Physics in medicine and biology最新文献

Objective: Cardiotoxicity is a devastating complication of thoracic radiotherapy. However, current practice ignores radiosensitivities and complex motion trajectories of individual substructures. Current imaging protocols in radiotherapy are insufficient to decouple and quantify cardiac motion, limiting substructure-specific motion considerations in treatment planning. We propose a 5D-MRI workflow for comprehensive substructure-specific motion analysis. Approach: Our 5D-MRI workflow was implemented in 10 healthy subjects (23-65 years) and two patients with lung cancer (67-69 years), with local low-rank iterative reconstruction at end-exhale/inhale and active-exhale/inhale for end-systole/diastole. For motion assessment, proximal coronary arteries, chambers, great vessels, and cardiac valves/nodes were contoured across all images and verified. Centroid/bounding box excursion was calculated for cardiac, respiratory, and hysteresis motion. Distance metrics were tested for statistical independence across substructure pairings. Three thoracic motion-perturbed radiotherapy plans were retrospectively analyzed using volunteer-derived IRVs. Main Results: 5D-MRI images were successfully acquired. Cardiac motion exceeded 1 cm for right-heart substructures and was greatest for the right coronary artery. Respiratory motion was largest for the inferior vena cava/left ventricle. Respiratory hysteresis was generally <5 mm but >5 mm for some subjects. For cardiac motion, statistically significant differences were observed between coronary arteries/chambers/great vessels and between right/left-sided substructures. Respiratory motion differed significantly between the heart base/apex for the volunteer cohort. 5DMRIs for 2 thoracic cancer patients demonstrated tumor-induced changes in motion patterns relative to the volunteer cohort. Motion-perturbed treatment plans in 3 thoracic cancer patients demonstrated an increase in D0.03cc up to 21.5 Gy across volunteer-derived cardiorespiratory IRVs. Significance: Our 5D-MRI workflow successfully decouples cardiorespiratory motion in a ~5-minute free-breathing acquisition. In volunteers, cardiac motion was >5mm for coronary arteries/chambers, while respiratory motion was >5 mm for all substructures. Statistically significant differences were observed between cardiac substructures for cardiac and respiratory motion. Interplay between tumor location, motion source, and motion magnitude affected substructure doses.

Objective: Ultrasound is commonly used to guide minimally invasive procedures; however, these are often hindered by poor needle-tip visibility. This work aims to develop a multilateration-based needle tracking system that is significantly faster than our previous one approach.

Approach: The proposed system integrates a fiber-optic hydrophone within a medical needle to receive ultrasound transmissions from a sparse 2D matrix array probe, used for 3D imaging. Chirped excitation was employed to improve the signal-to-noise ratio and enable robust time-of-arrival estimation required for multilateration-based 3D localization.

Main results: The system achieved spatial tracking accuracy of 2.49 ± 0.95 mm using only 13 active elements, representing an order-of-magnitude increase in tracking speed from 3.77 to 45.45 Hz compared to the previously used delay-and-sum-based tracking algorithm. 3D imaging and accurate needle-tip localization were demonstrated with ex vivo chicken tissue and a clinically realistic femoral nerve block phantom.

Significance: These results demonstrate the feasibility of the system that combines 3D imaging and accurate needle tracking, showing strong potential to improve the precision and safety of ultrasound-guided interventions.

Objective: The dose-weighted linear energy transfer (LETd) increases significantly at the distal edge of the proton Bragg peak, leading to distinct biological responses compared to proximal regions of the depth-dose profile. Normal tissue complications have been linked to composite LETd distributions from clinical treatment plans, but the associations between LETd and complications remain inconclusive. This study introduces a field-by-field analysis method to provide more detailed insights into these relationships.

Approach: LETd in composite plans was reformulated to account for weighted contributions from individual fields. Dose and LETd distributions for each field were calculated using the MCsquare Monte Carlo code. Field-specific dose volume histograms (DVH) and LETd volume histograms (LETdVHs) were generated for regions with elevated LETd in 101 pediatric craniopharyngioma cases treated with two-field plans (n=98) or three-field plans (n=3).

Main results: Individual fields contribute high LETd at the distal edge of the spread-out Bragg peak (SOBP) and lateral field edges. High LET particles delivered physical doses of several Gy exceeding the threshold for non-stochastic acute and late effects. Composite LETd distributions, however, show lower LET at the SOBP distal edge due to contributions from low LET particles in opposing fields. Information about high LET dose deposited by individual beams is diluted in composite plan LETd distributions.

Significance: Evaluating LETd distributions based solely on composite plans can obscure the contribution of high-LET regions from individual fields in to biological response of tissues. A field-by-field assessment may provide a more accurate understanding of LETd's role in normal tissue effects and may improve the prediction of complications in proton therapy.

Objective: To evaluate the uncertainty of physical features of low-energy electron transport in liquid water due to the use of different Monte Carlo track-structure (MCTS) codes. Approach. Five MCTS codes developed specifically for liquid water, namely, Geant4-DNA, PHITS-TS, RITRACKS, NASIC, and PARTRAC are compared and used to calculate the electronic stopping power, pathlength and absorption range, dose-point-kernel, and the frequency-mean (y ̅_F) and dose-mean (y ̅_D) lineal energy for primary electron energies from 20 eV to 100 keV. The uncertainty of each calculated quantity is evaluated by the relative standard deviation (RSD) and the maximum relative difference (MRD) among the codes. The medium-to-high-energy (1‒100 keV) performance of the codes is benchmarked against the stopping power and range data for liquid water reported in ICRU Report 90. Main Results. For energies above ~1 keV the RSD is moderate and mostly between 5-15%, but increases rapidly at lower energies, reaching 20-100% at sub-100 eV energies. It is noteworthy that the MRD may well exceed 100% below 100 eV, while remaining sizeable (>20%) even at relatively high energies (10-100 keV). Fairly good agreement between the MCTS codes and the ICRU data for the stopping power (1‒100 keV) and range (10‒100 keV) in liquid water is found with average deviations between 1‒16%, depending on the code. Significance: The present work reveals significant differences for low-energy electron transport among liquid water MCTS codes, especially below 100 eV. These differences potentially compromise the accuracy of nanoscale simulations where such electrons play a key role. The observed dispersion of results is a consequence of the limitations of the theoretical models used to calculate electron interaction cross sections and the lack of relevant experimental data for their validation and benchmarking. This highlights the need for further development of the physics models used in MCTS codes to reduce the uncertainties associated with low-energy electron transport calculations in liquid water.

Objective. Magnetic resonance imaging is essential in clinical practice due to its non-invasive nature and superior soft-tissue contrast. However, long acquisition times remain a major limitation, leading to motion artifacts and patient discomfort. Most deep learning approaches rely on fully sampled datasets, which are often difficult to obtain. This study aims to develop a self-supervised framework for MRI reconstruction that eliminates dependence on fully sampled training data.Approach. We propose consistency self-supervised learning with ISRVN (CSSL-ISRVN), a novel consistency self-supervised reconstruction framework. At its core lies SRVN, which combines an improved variational network (IVN) with a sensitivity refinement module (SRM). The IVN integrates a feature refinement and denoising module (FRDM), composed of residual blocks (RB) and a Gaussian context transformer (GCT), to jointly extract local and global features. Meanwhile, SRM iteratively refines a task-driven implicit sensitivity modulation variable using the previously reconstructed fullk-space in a reconstruction-sensitivity closed loop, adaptively modulating the multi-coil forward model and data consistency to reduce error accumulation induced by fixed auto-calibration signals-based sensitivity estimates under undersampling. Building on ISTANet and SRVN, we develop ISRVN, a heterogeneous alternating cascade of ISTANet and SRVN: ISTANet first suppresses undersampling artifacts in the multi-coil complex domain to provide cleaner intermediates, enabling SRVN to perform encoding-modulated, physics-consistent refinement for improved reconstruction quality and stability. To eliminate dependence on fully sampled data, we introduce a consistency self-supervised scheme that re-undersamples the originalk-space to train two pairs of consistency networks using calibration and consistency losses.Results. Experiments on three public datasets show that CSSL-ISRVN consistently surpasses existing self-supervised and scan-specific methods, particularly under 1D undersampling masks. It achieves performance competitive with state-of-the-art supervised models.Significance. CSSL-ISRVN offers an effective solution for accelerated MRI reconstruction without fully sampled labels. Its integration of sensitivity refinement, hybrid modeling, and consistency self-supervision enables robust, high-fidelity reconstructions, underscoring its potential for real-world clinical deployment.

Objective: While FLASH radiotherapy (FLASH-RT) is recognized for normal tissue sparing, its effect in mitigating the toxicity of late-responding organs remains uncertain, limiting clinical adoption. With its clinical importance and steep dose-response, spinal cord is an ideal model for evaluating the FLASH effect on late toxicity. This work introduces a robust image-guided research platform for high-precision irradiation at both conventional (CONV) and ultra-high dose rates (UHDR) to enable FLASH late toxicity studies using a rat spinal cord model.

Approach: A modified LINAC was employed to irradiate the C1-T2 rat spinal cord with 18 MeV UHDR and CONV beams. A custom rat immobilization device, a portable X-ray imaging system, and an ion-chamber-based UHDR output monitoring system were integrated to ensure accurate C1-T2 localization and precise dose delivery. A Monte Carlo (MC) dose engine was developed to provide accurate dosimetry and support the interpretation of in vivo results. Scintillator measurements at UHDR were performed within the spinal cord to verify MC results and the precision of our platform.

Results: We observed submillimeter deviation in C1-T2 localization between 2D X-ray and 3D CBCT imaging, as well as between pre- and post-irradiation 2D X-ray assessments. Ion chamber readings showed linear correlation with UHDR output (R²=1).MC calculations indicated uniform irradiation (<5% non-uniformity) along the central ~13 mm cord, avoiding dose-volume effect. Our CONV beam exhibited dose distribution close to that of the UHDR beam, with difference <3%, isolating dose rate as the only variable. Scintillator measured dose agreed with MC within 4%, with a 100% gamma passing rate (2%/2 mm), confirming both MC accuracy and the platform's high-precision delivery.

Significance: We developed the first comprehensive, image-guided preclinical platform for accurate UHDR and CONV irradiation to investigate FLASH-mitigated spinal cord toxicity in rats. This work thus establishes a robust foundation for systematic evaluation of the FLASH effect in late-responding organs and for assessing relevant clinical applicability of FLASH-RT.

Objective: Besides preferential tumour targeting, particle therapy has an increased relative biological effectiveness compared to X-rays, but uncertainties in this effectiveness prevent full exploitation of its clinical benefits. Mechanistic radiation response models can predict the effects of different radiation qualities but the model detail required to capture experimental data remains unclear. In this work, key DNA damage and chromosomal aberration endpoints were simulated and compared to experimental literature. Approach: The TOPAS-nBio and Medras models were used to simulate DNA double strand break (DSB) damage for different radiation exposures. The repair of this damage was simulated, modelling misrepair and chromosome aberration formation in an updated Medras DNA repair model. The characteristic rejoining range of DSB ends in the repair model was re-optimised against experimental photon dose data and tested against ion exposures. Main results: For DSBs, predictions were higher than experimental observations, attributed to the assay resolution limits. Predicted photon-induced chromosome aberrations were higher than observed, with a Root Mean Square Deviation (RMSD) of 1.28 and 1.41 for the Medras and TOPAS-nBio models respectively against the experimental data. The RMSD against the experimental data was lowered by over 70% for both models by re-optimisation of the analytically predicted characteristic DSB end rejoining range to a value of 0.0335 +- 0.0034 (80% of the previous value). This optimisation also performed well when predicting the dependence on ion LET, reducing the proton RMSD by 40% to 0.43 and 0.69 for the Medras and TOPAS-nBio models respectively. Significance: The Medras biological response model was updated and predicted good agreement in aberration yields with the experimental data for both the detailed TOPAS-nBio and less detailed Medras damage models. This highlights how simple mechanistic models, with the guidance of robust experimental data, can be used to explore the effects of radiation quality and guide future experiments.

Objective.Microcalcification (µCalc) detection plays an important role in breast cancer screening. Electronic noise in energy-integrating detectors (EIDs) is the major challenge for this task in current breast cone-beam CT (bCBCT) due to the tight dose constraint for breast imaging. bCBCT with a photon counting detector (PCD) can potentially offer a higher spatial resolution and lower noise. This study performed a direct comparison of bCBCTs with the two detector types via GPU-based Monte Carlo (MC) simulation.Approach.We employed Virtual Clinical Trial for Regulatory Evaluation toolkit to generate a realistic breast phantom with a 0.25mm3voxel size, 80% fat fraction and 14 cm diameter. We considered a bCBCT system with a 60 kV x-ray source filtered with 0.3 mm Cu and detector response functions for PCD and EID. A total of 360 projections were simulated with a total number of3.15×1012photons, corresponding to ∼4 mGy mean glandular dose, comparable to a two-view mammography. We modified our GPU-based MC simulation code to incorporate analytical descriptions ofµCalcs of spherical shapes with diameters ranging from 0.1 to 0.4 mm, in 0.1 mm increments, into the voxelized phantom. A nichrome wire with 0.07 mm diameter was simulated to calculate the modulation transfer functions (MTFs). bCBCT images were reconstructed with the Feldkamp-Davis-Kress algorithm, and image quality andµCalc detection performance were evaluated.Main results.EID-bCBCT had more profound image noise due to electronic noise. The image intensity standard deviations estimated within a region of interest were 0.055 cm^-1for EID-bCBCT and 0.038 cm^-1for PCD-bCBCT, respectively.µCalcs and breast anatomy such as ligaments were more visible in the PCD-bCBCT images. The 10% MTF cutoffs were 5.5 and 9.5 lp mm^-1for EID-bCBCT and PCD-bCBCT, respectively. Contrast-to-noise ratio ranged in 1.20-9.13 for EID-bCBCT and 3.07-14.74 for PCD-bCBCT, depending onµCalc sizes.Significance.We compared EID- and PCD-based bCBCT forµCalc detection using GPU-based MC simulations in a clinically realistic setting. Our results demonstrate a potential advantage of PCD-bCBCT for this detection task.

Objective: HDR brachytherapy is a widely adopted modality for cancer treatment. However, it is not free from error and uncertainty. In-vivo dosimetry (IVD) is the only technique that confirms correct dose delivery. This study details and validates a calibration method for Plastic Scintillation Detector (PSD), bypassing dose gradient and positioning issues in brachytherapy calibration.

Approach: The PRB-0057 PSD (Medscint, Québec, Canada), a 1x1-mm scintillating fiber coupled to a 20-m Eska GH-4001 clear optical fiber (Mitsubishi Rayon, Japan) of the same diameter, was calibrated and connected to the Hyperscint-RP200 research platform for optical signal collection. Hyperspectral calibration was performed at a LINAC with a 6-MV beam, enabling the independent stem effect removal. For validation, brachytherapy measurements with a Sk=29447-U Iridium-192 Flexisource (Elekta Brachy, The Netherlands) were performed in a motorized IBA-Blue-Phantom2 water tank. Dose rates were measured at 10Hz along the source's vertical z-axis at a fixed transverse distance of 1.2±0.05-cm in 0.2-cm steps. Calibration accuracy was evaluated using relative differences (RD) between measured and TG-43U1 dose rates, converted to inverse-square equivalent positional errors. A detailed uncertainty budget was established to the measurement setup.

Main results: Comparison agreed with RDs to around 2.5% at 1.2-cm, corresponding to positional uncertainties of <0.15-mm. At greater distances, up to 8-cm, RDs increase to about 5%, corresponding to positional uncertainties up to 3-mm, mainly due to reduced light-yield. Uncertainties found to depend on the source-detector distance, ranging from 3.92% to 6.42% (k=1) over the range of explored distances.

Significance: Results confirm the effectiveness of a 6-MV external beam PSD calibration to be used in time-resolved IVD. Uncertainties close to the source are consistent with the Afterloader/IBA motorized unit reproducibility and are mainly dominated by reduced detector sensitivity at larger distances. Our study further underlined the intrinsic limitation of IVD in the face of known uncertainties.

Objective: AAPM Task Group Report 203 (TG203) recommends implantable cardiac pacemaker (ICP) dependent patients receive elevated precautions and that maximum dose rates to ICPs should be less than 0.2 Gy/min. Unfortunately, there is little quantitative data published about how ICPs are impacted by radiation dose rates near 0.2 Gy/min. The objective of this paper is to report on modern ICP behavior in response to dose rates near this suggested limit.

Approach: Five single chamber (Azure XT SR) and five dual chamber (Azure XT DR) ICPs were submerged in 0.45% saline solution and placed 1 cm outside the field edge of a 10x10 cm 2 beam. Photon beams of energies 6 MV, 6 FFF, 10 MV, and 10 FFF were tested, with dose rates ranging from 0.15 to 0.92 Gy/min on Varian True Beam and Ethos LINACs. Real-time electrogram data were collected and analyzed for any malfunctions while the beam was on and off. Battery life of each ICP was also checked before irradiation and 6 months post-irradiation.

Main results: No ICP malfunctions or artifacts were observed, even as dose rate increased. Battery life showed normally expected depletion 6 months post irradiation.

Significance: This work studies ICP functionality in clinically relevant radiation therapy conditions and measures the performance of the devices in the context of an ICP dependent patient.