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Medical Physics

Wiley

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 0.02% match score for this journal, so anything above that is already an above-average fit.

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Radiation-induced disruption of cardiac mitochondrial bioenergetics and nucleotide homeostasis in mice

Stawarska, K.; Kawecka, A.; Urbanowicz, K.; Kaminska, J.; Posiewnik, M.; Braczko, A.; Michnowska, W.; Kutryb-Zajac, B.; Tomasik, B.

2026-06-10 biochemistry 10.64898/2026.06.08.730816 medRxiv
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AimsCardiac stereotactic body radiotherapy (SBRT) has emerged as a promising non-invasive treatment for refractory ventricular tachycardia (VT). Intriguingly, the clinical benefit of SBRT often occurs within days of treatment, preceding the development of radiation-induced fibrosis, suggesting alternative underlying mechanisms. This study aimed to investigate the acute and persistent effects of ionizing radiation on cardiac bioenergetics and mitochondrial function, providing mechanistic insights into early cardiac responses to radiation exposure. Methods and resultsWe employed a translational multi-model approach, including HL-1 mouse cardiomyocytes and ex vivo mouse left ventricular living myocardial slices (LMS). Bioenergetic profiling, assessment of mitochondrial respiration and calcium handling were performed following exposure to clinically relevant radiation doses (10 Gy and 25 Gy). In HL-1 cardiomyocytes, 10 Gy induced acute bioenergetic stress, characterized by reduced adenylate energy charge, cytoskeletal disorganization, and impaired mitochondrial respiration, accompanied by increased calcium oscillation amplitude. 25 Gy exposure led to NAD+ depletion but paradoxically enhanced mitochondrial respiratory capacity, suggesting an adaptive metabolic response. Murine myocardial slices demonstrated reduced creatine content while preserving energy balance as indicated by phosphocreatine/ATP ratio, indicating tissue-level metabolic resilience. These findings reveal model-specific metabolic perturbations induced by cardiac irradiation, underscoring the importance of tissue complexity in modulating the cardiac response to radiation. ConclusionThis study demonstrates that ionizing radiation at 10 Gy and 25 Gy induced dose- and model-dependent bioenergetic alterations in cardiac cells and tissues, including changes in mitochondrial respiration, nucleotide levels, and redox balance. While 10 Gy exacerbated metabolic disruption, 25 Gy triggered partial recovery, highlighting differential responses across cellular and tissue levels. These metabolic changes may contribute to the immediate effects of cardiac SBRT and potentially to long-term cardiotoxicity. Translational PerspectiveOur study provides novel mechanistic insights into the metabolic effects of cardiac irradiation, revealing acute mitochondrial stress, redox imbalance and alterations in calcium homeostasis in cardiomyocytes. These early bioenergetic changes may contribute to both the immediate anti-arrhythmic effects and the potential long-term cardiotoxicity of stereotactic body radiation therapy. Understanding these molecular responses is essential to optimize the therapeutic window of cardiac radioablation and minimize adverse effects. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/730816v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@d963d3org.highwire.dtl.DTLVardef@28e03dorg.highwire.dtl.DTLVardef@19a0165org.highwire.dtl.DTLVardef@1d1ca34_HPS_FORMAT_FIGEXP M_FIG C_FIG

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FreqFuseNet: Resolving Feature-Scale Mismatch in Dual-Frequency Fusion for Thin-Wall Head-and-Neck OAR Segmentation

Chen, W.-Y.; Wan, S.-Y.; Lin, G.-Y.

2026-07-13 radiology and imaging 10.64898/2026.07.09.26357642 medRxiv
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Accurate segmentation of thin-wall organs-at-risk (OARs)-the cochlea, vestibular semicircular canals, internal auditory canal, tympanic cavity, and middle ear-is clinically relevant for head-and-neck radiotherapy planning, yet these small, thin-wall structures remain among the most challenging targets for automated delineation. Dual-frequency feature fusion is a promising direction for boundary-sensitive representation, but under the investigated FP16 FFT-FcaNet setting, we observe an approximately 863-fold activation-scale mismatch between the FFT and FcaNet branches, causing a nominal 5 percent residual coefficient to behave as an approximately 43-fold dominant term. We propose FreqFuseNet, which resolves this mismatch by normalizing the FcaNet branch to the FFT activation scale before residual injection with a fixed low-amplitude coefficient (beta = 0.05), restoring beta as an interpretable 5 percent residual-amplitude coefficient relative to the FFT feature scale. Under a controlled binary per-OAR ROI protocol on the SegRap2023 head-and-neck CT benchmark across 10 clinically prioritized thin-wall OARs, FreqFuseNet achieves Dice of 0.849, HD95 of 0.824 mm, and SDice@1mm of 0.959 in the primary seed, with comparable performance in an independent second seed (Dice 0.843, HD95 0.823 mm). FreqFuseNet yields statistically significant case-level aggregate improvements over 3D U-Net and MedNeXt-S (Wilcoxon p < 0.01 and p < 0.05, respectively), using only 29.7 million parameters versus 414.6 million for the full wavelet baseline.

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Automated Design of Patient-Specific 4D-Printed Phantoms for Quality Assurance of Adaptive Radiotherapy on a 1.5T MR-Linac

Hamkins, H. M.; Tam, K. H.; Sobremonte, A.; Jogi, S.; Koay, E.; Hassanzadeh, C.; Segars, P.; Tyagi, N.; Subashi, E.

2026-07-13 radiology and imaging 10.64898/2026.07.09.26357659 medRxiv
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Background: Independent end-to-end verification of adaptive radiotherapy on MR-Linac systems is limited by the lack of patient-specific phantoms able to reproduce imaging and dosimetric properties from CT and MRI scanners. We present a method for automated generation of 4D, patient-specific, multi-material 3D-printable phantoms for quality assurance of adaptive radiotherapy on a 1.5T MR-Linac. Methods: Patient images were automatically segmented using a pretrained deep learning model. The segmented structures were converted into high-resolution 3D meshes and assembled into printable phantoms. A dosimeter holder was inserted at user-defined anatomical locations, with orientation optimized to avoid traversal across heterogeneous tissue interfaces. Physiological motion was incorporated by generating phantoms from images at different timepoints and interpolating deformation fields to create continuous 4D models. Multi-material organs designed by mixing a set of six polymers at various proportions were used to reproduce tissue-specific imaging properties. The properties of material mixtures were evaluated in a clinical CT simulator and a 1.5T MR-Linac. Results: The proposed workflow enables automated generation of anatomically realistic phantoms with several types of embedded dosimeters. A discrete search method was designed for placement and immobilization of OSLD, film, and ion chamber dosimeters. Calibration curves for Hounsfield units were derived through variations in radiopaque material content, while MR signal intensity was modulated by gel and tissue matrix mixtures. Patient-derived abdominal phantoms were fabricated at multiple scales while replicating internal anatomical detail. Multi-dimensional phantom generation enabled continuous representation of motion states with consistent mesh topology across phases. Conclusions: We demonstrate an end-to-end workflow for automated generation of 4D patient-specific phantoms for MR-Linac quality assurance. The method combines realistic anatomy, embedded dosimetry, multimodal imaging properties, and physiological motion within a single fabrication framework. This approachmay enable an improved validation of adaptive radiotherapy workflows in MR-guided treatment devices.

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Retrieval-Augmented Claude Opus 4.7 and GPT-5.5 Surpass Human Performance on the Nuclear Cardiology Board Preparation Exam (and Claude Drafts a Paper About it)

Killekar, A.; Shanbhag, A.; Miller, R. J.; Dey, D.; Bourque, J.; Phillips, L.; Chareonthaitawee, P.; Slomka, P.

2026-05-13 radiology and imaging 10.64898/2026.05.08.26352768 medRxiv
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BackgroundPrevious studies evaluated large language model (LLM) performance on the American Society of Nuclear Cardiology (ASNC) Board Preparation Exam. Without domain-specific context, the best model (GPT-4o) achieved 63.1%, below the estimated 65% passing threshold and the 78% mean score of human fellows-in-training (FITs). Providing textbook context improved GPT-4o to 73.8% on text-only questions, but still fell short of human trainees. Whether next-generation LLMs with retrieval-augmented generation (RAG) can exceed this gap is unknown. MethodsClaude Opus 4.7 and GPT-5.5 were administered all 168 questions (141 text-only, 27 image-based) from the 2023 ASNC Board Preparation Exam across 5 iterations each, using RAG with a nuclear cardiology textbook, companion atlas, and ASNC clinical guidelines. Claude used local FAISS-based semantic retrieval; GPT-5.5 used Azures cloud-hosted vector store. Performance was compared to prior LLM results and 13 human FITs. ResultsAcross 5 iterations, Claude Opus 4.7 achieved a mean accuracy of 86.3% {+/-} 1.4% (text 88.8%, image 73.3%). GPT-5.5 achieved 86.7% {+/-} 2.2% (text 88.5%, image 77.0%) but refused a mean of 12.2 questions (7.3%) per iteration due to safety filters. Both models surpassed the human FIT mean (78.0%) and the estimated passing threshold. Compared to GPT-4o without context (63.1%), this represents a 23-percentage-point improvement in 18 months. ConclusionNext-generation LLMs with RAG now surpass average human trainee performance on nuclear cardiology board preparation questions, suggesting significant potential as educational tools and knowledge-reference aids in cardiovascular imaging. Condensed AbstractAcross 5 iterations each, Claude Opus 4.7 and GPT-5.5 with retrieval-augmented generation achieved mean accuracies of 86.3% and 86.7% on the 2023 ASNC Board Preparation Exam (168 questions), both surpassing the mean human fellow-in-training score of 78%. GPT-5.5 refused a mean of 12.2 questions (7.3%) per iteration due to safety filters. These results represent a 23-percentage-point improvement over the best prior LLM without context (63.1%), demonstrating that RAG-enhanced LLMs have reached human-level proficiency in nuclear cardiology knowledge. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/26352768v2_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@5f2465org.highwire.dtl.DTLVardef@4e80d3org.highwire.dtl.DTLVardef@1ebbb93org.highwire.dtl.DTLVardef@167d3c1_HPS_FORMAT_FIGEXP M_FIG C_FIG Overview of the three-study research arc evaluating LLM performance on the 2023 ASNC Board Preparation Exam. Study 1 (2024) tested four LLMs without context (best: GPT-4o, 63.1%). Study 2 (2025) added textbook context to GPT-4o (73.8%). Study 3 (2026, current) evaluated Claude Opus 4.7 and GPT-5.5 with retrieval-augmented generation across 5 iterations each (mean 86.3% and 86.7%, respectively), both surpassing the human fellow-in-training mean of 78%. Right panel shows the performance scale with key thresholds.

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Dual-Filament 3D Printing of Patient-Specific CT Phantoms with Embedded Implants and Tunable Metal-Artifact Intensity

Pasyar, P.; Mei, K.; Im, J. Y.; Roshkovan, L.; Geagan, M.; Noël, P. B.

2026-07-20 radiology and imaging 10.64898/2026.07.17.26358319 medRxiv
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ABSTRACT Background: Metallic implants such as orthopedic screws, prostheses, and dental hardware produce beam-hardening, photon-starvation, and streak artifacts that degrade computed tomography (CT) image quality, and the metal artifact reduction (MAR) methods developed to mitigate them require objective, reproducible benchmarking. Purpose: Objective evaluation of MAR algorithms in CT is hindered by the absence of phantoms that simultaneously provide anatomically realistic backgrounds, embedded implants of known geometry, and controllable, ground-truth--referenced artifact intensity. We present a dual-filament, voxel-level three-dimensional (3D) printing method that fulfills these requirements and demonstrate its capabilities on a clinically representative cervical spine case with embedded orthopedic spinal screws. Methods: The proposed method extends the PixelPrint framework, a fused-deposition-modeling (FDM) workflow that converts clinical Digital Imaging and Communications in Medicine (DICOM) data directly into 3D-printer Geometric code (G-code) without intermediate segmentation or surface meshing, to interleaved, voxel-level deposition of two filaments: a calcium-doped polylactic acid (PLA) for soft tissue and bone, and a higher-attenuation metal-doped PLA for metallic implants. For demonstration, anonymized DICOM data of a healthy cervical spine were used to design and fabricate three matched phantoms, each with six embedded spinal screws at C4--C6: a 0% metal-infill ground-truth phantom, a 50% medium-metal-infill phantom, and an 85% high-metal-infill phantom. All phantoms were scanned on a clinical spectral CT system at 120 kVp and 1000 mAs, reconstructed at 0.67 mm slice thickness with virtual monoenergetic imaging (VMI) across 50--190 keV. Method performance was characterized by region of interest (ROI)-based Hounsfield Unit (HU) agreement with the source patient data and by the noise-independent Gumbel-distribution p-index metric. Results: The dual-filament method reproduced patient anatomy, soft-tissue contrast, and screw geometry with high fidelity. ROI HU values agreed with patient data within {+/-}25 HU for soft tissue and trabecular bone; cortical regions were underestimated owing to the current ceiling of the calcium-doped PLA used in this study. The tunable-artifact behavior was quantified as follows: the Gumbel location parameter scaled monotonically from 46.7 HU (no-metal background) to 57.1 HU (50% infill) to 90.5 HU (85% infill) for the VMI 70 keV with standard filter. High-keV VMI reconstructions substantially reduced streak and beam-hardening artifacts while preserving anatomic detail. Conclusions: The proposed dual-filament, voxel-level PixelPrint method enables the fabrication of patient-specific, multi-material CT phantoms with embedded metallic implants and controllable, ground-truth--referenced artifact intensity. Although demonstrated here in a single cervical-spine case, the workflow is anatomy- and implant-agnostic by construction and could in principle be adapted to other musculoskeletal sites (e.g., knee, hip, dental) and implant materials, providing a reproducible methodological foundation for benchmarking MAR algorithms, characterizing spectral CT performance, and validating emerging photon-counting detector systems. Keywords: 3D printing methodology; fused deposition modeling; voxel-level multi-material printing; spectral computed tomography; metal artifact reduction; phantom design; orthopedic implants; dual filament; PixelPrint.

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Standardised evaluation and monitoring of site-specific AI performance with physical CT phantoms

Genske, U.; Laudani, A.; Yan, L.; Peng, Y.; Boening, G.; Ulas, S. T.; Wagner, M. P.; Diekhoff, T.; Hamm, B.; Jahnke, P.

2026-07-02 radiology and imaging 10.64898/2026.07.01.26357033 medRxiv
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Artificial intelligence (AI) applications in computed tomography (CT) imaging require objective and continuous testing, yet standardised methods for this purpose have not been established. Here, we present a framework using physical phantoms for standardised testing and monitoring of AI, demonstrated in liver lesion detection. We begin by designing phantoms tailored to the anatomical input domain expected by AI algorithms, and then systematically assess how AI performance is affected by variations in scanner technology and operation across two clinical CT systems. Next, we perform longitudinal monitoring, yielding consistent results over fifteen months on both systems. Finally, we validate clinical relevance by demonstrating that AI models trained on phantom data generalize effectively to patients and exhibit no evidence of phantom-specific adaptation. Our findings show that anatomically realistic phantoms enable standardised, site-specific testing and monitoring of AI, providing a proactive method for local and cross-institutional quality assurance.

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An Open, Reproducible Gamma-Variate Pipeline for CT-Perfusion Time-Attenuation Curve Analysis, with Standardized (ASIST-Japan) Map Visualization

Yamamoto, S.

2026-06-29 radiology and imaging 10.64898/2026.06.26.26356666 medRxiv
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CT perfusion (CTP) is central to acute-stroke and oncologic imaging, yet quantitative outputs vary substantially across vendor software, undermining reproducibility. We present an open, transparent core (ctp-core) that fits first-pass time-attenuation curves with a gamma-variate model, derives perfusion indices (peak enhancement, time-to-peak, bolus-arrival time, and area under the curve) analytically from the fitted parameters, and renders parametric maps with the ASIST-Japan standardized lookup table (a-LUT) so that visualization is comparable across sites. Every parameter, bound, and processing step is exposed. The method is validated on Monte-Carlo synthetic curves with known ground truth; no confidential or patient data are used. Across signal-to-noise ratio (SNR) levels 5 to 100 (200 independent runs per level) the pipeline recovers peak time to within 0.03-0.52 s and peak amplitude to within 0.4-8.1% (mean absolute error), degrading monotonically with noise; at a representative SNR of 20 it recovers peak time within 0.13 s, peak amplitude within 2.0%, and bolus-arrival time within 0.51 s, with fit quality R-squared = 0.98. The reproducibility demonstration is deterministic (fixed seed) and re-runs to bit-stable metrics. All code, the synthetic-data generator, the standardized-visualization module, evaluation scripts, and a 34-test suite are released openly for independent verification. The contribution is a fully open, parameter-transparent gamma-variate plus standardized-visualization pipeline with reproducible synthetic benchmarks: a reference others can audit, reuse, and build on.

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Scan length as a major driver of CT radiation dose: a diagnostic reference level audit from Kosovo

Rudi, G.; Vula, F.; Bicaku, A.; Dedushi, K.; Ahmetgjekaj, I.

2026-05-17 radiology and imaging 10.64898/2026.05.12.26353024 medRxiv
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Computed tomography is the largest contributor to population radiation dose from medical imaging, yet no diagnostic reference levels (DRLs) have been published from Kosovo or the Western Balkans. This retrospective audit analyzed all CT examinations performed on a 128- slice scanner at the University Clinical Centre of Kosovo between January and March 2026. After exclusions, 1,535 acquisitions from 1,092 patients across nine examination categories were analyzed. Local DRLs were defined as the 75th percentile and compared against German (BfS 2022) and Turkish (Kahraman et al., 2024) reference values. Head CT (n = 590) demonstrated CTDIvol 4.7% below the BfS DRL yet scan length 98.5% above the orientation value (median 25.8 vs 13 cm). Abdomen-pelvis CTDIvol matched the BfS reference while scan length exceeded it by 28%. Coronary CTA showed CTDIvol +377%, consistent with retrospective ECG gating. Excess scan length, not CTDIvol, is the major driver of elevated dose at this institution. The identified excesses are correctable through technologist landmarking training, protocol review, and enabling iterative reconstruction.

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Feature-Based Parametric Response Mapping on Thoracic Computed Tomography for Robust Disease Classification in COPD

Namvar, A.; Shan, B.; Hoff, B.; Labaki, W. W.; Murray, S.; Bell, A. J.; Galban, S.; Kazerooni, E. A.; Martinez, F. J.; Hatt, C. R.; Han, M. K.; Galban, C. J.; Ram, S.

2026-04-27 radiology and imaging 10.64898/2026.04.24.26351675 medRxiv
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PurposeTo develop an interpretable feature-based Deep Parametric Response Mapping (PRMD) method that combines wavelet scattering convolution networks and machine learning to spatially detect and quantify functional small airways disease (fSAD) and emphysema on paired inspiratory-expiratory CT scans, with enhanced noise robustness. Materials and MethodsIn this retrospective analysis of prospectively acquired data (2007-2017), we developed and validated a deep learning-based PRM approach using paired CT scans from 8,972 tobacco-exposed COPDGene participants ([&ge;]10 pack-years; mean age 60.1 {+/-} 8.8 years; 46.5% women), including controls with normal spirometry (n = 3,872; controls), PRISm (n = 1,089), GOLD 1-4 COPD (n = 4,011). Data were stratified into training, validation, and testing sets (24:6:70). PRMD extracts translation-invariant image features using a wavelet scattering network and applies a subspace learning classifier to classify voxels as emphysema or non-emphysematous air trapping (fSAD). PRMD was compared with conventional density-based PRM for voxel-wise agreement, correlation with pulmonary function, robustness to noise, and sensitivity to misregistration using Pearson correlation, Bland-Altman analysis, and paired t tests. ResultsPRMD achieved 95% voxel-wise agreement with standard PRM (r = 0.98) while demonstrating significantly greater robustness under noise. PRMD showed stronger correlations with FEV (emphysema: r = -0.54; fSAD: r = -0.51; P < 0.0001) than standard PRM (r = -0.42 for both; P < 0.0001). Under simulated high-noise conditions, standard PRM overestimated disease by [~]15%, whereas PRMD limited error to < 5% (P < 0.001). ConclusionPRMD provides an interpretable, feature-driven and noise-resilient alternative to traditional PRM for emphysema and fSAD classification, enhancing the reliability of CT-based COPD phenotyping for multi-center studies and low-dose imaging applications. Key PointsO_LIThis study introduces combined wavelet scattering and subspace learning for medical image segmentation, enabling accurate, interpretable voxel-level classification of emphysema and functional small airways disease on paired CT scans. C_LIO_LIThe proposed Deep Parametric Response Mapping method demonstrated 95% voxel-wise agreement with standard Parametric Response Mapping and stronger correlations with spirometric measures, enhancing the clinical relevance of CT-based phenotyping for Chronic Obstructive Pulmonary Disease. C_LIO_LIDeep Parametric Response Mapping significantly improved robustness to image noise--reducing overestimation of emphysema and functional small airways disease from [~]15% to <5% (P < 0.001)--and benefits from reduced data requirements due to the fixed, mathematically defined filters used in wavelet scattering. C_LI Summary StatementDeep Parametric Response Mapping improves the accuracy and noise robustness of CT-based classification of emphysema and functional small airways disease using feature-based representations, enhancing the reliability of COPD phenotyping.

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RadGuide AI: Development and Technical Evaluation of a General Nuclear Medicine Agent for Traceable Radiopharmaceutical Decision Support

Gu, X.; Zhu, H.; Zhong, F.; Teng, G.-J.

2026-07-10 radiology and imaging 10.64898/2026.07.09.26357614 medRxiv
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Background: Nuclear medicine and radiopharmaceutical development require coordinated radiochemistry, dosimetry, molecular imaging, radiation-safety and clinical decision processes. Current workflows remain fragmented, difficult to audit and poorly standardised for evaluating domain-specific AI support. Methods: We developed RadGuide AI, a nuclear medicine agent built around a traceable data-model-tool loop. Patent, literature and clinical-trial records were converted into 15,596 initial QA items; relevance screening, completeness checks, semantic deduplication and cross-validation retained 5,474 core QA items. MedGemma-27B-Instruct served as the foundation model and was adapted with LoRA. The system incorporated 55 MCP-wrapped tools covering radiopharmaceutical R&D, clinical decision support, imaging analysis and radiation-safety/dosimetry. Evaluation used a locked N=200 benchmark with predefined denominators, leakage control, expert scoring, statistical procedures, factuality audits and tool-execution metrics. Results: RadGuide-LLM achieved 88.5% answer accuracy (177/200; 95% CI, 83.3-92.2%) and a Macro-Average score of 21.5/25 (bootstrap 95% CI, 20.9-22.0), exceeding GPT-4o, DeepSeek-V3.2 and the base MedGemma model in this technical evaluation. Supplementary audits reported guideline compliance, terminology recall, knowledge coverage, tool-routing success and preclinical/phantom dosimetry agreement with explicit denominators and confidence intervals. Interpretation: RadGuide AI converts nuclear medicine queries into auditable retrieval, tool selection, calculation, verification and reporting workflows. The findings support technical feasibility, not definitive patient-level clinical validation; prospective multicentre studies and external benchmark release remain required before clinical deployment.

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TCIA Radiology Image Processing for AI and Radiomics

Rich, J. M.; Kang, R.; Jin, D.; Subramanian, S.; Duddalwar, V.; Pachter, L.

2026-06-24 radiology and imaging 10.64898/2026.06.15.26354651 medRxiv
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We developed a standardized, reproducible preprocessing framework for computed tomography (CT) imaging data from multi-institutional repositories such The Cancer Imaging Archive (TCIA), enabling consistent radiomics and artificial intelligence (AI) analyses. Imaging data from TCGA-KIRC patients available on TCIA were used as a representative heterogeneous dataset characterized by variation in acquisition protocols, inconsistent metadata, and differing image quality. The proposed modular pipeline includes series filtering, DICOM-to-NIfTI conversion, orientation harmonization to a canonical coordinate system, voxel spacing normalization, intensity clipping and normalization, segmentation integration, and metadata validation, and is implemented in a reproducible, notebook-based framework compatible with common radiomics and deep learning workflows. This pipeline standardizes imaging data into analysis-ready volumes with consistent geometry, intensity distributions, and spatial alignment, reducing non-biological variability that can adversely affect radiomic feature stability and model performance. The modular design enables task-specific adaptation of individual preprocessing steps while maintaining overall consistency. Although demonstrated on TCIA, this framework is generalizable to other heterogeneous imaging datasets and provides a foundation for robust, large-scale computational imaging studies.

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Dosimetric Characterization and Workflow Optimization of the FLASH-SARRP for Reliable Preclinical Radiobiological Studies

Knol, M.; Goncalves Jorge, P.; Kunz, L. V.; Korysko, P.; Petit, B.; Durham, A.; Marie-catherine, V.; Tsoutsou, P.; Koutsouvelis, N.; Lascaud, J.

2026-07-07 cancer biology 10.64898/2026.07.06.736680 medRxiv
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Objective: Preclinical small-animal irradiators such as the FLASH-SARRP can support the advancement of photon-FLASH toward the clinic. This study aimed at characterizing the FLASH-SARRP and established a robust quality assurance (QA) workflow to enable accurate and reproducible preclinical experiments. Approach: Custom 3D-printed spacers were designed to ensure reproducible X-ray tube alignment, sample positioning and mounting of the dosimetric tools. Beam characteristics were evaluated using a combined dosimetric approach. High spatially resolved dose distributions were obtained from Gafchromic films, whereas a plastic scintillating fiber was employed to monitor in real-time the temporal pulse structure and synchronization between the two X-ray tubes. Day-to-day variability of the delivery was evaluated over several sessions. Main results: The FLASH-SARRP achieved dose-rates of around 80 Gy/s when both tubes were used simultaneously and provided a homogeneous irradiation field suitable for small-animal studies. A desynchronization between the two tubes was observed with an average delay of 10 ms, resulting in temporal dose-rate heterogeneity. Additionally, a substantial inter-session variability (~11%) was found, whereas the intra-session variability was relatively low (~4%). Inter-session variability was reduced to 5%, approaching the intra-session variability, by adding Gafchromic films/scintillator-based quality assurance (QA) workflow into the irradiation routine. Significance: This work highlights the importance of temporal dosimetry for preclinical FLASH studies. Additionally, a practical QA framework is proposed integrating real-time monitoring with reference dosimetry. The proposed work enables adaptive dose delivery, thereby enhancing the reproducibility of the irradiations, which is crucial for reliable preclinical studies on the FLASH effect.

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A Real-World Evaluation of Failure Detection for Liver CT Segmentation

Bennett, J.; Woodland, M.; Castelo, A.; Altaie, M.; Antony, A.; Siddiqi, N. S.; Long, J. P.; Brock, K. K.

2026-06-29 radiology and imaging 10.64898/2026.06.26.26356692 medRxiv
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Deep learning models deployed in clinical imaging frequently encounter distribution shifts, yet most out-of-distribution (OOD) detection methods are evaluated only on controlled research datasets. As a result, it is unclear whether existing approaches can reliably identify segmentation failures that arise in real-world clinical practice. We evaluated six OOD detection methods on a deployed liver CT segmentation model (3D nnU-Net) using internal data from 400 patients and external data from 100 patients collected across nearly 70 sites in 7 countries. One method was Pairwise Surface DSC, a surface-based extension of Pairwise DSC, that we introduced. OOD performance was measured using sensitivity, AUROC, and balanced accuracy, with thresholds determined on an independent cohort of 400 patients using the Youden J statistic. Statistical significance was assessed using McNemar tests and stratified bootstraps ( = 0.05) with Benjamini-Hochberg correction. Pairwise Surface DSC was the top-performing method, with perfect sensitivities (1.00), near-perfect AUROCs (0.97 internal; 1.00 external), and the highest balanced accuracies (0.94 internal; 0.88 external; p<0.001). These results show that automated failure detection for liver CT segmentation is clinically feasible and that Pairwise Surface DSC is a promising candidate for deployment. Our code is available at https://github.com/mckellwoodland/liver_ct_ood_translation.

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A quantitative proteomics dataset for assessment and prediction of low dose X-ray radiation exposure in mice.

Zelter, A.; Riffle, M.; Merrihew, G. E.; Mutawe, B.; Shulman, N.; Sanders, J. A.; Noble, W. S.; Johnson Erickson, D. P.; Morimoto, A.; Shaver, B. A.; Steins, T. N.; Cao, N.; Ford, E. C.; Rudnick, P. A.; Chelsky, D.; Wan, K. H.; Inman, J. L.; Chang, H.; Snijders, A. M.; Mao, J.-H.; Celniker, S. E.; De Chant, J.; Obst-Huebl, L.; Nakamura, K.; Wu, C. C.; MacCoss, M. J.

2026-05-19 biochemistry 10.64898/2026.05.18.725951 medRxiv
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Ionizing radiation induces molecular responses that may be used to estimate exposure when physical dosimeters are unavailable. Here we present two large-scale proteomics datasets generated from mouse dorsal skin punch samples collected following controlled X-ray exposures spanning multiple doses, dose rates, and post-exposure time points. Experiment 1 comprised 96 samples (including 16 reference samples) collected 6 days after exposure to 0-75 cGy delivered at either 30 or 300 cGy/min. Experiment 2 comprised 936 samples (including 236 reference samples) exposed to 0-100 cGy at either 3 or 28 cGy/min dose rates and harvested between 7 and 150 days post-exposure. All samples were processed using a standardized workflow involving automated bead-based digestion and data-independent acquisition mass spectrometry. The datasets include multiple pooled reference sample types, process controls, and system suitability standards ensuring high quality data. All data presented are available via ProteomeXchange at several levels of processing, from raw files through normalized peptide- and protein-level abundance matrices suitable for biomarker discovery and machine learning applications. This dataset will facilitate generation of new insights into the biological changes and molecular signatures resulting from X-ray exposure in mice and may also help inform future studies in humans.

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Correlation of OCT-Based Radiomic Signatures With Dose-Associated Radiation Response in Tumor Spheroids

Arndt, M. D.; Hansler, R.; Tirinato, L.; Tkachenko, A.; Seco, J.; Schepers, U.; Spadea, M. F.

2026-07-09 cancer biology 10.64898/2026.07.08.737210 medRxiv
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Background: Three-dimensional tumor spheroids are an established radiobiology model, but scalable, reproducible readouts of dose-dependent radiation response are lacking. We evaluated whether optical coherence tomography (OCT) radiomics can quantify dose-associated response in spheroids, and how it compares with conventional brightfield morphology. Methods: This in vitro, cross-sectional study used SAS oral squamous cell carcinoma spheroids seeded at two densities (5000 and 10000 cells), irradiated at 0 to 12 Gy, and imaged on days 1 to 11 post-irradiation. Each OCT acquisition yielded co-registered structural-intensity and speckle-variance volumes. Radiomic features (shape, first-order, texture) were extracted with Radiomics.jl, filtered for repeatability, correlation-pruned, and ensemble-ranked. Dose correlation was assessed by repeated 5-fold cross-validation across five regressors, comparing brightfield-only (BF), OCT-only, and combined OCT+BF feature sets with paired Wilcoxon tests. Results: OCT-only models consistently outperformed the BF baseline (median R2 0.77 to 0.85 versus 0.61 to 0.69; p<0.001 for all regressors). Adding brightfield to OCT gave no consistent benefit, reaching significance only for Random Forest (p=0.026, power 0.62). A compact shared feature subset combined brightfield area dynamics with OCT texture, shape, and speckle-variance descriptors, all showing low repeat-scan variability relative to cohort variability. Conclusions: OCT radiomics provides a sensitive, reproducible, label-free high-throughput readout of spheroid radiation dose response that outperforms the current brightfield-based approach, without requiring concurrent brightfield acquisition.

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Automated Anatomy-Based Subsegmentation of Pelvic and Proximal Femoral CT: Validation Across Clinically Relevant Regions and Landmarks

Rashed, M.; Alabdulrahman, H.

2026-05-19 radiology and imaging 10.64898/2026.05.14.26353237 medRxiv
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Background Automated pelvic CT segmentation has advanced to reliable coarse bone extraction. Yet the structured anatomical hierarchy required for morphometry, fixation planning, bone quality mapping, and arthroplasty workflows remains unachieved. This study developed and validated a fully automated anatomy-informed pipeline that converts standard pelvic CT into a comprehensive, surgeon-readable subsegmentation of the pelvis and proximal femur. Methods Pelvic CT datasets were retrospectively collected from anonymized archives of hospitals affiliated with the Directorate of Health Affairs, Sharqia, Egypt. After eligibility screening, 757 normal adult cases were processed using a custom one-click 3D Slicer pipeline integrating TotalSegmentator for coarse extraction, followed by deterministic anatomy-based subsegmentation into 81 segments. One hundred randomly selected cases were validated against expert-corrected reference segmentations using Dice similarity coefficient, volume difference, surface distance metrics, and bilateral symmetry analysis. Results Of 1,316 screened cases, 757 met eligibility criteria. Across 8,100 case-segment observations, the pipeline achieved a mean Dice of 0.9926 +/- 0.0465. Complete agreement was observed for the sacrum, ilium, acetabulum, anterior and posterior columns, sciatic buttress, and all landmarks. Relative decreases were confined to boundary-dependent regions. Bilateral symmetry analysis confirmed a median surface agreement of 99.85% within 5 mm. Conclusion The pipeline demonstrated high accuracy and reproducibility across a large normal adult dataset, establishing a structured anatomical foundation for quantitative pelvic analysis and surgical planning workflows. Clinical feasibility across abnormal anatomy and decision-level applications awaits dedicated validation.

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Three-dimensional printing of lifelike PET phantoms

Ge, Y.; Li, E. J.; McDonald, S.; Geagan, M.; Parma, M. J.; Gao, M.; Mei, K.; Pasyar, P.; Im, J. Y.; Muller, F. M.; Pantel, A. R.; Karp, J. S.; Noel, P. B.

2026-05-14 radiology and imaging 10.64898/2026.05.11.26352857 medRxiv
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BackgroundRealistic PET/CT phantoms are essential for system evaluation, protocol optimization, and validation of advanced reconstruction methods. However, existing phantoms are often limited by simplified geometries, spatially uniform activity patterns, and complex preparation procedures. PurposeTo develop and evaluate PixelPrintPET, a 3D printing-based method for fabricating anatomically realistic PET/CT phantoms with spatially heterogeneous radiotracer distributions and a single-solution filling workflow that avoids physical compartmentalization. MethodsPixelPrintPET generates voxel-based printing instructions that encode spatially varying infill, which is realized during printing through modulation of filament extrusion, enabling heterogeneous activity distributions without compartmentalization of radioactivity at different activity concentrations. Calibration phantoms and anatomically structured phantoms were designed and printed using high-flow polylactic acid (PLA), with anatomical inputs derived from either digital atlas-based models or patient imaging data. The printed phantoms were subsequently filled by immersion in a radioactive solution, allowing activity distribution to be controlled by the internal porous structure. A bottom-up filling procedure with reduced surface tension was developed to ensure uniform infiltration and minimize air entrapment. Phantoms were imaged on the PennPET Explorer PET/CT system, and quantitative performance was evaluated using contrast recovery coefficient (CRC), target-to-background ratio (TBR), and comparisons with simulated or patient-derived reference data. ResultsA strong linear relationship between infill ratio and normalized signal (R2 = 0.998) was demonstrated by the calibration phantom, enabling reliable mapping between structure and activity. Additionally, air entrapment was minimized to less than 1% of the total phantom volume. In the contrast recovery phantom, CRC values were consistent with measurements using traditional phantoms. The brain phantom reproduced atlas-derived contrast patterns, with gray-to-white matter differences within 5% after accounting for resolution and other system effects. The patient-based thorax phantom showed high reproducibility across repeated scans, with differences within 3%, and closely matched the input patient image with regional differences within 10% in all regions except the lung. ConclusionsPixelPrintPET enables the fabrication of realistic, reproducible, and versatile PET/CT phantoms with a voxel-level control of the activity distribution. This approach provides a practical solution for generating patient-specific and application-specific phantoms, with the potential to accelerate system validation, protocol development, and clinical translation of advanced PET/CT technologies.

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Cross-Domain Knowledge Transfer from Expert-Annotated Gated CT via Synthetic Ungated CT Improves Coronary Artery Calcium Scoring on CT Attenuation Correction Scans

Shanbhag, A.; Miller, R. J.; Killekar, A.; Marcinkiewicz, A. M.; Zhou, J.; Lemley, M.; Kamagate, A.; Van Kriekinge, S. D.; Kavanagh, P. B.; Feher, A.; Miller, E. J.; Liang, J. X.; Berman, D. S.; Dey, D.; Leahy, R. M.; Slomka, P.

2026-07-06 radiology and imaging 10.64898/2026.07.02.26356002 medRxiv
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Background: Coronary artery calcium (CAC) is an established measure of coronary atherosclerosis from computed tomography (CT). While deep learning (DL) can quantify CAC from non-dedicated CT, the accuracy is limited by image quality. Purpose: We derived and validated a novel method for DL CAC segmentation on ultra-low dose CT attenuation correction (CTAC) scans that is trained with synthetic low-dose, ungated images. Materials and Methods: Models were trained using one center and externally tested in two other centers. Synthetic, ungated CT scans were generated so that expert segmentations from dedicated CAC scans could be used as ground truth for perfectly registered synthetic images through knowledge adaptation (KAD-CAC). We evaluated agreement between CAC scoring methods vs expert readers on a per-patient and per-vessel basis, as well as associations with the primary outcome of death or myocardial infarction (MI). Results: The DL models were externally tested on 5969 patients with a median age of 64 (IQR 56 - 73), of whom 50.2% were male. The KAD-CAC model had higher Cohens kappa K (0.86, 95% CI 0.85 - 0.87) compared to previous convolutional LSTM model (K 0.78, 95% CI 0.76 - 0.80, p<0.01), or models trained with only gated images (K 0.81, 95% CI 0.80 - 0.82, p<0.01). Net reclassification improvement for CAC stratified risk of death or MI, was greatest for the KAD-CAC model over baseline including age, sex, hypertension, diabetes, dyslipidemia, family history, smoking, stress total perfusion deficit, and left ventricular ejection fraction. Conclusion: We use paired synthetic ungated scans to transfer expert gated CAC annotations into the ungated domain, resulting in substantially better vessel-level CAC scoring and improved risk stratification.

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Comparative Study on Image Quality of Deep Learning and Adaptive Statistical Iterative Reconstruction-V in Thin Layer CT of liver Lesions

Yang, J.; Li, L.; Cao, J.; Zhang, J.

2026-05-26 radiology and imaging 10.64898/2026.05.23.26353923 medRxiv
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Objective:This study aims to compare the advantages and disadvantages of DLIR and adaptive statistical iterative reconstruction-V (ASIR-V) in thin-slice (2.5 mm) CT images of hepatic lesions characterized by high and low contrast. Additionally, the study seeks to determine the optimal DLIR strength for the evaluation of liver lesions. Methods:A retrospective analysis was performed on 90 patients who underwent abdominal contrast-enhanced CT scans. Group A comprised 48 patients with low-contrast lesions, while Group B included 42 patients with high-contrast lesions. The acquired images were reconstructed using post-processing DLIR at low (DLIR-L), medium (DLIR-M), and high (DLIR-H) strengths, all with a slice thickness of 2.5 mm (subgroups A1-A3, B1-B3). Furthermore, images were reconstructed with ASIR-V at 50% strength at slice thicknesses of 2.5 mm and 5 mm (subgroups A4/B4 and A5/B5, respectively). CT values and standard deviations (SD) of the liver and lesions were measured, and the corresponding signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. The edge rise slope (ERS) was determined using ImageJ software by measuring CT values along a line from the liver parenchyma to the lesion. Objective metrics were compared using one-way ANOVA, with independent samples t-tests applied for inter-group differences. Subjective scoring, which encompassed noise level, diagnostic confidence, and lesion margin delineation, was conducted by two radiologists, with differences analyzed using the Kappa test. Results: Objective evaluation revealed a progressive decrease in lesion SD and a progressive increase in SNR and CNR from subgroups A1/B1 to A3/B3. The SD of Group A2 decreased by 57.4% compared to A4, while the SNR and CNR of A2 icreased by 19.3% and 24.6% compared to A4. Although subgroup B2 had a lower SNR than B5, the difference was not statistically significant. SNR and CNR in B2 increased by 24.1% and 11.9%, respectively, compared to B4. ERS gradually decreased from A1/B1 to A3/B3. ERS values in A2 and B2 increased by 27.0% and 39.4%, respectively, relative to A5 and B5. Although A3 had a lower ERS than A1 and A2, all DLIR subgroups exhibited higher ERS than A5; similar trends were observed in Group B. Subjective evaluation indicated good inter-reader agreement (Kappa > 0.61, p < 0.05). As DLIR strength increased, noise scores rose progressively in both groups. However, noise in A2 and B2 was lower than in A4/A5 and B4/B5. Diagnostic confidence and lesion margin delineation scores were highest in A2 and B2, while all subjective scores were lowest in A5 and B5. Discussion: Most prior studies evaluated the liver, vessels, or confirmed that image quality can be guaranteed at low doses. However, there are few studies on specific individual lesions. Therefore, this study aims to investigate specific individual lesions. The details and detection rate were analyzed separately to confirm the clinical acceptability of 2.5-mm DLIR image in different contrast lesions. Conclusion: For both high- and low-contrast hepatic lesions, DLIR provides superior image quality compared to ASIR-V, with the 2.5mm DLIR-M setting being optimal. DLIR-M reduces image noise, improves spatial resolution, and produces images more suitable for diagnostic purposes.

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Cardiac positronium lifetime in human PET: a reproducible right-left ventricular contrast that is not explained by blood oxygenation

Zermeno, E. D.

2026-06-16 radiology and imaging 10.64898/2026.06.14.26355630 medRxiv
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Background. Ortho-positronium (o-Ps) lifetime, now measurable in vivo on long-axial-field-of-view (LAFOV) PET/CT, has been proposed as a biomarker of tissue oxygenation and hypoxia. Because o-Ps lifetime is dominated by tissue free-volume structure while the oxygen- specific contribution is small, whether an in-vivo lifetime contrast reflects oxygenation rather than anatomy is an open, identifiability-limited question. Aim. To test the oxygenation hypothesis directly using the heart's natural arterial/venous oxygenation contrast, with a built-in anatomical control. Methods. We re-analysed a public [82Rb]Cl human cardiac LAFOV PET/CT dataset (5.30 x 10^8 evaluated three-photon events). Per-compartment o-Ps lifetimes were extracted with a background-plus-two-component exponentially-modified-Gaussian (EMG) model. The list-mode to image mapping and right/left ventricle (RV/LV) identity were established lifetime-free (the mapping reproduces the provider's reconstructed image at block-correlation 0.998 and wins a joint multi-organ alignment panel). We applied a confound battery: registration stress test, blood-core vs wall, lung-air and wall-myocardium partial-volume, tissue density; and a structure/position-matched control (pulmonary artery, deoxygenated, vs aorta, oxygenated). An isotope-matched 82Rb uniform-quartz reference bounded the instrument's positional behaviour. All results were produced by two independent analysis pipelines. Results. RV o-Ps lifetime exceeded LV by delta tau = +0.304 ns (RV 1.700 +/- 0.172, LV 1.396 +/- 0.130 ns; about 1.4 sigma), in the oxygen-expected direction; the contrast was stable across +/-16 mm registration perturbation (sign preserved in 100% of 342 shifts) and resided in the blood core, not the wall. However, the matched-vessel control was null: pulmonary artery minus aorta = -0.011 +/- 0.344 ns. Lung-air and wall-myocardium partial-volume were disfavoured, and the effect fell within the isotope-matched 82Rb instrumental positional envelope (about 0.1-0.35 ns over 40 mm in uniform material). Conclusion. On this single subject, the cardiac o-Ps lifetime contrast does not provide a clean readout of blood oxygenation: an oxygenation effect of the observed (about 0.3 ns) magnitude is ruled out by the matched control, while a small physiological effect cannot be excluded. We provide a reusable confound-control battery for evaluating future in-vivo o-Ps oxygenation claims. Multi-subject replication with anatomy decoupled from oxygenation is required.