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Low-dose computed tomography (LDCT) is the current standard for lung cancer screening, yet its adoption and accessibility remain limited. Many regions lack LDCT infrastructure, and even among those screened, early-stage cancer detection often yield false positives, as shown in the National Lung Screening Trial (NLST) with a sensitivity of 93.8 percent and a false-positive rate of 26.6 percent. We aim to investigate whether X-ray dark-field imaging (DFI) radiograph, a technique sensitive to small-angle scatter from alveolar microstructure and less susceptible to organ shadowing, can significantly improve early-stage lung tumor detection when coupled with deep-learning segmentation. Using paired attenuation (ATTN) and DFI radiograph images of euthanized mouse lungs, we generated realistic synthetic tumors with irregular boundaries and intensity profiles consistent with physical lung contrast. A U-Net segmentation network was trained on small patches using either ATTN, DFI, or a combination of ATTN and DFI channels.Results show that the DFI-only model achieved a true-positive detection rate of 83.7 percent, compared with 51 percent for ATTN-only, while maintaining comparable specificity (90.5 versus 92.9 percent). The combined ATTN and DFI input achieved 79.6 percent sensitivity and 97.6 percent specificity. In conclusion, DFI substantially improves early-tumor detectability in comparison to standard attenuation radiography and shows potential as an accessible, low-cost, low-dose alternative for pre-clinical or limited-resource screening where LDCT is unavailable.
Achieving an optimal biomechanical environment within bone scaffolds is critical for promoting tissue regeneration, particularly in load-bearing anatomical sites where rigid fixation can induce stress shielding and compromise healing. Functionally graded (FG) scaffolds, which incorporate controlled variations in porosity or material properties, have attracted significant attention as a strategy to mitigate stress shielding by promoting more favourable load transfer. In this study, the effects of porosity gradient magnitude (i.e., max-to-min ratio of porosity), gradient resolution, scaffold material properties, and fixation plate rigidity on the distribution of mechanical stimuli within FG scaffolds were systematically investigated. Finite element analyses (FEA) were conducted on a femoral segmental defect model stabilised with a bone plate, and multiple porosity gradient strategies were compared against a corresponding uniform scaffold composed of body-centred cubic (BCC) unit cells. Scaffolds composed of titanium alloy (Ti-6Al-4V), bioactive glass (45S5 Bio-glass), and polylactic acid (PLA) were evaluated to capture a range of material stiffnesses. Introducing porosity gradients consistently enhanced the mean octahedral shear strain within the scaffold, particularly in regions adjacent to the fixation plate affected by stress shielding. The magnitude of mechanical stimulus improvement increased with both greater porosity gradient magnitudes and higher gradient resolution. These improvements were more pronounced in stiffer materials, such as Ti-6Al-4V, emphasising the critical interplay between scaffold material properties and architectural design. These findings highlight the importance of tailoring both porosity profiles and material selection to optimise scaffold mechanics for bone regeneration.
X-ray microtomography at synchrotron sources is fundamentally limited by the high radiation dose applied to the samples, which restricts investigations to non-native tissue states and thereby compromises the biological relevance of the resulting data. The limitation stems from inefficient indirect detection schemes that require prolonged exposures. Efforts to extract additional contrast through multimodal techniques, like modulation-based imaging, worsen the problem by requiring multiple tomographic scans. In addition, the techniques suffer from low modulator pattern visibility, which reduces measurement efficiency and sensitivity. We address both the detection efficiency and modulation visibility challenges using a novel setup that combines an X-ray waveguide, a structured phase modulator, and a photon-counting detector. Our approach simultaneously achieves near-theoretical limits in both visibility (95%) and quantum efficiency (98%), thereby enabling dose-efficient multimodal microtomography at single-micrometer resolution. This advance will enable new classes of experiments on native-state biological specimens with the potential to advance biomedical research, disease diagnostics, and our understanding of tissue structure in physiological environments.
Radiation chemistry of model systems irradiated with ultra-high dose-rates (UHDR) is key to obtain a mechanistic understanding of the sparing of healthy tissue, which is called the FLASH effect. It is envisioned to be used for efficient treatment of cancer by FLASH radiotherapy. However, it seems that even the most simple model systems, water irradiated with varying dose-rates (DR), pose a challenge. This became evident, as differences within measured and predicted hydrogen peroxide (H2O2) yields (g-values) for exposure of liquid samples to conventional DR and UHDR were reported. Many of the recently reported values contradict older experiments and current Monte-Carlo simulations(MCS). In the present work, we aim to identify possible reasons of these discrepancies and propose ways to overcome this issue. Hereby a short review of recent and classical literature concerning experimental and simulational studies is performed. The studies cover different radiation sources, from gamma rays, high-energy electrons, heavy particles (protons and ions) with low and high linear energy transfer (LET), and samples of hypoxic & oxygenated water, with cosolutes such as bovine-serum albumine (BSA). Results are for additional experimental parameters, such as solvent, sample container and analysis methods used to determine the respective g-values of H2O2. Similarly the parameter of the MCS by the step-by-step approach, or the independent-reaction time (IRT) method are discussed. Here, UHDR induced modification of the radical-radical interaction and dynamics, not governed by diffusion processes, may cause problems. Approaches to test these different models are highlighted to allow progress: by making the step from a purely descriptive discourse of the effects observed, towards testable models, which should clarify the reasons of how and why such a disagreement came to light in the first place.
Quantitative computed tomography (QCT) plays a crucial role in assessing bone strength and fracture risk by enabling volumetric analysis of bone density distribution in the proximal femur. However, deploying automated segmentation models in practice remains difficult because deep networks trained on one dataset often fail when applied to another. This failure stems from domain shift, where scanners, reconstruction settings, and patient demographics vary across institutions, leading to unstable predictions and unreliable quantitative metrics. Overcoming this barrier is essential for multi-center osteoporosis research and for ensuring that radiomics and structural finite element analysis results remain reproducible across sites. In this work, we developed a domain-adaptive transformer segmentation framework tailored for multi-institutional QCT. Our model is trained and validated on one of the largest hip fracture related research cohorts to date, comprising 1,024 QCT images scans from Tulane University and 384 scans from Rochester, Minnesota for proximal femur segmentation. To address domain shift, we integrate two complementary strategies within a 3D TransUNet backbone: adversarial alignment via Gradient Reversal Layer (GRL), which discourages the network from encoding site-specific cues, and statistical alignment via Maximum Mean Discrepancy (MMD), which explicitly reduces distributional mismatches between institutions. This dual mechanism balances invariance and fine-grained alignment, enabling scanner-agnostic feature learning while preserving anatomical detail.
More than a century ago, Karl Bernhard Zoeppritz derived the equations that determine the reflected and transmitted coefficients at a planar interface for an incident seismic wave. The coefficients so obtained are a function of the elastic parameters of the media on each side of the interface and the angle of incidence. Approximations of the equations have been proposed and used in geophysical exploration, however, full use of the equations and their generalization to multiple layers could offer richer information about the properties of the media and be helpful in medical diagnosis via ultrasound. In this work, we investigate how to extract information from the angle-dependent reflection coefficients, including critical angles and the wave distortion at the interface between two and three media. It is shown that it is possible to separate the effect of density from speed of sound mismatch by measuring amplitudes as a function of angle of incidence (AVA). And examining the critical angle and waveform distortion of the reflected waves can reveal the thickness of an intermediate layer, even with subwavelength resolution. These studies could be integrated into medical imaging and also into the training of artificial intelligence systems that assist in diagnosis. In particular, they could help prevent cerebrovascular accidents by early detection of the formation and hardening of plaque in the arteries that irrigate the brain.
Background and Purpose: Increasing the number of arcs in volumetric modulated arc therapy (VMAT) allows for better intensity modulation and may improve plan quality. However, this leads to longer delivery times, which may cause patient discomfort and increase intra-fractional motion. In this study, it was investigated whether the delivery of different VMAT plans in different fractions may improve the dosimetric quality and delivery efficiency for the treatment of patients with complex tumor geometries. Materials and Methods: A direct aperture optimization algorithm was developed which allows for the simultaneous optimization of different VMAT plans to be delivered in different fractions, based on their cumulative physical dose. Each VMAT plan is constrained to deliver a uniform dose within the target volume, such that the entire treatment does not alter the fractionation scheme and is robust against inter-fractional setup errors. This approach was evaluated in-silico for ten patients with gynecological and head-and-neck cancer. Results: For all patients, fraction-variant treatments achieved better target coverage and reduced the dose to critical organs-at-risk compared to fraction-invariant treatments that deliver the same plan in every fraction, where the dosimetric benefit was shown to increase with the number of different plans to be delivered. In addition, 1-arc and 2-arc fraction-variant treatments could approximate the dosimetric quality of 3-arc fraction-invariant treatments, while reducing the delivery time from 180 s to 60 s and 120 s, respectively. Conclusions: Fraction-variant VMAT treatments may achieve excellent dosimetric quality for patients with complex tumor geometries, while keeping the delivery time per fraction viable.
When acquiring PET images, body motions are unavoidable, given that the acquisition time could last 10-20 minutes or more. These motions can seriously deteriorate the quality of the final image at the level of image reconstruction and attenuation corrections. Movements can have rhythmic patterns, related to respiratory or cardiac motions, or they can be abrupt reflexive actions caused by the patient's discomfort. Many approaches, software and hardware, have been developed to mitigate this problem where each approach has its own advantages and disadvantages. In this work we present a simulation study of a head monitoring device, named CrowN@22, intended to be used in conjunction with a dedicated brain PET scanner. The CrowN@22 device consists of six point sources of non-pure positron emitter isotopes, such as 22Na or 44Sc, mounted in crown-like rings around the head of the patient. The relative positions of the point sources are predefined and their actual position, once mounted, can be reconstructed by tagging the extra 1274 keV photon (in the case of 22Na). These two factors contribute to a superb signal-to-noise ratio, distinguishing between the signal from the 22Na monitor point sources and the background signal from the FDG in the brain. Hence, even with a low activity for the monitor point sources, as low as 10 kBq per point source, in the presence of 75 MBq activity of 18F in the brain, one can detect brain movements with a precision of less than 0.3 degrees, or 0.5 mm, which is of the order of the PET spatial resolution, at a sampling rate of 1 Hz.
Microplastics are increasingly recognized as a global environmental health threat, yet their detection and characterization remain constrained by the cost, form factor, and throughput of existing analytical tools. Portable micro/nanotechnology-based sensors are emerging to address this need, but most rely on the assumption of spherical particle geometry in their operating principle, limiting their relevance for environmental analysis. Here, we overcome this limitation by advancing microwave cytometry with machine learning-enabled shape recognition. Microwave cytometry is a flow-through electronic platform that integrates microwave resonator responses with low-frequency impedance signals to capture the dielectric signatures of individual particles. Using microscopy-derived shape measurements as ground truth, we trained a random forest model to decode these information-rich waveforms. Once trained, the system operates without optical input, enabling electronic-only determination of particle geometry. We demonstrate extraction of the major and minor axes of ellipsoidal microparticles with <8% relative error on average and use these predictions to derive the dielectric permittivity of ellipsoid particles. This approach removes long-standing shape assumptions in microplastic sensing and establishes a pathway toward portable, high-throughput, morphology-aware detection technologies.
Background and Purpose: Reirradiation for non-small cell lung cancer (NSCLC) is commonly delivered using coplanar techniques. In this study, we developed a beam orientation optimization algorithm for reirradiation planning to investigate whether the selection of favorable non-coplanar beam orientations may limit cumulative doses to critical organs-at-risk (OARs) and thus improve the therapeutic window. Materials and Methods: Fifteen cases of challenging high-dose reirradiation for locoregionally recurrent NSCLC were included in this in-silico study. For each patient, the dose distribution from the previous treatment was first mapped to the reirradiation planning CT using rigid dose registration, and subsequently converted to equivalent dose in 2 Gy fractions (EQD2). A 2-arc non-coplanar reirradiation plan, combining dynamic gantry and couch rotation, was then generated using an EQD2-based direct aperture optimization algorithm, which allows for the simultaneous optimization of the dynamic gantry-couch path and the cumulative EQD2 distribution. Non-coplanar reirradiation plans were benchmarked against 2-arc coplanar VMAT plans, which mimic state-of-the-art practice for reirradiation of NSCLC. Results: Non-coplanar reirradiation plans could reduce the maximum cumulative EQD2 to critical OARs such as bronchial tree, esophagus, thoracic wall and trachea by at least 5 Gy2 for 6 out of 15 patients compared to coplanar reirradiation plans. At the same time, target coverage and lung EQD2 metrics were comparable for both methods. Conclusions: The automated selection of favorable non-coplanar beam orientations may reduce the maximum cumulative EQD2 to critical OARs in challenging thoracic reirradiation cases. This allows to explore either better OAR sparing or dose-escalation in future clinical studies.
Purpose: To develop a virtual reality simulator for high dose rate prostate brachytherapy and to test whether participation is associated with immediate gains in self-reported confidence across predefined procedural domains in two cohorts. Methods: Two modules were developed and implemented using Unreal Engine: patient preparation and template guided needle insertion. Oncology staff and trainees completed pre and post surveys that assessed confidence for recalling steps, explaining steps, identifying equipment, and explaining equipment function. Studies were conducted at the Hands On Brachytherapy Workshop (HOWBT) in London, Ontario, and at Sunnybrook Odette Cancer Centre in Toronto, Ontario. Paired Wilcoxon signed rank tests with two-sided p values compared before and after scores within each module. Results: Patient preparation (N=11) confidence increased for recalling steps (W=65, p=0.002), explaining steps (W=51, p = 0.023), identifying equipment (W=65, p=0.002), and explaining equipment function (W=60, p=0.0078). Needle insertion (N=27) confidence increased for recalling steps (W=292, p<0.001), explaining steps (W=347, p<0.001), identifying equipment (W=355, p<0.001), and explaining equipment function (W=354, p<0.001). Conclusion: The simulator was feasible to deploy and was associated with higher self-reported confidence across key domains immediately after training. Findings may inform future curriculum design and implementation work.
Particle therapy relies on up-to-date knowledge of the stopping power of the patient tissues to deliver the prescribed dose distribution. The stopping power describes the average particle motion, which is encoded in the distribution of prompt-gamma photon emissions in time and space. We reconstruct the spatiotemporal emission distribution from multi-detector Prompt Gamma Timing (PGT) data. Solving this inverse problem relies on an accurate model of the prompt-gamma transport and detection including explicitly the dependencies on the time of emission and detection. Our previous work relied on Monte-Carlo (MC) based system models. The tradeoff between computational resources and statistical noise in the system model prohibits studies of new detector arrangements and beam scanning scenarios. Therefore, we propose here an analytical system model to speed up recalculations for new beam positions and to avoid statistical noise in the model. We evaluated the model for the MERLINO multi-detector-PGT prototype. Comparisons between the analytical model and a MC-based reference showed excellent agreement for single-detector setups. When several detectors were placed close together and partially obstructed each other, intercrystal scatter led to differences of up to 10 % between the analytical and MC-based model. Nevertheless, when evaluating the performance in reconstructing the spatiotemporal distribution and estimating the stopping power, no significant difference between the models was observed. Hence, the procedure proved robust against the small inaccuracies of the model for the tested scenarios. The model calculation time was reduced by 1500 times, now enabling many new studies for PGT-based systems.
Several centimeters below the skin lie multiple biomarkers, such as glucose, oxygenation, and blood flow. Monitoring these biomarkers regularly and in a non-invasive manner would enable early insight into metabolic status and vascular health. Currently, there are only a handful of non-invasive monitoring systems. Optical methods offer molecular specificity (i.e., multi-biomarker monitoring) but have shallow reach (a few millimeters); ultrasound penetrates deeper but lacks specificity; and MRI is large, slow, and costly. Photoacoustic (PA) sensing combines the best of optical and ultrasound methods. A laser transmitter emits pulses that are absorbed by different molecules, providing specificity. These light pulses generate pressure changes that are captured by an ultrasound receiver, providing depth. Photoacoustic sensing is promising, but the current platforms are bulky, complex, and costly. We propose the first embedded PA platform. Our contributions are fourfold. First, inspired by LiDAR technology, we propose a novel transmitter that emits pulses similar to those in the state-of-the-art (SoA), but instead of using high-voltage sources and complex electronic interfaces, we use a simple low-power microcontroller (MCU). Second, we carry out a thorough analysis of our custom transmitter and a commercial system. Third, we build a basic ultrasound receiver that is able to process the faint signal generated by our transmitter. Lastly, we compare the performance of our platform against a SoA commercial system, and show that we can detect glucose and (de)oxygenated hemoglobin in two controlled solution studies. The resulting signal characteristics indicate a plausible path toward noninvasive, real-time, at-home sensing relevant to diabetes care. More broadly, this platform lays the groundwork for translating the promise of PA sensing into a broader practical reality.
Diffusion MRI has revealed important insights into white matter microstructure, but its application to gray matter remains comparatively less explored. Here, we investigate whether global patterns of gray-matter microstructure can be captured through neurite orientation dispersion and density imaging (NODDI) and whether such patterns are predictive of cognitive performance. Our findings demonstrate that PCA-based global indicators of gray-matter microstructure provide complementary markers of structure-function relationships, extending beyond region-specific analyses. Our results suggest that general microstructure factors may serve as robust, interpretable biomarkers for studying cognition and cortical organization at the population level. Using diffusion MRI and behavioral data from the Human Connectome Project Young Adult study, we derived region-averaged NODDI parameters and applied principal component analysis (PCA) to construct general gray-matter microstructure factors. We found that the factor derived from isotropic volume fraction explained substantial inter-individual variability and was significantly correlated with specific cognitive scores collected from the NIH Toolbox. In particular, the isotropic volume fraction factor was linked to reading and vocabulary performance and to cognitive fluidity.
The cluster dose concept offers an alternative to the radiobiological effectiveness (RBE)-based model for describing radiation-induced biological effects. This study examines the application of a neural network to predict cluster dose distributions, with the goal of replacing the computationally intensive simulations currently required. Cluster dose distributions are predicted using a U-Net that was initially pretrained on conventional dose distributions. Using transfer learning techniques, the decoder path is adapted for cluster dose estimation. Both the training and pretraining datasets include head and neck regions from multiple patients and carbon ion beams of varying energies and positions. Monte Carlo (MC) simulations were used to generate the ground truth cluster dose distributions. The U-Net enables cluster dose estimation for a single pencil beam within milliseconds using a graphics processing unit (GPU). The predicted cluster dose distributions deviate from the ground truth by less than 0.35%. This proof-of-principle study demonstrates the feasibility of accurately estimating cluster doses within clinically acceptable computation times using machine learning (ML). By leveraging a pretrained neural network and applying transfer learning techniques, the approach significantly reduces the need for large-scale, computationally expensive training data.
Purpose: We presented a GPU-based MC framework, ARCHER-EPID, specifically designed for EPID transit dosimetry, with improving accuracy and efficiency. Methods: A comprehensive MC framework was developed to perform full radiation transport simulations through three distinct zones: a detailed linear accelerator head model, a CT-based patient/phantom geometry, and a realistic, multi-layered EPID model. To convert the simulated absorbed dose to a realistic detector signal, a dose-response correction model was implemented. The framework was validated by comparing simulations against experimental measurements for 25 IMRT fields delivered to both a solid water phantom and a anthropomorphic phantom. Agreement was quantified using Gamma analysis. Results: The GPU-accelerated ARCHER-EPID framework can complete the simulation for a complex IMRT field in about 90 seconds. A 2D correction factor lookup table is generated by parameterizing radiological thickness and effective field size to account for the EPID's energy-dependent response. The data revealed that for small fields, beam hardening is the dominant effect, while for large fields, the contribution from patient-generated scatter overwhelms this effect. The average 2D gamma passing rates (3%/3 mm criteria) between simulation and measurements are 98.43% for the solid water phantom and 97.86% for the anthropomorphic phantom, respectively. Visual comparison of the images and dose profiles between simulation and measurements show a high degree of agreement. Conclusions: We have successfully developed and validated a GPU-based MC framework that provides gold-standard accuracy for EPID transit dosimetry in radiotherapy. The results demonstrate that our proposed method has potential for routine application in PSQA.
Osteoporosis and osteopenia remain vastly underdiagnosed. Current clinical screening relies almost exclusively on dual-energy X-ray absorptiometry (DXA), which measures bone mineral density (BMD) but fails to capture the compositional changes that lead to BMD loss. We investigated whether Spatially Offset Raman Spectroscopy (SORS) applied to excised finger bones can assess subsurface biochemical markers capable of diagnosing osteoporosis and osteopenia and predicting wrist DXA T-scores. Raman spectra were acquired ex vivo on the mid-shaft of the proximal phalanx of the second digit from 25 female cadavers spanning the three T-score categories (n=8 normal, n=6 osteopenic, and n=11 osteoporotic) at spatial offsets of 0, 3, and 6 mm from a laser irradiation spot. After normalizing spectra to the PO43- peak, group-averaged spectra of the three categories, measured at 3-mm offset, showed clear differences in the CO32-, Amide III, CH2, and Amide I bands. Quantitatively, four out of five mineral-to-matrix ratios differed significantly (p < 0.05) between normal and osteopenic bone, and between osteopenic and osteoporotic bone, and all five ratios showed significant differences between normal and osteoporotic bone. In contrast, the 0-mm offset suffered diminished contrast, and the 6-mm offset did not enhance discrimination between different groups, compared with the 3-mm offset. A leave-one-out, partial-least-squares regression model built from the 3-mm spectra predicted distal radius DXA T-score with a Pearson correlation of r = 0.85 and a root-mean-square error of cross-validation of 1 T-score units, correctly classifying 92% of specimens.
Low-dose computed tomography (LDCT) reduces patient radiation exposure but introduces substantial noise that degrades image quality and hinders diagnostic accuracy. Existing denoising approaches often require many diffusion steps, limiting real-time applicability. We propose a Regularization-Enhanced Efficient Diffusion Probabilistic Model (RE-EDPM), a rapid and high-fidelity LDCT denoising framework that integrates a residual shifting mechanism to align low-dose and full-dose distributions and performs only four reverse diffusion steps using a Swin-based U-Net backbone. A composite loss combining pixel reconstruction, perceptual similarity (LPIPS), and total variation (TV) regularization effectively suppresses spatially varying noise while preserving anatomical structures. RE-EDPM was evaluated on a public LDCT benchmark across dose levels and anatomical sites. On 10 percent dose chest and 25 percent dose abdominal scans, it achieved SSIM = 0.879 (0.068), PSNR = 31.60 (2.52) dB, VIFp = 0.366 (0.121) for chest, and SSIM = 0.971 (0.000), PSNR = 36.69 (2.54) dB, VIFp = 0.510 (0.007) for abdomen. Visual and statistical analyses, including ablation and Wilcoxon signed-rank tests (p < 0.05), confirm significant contributions from residual shifting and regularization terms. RE-EDPM processes two 512x512 slices in about 0.25 s on modern GPUs, supporting near real-time clinical use. The proposed framework achieves an optimal balance between noise suppression and anatomical fidelity, offering an efficient solution for LDCT restoration and broader medical image enhancement tasks.