Observer studies of image quality of denoising reduced-count cardiac single photon emission computed tomography myocardial perfusion imaging by three-dimensional Gaussian post-reconstruction filtering and deep learning.

BACKGROUND: The aim of this research was to asses perfusion-defect detection-accuracy by human observers as a function of reduced-counts for 3D Gaussian post-reconstruction filtering vs deep learning (DL) denoising to determine if there was improved performance with DL. METHODS: SPECT projection data of 156 normally interpreted patients were used for these studies. Half were altered to include hybrid perfusion defects with defect presence and location known. Ordered-subset expectation-maximization (OSEM) reconstruction was employed with the optional correction of attenuation (AC) and scatter (SC) in addition to distance-dependent resolution (RC). Count levels varied from full-counts (100%) to 6.25% of full-counts. The denoising strategies were previously optimized for defect detection using total perfusion deficit (TPD). Four medical physicist (PhD) and six physician (MD) observers rated the slices using a graphical user interface. Observer ratings were analyzed using the LABMRMC multi-reader, multi-case receiver-operating-characteristic (ROC) software to calculate and compare statistically the area-under-the-ROC-curves (AUCs). RESULTS: For the same count-level no statistically significant increase in AUCs for DL over Gaussian denoising was determined when counts were reduced to either the 25% or 12.5% of full-counts. The average AUC for full-count OSEM with solely RC and Gaussian filtering was lower than for the strategies with AC and SC, except for a reduction to 6.25% of full-counts, thus verifying the utility of employing AC and SC with RC. CONCLUSION: We did not find any indication that at the dose levels investigated and with the DL network employed, that DL denoising was superior in AUC to optimized 3D post-reconstruction Gaussian filtering.

Improving detection accuracy of perfusion defect in standard dose SPECT-myocardial perfusion imaging by deep-learning denoising.

BACKGROUND: We previously developed a deep-learning (DL) network for image denoising in SPECT-myocardial perfusion imaging (MPI). Here we investigate whether this DL network can be utilized for improving detection of perfusion defects in standard-dose clinical acquisitions. METHODS: To quantify perfusion-defect detection accuracy, we conducted a receiver-operating characteristic (ROC) analysis on reconstructed images with and without processing by the DL network using a set of clinical SPECT-MPI data from 190 subjects. For perfusion-defect detection hybrid studies were used as ground truth, which were created from clinically normal studies with simulated realistic lesions inserted. We considered ordered-subset expectation-maximization (OSEM) reconstruction with corrections for attenuation, resolution, and scatter and with 3D Gaussian post-filtering. Total perfusion deficit (TPD) scores, computed by Quantitative Perfusion SPECT (QPS) software, were used to evaluate the reconstructed images. RESULTS: Compared to reconstruction with optimal Gaussian post-filtering (sigma = 1.2 voxels), further DL denoising increased the area under the ROC curve (AUC) from 0.80 to 0.88 (P-value < 10-4). For reconstruction with less Gaussian post-filtering (sigma = 0.8 voxels), thus better spatial resolution, DL denoising increased the AUC value from 0.78 to 0.86 (P-value < 10-4) and achieved better spatial resolution in reconstruction. CONCLUSIONS: DL denoising can effectively improve the detection of abnormal defects in standard-dose SPECT-MPI images over conventional reconstruction.

Cross-vender, cross-tracer, and cross-protocol deep transfer learning for attenuation map generation of cardiac SPECT.

It has been proved feasible to generate attenuation maps (µ-maps) from cardiac SPECT using deep learning. However, this assumed that the training and testing datasets were acquired using the same scanner, tracer, and protocol. We investigated a robust generation of CT-derived µ-maps from cardiac SPECT acquired by different scanners, tracers, and protocols from the training data. We first pre-trained a network using 120 studies injected with 99mTc-tetrofosmin acquired from a GE 850 SPECT/CT with 360-degree gantry rotation, which was then fine-tuned and tested using 80 studies injected with 99mTc-sestamibi acquired from a Philips BrightView SPECT/CT with 180-degree gantry rotation. The error between ground-truth and predicted µ-maps by transfer learning was 5.13 ± 7.02%, as compared to 8.24 ± 5.01% by direct transition without fine-tuning and 6.45 ± 5.75% by limited-sample training. The error between ground-truth and reconstructed images with predicted µ-maps by transfer learning was 1.11 ± 1.57%, as compared to 1.72 ± 1.63% by direct transition and 1.68 ± 1.21% by limited-sample training. It is feasible to apply a network pre-trained by a large amount of data from one scanner to data acquired by another scanner using different tracers and protocols, with proper transfer learning.

A novel deep-learning-based approach for automatic reorientation of 3D cardiac SPECT images.

PURPOSE: Reconstructed transaxial cardiac SPECT images need to be reoriented into standard short-axis slices for subsequent accurate processing and analysis. We proposed a novel deep-learning-based method for fully automatic reorientation of cardiac SPECT images and evaluated its performance on data from two clinical centers. METHODS: We used a convolutional neural network to predict the 6 rigid-body transformation parameters and a spatial transformation network was then implemented to apply these parameters on the input images for image reorientation. A novel compound loss function which balanced the parametric similarity and penalized discrepancy of the prediction and training dataset was utilized in the training stage. Data from a set of 322 patients underwent data augmentation to 6440 groups of images for the network training, and a dataset of 52 patients from the same center and 23 patients from another center were used for evaluation. Similarity of the 6 parameters was analyzed between the proposed and the manual methods. Polar maps were generated from the output images and the averaged count values of the 17 segments were computed from polar maps to evaluate the quantitative accuracy of the proposed method. RESULTS: All the testing patients achieved automatic reorientation successfully. Linear regression results showed the 6 predicted rigid parameters and the average count value of the 17 segments having good agreement with the reference manual method. No significant difference by paired t-test was noticed between the rigid parameters of our method and the manual method (p > 0.05). Average count values of the 17 segments show a smaller difference of the proposed and manual methods than those between the existing and manual methods. CONCLUSION: The results strongly indicate the feasibility of our method in accurate automatic cardiac SPECT reorientation. This deep-learning-based reorientation method has great promise for clinical application and warrants further investigation.

Retrospective fractional dose reduction in Tc-99m cardiac perfusion SPECT/CT patients: A human and model observer study.

BACKGROUND: In the ongoing efforts to reduce cardiac perfusion dose (injected radioactivity) for conventional SPECT/CT systems, we performed a human observer study to confirm our clinical model observer findings that iterative reconstruction employing OSEM (ordered-subset expectation-maximization) at 25% of the full dose (quarter-dose) has a similar performance for detection of hybrid cardiac perfusion defects as FBP at full dose. METHODS: One hundred and sixty-six patients, who underwent routine rest-stress Tc-99m sestamibi cardiac perfusion SPECT/CT imaging and clinically read as normally perfused, were included in the study. Ground truth was established by the normal read and the insertion of hybrid defects. In addition to the reconstruction of the 25% of full-dose data using OSEM with attenuation (AC), scatter (SC), and spatial resolution correction (RC), FBP and OSEM (with AC, SC, and RC) both at full dose (100%) were done. Both human observer and clinical model observer confidence scores were obtained to generate receiver operating characteristics (ROC) curves in a task-based image quality assessment. RESULTS: Average human observer AUC (area under the ROC curve) values of 0.725, 0.876, and 0.890 were obtained for FBP at full dose, OSEM at 25% of full dose, and OSEM at full dose, respectively. Both OSEM strategies were significantly better than FBP with P values of 0.003 and 0.01 respectively, while no significant difference was recorded between OSEM methods (P = 0.48). The clinical model observer results were 0.791, 0.822, and 0.879, respectively, for the same patient cases and processing strategies used in the human observer study. CONCLUSIONS: Cardiac perfusion SPECT/CT using OSEM reconstruction at 25% of full dose has AUCs larger than FBP and closer to those of full-dose OSEM when read by human observers, potentially replacing the higher dose studies during clinical reading.

Investigation of the physical effects of respiratory motion compensation in a large population of patients undergoing Tc-99m cardiac perfusion SPECT/CT stress imaging.

BACKGROUND: Respiratory motion can deteriorate image fidelity in cardiac perfusion SPECT. We determined the extent of respiratory motion, assessed its impact on image fidelity, and investigated the existence of gender differences, thereby examining the influence of respiratory motion in a large population of patients. METHODS: One thousand one hundred and three SPECT/CT patients underwent visual tracking of markers on their anterior surface during stress acquisition to track respiratory motion. The extent of motion was estimated by registration. Visual indicators of changes in cardiac slices with motion correction, and the correlation between the extent of motion with changes in segmental-counts were assessed. RESULTS: Respiratory motion in the head-to-feet direction was the largest component of motion, varying between 1.1 and 37.4 mm, and was statistically significantly higher (p = 0.002) for males than females. In 33.0% of the patients, motion estimates were larger than 10 mm. Patients progressively show more distinct visual changes with an increase in the extent of motion. The increase in segmental-count differences in the anterior, antero-lateral, and inferior segments correlated with the extent of motion. CONCLUSIONS: Respiratory motion correction diminished the artefactual reduction in anterior and inferior wall counts associated with respiratory motion. The extent of improvement was strongly related to the magnitude of motion.

Evaluation of different respiratory gating schemes for cardiac SPECT.

BACKGROUND: Respiratory gating reduces motion blurring in cardiac SPECT. Here we aim to evaluate the performance of three respiratory gating strategies using a population of digital phantoms with known truth and clinical data. METHODS: We analytically simulated 60 projections for 10 XCAT phantoms with 99mTc-sestamibi distributions using three gating schemes: equal amplitude gating (AG), equal count gating (CG), and equal time gating (TG). Clinical list-mode data for 10 patients who underwent 99mTc-sestamibi scans were also processed using the 3 gating schemes. Reconstructed images in each gate were registered to a reference gate, averaged and reoriented to generate the polar plots. For simulations, image noise, relative difference (RD) of averaged count for each of the 17 segment, and relative defect size difference (RSD) were analyzed. For clinical data, image intensity profile and FWHM were measured across the left ventricle wall. RESULTS: For simulations, AG and CG methods showed significantly lower RD and RSD compared to TG, while noise variation was more non-uniform through different gates for AG. In the clinical study, AG and CG had smaller FWHM than TG. CONCLUSIONS: AG and CG methods show better performance for motion reduction and are recommended for clinical respiratory gating SPECT implementation.

Evaluation of the effect of reducing administered activity on assessment of function in cardiac gated SPECT.

BACKGROUND: We previously optimized several reconstruction strategies in SPECT myocardial perfusion imaging (MPI) with low dose for perfusion-defect detection. Here we investigate whether reducing the administered activity can also maintain the diagnostic accuracy in evaluating cardiac function. METHODS: We quantified the myocardial motion in cardiac-gated stress 99m-Tc-sestamibi SPECT studies from 163 subjects acquired with full dose (29.8 ± 3.6 mCi), and evaluated the agreement of the obtained motion/thickening and ejection fraction (EF) measures at various reduced dose levels (uniform reduction or personalized dose) with that at full dose. We also quantified the detectability of abnormal motion via a receiver-operating characteristics (ROC) study. For reconstruction we considered both filtered backprojection (FBP) without correction for degradations, and iterative ordered-subsets expectation-maximization (OS-EM) with resolution, attenuation and scatter corrections. RESULTS: With dose level lowered to 25% of full dose, the obtained results on motion/thickening, EF and abnormal motion detection were statistically comparable to full dose in both reconstruction strategies, with Pearson's r > 0.9 for global motion measures between low dose and full dose. CONCLUSIONS: The administered activity could be reduced to 25% of full dose without degrading the function assessment performance. Low dose reconstruction optimized for perfusion-defect detection can be reasonable for function assessment in gated SPECT.

Improving perfusion defect detection with respiratory motion correction in cardiac SPECT at standard and reduced doses.

BACKGROUND: In cardiac SPECT perfusion imaging, respiratory motion can cause non-uniform blurring in the reconstructed myocardium. We investigate the potential benefit of respiratory correction with respiratory-binned acquisitions, both at standard dose and at reduced dose, for defect detection and for left ventricular (LV) wall resolution. METHODS: We applied two reconstruction methods for respiratory motion correction: post-reconstruction motion correction (PMC) and motion-compensated reconstruction (MCR), and compared with reconstruction without motion correction (Non-MC). We quantified the presence of perfusion defects in reconstructed images by using the total perfusion deficit (TPD) scores and conducted receiver-operating-characteristic (ROC) studies using TPD. We quantified the LV spatial resolution by using the FWHM of its cross-sectional intensity profile. RESULTS: The values in the area-under-the-ROC-curve (AUC) achieved by MCR, PMC, and Non-MC at standard dose were 0.835, 0.830, and 0.798, respectively. Similar AUC improvements were also obtained by MCR and PMC over Non-MC at 50%, 25%, and 12.5% of full dose. Improvements in LV resolution were also observed with motion correction. CONCLUSIONS: Respiratory-binned acquisitions can improve perfusion-defect detection accuracy over traditional reconstruction both at standard dose and at reduced dose. Motion correction may contribute to achieving further dose reduction while maintaining the diagnostic accuracy of traditional acquisitions.

Investigation of dose reduction in cardiac perfusion SPECT via optimization and choice of the image reconstruction strategy.

BACKGROUND: We investigated the extent to which the administered dose (activity) level can be reduced without sacrificing diagnostic accuracy for three reconstruction strategies for SPECT-myocardial perfusion imaging (MPI). METHODS: We optimized the parameters of the three reconstruction strategies for perfusion-defect detection over a range of simulated administered dose levels using a set of hybrid studies (derived from 190 subjects) consisting of clinical SPECT-MPI data modified to contain realistic simulated lesions. The optimized strategies we considered are filtered backprojection (FBP) with no correction for degradations, ordered-subsets expectation-maximization (OS-EM) with attenuation correction (AC), scatter correction (SC), and resolution correction (RC), and OS-EM with scatter and resolution correction only. Each study was evaluated using a total perfusion deficit (TPD) score computed by the Quantitative Perfusion SPECT (QPS) software package. We conducted a receiver operating characteristics (ROC) study based on the TPD scores for each dose level and reconstruction strategy. RESULTS: For FBP, the achieved optimum values of the area under the ROC curve (AUC) at 100%, 50%, 25%, and 12.5% of standard dose were 0.75, 0.74, 0.72, and 0.70, respectively, compared to 0.81, 0.79, 0.76, and 0.74 for OS-EM with AC-SC-RC and 0.78, 0.77, 0.74, 0.72 for OS-EM with SC-RC. CONCLUSIONS: Our results suggest that studies reconstructed by OS-EM with AC-SC-RC could possibly be reduced, on average, to 25% of the originally administered dose without causing diagnostic accuracy (AUC) to decrease below that of FBP.

Evaluation of Rigid-Body Motion Compensation in Cardiac Perfusion SPECT Employing Polar-Map Quantification.

We have recently been successful in the development and testing of rigid-body motion tracking, estimation and compensation for cardiac perfusion SPECT based on a visual tracking system (VTS). The goal of this study was to evaluate in patients the effectiveness of our rigid-body motion compensation strategy. Sixty-four patient volunteers were asked to remain motionless or execute some predefined body motion during an additional second stress perfusion acquisition. Acquisitions were performed using the standard clinical protocol with 64 projections acquired through 180 degrees. All data were reconstructed with an ordered-subsets expectation-maximization (OSEM) algorithm using 4 projections per subset and 5 iterations. All physical degradation factors were addressed (attenuation, scatter, and distance dependent resolution), while a 3-dimensional Gaussian rotator was used during reconstruction to correct for six-degree-of-freedom (6-DOF) rigid-body motion estimated by the VTS. Polar map quantification was employed to evaluate compensation techniques. In 54.7% of the uncorrected second stress studies there was a statistically significant difference in the polar maps, and in 45.3% this made a difference in the interpretation of segmental perfusion. Motion correction reduced the impact of motion such that with it 32.8 % of the polar maps were statistically significantly different, and in 14.1% this difference changed the interpretation of segmental perfusion. The improvement shown in polar map quantitation translated to visually improved uniformity of the SPECT slices.

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

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

Respiratory signal estimation for cardiac perfusion SPECT using deep learning.

BACKGROUND: Respiratory motion induces artifacts in reconstructed cardiac perfusion SPECT images. Correction for respiratory motion often relies on a respiratory signal describing the heart displacements during breathing. However, using external tracking devices to estimate respiratory signals can add cost and operational complications in a clinical setting. PURPOSE: We aim to develop a deep learning (DL) approach that uses only SPECT projection data for respiratory signal estimation. METHODS: A modified U-Net was implemented that takes temporally finely sampled SPECT sub-projection data (100 ms) as input. These sub-projections are obtained by reframing the 20-s list-mode data, resulting in 200 sub-projections, at each projection angle for each SPECT camera head. The network outputs a 200-time-point motion signal for each projection angle, which was later aggregated over all angles to give a full respiratory signal. The target signal for DL model training was from an external stereo-camera visual tracking system (VTS). In addition to comparing DL and VTS, we also included a data-driven approach based on the center-of-mass (CoM) strategy. This CoM method estimates respiratory signals by monitoring the axial changes of CoM for counts in the heart region of the sub-projections. We utilized 900 subjects with stress cardiac perfusion SPECT studies, with 302 subjects for testing and the remaining 598 subjects for training and validation. RESULTS: The Pearson's correlation coefficient between the DL respiratory signal and the reference VTS signal was 0.90, compared to 0.70 between the CoM signal and the reference. For respiratory motion correction on SPECT images, all VTS, DL, and CoM approaches partially de-blured the heart wall, resulting in a thinner wall thickness and increased recovered maximal image intensity within the wall, with VTS reducing blurring the most followed by the DL approach. Uptake quantification for the combined anterior and inferior segments of polar maps showed a mean absolute difference from the reference VTS of 1.7% for the DL method for patients with motion >12 mm, compared to 2.6% for the CoM method and 8.5% for no correction. CONCLUSION: We demonstrate the capability of a DL approach to estimate respiratory signal from SPECT projection data for cardiac perfusion imaging. Our results show that the DL based respiratory motion correction reduces artefacts and achieves similar regional quantification to that obtained using the stereo-camera VTS signals. This may enable fully automatic data-driven respiratory motion correction without relying on external motion tracking devices.

Data-driven respiratory signal estimation from temporally finely sampled projection data in conventional cardiac perfusion SPECT imaging.

PURPOSE: The aim of this work was to revisit the data-driven approach of axial center-of-mass (COM) measurements to recover a surrogate respiratory signal from finely sampled (100 ms) single photon emission computed tomography (SPECT) projection data derived from list-mode acquisitions. METHODS: For our initial evaluation, we acquired list-mode projection data from an anthropomorphic cardiac phantom mounted on a Quasar respiratory motion platform simulating 15 mm amplitude respiratory motion. We also selected 302 consecutive patients (138 males, 164 females) with list-mode acquisitions, external respiratory motion tracking, and written consent to evaluate the clinical efficacy of our data-driven approach. Linear regression, Pearson's correlation coefficient (r), and standard error of the estimates (SEE) between the respiratory signals obtained with a visual tracking system (VTS) and COM measurements were calculated for individual projection data sets and for the patient group as a whole. Both the VTS- and COM-derived respiratory signals were used to estimate and correct respiratory motion. The reconstruction for six-degree of freedom rigid-body motion estimation was done in two ways: (1) using three iterations of ordered-subsets expectation-maximization (OSEM) with four subsets (16 projection angles per subset), or 12 iterations of maximum-likelihood expectation-maximization (MLEM). Respiratory motion compensation was done employing either OSEM with 16 subsets (four projection angles per subset) and five iterations or MLEM and 80 iterations, using the two respiratory estimates, respectively. Polar map quantification was also performed, calculating the percentage count difference (%Diff) between polar maps without and with respiratory motion included. Average % Diff was calculated in 17 segments (defined according to ASNC Guidelines). Paired t-tests were used to determine significance (p-values). RESULTS: The r-value calculated when comparing the VTS and COM respiratory signals varied widely between -0.01 and 0.96 with an average of 0.70, while the SEE varied between 0.80 and 6.48 mm with an average of 2.05 mm for our patient set, while the same values for the one anthropomorphic phantom acquisition are 0.91 and 1.11 mm, respectively. A comparison between the respiratory motion estimates for VTS and COM in the S-I direction yielded an r = 0.90 (0.94), and an SEE of 1.56 mm (1.20 mm) for OSEM (MLEM), respectively. Bland-Altman plots and calculated intraclass correlation coefficients also showed excellent agreement between the VTS and COM respiratory motion estimates. Average S-I respiratory estimates for the VTS (COM) were 9.04 (9.2 mm) and 9.01 mm (9.14 mm) for the OSEM and MLEM, respectively. The paired t-test approached significance when comparing VTS and COM estimated respiratory signals with p-values of 0.069 and 0.051 for OSEM and MLEM. The respiratory estimates from the anthropomorphic cardiac phantom experiment using the VTS (COM) were 12.62 (14.10 mm) and 12.55 mm (14.29 mm) for OSEM and MLEM, respectively. Polar map quantification yielded average % Diff consistently better when employing VTS-derived respiratory estimates to correct for respiration compared to the COM-derived estimates. CONCLUSIONS: The results indicate that our COM method has the potential to provide an automated data-driven correction of cardiac respiratory motion without the drawbacks of our VTS methodology. However, it is not generally equivalent to the VTS method in extent of correction.

Dual gating myocardial perfusion SPECT denoising using a conditional generative adversarial network.

PURPOSE: Dual respiratory-cardiac gating reduces respiratory and cardiac motion blur in myocardial perfusion single-photon emission computed tomography (MP-SPECT). However, image noise is increased as detected counts are reduced in each dual gate (DG). We aim to develop a denoising method for dual gating MP-SPECT images using a 3D conditional generative adversarial network (cGAN). METHODS: Twenty extended cardiac-torso phantoms with various 99m Tc-sestamibi distributions, defect characteristics, and body and organ sizes were used in the simulation, modeling six respiratory and eight cardiac gates (CGs), that is, 48 DGs for ordered subset expectation maximization reconstruction. Twenty clinical 99m Tc-sestamibi SPECT/CT datasets were re-binned into 7 respiratory gates and 8 CGs, that is, 56 DGs for maximum likelihood expectation maximization reconstruction. We evaluated the use of (i) phantoms' own datasets (patient-specific denoising [PD]) or other phantoms' datasets (cross-patient denoising) for training; (ii) the CG or the static (non-gated [NG]) data as the training references for cGAN; and (iii) cGAN as compared to conventional 3D post-reconstruction filtering, cardiac gating methods, and convolutional neural network. Normalized mean squared error, noise as assessed by normalized standard deviation, spatial blurring measured as the full-width-at-half-maximum of left ventricular wall, ejection fraction, joint correlation histogram, and defect size were analyzed as metrics of image quality. RESULTS: Training using patients' own dataset is superior to conventional training based on other patients' data. Using CG image as training reference provides a better trade-off in terms of noise and image blur as compared to the use of NG. cGAN-CG-PD provides superior performance as compared to other denoising methods for all physical and diagnostic indices evaluated in both simulation and clinical studies. CONCLUSIONS: cGAN denoising is promising for dual gating MP-SPECT based on the metrics mentioned earlier.

Role of the Neuroradiologist and Neurosurgeon in Contouring with the Clinical Oncologist for Stereotactic Radiosurgery.

AIM: To evaluate the value of a multidisciplinary team (MDT), including a neuroradiologist and a neurosurgeon, review of contouring in stereotactic radiosurgery (SRS). MATERIALS AND METHODS: A sequential audit of all patients receiving intracranial SRS at local institution was conducted. Lesions were contoured first by a clinical oncologist, then reviewed/edited by the MDT. The initial contour was compared with the final contour using Jaccard conformity (JCI) and geographical miss indices (GMI). The dosimetric impact of a contouring change was assessed using plan metrics to both original and final contours. RESULTS: In total, 113 patients and 142 lesions treated over 22 months were identified. The mean JCI was 0.92 (0.32-1.00) and 38% needed significant editing (JCI <0.95). The mean GMI was 0.03 (0.0-0.65) and 17% showed significant miss (GMI >0.05). Resection cavities showed more changes, with lower JCI and higher GMI (P < 0.05). There was no significant improvement on JCI or GMI shown over time. The dosimetric analysis indicated a strong association of conformity metrics with planning target volume dose metrics; a 0.1 change in gross tumour volume conformity metric association with a 6-17% change in dose to 95% of the resulting planning target volume. Greater association was seen in the resection cavity, suggesting the geographical nature of a typical contouring error gives rise to greater potential change in dose. Clinical outcomes compared well with published series. The median survival was 20 months; the local relapse-free rate in the treated areas was 0.89 (0.8-0.94) at 40 months; the radionecrosis-free rate at 40 months was 0.9 (0.83-0.95) with a median of 17 months to developing radionecrosis. CONCLUSIONS: This work highlights that MDT contour review adds significant value to SRS and the approach translates into reduced local recurrence rates at the local institution compared with previously published data. No improvement in clinical oncologist contouring over time was shown, indicating that a collaborative approach is needed regardless of the experience of the clinical oncologist. MDT input is recommended in particular for contouring of resection cavities.

Characteristics, management and outcome of a large necrotising otitis externa case series: need for standardised case definition.

BACKGROUND: Necrotising otitis externa is a severe ear infection for which there are no established diagnostic or treatment guidelines. METHOD: This study described clinical characteristics, management and outcomes for patients managed as necrotising otitis externa cases at a UK tertiary referral centre. RESULTS: A total of 58 (63 per cent) patients were classified as definite necrotising otitis externa cases, 31 (34 per cent) as probable cases and 3 (3 per cent) as possible cases. Median duration of intravenous and oral antimicrobial therapy was 6.0 weeks (0.49-44.9 weeks). Six per cent of patients relapsed a median of 16.4 weeks (interquartile range, 23-121) after stopping antimicrobials. Twenty-eight per cent of cases had complex disease. These patients were older (p = 0.042), had a longer duration of symptoms prior to imaging (p < 0.0001) and higher C-reactive protein at diagnosis (p = 0.005). Despite longer courses of intravenous antimicrobials (23 vs 14 days; p = 0.032), complex cases were more likely to relapse (p = 0.016). CONCLUSION: A standardised case-definition of necrotising otitis externa is needed to optimise diagnosis, management and research.

Deep learning with noise-to-noise training for denoising in SPECT myocardial perfusion imaging.

PURPOSE: Post-reconstruction filtering is often applied for noise suppression due to limited data counts in myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT). We study a deep learning (DL) approach for denoising in conventional SPECT-MPI acquisitions, and investigate whether it can be more effective for improving the detectability of perfusion defects compared to traditional postfiltering. METHODS: Owing to the lack of ground truth in clinical studies, we adopt a noise-to-noise (N2N) training approach for denoising in SPECT-MPI images. We consider a coupled U-Net (CU-Net) structure which is designed to improve learning efficiency through feature map reuse. For network training we employ a bootstrap procedure to generate multiple noise realizations from list-mode clinical acquisitions. In the experiments we demonstrated the proposed approach on a set of 895 clinical studies, where the iterative OSEM algorithm with three-dimensional (3D) Gaussian postfiltering was used to reconstruct the images. We investigated the detection performance of perfusion defects in the reconstructed images using the non-prewhitening matched filter (NPWMF), evaluated the uniformity of left ventricular (LV) wall in terms of image intensity, and quantified the effect of smoothing on the spatial resolution of the reconstructed LV wall by using its full-width at half-maximum (FWHM). RESULTS: Compared to OSEM with Gaussian postfiltering, the DL denoised images with CU-Net significantly improved the detection performance of perfusion defects at all contrast levels (65%, 50%, 35%, and 20%). The signal-to-noise ratio (SNRD ) in the NPWMF output was increased on average by 8% over optimal Gaussian smoothing (P < 10-4 , paired t-test), while the inter-subject variability was greatly reduced. The CU-Net also outperformed a 3D nonlocal means (NLM) filter and a convolutional autoencoder (CAE) denoising network in terms of SNRD . In addition, the FWHM of the LV wall in the reconstructed images was varied by less than 1%. Furthermore, CU-Net also improved the detection performance when the images were processed with less post-reconstruction smoothing (a trade-off of increased noise for better LV resolution), with SNRD improved on average by 23%. CONCLUSIONS: The proposed DL with N2N training approach can yield additional noise suppression in SPECT-MPI images over conventional postfiltering. For perfusion defect detection, DL with CU-Net could outperform conventional 3D Gaussian filtering with optimal setting as well as NLM and CAE.

Hereditary tyrosinemia type 1 metabolites impair DNA excision repair pathways.

Hereditary tyrosinemia type 1 is an autosomal recessive metabolic disorder, which is caused by a defective fumarylacetoacetate hydrolase enzyme, and consequently metabolites such as succinylacetone and p-hydroxyphenylpyruvate accumulate. We used a modified comet assay to determine the effect of these metabolites on base- and nucleotide excision repair pathways. Our results indicate that the metabolites affected the repair mechanisms differently, since the metabolites had a bigger detrimental effect on BER than on NER.

Comparison of 18F PET and 99mTc SPECT imaging in phantoms and in tumored mice.

Our objective was to compare the performance of a micro-single photon emission computed tomography (micro-SPECT) with that of a micro-positron emission tomography (microPET) in a Her2+ tumored mice using an anti-Her2 nanoparticle radiolabeled with (99m)Tc and (18)F. Camera performance was first compared using phantoms; then a tumored mouse administered the (99m)Tc-nanoparticle was imaged on a Bioscan NanoSPECT/CT, while another tumored mouse received the identical nanoparticle, labeled now with (18)F, and was imaged on a Philips Mosaic HP PET camera. The nanoparticle was radiolabeled with (99m)Tc via MAG(3) chelation and with (18)F via SFB as an intermediate. Phantom imaging showed that the resolution of the SPECT camera was clearly superior, but even with 4 heads and multipinhole collimators, detection sensitivity was 15-fold lower. Radiolabeling of the nanoparticle by chelation with (99m)Tc was considerably easier and safer than manual covalent attachment of (18)F. Both cameras provided accurate quantitation of radioactivity over a broad range. In conclusion, when deciding between (99m)Tc vs (18)F, an advantage rests with the chelation of (99m)Tc over covalent attachment of (18)F, achieved manually or otherwise, but with these small animal cameras, this choice also results in trading lower sensitivity for higher resolution.