Medical Physics
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Preprints posted in the last 90 days, ranked by how well they match Medical Physics's content profile, based on 14 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.
Zhang, X.; OConnor, C.; Castelo, A.; Woodland, M.; Daoud, B.; Paolucci, I.; Albuquerque, J.; Altaie, M. A.; Siddiqi, N.; Patel, A.; Odisio, B.; Brock, K.
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Purpose: To build a 3D U-Net model, BioDeformUNet, to predict the deformation vector field (DVF) of the liver in near real-time, for efficient intra-procedural evaluation of the minimal ablative margin (MAM). Materials and Methods: This retrospective study included 170 contrast-enhanced computed tomography (CECT) image pairs from 157 patients who underwent liver ablation treatment between 2020-2024. Each data instance included one pre-ablation CECT (pre-CECT) and one post-ablation CECT (post-CECT). BioDeformUNet was trained under the guidance of DVFs generated by a biomechanical model-based deformable image registration (DIR) algorithm using a loss function that focused on large liver deformations. Data were split patient-wise into training (92-93 patients), validation (23-24 patients), and testing sets (42 patients). We compared our performance with two deep learning-based DIR methods: VoxelMorph and VFA. Evaluation metrics included: target registration error (TRE), Dice similarity coefficient (DSC), Minimum Ablation Margin (MAM), and inference time. For BioDeformUNet, we additionally evaluated the accuracy of the deformed tumor center-of-mass mapping by comparing the predicted tumor center location with that generated by Morfeus. A mapping error less than 3.0 mm (corresponding to the voxel size) was considered accurate. We used the Wilcoxon signed-rank test to assess the significancy of each test result. Our code is available at https://github.com/XinyueZhang831/BioDeformUNET. Results: The TRE of BioDeformUNet was not significantly different from Morfeus (3.31 BioDeformUNet; 3.23 Morfeus; p-value=0.41). The BioDeformUNet DVF magnitude was within 3.0 mm of Morfeus DVF for an average of 91.9% of the voxels. Tumor mapping errors greater than 3.0 mm occurred in only 8 cases. The inference time of BioDeformUNet was 0.6s per image pair, 0.2s for VoxelMorph, 0.3s for VFA, and 20.2s for Morfeus. Conclusion: BioDeformUNet achieved a similar performance to the biomechanical model-based algorithm but required fewer computational operations, resulting in a 34 times speedup in DVF computation.
Oyarzun Silva, R.; Hernandez Hernandez, P.
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Background. Accurate delineation of the gross tumour volume (GTV) - primary tumour (GTVp) and nodal disease (GTVn) - on FDG-PET/CT is a critical step of head and neck radiotherapy planning. Comparisons between lightweight custom networks and the auto-configured nnU-Net v2 are usually reported as end-to-end pipelines, conflating the contribution of the network with that of the inference-time post-processing applied on top of it. We separated the two. Methods. MiniUNet3D (custom 3D U-Net, 18.3 M parameters) and nnU-Net v2 (3d_fullres, 88.2 M parameters) were trained on the same 578 FDG-PET/CT cases (85/15 author-defined split of the HECKTOR 2025 Task 1 set, 8 centres) and evaluated on the same internal cohort. Three arms were compared pairwise: MiniUNet3D raw output at a fixed 0.5 threshold, MiniUNet3D with a locked adaptive post-processing pipeline, and nnU-Net v2. Comparisons used paired Wilcoxon tests with bootstrap confidence intervals, Bonferroni and Benjamini-Hochberg correction, and Cohen's d; catastrophic failure (Dice < 0.01) was compared with an exact McNemar test. Cases with an empty reference for a given target were excluded from that target's analysis (n = 98 GTVp, n = 93 GTVn). Results. With post-processing matched off, nnU-Net v2 was superior: median GTVp Dice 0.799 versus 0.592 (mean difference -0.244, 95 % CI -0.300 to -0.191; d = -0.88) and GTVn 0.774 versus 0.598 (d = -0.82). Post-processing raised MiniUNet3D to 0.800 (GTVp) and 0.738 (GTVn), recovering 79 % of that difference. Post-processed, MiniUNet3D matched nnU-Net v2 on GTVp Dice (p = 0.113) but remained inferior on nodal disease after Bonferroni correction (Dice p = 0.041; surface Dice p = 0.049). Catastrophic GTVp failures were 25/98 raw, 8/98 post-processed and 1/98 for nnU-Net v2 (McNemar p = 0.016). Inference took 34 s versus 78 s per case on the same GPU. Conclusions. Post-processing recovered most, but not all, of the difference between the two models, and it did not confer robustness: an eight-fold higher rate of empty contours on small primaries persisted, which is the more consequential difference for planning safety. Pipeline comparisons reported without a post-processing ablation risk attributing to a network what post-processing supplied.
Chau, G. N.; Biswas, B. A.; Wagle, B. R.; Maeder, M. E.; Yu, J. B.; Bhattacharya, I.
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Automated lesion segmentation is increasingly central to PSMA PET/CT interpretation, supporting staging, treatment planning, and response assessment at a scale that outpaces available nuclear-medicine expertise. However, automated PSMA-PET/CT whole-body lesion segmentation models are trained on images alone, with no knowledge of where in the body prostate metastases actually tend to occur. Radiologists use clinical domain knowledge of metastatic spread, but its absence in machine learning models produces false positives in anatomically implausible locations and missed lesions in high-risk sites such as the liver. In this work, we explore whether population-level spatial knowledge of metastatic spread can be used to augment deep learning segmentation predictions, and how such a prior should be fused with a network's output, without additional training. We build a data-driven metastasis atlas from 375 expert-annotated whole-body PSMA PET/CT scans and investigate its fusion with a trained segmentation network under a Bayesian framework, in which prediction probabilities from an nnU-Net-based lesion segmentation model serve as the likelihood and the data-driven atlas as the prior. Because metastases occupy only a small fraction of whole-body voxels, the atlas's peak probability is too low, and standard power-scaled or naive Bayesian pooling references lack the tools to deal with this shortcoming. This causes these standard fusion strategies to fail and, in the naive Bayesian case, to sharply degrade performance. We instead derive a calibrated, background-referenced log-odds fusion, one of many possible approaches to combine a population atlas with a deep learning model's predictions, distinct from classical multi-atlas label fusion in that it fuses a single population prior with a trained network's softmax rather than combining several registered atlases. Furthermore, this approach is neutral outside atlas support by construction, reduces exactly to the baseline network when unweighted, and requires no retraining. This atlas fusion significantly improved mean Dice over the baseline nnU-Net on a disjoint internal test set ($+0.011$, Holm-adjusted $p=0.021$) and on an independent external cohort ($+0.0129$, Holm-adjusted $p=3.8\times10^{-16}$), with lesion sensitivity improving from 0.849 to 0.861 internally and Dice improving over baseline in every stratified anatomic region, including the rare, high-risk sites motivating this work, while naive Bayesian pooling degrades performance sharply and power-scaled pooling underperforms it throughout. Our findings suggest that population-level spatial priors can meaningfully augment deep learning predictions in whole-body oncologic segmentation, provided the fusion rule is calibrated to where the prior actually carries signal.
dela Sotta, T.; Saavedra, J. M.; Chang, V.; Xavier, A.; Henriquez, H.; Orellana, Y.; Curimil, J.
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Diffusion models achieve high reconstruction quality in low-dose computed tomography (LDCT), but their iterative sampling trajectories impose substantial computational costs. Unlike unconditional generation, paired LDCT reconstruction starts from an image that already contains the anatomy and spatial structure of the standard-dose CT (SDCT) target; reconstruction primarily requires correcting dose-related noise and artifacts. We therefore introduce Residual Endpoint Flow Matching (REFM), an LDCT reconstruction method that learns to transport an LDCT image directly toward its paired SDCT endpoint rather than defining a noise-to-image trajectory. REFM predicts the residual velocity along linear interpolations between both images and supports single-step and multi-step reconstruction using the same trained network. We evaluate five model capacities using 1 to 50 Euler steps against deterministic U-Net and diffusion-based baselines. Across all REFM variants, one-step inference consistently provides the highest reconstruction quality. On the TCIA validation set, REFM Base achieves 50.98 dB PSNR and 0.9865 SSIM at 94.54 fps, compared with 50.92 dB, 0.9847, and 9.26 fps for DDPM-10. REFM Small retains 50.71 dB while increasing throughput to 198.56 fps. Without fine-tuning, REFM Base also matches the 25-step DDPM baseline on the external Mayo Clinic dataset, although DDPM remains stronger on synthetically degraded CRLM images. Thus, our results show that exploiting paired anatomical correspondence enables diffusion-level LDCT reconstruction with a single step reconstruction.
West, N. A.; McCullum, L.; Cheruvelil, J. T.; Dinh, V. T.; Ding, Y.; Wang, J.; Shah, K.; Learned, K.; Chen, M.; Phan, J.; Lee, A.; Garden, A.; Rosenthal, D.; Fuller, C. D.
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Head and neck radiation oncology, with its complex locality and epidemiology, requires various imaging techniques to achieve sufficient visualization. Through collaboration with medical physicists, radiation therapists, radiation oncologists, and neuroradiologists, our group clinically implemented a standard set of magnetic resonance imaging (MRI) sequences on an MR-simulation scanner for three anatomical regions: skull base, oral cavity, and larynx/pharynx. A total of 41 patients with head and neck cancer and 3 volunteers were scanned on either a 1.5T or 3T MR-simulation scanner. Sequences described include Dixon-based approaches, SPAIR-based approaches, short T2-based approaches, and quantitative imaging methods. We describe and outline the steps to optimize these notable MRI sequences to aid in successful implementation in a radiation oncology clinic.
Odnovol, M.; Lykova, E.
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Background: MRI is widely used in radiotherapy planning due to its high soft-tissue contrast, but geometric distortions can compromise target localization accuracy. Objective: This study aimed to develop an accessible method for assessing geometric distortion in MRI using two phantoms - a commercial anthropomorphic phantom and a custom-made phantom fabricated from ABS plastic. Approach: CT imaging was used as the reference standard. Distortion was assessed through linear measurements of periodic structures in a DICOM viewer, followed by statistical analysis. Significance: The study evaluates the clinical impact of distortion on radiotherapy planning and proposes a cost-effective solution for routine quality assurance in resource-limited settings.
Sandvold, O. F.; Proksa, R.; Perkins, A. E.; Daerr, H.; Koehler, T.; Jacob, T.; Brown, K. M.; Roessl, E.; Noël, P. B.
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Spectral computed tomography (CT) is a burgeoning quantitative imaging technique with applications in oncologic diagnostics, prognostic prediction, tissue perfusion studies, and treatment follow-up. While normalized iodine concentration values have been correlated with microenvironmental biophysical changes, obtaining accurate iodine concentrations, particularly at low concentrations remains difficult due to varying spectral CT instrumentation performance. Hybrid spectral CT systems, combining multiple spectral CT instrumentation techniques, address these quantitation insufficiencies by increasing spectral separation but have not been evaluated on a clinically analogous platform. We validate a hybrid spectral CT system, comprised of clinical-grade components, acquiring four distinct effective spectra and applying efficient noise-reducing weighting schemes to compare iodine noise and bias against conventional kVp-Switching (kVp-S). Two tube current levels (50, 350 mA) and three duty cycle ratios (33/67, 50/50, 75/25) were implemented to elucidate radiation dose exposure and kVp-S parameterization impact. A standard quality assurance (QA) and patient-derived, abdominal IodinePrint phantom were scanned on the system. The average absolute bias in iodine density images of the QA phantom was comparable across acquisition techniques, below 0.5 mg/mL, while quantitative noise improved by 22% using noise-optimized weighting schemes. In the IodinePrint phantom aorta and pancreas structures, the noise-optimized weighting scheme increased signal-to-noise ratio (SNR) by 1.3x compared to kVp-S alone. These results highlight the increased precision of hybrid, multi-channel spectral CT systems and motivate CT designs that enable robust CT biomarker development.
Peirispulle, T. A.; Ware, R.; Korevaar, S.; Hetti Mudiyanselage, P.; Thangarajah, J.; Tennakoon, R.
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Background: Patient-specific dosimetry in targeted radionuclide therapy (TRT) is increasingly supported by quantitative imaging; however, voxel-scale dose estimates cannot resolve cellular and subcellular heterogeneity present within tumor tissue. Conventional cellular dosimetry models often represent cells as regularly packed spheres, which may not capture realistic tumor microarchitecture. This study investigated how histopathology-informed three-dimensional (3D) tumor microarchitecture influences cellular absorbed-dose distributions, predicted radiobiological response, and treatment-related conclusions in TRT. Methods: Realistic 3D cellular tumor models were constructed from thick-section 3D cyclic immunofluorescence (3D CyCIF) imaging data. Monte Carlo radiation-transport simulations were performed for Lu-177, Pd-103, Tb-161 and Y-90, with activity localized in cancer-cell subcellular compartments and in non-cancer targets. Absorbed dose per total cluster decay was calculated individually for each cell nucleus and compared with corresponding simplified spherical tumor models. Cell survival fractions were estimated using the linear-quadratic model, and tumor control probability (TCP) was calculated from the individual cancer-cell survival probabilities. Results: Simplified model overestimated mean cancer-cell nuclear absorbed dose by 9.54% to 14.51% for nuclear localization and by 33.23% to 44.88% for cytoplasmic and membrane localization. In larger tissue models, simplified and realistic geometries produced comparable mean absorbed doses in several cases; however, the realistic models consistently generated broader cellular dose distributions, including low-dose cancer-cell subpopulations not captured by the simplified models. These dose-distribution differences propagated into wider survival-fraction distributions and altered TCP predictions. In the spatially heterogeneous tumor region, the realistic model required 1.11- to 1.33-fold higher activity to reach TCP90 for nuclear localization, and 1.49- to 5.93-fold higher activity for cytoplasmic and membrane localization. For similar tumor control, the radionuclide and source-localization combination associated with the greatest preservation of surrounding non-cancer cells differed between the simplified and realistic models. The intra-voxel analysis further showed that homogeneous voxel-scale activity assumptions can obscure biologically relevant microscopic dose heterogeneity. Conclusion: Native 3D tumor microarchitecture substantially influences cellular absorbed-dose distributions, predicted biological response, and treatment-related conclusions. Histopathology-informed 3D cellular models can be used as a complementary framework for characterizing cellular dose heterogeneity and may improve the evaluation of radionuclides and subcellular targeting strategies in heterogeneous tumor tissue.
Mengistu, S. T.; Flouris, K.
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Background. Deep denoisers restore low-dose chest radiographs but emit a single point estimate with no indication of where the output is reliable, so a confident-looking reconstruction can be locally wrong. In paediatric radiography, where the radiation-dose imperative is sharpest, we ask whether a per-pixel uncertainty map can be attached at no meaningful cost to reconstruction quality. Methods. We develop PP-VAE-Hformer, a hybrid convolution-transformer denoiser with a variational-autoencoder bottleneck (epistemic uncertainty map) and a heteroscedastic dual head (aleatoric map), and run a 19-arm ablation isolating five composite-loss terms on Poisson-Gaussian-degraded paediatric chest radiographs (Kermany collection; 624-image held-out test set), against eight discriminative baselines retrained on identical data and noise. Calibration is assessed by reliability diagrams and post-hoc-scaling; comparisons use Bonferroni-corrected Welch tests with Cohens d as the primary discriminant. Results. A heteroscedastic negative-log-likelihood (NLL) objective buys a calibrated aleatoric map for 1.2 dB PSNR, which two-stage fine-tuning recovers to a statistically indistinguishable 0.010 dB. For the variational variant the Kullback-Leibler (KL) annealing schedule, not the bottleneck itself, is decisive: cyclic annealing closes a 1.10 dB gap over posterior-collapsing linear warmup. Predicted uncertainty tracks realised error (Pearson r > 0.8) with an optimal recalibration scale within 1% of unity. A matched-severity cross-degradation test shows this calibration is model-circular, however: at equal severity the aleatoric map becomes modestly (8-16%, a lower bound) over-confident once the noise model changes, and the Monte-Carlo epistemic map is a weaker error predictor that does not compensate. We additionally document a previously unreported destructive interaction between structural-similarity and Sobel-edge supervision at literature-default weights. Conclusions. A calibrated per-pixel uncertainty map can be attached to a paediatric low-dose CXR denoiser at effectively no reconstruction cost. Its near-perfect calibration is tied to the trained (inverse-crime) noise model, and the Monte-Carlo epistemic map does not reliably substitute where the aleatoric map fails, so an architecture-independent uncertainty estimate (e.g. deep ensembling), a blinded reader study, and real low-dose data are the immediate next steps. Keywords. image denoising; uncertainty quantification; calibration; variational autoen-coder; paediatric chest radiography; low-dose imaging
Do, H. P.; Bekku, M.; Berkeley, D.; Golden, M.; Kitane, S.; Uike, M.; Shinoda, K.; Takayanagi, R.; Takai, H.; Kawai, T.; Seballos, K.; Conley, R.; Sorfleet, K.; Devries, D.; Tymkiw, B.; AlGhuraibawi, W.; Caruthers, S. D.; Kadbi, M.; Provencher, M.; Tashman, S.; Ho, C. P.
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Purpose: To determine the feasibility of a 2-minute multi-echo UTE (mecho-UTE) for CT-like bone-weighted contrast and T2* quantification of tissues with short T2/T2*. Methods: Mecho-UTE data acquired from four patients and five healthy subjects were used to assess image quality of the CT-like contrast. All data were reconstructed using conventional gridding (GRID+CONV) and compared with those reconstructed using conjugate gradient SENSE combined with deep learning-based denoising (CG+DLR). Image resolution and sharpness of the CT-like images were assessed using the full width at half maximum (FWHM) and relative edge sharpness (RESH), respectively. Calimetrix UTE-T2* phantom was used to assess the accuracy of T2* quantification of the mecho-UTE sequence. Results: Two-minute mecho-UTE with CG+DLR has similar accuracy (0.37 {+/-} 0.27 vs. 0.67 {+/-} 0.54 ms, p=0.20) and better precision (0.28 {+/-} 0.16 vs. 1.23 {+/-} 0.29 ms, p<0.001) compared to the 5-minute mecho-UTE with GRID+CONV. The 2-minute mecho-UTE with CG+DLR has higher resolution and sharpness compared to the 5-minute scan with GRID+CONV. Conclusion: It is feasible to achieve simultaneous CT-like contrast and T2* quantification of short-T2 tissues in two minutes. When appropriately used, it may simplify logistics, reduce costs, and eliminate radiation exposure risks.
Feemster, S. G.; Rashidi, A.; Azimi, N.; Yin, Z.; Cherkezyan, L.; Yue, M.; Nett, B. E.; Pourmorteza, A.
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Deep-silicon photon-counting CT uses a detector architecture distinct from cadmium-telluride systems and has not been evaluated for pediatric head imaging. To compare attenuation-dependent performance of deep-silicon photon-counting CT (dSi-PCCT) with energy-integrating detector CT (EID-CT) and assess spectral and ultra-high-resolution (UHR) reconstructions from one acquisition. Graded-thickness cranial attenuator and pediatric head phantoms were scanned at a matched target volume CT dose index of 18 mGy. dSi-PCCT used 120 kVp and generated 50-, 65-, and 100-keV images; EID-CT used 80 and 100 kVp. We measured CT-number bias, noise, contrast, and contrast-to-noise ratio (CNR) across 0--9 mm of nominal skull thickness. Mixed-effects models assessed imaging-condition effects. We compared matched standard-resolution and UHR temporal-bone images and generated calcium- and water-density maps from the same dSi-PCCT scan. Noise increased by 4.54%, 3.07%, and 1.35% per millimeter at 50, 65, and 100 keV, respectively, versus 8.38% and 7.84% at 80 and 100 kVp. Corresponding CNR decreases were 4.17%, 3.25%, and 1.75% versus 8.94% and 8.54% (interaction {rho} < 0.001). Changes in absolute CT-number bias and contrast did not differ among conditions ({rho} = 0.92 and {rho} = 0.59). In the pediatric head phantom, model-estimated 50-keV CNR ratios were 1.299 (95% CI, 1.163--1.452) versus 80 kVp and 1.424 (95% CI, 1.275--1.592) versus 100 kVp. Across three temporal-bone edges, UHR transition widths were 58.6%-61.9% narrower than standard-resolution widths. dSi-PCCT maintained CNR more consistently as nominal skull thickness increased and provided complementary spectral and UHR pediatric head images from one acquisition.
Mei, K.; Roshkovan, L.; Liu, L. P.; Halliburton, S. S.; Sharma, S.; Ross, S.; Stroud, T.; Akino, N.; Yu, Z.; Thompson, R.; Dhanaliwala, A. H.; Litt, H. I.; Noel, P. B.
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Objectives: To characterize image noise, lesion contrast, spatial resolution, and attenuation distribution for deep learning reconstruction (DLR) compared with hybrid iterative reconstruction (IR) in ultra-high-resolution (UHR) photon-counting CT (PCCT) of the lung, using a patient-derived 3D-printed phantom, and to apply the same analytical framework to patient examinations acquired on the same system. Materials and Methods: A patient CT scan-derived lung phantom containing three digitally inserted lesions of differing morphology was fabricated using PixelPrint 3D printing and imaged on a CZT-based PCCT prototype at four dose levels (CTDIvol 6, 4, 2, and 1 mGy). Images were reconstructed with hybrid iterative reconstruction at normal resolution (512 by 512) and UHR (1024 by 1024), and with DLR at UHR. Image noise, lesion contrast, and contrast-to-noise ratio (CNR) were measured within prespecified regions of interest replicated across reconstructions by coordinate transfer. Spatial resolution was assessed by the modulation transfer function (MTF) from a high-contrast edge at eight locations. Attenuation distribution and local texture were characterized using histograms and gray-level co-occurrence matrices (GLCMs) within a structured parenchymal region. Two patient examinations with part solid lung nodules acquired on the same prototype were analyzed as illustrative examples, with solid and ground-glass components segmented separately and their attenuation distributions compared. Results: In the phantom, DLR reduced image noise relative to UHR hybrid iterative reconstruction (7.8% at 6 mGy and 15.2% at 1 mGy). Lesion contrast was constant across reconstructions and dose levels, so CNR differences reflected differences in noise alone. MTF curves for DLR lay above those for hybrid iterative reconstruction across the evaluated spatial frequency range at both 6 and 1 mGy, averaged +0.4 lp/mm in MTF50. In a structured parenchymal region, the attenuation histogram mode became progressively narrower from hybrid iterative reconstruction at 1 mGy to DLR at 6 mGy (averaged -23%), while mode position and mean regional attenuation were preserved, consistent with reduced partial-volume mixing rather than altered attenuation. In the patient example, the attenuation distributions of solid and ground-glass components were more widely separated with UHR DLR (2.0) than with either hybrid iterative reconstruction (1.6). Conclusions: In UHR photon-counting CT of the lung, DLR reduced image noise while preserving lesion contrast and regional attenuation, increased measured MTF at a high-contrast edge, and produced attenuation distributions consistent with reduced partial-volume mixing at material boundaries. The same effect was observed in the separation of solid and ground-glass components in two patient examples.
Di Giovanni, D. A.; Takada, A.; McNabb, E.; Dana, J.; Yokota, H.; Tsuboyama, T.; Zakarian, R.; Vallieres, M.; Tsui, J. M. G.; Reinhold, C.
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Purpose: To evaluate how segmentation architecture and dataset-adaptive configuration influence uterine MRI segmentation across heterogeneous benign and malignant tasks. Methods: U-Net, Swin-UNETR, and MedNeXt were compared with nnU-Net as a self-configuring reference across T2-weighted MRI datasets: public multiclass UMD anatomy/fibroid segmentation (n=300), institutional endometrial cancer tumor segmentation (n=206), and institutional uterine mass lesion segmentation (n=234). A relabeled external UMD-style cohort (n=12) assessed domain shift. Models used fixed partitions, fold ensembling, Dice, HD95, ASSD, volume error, and paired bootstrap comparisons with Holm correction. Results: MedNeXt was the strongest manually controlled architecture. nnU-Net achieved the highest performance on all internal datasets and external testing. Macro-Dice reached 0.761, 0.746, and 0.814 for nnU-Net on UMD, endometrial cancer, and uterine mass datasets, respectively, versus 0.722, 0.726, and 0.789 for MedNeXt. The nnU-Net-MedNeXt gap was largest for multiclass UMD segmentation and smaller in binary tasks. External testing degraded all models; nnU-Net remained highest (0.542), followed by MedNeXt (0.490), U-Net (0.396), and Swin-UNETR (0.287). Conclusions: Uterine MRI segmentation performance depended on task, architecture, and evaluation domain. MedNeXt supported modern convolutional design as a strong manual baseline, but nnU-Net remained the most robust overall, emphasizing the importance of dataset-adaptive configuration and external validation.
Curtis, N.; Kim, M. M.; Verginadis, I.; Zou, W.; Diffenderfer, E. S.; Koumenis, C.; Koch, C. J.; Wiersma, R. D.
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Purpose: FLASH radiation with ultra-high dose rate delivery is less damaging to normal tissue than conventional radiation ( <1 Gy/s). Since radiation depletes oxygen (ROD), this damage reduction might occur via the oxygen effect. ROD experiments have shown an oxygen-independent reduction in dose effectiveness at FLASH dose rates. However, prior in vivo ROD measurements relied on extracellular oxygen probes that could not penetrate cell membranes, leaving intracellular effects unresolved. To investigate the ROD hypothesis more directly, we developed a novel three-component immunohistochemical assay with algorithmic image processing to quantitatively compare DNA damage following FLASH and conventional irradiation in mouse jejunum. Methods: Mice received intravenous EF5 2 hours before proton irradiation at FLASH (103.63 +/- 17.2 Gy/s) or conventional (0.73 +/- 0.1 Gy/s) dose rates of 2.5 Gy or 5 Gy, with unirradiated controls. Mice were euthanized 30 minutes post-irradiation, and 10 cm of jejunum was frozen as a 'Swiss Roll', sectioned, stained, and imaged. Tissue sections were stained for {gamma}-H2AX, DRAQ5, and EF5 to assess DNA double-strand breaks, total DNA content, and hypoxia, respectively. An in-house algorithm identified individual cell nuclei and registered each nucleus with its corresponding {gamma}-H2AX and EF5 signals, enabling quantitative measurement of DNA damage as a function of local tissue hypoxia. Results: Hypoxia was greatest in the villi and, to a lesser extent, the outer jejunal musculature, with substantial inter-animal variation. DNA damage decreased in hypoxic regions. FLASH enhanced the hypoxia-associated reduction in DNA damage compared with conventional dose rate and, separately, revealed an oxygen-independent reduction in DNA damage, suggesting an additional FLASH sparing mechanism. Conclusion: Current results suggest that FLASH compared to conventional dose rate radiation caused less DNA damage with increasing effect at low oxygen levels, a result consistent with ROD as a mechanism. Pronounced tissue heterogeneity in murine jejunum requires further studies to segment the effect for each tissue type.
Azimi, N.; Brian-Choux, A.; Feemster, S.; Rahbar, A.; Linder, H.; Crotty, D.; Yin, Z.; Balthazar, P.; Pourmorteza, A.
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To compare virtual noncontrast (VNC) error between deep-silicon photon-counting CT (PCCT) and dual-energy energy-integrating detector CT (EID-CT) in a matched phantom and characterize tissue-specific error in humans. This prospective exploratory study included a matched phantom experiment and pilot human evaluation. Prototype projection-domain water-density maps served as the VNC surrogate. Twenty-four vials containing 0.1--20 mg I/mL in deionized water or simulated blood were scanned with PCCT and EID-CT. Three men underwent true noncontrast and contrast-enhanced PCCT; 80 matched measurements were analyzed. Paired t tests and mixed-effects models assessed system differences and iodine associations. Three participants (mean age, 67 {+/-} 10 years; all men) were included. Mean VNC error was 29.1 HU lower with PCCT than EID-CT (95% CI, 15.5--42.7 HU; {rho} < 0.001). Error was not associated with iodine concentration for PCCT (slope, 0.03 HU per mg I/mL; 95% CI, -0.92 to 0.98; {rho} = 0.95) but increased for EID-CT (slope, 3.51 HU per mg I/mL; 95% CI, 2.56--4.46 HU; {rho} < 0.001). The slopes differed by 3.48 HU per mg I/mL ({rho} < 0.001). In humans, errors in five non-blood-pool tissues were within 5 HU. Error was not associated with iodine concentration among 61 non-blood-pool measurements (adjusted slope, -0.17 HU per mg I/mL; 95% CI, -1.22 to 0.88; {rho} = 0.75). PCCT provided VNC measurements with errors closer to zero and less dependent on iodine than EID-CT in the phantom. In humans, error was generally small in non-blood-pool tissues and was not associated with iodine concentration.
Li, X.; Kallman, C.; Zhang, D.; Guo, C.; Zhou, Y.
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Objective: To identify common photon-counting CT (PCCT) virtual monochromatic imaging (VMI) settings for accurate hepatic fat fraction (FF) quantification across different body sizes, including large body habitus. Methods: Six non-iodinated fat lesions (FF 5%-40%) were embedded in anthropomorphic liver phantoms representing medium-sized (25x32.5 cm^2) and large (31x39 cm^2) abdomens. Phantoms were scanned on a PCCT system (NAEOTOM Alpha) at 120 and 140 kV. CT numbers were measured in VMIs at 40-190 keV in 1-keV increments. Linear regression between the ground-truth FF and measured Hounsfield units (HU) was used to estimate FF. Common optimal VMI settings yielding the minimum relative root-mean-square error (rRMSE) in both phantoms were identified. Results: A single VMI setting of 70 keV at 140 kV demonstrated the best overall performance across body sizes, with FF (%) = -0.689HU + 36.51 (R^2 > 0.996), achieving rRMSE [≤]3.4% and absolute RMSE [≤]0.7% in both phantoms. Robust performance (rRMSE [≤] 5%) was consistently maintained across 69-71 keV using identical calibration parameters for both phantoms. These results represented a substantial improvement over previously reported dual-energy CT (DECT) performance, while enabling accurate quantification on PCCT at radiation doses approximately 40% lower than those used in prior DECT protocols. Conclusion: PCCT enables accurate and robust hepatic fat fraction quantification independent of body size. A single protocol at 140 kV with VMIs of 69-71 keV consistently achieved low quantification errors, demonstrating strong potential for opportunistic liver fat assessment using PCCT, especially in obese patients.
Azimi, N.; Holmes, T. W.; Brian-Choux, A. R.; Yin, Z.; Crotty, D.; Nezami, N.; Pourmorteza, A.
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To evaluate whether eight-bin deep-silicon photon-counting CT can quantify iodine and gadolinium separately and distinguish radiopaque embolic beads from vascular contrast in tumor phantoms. In this phantom study, two-input decomposition of scanner-generated iodine and water images was compared with three- and five-material decomposition of five reconstructed energy-bin images in 56 common test vials, including nine simulated-blood preparations. One tantalum and one bismuth vial were also tested with five-material decomposition. A separately calibrated two-input method using scanner-generated 70-keV and iodine images was applied to four static 3D-printed tumor vascular models: iodine-only and gadolinium-only controls and two models with iodine-containing beads and gadolinium-filled channels. Concentration errors were summarized by bias and root mean square error (RMSE). For iodine, RMSE was 0.40, 0.73, and 1.12 mg I/mL with two-input, three-material, and five-material decomposition, respectively; corresponding gadolinium RMSEs were 0.57, 0.55, and 0.46 mg Gd/mL. Two-input biases were +0.01 mg I/mL and +0.29 mg Gd/mL. Five-material decomposition distinguished tantalum and bismuth in the separate test vials. Beads and vascular gadolinium were spatially separated in the tumor models. In the two bead-containing models, gadolinium measured 32.56 {+/-} 8.02 and 37.02 {+/-} 7.93 mg Gd/mL (mean {+/-} spatial SD), compared with the prepared 35.00 mg Gd/mL. Deep-silicon photon-counting CT separately visualized radiopaque embolic beads and quantified vascular gadolinium from a single acquisition. Recalibrated scanner-generated images supported quantitative dual-contrast imaging, while research energy-bin decomposition distinguished additional materials.
Zareian, B.; Fontaine, K.; Bini, J.
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Background. Roughly, half of new type 1 diabetes (T1D) diagnoses occur in individuals under 18 years old and represent a more aggressive destruction of beta cell mass (BCM). [11C]-(+)-PHNO positron emission tomography (PET) imaging is used to assess BCM, but current pancreas PET imaging protocols are limited to adults. Previously published full count data from six healthy controls and five T1Ds (6M/5F; 22 to 53 years old) were used for retrospective analysis. Dynamic [11C]-(+)-PHNO PET/CT scans were acquired and reconstructed using full-count list-mode data. For the current comparison to full count data, 50%, 25% and 10% down-sampled count data were re-reconstructed. Pancreas and spleen (reference region) time-activity-curves (TACs) were assessed, and volume of distribution (VT, mL/cm3) was estimated using the reversible 1-tissue compartment model (1TC) with tmax of 30 min for all count levels. Pancreas and Spleen VT estimates (1TC; tmax= 30 min) were used to calculate non-displaceable binding potential (BPND) and were then correlated to semi-quantitative methods of standardized uptake value ratio (SUVR-1) (20-30 min; ref: spleen) to examine simplified methods using simulated low dose protocols. Finally, we performed dosimetry in adult, adolescent and pediatric phantoms to assess radiation dose for simulated low-dose protocols. Results. Qualitatively, increasing noise can be visualized at successive reduced-count levels images, compared to full-count images. Despite progressively increasing noise in reduced-count images, TACs at each reduced-count level remained similar to full-count TACs in both HC and individuals with T1D. Quantitatively, 1TC VT estimates were similar for all reduced count levels and range of tmax values, compared to full-count (all R2[≥]0.99). Pancreas SUVR-1 (20-30 min) and pancreas BPND (tmax = 30; ref: spleen) were highly correlated for all count levels (all R2[≥]0.80). All age groups were under both the yearly occupational and research scan radiation dose limits when examining mean effective dose equivalent with reduced (1/10th) injected dose protocols. Conclusion. Low-count reconstructed data and simplified reference region approaches provide accurate quantification compared to full-count reconstructions. These results provide evidence that it is possible to perform accurate quantification using simulated low dose protocols to quantify BCM for use in individuals with T1D under 18 years old.
Azamat, S.; Singh, A.; Midya, A.; Zhang, Z.; Gilkey, M.; Hajibonabi, F.; Sompalle, P.; Rastinehad, A.; Verma, S.; Kikano, E. G.; Sanda, M.; Hajiha, M. N.; Shiradkar, R.; Viswanath, S. E.; Madabhushi, A.
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Purpose: To evaluate whether visually assessed high-quality prostate MRI, as defined by the Prostate Imaging Quality (PI-QUAL) scoring system, is sufficient to ensure consistent AI model performance, or whether hidden acquisition-related technical effects introduce variability that cannot be detected through visual inspection. Methods: This retrospective study included 568 bpMRI scans from seven institutions, classified using PI-QUAL v2 into high-quality (scores 2-3) and low-quality (score 1) groups. Quantitative image quality features were extracted using MRQy from T2w and ADC sequences. Three experiments were conducted on high-quality scans: (1) unsupervised clustering to identify hidden technical batch effects; (2) V-Net models (M) for prostate capsule segmentation on T2w using single-cluster and balanced multi-cluster training strategies; and (3) VoxelMorph-based deformable registration (M2) to align ADC maps to T2w images. Performance metrics included DSC, precision, recall, volume ratio, HD95, ASSD, and TRE. Kruskal-Wallis tests assessed cross-cluster variability, Two One-Sided Tests (TOST) evaluated performance equivalence, and bootstrap resampling quantified training efficiency. Results: Clustering identified four clusters among 277 high-quality bpMRI scans. Single-cluster models showed variable performance (DSC=0.41-0.85) with significant batch effects (p<0.001), even with 140 training samples. The balanced multi-cluster model (n=60) eliminated batch effects (p=0.075), achieved equivalent performance (p<0.001), and demonstrated 2.23-fold greater training efficiency despite using 2.3-fold fewer samples. Registration performance also varied significantly across clusters (TRE=0.86-5.47 mm, p<0.001). Conclusion: Acquisition-related batch effects significantly impact AI generalizability in prostate MRI, even among high-quality scans. Quantitative clustering enables detection of technical variations and supports diversity-aware training strategies that achieve equivalent performance with 2.3-fold fewer samples while eliminating batch effects.
Chen, W.; Chen, J.
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Coarse to fine segmentation is a natural strategy for three dimensional lesion delineation becausefull resolution processing of an entire scan is expensive while only a small fraction of the volume contains pathology. Its main failure mode, however, is structural: a lesion missed by the coarse stage is usually absent from the region of interest and therefore cannot be recovered by the fine stage. This problem is most severe for small, low contrast, and multifocal lesions. We introduce RECALLREFINE, a coverage constrained coarse to fine framework that treats candidate-region selection as a recall critical learning problem rather than a deterministic crop around the coarse mask.A full-volume network first predicts coarse lesion probabilities and multi-scale features. A candidate score network then combines coarse probability, predictive uncertainty, feature novelty, and spatial context to score overlapping 3D blocks. During training, a differentiable selector is optimized with a component-wise coverage objective that requires every annotated lesion instance to remain covered by at least one selected block under a fixed refinement budget. Selected blocks are processed at native resolution by a local refiner with a context-ring branch, and overlapping predictions are merged back into the full volume. Across four public 3D lesion benchmarks, RECALLREFINE improves mean tumor Dice from 76.5% for the strongest matched coarse-to-fine baseline to 78.4%, while increasing sensitivity for lesions below 10 mm from 60.9% to 70.8%.At a 20% candidate budget, the selector covers 94.4% of lesion instances, substantially reducing irreversible coarse-stage misses. The results suggest that the central problem in cascaded lesion segmentation is not only how to refine a detected lesion, but how to guarantee that difficult lesions are still represented in the refinement set.