Arda Konik

GATE Simulations of Human and Small Animal PET for Determination of Scatter Fraction as a Function of Object Size

In 2D-mode positron emission tomography (PET), scatter is either compensated by approximate methods based on the existing emission data or ignored altogether as the magnitude of the scatter fraction (SF) is on the order of 10%-20%. In clinical PET studies, however, attenuation and sophisticated scatter correction methods are required along with CT or radionuclide transmission scans. With the growing interest in small animal imaging, these correction methods are being translated to small animal scanners, but there is little scientific information about the requirements associated with smaller size objects and scatter geometries. In this study, we focused on the magnitude of the scatter through a series of scatter fraction simulations. To determine the scatter as a function of object size, we performed Monte Carlo simulations using GATE (Geant4 application for emission tomography). Models of the ECAT HR+ PET scanner (included in the GATE package) and the Siemens Inveon small animal scanner (generated by the first author) were used. Simulations were performed for several digital phantoms including the NEMA, XCAT and MOBY phantoms over a wide range of sizes. Small animal NEMA-like phantoms indicated that for cylindrical objects less than 5 cm diameters (encompassing small rats and all mice), the scatter fraction was lower than 17.5% for the 350-650 keV and 20% for the 250-750 keV windows. Similar values were obtained for the MOBY phantoms for the respective sizes. On the other hand, the scatter fraction was more than 35% for even the smallest size human NEMA-like and XCAT phantoms. These results suggest that sophisticated scatter correction methods may not be required for the indicated sizes of mice and rats.

Evaluation of Attenuation and Scatter Correction Requirements as a Function of Object Size in Small Animal PET Imaging

In human emission tomography, an additional transmission scan (x-ray CT or external gamma-source) is often required to obtain accurate attenuation maps for attenuation correction (AC) and scatter correction (SC). These transmission-based correction methods have been translated to small animal imaging although the impact of photon interactions on the mouse/rat-reconstructed images is substantially less than that in human imaging. Considering the additional complexity in design and cost of these systems, the necessity of these correction methods is questionable for small animal emission tomography. In this study, we evaluate the requirement of these corrections for small animal positron emission tomography (PET) through Monte Carlo simulations of the Inveon PET scanner using various sizes of MOBY voxelized phantoms. The 3D sinogram data obtained from simulations were reconstructed in 6 different conditions: Accurate AC+SC, simple (water) AC+SC, accurate AC only, simple AC only, SC only and no correction (NC). Mean error% for 8 different ROIs and 6 different MOBY sizes were obtained against the accurate scatter and attenuation corrections (first on the list). In addition to simulations, real mouse data obtained from an Inveon PET scanner were analyzed using similar methods. Results from both simulation and real mouse data showed that attenuation correction based on solely emission data should be sufficient for imaging animals smaller than 4 cm diameter. For larger sizes, a scatter correction employing an additional transmission scan can also be included depending on the objective of the study.

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.

GATE Simulations of Small Animal SPECT for Determination of Scatter Fraction as a Function of Object Size

In human emission tomography, combined PET/CT and SPECT/CT cameras provide accurate attenuation maps for sophisticated scatter and attenuation corrections. Having proven their potential, these scanners are being adapted for small animal imaging using similar correction approaches. However, attenuation and scatter effects in small animal imaging are substantially less than in human imaging. Hence, the value of sophisticated corrections is not obvious for small animal imaging considering the additional cost and complexity of these methods. In this study, using GATE Monte Carlo package, we simulated the Inveon small animal SPECT (single pinhole collimator) scanner to find the scatter fractions of various sizes of the NEMA-mouse (diameter: 2-5.5 cm , length: 7 cm), NEMA-rat (diameter: 3-5.5 cm, length: 15 cm) and MOBY (diameter: 2.1-5.5 cm, length: 3.5-9.1 cm) phantoms. The simulations were performed for three radionuclides commonly used in small animal SPECT studies:99mTc (140 keV), 111In (171 keV 90% and 245 keV 94%) and 125I (effective 27.5 keV). For the MOBY phantoms, the total Compton scatter fractions ranged (over the range of phantom sizes) from 4-10% for 99mTc (126-154 keV), 7-16% for 111In (154-188 keV), 3-7% for 111In (220-270 keV) and 17-30% for 125I (15-45 keV) including the scatter contributions from the tungsten collimator, lead shield and air (inside and outside the camera heads). For the NEMA-rat phantoms, the scatter fractions ranged from 10-15% (99mTc), 17-23% 111In: 154-188 keV), 8-12% (111In: 220-270 keV) and 32-40% (125I). Our results suggest that energy window methods based on solely emission data are sufficient for all mouse and most rat studies for 99mTc and 111In. However, more sophisticated methods may be needed for 125I.

Design of a combined fan and multi-pinhole collimator combination for clinical I-123 DaTscan imaging on dual-headed SPECT systems

For the recently FDA approved Parkinsons Disease (PD) SPECT imaging agent I-123 labeled DaTscan the volume of interest (VOl) 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 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 SBRs. Herein we analyze 20 clinical DaTscan studies to provide information on the VOl, and then design a MPH collimator to image this VOl. Using standard collimator equations we determine a system spatial resolution for the MPH of 4.4 mm which is comparable to that of clinical PET systems, and significantly smaller than that of fan-beam collimators employed in SPECT. The combined sensitivity of the apertures of the MPH was larger than 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 early results we propose the exploration of further improvements in design, and the development of combined MPH and fan-beam reconstruction.

Combined respiratory and rigid body motion compensation in cardiac perfusion SPECT using a visual tracking system

We report on the validation of our combined respiratory and rigid body motion compensation strategy through acquisitions of the Data Spectrum anthropomorphic phantom, and investigation of clinical efficacy and robustness in 25 cardiac perfusion patient studies, employing a visual tracking system (VTS). The heart and liver was filled with a 2∶1 concentration of Tc-99m and two sets of SPECT data were acquired. Each set of SPECT data consisted of a rest-perfusion baseline frame-mode emission acquisition, a Beacon (Philips, Cleveland, OH) transmission acquisition, and a list-mode emission acquisition. Respiratory motion was simulated during the list-mode acquisitions using the Quasar (Modus Medical Devices Inc. ON, Canada). Rigid-body motion was introduced in one of the two list-mode acquisitions by rotating the phantom around the x-axis and translating the phantom in x, y, and z. Patient volunteers with written consent were similarly acquired and asked to execute some predefined body motion during the list-mode acquisition. Motion tracking was performed using 6 near infrared Vicon cameras in combination with 7 retro-reflective markers, 5 placed on the chests of both patient volunteers and phantom, 2 placed on the abdomen of patient volunteers, and 2 placed on the vertical motion stage of the Quasar to simulate abdominal phantom motion. Processing steps included, down sampling VTS positional data to 10 Hz (100 ms) and synchronized with 100 ms SPECT frames, separating rigid body and respiratory motion and estimating 6 DOF rigid body motion, amplitude bin 100 ms frames into respiratory projection sets, reconstruct with rigid body motion compensation respiratory projection sets, estimated respiratory motion employing intensity based estimation, combine rigid body and respiratory motion, and reconstruct with combined compensation. We showed for both phantom and patient acquisitions that combined respiratory and rigid body motion compensation improve the visual appearance of slices.

Correction of hysteretic respiratory motion in SPECT myocardial perfusion imaging: Simulation and patient studies

Purpose: Amplitude‐based respiratory gating is known to capture the extent of respiratory motion (RM) accurately but results in residual motion in the presence of respiratory hysteresis. In our previous study, we proposed and developed a novel approach to account for respiratory hysteresis by applying the Bouc–Wen (BW) model of hysteresis to external surrogate signals of anterior/posterior motion of the abdomen and chest with respiration. In this work, using simulated and clinical SPECT myocardial perfusion imaging (MPI) studies, we investigate the effects of respiratory hysteresis and evaluate the benefit of correcting it using the proposed BW model in comparison with the abdomen signal typically employed clinically. Methods: The MRI navigator data acquired in free‐breathing human volunteers were used in the specially modified 4D NCAT phantoms to allow simulating three types of respiratory patterns: monotonic, mild hysteresis, and strong hysteresis with normal myocardial uptake, and perfusion defects in the anterior, lateral, inferior, and septal locations of the mid‐ventricular wall. Clinical scans were performed using a Tc‐99m sestamibi MPI protocol while recording respiratory signals from thoracic and abdomen regions using a visual tracking system (VTS). The performance of the correction using the respiratory signals was assessed through polar map analysis in phantom and 10 clinical studies selected on the basis of having substantial RM. Results: In phantom studies, simulations illustrating normal myocardial uptake showed significant differences (P < 0.001) in the uniformity of the polar maps between the RM uncorrected and corrected. No significant differences were seen in the polar map uniformity across the RM corrections. Studies simulating perfusion defects showed significantly decreased errors (P < 0.001) in defect severity and extent for the RM corrected compared to the uncorrected. Only for the strong hysteretic pattern, there was a significant difference (P < 0.001) among the RM corrections. The errors in defect severity and extent for the RM correction using abdomen signal were significantly higher compared to that of the BW (severity = −4.0%, P < 0.001; extent = −65.4%, P < 0.01) and chest (severity = −4.1%, P < 0.001; extent = −52.5%, P < 0.01) signals. In clinical studies, the quantitative analysis of the polar maps demonstrated qualitative and quantitative but not statistically significant differences (P = 0.73) between the correction methods that used the BW signal and the abdominal signal. Conclusions: This study shows that hysteresis in respiration affects the extent of residual motion left in the RM‐binned data, which can impact wall uniformity and the visualization of defects. Thus, there appears to be the potential for improved accuracy in reconstruction in the presence of hysteretic RM with the BW model method providing a possible step in the direction of improvement.

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 Parkinsons 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 SBRs. 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.

Comparison of the scanning linear estimator (SLE) and ROI methods for quantitative SPECT imaging

In quantitative emission tomography, tumor activity is typically estimated from calculations on a region of interest (ROI) identified in the reconstructed slices. In these calculations, unpredictable bias arising from the null functions of the imaging system affects ROI estimates. The magnitude of this bias depends upon the tumor size and location. In prior work it has been shown that the scanning linear estimator (SLE), which operates on the raw projection data, is an unbiased estimator of activity when the size and location of the tumor are known. In this work, we performed analytic simulation of SPECT imaging with a parallel-hole medium-energy collimator. Distance-dependent system spatial resolution and non-uniform attenuation were included in the imaging simulation. We compared the task of activity estimation by the ROI and SLE methods for a range of tumor sizes (diameter: 1-3 cm) and activities (contrast ratio: 1-10) added to uniform and non-uniform liver backgrounds. Using the correct value for the tumor shape and location is an idealized approximation to how task estimation would occur clinically. Thus we determined how perturbing this idealized prior knowledge impacted the performance of both techniques. To implement the SLE for the non-uniform background, we used a novel iterative algorithm for pre-whitening stationary noise within a compact region. Estimation task performance was compared using the ensemble mean-squared error (EMSE) as the criterion. The SLE method performed substantially better than the ROI method (i.e. EMSE(SLE) was 23-174 times lower) when the background is uniform and tumor location and size are known accurately. The variance of the SLE increased when a non-uniform liver texture was introduced but the EMSE(SLE) continued to be 5-20 times lower than the ROI method. In summary, SLE outperformed ROI under almost all conditions that we tested.

Comparison of ECG derived respiratory signals and pneumatic bellows for respiratory motion tracking

The respiratory motion of the heart causes inaccuracies in the cardiac emission tomography reconstructions, which can mislead diagnosis. Various motion-tracking methods using specialized instruments have been developed to compensate for the cardiac respiratory motion. However, most of these methods tend to be time consuming, costly and require additional effort both from patients and technicians. In this study, we investigated the performance of a tool which derives a signal related to respiration from the patients ECG. The method is called ECG/EMG derived respiration (EDR) and with it the respiratory signal is obtained from the ECG signals already being acquired during a cardiac study, without needing any additional instrument or set-up. We compared the EDR with pneumatic bellows placed on chest and abdomen to determine if the signal from EDR may be used as a surrogate for the bellows for respiratory motion correction. Preliminary results show that the EDR had better amplitude and phase correlation with the abdominal bellow than that between the bellows or between the EDR and chest bellow. The EDR is also affected by volunteer motion like other external surrogate devices. However, this can be used to our advantage as a source of information about the timing of changes in patient motion states for use in data-driven motion correction.