Imaging Dose Research Articles

Feasibility of Using Pseudo-CT for Dosimetry, Radiomics, and Efficacy Assessment in IMRT/VMAT of Brain Tumors: A Multi-Omics Analysis

Pseudo-CT generated by convolutional neural networks (CNN) and planning MRI has facilitated the promotion of MRI-Only. The technology not only reduces the time and money spent on CT scans, but also eliminates the cumbersome CT-MR registration. The feasibility in Stereotactic Brain Radiotherapy has been analyzed in previous studies by our team. However, when the prescribed requirements are not met, IMRT/VMAT are still selected. The study aims to evaluate the feasibility of pseudo-CT in IMRT/VMAT for brain cancer via the following 5 aspects: (1) image difference, (2) dose accuracy, (3) radiomics feature, (4) efficacy assessment, and (5) correlation analysis. Brain tumor patients who had received radiotherapy at our institution and had planning MRI and CT were included in the study. Redesign of IMRT and VMAT radiotherapy plans according to 3 × 15Gy for each patient. Hounsfield unit (HU) values for PTV and OARs were used to assess image differences. And dose accuracy analysis contained a 2D dose volume histogram (DVH) metrics (Dmax, Dmean, D2%, D50%, D98%, HI, CI) and 3D gamma metrics (criteria: 1-3%/2mm, 1%/1mm, 10% threshold). Then 107 original image features of PTV and OARs were extracted for radiometry analysis. And tumor control probability (TCP) of PTV (Poisson model) and normal tissue complication probability (NTCP) of OARs (Lyman-Kutcher-Burman model) were used for the variance analysis of efficacy assessment. Wilcox-test was used for significance of differences test (0.05), and spearman correlation analysis was used to explore the key features of the dose bias. A total of 42 patients were included, with 42 planning CTs and pseudo-CTs (mDixon-T1), and 38 pseudo-CTs (mDixon-T1-CE). The median volume of PTV was 4.1 cc (range 0.5-27.3), with no significant differences in HU, DVH, 3D gamma, and NTCP/TCP metrics. The median local gamma passing rates (1%/1mm) between planning CTs and pseudo-CTs (mDixon-T1) were 93.1% (range 65.5%-99.7%, IMRT) and 93.3% (range 63.9%-99.6%, VMAT). And more than 85% original radiomics features have significant difference. Further, the feature HU-Min was found to be more correlated with dose metrics in the correlation analysis. We speculate that it may be caused by the smoothing of the low frequency signal before outputting image. And since Shape_MeshVolume, Shape_VoxelVolume and PTV volume difference are highly correlated with dose deviation, it indicates that dose deviation affected by CT-MR registration. This study has the potential to provide guidance for the clinical application of pseudo-CT in the MRI-Only workflow with IMRT/VMAT for brain tumors. These quantitative results strongly indicate pseudo-CT can be used as a substitute for the initial CT in IMRT/VMAT for small brain lesions (size <5 cm, numbers <5), but not for radiomics analysis. Additionally, the impact of inter-image differences on dose accuracy is less significant compared to the deviation caused by image registration.

Accuracy of Electron Density and Planning Dosimetry in a Novel High-Quality CBCT Imaging System

A high-quality Cone-Beam Computed Tomography (CBCT) imaging system has been FDA approved for imaging guidance and dose calculation in radiotherapy. This study aims to evaluate the accuracy of the relative electron density in CBCT images acquired in this CBCT imaging system in a phantom study and its dosimetric impact on treatment planning in a patient study. Astoichiometric CT calibration was performed with a CIRS phantom (SunNuclear, Model 062M) to generate the HU-electron density curve for two tube voltages, 125kVp and 140 kVp, respectively. The phantom has a longitudinal length of 26.5 cm and is equipped with interchangeable inserts of various compositions, supplied by the vendor. Measurements were taken with solid water plates added to both ends of the phantom to allow adequate scattering and repeated for various clinical protocols with different combinations of tube voltages and exposures. The accuracy of the relative electron density of the CBCT imaging system was verified by comparing the calculated electron density from the Hounsfield Units (HU) measurements obtained from a Gammex phantom to the relative electron densities provided in vendor's specifications. To benchmark the relative electron density of the CBCT imaging system against a standard helical CT simulator, ten clinical plans that were created on CT simulation images were copied and recalculated on the CBCT images acquired immediately after the CT simulation, the latter of which was a standard procedure in current radiotherapy care for all patients who had given their consent to participate in the IRB-approved imaging study. The dose grids used in these calculations were 2.5mm x 2.5mm x 3mm. The Gamma passing rate was calculated using a standard 3mm/3% criterion with a 10% threshold. Ourresults showed the difference between the averaged CBCT calibration curves acquired at tube voltages of 125 kVP and 140 kVp was less than 2%. The mean discrepancy of the relative electron densities from vendor's specification was 0.0045 with a range between -0.02 and 0.04. Relative electron densities in all inserts were within 2% from the vendor's specifications except the cortical bone insert. Gamma passing rate was between 96.02% and 98.49% with mean value of 97.4% and a standard deviation of 0.95%. We consider this reflects the fact that the CT simulation and CBCT imaging were performed in separated rooms, which resulted in slight anatomical deformation that could negatively impact the Gamma passing rate. The CBCT imaging system provides sufficient accuracy of electron density for dose calculation, and the dose distribution calculated on the CBCT images is clinically equivalent to those calculated on helical CT images. The enhanced imaging quality of CBCT could further extend the role of imaging guidance to planning for adaptive radiotherapy, potentially reducing the need for re-simulation and interruptions in the radiotherapy course.

Spot Scanning Proton Therapy for Pregnant Patients with Brain and Head and Neck Tumors

When radiotherapy is medically necessary, x-ray based treatments (XRT) have traditionally been used to treat pregnant patients. Treatment planning and delivery techniques may be modified to minimize dose to the fetus but results in less optimal plans due to avoiding posterior beams or arcs. Monte Carlo calculations and published case studies suggest spot scanning proton therapy (PRT) reduces the equivalent dose to the fetus by a factor of 10 compared to XRT and does not require modified treatment planning techniques. However, due to concern for dose uncertainties and neutron scatter with PRT, few centers have adopted PRT over XRT for pregnant patients. The purpose of this work is to perform a retrospective study on the pregnant patients previously treated at our institution with XRT to measure the equivalent dose that would be delivered to the fetus with spot scanning PRT compared to XRT. PRT plans were made for seven pregnant patients, 4 brain tumors and 3 head and neck tumors, who had received XRT. Due to the finite range of protons, the fetal exposure is dominated by neutrons and not the primary beam. Thus, no beam arrangement modifications were required to minimize fetal dose for PRT plans. Fetal dose measurements were performed with the patient plans using a Rando phantom and Wendi-2 (Thermo Scientific) meter placed at the phantom's abdomen. The Wendi-2 measures ambient dose equivalent, which accounts for the biological effect of the neutron energies. Measurements were made at various distances from isocenter to the center of the detector. The total dose equivalent from PRT at several out of field distances was compared to that from XRT. Patient specific measurements were used to determine the total fetal dose from each modality, accounting for the changing position of the fetus each week of the mother's treatment. The imaging dose for standard of practice imaging, including verification CT scans and daily alignment imaging, was also evaluated using a similar setup with a Fluke 451 dose meter. The average measured fetal equivalent dose for the brain plans was 0.4 mSv for PRT and 7 mSv for XRT. For the head and neck plans, it was 6 mSv for PRT and 90 mSv for XRT. The dose from PRT was consistently at least a factor of 10 less than the XRT plans. In addition, the PRT plans were preferred by the physicians when considering tumor coverage and other normal tissue sparing. Daily imaging added between 0.05 and 1.5 mSv to the total dose in the PRT treatments. This retrospective study showed that when treating brain or head and neck tumors in pregnant patients, the equivalent dose a fetus would receive with PRT is approximately a factor of 10 less than XRT without making any compromises in treatment planning. These results support changing the standard of practice to utilizing spot scanning PRT as the preferred method for treating pregnant patients with brain or head and neck tumors when available instead of XRT. We have brought this process to clinic at our center.

A constructive non-local means algorithm for low-dose computed tomography denoising with morphological residual processing.

Low-dose computed tomography (LDCT) has attracted significant attention in the domain of medical imaging due to the inherent risks of normal-dose computed tomography (NDCT) based X-ray radiations to patients. However, reducing radiation dose in CT imaging produces noise and artifacts that degrade image quality and subsequently hinders medical disease diagnostic performance. In order to address these problems, this research article presents a competent low-dose computed tomography image denoising algorithm based on a constructive non-local means algorithm with morphological residual processing to achieve the task of removing noise from the LDCT images. We propose an innovative constructive non-local image filtering algorithm by means of applications in low-dose computed tomography technology. The nonlocal mean filter that was recently proposed was modified to construct our denoising algorithm. It constructs the discrete property of neighboring filtering to enable rapid vectorized and parallel implantation in contemporary shared memory computer platforms while simultaneously decreases computing complexity. Subsequently, the proposed method performs faster computation compared to a non-vectorized and serial implementation in terms of speed and scales linearly with image dimension. In addition, the morphological residual processing is employed for the purpose of edge-preserving image processing. It combines linear lowpass filtering with a nonlinear technique that enables the extraction of meaningful regions where edges could be preserved while removing residual artifacts from the images. Experimental results demonstrate that the proposed algorithm preserves more textural and structural features while reducing noise, enhances edges and significantly improves image quality more effectively. The proposed research article obtains better results both qualitatively and quantitively when compared to other comparative algorithms on publicly accessible datasets.

Complete patient exposure during paediatric brain cancer treatment for photon and proton therapy techniques including imaging procedures.

In radiotherapy, especially when treating children, minimising exposure of healthy tissue can prevent the development of adverse outcomes, including second cancers. In this study we propose a validated Monte Carlo framework to evaluate the complete patient exposure during paediatric brain cancer treatment. Organ doses were calculated for treatment of a diffuse midline glioma (50.4 Gy with 1.8 Gy per fraction) on a 5-year-old anthropomorphic phantom with 3D-conformal radiotherapy, intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and intensity modulated pencil beam scanning (PBS) proton therapy. Doses from computed tomography (CT) for planning and on-board imaging for positioning (kV-cone beam CT and X-ray imaging) accounted for the estimate of the exposure of the patient including imaging therapeutic dose. For dose calculations we used validated Monte Carlo-based tools (PRIMO, TOPAS, PENELOPE), while lifetime attributable risk (LAR) was estimated from dose-response relationships for cancer induction, proposed by Schneider etal. Out-of-field organ dose equivalent data of proton therapy are lower, with doses between 0.6 mSv (testes) and 120 mSv (thyroid), when compared to photon therapy revealing the highest out-of-field doses for IMRT ranging between 43 mSv (testes) and 575 mSv (thyroid). Dose delivered by CT ranged between 0.01 mSv (testes) and 72 mSv (scapula) while a single imaging positioning ranged between 2 μSv (testes) and 1.3 mSv (thyroid) for CBCT and 0.03 μSv (testes) and 48 μSv (scapula) for X-ray. Adding imaging dose from CT and daily CBCT to the therapeutic demonstrated an important contribution of imaging to the overall radiation burden in the course of treatment, which is subsequently used to predict the LAR, for selected organs. The complete patient exposure during paediatric brain cancer treatment was estimated by combining the results from different Monte Carlo-based dosimetry tools, showing that proton therapy allows significant reduction of the out-of-field doses and secondary cancer risk in selected organs.

A comparative analysis of head computed tomography scans protocols and thyroid dosimetry

Computed Tomography (CT) is currently one of the most widely used imaging modalities for disease identification, benefiting numerous patients with its advanced technology. However, there is a concern regarding its inappropriate use, which can lead to higher radiation doses in patients and consequently increase the potential risks of developing stochastic effects. Therefore, it is crucial to explore methodologies for optimizing patient doses, particularly in organs with higher radiosensitivity. Within this context, the aim of the proposed study is to compare absorbed dose and noise among different head CT scans using a polymethylmethacrylate (PMMA) phantom, proposing a better relationship between image quality and dose reduction for protocol and thyroid in head CT scans. The tests were conducted using head acquisition protocols on two CT scanners: a GE LightSpeed VCT with 64 channels and a Toshiba CT with 4 channels. The PMMA head-neck phantom consisted of two cylinders, one with a diameter of 16 cm and another with a diameter of 11 cm was used in this work. Radiochromic films and an ionization chamber were also utilized. The study evaluated discrepancies in CT scans, including Noise Power Spectrum (NPS), dose profiles, and punctual doses in thyroid. Protocols P1A and P2B had the lowest and highest CTDIvol values, respectively. Radiochromic films facilitated precise dose analysis, identifying position 12 with the highest dose. NPS analysis revealed variations in noise distribution between the protocols.

283 The Effect of Real-Time Imaging Dose on OAR Constraints in Lung SBRT

283 The Effect of Real-Time Imaging Dose on OAR Constraints in Lung SBRT

Preclinical evaluation of a dual-receptor targeted tracer [68Ga]Ga-HX01 in 10 different subcutaneous and orthotopic tumor models.

The integrin αvβ3 and aminopeptidase N (APN/CD13) play vital roles in the tumor angiogenesis process. They are highly expressed in a variety of tumor cells and proliferating endothelial cells during angiogenesis, which have been considered as highly promising targets for tumor imaging. Arginine-glycine-aspartic (RGD) and asparagine-glycine-arginine (NGR) are two peptides specifically binding to the integrin αvβ3 and CD13, respectively. In this study, we optimized our previously developed probe and preclinically evaluated the new integrin αvβ3 and CD13 dual-targeted probe, NOTA-RGD-NGR (denoted as HX01) radiolabeled with 68Ga, in 10 different subcutaneous and orthotopic tumor models. The specific activity and radiochemical purity of [68Ga]Ga-HX01 were identified. The dual-receptor targeting ability was confirmed by a series of blocking studies and partly muted tracers using BxPC-3 xenograft model. The dynamic imaging study and dose escalation study were explored to determine the optimal imaging time point and dosage in the BxPC-3 xenograft model. Next, we established a variety of subcutaneous and orthotopic tumor models including pancreas (BxPC-3), breast (MCF-7), gallbladder (NOZ), lung (HCC827), ovary (SK-OV-3), colorectal (HCT-8), liver (HuH-7), stomach (NUGC-4), and glioma (U87) cancers. All models underwent [68Ga]Ga-HX01 PET/CT imaging about 2weeks post-inoculation, with a subset of them undergoing [18F]FDG PET/CT scan performed concurrently, and their results were compared. In addition, ex vivo biodistribution studies were also performed for verifying the semi-quantitative results of the non-invasive PET images. [68Ga]Ga-HX01 significantly outperformed single target probes in the BxPC-3 xenograft model. All blocking and single target groups exhibited significantly descending tumor uptake. The high tumor uptakes were found in BxPC-3, MCF-7, and NOZ subcutaneous tumors (%ID/g > 1.1), while middle uptakes were observed in HCC827, SK-OV-3, HCT-8, and HuH-7 subcutaneous tumor (%ID/g 0.7-1.0). Due to the low background, the tumor-to-muscle and tumor-to-blood ratios of [68Ga]Ga-HX01 were higher than that of [18F]FDG. [68Ga]Ga-HX01, as a dual target imaging agent, exhibited superior in vivo performance in different subcutaneous and orthotopic mice models of human tumors over [18F]FDG and its respectively mono-receptor targeted agents, which warrants the future clinical translation for tumor imaging.

Optimization of pediatric brain CT protocols

PurposeDue to the higher radiosensitivity of the tissues and the larger life expectancy in children than in adults, the present study presented the process of optimizing pediatric brain CT protocols, for the age groups 0 to 2 years, 3 to 5 years, and 6 to 12 years, evaluating the parameters of image acquisition and dose reduction, without loss of quality in image diagnostics. Methods: The CTDIvol index and DLP were verified in samples of routinely used protocols for patients in the age groups previously specified, as well as the image acquisition parameters. Based on these data, experimental protocols were developed and the contrast-to-noise ratios of the images produced were analyzed. The figure of merit (FOM) was used as a quality metric for quality analysis in comparison with CTDIvol and DLP levels. Results: The results showed a reduction in the CTDIvol index in the three studied protocols: 10.5% in the 0 to 2 years protocol, 33% in the 3 to 6 years protocol, and 16% in the 6 to 12 years protocol. DLP was also reduced by 14%, 41% and 25%, respectively, for the three age groups, in relation to previously used protocols. With regard to FOM, there were increases in quality of 6%, 19%, and 43%, respectively, for the three age groups. Conclusion: Considering the alteration of the image acquisition parameters, it was possible to achieve a dose reduction, without loss of diagnostic quality, according to the FOM metric.

Evaluation of the feasibility of a multisource CBCT for maxillofacial imaging

Objective. The aim of this study was to investigate the feasibility of improving the image quality and accuracy of cone beam computed tomography (CBCT) by replacing the conventional wide cone angle x-ray tube with a distributed x-ray source array positioned in the axial direction. Approach. The multisource CBCT (ms-CBCT) design was experimentally simulated using a benchtop scanner with a carbon nanotube x-ray tube and a flat-panel detector. The source was collimated and translated in the axial direction to simulate a source array with a reduced cone angle for each beam. An adjacent scatter ratio subtraction (ASRS) method was implemented for residual scatter reduction. Several phantoms were imaged using the ms-CBCT and conventional CBCT configurations under otherwise similar conditions. The Requirements of the ms-CBCT design on the x-ray source and detector were evaluated. Main results. Compared to the conventional CBCT, the ms-CBCT design with 8 sources and ASRS significantly improved the image quality and accuracy, including: (1) reducing the cupping artifact from 15% to 3.5%; (2) reducing the spatial nonuniformity of the CT Hounsfield unit values from 38.0 to 9.2; (3) improving the contrast-to-noise ratio of the low contrast objects (acrylic and low density polyethylene inserts) against the water-equivalent background by ∼20% and (4) reducing the root-mean-square error of the HU values by 70%, from 420.1 to 124.4. The imaging dose and scanning time used by the current clinical CBCT for maxillofacial imaging can be achieved by current source and detector technologies. Significance. The ms-CBCT design significantly reduces the scatter and improves the image quality and accuracy compared to the conventional CBCT.

Evaluation of the Influence on the Use of Additional Filtration in Pelvic Radiographic Examinations Using a Phantom Object

Aims: This study aimed to determine the effect of additional filtration on the image quality and dose reduction in pelvic radiographic examinations.&#x0D; Study Design: Mention the design of the study here.&#x0D; Place and Duration of Study: The research was conducted at a municipal emergency service radiology department in Rio Grande do Sul, Brazil.&#x0D; Methodology: Using a simulator object to replicate clinical examination conditions. The radiographic equipment was fitted with aluminum, copper, and copper-aluminum composition filters to identify the optimal filtration for reducing radiation doses and maintaining image quality.&#x0D; Results: Results showed that filtration effectively reduced dose and average absorbed dose in internal organs, with the greatest reduction observed with the copper filter. However, excessive filtration resulted in a decrease in image quality, particularly with the copper filter. The Figure of Merit (FOM) demonstrated that keeping the electrical factors of the X-ray tube consistent (70 kVp and 32 mAs) and using an additional 2.5 mmAl filter could optimize pelvic radiographic examinations, based on the diagnostic IQ criteria established by the service.&#x0D; Conclusion: In conclusion, the FOM revealed that using additional filtration of 2.5 mmAl and maintaining the X-ray tube's electrical factors at 70 kVp and 32 mAs could reduce the KERMA in air by 49.8% in the patient, 41.5% in the testes, 35.5% in the bladder, 30.4% in the ovaries, 29.7% in the bone marrow, and 35.3% in the total effective dose of the examination, while maintaining equivalent image quality.

Reduction of scan duration and radiation dose in cerebral CT perfusion imaging of acute stroke using a recurrent neural network

Objective. Cerebral CT perfusion (CTP) imaging is most commonly used to diagnose acute ischaemic stroke and support treatment decisions. Shortening CTP scan duration is desirable to reduce the accumulated radiation dose and the risk of patient head movement. In this study, we present a novel application of a stochastic adversarial video prediction approach to reduce CTP imaging acquisition time. Approach. A variational autoencoder and generative adversarial network (VAE-GAN) were implemented in a recurrent framework in three scenarios: to predict the last 8 (24 s), 13 (31.5 s) and 18 (39 s) image frames of the CTP acquisition from the first 25 (36 s), 20 (28.5 s) and 15 (21 s) acquired frames, respectively. The model was trained using 65 stroke cases and tested on 10 unseen cases. Predicted frames were assessed against ground-truth in terms of image quality and haemodynamic maps, bolus shape characteristics and volumetric analysis of lesions. Main results. In all three prediction scenarios, the mean percentage error between the area, full-width-at-half-maximum and maximum enhancement of the predicted and ground-truth bolus curve was less than 4 ± 4%. The best peak signal-to-noise ratio and structural similarity of predicted haemodynamic maps was obtained for cerebral blood volume followed (in order) by cerebral blood flow, mean transit time and time to peak. For the 3 prediction scenarios, average volumetric error of the lesion was overestimated by 7%–15%, 11%–28% and 7%–22% for the infarct, penumbra and hypo-perfused regions, respectively, and the corresponding spatial agreement for these regions was 67%–76%, 76%–86% and 83%–92%. Significance. This study suggests that a recurrent VAE-GAN could potentially be used to predict a portion of CTP frames from truncated acquisitions, preserving the majority of clinical content in the images, and potentially reducing the scan duration and radiation dose simultaneously by 65% and 54.5%, respectively.

Half-Dose versus Single-Dose Gadobutrol for Extracellular Volume Measurements in Cardiac Magnetic Resonance.

Cardiac magnetic resonance (CMR) imaging with gadolinium-based contrast agents offers unique non-invasive insights into cardiac tissue composition. Myocardial extracellular volume (ECV) has evolved as an objective and robust parameter with broad diagnostic and prognostic implications. For the gadolinium compound gadobutrol, the recommended dose for cardiac imaging, including ECV measurements, is 0.1 mmol/kg (single dose). This dose was optimized for late enhancement imaging, a measure of focal fibrosis. Whether a lower dose is sufficient for ECV measurements is unknown. We aim to evaluate the accuracy of ECV measurements using a half dose of 0.05 mmol/kg gadobutrol compared to the standard single dose of 0.1 mmol/kg. From a contemporary trial (NCT04747366, registered 10 February 2021), a total of 25 examinations with available T1 mapping before and after 0.05 and 0.1 mmol/kg gadobutrol were analyzed. ECV values were calculated automatically from pre- and post-contrast T1 relaxation times. T1 and ECV Measurements were performed in the midventricular septum. ECV values after 0.05 and 0.1 mmol/kg gadobutrol were correlated (R2 = 0.920, p < 0.001). ECV values after 0.05 mmol/kg had a bias of +0.9% (95%-CI [0.4; 1.4], p = 0.002) compared to 0.1 mmol/kg gadobutrol, with limits of agreement from -1.5 to 3.3%. CMR with a half dose of 0.05 mmol/kg gadobutrol overestimated ECV by 0.9% compared with a full dose of 0.1 mmol/kg, necessitating adjustment of normal values when using half-dose ECV imaging.

Radiation dose considerations in digital radiography with an anti-scatter grid: A study using adult and pediatric phantoms.

When using an anti-scatter grid, a decrease in receptor dose caused by its X-ray absorption seems to lead to the misperception that radiation dose needs to be increased even in digital radiography (DR). To demonstrate that there is no need to increase radiation dose in DR with a grid, based on a visual evaluation using an adult and a pediatric abdomen phantom (PAD and PPD , respectively). Phantom images with and without a grid were obtained with exposure parameters determined based on a preliminarily measured signal-to-noise ratio improvement factor (SIF), an index for potential dose reduction when using a grid. In visual evaluation, four radiologists compared phantom images with a grid applied at different dose reduction rates (0% [no reduction], 18%, 36%, and 59% for PAD and 0% and 11% for PPD ) against an image without a grid at the baseline dose (as the reference). They graded the overall image quality of the former relative to that of the latter (reference) on a 3-point scale (3=better, 2=almost equal, 1=worse). The mean scores for dose reduction rates of 0%, 18%, 36%, and 59% were 3.00, 3.00, 2.75, and 1.00, respectively, for PAD ; those for 0% and 11% were 2.13 and 1.63, respectively, for PPD . These results support the validity of our view that no dose increase is necessary when using an anti-scatter grid. Actually, there is even a potential for improvement in image quality with dose reduction rates of ≤36% for PAD . It is worth reconsidering the necessity of increasing radiation dose in the DR imaging of the adult and pediatric abdomens with an anti-scatter grid.

A deep-learning assisted bioluminescence tomography method to enable radiation targeting in rat glioblastoma

Objective. A novel solution is required for accurate 3D bioluminescence tomography (BLT) based glioblastoma (GBM) targeting. The provided solution should be computationally efficient to support real-time treatment planning, thus reducing the x-ray imaging dose imposed by high-resolution micro cone-beam CT. Approach. A novel deep-learning approach is developed to enable BLT-based tumor targeting and treatment planning for orthotopic rat GBM models. The proposed framework is trained and validated on a set of realistic Monte Carlo simulations. Finally, the trained deep learning model is tested on a limited set of BLI measurements of real rat GBM models. Significance. Bioluminescence imaging (BLI) is a 2D non-invasive optical imaging modality geared toward preclinical cancer research. It can be used to monitor tumor growth in small animal tumor models effectively and without radiation burden. However, the current state-of-the-art does not allow accurate radiation treatment planning using BLI, hence limiting BLI’s value in preclinical radiobiology research. Results. The proposed solution can achieve sub-millimeter targeting accuracy on the simulated dataset, with a median dice similarity coefficient (DSC) of 61%. The provided BLT-based planning volume achieves a median encapsulation of more than 97% of the tumor while keeping the median geometrical brain coverage below 4.2%. For the real BLI measurements, the proposed solution provided median geometrical tumor coverage of 95% and a median DSC of 42%. Dose planning using a dedicated small animal treatment planning system indicated good BLT-based treatment planning accuracy compared to ground-truth CT-based planning, where dose-volume metrics for the tumor fall within the limit of agreement for more than 95% of cases. Conclusion. The combination of flexibility, accuracy, and speed of the deep learning solutions make them a viable option for the BLT reconstruction problem and can provide BLT-based tumor targeting for the rat GBM models.

Exploring contrast generalisation in deep learning-based brain MRI-to-CT synthesis

Background:Synthetic computed tomography (sCT) has been proposed and increasingly clinically adopted to enable magnetic resonance imaging (MRI)-based radiotherapy. Deep learning (DL) has recently demonstrated the ability to generate accurate sCT from fixed MRI acquisitions. However, MRI protocols may change over time or differ between centres resulting in low-quality sCT due to poor model generalisation. Purpose:investigating domain randomisation (DR) to increase the generalisation of a DL model for brain sCT generation. Methods:CT and corresponding T1-weighted MRI with/without contrast, T2-weighted, and FLAIR MRI from 95 patients undergoing RT were collected, considering FLAIR the unseen sequence where to investigate generalisation.A “Baseline” generative adversarial network was trained with/without the FLAIR sequence to test how a model performs without DR. Image similarity and accuracy of sCT-based dose plans were assessed against CT to select the best-performing DR approach against the Baseline. Results:The Baseline model had the poorest performance on FLAIR, with mean absolute error (MAE) = 106 ± 20.7 HU (mean ±σ). Performance on FLAIR significantly improved for the DR model with MAE = 99.0 ± 14.9 HU, but still inferior to the performance of the Baseline+FLAIR model (MAE = 72.6 ± 10.1 HU). Similarly, an improvement in γ-pass rate was obtained for DR vs Baseline. Conclusion:DR improved image similarity and dose accuracy on the unseen sequence compared to training only on acquired MRI. DR makes the model more robust, reducing the need for re-training when applying a model on sequences unseen and unavailable for retraining.

Nerve-Sparing Gynecologic Surgery Enabled by A Near-Infrared Nerve-Specific Fluorophore Using Existing Clinical Fluorescence Imaging Systems.

Patients undergoing gynecological procedures suffer from lasting side effects due to intraoperative nerve damage. Small, delicate nerves with complex and nonuniform branching patterns in the female pelvic neuroanatomy make nerve-sparing efforts during standard gynecological procedures such as hysterectomy, cystectomy, and colorectal cancer resection difficult, and thus many patients are left with incontinence and sexual dysfunction. Herein, a near-infrared (NIR) fluorescent nerve-specific contrast agent, LGW08-35, that is spectrally compatible with clinical fluorescence guided surgery (FGS) systems is formulated and characterized for rapid implementation for nerve-sparing gynecologic surgeries. The toxicology, pharmacokinetics (PK), and pharmacodynamics (PD) of micelle formulated LGW08-35 are examined, enabling the determination of the optimal imaging doses and time points, blood and tissue uptake parameters, and maximum tolerated dose (MTD). Application of the formulated fluorophore to imaging of female rat and swine pelvic neuroanatomy validates the continued clinical translation and use for real-time identification of important nerves such as the femoral, sciatic, lumbar, iliac, and hypogastric nerves. Further development of LGW08-35 for clinical use will unlock a valuable tool for surgeons in direct visualization of important nerves and contribute to the ongoing characterization of the female pelvic neuroanatomy to eliminate the debilitating side effects of nerve damage during gynecological procedures.

Faster and lower dose imaging: evaluating adaptive, constant gantry velocity and angular separation in fast low-dose 4D cone beam CT imaging.

The adoption of four-dimensional cone beam computed tomography (4DCBCT) for image-guided lung cancer radiotherapy is increasing, especially for hypofractionated treatments. However, the drawbacks of 4DCBCT include long scan times (∼240s), inconsistent image quality, higher imaging dose than necessary, and streaking artifacts. With the emergence of linear accelerators that can acquire 4DCBCT scans in a short period of time (9.2s) there is a need to examine the impact that these very fast gantry rotations have on 4DCBCT image quality. This study investigates the impact of gantry velocity and angular separation between x-ray projections on image quality and its implication for fast low-dose 4DCBCT with emerging systems, such as the Varian Halcyon that provide fast gantry rotation and imaging. Large and uneven angular separation between x-ray projections is known to reduce 4DCBCT image quality through increased streaking artifacts. However, it is not known when angular separation starts degrading image quality. The study assesses the impact of constant and adaptive gantry velocity and determines the level when angular gaps impair image quality using state-of-the-art reconstruction methods. This study considers fast low-dose 4DCBCT acquisitions (60-80s, 200-projection scans). To assess the impact of adaptive gantry rotations, the angular position of x-ray projections from adaptive 4DCBCT acquisitions from a 30-patient clinical trial were analyzed (referred to as patient angular gaps). To assess the impact of angular gaps, variable and static angular gaps (20°, 30°, 40°) were introduced into evenly separated 200 projections (ideal angular separation). To simulate fast gantry rotations, which are on emerging linacs, constant gantry velocity acquisitions (9.2s, 60s, 120s, 240s) were simulated by sampling x-ray projections at constant intervals using the patient breathing traces from the ADAPT clinical trial (ACTRN12618001440213). The 4D Extended Cardiac-Torso (XCAT) digital phantom was used to simulate projections to remove patient-specific image quality variables. Image reconstruction was performed using Feldkamp-Davis-Kress (FDK), McKinnon-Bates (MKB), and Motion-Compensated-MKB (MCMKB) algorithms. Image quality was assessed using Structural Similarity-Index-Measure (SSIM), Contrast-to-Noise-Ratio (CNR), Signal-to-Noise-Ratio (SNR), Tissue-Interface-Width-Diaphragm (TIW-D), and Tissue-Interface-Width-Tumor (TIW-T). Patient angular gaps and variable angular gap reconstructions produced similar results to ideal angular separation reconstructions, while static angular gap reconstructions produced lower image quality metrics. For MCMKB-reconstructions, average patient angular gaps produced SSIM-0.98, CNR-13.6, SNR-34.8, TIW-D-1.5mm, and TIW-T-2.0mm, static angular gap 40° produced SSIM-0.92, CNR-6.8, SNR-6.7, TIW-D-5.7mm, and TIW-T-5.9mm and ideal produced SSIM-1.00, CNR-13.6, SNR-34.8, TIW-D-1.5mm, and TIW-T-2.0mm. All constant gantry velocity reconstructions produced lower image quality metrics than ideal angular separation reconstructions regardless of the acquisition time. Motion compensated reconstruction (MCMKB) produced the highest contrast images with low streaking artifacts. Very fast 4DCBCT scans can be acquired provided that the entire scan range is adaptively sampled, and motion-compensated reconstruction is performed. Importantly, the angular separation between x-ray projections within each individual respiratory bin had minimal effect on the image quality of fast low-dose 4DCBCT imaging. The results will assist the development of future 4DCBCT acquisition protocols that can now be achieved in very short time frames with emerging linear accelerators.

ScatterNet for projection-based 4D cone-beam computed tomography intensity correction of lung cancer patients.

Background and purpose: In radiotherapy, dose calculations based on 4D cone beam CTs (4DCBCTs) require image intensity corrections. This retrospective study compared the dose calculation accuracy of a deep learning, projection-based scatter correction workflow (ScatterNet), to slower workflows: conventional 4D projection-based scatter correction (CBCTcor) and a deformable image registration (DIR)-based method (4DvCT). Materials and methods: For 26 lung cancer patients, planning CTs (pCTs), 4DCTs and CBCT projections were available. ScatterNet was trained with pairs of raw and corrected CBCT projections. Corrected projections from ScatterNet and the conventional workflow were reconstructed using MA-ROOSTER, yielding 4DCBCTSN and 4DCBCTcor. The 4DvCT was generated by 4DCT to 4DCBCT DIR, as part of the 4DCBCTcor workflow. Robust intensity modulated proton therapy treatment plans were created on free-breathing pCTs. 4DCBCTSN was compared to 4DCBCTcor and the 4DvCT in terms of image quality and dose calculation accuracy (dose-volume-histogram parameters and / gamma analysis). Results: 4DCBCTSN resulted in an average mean absolute error of and when compared to 4DCBCTcor and 4DvCT respectively. High agreement was observed in targets with median dose differences of (4DCBCTSN-4DCBCTcor) and (4DCBCTSN-4DvCT). The gamma analysis showed high average / pass rates of for both 4DCBCTSN vs. 4DCBCTcor and 4DCBCTSN vs. 4DvCT. Conclusions: Accurate 4D dose calculations are feasible for lung cancer patients using ScatterNet for 4DCBCT correction. Average scatter correction times could be reduced from (4DCBCTcor) to , showing the clinical suitability of the proposed deep learning-based method.

Weight-bearing gantry-free cone-beam CT of the lumbar spine: Image quality analysis and dose efficiency

PurposeThe effect of static forces under load limits the prognostic value of lumbar spine CT in a horizontal position. Using a gantry-free scanner architecture, this study was designed to assess the feasibility of weight-bearing cone-beam CT (CBCT) of the lumbar spine and to establish the most dose-effective combination of scan parameters. MethodsEight formalin-fixated cadaveric specimens were examined with a gantry-free CBCT system in upright position with the aid of a dedicated positioning backstop. Cadavers were scanned with eight combinations of tube voltage (102 or 117 kV), detector entrance dose level (high or low), and frame rates (16 or 30 fps). Five radiologists independently analyzed datasets for overall image quality and posterior wall assessability. Additionally, image noise and signal-to-noise ratio (SNR) were compared based on region-of-interest (ROI) measurements in the gluteal muscles. ResultsRadiation dose ranged from 6.8 ± 1.6 (117 kV, dose level low, 16 fps) to 24.3 ± 6.3 mGy (102 kV, dose level high, 30 fps). Both image quality and posterior wall assessability were favored with 30 over 16 fps (all p ≤ 0.008). In contrast, both tube voltage (all p > 0.999) and dose level (all p > 0.096) did not significantly impact reader assessment. Image noise decreased considerably with higher frame rates (all p ≤ 0.040), while SNR ranged from 0.56 ± 0.03 to 1.11 ± 0.30 without a significant difference between scan protocols (all p ≥ 0.060). ConclusionsEmploying an optimized scan protocol, weight-bearing gantry-free CBCT of the lumbar spine allows for diagnostic imaging at reasonable radiation dose.