Observer studies of image quality of denoising reduced-count cardiac single photon emission computed tomography myocardial perfusion imaging by three-dimensional Gaussian post-reconstruction filtering and deep learning.

BACKGROUND: The aim of this research was to asses perfusion-defect detection-accuracy by human observers as a function of reduced-counts for 3D Gaussian post-reconstruction filtering vs deep learning (DL) denoising to determine if there was improved performance with DL. METHODS: SPECT projection data of 156 normally interpreted patients were used for these studies. Half were altered to include hybrid perfusion defects with defect presence and location known. Ordered-subset expectation-maximization (OSEM) reconstruction was employed with the optional correction of attenuation (AC) and scatter (SC) in addition to distance-dependent resolution (RC). Count levels varied from full-counts (100%) to 6.25% of full-counts. The denoising strategies were previously optimized for defect detection using total perfusion deficit (TPD). Four medical physicist (PhD) and six physician (MD) observers rated the slices using a graphical user interface. Observer ratings were analyzed using the LABMRMC multi-reader, multi-case receiver-operating-characteristic (ROC) software to calculate and compare statistically the area-under-the-ROC-curves (AUCs). RESULTS: For the same count-level no statistically significant increase in AUCs for DL over Gaussian denoising was determined when counts were reduced to either the 25% or 12.5% of full-counts. The average AUC for full-count OSEM with solely RC and Gaussian filtering was lower than for the strategies with AC and SC, except for a reduction to 6.25% of full-counts, thus verifying the utility of employing AC and SC with RC. CONCLUSION: We did not find any indication that at the dose levels investigated and with the DL network employed, that DL denoising was superior in AUC to optimized 3D post-reconstruction Gaussian filtering.

Measurement of neurodegeneration using a multivariate early frame amyloid PET classifier.

Introduction: Amyloid measurement provides important confirmation of pathology for Alzheimer's disease (AD) clinical trials. However, many amyloid positive (Am+) early-stage subjects do not worsen clinically during a clinical trial, and a neurodegenerative measure predictive of decline could provide critical information. Studies have shown correspondence between perfusion measured by early amyloid frames post-tracer injection and fluorodeoxyglucose (FDG) positron emission tomography (PET), but with limitations in sensitivity. Multivariate machine learning approaches may offer a more sensitive means for detection of disease related changes as we have demonstrated with FDG. Methods: Using summed dynamic florbetapir image frames acquired during the first 6 minutes post-injection for 107 Alzheimer's Disease Neuroimaging Initiative subjects, we applied optimized machine learning to develop and test image classifiers aimed at measuring AD progression. Early frame amyloid (EFA) classification was compared to that of an independently developed FDG PET AD progression classifier by scoring the FDG scans of the same subjects at the same time point. Score distributions and correlation with clinical endpoints were compared to those obtained from FDG. Region of interest measures were compared between EFA and FDG to further understand discrimination performance. Results: The EFA classifier produced a primary pattern similar to that of the FDG classifier whose expression correlated highly with the FDG pattern (R-squared 0.71), discriminated cognitively normal (NL) amyloid negative (Am-) subjects from all Am+ groups, and that correlated in Am+ subjects with Mini-Mental State Examination, Clinical Dementia Rating Sum of Boxes, and Alzheimer's Disease Assessment Scale-13-item Cognitive subscale (R = 0.59, 0.63, 0.73) and with subsequent 24-month changes in these measures (R = 0.67, 0.73, 0.50). Discussion: Our results support the ability to use EFA with a multivariate machine learning-derived classifier to obtain a sensitive measure of AD-related loss in neuronal function that correlates with FDG PET in preclinical and early prodromal stages as well as in late mild cognitive impairment and dementia. Highlights: The summed initial post-injection minutes of florbetapir positron emission tomography  correlate with fluorodeoxyglucose.A machine learning classifier enabled sensitive detection of early prodromal Alzheimer's disease.Early frame amyloid (EFA) classifier scores correlate with subsequent change in Mini-Mental State Examination, Clinical Dementia Rating Sum of Boxes, and Alzheimer's Disease Assessment Scale-13-item Cognitive subscale.EFA classifier effect sizes and clinical prediction outperformed region of interest standardized uptake value ratio.EFA classification may aid in stratifying patients to assess treatment effect.

Improving detection accuracy of perfusion defect in standard dose SPECT-myocardial perfusion imaging by deep-learning denoising.

BACKGROUND: We previously developed a deep-learning (DL) network for image denoising in SPECT-myocardial perfusion imaging (MPI). Here we investigate whether this DL network can be utilized for improving detection of perfusion defects in standard-dose clinical acquisitions. METHODS: To quantify perfusion-defect detection accuracy, we conducted a receiver-operating characteristic (ROC) analysis on reconstructed images with and without processing by the DL network using a set of clinical SPECT-MPI data from 190 subjects. For perfusion-defect detection hybrid studies were used as ground truth, which were created from clinically normal studies with simulated realistic lesions inserted. We considered ordered-subset expectation-maximization (OSEM) reconstruction with corrections for attenuation, resolution, and scatter and with 3D Gaussian post-filtering. Total perfusion deficit (TPD) scores, computed by Quantitative Perfusion SPECT (QPS) software, were used to evaluate the reconstructed images. RESULTS: Compared to reconstruction with optimal Gaussian post-filtering (sigma = 1.2 voxels), further DL denoising increased the area under the ROC curve (AUC) from 0.80 to 0.88 (P-value < 10-4). For reconstruction with less Gaussian post-filtering (sigma = 0.8 voxels), thus better spatial resolution, DL denoising increased the AUC value from 0.78 to 0.86 (P-value < 10-4) and achieved better spatial resolution in reconstruction. CONCLUSIONS: DL denoising can effectively improve the detection of abnormal defects in standard-dose SPECT-MPI images over conventional reconstruction.

Retrospective fractional dose reduction in Tc-99m cardiac perfusion SPECT/CT patients: A human and model observer study.

BACKGROUND: In the ongoing efforts to reduce cardiac perfusion dose (injected radioactivity) for conventional SPECT/CT systems, we performed a human observer study to confirm our clinical model observer findings that iterative reconstruction employing OSEM (ordered-subset expectation-maximization) at 25% of the full dose (quarter-dose) has a similar performance for detection of hybrid cardiac perfusion defects as FBP at full dose. METHODS: One hundred and sixty-six patients, who underwent routine rest-stress Tc-99m sestamibi cardiac perfusion SPECT/CT imaging and clinically read as normally perfused, were included in the study. Ground truth was established by the normal read and the insertion of hybrid defects. In addition to the reconstruction of the 25% of full-dose data using OSEM with attenuation (AC), scatter (SC), and spatial resolution correction (RC), FBP and OSEM (with AC, SC, and RC) both at full dose (100%) were done. Both human observer and clinical model observer confidence scores were obtained to generate receiver operating characteristics (ROC) curves in a task-based image quality assessment. RESULTS: Average human observer AUC (area under the ROC curve) values of 0.725, 0.876, and 0.890 were obtained for FBP at full dose, OSEM at 25% of full dose, and OSEM at full dose, respectively. Both OSEM strategies were significantly better than FBP with P values of 0.003 and 0.01 respectively, while no significant difference was recorded between OSEM methods (P = 0.48). The clinical model observer results were 0.791, 0.822, and 0.879, respectively, for the same patient cases and processing strategies used in the human observer study. CONCLUSIONS: Cardiac perfusion SPECT/CT using OSEM reconstruction at 25% of full dose has AUCs larger than FBP and closer to those of full-dose OSEM when read by human observers, potentially replacing the higher dose studies during clinical reading.

Deep learning with noise-to-noise training for denoising in SPECT myocardial perfusion imaging.

PURPOSE: Post-reconstruction filtering is often applied for noise suppression due to limited data counts in myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT). We study a deep learning (DL) approach for denoising in conventional SPECT-MPI acquisitions, and investigate whether it can be more effective for improving the detectability of perfusion defects compared to traditional postfiltering. METHODS: Owing to the lack of ground truth in clinical studies, we adopt a noise-to-noise (N2N) training approach for denoising in SPECT-MPI images. We consider a coupled U-Net (CU-Net) structure which is designed to improve learning efficiency through feature map reuse. For network training we employ a bootstrap procedure to generate multiple noise realizations from list-mode clinical acquisitions. In the experiments we demonstrated the proposed approach on a set of 895 clinical studies, where the iterative OSEM algorithm with three-dimensional (3D) Gaussian postfiltering was used to reconstruct the images. We investigated the detection performance of perfusion defects in the reconstructed images using the non-prewhitening matched filter (NPWMF), evaluated the uniformity of left ventricular (LV) wall in terms of image intensity, and quantified the effect of smoothing on the spatial resolution of the reconstructed LV wall by using its full-width at half-maximum (FWHM). RESULTS: Compared to OSEM with Gaussian postfiltering, the DL denoised images with CU-Net significantly improved the detection performance of perfusion defects at all contrast levels (65%, 50%, 35%, and 20%). The signal-to-noise ratio (SNRD ) in the NPWMF output was increased on average by 8% over optimal Gaussian smoothing (P < 10-4 , paired t-test), while the inter-subject variability was greatly reduced. The CU-Net also outperformed a 3D nonlocal means (NLM) filter and a convolutional autoencoder (CAE) denoising network in terms of SNRD . In addition, the FWHM of the LV wall in the reconstructed images was varied by less than 1%. Furthermore, CU-Net also improved the detection performance when the images were processed with less post-reconstruction smoothing (a trade-off of increased noise for better LV resolution), with SNRD improved on average by 23%. CONCLUSIONS: The proposed DL with N2N training approach can yield additional noise suppression in SPECT-MPI images over conventional postfiltering. For perfusion defect detection, DL with CU-Net could outperform conventional 3D Gaussian filtering with optimal setting as well as NLM and CAE.

Improving Diagnostic Accuracy in Low-Dose SPECT Myocardial Perfusion Imaging With Convolutional Denoising Networks.

Lowering the administered dose in SPECT myocardial perfusion imaging (MPI) has become an important clinical problem. In this study we investigate the potential benefit of applying a deep learning (DL) approach for suppressing the elevated imaging noise in low-dose SPECT-MPI studies. We adopt a supervised learning approach to train a neural network by using image pairs obtained from full-dose (target) and low-dose (input) acquisitions of the same patients. In the experiments, we made use of acquisitions from 1,052 subjects and demonstrated the approach for two commonly used reconstruction methods in clinical SPECT-MPI: 1) filtered backprojection (FBP), and 2) ordered-subsets expectation-maximization (OSEM) with corrections for attenuation, scatter and resolution. We evaluated the DL output for the clinical task of perfusion-defect detection at a number of successively reduced dose levels (1/2, 1/4, 1/8, 1/16 of full dose). The results indicate that the proposed DL approach can achieve substantial noise reduction and lead to improvement in the diagnostic accuracy of low-dose data. In particular, at 1/2 dose, DL yielded an area-under-the-ROC-curve (AUC) of 0.799, which is nearly identical to the AUC = 0.801 obtained by OSEM at full-dose ( p -value = 0.73); similar results were also obtained for FBP reconstruction. Moreover, even at 1/8 dose, DL achieved AUC = 0.770 for OSEM, which is above the AUC = 0.755 obtained at full-dose by FBP. These results indicate that, compared to conventional reconstruction filtering, DL denoising can allow for additional dose reduction without sacrificing the diagnostic accuracy in SPECT-MPI.

Evaluation of the effect of reducing administered activity on assessment of function in cardiac gated SPECT.

BACKGROUND: We previously optimized several reconstruction strategies in SPECT myocardial perfusion imaging (MPI) with low dose for perfusion-defect detection. Here we investigate whether reducing the administered activity can also maintain the diagnostic accuracy in evaluating cardiac function. METHODS: We quantified the myocardial motion in cardiac-gated stress 99m-Tc-sestamibi SPECT studies from 163 subjects acquired with full dose (29.8 ± 3.6 mCi), and evaluated the agreement of the obtained motion/thickening and ejection fraction (EF) measures at various reduced dose levels (uniform reduction or personalized dose) with that at full dose. We also quantified the detectability of abnormal motion via a receiver-operating characteristics (ROC) study. For reconstruction we considered both filtered backprojection (FBP) without correction for degradations, and iterative ordered-subsets expectation-maximization (OS-EM) with resolution, attenuation and scatter corrections. RESULTS: With dose level lowered to 25% of full dose, the obtained results on motion/thickening, EF and abnormal motion detection were statistically comparable to full dose in both reconstruction strategies, with Pearson's r > 0.9 for global motion measures between low dose and full dose. CONCLUSIONS: The administered activity could be reduced to 25% of full dose without degrading the function assessment performance. Low dose reconstruction optimized for perfusion-defect detection can be reasonable for function assessment in gated SPECT.

Cardiac motion correction for improving perfusion defect detection in cardiac SPECT at standard and reduced doses of activity.

In cardiac SPECT perfusion imaging, cardiac motion can lead to motion blurring of anatomical detail and perfusion defects in the reconstructed myocardium. In this study, we investigated the potential benefit of cardiac motion correction for improving the detectability of perfusion defects. We considered a post-reconstruction motion correction (PMC) approach in which the image motion between two cardiac gates is obtained with optical flow estimation. In the experiments, we demonstrated the proposed post-reconstruction motion correction with optical flow estimation (PMC-OFE) approach on a set of clinical acquisitions from 194 subjects. We quantified the detectability of perfusion defects in the reconstructed images by using the total perfusion deficit scores, calculated by the clinical software tool QPS, and conducted a receiver-operating-characteristic (ROC) study to obtain the detection performance. Besides imaging with conventional standard dose, we also evaluated the approach for reduced dose SPECT imaging where the imaging dose was retrospectively reduced to 50%, 25%, and 12.5% of the standard dose. The proposed PMC-OFE approach achieved at each dose level higher area-under-the-ROC-curve (AUC) for perfusion defect detection than the traditional approach of using ungated data (Non-MC) (p -value < 0.05); in particular, with half dose, PMC-OFE achieved AUC = 0.813, which is comparable to Non-MC with standard dose (AUC = 0.795). Moreover, the proposed PMC-OFE approach also outperformed the 'Motion Frozen' (MF) method implemented in the clinical quantitative gated SPECT (QGS) software. In particular, at 25% and 12.5% of standard dose, the AUC values obtained by PMC-OFE are 0.788 and 0.779, respectively, compared to 0.758 and 0.731 for MF (p -value < 0.05).

Prediction of cardiac death after adenosine myocardial perfusion SPECT based on machine learning.

BACKGROUND: We developed machine-learning (ML) models to estimate a patient's risk of cardiac death based on adenosine myocardial perfusion SPECT (MPS) and associated clinical data, and compared their performance to baseline logistic regression (LR). We demonstrated an approach to visually convey the reasoning behind a patient's risk to provide insight to clinicians beyond that of a "black box." METHODS: We trained multiple models using 122 potential clinical predictors (features) for 8321 patients, including 551 cases of subsequent cardiac death. Accuracy was measured by area under the ROC curve (AUC), computed within a cross-validation framework. We developed a method to display the model's rationale to facilitate clinical interpretation. RESULTS: The baseline LR (AUC = 0.76; 14 features) was outperformed by all other methods. A least absolute shrinkage and selection operator (LASSO) model (AUC = 0.77; p = .045; 6 features) required the fewest features. A support vector machine (SVM) model (AUC = 0.83; p < .0001; 49 features) provided the highest accuracy. CONCLUSIONS: LASSO outperformed LR in both accuracy and simplicity (number of features), with SVM yielding best AUC for prediction of cardiac death in patients undergoing MPS. Combined with presenting the reasoning behind the risk scores, our results suggest that ML can be more effective than LR for this application.

Improving perfusion defect detection with respiratory motion correction in cardiac SPECT at standard and reduced doses.

BACKGROUND: In cardiac SPECT perfusion imaging, respiratory motion can cause non-uniform blurring in the reconstructed myocardium. We investigate the potential benefit of respiratory correction with respiratory-binned acquisitions, both at standard dose and at reduced dose, for defect detection and for left ventricular (LV) wall resolution. METHODS: We applied two reconstruction methods for respiratory motion correction: post-reconstruction motion correction (PMC) and motion-compensated reconstruction (MCR), and compared with reconstruction without motion correction (Non-MC). We quantified the presence of perfusion defects in reconstructed images by using the total perfusion deficit (TPD) scores and conducted receiver-operating-characteristic (ROC) studies using TPD. We quantified the LV spatial resolution by using the FWHM of its cross-sectional intensity profile. RESULTS: The values in the area-under-the-ROC-curve (AUC) achieved by MCR, PMC, and Non-MC at standard dose were 0.835, 0.830, and 0.798, respectively. Similar AUC improvements were also obtained by MCR and PMC over Non-MC at 50%, 25%, and 12.5% of full dose. Improvements in LV resolution were also observed with motion correction. CONCLUSIONS: Respiratory-binned acquisitions can improve perfusion-defect detection accuracy over traditional reconstruction both at standard dose and at reduced dose. Motion correction may contribute to achieving further dose reduction while maintaining the diagnostic accuracy of traditional acquisitions.

Personalized Models for Injected Activity Levels in SPECT Myocardial Perfusion Imaging.

We propose a patient-specific ("personalized") approach for tailoring the injected activities to individual patients in order to achieve dose reduction in SPECT-myocardial perfusion imaging (MPI). First, we develop a strategy to determine the minimum dose levels required for each patient in a large set of clinical acquisitions (857 subjects) such that the reconstructed images are sufficiently similar to that obtained at conventional clinical dose. We then apply machine learning models to predict the required dose levels on an individual basis based on a set of patient attributes which include body measurements and various clinical variables. We demonstrate the personalized dose models for two commonly used reconstruction methods in clinical SPECT-MPI: 1) conventional filtered backprojection (FBP) with post-filtering and 2) ordered-subsets expectation-maximization (OS-EM) with corrections for attenuation, scatter and resolution, and evaluate their performance in perfusion-defect detection by using the clinical Quantitative Perfusion SPECT software package. The results indicate that the achieved dose reduction can vary greatly among individuals from their conventional clinical dose and that the personalized dose models can achieve further reduction on average compared with a global (non-patient specific) dose reduction approach. In particular, the average personalized dose level can be reduced to 58% and 54% of the full clinical dose, respectively, for FBP and OS-EM reconstruction, while without deteriorating the accuracy in perfusion-defect detection. Furthermore, with the average personalized dose further reduced to only 16% of full dose, OS-EM can still achieve a detection accuracy level comparable to that of FBP with full dose.

FDG PET Parkinson's disease-related pattern as a biomarker for clinical trials in early stage disease.

Background: The development of therapeutic interventions for Parkinson disease (PD) is challenged by disease complexity and subjectivity of symptom evaluation. A Parkinson's Disease Related Pattern (PDRP) of glucose metabolism via fluorodeoxyglucose positron emission tomography (FDG-PET) has been reported to correlate with motor symptom scores and may aid the detection of disease-modifying therapeutic effects. Objectives: We sought to independently evaluate the potential utility of the PDRP as a biomarker for clinical trials of early-stage PD. Methods: Two machine learning approaches (Scaled Subprofile Model (SSM) and NPAIRS with Canonical Variates Analysis) were performed on FDG-PET scans from 17 healthy controls (HC) and 23 PD patients. The approaches were compared regarding discrimination of HC from PD and relationship to motor symptoms. Results: Both classifiers discriminated HC from PD (p < 0.01, p < 0.03), and classifier scores for age- and gender- matched HC and PD correlated with Hoehn & Yahr stage (R2 = 0.24, p < 0.015) and UPDRS (R2 = 0.23, p < 0.018). Metabolic patterns were highly similar, with hypometabolism in parieto-occipital and prefrontal regions and hypermetabolism in cerebellum, pons, thalamus, paracentral gyrus, and lentiform nucleus relative to whole brain, consistent with the PDRP. An additional classifier was developed using only PD subjects, resulting in scores that correlated with UPDRS (R2 = 0.25, p < 0.02) and Hoehn & Yahr stage (R2 = 0.16, p < 0.06). Conclusions: Two independent analyses performed in a cohort of mild PD patients replicated key features of the PDRP, confirming that FDG-PET and multivariate classification can provide an objective, sensitive biomarker of disease stage with the potential to detect treatment effects on PD progression.

Motion-compensated image reconstruction vs postreconstruction correction in respiratory-binned SPECT with standard and reduced-dose acquisitions.

PURPOSE: Cardiac perfusion images in single-photon emission computed tomography (SPECT) can suffer from respiratory motion blur. We investigated a reconstruction approach for correcting respiratory motion in respiratory-binned acquisitions and assessed the benefit of this approach in both standard dose and reduced dose. METHODS: We modeled the acquired data from different respiratory bins by a joint probability distribution which was parameterized with respect to a common reference bin. The acquired data from all the respiratory bins were then utilized simultaneously for determining the source distribution in the reference bin using maximum a posteriori (MAP) estimation. We evaluated this approach with simulated imaging data and ten sets of clinical acquisitions, and compared it with a postreconstruction motion correction approach developed previously. We quantified the accuracy of the reconstruction results both at standard dose and with imaging dose reduced by 50% and 75%, respectively. RESULTS: The proposed motion-compensated reconstruction (MCR) approach led to improved reconstruction of the myocardium in terms of both noise level and LV wall resolution. Compared to traditional acquisition (without motion correction), the proposed approach reduced the mean squared error of the image intensity in the myocardium by 27.59%, 20.59%, and 12.05% at full, half-, and quarter dose, respectively; the LV resolution, quantified by the full width at half-maximum (FWHM), was improved by 17.34%, 14.35%, and 12.95% at full, half-, and quarter dose, respectively; in addition, the proposed approach also improved the perfusion defect detectability at both full dose and reduced dose. Furthermore, with motion correction, the reconstruction results obtained at half-dose were comparable to that obtained at full dose without correction. Similar improvements were also demonstrated in the clinical acquisitions at different dose levels. CONCLUSIONS: Respiratory motion correction in perfusion SPECT can improve the reconstruction of the myocardium at both standard and reduced dose. At half-dose, the results obtained with motion correction are comparable to that of traditional reconstruction obtained at full dose. MCR can be more accurate than postreconstruction correction.

Investigation of dose reduction in cardiac perfusion SPECT via optimization and choice of the image reconstruction strategy.

BACKGROUND: We investigated the extent to which the administered dose (activity) level can be reduced without sacrificing diagnostic accuracy for three reconstruction strategies for SPECT-myocardial perfusion imaging (MPI). METHODS: We optimized the parameters of the three reconstruction strategies for perfusion-defect detection over a range of simulated administered dose levels using a set of hybrid studies (derived from 190 subjects) consisting of clinical SPECT-MPI data modified to contain realistic simulated lesions. The optimized strategies we considered are filtered backprojection (FBP) with no correction for degradations, ordered-subsets expectation-maximization (OS-EM) with attenuation correction (AC), scatter correction (SC), and resolution correction (RC), and OS-EM with scatter and resolution correction only. Each study was evaluated using a total perfusion deficit (TPD) score computed by the Quantitative Perfusion SPECT (QPS) software package. We conducted a receiver operating characteristics (ROC) study based on the TPD scores for each dose level and reconstruction strategy. RESULTS: For FBP, the achieved optimum values of the area under the ROC curve (AUC) at 100%, 50%, 25%, and 12.5% of standard dose were 0.75, 0.74, 0.72, and 0.70, respectively, compared to 0.81, 0.79, 0.76, and 0.74 for OS-EM with AC-SC-RC and 0.78, 0.77, 0.74, 0.72 for OS-EM with SC-RC. CONCLUSIONS: Our results suggest that studies reconstructed by OS-EM with AC-SC-RC could possibly be reduced, on average, to 25% of the originally administered dose without causing diagnostic accuracy (AUC) to decrease below that of FBP.

PET Imaging of Tau Pathology and Relationship to Amyloid, Longitudinal MRI, and Cognitive Change in Down Syndrome: Results from the Down Syndrome Biomarker Initiative (DSBI).

BACKGROUND: Adults with Down syndrome (DS) represent an enriched population for the development of Alzheimer's disease (AD), which could aid the study of therapeutic interventions, and in turn, could benefit from discoveries made in other AD populations. OBJECTIVES: 1) Understand the relationship between tau pathology and age, amyloid deposition, neurodegeneration (MRI and FDG PET), and cognitive and functional performance; 2) detect and differentiate AD-specific changes from DS-specific brain changes in longitudinal MRI. METHODS: Twelve non-demented adults, ages 30 to 60, with DS were enrolled in the Down Syndrome Biomarker Initiative (DSBI), a 3-year, observational, cohort study to demonstrate the feasibility of conducting AD intervention/prevention trials in adults with DS. We collected imaging data with 18F-AV-1451 tau PET, AV-45 amyloid PET, FDG PET, and volumetric MRI, as well as cognitive and functional measures and additional laboratory measures. RESULTS: All amyloid negative subjects imaged were tau-negative. Among the amyloid positive subjects, three had tau in regions associated with Braak stage VI, two at stage V, and one at stage II. Amyloid and tau burden correlated with age. The MRI analysis produced two distinct volumetric patterns. The first differentiated DS from normal (NL) and AD, did not correlate with age or amyloid, and was longitudinally stable. The second pattern reflected AD-like atrophy and differentiated NL from AD. Tau PET and MRI atrophy correlated with several cognitive and functional measures. CONCLUSIONS: Tau accumulation is associated with amyloid positivity and age, as well as with progressive neurodegeneration measurable using FDG and MRI. Tau correlates with cognitive decline, as do AD-specific hypometabolism and atrophy.

4-D Reconstruction With Respiratory Correction for Gated Myocardial Perfusion SPECT.

Cardiac single photon emission computed tomography (SPECT) images are known to suffer from both cardiac and respiratory motion blur. In this paper, we investigate a 4-D reconstruction approach to suppress the effect of respiratory motion in gated cardiac SPECT imaging. In this approach, the sequence of cardiac gated images is reconstructed with respect to a reference respiratory amplitude bin in the respiratory cycle. To combat the challenge of inherent high-imaging noise, we utilize the data counts acquired during the entire respiratory cycle by making use of a motion-compensated scheme, in which both cardiac motion and respiratory motion are taken into account. In the experiments, we first use Monte Carlo simulated imaging data, wherein the ground truth is known for quantitative comparison. We then demonstrate the proposed approach on eight sets of clinical acquisitions, in which the subjects exhibit different degrees of respiratory motion blur. The quantitative evaluation results show that the 4-D reconstruction with respiratory correction could effectively reduce the effect of motion blur and lead to a more accurate reconstruction of the myocardium. The mean-squared error of the myocardium is reduced by 22%, and the left ventricle (LV) resolution is improved by 21%. Such improvement is also demonstrated with the clinical acquisitions, where the motion blur is markedly improved in the reconstructed LV wall and blood pool. The proposed approach is also noted to be effective on correcting the spill-over effect in the myocardium from nearby bowel or liver activities.

Limited-angle effect compensation for respiratory binned cardiac SPECT.

PURPOSE: In cardiac single photon emission computed tomography (SPECT), respiratory-binned study is used to combat the motion blur associated with respiratory motion. However, owing to the variability in respiratory patterns during data acquisition, the acquired data counts can vary significantly both among respiratory bins and among projection angles within individual bins. If not properly accounted for, such variation could lead to artifacts similar to limited-angle effect in image reconstruction. In this work, the authors aim to investigate several reconstruction strategies for compensating the limited-angle effect in respiratory binned data for the purpose of reducing the image artifacts. METHODS: The authors first consider a model based correction approach, in which the variation in acquisition time is directly incorporated into the imaging model, such that the data statistics are accurately described among both the projection angles and respiratory bins. Afterward, the authors consider an approximation approach, in which the acquired data are rescaled to accommodate the variation in acquisition time among different projection angles while the imaging model is kept unchanged. In addition, the authors also consider the use of a smoothing prior in reconstruction for suppressing the artifacts associated with limited-angle effect. In our evaluation study, the authors first used Monte Carlo simulated imaging with 4D NCAT phantom wherein the ground truth is known for quantitative comparison. The authors evaluated the accuracy of the reconstructed myocardium using a number of metrics, including regional and overall accuracy of the myocardium, uniformity and spatial resolution of the left ventricle (LV) wall, and detectability of perfusion defect using a channelized Hotelling observer. As a preliminary demonstration, the authors also tested the different approaches on five sets of clinical acquisitions. RESULTS: The quantitative evaluation results show that the three compensation methods could all, but to different extents, reduce the reconstruction artifacts over no compensation. In particular, the model based approach reduced the mean-squared-error of the reconstructed myocardium by as much as 40%. Compared to the approach of data rescaling, the model based approach further improved both the overall and regional accuracy of the myocardium; it also further improved the lesion detectability and the uniformity of the LV wall. When ML reconstruction was used, the model based approach was notably more effective for improving the LV wall; when MAP reconstruction was used, the smoothing prior could reduce the noise level and artifacts with little or no increase in bias, but at the cost of a slight resolution loss of the LV wall. The improvements in image quality by the different compensation methods were also observed in the clinical acquisitions. CONCLUSIONS: Compensating for the uneven distribution of acquisition time among both projection angles and respiratory bins can effectively reduce the limited-angle artifacts in respiratory-binned cardiac SPECT reconstruction. Direct incorporation of the time variation into the imaging model together with a smoothing prior in reconstruction can lead to the most improvement in the accuracy of the reconstructed myocardium.

Dissociation of Down syndrome and Alzheimer's disease effects with imaging.

INTRODUCTION: Down Syndrome (DS) adults experience accumulation of Alzheimer's disease (AD)-like amyloid plaques and tangles and a high incidence of dementia and could provide an enriched population to study AD-targeted treatments. However, to evaluate effects of therapeutic intervention, it is necessary to dissociate the contributions of DS and AD from overall phenotype. Imaging biomarkers offer the potential to characterize and stratify patients who will worsen clinically but have yielded mixed findings in DS subjects. METHODS: We evaluated 18F fluorodeoxyglucose positron emission tomography (PET), florbetapir PET, and structural magnetic resonance (sMR) image data from 12 nondemented DS adults using advanced multivariate machine learning methods. RESULTS: Our results showed distinctive patterns of glucose metabolism and brain volume enabling dissociation of DS and AD effects. AD-like pattern expression corresponded to amyloid burden and clinical measures. DISCUSSION: These findings lay groundwork to enable AD clinical trials with characterization and disease-specific tracking of DS adults.

A computational model to generate simulated three-dimensional breast masses.

PURPOSE: To develop algorithms for creating realistic three-dimensional (3D) simulated breast masses and embedding them within actual clinical mammograms. The proposed techniques yield high-resolution simulated breast masses having randomized shapes, with user-defined mass type, size, location, and shape characteristics. METHODS: The authors describe a method of producing 3D digital simulations of breast masses and a technique for embedding these simulated masses within actual digitized mammograms. Simulated 3D breast masses were generated by using a modified stochastic Gaussian random sphere model to generate a central tumor mass, and an iterative fractal branching algorithm to add complex spicule structures. The simulated masses were embedded within actual digitized mammograms. The authors evaluated the realism of the resulting hybrid phantoms by generating corresponding left- and right-breast image pairs, consisting of one breast image containing a real mass, and the opposite breast image of the same patient containing a similar simulated mass. The authors then used computer-aided diagnosis (CAD) methods and expert radiologist readers to determine whether significant differences can be observed between the real and hybrid images. RESULTS: The authors found no statistically significant difference between the CAD features obtained from the real and simulated images of masses with either spiculated or nonspiculated margins. Likewise, the authors found that expert human readers performed very poorly in discriminating their hybrid images from real mammograms. CONCLUSIONS: The authors' proposed method permits the realistic simulation of 3D breast masses having user-defined characteristics, enabling the creation of a large set of hybrid breast images containing a well-characterized mass, embedded within real breast background. The computational nature of the model makes it suitable for detectability studies, evaluation of computer aided diagnosis algorithms, and teaching purposes.

Limited-angle tomography for analyzer-based phase-contrast x-ray imaging.

Multiple-image radiography (MIR) is an analyzer-based phase-contrast x-ray imaging method, which is emerging as a potential alternative to conventional radiography. MIR simultaneously generates three planar parametric images containing information about scattering, refraction and attenuation properties of the object. The MIR planar images are linear tomographic projections of the corresponding object properties, which allows reconstruction of volumetric images using computed tomography (CT) methods. However, when acquiring a full range of linear projections around the tissue of interest is not feasible or the scanning time is limited, limited-angle tomography techniques can be used to reconstruct these volumetric images near the central plane, which is the plane that contains the pivot point of the tomographic movement. In this work, we use computer simulations to explore the applicability of limited-angle tomography to MIR. We also investigate the accuracy of reconstructions as a function of number of tomographic angles for a fixed total radiation exposure. We use this function to find an optimal range of angles over which data should be acquired for limited-angle tomography MIR (LAT-MIR). Next, we apply the LAT-MIR technique to experimentally acquired MIR projections obtained in a cadaveric human thumb study. We compare the reconstructed slices near the central plane to the same slices reconstructed by CT-MIR using the full angular view around the object. Finally, we perform a task-based evaluation of LAT-MIR performance for different numbers of angular views, and use template matching to detect cartilage in the refraction image near the central plane. We use the signal-to-noise ratio of this test as the detectability metric to investigate an optimum range of tomographic angles for detecting soft tissues in LAT-MIR. Both results show that there is an optimum range of angular view for data acquisition where LAT-MIR yields the best performance, comparable to CT-MIR only if one considers volumetric images near the central plane and not the whole volume.