CT-based Attenuation Correction Research Articles

Synthetic PET via Domain Translation of 3-D MRI.

Historically, patient datasets have been used to develop and validate various reconstruction algorithms for PET/MRI and PET/CT. To enable such algorithm development, without the need for acquiring hundreds of patient exams, in this article we demonstrate a deep learning technique to generate synthetic but realistic whole-body PET sinograms from abundantly available whole-body MRI. Specifically, we use a dataset of 56 18F-FDG-PET/MRI exams to train a 3-D residual UNet to predict physiologic PET uptake from whole-body T1-weighted MRI. In training, we implemented a balanced loss function to generate realistic uptake across a large dynamic range and computed losses along tomographic lines of response to mimic the PET acquisition. The predicted PET images are forward projected to produce synthetic PET (sPET) time-of-flight (ToF) sinograms that can be used with vendor-provided PET reconstruction algorithms, including using CT-based attenuation correction (CTAC) and MR-based attenuation correction (MRAC). The resulting synthetic data recapitulates physiologic 18F-FDG uptake, e.g., high uptake localized to the brain and bladder, as well as uptake in liver, kidneys, heart, and muscle. To simulate abnormalities with high uptake, we also insert synthetic lesions. We demonstrate that this sPET data can be used interchangeably with real PET data for the PET quantification task of comparing CTAC and MRAC methods, achieving ≤ 7.6% error in mean-SUV compared to using real data. These results together show that the proposed sPET data pipeline can be reasonably used for development, evaluation, and validation of PET/MRI reconstruction methods.

Optimization of the Attenuation Coefficient for Chang Attenuation Correction in 123I Brain Perfusion SPECT.

N-isopropyl-p-123I-iodoamphetamine brain perfusion SPECT has been used with various attenuation coefficients (μ-values); however, optimization is required. This study aimed to determine the optimal μ-value (μopt-value) for Chang attenuation correction (AC) using clinical data by comparing the Chang method and CT-based AC. Methods: We used 100 patients (reference group, 60; disease group, 40) who underwent N-isopropyl-p-123I-iodoamphetamine SPECT. SPECT images of the reference group were obtained to calculate the AC using the Chang method (μ-values, 0.07-0.20; 0.005 interval) and the CT-based method, both without scatter correction (SC) and with SC. The μopt-value with the smallest mean percentage error for the brain regions of the reference group was calculated. Agreement between the Chang and CT-based methods applying the μopt-value was evaluated using Bland-Altman analysis. Additionally, the percentage error in the region of hypoperfusion in the diseased group was compared with the percentage error in the same region in the reference group when the μopt-value was applied. Results: The μopt-values were 0.140 for Chang without SC and 0.160 for Chang with SC. In the Chang method, with the μopt-value applied, fixed and proportional biases were observed in the Bland-Altman analysis (both P < 0.05), and there was a tendency for the percentage error to be underestimated in the limbic regions and overestimated in the central brain regions. There was no significant difference between the disease group and the reference group in the region of hypoperfusion in either Chang without SC or Chang with SC. Conclusion: The present study revealed that the μopt-values of the Chang method are 0.140 without SC and 0.160 with SC.

Attenuation Correction for Dedicated Cardiac SPECT Imaging Without Using Transmission Data.

Attenuation correction (AC) using transmission scanning-like computed tomography (CT) is the standard method to increase the accuracy of cardiac single-photon emission computed tomography (SPECT) images. Recently developed dedicated cardiac SPECT do not support CT, and thus, scans on these systems are vulnerable to attenuation artifacts. This study presented a new method for generating an attenuation map directly from emission data by segmentation of precisely non-rigid registration extended cardiac-torso (XCAT)-digital phantom with cardiac SPECT images. In-house developed non-rigid registration algorithm automatically aligns the XCAT- phantom with cardiac SPECT image to precisely segment the contour of organs. Pre-defined attenuation coefficients for given photon energies were assigned to generate attenuation maps. The CT-based attenuation maps were used for validation with which cardiac SPECT/CT data of 38 patients were included. Segmental myocardial counts of a 17-segment model from these databases were compared based on the basis of the paired t-test. The mean, and standard deviation of the mean square error and structural similarity index measure of the female stress phase between the proposed attenuation maps and the CT attenuation maps were 6.99±1.23% and 92±2.0%, of the male stress were 6.87±3.8% and 96±1.0%. Proposed attenuation correction and computed tomography based attenuation correction average myocardial perfusion count was significantly higher than that in non-AC in the mid-inferior, mid-lateral, basal-inferior, and lateral regions (p<0.001). The proposed attenuation maps showed good agreement with the CT-based attenuation map. Therefore, it is feasible to enable AC for a dedicated cardiac SPECT or SPECT standalone scanners.

Biodistribution and dosimetry for combined [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T therapy using multi-isotope quantitative SPECT imaging

PurposeQuantitative SPECT for patient-specific dosimetry is a valuable tool in the scope of radionuclide therapy, although its clinical application for 225Ac-based treatments may be limited due to low therapeutic activities. Therefore, the aim of this study was to demonstrate the feasibility of clinical quantitative low-count SPECT imaging during [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T treatment.MethodsEight prostate cancer patients (1000 MBq/8 MBq [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T) received a single-bed quantitative 177Lu/225Ac SPECT/CT acquisition (1 h) at 24 h post treatment (high-energy collimator, 16 projections p. head à 3.5 min, 128 × 128 pixel). The gamma peak at 440 keV (width: 10%) of the progeny 213Bi was imaged along with the peak at 208 keV (width: 15%) of 177Lu. Quantification included CT-based attenuation and window-based scatter correction plus resolution modelling. Gaussian post-filtering with a full-width-half-maximum of 30 mm and 40–45 mm was employed to match the signal-to-noise ratio of 225Ac and 177Lu, respectively.ResultsKidney (r = 0.96, p < 0.01) and lesion (r = 0.94, p < 0.01) SUV for [177Lu]Lu-PSMA-I&T and [225Ac]Ac-PSMA-I&T showed a strong and significant correlation. Kidney SUV were significantly higher (p < 0.01) for [225Ac]Ac-PSMA-I&T (2.5 ± 0.8 vs. 2.1 ± 0.9), while for [177Lu]Lu-PSMA-I&T lesion SUV were significantly higher (p = 0.03; 1.8 ± 1.1 vs. 2.1 ± 1.5). For absorbed dose estimates, significant differences regarding the kidneys remained, while no significant differences for lesion dosimetry were found.ConclusionQuantitative low-count SPECT imaging of the peak at 440 keV during [225Ac]Ac-PSMA-I&T therapy is feasible. Multi-isotope imaging for [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T therapy indicates accumulation of free 213Bi in the kidneys.

Brain imaging of sequential acquisition using a flexible PET scanner and 3-T MRI: quantitative and qualitative assessment.

A mobile PET scanner termed flexible PET (fxPET) has been designed to fit existing MRI systems. The purpose of this study was to assess brain imaging with fxPET combined with 3-T MRI in comparison with conventional PET (cPET)/CT. In this prospective study, 29 subjects with no visible lesions except for mild leukoaraiosis on whole brain imaging underwent 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) cPET/CT followed by fxPET and MRI. The registration differences between fxPET and MRI and between cPET and CT were compared by measuring spatial coordinates. Three-dimensional magnetization-prepared rapid acquisition gradient-echo T1-weighted imaging (T1WI) was acquired. We applied two methods of attenuation correction to the fxPET images: MR-based attenuation correction, which yielded fxPETMRAC; and CT-based attenuation correction, which yielded fxPETCTAC. The three PET datasets were co-registered to the T1WI. Following subcortical segmentation and cortical parcellation, volumes of interest were placed in each PET image to assess physiological accumulation in the brain. SUVmean was obtained and compared between the three datasets. We also visually evaluated image distortion and clarity of fxPETMRAC. Mean misregistration of fxPET/MRI was < 3mm for each margin. Mean registration differences were significantly larger for fxPET/MRI than for cPET/CT except for the superior margin. There were high correlations between the three PET datasets regarding SUVmean. On visual evaluation of image quality, the grade of distortion was comparable between fxPETMRAC and cPET, and the grade of clarity was acceptable but inferior for fxPETMRAC compared with cPET. fxPET could successfully determine physiological [18F]FDG uptake; however, improved image clarity is desirable. In this study, fxPET/MRI at 3-T was feasible for brain imaging.

Influence of Metal Implants on Quantitative Evaluation of Bone Single-Photon Emission Computed Tomography/Computed Tomography.

When visualizing biological activity at nonunion sites by the radioisotopes, gamma rays are more attenuated if metal implants are placed in the bone. However, the effects of various implant types and their placement on gamma ray attenuation in quantitative evaluation remain unknown. To elucidate these effects, we created a phantom that simulated the nonunion of the femur in this study. The count of gamma rays was measured by single-photon emission computed tomography/computed tomography (SPECT/CT) while considering CT-based attenuation correction (CTAC), metal implant placement, type (intramedullary nail or plate), and position. The count differed significantly with and without CTAC and with and without implants (both types) under CTAC. Significantly different counts were observed between the intramedullary nail and plate placed contralaterally to the lesion (i.e., non-lesion side). No significant difference was observed between the intramedullary nail and plate on the lesion side or between plates on the non-lesion and lesion sides. The measured standardized uptake value (SUV) was closer to the true SUV with CTAC than without. Moreover, the count was higher with implants than without. However, even with implants, it was lower than the actual count, indicating the absence of overcorrection. Implant type and position do not seem to influence the count.

A Headrest Made of Extruded Polystyrene Reduces the Influence of Attenuation Correction on Human Brain SPECT Images.

Previous reports suggest that a headrest made of carbon significantly influences cerebral blood flow in the anterior and posterior regions by image reconstruction and attenuation correction (AC). The present study aimed to develop a headrest that reduces the influence of the AC process on human brain SPECT. Methods: To validate the performance of a headrest made of extruded polystyrene (XPS), 10 healthy controls and 43 patients with cerebrovascular disease underwent 99mTc-ethyl cysteinate dimer SPECT using a carbon headrest and an XPS headrest. We evaluated the anterior-to-posterior and middle-to-posterior ratio of the brain regions in filtered backprojection (FBP) Chang AC, ordered-subset expectation maximization (OSEM) Chang AC, and OSEM CT-based AC. Results: The anterior-to-posterior ratio was significantly higher with the carbon headrest than with the XPS headrest in FBP Chang AC and OSEM Chang AC (P < 0.001). There was no significant difference between the materials in OSEM CT-based AC. The middle-to-posterior ratio did not differ to a statistically significant extent in any correction process. Conclusion: Acquisition of brain SPECT images with an XPS headrest and processing by the FBP or OSEM Chang AC method enables the influence of the headrest to be reduced, especially in anterior and posterior brain regions.

Impact of CT tube-voltage and bone density on the quantitative assessment of tracer uptake in Tc-99m bone SPECT/CT: A phantom study

PurposeTo evaluate the effect of computed tomography (CT) tube voltage and CT density for CT-based attenuation correction (CTAC) on quantification of tracer uptake in single photon emission computed tomography (SPECT)/CT. MethodsA cylindrical phantom contained 7 cylinders with diameter of 30 mm. The central cylinder and background part were filled with 17 kBq/ml of 99mTc-pertechnetate solution. Of the remaining 6 cylinders, one cylinder was filled with water and 5 cylinders were filled with each own different concentration of K2HPO4 solution (120, 275, 450, 666, and 960 mg/cm3) to simulate different bone densities. The 6 cylinders also contained 99mTc-pertechnetate solution with the same radioactivity concentration (207 kBq/ml). CT scans were performed with 4 different tube voltages of 80, 100, 120, and 140 kVp for CTAC. The radioactivity concentration in the 6 cylinders were measured on the SPECT images processed with 4 different attenuation coefficient maps derived from each tube voltage of CT images. ResultsCompared with the water cylinder without K2HPO4 solution, the measured radioactivity of the highest density cylinder (K2HPO4 solution concentration: 960 mg/cm3) was found to be overestimated by 3.3 % and 4.3 %, respectively, when the tube voltage was 120 kVp and 140 kVp (p = 0.022). The use of low-tube voltage, such as 80 kVp, has improved the quantitative accuracy of bone SPECT/CT. ConclusionsSPECT quantitative evaluation of tracers in high-density objects tends to overestimate as tube voltage for CTAC increases. However, the overestimation in quantitative SPECT/CT evaluation in simulated bone area is less than 5% at most.

Impact of Treatment Modality on Post-Radiation Imaging in Post-Operative Head and Neck Cancers

<h3>Purpose/Objective(s)</h3> Despite frequent dosimetric advantages to proton therapy over photon therapy in head and neck (H&N) cancers, there is concern for end of range biologic dose enhancement and subsequent increased mucosal toxicity with proton therapy. Herein, we evaluated differences in mucosal FDG avidity on post-treatment FDG PET-CTs between proton and photon therapy patients, as persistent activity is a surrogate for residual mucosal toxicity. <h3>Materials/Methods</h3> The cohort comprised ten proton and ten photon patients who received ≥40 Gy to a mucosal oropharyngeal site with curative intent after initial surgery and who remained loco-regional disease free ≥6 months post-treatment. All patients underwent follow-up PET-CT scans 3 months post-radiotherapy. Images centered over the treated primary were acquired 60 minutes after intravenous administration of 10 mCi of FDG. CT-based attenuation correction was applied to the data sets. The PET-CTs were fused to the planning CT using deformable registration using a commercial treatment planning system (TPS). Contours were generated in the deformed PET datasets using a 1.5 × Liver_SUV threshold, i.e., 50% above background; these uptake areas were later intersected with the mucosal CTV plus a 5 mm margin to create the region of interest (ROI). SUV maximum (SUV_MAX) values based on lean body mass were extracted for this ROI. <h3>Results</h3> The SUV_MAX values found in the post-treatment PET-CTs in the intersected ROI for the proton group ranged between 7.08 and 9.38, whereas in the photon group, SUV_MAX values ranged from 3.89 and 6.49. The likelihood of having SUV_MAX values above the 1.5 × Liver_SUV threshold was higher in the proton group (4 of 10 patients) compared to the photon group (2 of 10 patients). Clinically, an ulcer was visible in one proton patient at the area of FDG avidity. <h3>Conclusion</h3> Our results indicate that post-radiotherapy FDG avidity was more commonly observed in proton patients, which correlated with clinical mucosal toxicity.

Using domain knowledge for robust and generalizable deep learning-based CT-free PET attenuation and scatter correction

Despite the potential of deep learning (DL)-based methods in substituting CT-based PET attenuation and scatter correction for CT-free PET imaging, a critical bottleneck is their limited capability in handling large heterogeneity of tracers and scanners of PET imaging. This study employs a simple way to integrate domain knowledge in DL for CT-free PET imaging. In contrast to conventional direct DL methods, we simplify the complex problem by a domain decomposition so that the learning of anatomy-dependent attenuation correction can be achieved robustly in a low-frequency domain while the original anatomy-independent high-frequency texture can be preserved during the processing. Even with the training from one tracer on one scanner, the effectiveness and robustness of our proposed approach are confirmed in tests of various external imaging tracers on different scanners. The robust, generalizable, and transparent DL development may enhance the potential of clinical translation.

Effect of respiratory motion correction and CT-based attenuation correction on dual-gated cardiac PET image quality and quantification

BackgroundDual-gating reduces respiratory and cardiac motion effects but increases noise. With motion correction, motion is minimized and image quality preserved. We applied motion correction to create end-diastolic respiratory motion corrected images from dual-gated images. Methods[18F]-fluorodeoxyglucose ([18F]-FDG) PET images of 13 subjects were reconstructed with 4 methods: non-gated, dual-gated, motion corrected, and motion corrected with 4D-CT (MoCo-4D). Image quality was evaluated using standardized uptake values, contrast ratio, signal-to-noise ratio, coefficient of variation, and contrast-to-noise ratio. Motion minimization was evaluated using myocardial wall thickness. ResultsMoCo-4D showed improvement for contrast ratio (2.83 vs 2.76), signal-to-noise ratio (27.5 vs 20.3) and contrast-to-noise ratio (14.5 vs 11.1) compared to dual-gating. The uptake difference between MoCo-4D and non-gated images was non-significant (P > .05) for the myocardium (2.06 vs 2.15 g/mL), but significant (P < .05) for the blood pool (.80 vs .86 g/mL). Non-gated images had the lowest coefficient of variation (27.3%), with significant increase for all other methods (31.6-32.5%). MoCo-4D showed smallest myocardial wall thickness (16.6 mm) with significant decrease compared to non-gated images (20.9 mm). ConclusionsEnd-diastolic respiratory motion correction and 4D-CT resulted in improved motion minimization and image quality over standard dual-gating.

Deep Learning-Based Attenuation Correction Improves Diagnostic Accuracy of Cardiac SPECT.

To improve diagnostic accuracy, myocardial perfusion imaging (MPI) SPECT studies can use CT-based attenuation correction (AC). However, CT-based AC is not available for most SPECT systems in clinical use, increases radiation exposure, and is impacted by misregistration. We developed and externally validated a deep-learning model to generate simulated AC images directly from non-AC (NC) SPECT, without the need for CT. Methods: SPECT myocardial perfusion imaging was performed using 99mTc-sestamibi or 99mTc-tetrofosmin on contemporary scanners with solid-state detectors. We developed a conditional generative adversarial neural network that applies a deep learning model (DeepAC) to generate simulated AC SPECT images. The model was trained with short-axis NC and AC images performed at 1 site (n = 4,886) and was tested on patients from 2 separate external sites (n = 604). We assessed the diagnostic accuracy of the stress total perfusion deficit (TPD) obtained from NC, AC, and DeepAC images for obstructive coronary artery disease (CAD) with area under the receiver-operating-characteristic curve. We also quantified the direct count change among AC, NC, and DeepAC images on a per-voxel basis. Results: DeepAC could be obtained in less than 1 s from NC images; area under the receiver-operating-characteristic curve for obstructive CAD was higher for DeepAC TPD (0.79; 95% CI, 0.72-0.85) than for NC TPD (0.70; 95% CI, 0.63-0.78; P < 0.001) and similar to AC TPD (0.81; 95% CI, 0.75-0.87; P = 0.196). The normalcy rate in the low-likelihood-of-coronary-disease population was higher for DeepAC TPD (70.4%) and AC TPD (75.0%) than for NC TPD (54.6%, P < 0.001 for both). The positive count change (increase in counts) was significantly higher for AC versus NC (median, 9.4; interquartile range, 6.0-14.2; P < 0.001) than for AC versus DeepAC (median, 2.4; interquartile range, 1.3-4.2). Conclusion: In an independent external dataset, DeepAC provided improved diagnostic accuracy for obstructive CAD, as compared with NC images, and this accuracy was similar to that of actual AC. DeepAC simplifies the task of artifact identification for physicians, avoids misregistration artifacts, and can be performed rapidly without the need for CT hardware and additional acquisitions.

Standardized uptake values and attenuation correction in 18 F-sodium fluoride PET of the equine foot and fetlock.

Maximal standardized uptake values (SUVmax ) are commonly used for the interpretation of PET studies. Limited information regarding the SUVmax of 18 F-NaF PET in horses is currently available in the literature. The goals of this retrospective secondary analysis study were to provide reference values for 18 F-NaF SUVmax in the equine distal extremity and assess the effect of attenuation correction. Nonattenuation corrected (NAC) and CT-based attenuation corrected (CTAC) SUVmax were obtained from 19 feet and 19 fetlocks. Twenty regions of interest (ROIs) were defined for the foot and 22 for the fetlock. Areas presenting abnormal uptake were excluded. The overall NAC and CTAC SUVmax were 3.6 +/- 1.5 (mean +/- sd) and 5.0 +/- 1.8 for the feet and 2.9 +/- 1.1 and 3.8 +/- 1.4 for the fetlocks, respectively. The 3 ROIs showing the highest attenuation correction were the navicular center (83.4%), navicular flexor surface (74.9%) and distal phalanx flexor surface (81.3%), whereas attenuation correction was only 5.2% at the dorsal aspect of the proximal phalanx. Significant SUVmax differences were observed between the different ROIs (P<0.0001), with the toe (CTAC SUVmax 7.7 +/- 3.7), dorsal (7.5 +/- 1.9) and central (6.1 +/- 2.2) ROIs of the distal phalanx being significantly higher than those of the other areas. This study demonstrates that attenuation correction affects SUVmax in the equine distal extremity and should be performed if CT data are available. However, as the maximal attenuation correction results in less than doubling the signal intensity, nonattenuation corrected images likely remain relevant for subjective clinical interpretation.

Intra-Individual Comparison of 124I-PET/CT and 124I-PET/MR Hybrid Imaging of Patients with Resected Differentiated Thyroid Carcinoma: Aspects of Attenuation Correction.

Simple SummaryThis study evaluates the qualitative and quantitative differences between 124-iodine PET/CT and PET/MR in oncologic patients with differentiated thyroid carcinoma after thyroidectomy. The impact of improved MR-based attenuation correction (AC) using a bone atlas was analysed in PET/MR data. Despite different patient positioning and AC methods PET/CT and PET/MR provide overall comparable results in a clinical setting. The overall number of detected 124I-active lesions and the measured average SUVmean values for congruent lesions were higher for PET/MR when compared to PET/CT. The addition of bone to the MR-based AC in PET/MR slightly increased the SUVmean values for all detected lesions.Background: This study evaluates the quantitative differences between 124-iodine (I) positron emission tomography/computed tomography (PET/CT) and PET/magnetic resonance imaging (PET/MR) in patients with resected differentiated thyroid carcinoma (DTC). Methods: N = 43 124I PET/CT and PET/MR exams were included. CT-based attenuation correction (AC) in PET/CT and MR-based AC in PET/MR with bone atlas were compared concerning bone AC in the head-neck region. AC-map artifacts (e.g., dentures) were noted. Standardized uptake values (SUV) were measured in lesions in each PET data reconstruction. Relative differences in SUVmean were calculated between PET/CT and PET/MR with bone atlas. Results: Overall, n = 111 124I-avid lesions were detected in all PET/CT, while n = 132 lesions were detected in PET/MR. The median in SUVmean for n = 98 congruent lesions measured in PET/CT was 12.3. In PET/MR, the median in SUVmean was 16.6 with bone in MR-based AC. Conclusions: 124I-PET/CT and 124I-PET/MR hybrid imaging of patients with DTC after thyroidectomy provides overall comparable quantitative results in a clinical setting despite different patient positioning and AC methods. The overall number of detected 124I-avid lesions was higher for PET/MR compared to PET/CT. The measured average SUVmean values for congruent lesions were higher for PET/MR.

Are Quantitative Errors Reduced with Time-of-Flight Reconstruction When Using Imperfect MR-Based Attenuation Maps for 18F-FDG PET/MR Neuroimaging?

We studied whether TOF reduces error propagation from attenuation correction to PET image reconstruction in PET/MR neuroimaging, by using imperfect attenuation maps in a clinical PET/MR system with 525 ps timing resolution. Ten subjects who had undergone 18F-FDG PET neuroimaging were included. Attenuation maps using a single value (0.100 cm−1) with and without air, and a 3-class attenuation map with soft tissue (0.096 cm−1), air and bone (0.151 cm−1) were used. CT-based attenuation correction was used as a reference. Volume-of-interest (VOI) analysis was conducted. Mean bias and standard deviation across the brain was studied. Regional correlations and concordance were evaluated. Statistical testing was conducted. Average bias and standard deviation were slightly reduced in the majority (23–26 out of 35) of the VOI with TOF. Bias was reduced near the cortex, nasal sinuses, and in the mid-brain with TOF. Bland–Altman and regression analysis showed small improvements with TOF. However, the overall effect of TOF to quantitative accuracy was small (3% at maximum) and significant only for two attenuation maps out of three at 525 ps timing resolution. In conclusion, TOF might reduce the quantitative errors due to attenuation correction in PET/MR neuroimaging, but this effect needs to be further investigated on systems with better timing resolution.

Anger recall mental stress decreases 123I-metaiodobenzylguanidine (123I-MIBG) uptake and increases heterogeneity of cardiac sympathetic activity in the myocardium in patients with ischemic cardiomyopathy

BackgroundAcute psychological stressors such as anger can precipitate ventricular arrhythmias, but the mechanism is incompletely understood. Quantification of regional myocardial sympathetic activity with 123I-metaiodobenzylguanidine (123I-mIBG) SPECT imaging in conjunction with perfusion imaging during mental stress may identify a mismatch between perfusion and sympathetic activity that may exacerbate a mismatch between perfusion and sympathetic activity that could create a milieu of increased vulnerability to ventricular arrhythmia. MethodsFive men with ischemic cardiomyopathy (ICM), and five age-matched healthy male controls underwent serial 123I-mIBG and 99mTc-Tetrofosmin SPECT/CT imaging during an anger recall mental stress task and dual isotope imaging was repeated approximately 1 week later during rest. Images were reconstructed using an iterative reconstruction algorithm with CT-based attenuation correction. The mismatch of left ventricular myocardial 123I-mIBG and 99mTc-Tetrofosmin was assessed along with radiotracer heterogeneity and the 123I-mIBG heart-to-mediastinal ratios (HMR) were calculated using custom software developed at Yale. ResultsThe hemodynamic response to mental stress was similar in both groups. The resting-HMR was greater in healthy control subjects (3.67 ± 0.95) than those with ICM (3.18 ± 0.68, P = .04). Anger recall significantly decreased the HMR in ICM patients (2.62 ± 0.3, P = .04), but not in normal subjects. The heterogeneity of 123I-mIBG uptake in the myocardium was significantly increased in ICM patients during mental stress (26% ± 8.23% vs. rest: 19.62% ± 9.56%; P = .01), whereas the 99mTc-Tetrofosmin uptake pattern was unchanged. ConclusionMental stress decreased the 123I-mIBG HMR, increased mismatch between sympathetic activity and myocardial perfusion, and increased the heterogeneity of 123I-mIBG uptake in ICM patients, while there was no significant change in myocardial defect size or the heterogeneity of 99mTc-Tetrofosmin perfusion. The changes observed in this proof-of-concept study may provide valuable information about the trigger–substrate interaction and the potential vulnerability for ventricular arrhythmias.

Optimized Methodology for Reference Region and Image-Derived Input Function Kinetic Modeling in Preclinical PET.

PET imaging of small animals is often used for assessing biodistribution of a novel radioligand and pharmacology in small animal models of disease. PET acquisition and processing settings may affect reference region or image-derived input function (IDIF) kinetic modeling estimates. We examined four different factors in comparing quantitative results: 1) effect of reconstruction algorithm, 2) number of MAP iterations, 3) strength of the MAP prior, and 4) Attenuation and scatter. The effect of these parameters has not been explored for small-animal reference region and IDIF kinetic modeling approaches. Dynamic PET/CT scans were performed in 3 species with 3 different tracers: house sparrows with [11C]raclopride, rats with [18F]AS2471907 (11βHSD1) and mice with [11C]UCB-J (SV2A). FBP yielded lower kinetic modeling estimates compared to 3D-OSEM-MAP reconstructions, in sparrow and rat studies. Target resolutions (MAP prior strength) of 1.5 and 3.0mm demonstrated reduced VT in rats but only 3.0mm reduced BP ND in sparrows. Therefore, use of the highest target resolution (0.8mm) is warranted. We demonstrated using kinetic modeling that forgoing CT-based attenuation and scatter correction may be appropriate to improve animal throughput when using short-lived radioisotopes in sparrows and mice. This work provides recommendations and a framework for future optimization of kinetic modeling for preclinical PET methodology with novel radioligands.

Evaluation of three methods for delineation and attenuation estimation of the sinus region in MR-based attenuation correction for brain PET-MR imaging

BackgroundAttenuation correction is crucial in quantitative positron emission tomography-magnetic resonance (PET-MRI) imaging. We evaluated three methods to improve the segmentation and modelling of the attenuation coefficients in the nasal sinus region. Two methods (cuboid and template method) included a MRI-CT conversion model for assigning the attenuation coefficients in the nasal sinus region, whereas one used fixed attenuation coefficient assignment (bulk method).MethodsThe study population consisted of data of 10 subjects which had undergone PET-CT and PET-MRI. PET images were reconstructed with and without time-of-flight (TOF) using CT-based attenuation correction (CTAC) as reference. Comparison was done visually, using DICE coefficients, correlation, analyzing attenuation coefficients, and quantitative analysis of PET and bias atlas images.ResultsThe median DICE coefficients were 0.824, 0.853, 0.849 for the bulk, cuboid and template method, respectively. The median attenuation coefficients were 0.0841 cm−1, 0.0876 cm−1, 0.0861 cm−1 and 0.0852 cm−1, for CTAC, bulk, cuboid and template method, respectively. The cuboid and template methods showed error of less than 2.5% in attenuation coefficients. An increased correlation to CTAC was shown with the cuboid and template methods. In the regional analysis, improvement in at least 49% and 80% of VOI was seen with non-TOF and TOF imaging. All methods showed errors less than 2.5% in non-TOF and less than 2% in TOF reconstructions.ConclusionsWe evaluated two proof-of-concept methods for improving quantitative accuracy in PET/MRI imaging and showed that bias can be further reduced by inclusion of TOF. Largest improvements were seen in the regions of olfactory bulb, Heschl's gyri, lingual gyrus and cerebellar vermis. However, the overall effect of inclusion of the sinus region as separate class in MRAC to PET quantification in the brain was considered modest.

Deep learning-guided attenuation correction in the image domain for myocardial perfusion SPECT imaging

Abstract We investigate the accuracy of direct attenuation correction (AC) in the image domain for myocardial perfusion SPECT (single-photon emission computed tomography) imaging (MPI-SPECT) using residual (ResNet) and UNet deep convolutional neural networks. MPI-SPECT 99mTc-sestamibi images of 99 patients were retrospectively included. UNet and ResNet networks were trained using non-attenuation-corrected SPECT images as input, whereas CT-based attenuation-corrected (CT-AC) SPECT images served as reference. Chang’s calculated AC approach considering a uniform attenuation coefficient within the body contour was also implemented. Clinical and quantitative evaluations of the proposed methods were performed considering SPECT CT-AC images of 19 subjects (external validation set) as reference. Image-derived metrics, including the voxel-wise mean error (ME), mean absolute error, relative error, structural similarity index (SSI), and peak signal-to-noise ratio, as well as clinical relevant indices, such as total perfusion deficit (TPD), were utilized. Overall, AC SPECT images generated using the deep learning networks exhibited good agreement with SPECT CT-AC images, substantially outperforming Chang’s method. The ResNet and UNet models resulted in an ME of −6.99 ± 16.72 and −4.41 ± 11.8 and an SSI of 0.99 ± 0.04 and 0.98 ± 0.05, respectively. Chang’s approach led to ME and SSI of 25.52 ± 33.98 and 0.93 ± 0.09, respectively. Similarly, the clinical evaluation revealed a mean TPD of 12.78 ± 9.22% and 12.57 ± 8.93% for ResNet and UNet models, respectively, compared to 12.84 ± 8.63% obtained from SPECT CT-AC images. Conversely, Chang’s approach led to a mean TPD of 16.68 ± 11.24%. The deep learning AC methods have the potential to achieve reliable AC in MPI-SPECT imaging.

11C-methionine PET/MRI in postoperative patients after craniotomy: zero echo time and head atlas versus CT-based attenuation correction.

Attenuation correction (AC) is an important topic in PET/MRI and particularly challenging after brain tumor surgery, near metal implants, adjacent bone and burr holes. In this study, we evaluated the performance of two MR-driven AC methods, zero-echo-time AC (ZTE-AC) and atlas-AC, in comparison to reference standard CT-AC in patients with surgically treated brain tumors at 11C-methionine PET/MRI. This retrospective study investigated seven postoperative patients with neuropathologically confirmed brain tumor at 11C-methionine PET/MRI. Three AC maps - ZTE-AC, atlas-AC and reference standard CT-AC - were generated for each patient. Standardized uptake values (SUV) were obtained at the metal implant, adjacent bone and burr hole. Standard uptake ratio (SUR) SURmetal/mirror, SURbone/mirror and SURburrhole/mirror were then calculated and analyzed with Bland-Altman, Pearson correlation and intraclass correlation reliability. Smaller mean percent bias range (Bland-Altman) was found for ZTE-AC than atlas-AC in all analyses (metal ZTE -0.46 to -0.02, metal atlas -3.57 to -3.26; bone ZTE -4.60 to -2.16, bone atlas -5.25 to -3.81; burr hole ZTE -0.95 to -0.52, burr hole atlas 7.86 to 8.87). Percent SD range (Bland-Altman) was large for both methods in all analyses, with lower absolute values for ZTE-AC (ZTE 7.02-8.49; atlas 11.47-14.83). A very strong correlation (Pearson correlation) was demonstrated for both methods compared to CT-AC (ZTE ρ 0.97-0.99, P<0.001; atlas ρ 0.88-0.91, P≤0.009) with higher absolute values for ZTE. An excellent intraclass correlation coefficient was found across all analyses for ZTE, atlas and CT maps (ICC ≥0.88). ZTE for MR-driven PET attenuation correction presented a more comparable performance to reference standard CT-AC at the postoperative site. ZTE-AC may serve as a useful diagnostic tool for MR-driven AC in patients with surgically treated brain tumors.