three-dimensional (3D) models of the coronary artery tree created from biplane angiograms were automatically aligned with 3D models of the left ventricular epicardial surface created from perfusion SPECT. Myocardial mass at risk was used as a unique measure to validate the accuracy of the unification., Methods: Thirty patients were injected with the perfusion agent (99m)Tc-tetrosfosmin during balloon occlusion while undergoing percutaneous transluminal coronary angioplasty for single-vessel coronary artery disease. Thus, a single, severe perfusion defect was induced by a single coronary artery occlusion of known severity and placement. The accuracy of the unification was measured by computing the overlap between physiologic area at risk, determined using SPECT perfusion quantification techniques only, and anatomic area at risk, determined using coronary artery anatomy aligned with the epicardial surface of the left ventricle., Results: The unification resulted in an 80% overlap of areas at risk, and an overlap of 84% of normal areas, for all coronary artery distributions. The mass at risk measured based on the unified anatomic information correlated with the physiologically based mass at risk as y = 0.92x + 10.3 g; r = 0.76, SEE = 10.4 g., Conclusion: A unification algorithm for automatically registering 3D models of the epicardial surface from perfusion SPECT and 3D coronary artery trees from coronary angiography has been presented and validated in 30 patient studies.

Background: Cardiac gating is not routinely used in cardiac positron emission tomography (PET). The aim of this study was to determine the feasibility of assessing regional wall motion, ejection fraction (EF), cardiac volumes, and mass with nitrogen-13 ammonia (N-13 ammonia) at the time of PET myocardial perfusion imaging., Methods: We studied 12 healthy volunteers (mean age, 28 +/- 8 years) and 53 patients with documented coronary artery disease (CAD) (mean age, 59 +/- 11 years). All subjects received a single administration of approximately 600 MBq (16 mCi) of N-13 ammonia intravenously. A 6-minute dynamic scan was performed for quantitative assessment of myocardial perfusion at rest, followed by a separate, 13-minute static scan acquired in the gated mode (8 equal bins). Gated data was imported into the Emory Toolbox. Wall motion was evaluated by dividing the myocardium into 9 anatomic regions graded semiquantitatively., Results: Healthy volunteers had a normal EF (61 +/- 6), end systolic volume (ESV) (37 +/- 15 mL), end diastolic volume (EDV) (89 +/- 25 mL), and cardiac mass (116 +/- 18 g). In contrast, patients with CAD showed reduced EF (32 +/- 13%) and increased ESV (129 +/- 56 mL), EDV (188 +/- 68 mL), and cardiac mass (173 +/- 45 g) (P < 0.001 for each). In patients with CAD, EF measured by gated PET correlated significantly to independent measurements of EF (P < 0.001)., Conclusions: Gating of cardiac perfusion images obtained after administration of N-13 ammonia is feasible and appears to be an accurate means of evaluating regional and global cardiac function. Gating can provide important additional diagnostic and prognostic information.

Unlabelled: The aim of this study was to do an initial assessment of the usefulness of 2beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(2-(18)F-fluoroethyl)nortropane ((18)F-FECNT) PET scanning in determining in vivo brain dopamine transporter (DAT) density in healthy humans and subjects with Parkinson's disease (PD)., Methods: We investigated 6 neurologically healthy subjects and 5 PD patients: 2 with mild unilateral disease, 1 with mild-to-moderate bilateral disease, and 2 with moderately severe bilateral disease. The healthy subjects underwent a 3-h PET scan (26 frames) and the PD subjects underwent a 2-h PET scan (23 frames) while (18)F-FECNT was being injected over the first 5 min of the scan. Arterial blood samples were taken throughout scanning for well-counter and metabolite analysis to determine the presence of possible active metabolites. The scans were reconstructed; then we placed spheric regions of interest in the caudate nuclei, putamena, thalami, brain stem, cerebellum, and occipital cortex of each subject. The radioactivity level in each region was calculated for each frame of a subject's PET scan. Then we calculated target tissue-to-cerebellum ratios for each time frame., Results: The analysis of arterial blood samples revealed that metabolism of the tracer was rapid. The ether-extractable component of the arterial input was >98% pure (18)F-FECNT. The caudate nucleus and putamen exhibited the highest uptake and prolonged retention of the radioligand. They both attained maximum uptake at approximately 90 min, with the healthy subjects' average caudate- and putamen-to-cerebellum ratios (+/-SD) at that time being 9.0 +/- 1.2 and 7.8 +/- 0.7, respectively. The maximal caudate-to-cerebellum ratios for the healthy subjects ranged from 7.6 to 10.5 and their maximal putamen-to-cerebellum ratios ranged from 7.1 to 9.3. The 2 early-stage, unilateral PD patients had, at 90 min, an average right caudate-to-cerebellum ratio of 5.3 +/- 1.1 and a left ratio of 5.9 +/- 0.7 and an average right putamen-to cerebellum ratio of 2.8 +/- 0.1 and a left ratio of 3.0 +/- 0.6. The late-stage PD patients had, at 90 min, an average right caudate-to-cerebellum ratio of 3.7 +/- 0.4 and a left ratio of 3.9 +/- 0 and an average right putamen-to cerebellum ratio of 1.8 +/- 0.1 and a left ratio of 1.8 +/- 0., Conclusion: These results indicate that (18)F-FECNT is an excellent candidate radioligand for in vivo imaging of the DAT system in humans. It has a much higher affinity for DAT than for the serotonin transporter and yields the highest peak striatum-to-cerebellum ratios and has among the most favorable kinetics of (18)F-radiolabeled DAT ligands. Having picked up presymptomatic changes in the hemisphere opposite the unaffected side of the body in our early-stage (unilateral) PD patients, it appears that, like other DAT radioligands, it may be able to identify presymptomatic PD.

In today's cost containment environment it is important to consider changes to standard protocols which would reduce cost, particularly if there is no significant loss of diagnostic accuracy. The aim of the present study was to assess the usefulness of a gated stress-only Tc sestamibi protocol in comparison to conventional gated dual isotope rest-stress myocardial perfusion single photon emission computed tomography (SPECT) in the detection and localization of coronary artery disease (CAD). Sixty-five consecutive patients (65+/-10 years, 22 women) who had undergone conventional gated perfusion SPECT were chosen retrospectively. Fifty-three of these 65 patients had previous coronary arteriography, 45 with at least one stenosis, eight without stenosis, and 12 of these 65 patients had <5% likelihood of CAD. Three readers interpreted the gated stress-only and dual isotope studies in separate sessions blinded to (1). their previous readings, (2). the interpretation by others, and (3). the angiographic results. Readers used a five-point scale to score their visual and quantitative assessment of perfusion, function and compromised vascular territory. Their average score was used for determination of the accuracy by using receiver operating characteristic (ROC) analysis of the techniques. The areas under ROC curves were determined for the detection of CAD and localization of vascular territories. Fifty-four of these patients had 97 significant stress induced perfusion defects as determined by the CEqual quantitative program. The agreement between protocols for the assessment of reversibility in these 97 defects was analysed. There were no statistically significant differences between dual isotope rest/stress and gated stress-only studies for the detection and localization of CAD. The area under the dual isotope rest/stress ROC curve was 0.78+/-0.07 compared to the area under the gated stress-only ROC curve of 0.80+/-0.06, resulting in P=0.30. For the combined vessels comparison of the area under the dual isotope rest/stress ROC curve was 0.73+/-0.04 versus the area under the gated stress-only ROC curve of 0.74+/-0.04, resulting in P=0.27. Similar non-significant differences were obtained when comparing the area under the dual isotope versus gated stress-only ROC curves for the left anterior descending vascular territory (LAD, 0.61+/-0.08 vs 0.660.08, P=0.14), the left circumflex vascular territory (LCX, 0.82+/-0.07 vs 0.81+/-0.06, P =0.47) or the right coronary vascular territory (RCA, 0.80+/-0.06 vs 0.78+/-0.06, P=0.28). The analysis of the reversibility of stress induced perfusion defects yielded a global agreement between protocols of 93% (kappa=0.42). The differences were due to the expert readers, using the gated stress-only protocol, misinterpreting some patients with attenuation artefacts, subendocardial infarction and functional stunning. These results show that the lower cost gated stress-only myocardial Tc myocardial perfusion SPECT studies are comparable to the conventional dual isotope studies when the clinical question is the detection and localization of coronary artery disease. Nevertheless, we also showed that this approach is limited when attempting to interpret the reversibility of stress induced perfusion defects in patients who exhibit attenuation artefacts, subendocardial infarction and functional stunning.

Background: The dynamic twisting component of cardiac motion is not accounted for by radionuclide techniques so that maps of perfusion and wall thickening are motion-blurred by torsion. This study examined whether torsion can be estimated from gated single photon emission computed tomography data and whether torsion corrections affect cardiac measurements., Methods and Results: Technetium 99m sestamibi myocardial perfusion gated tomograms were selected retrospectively for 52 patients who had x-ray contrast arteriograms: 12 with normal perfusion (group 1), 12 with abnormal perfusion (group 2), and 28 studied after angioplasty (group 3). The 8 gated perfusion maps were transformed by contrast normalization, the count minimums of which were tracked to quantify torsion. Measured torsion was used to correct maps of perfusion and wall thickening. Torsion was found to be visually detectable equally well in groups 1 and 2. Apical torsion was significantly greater for group 1 than groups 2 and 3 (15 degrees +/- 9 degrees vs 9 degrees +/- 15 degrees and 2 degrees +/- 12 degrees ) and was opposite in sign for patients with apical aneurysms (-4 degrees +/- 13 degrees ) and for patients after coronary artery bypass grafting (CABG) (-4 degrees +/- 15 degrees ). Maximum percent count differences were 10% +/- 16% between torsion-corrected versus uncorrected perfusion maps. The greatest wall thickening differences were seen for patients with left ventricular apical aneurysms and for patients after CABG versus group 1 (10% +/- 6% and 8% +/- 6% vs 3% +/- 1%, respectively)., Conclusions: It is feasible to detect cardiac torsion in the majority of Tc-99m sestamibi myocardial perfusion scans. Abnormal twisting patterns distinguished patients after CABG and those with left ventricular aneurysms from subjects with normal perfusion in a manner similar to magnetic resonance imaging observations.

Background: The most widely distributed software packages to compute left ventricular (LV) volume and ejection fraction (EF) from gated perfusion tomograms are QGS and the Emory Cardiac Toolbox (ECTb). Because LV modeling and time sampling differ between the algorithms, it is necessary to document relationships between values produced by them and to establish normal limits individually for each software package in order to interpret results obtained for individual patients., Methods and Results: Gated single photon emission computed tomography technetium 99m sestamibi myocardial perfusion studies were collected and analyzed for 246 patients evaluated for coronary artery disease. QGS and ECTb values of ejection fraction (EF), end-diastolic volume (EDV), and end-systolic volume were found to correlate linearly (r = 0.90, 0.91, and 0.94, respectively), but EF and EDV were significantly lower for QGS than with ECTb (53% +/- 13% vs 61% +/- 13 and 102 +/- 45 mL vs 114 +/- 50 mL, respectively). To compare calculations for healthy subjects between the two software packages, data were also selected for 50 other patients at low likelihood for coronary artery disease, for whom EF and EDV were significantly lower for QGS compared with ECTb (62% +/- 9% vs 67% +/- 8% and 84 +/- 26 mL vs 105 +/- 33 mL, respectively). The ECTb lower limit was 51% for EF and the upper limits were 171 mL for EDV and 59 mL/m(2) for mass-indexed EDV, compared with limits of 44%, 137 mL, and 47 mL/m(2) for QGS., Conclusions: Although correlations were strong between the two methods of computing LV functional values, statistical scatter was substantial and significant biases and trends observed. Therefore, when both software packages are used at the same site, it will be important to take these differences into consideration and to apply normal limits specific to each set of algorithms.

Introduction and Objectives: In everyday clinical practice, the cardiologist needs to integrate anatomical and functional information from patients with coronary artery disease. The aim of this study is to present a way to unify, in three-dimensional images, anatomical information from coronary angiography with physiological information from myocardial perfusion scintigraphy., Methods: Three patients with one vessel disease (left anterior descending, right coronary and left circumflex arteries, respectively) scheduled for percutaneous coronary revascularization were selected. Two-dimensional angiographic images were obtained before and after revascularization. 99mTc-tetrofosmin was administered during coronary occlusion and tomographic images corresponding to the occlusion were detected after coronary dilatation. Control rest scintigraphic images were obtained after two days. The three-dimensional coronary tree from coronary angiography was superposed on the epicardial contours of the myocardial perfusion images following a method of our own., Results: A correct three-dimensional reconstruction of myocardial contour and coronary tree was achieved for each patient. The three-dimensional unified images showed excellent concordance between the extent of perfusion defects and the anatomic distribution of the occluded vessel., Conclusions: Three-dimensional unification of myocardial perfusion images and coronary angiography is technically possible. This technology integrates anatomical and functional information to facilitate the cardiologist's decision-making and so improve coronary patient management.

Purpose: This work determined if 2, 6-diisopropylphenol (propofol) selectively affects cerebral blood flow in regions associated with wakefulness., Procedures: Cerebral blood flow (CBF) was measured with positron emission tomography (PET) using the 15O-water bolus technique in 10 subjects while awake and during light and deep sedation. Arterial blood was sampled for CBF estimation, blood gases and propofol plasma concentrations., Results: Global CBF decreased under deep sedation. A regression analysis of CBF vs. propofol concentration showed significant decreases in CBF in the thalamus and posterior cingulate and increases in the hippocampus and cerebellum. An ANCOVA analysis on condition (controlling for pCO(2) levels) showed mean CBF decreased in the thalamus and posterior cingulate cortex and increased in the primary motor and hippocampal areas during the light and deep sedation compared to awake conditions., Conclusions: These data support the hypothesis that propofol preferentially alters CBF in specific brain regions necessary to maintain wakefulness.

Background: Two methods of computing left ventricular volumes and ejection fraction (EF) from 8-frame gated perfusion single photon emission computed tomography (SPECT) were compared with each other and with magnetic resonance (MR) imaging., Methods and Results: Thirty-five subjects underwent 8-frame gated dual-isotope SPECT imaging and 12- to 16-frame gated MR imaging. Endocardial boundaries on short-axis MR images were hand traced by experts blinded to any SPECT results. Volumes and EF were computed with the use of Simpson's rule. SPECT images were analyzed for the same functional variables with the use of 2 automatic programs, Quantitative Gated SPECT (QGS) and the Emory Cardiac Toolbox (ECTb). The mean difference between MR and SPECT EF was 0.008 for ECTb and 0.08 for QGS. QGS showed a slight trend toward higher correlation for EF (r = 0.72, SE of the estimate = 0.08) than ECTb (r = 0.70, SE of the estimate = 0.09). For both SPECT methods, left ventricular volumes were similarly correlated with MR, although SPECT volumes were higher than MR values by approximately 30%., Conclusions: QGS and ECTb values of cardiac function computed from 8-frame gated perfusion SPECT correlate very well with each other and correlate well with MR. Averaged over all subjects, ECTb measurements of EF are not significantly different from MR values but QGS significantly underestimates the MR values.

Background: Crack cocaine dependence and addiction is typically associated with frequent and intense drug wanting or craving triggered by internal or environmental cues associated with past drug use., Methods: Water O 15 positron emission tomography (PET) studies were used to localize alterations in synaptic activity related to cue-induced drug craving in 8 crack cocaine-dependent African American men. In a novel approach, script-guided imagery of autobiographical memories were used as individualized cues to internally generate a cocaine craving state and 2 control (ie, anger and neutral episodic memory recall) states during PET image acquisition., Results: The mental imagery of personalized drug use and anger-related scripts was associated with self-ratings of robust drug craving or anger, and comparable alterations in heart rate. Compared with the neutral imagery control condition, imagery-induced drug craving was associated with bilateral (right hemisphere amygdala activation greater than left) activation of the amygdala, the left insula and anterior cingulate gyrus, and the right subcallosal gyrus and nucleus accumbens area. Compared with the anger control condition, internally generated drug craving was associated with bilateral activation of the insula and subcallosal cortex, left hippocampus, and anterior cingulate cortex and brainstem. A brain-wide pixel-by-pixel search indicated significant positive and negative correlations between imagery-induced cocaine craving and regional cerebral blood flow (rCBF) in distributed sites., Conclusions: The collected findings suggest the craving-related activation of a network of limbic, paralimbic, and striatal brain regions, including structures involved in stimulus-reward association (amygdala), incentive motivation (subcallosal gyrus/nucleus accumbens), and anticipation (anterior cingulate cortex).

We describe two studies that used repetition priming paradigms to investigate brain activity during the reading of single words. Functional magnetic resonance images were collected during a visual lexical decision task in which nonword stimuli were manipulated with regard to phonological properties and compared to genuine English words. We observed a region in left-hemisphere primary auditory cortex linked to a repetition priming effect. The priming effect activity was observed only for stimuli that sound like known words; moreover, this region was sensitive to strategic task differences. Thus, a brain region involved in the most basic aspects of auditory processing appears to be engaged in reading even when there is no environmental oral or auditory component., (Copyright 2001 Academic Press.)

Background: We reported previously that mean quantified cardiac functional parameters computed by one gated single photon emission computed tomography (SPECT) technique were not significantly altered by common gating errors. However, it is not known to what extent other gated SPECT approaches that are based on different ventricular modeling assumptions are influenced by arrhythmias, nor are the effects of gating errors on visual analyses and their subsequent clinical implications known., Methods: Projection data for 50 patients (aged 64 +/- 12 years; 68% men; 76% with myocardial perfusion defects) undergoing technetium-99m sestamibi gated SPECT who were in sinus rhythm during data acquisition were altered to simulate common arrhythmias. To determine quantitative effects, we performed calculations for original control and altered images by Gaussian myocardial detection (Quantitative Gated SPECT [QGS] program) and by wall thickening derived from gated perfusion polar maps (Emory Cardiac Toolbox program). To evaluate visual assessment in control and simulated-arrhythmia tomograms, 2 experienced blinded observers independently interpreted perfusion from polar maps and wall motion and thickening from tomographic cines, using a 4-point scale., Results: Although mean functional parameters were scarcely altered, paired t tests showed ejection fraction fluctuations to be significantly different from control values, causing patients to change between abnormal and normal ejection fraction categories (2% of patients by QGS and 14% by Emory Cardiac Toolbox). Visual examination of QGS polar perfusion and function maps showed changes for 72% of cases, although in only 4% were these considered to have potential clinical consequences. The kappa statistic for visual analysis of concordance between control and arrhythmia readings showed that agreement was "excellent" for perfusion, "good" for motion, and "marginal" for thickening., Conclusions: As with quantitative measurements, thickening is the parameter most prone to error in the presence of arrhythmias. It is important to test data for gating errors to avoid potentially erroneous measurements and visual readings.

Unlabelled: The objective of this study was to compare visual assessment of 3-dimensional color-modulated (to counts) surface displays with visual assessment of oblique tomographic slices of myocardial SPECT perfusion distributions in the detection and localization of coronary artery disease (CAD)., Methods: Sixty-two consecutive patients (41 men, 21 women; mean age, 61 +/- 11 y) who had undergone conventional dual-isotope perfusion SPECT were retrospectively chosen; 50 had undergone coronary arteriography previously, and 12 had less than a 5% likelihood of CAD. Four readers interpreted the 3-dimensional displays and slices in separate sessions while unaware of the findings of previous readings, the interpretations of others, and the angiographic results. The readers used a 5-point scoring system. Their average score was used for receiver operating characteristic (ROC) analysis. The area under the ROC curves was determined so that the ability of the 2 methods to detect and localize CAD could be compared., Results: No significant differences were found between visual interpretation of 3-dimensional displays and visual interpretation of slices., Conclusion: These preliminary results indicate that visual interpretation of 3-dimensional displays of myocardial perfusion SPECT distributions may someday replace visual assessment of conventional slices without loss of diagnostic accuracy.

Objective: The authors used a functional neuroimaging study with a working memory probe to investigate the pathophysiology of attention deficit hyperactivity disorder (ADHD). Their goal was to compare regional cerebral blood flow (rCBF) changes related to working memory in adults with and without ADHD., Method: Using [(15)O]H(2)O positron emission tomography (PET) studies, the authors compared the sites of neural activation related to working memory in six adult men diagnosed with ADHD and six healthy men without ADHD who were matched in age and general intelligence., Results: Task-related changes in rCBF in the men without ADHD were more prominent in the frontal and temporal regions, but rCBF changes in men with ADHD were more widespread and primarily located in the occipital regions., Conclusions: These data suggest the use of compensatory mental and neural strategies by subjects with ADHD in response to a disrupted ability to inhibit attention to nonrelevant stimuli and the use of internalized speech to guide behavior.

This work uses the well-established (by PET) confrontation naming task to compare PET and fMRI in a cognitive activation experiment. The signal changes from this task are much less than the changes caused by visual or motor activation tasks used in previous comparisons. ANOVA methods adjusted for multiple comparisons were used to determine significant changes in signal between confrontation naming and figure size discrimination tasks. All 17 significantly increased regions (confrontation naming signal greater) seen on one modality were increased on both modalities. Ten of 13 regions that were significantly decreased on one modality were decreased on the other. Three mismatched regions showed a significant decrease on one modality and a nonsignificant increase on the other. This study could not detect a consistent difference in activation site location between PET and fMRI., (Copyright 1999 Academic Press.)

Unlabelled: A new technique for computing left ventricular function, including left ventricular volumes, mass and ejection fraction, has been developed. This method is a logical extension of the results of a standard perfusion quantification technique; thus, it allows integration of perfusion and functional information., Methods: Anatomically based models of the endocardial and epicardial surfaces are generated using the myocardial samples for which perfusion values are quantified, for all frames in the cardiac cycle. With these surface points, left ventricular chamber volume and myocardial volume can be computed. A computer simulation was used to determine the sensitivity of the approach to the assumptions of the model. Validation of volume, mass and ejection fraction was performed with correlative MR studies, and ejection fraction and left ventricular volumes were further investigated using correlative first-pass studies., Results: Automated processing was successful in 96% of the cases analyzed. End diastolic volume, end systolic volume, left ventricular mass and left ventricular ejection fraction correlated with MRI with r = 0.97, 0.99, 0.87, and 0.85, respectively. Ejection fraction from tomography correlated with first-pass values with r = 0.82, and end diastolic and end systolic volumes from tomography correlated with first-pass values with r = 0.85 and r = 0.91, respectively., Conclusion: The new integrated approach is accurate and robust for computing both perfusion and function from perfusion tomograms.

Purpose: Left cervical vagus nerve stimulation (VNS) decreases complex partial seizures (CPS) by unknown mechanisms of action. We hypothesized that therapeutic VNS alters synaptic activities at vagal afferent terminations and in sites that receive polysynaptic projections from these medullary nuclei., Methods: Ten patients with partial epilepsy underwent positron emission tomographic (PET) measurements of cerebral blood flow (BF) three times before and three times during VNS. Parameters for VNS were at high levels for 5 patients and at low levels for 5. Resting BF measurements were subtracted from measurements during VNS in each subject. Subtraction data were averaged in each of 2 groups of 5 patients. t Tests were applied to BF changes in brain regions that receive vagal afferents and projections (significant at p < 0.05, corrected for repeated measures)., Results: In both the low- and high-stimulation groups during VNS, brain BF was (a) increased in the rostral, dorsal-central medulla; (b) increased in the right postcentral gyrus, (c) increased bilaterally in the hypothalami, thalami, and insular cortices, and in cerebellar hemispheres inferiorly; and (d) decreased bilaterally in hippocampus, amygdala, and posterior cingulate gyri. The high-stimulation group had greater volumes of activation and deactivation sites., Conclusions: Our findings suggest that left cervical VNS acutely increases synaptic activity in structures directly innervated by central vagal structures and areas that process left-sided somatosensory information, but VNS also acutely alters synaptic activity in multiple limbic system structures bilaterally. These findings may reflect sites of therapeutic actions of VNS.

Background: Two-dimensional polar maps have been validated previously with coronary arteriography for determining vascular involvement of defects from a patient's myocardial perfusion distributions with and without quantification. The purpose of this study was to validate previously developed three-dimensional color-modulated surface displays representing myocardial perfusion., Methods and Results: The validation consisted of comparing the agreement between the three-dimensional displays and two-dimensional polar maps in localizing perfusion defects to vascular territories in 30 patients (16 men/14 women) who underwent both a 1-day rest/stress exercise 99mTc-labeled sestamibi study and coronary arteriography. Reading by two experts was used to identify the size and location of quantified defects and corresponding areas of reversibility seen in the polar maps and, on a separate day, in the three-dimensional displays. Agreement between the two-dimensional polar maps and the three-dimensional displays resulted in identical percentages for the localization of both defects and reversibilities: left anterior descending coronary artery, 87% (26/30); left circumflex coronary artery, 97% (29/30); right coronary artery, 97% (29/30); and coronary artery disease, 97% (29/30)., Conclusions: These results show that the color-modulated three-dimensional displays are at least as good as the CEqual polar maps in localizing a perfusion defect and its reversibility to angiographically defined vascular territories and thus could be used in the routine clinical evaluation of myocardial perfusion.