Mitchel R. Stacy

Radial Basis Functions for Combining Shape and Speckle Tracking in 4D Echocardiography

Quantitative analysis of left ventricular deformation can provide valuable information about the extent of disease as well as the efficacy of treatment. In this work, we develop an adaptive multi-level compactly supported radial basis approach for deformation analysis in 3D+time echocardiography. Our method combines displacement information from shape tracking of myocardial boundaries (derived from B-mode data) with mid-wall displacements from radio-frequency-based ultrasound speckle tracking. We evaluate our methods on open-chest canines (N=8) and show that our combined approach is better correlated to magnetic resonance tagging-derived strains than either individual method. We also are able to identify regions of myocardial infarction (confirmed by postmortem analysis) using radial strain values obtained with our approach.

Multimodality Imaging Approach for Serial Assessment of Regional Changes in Lower Extremity Arteriogenesis and Tissue Perfusion in a Porcine Model of Peripheral Arterial Disease

Background—A standard quantitative imaging approach to evaluate peripheral arterial disease does not exist. Quantitative tools for evaluating arteriogenesis in vivo are not readily available, and the feasibility of monitoring serial regional changes in lower extremity perfusion has not been examined. Methods and Results—Serial changes in lower extremity arteriogenesis and muscle perfusion were evaluated after femoral artery occlusion in a porcine model using single photon emission tomography (SPECT)/CT imaging with postmortem validation of in vivo findings using gamma counting, postmortem imaging, and histological analysis. Hybrid 201Tl SPECT/CT imaging was performed in pigs (n=8) at baseline, immediately postocclusion, and at 1 and 4 weeks postocclusion. CT imaging was used to identify muscle regions of interest in the ischemic and nonischemic hindlimbs for quantification of regional changes in CT-defined arteriogenesis and quantification of 201Tl perfusion. Four weeks postocclusion, postmortem tissue 201Tl activity was measured by gamma counting, and immunohistochemistry was performed to assess capillary density. Relative 201Tl retention (ischemic/nonischemic) was reduced immediately postocclusion in distal and proximal muscles and remained lower in calf and gluteus muscles 4 weeks later. Analysis of CT angiography revealed collateralization at 4 weeks within proximal muscles (P<0.05). SPECT perfusion correlated with tissue gamma counting at 4 weeks (P=0.01). Increased capillary density was seen within the ischemic calf at 4 weeks (P=0.004). Conclusions—201Tl SPECT/CT imaging permits serial, regional quantification of arteriogenesis and resting tissue perfusion after limb ischemia. This approach may be effective for detection of disease and monitoring therapy in peripheral arterial disease.

Radiotracer Imaging of Peripheral Vascular Disease

Peripheral vascular disease (PVD) is an atherosclerotic disease affecting the lower extremities, resulting in skeletal muscle ischemia, intermittent claudication, and, in more severe stages of disease, limb amputation and death. The evaluation of therapy in this patient population can be challenging, as the standard clinical indices are insensitive to assessment of regional alterations in skeletal muscle physiology. Radiotracer imaging of the lower extremities with techniques such as PET and SPECT can provide a noninvasive quantitative technique for the evaluation of the pathophysiology associated with PVD and may complement clinical indices and other imaging approaches. This review discusses the progress in radiotracer-based evaluation of PVD and highlights recent advancements in molecular imaging with potential for clinical application.Peripheral vascular disease (PVD) is an atherosclerotic disease affecting the lower extremities, resulting in skeletal muscle ischemia, intermittent claudication, and, in more severe stages of disease, limb amputation and death. The evaluation of therapy in this patient population can be challenging, as the standard clinical indices are insensitive to assessment of regional alterations in skeletal muscle physiology. Radiotracer imaging of the lower extremities with techniques such as PET and SPECT can provide a noninvasive quantitative technique for the evaluation of the pathophysiology associated with PVD and may complement clinical indices and other imaging approaches. This review discusses the progress in radiotracer-based evaluation of PVD and highlights recent advancements in molecular imaging with potential for clinical application.

Scatter and crosstalk corrections for (99m)Tc/(123)I dual-radionuclide imaging using a CZT SPECT system with pinhole collimators.

PURPOSE The energy spectrum for a cadmium zinc telluride (CZT) detector has a low energy tail due to incomplete charge collection and intercrystal scattering. Due to these solid-state detector effects, scatter would be overestimated if the conventional triple-energy window (TEW) method is used for scatter and crosstalk corrections in CZT-based imaging systems. The objective of this work is to develop a scatter and crosstalk correction method for (99m)Tc/(123)I dual-radionuclide imaging for a CZT-based dedicated cardiac SPECT system with pinhole collimators (GE Discovery NM 530c/570c). METHODS A tailing model was developed to account for the low energy tail effects of the CZT detector. The parameters of the model were obtained using (99m)Tc and (123)I point source measurements. A scatter model was defined to characterize the relationship between down-scatter and self-scatter projections. The parameters for this model were obtained from Monte Carlo simulation using SIMIND. The tailing and scatter models were further incorporated into a projection count model, and the primary and self-scatter projections of each radionuclide were determined with a maximum likelihood expectation maximization (MLEM) iterative estimation approach. The extracted scatter and crosstalk projections were then incorporated into MLEM image reconstruction as an additive term in forward projection to obtain scatter- and crosstalk-corrected images. The proposed method was validated using Monte Carlo simulation, line source experiment, anthropomorphic torso phantom studies, and patient studies. The performance of the proposed method was also compared to that obtained with the conventional TEW method. RESULTS Monte Carlo simulations and line source experiment demonstrated that the TEW method overestimated scatter while their proposed method provided more accurate scatter estimation by considering the low energy tail effect. In the phantom study, improved defect contrasts were observed with both correction methods compared to no correction, especially for the images of (99m)Tc in dual-radionuclide imaging where there is heavy contamination from (123)I. In this case, the nontransmural defect contrast was improved from 0.39 to 0.47 with the TEW method and to 0.51 with their proposed method and the transmural defect contrast was improved from 0.62 to 0.74 with the TEW method and to 0.73 with their proposed method. In the patient study, the proposed method provided higher myocardium-to-blood pool contrast than that of the TEW method. Similar to the phantom experiment, the improvement was the most substantial for the images of (99m)Tc in dual-radionuclide imaging. In this case, the myocardium-to-blood pool ratio was improved from 7.0 to 38.3 with the TEW method and to 63.6 with their proposed method. Compared to the TEW method, the proposed method also provided higher count levels in the reconstructed images in both phantom and patient studies, indicating reduced overestimation of scatter. Using the proposed method, consistent reconstruction results were obtained for both single-radionuclide data with scatter correction and dual-radionuclide data with scatter and crosstalk corrections, in both phantom and human studies. CONCLUSIONS The authors demonstrate that the TEW method leads to overestimation in scatter and crosstalk for the CZT-based imaging system while the proposed scatter and crosstalk correction method can provide more accurate self-scatter and down-scatter estimations for quantitative single-radionuclide and dual-radionuclide imaging.

Simultaneous CT-MRI Reconstruction for Constrained Imaging Geometries Using Structural Coupling and Compressive Sensing

Objective: A unified reconstruction framework is presented for simultaneous CT-MRI reconstruction. Methods: In an ideal CT-MRI scanner, CT and MRI acquisitions would occur simultaneously, and would be inherently registered in space and time. Alternatively, separately acquired CT and MRI scans can be fused to simulate an instantaneous acquisition. In this study, structural coupling and compressive sensing techniques are combined to unify CT and MRI reconstructions. A bidirectional image estimation method was proposed to connect images from different modalities. Hence, CT and MRI data serve as prior knowledge to each other for better CT and MRI image reconstruction than what could be achieved with separate reconstruction. Significance: Combined CT-MRI imaging has the potential for improved results in existing preclinical and clinical applications, as well as opening novel research directions for future applications. Results: Our integrated reconstruction methodology is demonstrated with numerical phantom and real-dataset-based experiments, and has yielded promising results.

The role of molecular imaging in the evaluation of myocardial and peripheral angiogenesis

Angiogenesis, or the formation of new microvasculature, is a physiological process that may occur in the setting of chronic tissue ischemia and can play an important role in improving tissue perfusion and blood flow following myocardial infarction or in the presence of peripheral vascular disease (PVD). Molecular imaging of angiogenesis within the cardiovascular system is a developing field of study. Targeted imaging of angiogenesis has the potential for non-invasive assessment of the underlying molecular signaling events associated with the angiogenic process and, when applied in conjunction with physiological perfusion imaging, may be utilized to predict and evaluate clinical outcomes in the setting of ischemic heart disease or PVD. This review discusses the developing radiotracer-based imaging techniques and technology currently in use that possess potential for clinical translation, with specific focus on PET and SPECT imaging of myocardial and peripheral angiogenesis.

Anatomical-based partial volume correction for low-dose dedicated cardiac SPECT/CT

Due to the limited spatial resolution, partial volume effect has been a major degrading factor on quantitative accuracy in emission tomography systems. This study aims to investigate the performance of several anatomical-based partial volume correction (PVC) methods for a dedicated cardiac SPECT/CT system (GE Discovery NM/CT 570c) with focused field-of-view over a clinically relevant range of high and low count levels for two different radiotracer distributions. These PVC methods include perturbation geometry transfer matrix (pGTM), pGTM followed by multi-target correction (MTC), pGTM with known concentration in blood pool, the former followed by MTC and our newly proposed methods, which perform the MTC method iteratively, where the mean values in all regions are estimated and updated by the MTC-corrected images each time in the iterative process. The NCAT phantom was simulated for cardiovascular imaging with (99m)Tc-tetrofosmin, a myocardial perfusion agent, and (99m)Tc-red blood cell (RBC), a pure intravascular imaging agent. Images were acquired at six different count levels to investigate the performance of PVC methods in both high and low count levels for low-dose applications. We performed two large animal in vivo cardiac imaging experiments following injection of (99m)Tc-RBC for evaluation of intramyocardial blood volume (IMBV). The simulation results showed our proposed iterative methods provide superior performance than other existing PVC methods in terms of image quality, quantitative accuracy, and reproducibility (standard deviation), particularly for low-count data. The iterative approaches are robust for both (99m)Tc-tetrofosmin perfusion imaging and (99m)Tc-RBC imaging of IMBV and blood pool activity even at low count levels. The animal study results indicated the effectiveness of PVC to correct the overestimation of IMBV due to blood pool contamination. In conclusion, the iterative PVC methods can achieve more accurate quantification, particularly for low count cardiac SPECT studies, typically obtained from low-dose protocols, gated studies, and dynamic applications.

Simultaneous partial volume correction and noise regularization for cardiac SPECT/CT

Partial volume correction (PVC) methods typically improve quantification at the expense of increasing image noise. In this study, we developed a novel voxel-based PVC method that incorporates anatomical knowledge to improve quantification while suppressing noise for cardiac SPECT/CT imaging. In the proposed method, the SPECT images were first reconstructed using anatomical based maximum-a-posteriori with Bowshers prior (AMAP) to penalize noise while preserving boundaries. A template was then obtained by assigning initial estimations of the mean activity in the target regions on a segmented contrast CT dataset. This template was forward projected, and reconstructed using AMAP to derive a correction map that reflects the partial volume effects (PVE) introduced by both the intrinsic system resolution and the smoothing applied during reconstruction. This map was then applied to the non-PVC SPECT images on a voxel-by-voxel basis to correct PVE. To evaluate the proposed Simultaneous PVC and Regularization method (SPR), we first simulated two SPECT scans with 99mTc-tetrofosmin and 99mTcred blood cell (RBC) tracers on a dedicated cardiac multiple pinhole SPECT/CT at low count levels. We then applied the proposed method on a dog study injected with 99mTc-RBC tracer. We also retrospectively rebinned the dog study into shorter acquisitions to assess the performance of SPR on high-noise low-count data. The proposed method was compared to MLEM, a conventional multi-target correction (MTC) PVC method applied on the MLEM reconstruction and the AMAP reconstruction, in terms of quantification, noise level and visual quality. The results show that MTC corrected PVE but amplified noise and yielded the worst performance among all the methods tested on the low-count data. AMAP suppressed noise effectively, however, it was unable to recover the activity in the myocardium and other organs. SPR yielded superior performance in both quantitative assessment and image quality for visual detection by recovering the activity in each organ while suppressing noise. The results also show that SPR was robust to the initial estimation of the regional mean values in the template.

The Yale Fitness Intervention Trial in female cancer survivors: Cardiovascular and physiological outcomes

Background Induced premature menopause and cardio‐toxic therapy increase cardiovascular disease risk in female cancer survivors. Objective To compare the effects of a 12 month aerobic‐resistance fitness center intervention to home based physical activity on cardiovascular function and metabolic risk factors. Methods Subjects (N = 154) who had completed primary and/or adjuvant chemotherapy (past 3 years) were randomized to a fitness center intervention or a home based group. The fitness center intervention was a structured thrice weekly aerobic (30 min brisk walking treadmill in target heart range) combined with resistance (30 min of lower body strength training) exercise program, supervised for the first 6 months. The home based group received national guidelines for 30 min moderate intensity exercise most days of the week. Fasting serum samples were collected at baseline, 6 and 12 months for insulin, glucose, lipids and hemoglobin A‐1C. A graded exercise stress test was also performed at baseline and 6 months. Results The majority of subjects were white (85.7%), had breast cancer (83.1%) and the average age was 51.9 years. Subjects in the fitness center intervention had significantly improved time on treadmill (p = .039), improved heart rate recovery at 1 min (p = .028), greater MET minutes/week (p ≤ .0001), a trend for improved insulin resistance (p = .067) and stable insulin levels (p = .045) compared to the home based physical activity group. Conclusions Exercise represents a potential cardiac risk reduction intervention for cancer survivors. Clinical Trials.gov NCT01102985.

Comparison of regional skeletal muscle tissue oxygenation in college athletes and sedentary control subjects using quantitative BOLD MR imaging

Blood oxygen level‐dependent (BOLD) magnetic resonance (MR) imaging permits noninvasive assessment of tissue oxygenation. We hypothesized that BOLD imaging would allow for regional evaluation of differences in skeletal muscle oxygenation between athletes and sedentary control subjects, and dynamic BOLD responses to ischemia (i.e., proximal cuff occlusion) and reactive hyperemia (i.e., rapid cuff deflation) would relate to lower extremity function, as assessed by jumping ability. College football athletes (linemen, defensive backs/wide receivers) were compared to sedentary healthy controls. BOLD signal of the gastrocnemius, soleus, anterior tibialis, and peroneus longus was assessed for peak hyperemic value (PHV), time to peak (TTP), minimum ischemic value (MIV), and time to recovery (TTR). Significantly higher PHVs were identified in athletes versus controls for the gastrocnemius (linemen, 15.8 ± 9.1%; defensive backs/wide receivers, 17.9 ± 5.1%; controls, 7.4 ± 3.5%), soleus (linemen, 25.9 ± 11.5%; backs/receivers, 22.0 ± 9.4%; controls, 12.9 ± 5.8%), and anterior tibialis (linemen, 12.8 ± 5.3%; backs/receivers, 12.6 ± 3.9%; controls, 7.7 ± 4.0%), whereas no differences in PHV were found for the peroneus longus (linemen, 14.1 ± 6.9%; backs/receivers, 11.7 ± 4.6%; controls, 9.0 ± 4.9%). In all subject groups, the gastrocnemius and soleus muscles exhibited the lowest MIVs during cuff occlusion. No differences in TTR were found between muscles for any subject group. PHV of the gastrocnemius muscle was significantly and positively related to maximal vertical (r = 0.56, P = 0.002) and broad jump (r = 0.47, P = 0.01). These results suggest that BOLD MR imaging is a useful noninvasive tool for evaluating differences in tissue oxygenation of specific muscles between active and sedentary individuals, and peak BOLD responses may relate to functional capacity.