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Physics in Medicine & Biology

IOP Publishing

Preprints posted in the last 90 days, ranked by how well they match Physics in Medicine & Biology's content profile, based on 17 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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Technical Development and Implementation of 3D-QALAS on a 1.5T MR-Linac for the Brain: A Prospective R-IDEAL Stage 0/1 Technology Development Report

McCullum, L.; Harrington, A.; Taylor, B. A.; Hwang, K.-P.; Fuller, C. D.

2026-03-10 radiology and imaging 10.64898/2026.03.09.26347967 medRxiv
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Background and PurposeQuantitative relaxometry on the integrated MRI / linear accelerator (MR-Linac) at high isotropic resolution is currently limited due to prohibitively long scan times and limited field-of-views. Therefore, the purpose of this study was to assess the technical feasibility of the 3D-QALAS technique on the 1.5T MR-Linac which has the ability to acquire whole-brain 1 mm isotropic quantitative T1, T2, and PD maps along with multiple synthetic images in a 7 minute acquisition time. Materials and MethodsA 1 mm isotropic 3D-QALAS acquisition was scanned in both phantoms and a healthy volunteer on the 1.5T Elekta Unity MR-Linac device with scan times around seven minutes. A test-retest protocol across five independent sessions for the phantom was conducted. The correlation, repeatability, and reproducibility between measured and reference quantitative T1, T2, and PD values were determined in the phantom. Distortion was also studied. Vendor-provided reconstruction through SyMRI was performed to extract synthetic images and brain volume metric assessments on a healthy volunteer. ResultsThe slope and concordance between the measured and phantom reference values was 1.02 (1.00), 1.09 (0.90), and 0.99 (1.00) for T1, T2, and PD, respectively. Median distortion across the phantom remained below 2 mm. The repeatability and reproducibility coefficient-of-variation (CoV) was under 8% for all measured values. The measured brain volumes in the healthy volunteer was within expected age-adjusted reference values. DiscussionThe technical feasibility of using 3D-QALAS on the integrated 1.5T MR-Linac was confirmed. Applying this technique to the head and neck adaptive radiation therapy workflow will provide new opportunities to integrate quantitative imaging relaxometry biomarkers at 1 mm isotropic resolution. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/26347967v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@1f43093org.highwire.dtl.DTLVardef@a1320eorg.highwire.dtl.DTLVardef@dd750eorg.highwire.dtl.DTLVardef@1300853_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Quantitative Dixon-Based PDFF and R2* Estimation and Optimization on MR-Simulation and MR-Linac Devices for the Pelvis and Head and Neck: A Prospective R-IDEAL Stage 0-2a Study

McCullum, L.; West, N. A.; Shin, K.; Taylor, B. A.; Augustyn, A.; Saifi, O.; Thrower, S.; Wang, J.; Shah, S.; Choi, S.; Anakwenze, C. P.; Fuller, C. D.; Floyd, W.

2026-03-10 radiology and imaging 10.64898/2026.03.09.26347965 medRxiv
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Background and PurposeThe use of MRI-based fat quantification can be applied to automatically identify red bone marrow which is highly sensitive to radiation and systemic therapies and could be used as an organ-of-interest for adaptive radiation therapy. Currently, the tradeoff of scan time and PDFF/R2* quantification accuracy from the 2-/3-/6-point methods, particularly for the time-constrained MR-Linac, remain unanswered. Therefore, the purpose of this study was to investigate the technical feasibility and quantitative performance of quantitative Dixon-based imaging for scanners within the radiation oncology department. Materials and MethodsA 2-/3-/6-point version of the quantitative Dixon sequence was developed and scanned on a 1.5T MR-Simulation, 3T MR-Simulation, and 1.5T MR-Linac scanner for five repetitions using the Calimetrix Model 725 PDFF-R2* phantom as a nominal reference for quantitative PDFF/R2* values. The image geometric distortion as well as the quantitative concordance, Bland-Altman agreement, repeatability, and reproducibility of both the PDFF/R2* values were determined. Each sequence was evaluated in both the pelvis and head and neck across both healthy volunteers and patients. ResultsThe most severe geometric distortion was less than 2 mm except for the 1.5T MR-Linac when using the 2-point Dixon sequence with distortions exceeding 5 mm. The 6-point Dixon sequence showed the highest concordance at above 0.97 across all scanners for both PDFF and R2* followed by the 3-point and 2-point sequence. The 2-point Dixon sequence exhibited significant PDFF biases particularly at the higher R2* values since it did not correct for it during reconstruction. For the Bland-Altman analysis, the 2-point Dixon sequence had the widest 95% limits of agreement followed by the 3-point and 6-point Dixon sequence with the narrowest bands. The goodness-of-fit is generally lowest at higher PDFF values and lower R2* values. Both repeatability and reproducibility were the lowest for the 6-point Dixon sequence. DiscussionThe 6-point quantitative Dixon sequence demonstrated superiority for the chosen evaluation metrics. The results of this work can be used to determine the threshold for true quantitative changes of PDFF/R2* while considering acquisition variabilities, enabling future biomarker studies and clinical trials. Further, this work provides validation for future investigations into quantitative bone marrow characterization. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/26347965v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@8b2139org.highwire.dtl.DTLVardef@322a97org.highwire.dtl.DTLVardef@18a3a46org.highwire.dtl.DTLVardef@1f7ef62_HPS_FORMAT_FIGEXP M_FIG C_FIG

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The Effects of External Laser Positioning Systems for MRI Simulation on Image Quality and Quantitative MRI Values

McCullum, L.; Ding, Y.; Fuller, C. D.; Taylor, B. A.

2026-03-07 radiology and imaging 10.64898/2026.03.06.26347809 medRxiv
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Background and PurposeMagnetic resonance imaging (MRI) for radiation therapy treatment planning is currently being used in many anatomical sites to better visualize soft tissue landmarks, a technique known as an MRI simulation. A core component of modern MRI simulation configurations are the use of external laser positioning systems (ELPS) to help set up the patient. Though necessary for accurate and reproducible patient setup, the ELPS, if left on during imaging, may interfere negatively with image quality due to leaking electronic noise, of which MRI is sensitive to. It is currently unknown whether this leakage of electronic noise may further affect quantitative values derived from clinically employed relaxometric, diffusion, and fat fraction sequences. Therefore, in this study, we aim to characterize the impact of MRI simulation lasers on general image quality and quantitative imaging accuracy. Materials and MethodsFirst, a cine acquisition was used to visualize the real-time changes in image signal-to-noise ratio (SNR) from when the ELPS was deactivated to activated. To validate this effect quantitatively, the SNR was measured using the American College of Radiology (ACR) recommended protocol in a homogeneous phantom with the integrated body, 18-channel UltraFlex small, 18-channel UltraFlex large, 32-channel spine, and 16-channel shoulder coils. Next, a geometric distortion algorithm was tested in two vendor-provided phantoms while using the integrated body coil and the ACR Large Phantom protocol was tested. Finally, a series of quantitative MRI scans were performed using a CaliberMRI Model 137 Mini Hybrid phantom to validate quantitative T1, T2, and ADC while a Calimetrix PDFF-R2* phantom was used for quantitative PDFF and R2*. All scans were performed with both the ELPS both deactivated and activated. ResultsVisible electronic noise artifacts were seen when using the integrated body coil when the ELPS was activated on the cine acquisition which led to a four-fold decrease in SNR using the ACR protocol. This SNR drop was not seen when using the remaining tested coils. The automatic fiducial detection algorithm was affected negatively by ELPS activation leading to misidentification when identified perfectly with the ELPS deactivated. Degradation in image intensity uniformity, percent signal ghosting, and low contrast object detectability was seen during ACR Large Phantom testing using the 20-channel Head/Neck coil. Concordance across quantitative MRI values was similar when the ELPS was both deactivated and activated while a consistent increase in standard deviation inside the ADC vials was seen when the ELPS was activated. DiscussionThe extra noise induced from the activation of the ELPS during imaging should be avoided due to its potential to unnecessarily increase image noise. This is particularly true when conducting mandatory quality assurance testing for image quality and geometric distortion which utilize the integrated body coil which is most susceptible to ELPS-induced noise. Clear clinical guidelines should be implemented to make this issue known to the MRI technologists, physicists, and other relevant staff using an MRI with a supplementary ELPS for patient alignment. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/26347809v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@dd725borg.highwire.dtl.DTLVardef@7ed081org.highwire.dtl.DTLVardef@1aac775org.highwire.dtl.DTLVardef@10ce397_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Automated Segmentation of Head and Neck Cancer from CT Images Using 3D Convolutional Neural Networks

Prabhanjans, P.; Punathil, A. N.; V K, A.; Thomas T, H. M.; Sasidharan, B. K.; Shaikh, H.; Varghese, A. J.; Kuchipudi, R. B.; Pavamani, S.; Rajan, J.

2026-03-13 radiology and imaging 10.64898/2026.03.12.26347996 medRxiv
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Head and neck cancer (HNC) requires accurate tumor delineation for effective radiotherapy planning. Manual segmentation of tumor regions is time-consuming and subject to considerable inter-observer variability. Although several automated approaches have been proposed, many rely on multimodal imaging such as PET/CT, which is expensive, less accessible in many clinical settings, and increases the burden on patients. In this work, we investigate a CT-only three-dimensional segmentation framework that provides a clinically practical and resource-efficient alternative. CT images of 136 head and neck cancer patients from the publicly available HN1 dataset in The Cancer Imaging Archive (TCIA) were used along with 30 additional cases from a private dataset collected at a tertiary care centre, Christian Medical College (CMC), Vellore, India. A fully automated segmentation model was developed to delineate the primary gross tumor volume (GTV) using the 3D nnU-Net framework. The models were trained using the HN1 dataset and an extended HN1+CMC dataset that included the additional private cases. Performance was evaluated using three-fold cross-validation with standard segmentation metrics including Dice Similarity Coefficient (DSC), Intersection over Union (IoU), and the 95th percentile Hausdorff Distance (HD95). The proposed CT-based model achieved a Global Dice of 0.63 and a Median Dice of 0.60 on the HN1 dataset. When the additional CMC cases were incorporated during training, the performance improved to a Global Dice of 0.65 and a Median Dice of 0.71. These results demonstrate that 3D nnU-Net can effectively segment head and neck tumors from CT images alone. The proposed CT-only approach provides a cost-effective and scalable solution that can support radiotherapy treatment planning and help reduce variability in clinical workflows.

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Efficient and Practical Framework for Bias Estimation in Spectral CT

Sandvold, O. F.; Proksa, R.; Perkins, A. E.; Noël, P. B.

2026-03-12 radiology and imaging 10.64898/2026.03.11.26346993 medRxiv
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BackgroundSpectral computed tomography (CT) is increasingly used for quantitative imaging, yet accurate prediction of spectral quantitative bias remains challenging and computationally expensive with conventional approaches. Bias manifests as systematic deviations in reconstructed quantities (e.g., Hounsfield units, iodine density) from their true physical values. It arises from a combination of model mismatch, hardware/processing imperfections, exam-dependent factors, and noise-induced effects amplified by nonlinear operations such as the logarithmic transformation and material decomposition. PurposeWe present a practical, projection-based statistical framework to estimate noise-induced spectral bias efficiently, without the runtime burden of Monte Carlo (MC) simulation. MethodsTo demonstrate the bias estimator, we modeled the central-ray of a clinical X-ray tube attenuating through a 300 mm patient-equivalent path with a 10 mm insert containing 10 mg/mL iodine. A 120 kVp tube voltage and tube currents from 100-350 mA were used. Ideal and realistic photon-counting detector responses were simulated across 50 bin threshold settings. Quantum Poisson noise was modeled, and Bayesian probabilities of material decomposition outputs centered on ground truth iodine and water bases were computed. Expected material decomposition outputs [Formula] were derived from a 2D probability map, and bias was measured. A simple Python Monte Carlo (MC) simulation served as a reference. ResultsThe proposed bias estimator closely matched MC-derived bias, with an average relative iodine bias percent difference between the estimators of 0.44% across all tube currents and bin thresholds. Average runtime of the bias estimator was only 0.5% of the MC simulation. Optimal thresholds for minimizing iodine noise (via the Cramer-Rao lower bound) differed from those minimizing iodine bias, highlighting key noise-bias tradeoffs. ConclusionEfficient spectral bias and noise estimation are essential for quantitative CT system design. This modular framework enables rapid, bias-aware optimization of spectral acquisition parameters and is adaptable to alternative spectral CT technologies beyond photon counting. Novelty and Significance of StudyPlease briefly (150 words or less) describe the novelty and/or significance of your study. Bias estimation is paramount for designing accurate spectral CT systems that deliver improved diagnostic performance. Traditional approaches rely on computationally intensive Monte Carlo simulations. We propose an efficient and practical bias estimator that uses Bayesian statistics and expected material decomposition values derived from a flexible, modular CT forward model. Unlike conventional Monte Carlo approaches, this framework enables rapid exploration of spectral design tradeoffs between bias and noise. We demonstrate both the accuracy and speed of this bias estimator relative to Monte Carlo approaches.

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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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Evaluation of Neuronal Activation Thresholds for Low-Frequency Electromagnetic Exposure Using Morphologically Realistic Neuron Models

Gazquez, J.; Camacho Cadena, C.; He, W.; Yamada, E.; Altekoester, C.; Soyka, F.; Laakso, I.; Hirata, A.; Joseph, W.; Tarnaud, T.; Tanghe, E.

2026-04-21 neuroscience 10.64898/2026.04.17.719188 medRxiv
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International guidelines for low-frequency electromagnetic field exposure (LF EMF) are primarily intended to prevent substantiated adverse effects. In the frameworks, limits on internal electric fields are linked to external exposure levels through computational dosimetry. However, the relationship between internal electric fields and these adverse effects remains incompletely understood. In particular, current approaches often overlook the morphological complexity and diversity of cortical neurons, which may limit the realism of neuronal activation estimates used to support these assessments. This study evaluates LF EMF-induced neural activation using 25 morphologically realistic neuron models spanning all cortical layers, embedded within 11 detailed human head models. The internal electric fields were simulated for uniform magnetic field exposures (100 Hz-100 kHz) along the three anatomical directions, and excitation thresholds were computed using a multi-scale framework combining voxel-based dosimetry with biophysical neuron simulations. A real-world exposure scenario involving a child near an acousto-magnetic article-surveillance deactivator was also analyzed. Thresholds varied across cell type, morphology, cortical location, subject anatomy, frequency, and exposure direction, with L2/3 pyramidal, L4 basket, and L5 thick-tufted pyramidal cells showing the lowest thresholds. Despite this variability, all simulated thresholds were conservative with respect to the basic restrictions and dosimetric reference limits set by IEEE ICES and ICNIRP. The smallest margin occurred at 100 kHz, where the threshold remained a factor of 2.8 above the corresponding limit. These findings indicate that current LF EMF exposure limits remain conservative when evaluated using highly detailed, morphology-based CNS activation models.

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Quantitative imaging of the central lymphatic system with spectral CT iodine mapping: a feasibility study in swine

Liu, L. P.; Gurevich, A.; McClung, G.; Itkin, M.; Noël, P. B.

2026-05-07 radiology and imaging 10.64898/2026.05.06.26352364 medRxiv
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PurposeImaging of the central lymphatic system enables characterization of patient-specific lymphatic anatomy and accurate localization of leaks. Advancements in CT technology, particularly spectral CT, can enhance CT lymphangiography (CTL) with improved visualization and quantification. This study aimed to assess the feasibility of spectral CTL in both static and dynamic scans. Materials and Methods50% diluted iodinated contrast was injected into the bilateral superficial inguinal lymph nodes of a pig. The pig was scanned with a dual-layer spectral CT every 60 seconds for 10 minutes. To optimize contrast and visualize peristalsis, a second animal was injected with 25% and 10% diluted contrast and scanned dynamically 4 and 6.25 minutes after contrast injection. Conventional images and iodine maps were reconstructed to calculate the contrast-to-noise ratio (CNR). Additionally, the iodine density was measured adjacent to the lymphovenous junction to show fluctuations from peristalsis and contrast washout. ResultsIodine maps, compared to conventional images, separated the contrast-filled central lymphatic system from surrounding soft tissue and increased CNR to 895 compared to 43 with conventional images. 25% diluted contrast provided the best balance between visualization and quantification of the central lymphatic system, showing high and low iodine density regions corresponding to peristalsis. Iodine density peaked at 15.4 {+/-} 0.6 mg/mL and decreased to 2.0 {+/-} 0.1 mg/mL at 10.5 minutes. ConclusionSpectral CTL not only improves visualization of the central lymphatic system compared to CTL but also provides quantitative information for physiological characterization of lymphatic disease that can enhance current subjective assessment. Research highlights- Iodine maps from spectral CT lymphangiography separated contrast-filled lymphatic structures from surrounding soft tissue and provided better contrast-to-noise compared to conventional images. - Spectral CT lymphangiography enabled quantification of contrast in the central lymphatic system that demonstrated contrast washout and may be utilized for physiological characterization of disease. - Dynamic spectral CT imaging of the lymphatic system visually showed peristalsis in the thoracic duct and was further reflected in quantitative iodine density measurements.

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Dual-view Guided Context-aware Network for Automated Bone Lesion Segmentation and Quantification in Whole-body SPECT

chen, w.; Yang, X.; Lu, J.; Miao, M.; Huang, Y.; Zheng, S.; Zhang, C.; Xie, L.; Zhang, Y.

2026-05-12 bioinformatics 10.64898/2026.05.07.723665 medRxiv
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Whole-body SPECT bone scintigraphy reflects skeletal metabolic activity throughout the body and plays an indispensable role in the screening, treatment evaluation, and prognostic assessment of bone metastases in tumors. However, the automatic detection and segmentation of hypermetabolic bone lesions remain challenging due to low contrast, limited spatial resolution, and complex lesion distributions. In this study, we proposed Bone-Segnet, a dual-view guided automatic segmentation network for hypermetabolic bone lesions that integrated multi-scale feature modeling, global context modeling, and view-conditioned modulation. Pixel-level annotated anterior and posterior whole-body bone scintigraphy images were used for model training and prediction. The proposed network enhanced the recognition of low-contrast and small-scale lesions through small-lesion enhancement and multi-scale contextual modeling. A Transformer module was further introduced to strengthen global feature representation, while cross-view collaborative modeling was achieved by incorporating the complementary characteristics of anterior and posterior imaging. Experimental results demonstrated that the proposed method outperformed existing approaches across multiple evaluation metrics, with the Dice score improving from 0.7440 to 0.8750, indicating a substantial improvement in segmentation performance. Further quantitative analysis based on the segmentation results revealed significant differences among disease types in lesion count, pixel burden, and spatial distribution patterns, reflecting the heterogeneity of disease-related skeletal metabolic activity. Overall, the proposed method improved automatic lesion segmentation performance and enabled quantitative analysis of lesion burden and spatial distribution patterns, providing objective data support for the assessment of related diseases. Index Terms--Whole-body SPECT, bone lesion segmentation, dual-view modeling, quantitative analysis.

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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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Contrast-induced changes in chemical exchange saturation transfer MRI differentiate tumor progression from pseudoprogression

Benyard, B.; Soni, N. D.; Swain, A.; Srivastava, N.; Shin, J.; Nanga, R. P. R.; Yehya, N.; Fan, Y.; Reddy, R.; Haris, M.

2026-05-05 cancer biology 10.64898/2026.05.01.722099 medRxiv
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Tumor pseudo-progression (PsP) refers to an initial increase in tumor size or the appearance of new lesions. These pseudo-progressive lesions are predominantly composed of infiltrative inflammatory cells, such as macrophages. This phenomenon commonly occurs in patients undergoing radiation therapy or immunotherapy and typically indicates a positive treatment response. However, it often leads to premature treatment cessation due to misinterpretation as disease progression. Non-invasive imaging biomarkers capable of distinguishing pseudo-progression from true progression would greatly aid in treatment decision-making. In our preliminary study, we explored the potential of gadoterate meglumine (Gd-DOTA, a macrocyclic Gd-contrast) in combination with amine chemical-exchange saturation transfer (amine-CEST) imaging to differentiate tumor from radiation necrosis by assessing Gd-DOTA uptake by infiltrating immune cells, such as macrophages. To evaluate whether amine-CEST, in combination with Gd-DOTA, can differentiate macrophages from cancer cells, we incubated them with Gd-DOTA for 30 minutes. Subsequently, the cells were processed, and amine-CEST imaging was performed on a 9.4 Tesla preclinical scanner. Upon treatment with Gd-DOTA, we did not observe a significant change in amine-CEST contrast in F98 cells compared with untreated cells, whereas treated macrophages exhibited a marked decrease (~40%) in amine-CEST signal compared with untreated macrophages. This reduction in signal was attributed to the uptake of Gd-DOTA by macrophages, which notably shortened water T1 relaxation, thereby quenching the amine-CEST signal. Conversely, cancer cells showed no appreciable change in the amine-CEST signal, indicating no Gd-DOTA uptake. Furthermore, to validate that T1 shortening influences amine-CEST signal, cancer cells were also treated with manganese chloride (MnCl2) for 30 minutes. The uptake of MnCl2 by cancer cells similarly induced T1 shortening, as observed in macrophages, resulting in a decrease in the amine-CEST signal from these cells. Next, we performed the amin-CEST imaging on F98 tumor-bearing rats and radiation necrotic rats. Post-injection with Gd-DOTA showed no appreciable change in the amine-CEST contrast in the tumor-bearing rat, whereas a significant decrease in contrast was observed in the radiation necrotic rat. This further demonstrates that no change in the amine-CEST contrast in tumor-bearing rats is due to cancer cells failing to take up Gd-DOTA. The decrease in amine-CEST contrast in radiation-treated rats reflects the uptake of Gd-DOTA by macrophages infiltrating the radiation-necrotic regions. This straightforward imaging approach holds promise for clinical translation. It offers a novel method for characterizing pseudo-progressive lesions and monitoring diverse treatment responses in cancer patients using standard clinical scanners.

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Null Subtraction Imaging for Functional Ultrasound Brain Activation Mapping

Garay, G.; Barolin, J.; Sorriba, V.; Damian, J. P.; Kou, Z.; Oelze, M.; Negreira, C.; Kun, A.; Brum, J.

2026-04-17 bioengineering 10.64898/2026.04.14.718533 medRxiv
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Null Subtraction Imaging (NSI) is a nonlinear beamforming approach that combines multiple receive apodizations and subtraction to improve spatial resolution in ultrasound imaging. In NSI, a DC offset parameter is introduced in the apodization design to control the sharpening of the effective beam pattern and, therefore, the degree of spatial-resolution enhancement. Here, we investigate the use of NSI in functional ultrasound (fUS) imaging of the mouse brain and compare its performance with conventional delay-and-sum (DAS) beamforming across a range of DC offset values. fUS acquisitions were performed in three anesthetized wild-type mice during periodic vibrissae stimulation. Activation maps were computed by correlating cerebral blood volume (CBV) signals with the stimulation pattern. Activation area, edge gradient, Dice similarity coefficient, and signal-to-noise ratio (SNR) were used to evaluate spatial localization, boundary sharpness, vascular alignment and signal stability, respectively. NSI yielded more spatially confined activation maps than DAS and produced sharper activation boundaries. However, for low DC offsets (DC < 0.5), the CBV signal exhibited increased fluctuations, which reduced temporal stability and limited the reliability of the functional maps. As the DC offset increased, temporal SNR improved, while the spatial-resolution gain progressively decreased. In our imaging configuration, intermediate DC values around DC {approx} 0.5 provided the most favorable compromise between improved spatial localization and sufficient temporal stability for reliable functional activation detection. These results demonstrate the feasibility of applying NSI to functional ultrasound imaging and provide a quantitative framework for selecting the DC parameter in fUS studies.

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Assessment of patient radiation dose in conventional lumbar spine radiography: A multicenter study in the Souss Massa region, Morocco

SOUDI, A.; MENHOUR, Y.

2026-03-26 radiology and imaging 10.64898/2026.03.24.26349174 medRxiv
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BackgroundPatient radiation exposure in diagnostic radiology is an important concern for radiation protection and patient safety. Monitoring radiation dose levels during radiographic examinations is essential to ensure compliance with diagnostic reference levels (DRLs) and to optimize radiological practices. ObjectiveThe aim of this study was to evaluate patient radiation dose during conventional lumbar spine radiography and compare the obtained values with diagnostic reference levels. MethodsA descriptive cross-sectional multicenter study was conducted in four hospitals in the Sous Massa region, Morocco, between April and June 2017. Data were collected from 142 patients undergoing lumbar spine radiography examinations and from 20 radiology technicians. Exposure parameters including tube voltage, tube current, exposure time, focus-to-film distance, and field size were recorded. Entrance surface dose (ESD) was estimated using MICADO software, and dose area product (DAP) values were subsequently calculated. The 75th percentile values were determined and compared with diagnostic reference levels. ResultsThe regional 75th percentile ESD values were 5.33 mGy for the anteroposterior projection and 7.38 mGy for the lateral projection. Corresponding DAP values were 1840.9 mGy.cm2 and 2783.65 mGy.cm2, respectively. All obtained values were below the diagnostic reference levels used for comparison. However, variations between hospitals were observed, likely due to differences in imaging protocols and equipment. ConclusionRadiation doses associated with lumbar spine radiography in the evaluated hospitals were within acceptable limits according to diagnostic reference levels. Continuous monitoring of patient radiation exposure and optimization of radiographic techniques remain essential to ensure effective radiation protection.

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FLASH Radiotherapy is faster than a heartbeat: A compartmental model to illustrate the interplay between tissue oxygen perfusion and ultra-high dose rate effects.

Ballesteros-Zebadua, P.; Jansen, J.; Grilij, V.; Franco-Perez, J.; Vozenin, M.-C.; Abolfath, R.

2026-03-16 biochemistry 10.64898/2026.03.12.711443 medRxiv
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Ultra-high-dose-rate therapy enhances the protection of normal tissues and reduces side effects while effectively controlling tumors. This biological phenomenon is called the FLASH effect, and when observed, therapy is called FLASH Radiotherapy (FLASH-RT). Various hypotheses have been proposed to explain how ultra-high dose rates achieve these effects under different conditions, with the impact of tissue oxygen perfusion still needing further investigation. FLASH-RT involves brief exposure to radiation, which results in fewer heartbeats occurring during the irradiation period, which could lead to reduced tissue oxygen perfusion occurring during the treatment timeframe. Therefore, we developed a compartmental model to simulate oxygen transfer and its interaction with radiation. The proposed model consists of three compartments: 1) the heart and arteries; 2) the irradiated brains blood vessels and capillaries; and 3) the irradiated brain tissue. We employed a system of differential equations, incorporating experimental data from in vivo oxygen measurements using the Oxyphor probe in the brain, to fit the model parameters to the experimental results. This model shows how dose rate and oxygen perfusion could influence chemical processes such as lipid peroxidation, potentially leading to differential biological effects. Our analysis of lipid peroxidation as a function of dose rate revealed a sigmoidal dose-rate-response curve that correlates well with several published biological response datasets. Our results indicate that the differential chemical effects of FLASH-RT compared with conventional dose rates may depend on factors such as oxygen perfusion, consumption, and tissue oxygen tension. This suggests that the temporal dynamics of oxygen could play a crucial role in enhancing the therapeutic window for FLASH-RT treatments. Furthermore, it suggests that the magnitude of some observed FLASH effects may vary across tissues or tumors and across experimental models, given differential oxygen dynamics.

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Evaluating the Large Language Model-Based Quality Assurance Tool for Auto-Contouring

Tozuka, R.; Akita, T.; Matsuda, M.; Tanno, H.; Saito, M.; Nemoto, H.; Mitsuda, K.; Kadoya, N.; Jingu, K.; Onishi, H.

2026-04-01 radiology and imaging 10.64898/2026.03.31.26349802 medRxiv
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Purpose: Manual verification of AI-based auto-contouring is labor-intensive and prone to fatigue-related errors. This study developed the large language model (LLM)-based automated Quality Assurance (QA) for auto-contouring (LAQUA) system using a multimodal LLM, Gemini 2.5 Pro, and evaluated its feasibility as a clinical primary screening tool to streamline the QA workflow. Methods: Twenty male pelvic CT scans from an open dataset were utilized. Three distinct auto-contouring software packages (OncoStudio, RatoGuide prototype and syngo.via) were evaluated. Auto-contouring results for each slice were exported as PDF images with overlaid contours and input into Gemini 2.5 Pro. The LLM was instructed to rate the contour quality on a 5-point clinical scale (5: Optimal; 4: Acceptable; 3: Suboptimal; 2: Unacceptable; redraw from scratch; 1: Unacceptable; organ not detected). Using evaluations by two board-certified radiation oncologists as ground truth, Spearman's rank correlation coefficients ({rho}) and weighted kappa coefficients ({kappa}) were calculated. Additionally, to assess screening performance, sensitivity and specificity were calculated by dichotomizing the scores into "Pass" and "Fail" using two different cutoffs (scores [&ge;] 3 and [&ge;] 4 as "Pass"). Finally, the alignment of the rationales provided by the LLM with the auto-contouring quality was evaluated by two board-certified radiation oncologists. This was conducted using a Likert scale assessing four domains (error detection, hallucination, clinical relevance, and anatomical understanding), each scored out of 2 points. Results: The LAQUA system demonstrated moderate to strong agreement with expert judgments across all evaluated organs ({rho}: 0.567 - 0.835; quadratic weighted {kappa} : 0.639 - 0.804), with the rectum showing the highest correlation. Regarding screening performance, a cutoff of [&ge;]3 as "Pass" achieved the highest sensitivity and specificity in specific subgroups, but with wide 95% confidence intervals (CIs). A cutoff of [&ge;]4 as "Pass" narrowed the CIs, yielding the highest sensitivity in the rectum (0.976) and the highest specificity in the left femoral head (0.933). Qualitatively, the LLM's rationales achieved an overall mean score of 1.70 {+/-} 0.48 (out of 2), with 155 of 291 outputs receiving perfect scores across all criteria. Conclusions: The LAQUA system demonstrated substantial agreement with expert evaluations in AI-based auto-contouring quality assessment. While potential overestimation bias (risk of missing "Fail" cases) warrants caution, the observed sensitivity suggests its feasibility as a primary screening QA tool to efficiently filter acceptable contours, thereby reducing the clinical workload.

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Quantitative Assessment of Dual and Triple Energy Window Scatter Correction in Myocardial Perfusion SPECT with a 4D Phantom

El Bab, M.; Guvenis, A.

2026-04-25 cardiovascular medicine 10.64898/2026.04.17.26351095 medRxiv
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Conflicting evidence on scatter correction (SC) methods plagues quantitative myocardial perfusion SPECT (MPI), hindering standardized clinical protocols. This simulation study, utilizing the SIMIND Monte Carlo program and a highly realistic 4D XCAT phantom, systematically evaluates Dual Energy Window (DEW, with k=0.5) and Triple Energy Window (TEW) SC techniques. We uniquely investigate their performance across various photopeak window widths (2, 4, and 6 keV) and novel overlapped/non-overlapped configurations specifically for Tc 99m MPI - parameters largely unexplored in realistic cardiac models. Images were reconstructed with OSEM under uncorrected (UC), SC, and combined attenuation and scatter corrected (ACSC) conditions. Quantitative analysis focused on signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), defect contrast, and relative noise to background (RNB). Our findings consistently show ACSCs superior performance in CNR, SNR, and defect contrast, confirming its critical role. Interestingly, SC alone reduced noise but compromised defect contrast relative to UC, highlighting a potential trade-off without attenuation correction. Crucially, this study reveals minimal influence of photopeak window width and overlap configuration on image quality, and no significant difference between DEW and TEW across most metrics. These results provide essential evidence for optimizing quantitative MPI protocols, suggesting that for Tc-99m, the choice between DEW and TEW, and specific window settings, may be less critical than ensuring robust attenuation correction.

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Evaluation of Diffusion Tensor Imaging in the Corpus Callosum on a Portable 100 mT MRI System

Lee, P. K.; Chen, S.; Zhong, S.; Wang, C.; Zhang, Z.

2026-04-28 bioengineering 10.64898/2026.04.24.717780 medRxiv
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Low-cost portable MRI has the potential to improve the accessibility of MRI, but new acquisition methods and protocols must be developed and evaluated to accommodate the reduction in SNR and greater impact of system imperfections. Diffusion tensor imaging (DTI) is a candidate tool for monitoring population health, but the bias and variance of quantitative diffusion tensor-derived metrics must be evaluated prior to designing such studies. DTI of the corpus callosum was performed on an in-house, portable 100 mT MRI system using a slab diffusion weighted Fast Spin Echo with radiofrequency (RF) encoding. Slice coverage was restricted to the corpus callosum to shorten scan time and reduce sensitivity to large rigid motion. In vivo DTI images were obtained in two healthy volunteers with nominal voxel size 50 mm3, scan time 25 minutes, and two different volunteers using nominal voxel size 25 mm3, scan time 35 minutes. Mean diffusivity (MD) and fractional anisotropy (FA) coefficients of variation were estimated in the 50 mm3 acquisition using a bootstrap approach and compared to resolution-matched data obtained on a conventional 1.5T system. MD / FA maps were compared quantitatively and qualitatively. Mean MD values in the corpus callosum obtained on the 100 mT system were within 10% of the reference 1.5T acquisition, but FAs were underestimated by 20-30%. The corpus callosum median MD coefficient of variation was 3.7%, and the median FA coefficient of variation was 7.5%. FA maps obtained at 100 mT had an elevated FA noise floor and color FA maps had lower apparent resolution but some white matter tracts were still distinguishable. HighlightsO_LIDiffusion Tensor Imaging (DTI) of the corpus callosum was performed on a portable 100 mT MRI scanner with 50 mm3 voxels in 25 minutes scan time. C_LIO_LIMean Diffusivity estimates in the corpus callosum obtained at 100 mT and 1.5T differed by less than 0.1 x 10-3 mm2/s. C_LIO_LISome white matter tracts were visible in color Fractional Anisotropy maps obtained at 100 mT but FA maps were underestimated by 20- 30% when compared to a resolution-matched 1.5T acquisition, and had lower apparent resolution. C_LI

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Generalizable Deep Learning Framework for Radiotherapy Dose Prediction Across Cancer Sites, Prescriptions and Treatment Modalities

Chang, H.-h.; Cardan, R.; Nedunoori, R.; Fiveash, J.; Popple, R.; Bodduluri, S.; Stanley, D. N.; Harms, J.; Cardenas, C.

2026-04-22 radiology and imaging 10.64898/2026.04.17.26350770 medRxiv
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Optimizing radiotherapy dose distributions remain a resource-intensive bottleneck. Existing AI-based dose prediction methods often have limited generalizability because they rely on small, heterogeneous datasets. We present nnDoseNetv2, an auto-configured, end-to-end framework for dose prediction across diverse disease sites (head and neck, prostate, breast, and lung), prescription levels (1.5-84 Gy), and treatment modalities (IMRT, VMAT, and 3D-CRT). By integrating machine-specific beam geometry with 3D structural information, the framework is designed to generalize across varied clinical scenarios. A single multi-site model was trained on 1,000 clinical plans. On sites seen during training, performance was comparable to specialized site-specific models. On unseen sites (liver and whole brain), the model outperformed site-specific models, with mean absolute errors of 2.46% and 6.97% of prescription, respectively. These results suggest that geometric awareness can bridge disparate anatomical domains while eliminating the need for site-specific model maintenance, providing a scalable and high-fidelity approach for personalized radiotherapy planning.

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Distant Dipoles: A Multi-Parameter and Multi-Objective Analysis of RF Coil Performance For 7T Body MRI

Haluptzok, T. D.; Sadeghi-Tarakameh, A.; Lagore, R. L.; Metzger, G. J.

2026-05-03 biophysics 10.64898/2026.04.29.721770 medRxiv
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PurposeTo address the limitations of single-distance, 1D performance metrics in RF coil design. This work introduces a multi-objective, volume-of-interest (VOI) based analysis to systematically characterize the trade-offs between power efficiency, pSAR efficiency, and homogeneity as a function of dipole length (l) and distance-to-load (d) for multiple dipole geometries and target anatomies. MethodsElectromagnetic simulations of straight and end-meandered dipole antennas were performed with varying lengths (100-500 mm) and distance-to-load (1-81 mm) over three anatomical targets (prostate, kidney, heart). Homogeneity, power efficiency, pSAR efficiency, and load sensitivity performance metrics were calculated within each anatomical VOI. Inter-element coupling at variable d was assessed in a 3-element array, and a subset of single-element simulations was experimentally validated using B1+ mapping. ResultsA fundamental trade-off was found between power efficiency and pSAR efficiency. Optimal power efficiency was achieved with shorter dipoles (150 mm < l < 300 mm) closer to the sample (d < 30 mm), while optimal pSAR efficiency and homogeneity were achieved with longer dipoles at further from the sample (d > 60 mm). Inter-element coupling increased with distance-to-load but could be managed by increasing element spacing. Experimental measurements were in good agreement with simulation trends. ConclusionIncreasing distance-to-load to 40-60 mm, compared with commonly used distances of 20-30 mm, offers a practical strategy for improving pSAR efficiency and homogeneity with a minimal decrease in power efficiency. This work provides a quantitative analysis that enables RF coil designers to make informed, data-driven decisions when developing next-generation body arrays and suggests that unshielded end-meandered dipoles could be an optimal transmit element geometry.

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Extracting Parsimonious Quantitative Predictors of Biological Effectiveness from 'First-Principles' Radiobiology: Application to the Mixed-Quality Problem

Yusufaly, T.; Transtrum, M.; Huang, L.; Sabok-Sayr, S.; Sgouros, G.; Hobbs, R.; Jia, X.

2026-05-06 biophysics 10.64898/2026.05.02.722446 medRxiv
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Developing parsimonious, mechanism-aware quantitative models that predict how biological effectiveness changes with different modifiers remains, in general, an unsolved problem. Advances in radiobiological research have created a large knowledge base of first-principles mechanistic models of radiation response that, in principle, could accurately predict radiosensitivity across different experimental and clinical conditions. However, in practice these mechanistic models come with an overabundance of parameters, the majority of which are practically unidentifiable and, moreover, likely unnecessary if one simply wishes to predict how radiosensitivity changes for some specific modifier of interest. Nevertheless, determining which few details in the full mechanistic model are relevant for a given purpose, as well as how to remove any other extraneous details, remains a highly non-trivial task. In this study, we demonstrate the potential of model reduction, starting from a detailed mechanistic description, as a systematic strategy for deriving parsimonious, experimentally falsifiable radiobiological descriptors. As a proof-of-concept demonstration, we apply the Manifold Boundary Approximation Method (MBAM) to a Mechanistic Model of DNA Repair and Survival (MEDRAS), for the problem of cell survival prediction following an acute exposure. Our findings reveal that the complete MEDRAS model for an arbitrary mixed-quality exposure can be structurally simplified to a reduced three-parameter model for an effective uniform-quality, named MEDRAS-LPL. Additional MBAM analysis on MEDRAS-LPL identifies two boundaries in parameter space, corresponding to sparsely ionizing and densely ionizing radiation. Mapping of MEDRAS-LPL parameter space on to effective LQ space further demonstrates that parameters close to the sparsely ionizing boundary line up with expectations from the theory of dual radiation, while parameters close to the densely ionizing boundary line up with expectations from a purely linear model based on a target-theory description. Moreover, our formalism predicts enhanced synergistic interactions between sparsely ionizing and densely ionizing radiation beyond the Zaider Rossi model (ZRM) paradigm, in line with empirical observations. The results highlight the potential for using reduced-order models not only for predictive applications but also for generating novel hypotheses that can inform future experimental designs and optimization strategies in radiobiology.