A combined static-dynamic single-dose imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT.

BACKGROUND: SPECT myocardial perfusion imaging (MPI) is a clinical mainstay that is typically performed with static imaging protocols and visually or semi-quantitatively assessed for perfusion defects based upon the relative intensity of myocardial regions. Dynamic cardiac SPECT presents a new imaging technique based on time-varying information of radiotracer distribution, which permits the evaluation of regional myocardial blood flow (MBF) and coronary flow reserve (CFR). In this work, a preliminary feasibility study was conducted in a small patient sample designed to implement a unique combined static-dynamic single-dose one-day visit imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT for improving the diagnosis of coronary artery disease (CAD). METHODS: Fifteen patients (11 males, four females, mean age 71 ± 9 years) were enrolled for a combined dynamic and static SPECT (Infinia Hawkeye 4, GE Healthcare) imaging protocol with a single dose of 99mTc-tetrofosmin administered at rest and a single dose administered at stress in a one-day visit. Out of 15 patients, eleven had selective coronary angiography (SCA), 8 within 6 months and the rest within 24 months of SPECT imaging, without intervening symptoms or interventions. The extent and severity of perfusion defects in each myocardial region was graded visually. Dynamically acquired data were also used to estimate the MBF and CFR. Both visually graded images and estimated CFR were tested against SCA as a reference to evaluate the validity of the methods. RESULTS: Overall, conventional static SPECT was normal in ten patients and abnormal in five patients, dynamic SPECT was normal in 12 patients and abnormal in three patients, and CFR from dynamic SPECT was normal in nine patients and abnormal in six patients. Among those 11 patients with SCA, conventional SPECT was normal in 5, 3 with documented CAD on SCA with an overall accuracy of 64%, sensitivity of 40% and specificity of 83%. Dynamic SPECT image analysis also produced a similar accuracy, sensitivity, and specificity. CFR was normal in 6, each with CAD on SCA with an overall accuracy of 91%, sensitivity of 80%, and specificity of 100%. The mean CFR was significantly lower for SCA detected abnormal than for normal patients (3.86±1.06 vs 1.94±0. 0.67, P < 0.001). CONCLUSIONS: The visually assessed image findings in static and dynamic SPECT are subjective, and may not reflect direct physiologic measures of coronary lesion based on SCA. The CFR measured with dynamic SPECT is fully objective, with better sensitivity and specificity, available only with the data generated from the dynamic SPECT method.

Longitudinal Evaluation of Myocardial Fatty Acid and Glucose Metabolism in Fasted and Nonfasted Spontaneously Hypertensive Rats Using MicroPET/CT.

Using longitudinal micro positron emission tomography (microPET)/computed tomography (CT) studies, we quantified changes in myocardial metabolism and perfusion in spontaneously hypertensive rats (SHRs), a model of left ventricular hypertrophy (LVH). Fatty acid and glucose metabolism were quantified in the hearts of SHRs and Wistar-Kyoto (WKY) normotensive rats using long-chain fatty acid analog 18F-fluoro-6-thia heptadecanoic acid (18F-FTHA) and glucose analog 18F-fluorodeoxyglucose (18F-FDG) under normal or fasting conditions. We also used 18F-fluorodihydrorotenol (18F-FDHROL) to investigate perfusion in their hearts without fasting. Rats were imaged at 4 or 5 times over their life cycle. Compartment modeling was used to estimate the rate constants for the radiotracers. Blood samples were obtained and analyzed for glucose and free fatty acid concentrations. SHRs demonstrated no significant difference in 18F-FDHROL wash-in rate constant ( P = .1) and distribution volume ( P = .1), significantly higher 18F-FDG myocardial influx rate constant ( P = 4×10-8), and significantly lower 18F-FTHA myocardial influx rate constant ( P = .007) than WKYs during the 2009-2010 study without fasting. SHRs demonstrated a significantly higher 18F-FDHROL wash-in rate constant ( P = 5×10-6) and distribution volume ( P = 3×10-8), significantly higher 18F-FDG myocardial influx rate constant ( P = 3×10-8), and a higher trend of 18F-FTHA myocardial influx rate constant (not significant, P = .1) than WKYs during the 2011-2012 study with fasting. Changes in glucose plasma concentrations were generally negatively correlated with corresponding radiotracer influx rate constant changes. The study indicates a switch from preferred fatty acid metabolism to increased glucose metabolism with hypertrophy. Increased perfusion during the 2011-2012 study may be indicative of increased aerobic metabolism in the SHR model of LVH.

Noninvasive PET quantitative myocardial blood flow with regadenoson for assessing cardiac allograft vasculopathy in orthotopic heart transplantation patients.

BACKGROUND: Risk stratification and early detection of cardiac allograft vasculopathy (CAV) is essential in orthotopic heart transplantation (OHT) patients. This study assesses the changes in myocardial blood flow (MBF) noninvasively in OHT patients using quantitative cardiac PET with regadenoson. METHODS: Twelve patients (Group 1) (8 males, 4 females, mean age 55 ± 7 years) with no history of post OHT myocardial ischemia were enrolled 5.4 ± 2.0 years after OHT. Fifteen patients (Group 2) (9 males, 6 females, mean age 71 ± 9 years) with intermediate pretest probability but not documented evidence for coronary artery disease (CAD) were also included to serve as control. Global and regional MBFs were assessed using dynamic 13N-NH3 PET at rest and during regadenoson-induced hyperemia. The coronary flow reserve (CFR) was also calculated as the ratio of hyperemic to resting MBF. RESULTS: Mean regadenoson-induced rate-pressure products were similar in both groups, while there was an increase in resting rate-pressure product in Group 1 patients. Both mean and median values of resting MBF were higher in Group 1 than Group 2 patients (1.33 ± 0.31 and 1.01 ± 0.21 mL/min/g for Groups 1 and 2, respectively, P < .001), while mean hyperemic MBF values were similar in both Groups (2.68 ± 0.84 and 2.64 ± 0.94 mL/min/g, P = NS) but median hyperemic MBF values were lower in Group 1 than Group 2 patients (2.0 vs. 2.60 mL/min/g, P = .018). Both mean and median CFR values demonstrated a significant reduction for Group 1 compared to Group 2 patients (2.07 ± 0.74 vs 2.63 ± 0.48, P = .025). CONCLUSIONS: This study suggests that the MBF in OHT patients may be abnormal at resting state with diminished CFR. This hints that the epicardial and microvascular coronary subsystem may be exacerbated after OHT leading to the gradual progression of CAV.

Measurement of absolute myocardial blood flow in humans using dynamic cardiac SPECT and 99mTc-tetrofosmin: Method and validation.

BACKGROUND: The objective of this study was to measure myocardial blood flow (MBF) in humans using 99mTc-tetrofosmin and dynamic single-photon emission computed tomography (SPECT). METHODS: Dynamic SPECT using 99mTc-tetrofosmin and dynamic positron emission tomography (PET) was performed on a group of 16 patients. The SPECT data were reconstructed using a 4D-spatiotemporal iterative reconstruction method. The data corresponding to 9 patients were used to determine the flow-extraction curve for 99mTc-tefrofosmin while data from the remaining 7 patients were used for method validation. The nonlinear tracer correction parameters A and B for 99mTc-tefrofosmin were estimated for the 9 patients by fitting the flow-extraction curve [Formula: see text] for K 1 values estimated with 99mTc-tefrofosmin using SPECT and MBF values estimated with 13N-NH3 using PET. These parameters were then used to calculate MBF and coronary flow reserve (CFR) in three coronary territories (LAD, RCA, and LCX) using SPECT for an independent cohort of 7 patients. The results were then compared with that estimated with 13N-NH3 PET. The flow-dependent permeability surface-area product (PS) for 99mTc-tefrofosmin was also estimated. RESULTS: The estimated flow-extraction parameters for 99mTc-tefrofosmin were found to be A = 0.91 ± 0.11, B = 0.34 ± 0.20 (R 2 = 0.49). The range of MBF in LAD, RCA, and LCX was 0.44-3.81 mL/min/g. The MBF between PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r = 0.71 (P < .001). However, the corresponding CFR correlation was moderate r = 0.39 yet statistically significant (P = .037). The PS for 99mTc-tefrofosmin was (0.019 ± 0.10)*MBF + (0.32 ± 0.16). CONCLUSIONS: Dynamic cardiac SPECT using 99mTc-tetrofosmin and a clinical two-headed SPECT/CT scanner can be a useful tool for estimation of MBF.

Longitudinal Evaluation of Sympathetic Nervous System and Perfusion in Normal and Spontaneously Hypertensive Rat Hearts with Dynamic Single-Photon Emission Computed Tomography.

The objective of this work was to evaluate the sympathetic nervous system and structure remodeling during the progression of heart failure in a rodent model using dynamic cardiac single-photon emission computed tomography (SPECT). The spontaneously hypertensive rat (SHR) model was used to study changes in the nervous system innervation and perfusion in the left ventricular (LV) myocardium with the progression of left ventricular hypertrophy (LVH) to heart failure. Longitudinal dynamic SPECT studies were performed with seven SHR and seven Wistar-Kyoto (WKY) rats over 1.5 years using a dual-head SPECT scanner with pinhole collimators. Time-activity curves (TACs) of the 123I-MIBG and 201Tl distribution in the LV blood pool and myocardium were extracted from dynamic SPECT data and fitted to compartment models to determine the influx rate, washout rate, and distribution volume (DV) of 123I-MIBG and 201Tl in the LV myocardium. The standardized uptake values (SUVs) of 123I-MIBG and 201Tl in the LV myocardium were also calculated from the static reconstructed images. The influx and washout rates of 123I-MIBG did not show a significant difference between SHRs and WKY rats. The DVs of 123I-MIBG were greater in the SHRs than in the WKY rats (p = .0028). Specifically, the DV of 123I-MIBG became greater in the SHRs by 6 months of age (p = .0017) and was still significant at the age of 22 months. The SUV of 123I-MIBG in SHRs exhibited abnormal values compared to WKY rats from the age of 18 months. There was no difference in the influx rate and the washout rate of 201Tl between the SHRs and WKY rats. The SHRs exhibited greater DV of 201Tl than WKY rats after the age of 18 months (p = .034). The SUV of 201Tl in SHRs did not show any significant difference from WKY at all ages. The higher DV of 123I-MIBG in the LV myocardium reveals abnormal nervous system activity of the SHRs at an age of 6 months, whereas a greater DV of 201Tl in the LV myocardium can only be detected at an age of 18 months. The results show that the abnormal nervous system activity appears earlier than perfusion. Furthermore, the comparison between the DV and the SUV indicates that dynamic SPECT with 123I-MIBG and 201Tl with the kinetic parameter DV is capable of detecting abnormalities of the LV at an early age.

The direct incorporation of perfusion defect information to define ischemia and infarction in a finite element model of the left ventricle.

This paper describes the process in which complex lesion geometries (specified by computer generated perfusion defects) are incorporated in the description of nonlinear finite element (FE) mechanical models used for specifying the motion of the left ventricle (LV) in the 4D extended cardiac torso (XCAT) phantom to simulate gated cardiac image data. An image interrogation process was developed to define the elements in the LV mesh as ischemic or infarcted based upon the values of sampled intensity levels of the perfusion maps. The intensity values were determined for each of the interior integration points of every element of the FE mesh. The average element intensity levels were then determined. The elements with average intensity values below a user-controlled threshold were defined as ischemic or infarcted depending upon the model being defined. For the infarction model cases, the thresholding and interrogation process were repeated in order to define a border zone (BZ) surrounding the infarction. This methodology was evaluated using perfusion maps created by the perfusion cardiac-torso (PCAT) phantom an extension of the 4D XCAT phantom. The PCAT was used to create 3D perfusion maps representing 90% occlusions at four locations (left anterior descending (LAD) segments 6 and 9, left circumflex (LCX) segment 11, right coronary artery (RCA) segment 1) in the coronary tree. The volumes and shapes of the defects defined in the FE mechanical models were compared with perfusion maps produced by the PCAT. The models were incorporated into the XCAT phantom. The ischemia models had reduced stroke volume (SV) by 18-59 ml. and ejection fraction (EF) values by 14-50% points compared to the normal models. The infarction models, had less reductions in SV and EF, 17-54 ml. and 14-45% points, respectively. The volumes of the ischemic/infarcted regions of the models were nearly identical to those volumes obtained from the perfusion images and were highly correlated (R² = 0.99).

Improved trabecular bone structure of 20-month-old male spontaneously hypertensive rats.

A few clinical studies have reported that elderly male participants with hypertensive disease frequently have higher bone mineral density (BMD) than the normotensive participants at several skeletal sites. The detailed mechanism is still unknown; therefore, a study of bone structure and density using the hypertensive animal models could be informative. We used micro-computed tomography to quantitatively evaluate the tibial and 3rd lumbar vertebral bones in the 20-month-old male spontaneous hypertensive rat (SHR). The BMD, volume fraction, and the microarchitecture changes of the SHR were compared to those of same-age normotensive controls (Wistar-Kyoto rat, WKY). We found that in the very old (20 month) male rats, the trabecular bone fraction and microstructure were higher than those in the same-age normotensive controls. The observation of the association of hypertension with BMD and bone strength in hypertensive rats warrants further investigations of bone mass and strength in elderly males with hypertension.

A Technique to Quantify Very Low Activities in Regions of Interest With a Collimatorless Detector.

We present a new method to measure sub-microcurie activities of photon-emitting radionuclides in organs and lesions of small animals in vivo. Our technique, named the collimator-less likelihood fit, combines a very high sensitivity collimatorless detector with a Monte Carlo-based likelihood fit in order to estimate the activities in previously segmented regions of interest along with their uncertainties. This is done directly from the photon projections in our collimatorless detector and from the region of interest segmentation provided by an x-ray computed tomography scan. We have extensively validated our approach with 225Ac experimentally in spherical phantoms and mouse phantoms, and also numerically with simulations of a realistic mouse anatomy. Our method yields statistically unbiased results with uncertainties smaller than 20% for activities as low as ~111Bq (3nCi) and for exposures under 30 minutes. We demonstrate that our method yields more robust recovery coefficients when compared to SPECT imaging with a commercial pre-clinical scanner, specially at very low activities. Thus, our technique is complementary to traditional SPECT/CT imaging since it provides a more accurate and precise organ and tumor dosimetry, with a more limited spatial information. Finally, our technique is specially significant in extremely low-activity scenarios when SPECT/CT imaging is simply not viable.

A generalization of the maximum likelihood expectation maximization (MLEM) method: Masked-MLEM.

Objective.In our previous work on image reconstruction for single-layer collimatorless scintigraphy, we developed the min-min weighted robust least squares (WRLS) optimization algorithm to address the challenge of reconstructing images when both the system matrix and the projection data are uncertain. Whereas the WRLS algorithm has been successful in two-dimensional (2D) reconstruction, expanding it to three-dimensional (3D) reconstruction is difficult since the WRLS optimization problem is neither smooth nor strongly-convex. To overcome these difficulties and achieve robust image reconstruction in the presence of system uncertainties and projection noise, we propose a generalized iterative method based on the maximum likelihood expectation maximization (MLEM) algorithm, hereinafter referred to as the Masked-MLEM algorithm.Approach.In the Masked-MLEM algorithm, only selected subsets ('masks') from the system matrix and the projection contribute to the image update to satisfy the constraints imposed by the system uncertainties. We validate the Masked-MLEM algorithm and compare it to the standard MLEM algorithm using experimental data obtained from both collimated and uncollimated imaging instruments, including parallel-hole collimated SPECT, 2D collimatorless scintigraphy, and 3D collimatorless tomography. Additionally, we conduct comprehensive Monte Carlo simulations for 3D collimatorless tomography to further validate the effectiveness of the Masked-MLEM algorithm in handling different levels of system uncertainties.Main results.The Masked-MLEM and standard MLEM reconstructions are similar in cases with negligible system uncertainties, whereas the Masked-MLEM algorithm outperforms the standard MLEM algorithm when the system matrix is an approximation. Importantly, the Masked-MLEM algorithm ensures reliable image reconstruction across varying levels of system uncertainties.Significance.With a good choice of system uncertainty and without requiring accurate knowledge of the actual system matrix, the Masked-MLEM algorithm yields more robust image reconstruction than the standard MLEM algorithm, effectively reducing the likelihood of erroneously reconstructing higher activities in regions without radioactive sources.

Fourier domain closed-form formulas for estimation of kinetic parameters in reversible multi-compartment models.

BACKGROUND: Compared with static imaging, dynamic emission computed tomographic imaging with compartment modeling can quantify in vivo physiologic processes, providing useful information about molecular disease processes. Dynamic imaging involves estimation of kinetic rate parameters. For multi-compartment models, kinetic parameter estimation can be computationally demanding and problematic with local minima. METHODS: This paper offers a new perspective to the compartment model fitting problem where Fourier linear system theory is applied to derive closed-form formulas for estimating kinetic parameters for the two-compartment model. The proposed Fourier domain estimation method provides a unique solution, and offers very different noise response as compared to traditional non-linear chi-squared minimization techniques. RESULTS: The unique feature of the proposed Fourier domain method is that only low frequency components are used for kinetic parameter estimation, where the DC (i.e., the zero frequency) component in the data is treated as the most important information, and high frequency components that tend to be corrupted by statistical noise are discarded. Computer simulations show that the proposed method is robust without having to specify the initial condition. The resultant solution can be fine tuned using the traditional iterative method. CONCLUSIONS: The proposed Fourier-domain estimation method has closed-form formulas. The proposed Fourier-domain curve-fitting method does not require an initial condition, it minimizes a quadratic objective function and a closed-form solution can be obtained. The noise is easier to control, simply by discarding the high frequency components, and emphasizing the DC component.

Imaging and modeling of flow in porous media using clinical nuclear emission tomography systems and computational fluid dynamics.

This paper presents experimental and modeling aspects of applying nuclear emission tomography to study fluid flow in laboratory packed porous media columns of the type frequently used in geophysics, geochemistry and hydrology research. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are used as non-invasive tools to obtain dynamic 3D images of radioactive tracer concentrations. Dynamic sequences obtained using 18F-FDG PET are used to trace flow through a 5 cm diameter × 20 cm tall sand packed column with and without an impermeable obstacle. In addition, a custom-made rotating column setup placed in a clinical two-headed SPECT camera is used to image 99mTc-DTPA tracer propagation in a through-flowing column (10 cm diameter × 30 cm tall) packed with recovered aquifer sediments. A computational fluid dynamics software package FLUENT is used to model the observed flow dynamics. Tracer distributions obtained in the simulations in the smaller column uniformly packed with sand and in the column with an obstacle are remarkably similar to the reconstructed images in the PET experiments. SPECT results demonstrate strongly non-uniform flow patterns for the larger column slurry-packed with sub-surface sediment and slow upward flow. In the numerical simulation of the SPECT study, two symmetric channels with increased permeability are prescribed along the column walls, which result in the emergence of two well-defined preferential flow paths. Methods and results of this work provide new opportunities in hydrologic and biogeochemical research. The primary target application for developed technologies is non-destructive, non-perturbing, quantitative imaging of flow dynamics within laboratory scale porous media systems.

Compton and proximity imaging of 225Ac in vivo with a CZT gamma camera: a proof of principle with simulations.

In vivo imaging of 225Ac is a major challenge in the development of targeted alpha therapy radiopharmaceuticals due to the extremely low injected doses. In this paper, we present the design of a multi-modality gamma camera that integrates both proximity and Compton imaging in order to achieve the demanding sensitivities required to image 225Ac with good image quality. We consider a dual-head camera, each of the heads consisting of two planar cadmium zinc telluride detectors acting as scatterer and absorber for Compton imaging, and with the scatterer practically in contact with the subject to allow for proximity imaging. We optimize the detector's design and characterize the detector's performance using Monte Carlo simulations. We show that Compton imaging can resolve features of up to 1.5 mm for hot rod phantoms with an activity of 1 µCi, and can reconstruct 3D images of a mouse injected with 0.5 µCi after a 15 minutes exposure and with a single bed position, for both 221Fr and 213Bi. Proximity imaging is able to resolve two 1 mm-radius sources of less than 0.1 µCi separated by 1 cm and at 1 mm from the detector, as well as it can provide planar images of 221Fr and 213Bi biodistributions of the mouse phantom in 5 minutes.

An Analytical Algorithm for Tensor Tomography From Projections Acquired About Three Axes.

Tensor fields are useful for modeling the structure of biological tissues. The challenge to measure tensor fields involves acquiring sufficient data of scalar measurements that are physically achievable and reconstructing tensors from as few projections as possible for efficient applications in medical imaging. In this paper, we present a filtered back-projection algorithm for the reconstruction of a symmetric second-rank tensor field from directional X-ray projections about three axes. The tensor field is decomposed into a solenoidal and irrotational component, each of three unknowns. Using the Fourier projection theorem, a filtered back-projection algorithm is derived to reconstruct the solenoidal and irrotational components from projections acquired around three axes. A simple illustrative phantom consisting of two spherical shells and a 3D digital cardiac diffusion image obtained from diffusion tensor MRI of an excised human heart are used to simulate directional X-ray projections. The simulations validate the mathematical derivations and demonstrate reasonable noise properties of the algorithm. The decomposition of the tensor field into solenoidal and irrotational components provides insight into the development of algorithms for reconstructing tensor fields with sufficient samples in terms of the type of directional projections and the necessary orbits for the acquisition of the projections of the tensor field.

Monte Carlo Simulation and Reconstruction: Assessment of Myocardial Perfusion Imaging of Tracer Dynamics With Cardiac Motion Due to Deformation and Respiration Using Gamma Camera With Continuous Acquisition.

Purpose: Myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) is routinely used for stress testing in nuclear medicine. Recently, our group extended its potential going from 3D visual qualitative image analysis to 4D spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration and the estimated myocardial blood flow (MBF) and coronary flow reserve (CFR). However, the quality of reconstructed image is compromised due to cardiac deformation and respiration. The work presented here develops an algorithm that reconstructs the dynamic sequence of separate respiratory and cardiac phases and evaluates the algorithm with data simulated with a Monte Carlo simulation for the continuous image acquisition and processing with a slowly rotating SPECT camera. Methods: A clinically realistic Monte Carlo (MC) simulation is developed using the 4D Extended Cardiac Torso (XCAT) digital phantom with respiratory and cardiac motion to model continuous data acquisition of dynamic cardiac SPECT with slowly rotating gamma cameras by incorporating deformation and displacement of the myocardium due to cardiac and respiratory motion. We extended our previously developed 4D maximum-likelihood expectation-maximization (MLEM) reconstruction algorithm for a data set binned from a continuous list mode (LM) simulation with cardiac and respiratory information. Our spatiotemporal image reconstruction uses splines to explicitly model the temporal change of the tracer for each cardiac and respiratory gate that delineates the myocardial spatial position as the tracer washes in and out. Unlike in a fully list-mode data acquisition and reconstruction the accumulated photons are binned over a specific but very short time interval corresponding to each cardiac and respiratory gate. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it continuously deforms. These results are then compared with the conventional 4D spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. Mean Stabilized Activity (MSA), signal to noise ratio (SNR) and Bias for the myocardium activities for three different target-to-background ratios (TBRs) are evaluated. Dynamic quantitative indices such as wash-in (K1) and wash-out (k2) rates at each gate were also estimated. Results: The MSA and SNR are higher with higher TBRs while biases were improved with higher TBRs to less than 10%. The correlation between exhalation-inhalation sequence with the ground truth during respiratory cycle was excellent. Our reconstruction method showed better resolved myocardial walls during diastole to systole as compared to the ungated 4D image. Estimated values of K1 and k2 were also consistent with the ground truth. Conclusion: The continuous image acquisition for dynamic scan using conventional two-head gamma cameras can provide valuable information for MPI. Our study demonstrated the viability of using a continuous image acquisition method on a widely used clinical two-head SPECT system. Our reconstruction method showed better resolved myocardial walls during diastole to systole as compared to the ungated 4D image. Precise implementation of reconstruction algorithms, better segmentation techniques by generating images of different tissue types and background activity would improve the feasibility of the method in real clinical environment.

Data Management and Network Architecture Effect on Performance Variability in Direct Attenuation Correction via Deep Learning for Cardiac SPECT: A Feasibility Study.

Attenuation correction (AC) is important for accurate interpretation of SPECT myocardial perfusion imaging (MPI). However, it is challenging to perform AC in dedicated cardiac systems not equipped with a transmission imaging capability. Previously, we demonstrated the feasibility of generating attenuation-corrected SPECT images using a deep learning technique (SPECTDL) directly from non-corrected images (SPECTNC). However, we observed performance variability across patients which is an important factor for clinical translation of the technique. In this study, we investigate the feasibility of overcoming the performance variability across patients for the direct AC in SPECT MPI by proposing to develop an advanced network and a data management strategy. To investigate, we compared the accuracy of the SPECTDL for the conventional U-Net and Wasserstein cycle GAN (WCycleGAN) networks. To manage the training data, clustering was applied to a representation of data in the lower-dimensional space, and the training data were chosen based on the similarity of data in this space. Quantitative analysis demonstrated that DL model with an advanced network improves the global performance for the AC task with the limited data. However, the regional results were not improved. The proposed data management strategy demonstrated that the clustered training has potential benefit for effective training.

Accuracy and Reproducibility of Myocardial Blood Flow Quantification by Single Photon Emission Computed Tomography Imaging in Patients With Known or Suspected Coronary Artery Disease.

BACKGROUND: Single photon emission computed tomography (SPECT) has limited ability to identify multivessel and microvascular coronary artery disease. Gamma cameras with cadmium zinc telluride detectors allow the quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR). However, evidence of its accuracy is limited, and of its reproducibility is lacking. We aimed to validate 99mTc-sestamibi SPECT MBF and MFR using standard and spline-fitted reconstruction algorithms compared with 13N-ammonia positron emission tomography in a cohort of patients with known or suspected coronary artery disease and to evaluate the reproducibility of this technique. METHODS: Accuracy was assessed in 34 participants who underwent dynamic 99mTc-sestamibi SPECT and 13N-ammonia positron emission tomography and reproducibility in 14 participants who underwent 2 99mTc-sestamibi SPECT studies, all within 2 weeks. A rest/pharmacological stress single-day SPECT protocol was performed. SPECT images were reconstructed using a standard ordered subset expectation maximization (OSEM) algorithm with (N=21) and without (N=30) application of spline fitting. SPECT MBF was quantified using a net retention kinetic model' and MFR was derived as the stress/rest MBF ratio. RESULTS: SPECT global MBF with splines showed good correlation with 13N-ammonia positron emission tomography (r=0.81, P<0.001) and MFR estimates (r=0.74, P<0.001). Correlations were substantially weaker for standard reconstruction without splines (r=0.61, P<0.001 and r=0.34, P=0.07, for MBF and MFR, respectively). Reproducibility of global MBF estimates with splines in paired SPECT scans was good (r=0.77, P<0.001), while ordered subset expectation maximization without splines led to decreased MBF (r=0.68, P<0.001) and MFR correlations (r=0.33, P=0.3). There were no significant differences in MBF or MFR between the 2 reproducibility scans independently of the reconstruction algorithm (P>0.05 for all). CONCLUSIONS: MBF and MFR quantification using 99mTc-sestamibi cadmium zinc telluride SPECT with spatiotemporal spline fitting improved the correlation with 13N-ammonia positron emission tomography flow estimates and test/retest reproducibility. The use of splines may represent an important step toward the standardization of SPECT flow estimation.

X-ray bi-prism interferometry-A design study of proposed novel hardware.

PURPOSE: Advances in X-ray phase-contrast imaging can obtain excellent soft-tissue contrast of phase-shift, attenuation, and small-angle scatter. Here, we present fringe patterns for different design parameters of X-ray bi-prism interferometry imaging systems. Our aim is to develop bi-prism interferometry imaging systems with excellent polychromatic performance that produce high-contrast fringes with spatially incoherent X-ray illumination. We also introduce a novel X-ray tube design that uses temporal multiplexing to provide simultaneous virtual "electronic phase stepping" that replace "mechanical phase stepping" popular with grating-based interferometry setups. METHODS: In our investigation, we develop expressions for the irradiance distribution pattern of a bi-prism interferometer composed of multiple point sources and multiple bi-prisms. These expressions are used to plot fringe patterns for X-ray design parameters, including size of point source, number of point sources, and point source separation, and bi-prism design parameters including material, angle, number of bi-prisms, period, and bi-prism array to X-ray source and detector distances. RESULTS: Results show that the fringe patterns for a bi-prism interferometry system are not longitudinally periodic as with grating interferometers that produce a Talbot-Lau carpet. It is also shown that at 59 keV X-rays the bi-prism material should be something comparable to nickel to obtain reasonable fringe visibility. CONCLUSION: The irradiance distribution pattern demonstrates that bi-prism interferometry may provide comparable or improved fringe visibility to that of gratings. Special care is given to present our findings within the context of previous advancements. A single-shot image acquisition approach using a temporal multiplexed, high-power X-ray source provides virtual electronic phase stepping without focal spot sweeping. This provides multiple images, each at the same exposure and the same projection view, from different fringe locations that allow one to derive the attenuation, phase, and dark-field images of the sample without mechanical phase stepping of a grating.

CT-less Direct Correction of Attenuation and Scatter in the Image Space Using Deep Learning for Whole-Body FDG PET: Potential Benefits and Pitfalls.

PURPOSE: To demonstrate the feasibility of CT-less attenuation and scatter correction (ASC) in the image space using deep learning for whole-body PET, with a focus on the potential benefits and pitfalls. MATERIALS AND METHODS: In this retrospective study, 110 whole-body fluorodeoxyglucose (FDG) PET/CT studies acquired in 107 patients (mean age ± standard deviation, 58 years ± 18; age range, 11-92 years; 72 females) from February 2016 through January 2018 were randomly collected. A total of 37.3% (41 of 110) of the studies showed metastases, with diverse FDG PET findings throughout the whole body. A U-Net-based network was developed for directly transforming noncorrected PET (PETNC) into attenuation- and scatter-corrected PET (PETASC). Deep learning-corrected PET (PETDL) images were quantitatively evaluated by using the standardized uptake value (SUV) of the normalized root mean square error, the peak signal-to-noise ratio, and the structural similarity index, in addition to a joint histogram for statistical analysis. Qualitative reviews by radiologists revealed the potential benefits and pitfalls of this correction method. RESULTS: The normalized root mean square error (0.21 ± 0.05 [mean SUV ± standard deviation]), mean peak signal-to-noise ratio (36.3 ± 3.0), mean structural similarity index (0.98 ± 0.01), and voxelwise correlation (97.62%) of PETDL demonstrated quantitatively high similarity with PETASC. Radiologist reviews revealed the overall quality of PETDL. The potential benefits of PETDL include a radiation dose reduction on follow-up scans and artifact removal in the regions with attenuation correction- and scatter correction-based artifacts. The pitfalls involve potential false-negative results due to blurring or missing lesions or false-positive results due to pseudo-low-uptake patterns. CONCLUSION: Deep learning-based direct ASC at whole-body PET is feasible and potentially can be used to overcome the current limitations of CT-based approaches, benefiting patients who are sensitive to radiation from CT.Supplemental material is available for this article.© RSNA, 2020.