A modular dose delivery system for treating moving targets with scanned ion beams: Performance and safety characteristics, and preliminary tests.

PURPOSE: The purpose of this study was to develop a modular dose-delivery system (DDS) for scanned-ion radiotherapy that mitigates against organ motion artifacts by synchronizing the motion of the beam with that of the moving anatomy. METHODS: We integrated a new motion synchronization system and an existing DDS into two centers. The modular approach to integration utilized an adaptive layer of software and hardware interfaces. The method of synchronization comprised three major tasks, namely, the creation of 3D treatment plans (each representing one phase of respiratory motion and together comprising a 4D plan), monitoring anatomic motion during treatment, and synchronization of the beam to anatomic motion. The synchronization was accomplished in real time by repeatedly selecting and delivering a 3D plan, i.e., the one that most closely corresponded to the current anatomic state, until all plans were delivered. The performance characteristics of the motion mitigation system were tested by delivering 4D treatment plans to a moving phantom and comparing planned and measured dose distributions. Dosimetric performance was considered acceptable when the gamma-index pass rate was >90%, homogeneity-index value was >95%, and conformity-index value was >60%. Selected safety characteristics were tested by introducing errors during treatment and testing DDS response. RESULTS: Acceptable dosimetric performance and safety characteristics were observed for all treatment plans. CONCLUSIONS: We demonstrated, for the first time, that a modular prototype system, synchronizing scanned ion beams with moving targets can deliver conformal, motion-compensated dose distributions. The prototype system was implemented and characterized at GSI and CNAO.

X-ray interferometry without analyzer for breast CT application: a simulation study.

Purpose: We investigate an analyzer-less x-ray interferometer with a spatially modulated phase grating (MPG) that can deliver three modalities (attenuation image, phase image, and scatter images) in breast computed tomography (BCT). The system can provide three x-ray modalities while preserving the dose to the object and can achieve attenuation image sensitivity similar to that of a standard absorption-only BCT. The MPG system works with a source, a source-grating, a single phase grating, and a detector. No analyzer is necessary. Thus, there is an approximately 2x improvement in fluence at the detector for our system compared with the same source-detector distance Talbot-Lau x-ray interferometry (TLXI) because the TLXI has an analyzer after the object, which is not required for the MPG. Approach: We investigate the MPG BCT system in simulations and find a clinically feasible system geometry. First, the mechanism of MPG interferometry is conceptually shown via Sommerfeld-Rayleigh diffraction integral simulations. Next, we investigate source coherence requirements, fringe visibility, and phase sensitivity dependence on different system parameters and find clinically feasible system geometry. Results: The phase sensitivity of MPG interferometry is proportional to object-detector distance and inversely proportional to a period of broad fringes at the detector, which is determined by the grating spatial modulation period. In our simulations, the MPG interferometry can achieve about 27% fringe visibility with clinically realistic BCT geometry of a total source-detector distance of 950 mm and source-object distance of 500 mm. Conclusions: We simulated a promising analyzer-less x-ray interferometer, with a spatially sinusoidal MPG. Our system is expected to deliver the attenuation, phase and scatter image in a single acquisition without dose or fluence detriment, compared with conventional BCT.

Computational feasibility of calculating the steady-state blood flow rate through the vasculature of the entire human body.

The human body contains approximately 20 billion individual blood vessels that deliver nutrients and oxygen to tissues. While blood flow is a well-developed field of research, no previous studies have calculated the blood flow rates through more than 5 million connected vessels. The goal of this study was to test if it is computationally feasible to calculate the blood flow rates through a vasculature equal in size to that of the human body. We designed and implemented a two-step algorithm to calculate the blood flow rates using principles of steady-state fluid dynamics. Steady-state fluid dynamics is an accurate approximation for the microvascular and venous structures in the human body. To determine the computational feasibility, we measured and evaluated the execution time, scalability, and memory usage to quantify the computational requirements. We demonstrated that it is computationally feasible to calculate the blood flow rate through 17 billion vessels in 6.5 hours using 256 compute nodes. The computational modeling of blood flow rate in entire organisms may find application in research on drug delivery, treatment of cancer metastases, and modulation of physiological performance.

Computational feasibility of simulating changes in blood flow through whole-organ vascular networks from radiation injury.

Vasculature is necessary to the healthy function of most tissues. In radiation therapy, injury of the vasculature can have both beneficial and detrimental effects, such as tumor starvation, cardiac fibrosis, and white-matter necrosis. These effects are caused by changes in blood flow due to the vascular injury. Previously, research has focused on simulating the radiation injury of vasculature in small volumes of tissue, ignoring the systemic effects of local damage on blood flow. Little is known about the computational feasibility of simulating the radiation injury to whole-organ vascular networks. The goal of this study was to test the computational feasibility of simulating the dose deposition to a whole-organ vascular network and the resulting change in blood flow. To do this, we developed an amorphous track-structure model to transport radiation and combined this with existing methods to model the vasculature and blood flow rates. We assessed the algorithm's computational scalability, execution time, and memory usage. The data demonstrated it is computationally feasible to calculate the radiation dose and resulting changes in blood flow from 2 million protons to a network comprising 8.5 billion blood vessels (approximately the number in the human brain) in 87 hours using a 128-node cluster. Furthermore, the algorithm demonstrated both strong and weak scalability, meaning that additional computational resources can reduce the execution time further. These results demonstrate, for the first time, that it is computationally feasible to calculate radiation dose deposition in whole-organ vascular networks. These findings provide key insights into the computational aspects of modeling whole-organ radiation damage. Modeling the effects radiation has on vasculature could prove useful in the study of radiation effects on tissues, organs, and organisms.

Performance analysis of a high-sensitivity multi-pinhole cardiac SPECT system with hemi-ellipsoid detectors.

PURPOSE: Single-photon emission computed tomography (SPECT) is a noninvasive imaging modality, used in myocardial perfusion imaging. The challenges facing the majority of clinical SPECT systems are low sensitivity, poor resolution, and the relatively high radiation dose to the patient. New generation systems (GE Discovery, DSPECT) dedicated to cardiac imaging improve sensitivity by a factor of 5-8. This improvement can be used to decrease acquisition time and/or dose. However, in the case of ultra-low dose (~3 mCi) injections, acquisition times are still significantly long, taking 10-12 min. The purpose of this work is to investigate a new gamma camera design with 21 hemi-ellipsoid detectors each with a pinhole collimator for cardiac SPECT for further improvement in sensitivity and resolution and reduced patient exposures and imaging times. METHODS: To evaluate the resolution of our hemi-ellipsoid system, GATE Monte-Carlo simulations were performed on point-sources, rod-sources, and NCAT phantoms. For average full-width-half-maximum (FWHM) equivalence with base flat-detector, the pinhole-diameter for the curved hemi-ellipsoid detector was found to be 8.68 mm, an operating pinhole-diameter nominally expected to be ~3 times more sensitive than state-of-the-art systems. Rod-sources equally spaced within the region of interest were acquired with a 21-detector system and reconstructed with our multi-pinhole (MPH) iterative OSEM algorithm with collimator resolution recovery. The results were compared with the results of a state-of-the-art system (GE Discovery) available in the literature. The system was also evaluated using the mathematical anthropomorphic NCAT (NURBS-based Cardiac Torso; Segars et al. IEEE Trans Nucl Sci. 1999;46:503-506) phantom with a full (clinical)-dose acquisition (25 mCi) for 2 min and an ultra-low dose acquisition of 3 mCi for 5.44 min. The estimated left ventricle (LV) counts were compared with the available literature on a state-of-the-art system (DSPECT). FWHM of the LV wall on MPH-OSEM-reconstructed images with collimator resolution recovery was estimated. RESULTS: On acquired rod-sources, the average resolution (FWHM) after reconstruction with resolution recovery in the entire region of interest (ROI) for cardiac imaging was on the average 4.44 mm (±2.84), compared to 6.9 mm (±1 mm) reported for GE Discovery (Kennedy et al., J Nucl Cardiol. 2014:21:443-452). For NCAT studies, improved sensitivity allowed a full-dose (25 mCi) 2-min acquisition (Ell8.68mmFD) which yielded 3.79 M LV counts. This is ~3.35 times higher compared to 1.13 M LV counts acquired in 2 min for clinical full dose for state-of-the-art DSPECT. The increased sensitivity also allowed an ultra-low dose acquisition protocol (Ell8.68 mmULD), 3 mCi (eight times less injected dose) in 5.44 min. This ultra-low dose protocol yielded ~1.23 M LV counts which was comparable to the full-dose 2-min acquisition for DSPECT. The estimated NCAT average FWHM at the LV wall after 12 iterations of the OSEM reconstruction was 4.95 and 5.66 mm around the mid-short-axis slices for Ell8.68mmFD and Ell8.68mmULD, respectively. CONCLUSION: Our Monte-Carlo simulation studies and reconstruction suggest using (inverted wineglass sized) hemi-ellipsoid detectors with pinhole collimators can increase the sensitivity ~3.35 times over the new generation of dedicated cardiac SPECT systems, while also improving the reconstructed resolution for rod-sources with an average of 4.44 mm in region of interest. The extra sensitivity may be used for ultra-low dose imaging (3 mCi) at ~5.44 min for comparable clinical counts as state-of-the-art systems.

Experimental method and statistical analysis to fit tumor growth model using SPECT/CT imaging: a preclinical study.

BACKGROUND: Over the last decade, several theoretical tumor-models have been developed to describe tumor growth. Oncology imaging is performed using various modalities including computed tomography (CT), magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT) and fluorodeoxyglucose-positron emission tomography (FDG-PET). Our goal is to extract useful, otherwise hidden, quantitative biophysical parameters (such as growth-rate, tumor-necrotic-factor, etc.) from these serial images of tumors by fitting mathematical models to images. These biophysical features are intrinsic to the tumor types and specific to the study-subject, and expected to add valuable information on the tumor containment or spread and help treatment plans. Thus, fitting realistic but practical models and assessing parameter-errors and degree of fit is important. METHODS: We implemented an existing theoretical ode-compartment model and variants and applied them for the first time, in vivo. We developed an inversion algorithm to fit the models for tumor growth for simulated as well as in vivo experimental data. Serial SPECT/CT scans of mice breast-tumors were acquired, and SPECT data was used to segment the proliferating-layers of tumors. RESULTS: Results of noisy data simulation and inversion show that 5 out of 7 parameters were recovered to within 4.3% error. In particular, tumor "growth-rate" parameter was recovered to 0.07% error. For model fitting to in vivo mice-tumors, regression analysis on the P-layer volume showed R2 of 0.99 for logistic and Gompertzian while surface area model yielded R2=0.96. For the necrotic layer the R2 values were 0.95, 0.93 and 0.94 respectively for surface-area, logistic and Gompertzian. The Akaike Information Criterion (AIC) weights of the models (giving their relative probability of being the best Kullback-Leibler (K-L) model among the set of candidate models) were ~0, 0.43 and 0.57 for surface-area, logistic and Gompertzian models. CONCLUSIONS: Model-fitting to mice tumor studies demonstrates feasibility of applying the models to in vivo imaging data to extract features. Akaike information criterion (AIC) evaluations show Gompertzian or logistic growth model fits in vivo breast-tumors better than surface-area based growth model.

Design of a Multi-Pinhole Collimator for I-123 DaTscan Imaging on Dual-Headed SPECT Systems in Combination with a Fan-Beam Collimator.

For the 2011 FDA approved Parkinson's Disease (PD) SPECT imaging agent I-123 labeled DaTscan, the volume of interest (VOI) is the interior portion of the brain. However imaging of the occipital lobe is also required with PD for calculation of the striatal binding ratio (SBR), a parameter of significance in early diagnosis, differentiation of PD from other disorders with similar clinical presentations, and monitoring progression. Thus we propose the usage of a combination of a multi-pinhole (MPH) collimator on one head of the SPECT system and a fan-beam on the other. The MPH would be designed to provide high resolution and sensitivity for imaging of the interior portion of the brain. The fan-beam collimator would provide lower resolution but complete sampling of the brain addressing data sufficiency and allowing a volume-of-interest to be defined over the occipital lobe for calculation of SBR's. Herein we focus on the design of the MPH component of the combined system. Combined reconstruction will be addressed in a subsequent publication. An analysis of 46 clinical DaTscan studies was performed to provide information to define the VOI, and design of a MPH collimator to image this VOI. The system spatial resolution for the MPH was set to 4.7 mm, which is comparable to that of clinical PET systems, and significantly smaller than that of fan-beam collimators employed in SPECT. With this set, we compared system sensitivities for three aperture array designs, and selected the 3 × 3 array due to it being the highest of the three. The combined sensitivity of the apertures for it was similar to that of an ultra-high resolution fan-beam (LEUHRF) collimator, but smaller than that of a high-resolution fan-beam collimator (LEHRF). On the basis of these results we propose the further exploration of this design through simulations, and the development of combined MPH and fan-beam reconstruction.

LROC Investigation of Three Strategies for Reducing the Impact of Respiratory Motion on the Detection of Solitary Pulmonary Nodules in SPECT.

The objective of this investigation was to determine the effectiveness of three motion reducing strategies in diminishing the degrading impact of respiratory motion on the detection of small solitary pulmonary nodules (SPN) in single photon emission computed tomographic (SPECT) imaging in comparison to a standard clinical acquisition and the ideal case of imaging in the absence of respiratory motion. To do this non-uniform rational B-spline cardiac-torso (NCAT) phantoms based on human-volunteer CT studies were generated spanning the respiratory cycle for a normal background distribution of Tc-99m NeoTect. Similarly, spherical phantoms of 1.0 cm diameter were generated to model small SPN for each of 150 uniquely located sites within the lungs whose respiratory motion was based on the motion of normal structures in the volunteer CT studies. The SIMIND Monte Carlo program was used to produce SPECT projection data from these. Normal and single-lesion containing SPECT projection sets with a clinically realistic Poisson noise level were created for the cases of: 1) the end-expiration (EE) frame with all counts, 2) respiration-averaged motion with all counts, 3) one-fourth of the 32 frames centered around EE (Quarter-Binning), 4) one-half of the 32 frames centered around EE (Half-Binning), and 5) eight temporally binned frames spanning the respiratory cycle. Each of the sets of combined projection data were reconstructed with RBI-EM with system spatial-resolution compensation (RC). Based on the known motion for each of the 150 different lesions, the reconstructed volumes of respiratory bins were shifted so as to superimpose the locations of the SPN onto that in the first bin (Reconstruct and Shift). Five human-observers performed localization receiver operating characteristics (LROC) studies of SPN detection. The observer results were analyzed for statistical significance differences in SPN detection accuracy among the three correction strategies, the standard acquisition, and the ideal case of the absence of respiratory motion. Our human-observer LROC determined that Quarter-Binning and Half-Binning strategies resulted in SPN detection accuracy statistically significantly below (P < 0.05) that of standard clinical acquisition, whereas the Reconstruct and Shift strategy resulted in a detection accuracy not statistically significantly different from that of the ideal case. This investigation demonstrates that tumor detection based on acquisitions associated with less than all the counts which could potentially be employed may result in poorer detection despite limiting the motion of the lesion. The Reconstruct and Shift method results in tumor detection that is equivalent to ideal motion correction.

New compartment model analysis of lean-mass and fat-mass growth with overfeeding.

OBJECTIVES: Mathematical models of lean- and fat-mass growth with diet are useful to help describe and potentially predict the fat- and lean-mass change with different diets as a function of consumed protein and fat calories. Most of the existing models do not explicitly account for interdependence of fat-mass on the lean-mass and vice versa. The aim of this study was to develop a new compartmental model to describe the growth of lean and fat mass depending on the input of dietary protein and fat, and accounting for the interdependence of adipose tissue and muscle growth. METHODS: The model was fitted to existing clinical data of an overfeeding trial for 23 participants (with a high-protein diet, a normal-protein diet, and a low-protein diet) and compared with the existing Forbes model. RESULTS: Qualitatively and quantitatively, the compartment model data fit was smoother with less overall error than the Forbes model. The root means square error were 0.39, 0.93 and 0.72 kg for the new model, the Forbes model, and the modified Forbes model, respectively. Additionally, for the present model, the differences between some of the coefficients (on the cross dependence of fat and lean mass as well as on the intake diet dependence) across different diets were statistically significant (P < 0.05). CONCLUSIONS: Our new Dey-model showed excellent fit to overfeeding data for 23 normal participants with some significant differences of model coefficients across diets, enabling further studies of the model coefficients for larger groups of participants with obesity or other diseases.

The impact of system matrix dimension on small FOV SPECT reconstruction with truncated projections.

PURPOSE: A dedicated cardiac hybrid single photon emission computed tomography (SPECT)/CT scanner that uses cadmium zinc telluride detectors and multiple pinhole collimators for stationary acquisition offers many advantages. However, the impact of the reconstruction system matrix (SM) dimension on the reconstructed image quality from truncated projections and 19 angular samples acquired on this scanner has not been extensively investigated. In this study, the authors aimed to investigate the impact of the dimensions of SM and the use of body contour derived from adjunctive CT imaging as an object support in reconstruction on this scanner, in relation to background extracardiac activity. METHODS: The authors first simulated a generic SPECT/CT system to image four NCAT phantoms with various levels of extracardiac activity and compared the reconstructions using SM in different dimensions and with/without body contour as a support for quantitative evaluations. The authors then compared the reconstructions of 18 patient studies, which were acquired on a GE Discovery NM570c scanner following injection of different radiotracers, including (99m)Tc-Tetrofosmin and (123)I-mIBG, comparing the scanner's default SM that incompletely covers the body with a large SM that incorporates a patient specific full body contour. RESULTS: The simulation studies showed that the reconstructions using a SM that only partially covers the body yielded artifacts on the edge of the field of view (FOV), overestimation of activity and increased nonuniformity in the blood pool for the phantoms with higher relative levels of extracardiac activity. However, the impact on the quantitative accuracy in the high activity region, such as the myocardium, was subtle. On the other hand, an excessively large SM that enclosed the entire body alleviated the artifacts and reduced overestimation in the blood pool, but yielded slight underestimation in myocardium and defect regions. The reconstruction using the larger SM with body contour yielded the most quantitatively accurate results in all the regions of interest for a range of uptake levels in the extracardiac regions. In patient studies, the SM incorporating patient specific body contour minimized extracardiac artifacts, yielded similar myocardial activity, lower blood pool activity, and subsequently improved myocardium-to-blood pool contrast (p < 0.0001) by an average of 7% (range 0%-18%) across all the patients, compared to the reconstructions using the scanner's default SM. CONCLUSIONS: Their results demonstrate that using a large SM that incorporates a CT derived body contour in the reconstruction could improve quantitative accuracy within the FOV for clinical studies with high extracardiac activity.

Effect of Non-Alignment/Alignment of Attenuation Map Without/With Emission Motion Correction in Cardiac SPECT/CT.

PURPOSE: We investigate the differences without/with respiratory motion correction in apparent imaging agent localization induced in reconstructed emission images when the attenuation maps used for attenuation correction (from CT) are misaligned with the patient anatomy during emission imaging due to differences in respiratory state. METHODS: We investigated use of attenuation maps acquired at different states of a 2 cm amplitude respiratory cycle (at end-expiration, at end-inspiration, the center map, the average transmission map, and a large breath-hold beyond range of respiration during emission imaging) to correct for attenuation in MLEM reconstruction for several anatomical variants of the NCAT phantom which included both with and without non-rigid motion between heart and sub-diaphragmatic regions (such as liver, kidneys etc). We tested these cases with and without emission motion correction and attenuation map alignment/non-alignment. RESULTS: For the NCAT default male anatomy the false count-reduction due to breathing was largely removed upon emission motion correction for the large majority of the cases. Exceptions (for the default male) were for the cases when using the large-breathhold end-inspiration map (TI_EXT), when we used the end-expiration (TE) map, and to a smaller extent, the end-inspiration map (TI). However moving the attenuation maps rigidly to align the heart region, reduced the remaining count-reduction artifacts. For the female patient count-reduction remained post motion correction using rigid map-alignment due to the breast soft-tissue misalignment. Quantitatively, after the transmission (rigid) alignment correction, the polar-map 17-segment RMS error with respect to the reference (motion-less case) reduced by 46.5% on average for the extreme breathhold case. The reductions were 40.8% for end-expiration map and 31.9% for end-inspiration cases on the average, comparable to the semi-ideal case where each state uses its own attenuation map for correction. CONCLUSIONS: Two main conclusions are that even rigid emission motion correction to rigidly align the heart region to the attenuation map helps in average cases to reduce the count-reduction artifacts and secondly, within the limits of the study (ex. rigid correction) when there is lung tissue inferior to the heart as with the NCAT phantom employed in this study endexpiration maps (TE) might best be avoided as they may create more artifacts than the end-inspiration (TI) maps.

Digital anthropomorphic phantoms of non-rigid human respiratory and voluntary body motion for investigating motion correction in emission imaging.

The development of methods for correcting patient motion in emission tomography has been receiving increased attention. Often the performance of these methods is evaluated through simulations using digital anthropomorphic phantoms, such as the commonly used extended cardiac torso (XCAT) phantom, which models both respiratory and cardiac motion based on human studies. However, non-rigid body motion, which is frequently seen in clinical studies, is not present in the standard XCAT phantom. In addition, respiratory motion in the standard phantom is limited to a single generic trend. In this work, to obtain a more realistic representation of motion, we developed a series of individual-specific XCAT phantoms, modeling non-rigid respiratory and non-rigid body motions derived from the magnetic resonance imaging (MRI) acquisitions of volunteers. Acquisitions were performed in the sagittal orientation using the Navigator methodology. Baseline (no motion) acquisitions at end-expiration were obtained at the beginning of each imaging session for each volunteer. For the body motion studies, MRI was again acquired only at end-expiration for five body motion poses (shoulder stretch, shoulder twist, lateral bend, side roll, and axial slide). For the respiratory motion studies, an MRI was acquired during free/regular breathing. The magnetic resonance slices were then retrospectively sorted into 14 amplitude-binned respiratory states, end-expiration, end-inspiration, six intermediary states during inspiration, and six during expiration using the recorded Navigator signal. XCAT phantoms were then generated based on these MRI data by interactive alignment of the organ contours of the XCAT with the MRI slices using a graphical user interface. Thus far we have created five body motion and five respiratory motion XCAT phantoms from the MRI acquisitions of six healthy volunteers (three males and three females). Non-rigid motion exhibited by the volunteers was reflected in both respiratory and body motion phantoms with a varying extent and character for each individual. In addition to these phantoms, we recorded the position of markers placed on the chest of the volunteers for the body motion studies, which could be used as external motion measurement. Using these phantoms and external motion data, investigators will be able to test their motion correction approaches for realistic motion obtained from different individuals. The non-uniform rational B-spline data and the parameter files for these phantoms are freely available for downloading and can be used with the XCAT license.

MRI Investigation of the Linkage Between Respiratory Motion of the Heart and Markers on Patient's Abdomen and Chest: Implications for Respiratory Amplitude Binning List-Mode PET and SPECT Studies.

Respiratory motion of the heart impacts the diagnostic accuracy of myocardial-perfusion emission-imaging studies. Amplitude binning has come to be the method of choice for binning list-mode based acquisitions for correction of respiratory motion in PET and SPECT. In some subjects respiratory motion exhibits hysteretic behavior similar to damped non-linear cyclic systems. The detection and correction of hysteresis between the signals from surface movement of the patient's body used in binning and the motion of the heart within the chest remains an open area for investigation. This study reports our investigation in nine volunteers of the combined MRI tracking of the internal respiratory motion of the heart using Navigators with stereo-tracking of markers on the volunteer's chest and abdomen by a visual-tracking system (VTS). The respiratory motion signals from the internal organs and the external markers were evaluated for hysteretic behavior analyzing the temporal correspondence of the signals. In general, a strong, positive correlation between the external marker motion (AP direction) and the internal heart motion (SI direction) during respiration was observed. The average ± standard deviation in the Spearman's ranked correlation coefficient (ρ) over the nine volunteer studied was 0.92 ± 0.1 between the external abdomen marker and the internal heart, and 0.87 ± 0.2 between the external chest marker and the internal heart. However despite the good correlation on average for the nine volunteers, in three studies a poor correlation was observed due to hysteretic behavior between inspiration and expiration for either the chest marker and the internal motion of the heart, or the abdominal marker and the motion of the heart. In all cases we observed a good correlation of at least either the abdomen or the chest with the heart. Based on this result, we propose the use of marker motion from both the chest and abdomen regions when estimating the internal heart motion to detect and address hysteresis when binning list-mode emission data.

Use of MRI to assess the prediction of heart motion with gross body motion in myocardial perfusion imaging by stereotracking of markers on the body surface.

PURPOSE: The aim of this study is to determine using MRI in volunteers whether the rigid-body-motion (RBM) model can be approximately used to estimate the gross body-motion of the heart from that of external markers on patient's chest. Our target clinical application is to use a visual-tracking-system (VTS) which employs stereoimaging to estimate heart motion during SPECT/CT and PET∕CT myocardial perfusion imaging. METHODS: To investigate body-motion separate from the respiration the authors had the volunteers hold their breath during the acquisition of a sequence of two sets of EKG-triggered MRI sagittal slices. The first set was acquired pre-motion, and the second postmotion. The motion of the heart within each breath-hold set of slices was estimated by registration to the semiautomatic 3D segmentation of the heart region in a baseline set acquired using the Navigator technique. The motion of the heart between the pre- and postmotion sets was then determined as the difference in the individual motions in comparison to the Navigator sets. An analysis of the combined motion of the individual markers on the chest was used to obtain an estimate of the six-degree-of-freedom RBM from the VTS system. The metric for judging agreement between the motion estimated by MRI and the VTS was the average error. This was defined as the average of the magnitudes of the differences in the vector displacements of all voxels in the heart region. Studies with the Data Spectrum Anthropomorphic Phantom and "No-Motion" studies in which the volunteer did not intentionally move were used to establish a baseline for agreement. With volunteer studies a t-test was employed to determine when statistically significant differences in Average Errors occurred compared to the No-motion studies. RESULTS: For phantom acquisitions, the Average Error when the motion was just translation was 0.1 mm. With complex motions, which included a combination of rotations and translations, the Average Error increased to 3.6 mm. In the volunteers the Average Error averaged over all No-Motion acquisitions was 1.0 mm. For the case of translational motion, which might be expected to be RBM, the Average Error averaged over all volunteer studies increased to 2.6 mm, which was statistically different from the No-Motion studies. For the case of bends and twists of the torso, which would be expected to challenge the RBM model, the Average Error averaged over all such volunteer studies was 4.9 mm and was again statistically different. Investigations of motion of the arm including just bending at the elbow and leg motion resulted in Average Errors which were not statistically different from the No-Motion studies. However, when shoulder movement was included with arm motion the Average Error was near that of torso bends and twists, and statistically different. CONCLUSIONS: Use of the RBM model with VTS predictions of heart motion during reconstruction should decrease the extent of artifacts for the types of patient motion studied. The impact of correction would be less for torso bends and twists, and arm motion which includes the shoulders.

4D reconstruction for low-dose cardiac gated SPECT.

PURPOSE: Due to the combination of high-frequency use and relatively high diagnostic radiation dose (>9 mSv for one scan), there is a need to lower the radiation dose used in myocardial perfusion imaging (MPI) studies in cardiac gated single photon emission computed tomography (GSPECT) in order to reduce its population based cancer risk. The aim of this study is to assess quantitatively the potential utility of advanced 4D reconstruction for GSPECT for significantly lowered imaging dose. METHODS: For quantitative evaluation, Monte Carlo simulation with the 4D NURBS-based cardiac-torso (NCAT) phantom is used for GSPECT imaging at half and quarter count levels in the projections emulating lower injected activity (dose) levels. Both 4D and 3D reconstruction methods are applied at these lowered dose levels, and compared with standard clinical spatiotemporal reconstruction (ST121) at full dose using a number of metrics on the reconstructed images: (1) overall reconstruction accuracy of the myocardium, (2) regional bias-variance analysis of the left ventricle (LV) wall, (3) uniformity of the LV wall, (4) accuracy of the time activity curve (TAC) of the LV wall, and (5) detectability of perfusion defects using channelized Hotelling observer. As a preliminary demonstration, two sets of patient data acquired in list-mode are used to illustrate the conservation of both image quality and LV ejection fraction (LVEF) by 4D reconstruction where only a portion of the acquired counts at each projection angle are used to mimic low-dose acquisitions. RESULTS: Compared to ST121 at standard dose, even at quarter dose 4D achieved better performance on overall reconstruction accuracy of the myocardium (28.7% improvement on relative root mean square error: standard vs 4D quarter p-value < 10(-30)), regional bias-variance analysis, and similar performance on accuracy of the TAC of the LV wall and detectability of perfusion defects. A slight degradation in uniformity of the LV wall was observed in 4D at quarter dose due to use of scatter correction which increases reconstruction variance. The reconstructed images from simulated and patient data show that 4D at quarter dose is visually comparable to ST121 at standard dose, if not better. Compared to ST121 and 3D, 4D images exhibit less noise artifacts and better definition of the LV wall. The 4D images are also observed to be more consistent between half dose and quarter dose. 4D also yields more consistent LVEF results at different count levels on the patient data. CONCLUSIONS: With various quantitative metrics 4D reconstruction is demonstrated to achieve better or comparable performance at quarter dose (∼2.25 mSv, 75% dose reduction) compared to conventional clinical reconstruction at standard dose (∼9 mSv). Preliminary results from two patient datasets also show that 4D at an equivalent quarter dose can achieve better performance than clinical and 3D methods at higher dose levels. Such a significant dose reduction (75%) has not been demonstrated quantitatively in previous studies in GSPECT. These promising results warrant further investigations on the lower bound of dose reduction with different reconstruction strategies and more comprehensive clinical studies with greater patient variability.

Improvement of Performance of Cardiac SPECT Camera Using Curved Detectors With Pinholes.

SPECT is primarily used in the clinic for cardiac myocardial perfusion imaging. However, for SPECT, sensitivity is impaired due to the need for collimation. System resolution FWHM is poor as well (~ 1 cm). In this work the resolution of a curved detector was theoretically derived. The advantage of a curved detector over a flat detector with pinhole collimation was demonstrated for cardiac applications using theoretical derivations as well as a ray-tracing voxel-based forward projector. For the flat detector using parameters close to what was expected for the new multi-pinhole GE Discovery system, it is shown that using a paraboloid detector one may obtain a better system resolution (about 29% better on the average), keeping same pinhole opening. Alternately, sensitivity gains of as much as 2.25 may be obtained, for similar resolutions as a flat detector by just using a different pinhole with higher hole-diameter.

Estimation and correction of cardiac respiratory motion in SPECT in the presence of limited-angle effects due to irregular respiration.

PURPOSE: One issue with amplitude binning list-mode studies in SPECT for respiratory motion correction is that variation in the patient's respiratory pattern will result in binned motion states with little or no counts at various projection angles. The reduced counts result in limited-angle reconstruction artifacts which can impact the accuracy of the necessary motion estimation needed to correct the images. In this work, the authors investigate a method to overcome the effect of limited-angle reconstruction artifacts in SPECT when estimating respiratory motion. METHODS: In the first pass of the reconstruction method, only the projection angles with significant counts in common between the binned respiratory states are used in order to better estimate the motion between them. After motion estimation, the estimates are used to correct for motion within iterative reconstruction using all of the acquired projection data. RESULTS: Using simulated SPECT studies based on the NCAT phantom, the authors demonstrate the problem caused by having data available for only a limited number of angles when estimating motion and the utility of the proposed method in diminishing this error. For NCAT data sets with a clinically appropriate level of Poisson noise, the average registration error for motion with the proposed method was always less with the use of their algorithm, the reduction being statistically significant (p<0.05) in the majority of cases. The authors illustrate the ability of their method to correct the degradations caused by respiratory motion in short-axis slices and polar maps of the NCAT phantom for cases with 1 and 2 cm amplitudes of respiratory motion. In four cardiac-perfusion patients acquired on the same day, the authors demonstrate the large variability of the number of counts in the amplitude-binned projections. Finally, the authors demonstrate a visual improvement in the slices and polar maps of patient studies with the algorithm for respiratory motion correction. CONCLUSIONS: The authors' method shows promise in reducing errors in respiratory motion estimation despite the presence of limited-angle reconstruction effects due to irregularity in respiration. Improvements in image quality were observed in both simulated and clinical studies.

A flexible multicamera visual-tracking system for detecting and correcting motion-induced artifacts in cardiac SPECT slices.

Patient motion is inevitable in SPECT and PET due to the lengthy period of time patients are imaged. The authors hypothesized that the use of external-tracking devices which provide additional information on patient motion independent of SPECT data could be employed to provide a more robust correction than obtainable from data-driven methods. Therefore, the authors investigated the Vicon MX visual-tracking system (VTS) which utilizes near-infrared (NIR) cameras to stereo-image small retroreflective markers on stretchy bands wrapped about the chest and abdomen of patients during cardiac SPECT. The chest markers are used to provide an estimate of the rigid-body (RB) motion of the heart. The abdomen markers are used to provide a signal used to bin list-mode acquisitions as part of correction of respiratory motion of the heart. The system is flexible in that the layout of the cameras can be designed to facilitate marker viewing. The system also automatically adapts marker tracking to employ all of the cameras visualizing a marker at any instant, with visualization by any two being sufficient for stereo-tracking. Herein the ability of this VTS to track motion with submillimeter and subdegree accuracy is established through studies comparing the motion of Tc-99m containing markers as assessed via stereo-tracking and from SPECT reconstructions. The temporal synchronization between motion-tracking data and timing marks embedded in list-mode SPECT acquisitions is shown to agree within 100 ms. In addition, motion artifacts were considerably reduced in reconstructed SPECT slices of an anthropomorphic phantom by employing within iterative reconstruction the motion-tracking information from markers attached to the phantom. The authors assessed the number and placement of NIR cameras required for robust motion tracking of markers during clinical imaging in 77 SPECT patients. They determined that they were able to track without loss during the entire period of SPECT and transmission imaging at least three of the four markers on the chest and one on the abdomen bands 94% and 92% of the time, respectively. The ability of the VTS to correct motion clinically is illustrated for ten patients who volunteered to undergo repeat-rest imaging with the original-rest SPECT study serving as the standard against which to compare the success of correction. Comparison of short-axis slices shows that VTS-based motion correction provides better agreement with the original-rest-imaging slices than either no correction or the vendor-supplied software for motion correction on, our SPECT system. Comparison of polar maps shows that VTS-based motion-correction results in less numerical difference on average in the segments of the polar maps between the original-rest study and the second-rest study than the other two strategies. The difference was statistically significant for the comparison between VTS-based and clinical vendor-supplied software correction. Taken together, these findings suggest that VTS-based motion correction is superior to either no-motion correction or the vendor-supplied software the authors investigated in clinical practice.

Estimation of Rigid-Body and Respiratory Motion of the Heart From Marker-Tracking Data for SPECT Motion Correction.

Motion of patients undergoing cardiac SPECT perfusion imaging causes artifacts in the acquired images which may lead to difficulty in interpretation. Our work investigates a technique of obtaining patient motion estimates from retro-reflective markers on stretchy bands wrapped around the chest and abdomen of patients being imaged clinically. Motion signals obtained from the markers consist of at least two components, body motion (BM) and periodic motion (PM) due to respiration. We present a method for separating these components from the motion-tracking data of each marker, and then report a method for combining the BM estimated from chest markers to estimate the 6-degree-of-freedom (6-DOF) rigid-body motion (RBM) of the heart. Motion studies of volunteers and patients are used to evaluate the methods. Illustrative examples of the motion of the heart due to patient body movement and respiration (upward creep) are presented and compared to estimates of the motion of the heart obtained directly from SPECT data. Our motion-tracking method is seen to give reasonable agreement with the motion-estimates from the SPECT data while being considerably less noisy.

Estimation of Cardiac Respiratory-Motion by Semi-Automatic Segmentation and Registration of Non-Contrast-Enhanced 4D-CT Cardiac Datasets.

The goal of this work is to investigate, for a large set of patients, the motion of the heart with respiration during free-breathing supine medical imaging. For this purpose we analyzed the motion of the heart in 32 non-contrast enhanced respiratory-gated 4D-CT datasets acquired during quiet unconstrained breathing. The respiratory-gated CT images covered the cardiac region and were acquired at each of 10 stages of the respiratory cycle, with the first stage being end-inspiration. We devised a 3-D semi-automated segmentation algorithm that segments the heart in the 4D-CT datasets acquired without contrast enhancement for use in estimating respiratory motion of the heart. Our semi-automated segmentation results were compared against interactive hand segmentations of the coronal slices by a cardiologist and a radiologist. The pairwise difference in segmentation among the algorithm and the physicians was on the average 11% and 10% of the total average segmented volume across the patient, with a couple of patients as outliers above the 95% agreement limit. The mean difference among the two physicians was 8% with an outlier above the 95% agreement limit. The 3-D segmentation was an order of magnitude faster than the Physicians' manual segmentation and represents significant reduction of Physicians' time. The segmented first stages of respiration were used in 12 degree-of-freedom (DOF) affine registration to estimate the motion at each subsequent stage of respiration. The registration results from the 32 patients indicate that the translation in the superior-inferior direction was the largest component motion, with a maximum of 10.7 mm, mean of 6.4 mm, and standard deviation of 2.2 mm. Translation in the anterior-posterior direction was the next largest component of motion, with a maximum of 4.0 mm, mean of 1.7 mm, and standard deviation of 1.0 mm. Rotation about the right-left axis was on average the largest component of rotation observed, with a maximum of 4.6 degrees, mean of 1.6 degrees, and standard deviation of 2.1 degrees. The other rotation and shear parameters were all close to zero on average indicting the motion could be reasonably well approximated by rigid-body motion. However, the product of the three scale factors averaged about 0.97 indicating the possibility of a small decrease in heart volume with expiration. The motion results were similar whether we used the Physician's segmentation or the 3-D algorithm.