Edward P. Ficaro

Single photon-emission computed tomography

The current document is an update of an earlier version of single photon emission tomography (SPECT) guidelines that was developed by the American Society of Nuclear Cardiology. Although that document was only published a few years ago, there have been significant advances in camera technology, imaging protocols, and reconstruction algorithms that prompted the need for a revised document. This publication is designed to provide imaging guidelines for physicians and technologists who are qualified to practice nuclear cardiology. While the information supplied in this document has been carefully reviewed by experts in the field, the document should not be considered medical advice or a professional service. We are cognizant that SPECT technology is evolving rapidly and that these recommendations may need further revision in the near future. Hence, the imaging guidelines described in this publication should not be used in clinical studies until they have been reviewed and approved by qualified physicians and technologists from their own particular institutions. 2. INSTRUMENTATION QUALITY ASSURANCE AND PERFORMANCE

Simultaneous Transmission/Emission Myocardial Perfusion Tomography: Diagnostic Accuracy of Attenuation-Corrected 99mTc-Sestamibi Single-Photon Emission Computed Tomography

BACKGROUND The purpose of the present study was to assess the diagnostic performance of attenuation-corrected (AC) stress 99mTc-sestamibi cardiac single-photon emission computed tomography (SPECT) for the identification of coronary heart disease (CHD). METHODS AND RESULTS With a triple-detector SPECT system with a 241Am transmission line source, simultaneous transmission/emission tomography (TCT/ECT) was performed on 60 patients with angiographic coronary disease and 59 patients with < or = 5% likelihood of CHD. Iteratively reconstructed AC stress 99mTc-sestamibi perfusion images were compared with uncorrected (NC) filtered-backprojection images. Normal database polar maps were constructed from AC and NC images for quantitative analyses. From the low-likelihood patients, the visual and quantitative normalcy rates increased from 0.88 and 0.76 for NC to 0.98 and 0.95 for AC (P < .05). For the detection of CHD, the receiver operating characteristic curves for the AC images demonstrated improved discrimination capacity (P < .05), and sensitivity/specificity values increased from 0.78/0.46 (NC) to 0.84/0.82 (AC) with visual analysis and from 0.84/0.46 (NC) to 0.88/0.82 (AC) with quantitative analysis. For localization of stenosed vessels, visual and quantitative sensitivity values were 0.51 and 0.63 for NC and 0.64 and 0.78 for AC images (P < .05), respectively. CONCLUSIONS TCT/ECT myocardial perfusion imaging significantly improves the diagnostic accuracy of cardiac SPECT for the detection and localization of CHD. Clinical use of TCT/ECT imaging deserves serious consideration.

In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer’s disease

Objective: To validate an in vivo method for mapping acetylcholinesterase (AChE) activity in human brain, preparatory to monitoring inhibitor therapy in AD. Background: AChE activity is decreased in postmortem AD brain. Lacking a reliable in vivo measure, little is known about central activity in early AD, when the disease is commonly targeted by AChE inhibitor drug therapy. Methods: Intravenous N-[11C]methylpiperidin-4-yl propionate ([11C]PMP) served as an in vivo AChE substrate. AChE activity was defined using cerebral PET for tracer kinetic estimates of the local rate of [11C]PMP hydrolysis in 26 normal controls and 14 patients with AD. Eleven AD patients also had concomitant in vivo cerebral measures of vesicular acetylcholine transporter (cholinergic terminal) density and glucose metabolism. Results: Cerebral AChE activity measures 1) were independent of changes in tracer delivery to cerebral cortex; 2) agreed with reported postmortem data concerning normal relative cerebral distributions, absence of large age-effect in normal aging, and deficits in AD; 3) correlated in AD cerebral cortex with concomitant in vivo measures of cholinergic terminal deficits, but not with metabolic deficits; and 4) agreed quantitatively with predicted level of cerebral AChE inhibition induced by physostimine. Conclusions: This in vivo PET method provided valid measures of central AChE activity in normal subjects and AD patients. Applied in early AD, it should facilitate inhibitor treatment by confirming central inhibition, optimizing drug dosage, identifying likely responders, and testing surrogate markers of therapeutic response.

Recommendations for reducing radiation exposure in myocardial perfusion imaging

Radionuclide myocardial perfusion imaging (MPI) using single photon emission computed tomography (SPECT) or positron emission tomography (PET) for the detection of ischemia in patients with known or suspected coronary artery disease (CAD) has widespread clinical utilization and has been shown to have high accuracy and incremental prognostic value. Amidst the recent publicity regarding the increasing use of all types of ionizing radiation in the United States, patients and medical professionals are scrutinizing the need for diagnostic testing and how radiation exposure can be reduced. There are three critical questions that physicians must consider and answer with regard to radiation exposure and performing MPI in a particular patient:

Grouped-coordinate ascent algorithms for penalized-likelihood transmission image reconstruction

Presents a new class of algorithms for penalized-likelihood reconstruction of attenuation maps from low-count transmission scans. We derive the algorithms by applying to the transmission log-likelihood a version of the convexity technique developed by De Pierro for emission tomography. The new class includes the single-coordinate ascent (SCA) algorithm and Langes convex algorithm for transmission tomography as special cases. The new grouped-coordinate ascent (GCA) algorithms in the class overcome several limitations associated with previous algorithms. (1) Fewer exponentiations are required than in the transmission maximum likelihood-expectation maximization (ML-EM) algorithm or in the SCA algorithm. (2) The algorithms intrinsically accommodate nonnegativity constraints, unlike many gradient-based methods. (3) The algorithms are easily parallelizable, unlike the SCA algorithm and perhaps line-search algorithms. We show that the GCA algorithms converge faster than the SCA algorithm, even on conventional workstations. An example from a low-count positron emission tomography (PET) transmission scan illustrates the method.

Decreased striatal monoaminergic terminals in Huntington disease

Objective: To evaluate the integrity of the dorsal striatal dopaminergic innervation in rigid and choreic Huntington disease (HD). Background: Some patients with HD have an akinetic-rigid phenotype. It has been suggested that nigrostriatal in addition to striatal pathology is present in this subgroup. The authors sought to determine whether in vivo measures of striatal vesicular monoamine transporter type-2 (VMAT2) binding could distinguish patients with akinetic-rigid (HDr) from typical choreiform (HDc) HD. Methods: Nineteen patients with HD (mean age 48 ± 16 years) and 64 normal controls (mean age 50 ± 14 years) underwent (+)-α-[11C]dihydrotetrabenazine (DTBZ) PET imaging. DTBZ blood to brain ligand transport (K1) and tissue to plasma distribution volume (DV) in the caudate nucleus, anterior putamen, and posterior putamen were normalized to the occipital cortex. Results: The normalized striatal specific DV was reduced in HDr (n = 6) when compared with controls: caudate nucleus −33% (p < 0.001), anterior putamen −56% (p < 0.0001), and posterior putamen −75% (p < 0.0001). Patients with HDc (n = 13) also had reduced striatal DV: caudate nucleus −6% (NS), anterior putamen −19% (p < 0.01), and posterior putamen −35% (p < 0.0001). Patients with HDr had significantly lower striatal (+)-α-[11C]DTBZ binding than HDc patients. After correction for tissue atrophy effects, normalized DV differences were less significant, with values somewhat increased in the caudate, slightly reduced in the anterior putamen, and moderately decreased in the posterior putamen. There were no significant regional differences in K1 reductions among caudate, anterior, and posterior putamen in HD. Conclusions: Reduced striatal VMAT2 binding suggests nigrostriatal pathology in HD, most severely in the HDr phenotype. Striatal DV reductions were most prominent in the posterior putamen, similar to PD.

Clinical review of attenuation-corrected cardiac SPECT.

SummaryRather than the introduction of a heralded technologic advancement in cardiac SPECT imaging challenging the accuracy of PET perfusion imaging, the commercial introduction of attenuation correction, has been met with at least as many negative as positive reports. Some studies have reported significant improvements in specificity or specificity and sensitivity, especially for high-risk patterns of coronary artery disease; others have reported no improvement or a decrease in accuracy resulting from the introduction of troublesome artifacts. Although this review has attempted to emphasize the positive aspects of attenuation-corrected cardiac SPECT perfusion imaging and the potential for improved patient care it may provide, several negative reports continue to appear.68,69,108,109 Still there has been sufficient positive data reported to suggest that with fully developed, accurate, and robust correction methods, significant gains in SPECT assessments, of the presence and extent of CHD, patient risk, and myocardial viability can be anticipated. Ultimately attenuation correction for cardiac SPECT should have a positive impact on the management of patients with coronary artery disease with important savings in lives and health care dollars.

Attenuation-corrected 99mTc-tetrofosmin single-photon emission computed tomography in the detection of viable myocardium: comparison with positron emission tomography using 18F-fluorodeoxyglucose

OBJECTIVES The purpose of this study was to assess the efficacy of attenuation-corrected (AC) technetium-99m (99mTc)-tetrofosmin single-photon emission computed tomography (SPECT) in detecting viable myocardium compared to 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). BACKGROUND The role of 99mTc-labeled perfusion tracers in the assessment of myocardial viability remains controversial. Attenuation artifacts affect the diagnostic accuracy of SPECT images. METHODS Twenty-four patients with coronary artery disease (mean left ventricular ejection fraction 30%) underwent resting 99mTc-tetrofosmin SPECT and FDG PET imaging. Both AC and non-attenuation-corrected (NC) SPECT images were generated. RESULTS Using a 50% threshold for viability by FDG PET, the percentage of concordant segments of viability between 99mTc-tetrofosmin and FDG on the patient basis increased from 79.8%+/-14.0% (mean+/-SD) on the NC images to 90.8%+/-10.6% on the AC images (p=0.002). The percentage of 99mTc-tetrofosmin defect segments within PET-viable segments, an estimate for the degree of underestimation of viability, decreased from 19.8%+/-15.2% on the NC images to 9.7%+/-12.6% on the AC images (p=0.01). Similar results were obtained when a 60% threshold was used to define viability by FDG PET. When the anterior-lateral and inferior-septal regions were separately analyzed, the effect of attenuation correction was significant only in the inferior-septal region. CONCLUSIONS The results indicate that AC 99mTc-tetrofosmin SPECT improves the detection of viable myocardium mainly by decreasing the underestimation of viability particularly in the inferior-septal region, although some underestimation/overestimation of viability may still occur even with attenuation correction.

Dual-[11C]Tracer Single-Acquisition Positron Emission Tomography Studies

The ability to study multiple physiologic processes of the brain simultaneously within the same subject would provide a new means to explore the interactions between neurotransmitter systems in vivo. Currently, examination of two distinct neuropharmacologic measures with positron emission tomography (PET) necessitates performing two separate scans spaced in time to allow for radionuclide decay. The authors present results from a dual-tracer PET study protocol using a single dynamic-scan acquisition where the injections of two tracers are offset by several minutes. Kinetic analysis is used to estimate neuropharmacologic parameters for both tracers simultaneously using a combined compartmental model configuration. This approach results in a large reduction in total study time of nearly 2 hours for carbon-11–labeled tracers. As multiple neuropharmacologic measures are obtained at nearly the same time, interventional protocols involving a pair of dual-tracer scans become feasible in a single PET session. Both computer simulations and actual human PET studies were performed using combinations of three different tracers: [11C]flumazenil, N-[11C]methylpiperidinyl propionate, and [11C]dihydrotetrabenazine. Computer simulations of tracer-injection separations of 10 to 30 minutes showed the feasibility of the approach for separations down to 15 to 20 minutes or less. Dual-tracer PET studies were performed in 32 healthy volunteers using injection separations of 10, 15, or 20 minutes. Model parameter estimates for each tracer were similar to those obtained from previously performed single-injection studies. Voxel-by-voxel parametric images were of good quality for injections spaced by 20 minutes and were nearly as good for 15-minute separations, but were degraded noticeably for some model parameters when injections were spaced by only 10 minutes. The authors conclude that dual-tracer single-scan PET is feasible, yields accurate estimates of multiple neuropharmacologic measures, and can be implemented with a number of different radiotracer pairs.

Comparison and Prognostic Validation of Multiple Methods of Quantification of Myocardial Blood Flow with 82Rb PET

The quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) using PET with 82Rb in patients with known or suspected coronary artery disease has been demonstrated to have substantial prognostic and diagnostic value. However, multiple methods for estimation of an image-derived input function and several models for the nonlinear first-pass extraction of 82Rb by myocardium have been used. We sought to compare the differences in these methods and models and their impact on prognostic assessment in a large clinical dataset. Methods: Consecutive patients (n = 2,783) underwent clinically indicated rest–stress myocardial perfusion PET with 82Rb. The input function was derived using a region of interest (ROI) semiautomatically placed in the region of the mitral valve, factor analysis, and a hybrid method that creates an ROI from factor analysis. We used 5 commonly used extraction models for 82Rb to estimate MBF and MFR. Pearson correlations, bias, and Cohen κ were computed for the various measures. The relationship between MFR/stress MBF and annual rate of cardiac mortality was estimated with spline fits using Poisson regression. Finally, incremental value was assessed with the net reclassification improvement using Cox proportional hazards regression. Results: Correlations between MFR or stress MBF measures made with the same input function derivation method were generally high, regardless of extraction model used (Pearson r > 0.90). However, correlations between measures derived with the ROI method and other methods were only moderate (Pearson r = 0.42–0.62). Importantly, substantial biases were seen for most combinations. We saw that the relationship between cardiac mortality and stress MBF was variable depending on the input function method and extraction model, whereas the relationship between MFR and risk was highly consistent. Net reclassification improvement was comparable for most methods and models for MFR but was highly variable for stress MBF. Conclusion: Although both stress MBF and MFR can improve prognostic assessment, MFR is substantially more consistent, regardless of choice of input function derivation method and extraction model used.