An automated technique for global noise level measurement in CT image with a conjunction of image gradient.

Automated assessment of noise level in clinical computed tomography (CT) images is a crucial technique for evaluating and ensuring the quality of these images. There are various factors that can impact CT image noise, such as statistical noise, electronic noise, structure noise, texture noise, artifact noise, etc. In this study, a method was developed to measure the global noise index (GNI) in clinical CT scans due to the fluctuation of x-ray quanta. Initially, a noise map is generated by sliding a 10 × 10 pixel for calculating Hounsfield unit (HU) standard deviation and the noise map is further combined with the gradient magnitude map. By employing Boolean operation, pixels with high gradients are excluded from the noise histogram generated with the noise map. By comparing the shape of the noise histogram from this method with Christianson's tissue-type global noise measurement algorithm, it was observed that the noise histogram computed in anthropomorphic phantoms had a similar shape with a close GNI value. In patient CT images, excluding the HU deviation due the structure change demonstrated to have consistent GNI values across the entire CT scan range with high heterogeneous tissue compared to the GNI values using Christianson's tissue-type method. The proposed GNI was evaluated in phantom scans and was found to be capable of comparing scan protocols between different scanners. The variation of GNI when using different reconstruction kernels in clinical CT images demonstrated a similar relationship between noise level and kernel sharpness as observed in uniform phantom: sharper kernel resulted in noisier images. This indicated that GNI was a suitable index for estimating the noise level in clinical CT images with either a smooth or grainy appearance. The study's results suggested that the algorithm can be effectively utilized to screen the noise level for a better CT image quality control.

Deep learning-based target decomposition for markerless lung tumor tracking in radiotherapy.

BACKGROUND: In radiotherapy, real-time tumor tracking can verify tumor position during beam delivery, guide the radiation beam to target the tumor, and reduce the chance of a geometric miss. Markerless kV x-ray image-based tumor tracking is challenging due to the low tumor visibility caused by tumor-obscuring structures. Developing a new method to enhance tumor visibility for real-time tumor tracking is essential. PURPOSE: To introduce a novel method for markerless kV image-based tracking of lung tumors via deep learning-based target decomposition. METHODS: We utilized a conditional Generative Adversarial Network (cGAN), known as Pix2Pix, to build a patient-specific model and generate the synthetic decomposed target image (sDTI) to enhance tumor visibility on the real-time kV projection images acquired by the onboard kV imager equipped on modern linear accelerators. We used 4DCT simulation images to generate the digitally reconstructed radiograph (DRR) and DTI image pairs for model training. We augmented the training dataset by randomly shifting the 4DCT in the superior-inferior, anterior-posterior, and left-right directions during the DRR and DTI generation process. We performed real-time 2D tumor tracking via template matching between the DTI generated from the CT simulation and the sDTI generated from the real-time kV projection images. We validated the proposed method using nine patients' datasets with implanted beacons near the tumor. RESULTS: The sDTI can effectively improve the image contrast around the lung tumors on the kV projection images for the nine patients. With the beacon motion as ground truth, the tracking errors were on average 0.8 ± 0.7 mm in the superior-inferior (SI) direction and 0.9 ± 0.8 mm in the in-plane left-right (IPLR) direction. The percentage of successful tracking, defined as a tracking error less than 2 mm in the SI direction, is 92.2% on the 4312 tested images. The patient-specific model took approximately 12 h to train. During testing, it took approximately 35 ms to generate one sDTI, and 13 ms to perform the tumor tracking using template matching. CONCLUSIONS: Our method offers the potential solution for nearly real-time markerless lung tumor tracking. It achieved a high level of accuracy and an impressive tracking rate. Further development of 3D lung tumor tracking is warranted.

Automated planning of stereotactic spine re-irradiation using cumulative dose limits.

Background and Purpose: The lack of dedicated tools in commercial planning systems currently restricts efficient review and planning for re-irradiation. The aim of this study was to develop an automated re-irradiation planning framework based on cumulative doses. Materials and Methods: We performed a retrospective study of 14 patients who received spine SBRT re-irradiation near a previously irradiated treatment site. A fully-automated workflow, DART (Dose Accumulation-based Re-irradiation Tool), was implemented within Eclipse by leveraging a combination of a dose accumulation script and a proprietary automated optimization algorithm. First, we converted the prior treatment dose into equivalent dose in 2 Gy fractions (EQD2) and mapped it to the current anatomy, utilizing deformable image registration. Subsequently, the intersection of EQD2 isodose lines with relevant organs at risk defines a series of optimization structures. During plan optimization, the residual allowable dose at a specified tissue tolerance was treated as a hard constraint. Results: All DART plans met institutional physical and cumulative constraints and passed plan checks by qualified medical physicists. DART demonstrated significant improvements in target coverage over clinical plans, with an average increase in PTV D99% and V100% of 2.3 Gy [range -0.3-7.7 Gy] and 3.4 % [range -0.4 %-7.6 %] (p < 0.01, paired t-test), respectively. Moreover, high-dose spillage (>105 %) outside the PTV was reduced by up to 7 cm3. The homogeneity index for DART plans was improved by 19 % (p < 0.001). Conclusions: DART provides a powerful framework to achieve more tailored re-irradiation plans by accounting for dose distributions from the previous treatments. The superior plan quality could improve the therapeutic ratio for re-irradiation patients.

Clinical Experience With an Offline Adaptive Radiation Therapy Head and Neck Program: Dosimetric Benefits and Opportunities for Patient Selection.

PURPOSE: The objective of this study was to develop a linear accelerator (LINAC)-based adaptive radiation therapy (ART) workflow for the head and neck that is informed by automated image tracking to identify major anatomic changes warranting adaptation. In this study, we report our initial clinical experience with the program and an investigation into potential trigger signals for ART. METHODS AND MATERIALS: Offline ART was systematically performed on patients receiving radiation therapy for head and neck cancer on C-arm LINACs. Adaptations were performed at a single time point during treatment with resimulation approximately 3 weeks into treatment. Throughout treatment, all patients were tracked using an automated image tracking system called the Automated Watchdog for Adaptive Radiotherapy Environment (AWARE). AWARE measures volumetric changes in gross tumor volumes (GTVs) and selected normal tissues via cone beam computed tomography scans and deformable registration. The benefit of ART was determined by comparing adaptive plan dosimetry and normal tissue complication probabilities against the initial plans recalculated on resimulation computed tomography scans. Dosimetric differences were then correlated with AWARE-measured volume changes to identify patient-specific triggers for ART. Candidate trigger variables were evaluated using receiver operator characteristic analysis. RESULTS: In total, 46 patients received ART in this study. Among these patients, we observed a significant decrease in dose to the submandibular glands (mean ± standard deviation: -219.2 ± 291.2 cGy, P < 10-5), parotids (-68.2 ± 197.7 cGy, P = .001), and oral cavity (-238.7 ± 206.7 cGy, P < 10-5) with the adaptive plan. Normal tissue complication probabilities for xerostomia computed from mean parotid doses also decreased significantly with the adaptive plans (P = .008). We also observed systematic intratreatment volume reductions (ΔV) for GTVs and normal tissues. Candidate triggers were identified that predicted significant improvement with ART, including parotid ΔV = 7%, neck ΔV = 2%, and nodal GTV ΔV = 29%. CONCLUSIONS: Systematic offline head and neck ART was successfully deployed on conventional LINACs and reduced doses to critical salivary structures and the oral cavity. Automated cone beam computed tomography tracking provided information regarding anatomic changes that may aid patient-specific triggering for ART.

Toward quantitative intrafractional monitoring in paraspinal SBRT using a proprietary software application: clinical implementation and patient results.

Objective.We report on paraspinal motion and the clinical implementation of our proprietary software that leverages Varian's intrafraction motion review (IMR) capability for quantitative tracking of the spine during paraspinal SBRT. The work is based on our prior development and analysis on phantoms.Approach.To address complexities in patient anatomy, digitally reconstructed radiographs (DRR's) that highlight only the spine or hardware were constructed as tracking reference. Moreover, a high-pass filter and first-pass coarse search were implemented to enhance registration accuracy and stability. For evaluation, 84 paraspinal SBRT patients with sites spanning across the entire vertebral column were enrolled with prescriptions ranging from 24 to 40 Gy in one to five fractions. Treatments were planned and delivered with 9 IMRT beams roughly equally distributed posteriorly. IMR was triggered every 200 or 500 MU for each beam. During treatment, the software grabbed the IMR image, registered it with the corresponding DRR, and displayed the motion result in near real-time on auto-pilot mode. Four independent experts completed offline manual registrations as ground truth for tracking accuracy evaluation.Main results.Our software detected ≥1.5 mm and ≥2 mm motions among 17.1% and 6.6% of 1371 patient images, respectively, in either lateral or longitudinal direction. In the validation set of 637 patient images, 91.9% of the tracking errors compared to manual registration fell within ±0.5 mm in either direction. Given a motion threshold of 2 mm, the software accomplished a 98.7% specificity and a 93.9% sensitivity in deciding whether to interrupt treatment for patient re-setup.Significance.Significant intrafractional motion exists in certain paraspinal SBRT patients, supporting the need for quantitative motion monitoring during treatment. Our improved software achieves high motion tracking accuracy clinically and provides reliable guidance for treatment intervention. It offers a practical solution to ensure accurate delivery of paraspinal SBRT on a conventional Linac platform.

Creating patient-specific digital phantoms with a longitudinal atlas for evaluating deformable CT-CBCT registration in adaptive lung radiotherapy.

BACKGROUND: Quality assurance of deformable image registration (DIR) is challenging because the ground truth is often unavailable. In addition, current approaches that rely on artificial transformations do not adequately resemble clinical scenarios encountered in adaptive radiotherapy. PURPOSE: We developed an atlas-based method to create a variety of patient-specific serial digital phantoms with CBCT-like image quality to assess the DIR performance for longitudinal CBCT imaging data in adaptive lung radiotherapy. METHODS: A library of deformations was created by extracting the longitudinal changes observed between a planning CT and weekly CBCT from an atlas of lung radiotherapy patients. The planning CT of an inquiry patient was first deformed by mapping the deformation pattern from a matched atlas patient, and subsequently appended with CBCT artifacts to imitate a weekly CBCT. Finally, a group of digital phantoms around an inquiry patient was produced to simulate a series of possible evolutions of tumor and adjacent normal structures. We validated the generated deformation vector fields (DVFs) to ensure numerically and physiologically realistic transformations. The proposed framework was applied to evaluate the performance of the DIR algorithm implemented in the commercial Eclipse treatment planning system in a retrospective study of eight inquiry patients. RESULTS: The generated DVFs were inverse consistent within less than 3 mm and did not exhibit unrealistic folding. The deformation patterns adequately mimicked the observed longitudinal anatomical changes of the matched atlas patients. Worse Eclipse DVF accuracy was observed in regions of low image contrast or artifacts. The structure volumes exhibiting a DVF error magnitude of equal or more than 2 mm ranged from 24.5% (spinal cord) to 69.2% (heart) and the maximum DVF error exceeded 5 mm for all structures except the spinal cord. Contour-based evaluations showed a high degree of alignment with dice similarity coefficients above 0.8 in all cases, which underestimated the overall DVF accuracy within the structures. CONCLUSIONS: It is feasible to create and augment digital phantoms based on a particular patient of interest using multiple series of deformation patterns from matched patients in an atlas. This can provide a semi-automated procedure to complement the quality assurance of CT-CBCT DIR and facilitate the clinical implementation of image-guided and adaptive radiotherapy that involve longitudinal CBCT imaging studies.

Development of automated region of interest selection algorithms for surface-guided radiation therapy of breast cancer.

To investigate automation of the preparation of the region of interest (ROI) for surface-guided radiotherapy (SGRT) of the whole breast with two algorithms based on contour anatomies: using the body contour, and using the breast contour. The patient dataset used for modeling consisted of 39 breast cancer patients previously treated with SGRT. The patient's anatomical structures (body and ipsilateral breast) were retrieved from the planning system, and the clinical ROI (cROI) drawn by the planners was retrieved from the SGRT system for comparison. For the body-contour-based algorithm, a convolutional neural network (MobileNet-v2) was utilized to train a synthetic human model dataset to predict body joint locations. With the body joint location knowledge, an automated ROI (aROIbody ) can be created based on: (1) the superior-inferior (S-I) borders defined by the joint locations, (2) the left-right (L-R) borders defined with 3/4 of chest width, and (3) a curation of the ROI to avoid the ipsilateral armpit. For the breast-contour-based algorithm, an aROIbreast was created by first defining the ROI in the S-I direction with the ipsilateral breast boundaries. Other steps are the same as with the body-contour-based algorithm. Among the 39 patients, 24 patients were used to fine-tune the algorithm parameters, and the remaining 15 patients were used to evaluate the quality of the aROIs against the cROIs. A blinded evaluation was performed by three SGRT expert physicists to rate the acceptability and the quality (1-10 scale) of the aROIs and cROIs, and the dice similarity coefficient (DSC) was also calculated to compare the similarity between the aROIs and cROIs. The results showed that the average acceptability was 14/15 (range: 13/15-15/15) for cROIs, 13.3/15 (range: 13/15-14/15) for aROIbody , and 14.6/15 (range: 14/15-15/15) for aROIbreast . The average quality was 7.4 ± 0.8 for cROIs, 8.1 ± 1.2 for aROIbody , and 8.2 ± 0.9 for aROIbreast . The DSC with cROIs was 0.81 ± 0.06 for aROIbody , and 0.83 ± 0.04 for aROIbreast . The ROI creation time was ∼120 s for clinical, 1.3 s for aROIbody , and 1.2 s for aROIbreast . The proposed automated algorithms can improve the ROI compliance with the SGRT protocol, with a shortened preparation time. It is ready to be integrated into the clinical workflow for automated ROI preparation.

A Potential Pitfall and Clinical Solutions in Surface-Guided Deep Inspiration Breath Hold Radiation Therapy for Left-Sided Breast Cancer.

Purpose: Deep inspiration breath hold (DIBH) is an effective technique to spare the heart in treating left-sided breast cancer. Surface-guided radiation therapy (SGRT) is increasingly applied in DIBH setup and motion monitoring. Patient-specific breathing behavior, either thoracically driven or abdominally driven (A-DIBH), should be unaltered, online identified, and monitored accordingly to ensure reproducible heart-sparing treatment. Methods and Materials: Sixty patients with left-sided breast cancer treated with SGRT were analyzed: 20 A-DIBH patients with vertical chest elevation (VCE ≤ 5 mm) were prospectively identified, and 40 control patients were retrospectively and randomly selected for comparison. At simulation, both free-breathing (FB) and DIBH computed tomography (CT) were acquired, guided by a motion surrogate placed around the xiphoid process. For SGRT treatment setups, the region of interest (ROI) was defined on the CT chest surface, and the surrogate-based setup was a backup. For all 60 patients, the VCE was measured as the average of the FB-to-DIBH elevations at the breast and xiphoid process, together with abdominal elevation. In the 40-patient control group, A-DIBH patients (VCE ≤ 5 mm) were identified. Of the 20 A-DIBH patients, 10 were treated with volumetric modulated arc therapy plans, and 10 patients were treated with tangent plans. Clinical DIBH plans were recalculated on FB CT to compare maximum dose (DMax), 5% of the maximum dose (D5%), mean dose (DMean), and V30Gy, V20Gy, and V5Gy of the heart and lungs and their significance. Results: In the 20 A-DIBH patients, VCE = 3 ± 2 mm, surrogate motion (9 ± 6 mm), and abdomen motion of 14 ± 5 mm are found. Heart dose reduction from FB to DIBH is significant (P < .01): ∆DMax = -8.4 ± 9.8 Gy, ∆D5% = -2.4 ± 4.4 Gy, and ∆DMean = -0.6 ± 0.9 Gy. Six out of 40 control patients (15%) are found to have VCE ≤ 5 mm. Conclusions: A-DIBH (VCE ≤ 5 mm) patient population is significant (15%), and they should be identified in the SGRT workflow and monitored accordingly. A new abdominal ROI or an abdominal surrogate should be used instead of the conventional chest-only ROI. Patient-specific DIBH should be preserved for higher reproducibility to ensure heart sparing.

Automatically tracking brain metastases after stereotactic radiosurgery.

Background and purpose: Patients with brain metastases (BMs) are surviving longer and returning for multiple courses of stereotactic radiosurgery. BMs are monitored after radiation with follow-up magnetic resonance (MR) imaging every 2-3 months. This study investigated whether it is possible to automatically track BMs on longitudinal imaging and quantify the tumor response after radiotherapy. Methods: The METRO process (MEtastasis Tracking with Repeated Observations was developed to automatically process patient data and track BMs. A longitudinal intrapatient registration method for T1 MR post-Gd was conceived and validated on 20 patients. Detections and volumetric measurements of BMs were obtained from a deep learning model. BM tracking was validated on 32 separate patients by comparing results with manual measurements of BM response and radiologists' assessments of new BMs. Linear regression and residual analysis were used to assess accuracy in determining tumor response and size change. Results: A total of 123 irradiated BMs and 38 new BMs were successfully tracked. 66 irradiated BMs were visible on follow-up imaging 3-9 months after radiotherapy. Comparing their longest diameter changes measured manually vs. METRO, the Pearson correlation coefficient was 0.88 (p < 0.001); the mean residual error was -8 ± 17%. The mean registration error was 1.5 ± 0.2 mm. Conclusions: Automatic, longitudinal tracking of BMs using deep learning methods is feasible. In particular, the software system METRO fulfills a need to automatically track and quantify volumetric changes of BMs prior to, and in response to, radiation therapy.

Comparison of setup accuracy of optical surface image versus orthogonal x-ray images for VMAT of the left breast using deep-inspiration breath-hold.

To compare the setup accuracy of optical surface image (OSI) versus orthogonal x-ray images (2DkV) using cone beam computed tomography (CBCT) as ground truth for radiotherapy of left breast cancer in deep-inspiration breath-hold (DIBH). Ten left breast DIBH patients treated with volumetric modulated arc therapy (VMAT) were studied retrospectively. OSI, 2DkV, and CBCT were acquired weekly at treatment setup. OSI, 2DkV, and CBCT were registered to planning CT or planning DRR based on a breast surface region of interest (ROI), bony anatomy (chestwall and sternum), and both bony anatomy and breast surface, respectively. These registrations provided couch shifts for each imaging system. The setup errors, or the difference in couch shifts between OSI and CBCT were compared to those between 2DkV and CBCT. A second OSI was acquired during last beam delivery to evaluate intrafraction motion. The median absolute setup errors were (0.21, 0.27, 0.23 cm, 0.6°, 1.3°, 1.0°) for OSI, and (0.26, 0.24, 0.18 cm, 0.9°, 1.0°, 0.6°) for 2DkV in vertical, longitudinal and lateral translations, and in rotation, roll and pitch, respectively. None of the setup errors was significantly different between OSI and 2DkV. For both systems, the systematic and random setup errors were ≤0.6 cm and ≤1.5° in all directions. Nevertheless, larger setup errors were observed in some sessions in both systems. There was no correlation between OSI and CBCT whereas there was modest correlation between 2DkV and CBCT. The intrafraction motion in DIBH detected by OSI was small with median absolute translations <0.2 cm, and rotations ≤0.4°. Though OSI showed comparable and small setup errors as 2DkV, it showed no correlation with CBCT. We concluded that to achieve accurate setup for both bony anatomy and breast surface, daily 2DkV can't be omitted following OSI for left breast patients treated with DIBH VMAT.

Patient specific prior cross attention for kV decomposition in paraspinal motion tracking.

BACKGROUND: X-ray image quality is critical for accurate intrafraction motion tracking in radiation therapy. PURPOSE: This study aims to develop a deep-learning algorithm to improve kV image contrast by decomposing the image into bony and soft tissue components. In particular, we designed a priori attention mechanism in the neural network framework for optimal decomposition. We show that a patient-specific prior cross-attention (PCAT) mechanism can boost the performance of kV image decomposition. We demonstrate its use in paraspinal SBRT motion tracking with online kV imaging. METHODS: Online 2D kV projections were acquired during paraspinal SBRT for patient motion monitoring. The patient-specific prior images were generated by randomly shifting and rotating spine-only DRR created from the setup CBCT, simulating potential motions. The latent features of the prior images were incorporated into the PCAT using multi-head cross attention. The neural network aimed to learn to selectively amplify the transmission of the projection image features that correlate with features of the priori. The PCAT network structure consisted of (1) a dual-branch generator that separates the spine and soft tissue component of the kV projection image and (2) a dual-function discriminator (DFD) that provides the realness score of the predicted images. For supervision, we used a loss combining mean absolute error loss, discriminator loss, perceptual loss, total variation, and mean squared error loss for soft tissues. The proposed PCAT approach was benchmarked against previous work using the ResNet generative adversarial network (ResNetGAN) without prior information. RESULTS: The trained PCAT had improved performance in effectively retaining and preserving the spine structure and texture information while suppressing the soft tissues from the kV projection images. The decomposed spine-only x-ray images had the submillimeter matching accuracy at all beam angles. The decomposed spine-only x-ray significantly reduced the maximum errors to 0.44 mm (<2 pixels) in comparison to 0.92 mm (∼4 pixels) of ResNetGAN. The PCAT decomposed spine images also had higher PSNR and SSIM (p-value < 0.001). CONCLUSION: The PCAT selectively learned the important latent features by incorporating the patient-specific prior knowledge into the deep learning algorithm, significantly improving the robustness of the kV projection image decomposition, and leading to improved motion tracking accuracy in paraspinal SBRT.

Trends in Radiation Dose to the Contralateral Breast During Breast Cancer Radiation Therapy.

Over 4 million survivors of breast cancer live in the United States, 35% of whom were treated before 2009. Approximately half of patients with breast cancer receive radiation therapy, which exposes the untreated contralateral breast to radiation and increases the risk of a subsequent contralateral breast cancer (CBC). Radiation oncology has strived to reduce unwanted radiation dose, but it is unknown whether a corresponding decline in actual dose received to the untreated contralateral breast has occurred. The purpose of this study was to evaluate trends in unwanted contralateral breast radiation dose to inform risk assessment of second primary cancer in the contralateral breast for long-term survivors of breast cancer. Individually estimated radiation absorbed doses to the four quadrants and areola central area of the contralateral breast were estimated for 2,132 women treated with radiation therapy for local/regional breast cancers at age <55 years diagnosed between 1985 and 2008. The two inner quadrant doses and two outer quadrant doses were averaged. Trends in dose to each of the three areas of the contralateral breast were evaluated in multivariable models. The population impact of reducing contralateral breast dose on the incidence of radiation-associated CBC was assessed by estimating population attributable risk fraction (PAR) in a multivariable model. The median dose to the inner quadrants of the contralateral breast was 1.70 Gy; to the areola, 1.20 Gy; and to the outer quadrants, 0.72 Gy. Ninety-two percent of patients received ≥1 Gy to the inner quadrants. For each calendar year of diagnosis, dose declined significantly for each location, most rapidly for the inner quadrants (0.04 Gy/year). Declines in dose were similar across subgroups defined by age at diagnosis and body mass index. The PAR for CBC due to radiation exposure >1 Gy for women <40 years of age was 17%. Radiation dose-reduction measures have reduced dose to the contralateral breast during breast radiation therapy. Reducing the dose to the contralateral breast to <1 Gy could prevent an estimated 17% of subsequent radiation-associated CBCs for women treated under 40 years of age. These dose estimates inform CBC surveillance for the growing number of breast cancer survivors who received radiation therapy as young women in recent decades. Continued reductions in dose to the contralateral breast could further reduce the incidence of radiation-associated CBC.

Enhancing the target visibility with synthetic target specific digitally reconstructed radiograph for intrafraction motion monitoring: A proof-of-concept study.

BACKGROUND: Intrafraction motion monitoring in External Beam Radiation Therapy (EBRT) is usually accomplished by establishing a correlation between the tumor and the surrogates such as an external infrared reflector, implanted fiducial markers, or patient skin surface. These techniques either have unstable surrogate-tumor correlation or are invasive. Markerless real-time onboard imaging is a noninvasive alternative that directly images the target motion. However, the low target visibility due to overlapping tissues along the X-ray projection path makes tumor tracking challenging. PURPOSE: To enhance the target visibility in projection images, a patient-specific model was trained to synthesize the Target Specific Digitally Reconstructed Radiograph (TS-DRR). METHODS: Patient-specific models were built using a conditional Generative Adversarial Network (cGAN) to map the onboard projection images to TS-DRR. The standard Pix2Pix network was adopted as our cGAN model. We synthesized the TS-DRR based on the onboard projection images using phantom and patient studies for spine tumors and lung tumors. Using previously acquired CT images, we generated DRR and its corresponding TS-DRR to train the network. For data augmentation, random translations were applied to the CT volume when generating the training images. For the spine, separate models were trained for an anthropomorphic phantom and a patient treated with paraspinal stereotactic body radiation therapy (SBRT). For lung, separate models were trained for a phantom with a spherical tumor insert and a patient treated with free-breathing SBRT. The models were tested using Intrafraction Review Images (IMR) for the spine and CBCT projection images for the lung. The performance of the models was validated using phantom studies with known couch shifts for the spine and known tumor deformation for the lung. RESULTS: Both the patient and phantom studies showed that the proposed method can effectively enhance the target visibility of the projection images by mapping them into synthetic TS-DRR (sTS-DRR). For the spine phantom with known shifts of 1 mm, 2 mm, 3 mm, and 4 mm, the absolute mean errors for tumor tracking were 0.11 ± 0.05 mm in the x direction and 0.25 ± 0.08 mm in the y direction. For the lung phantom with known tumor motion of 1.8 mm, 5.8 mm, and 9 mm superiorly, the absolute mean errors for the registration between the sTS-DRR and ground truth are 0.1 ± 0.3 mm in both the x and y directions. Compared to the projection images, the sTS-DRR has increased the image correlation with the ground truth by around 83% and increased the structural similarity index measure with the ground truth by around 75% for the lung phantom. CONCLUSIONS: The sTS-DRR can greatly enhance the target visibility in the onboard projection images for both the spine and lung tumors. The proposed method could be used to improve the markerless tumor tracking accuracy for EBRT.

Automated VMAT treatment planning using sequential convex programming: algorithm development and clinical implementation.

Objective.To develop and clinically implement a fully automated treatment planning system (TPS) for volumetric modulated arc therapy (VMAT).Approach.We solve two constrained optimization problems sequentially. The tumor coverage is maximized at the first step while respecting all maximum/mean dose clinical criteria. The second step further reduces the dose at the surrounding organs-at-risk as much as possible. Our algorithm optimizes the machine parameters (leaf positions and monitor units) directly and the resulting mathematical non-convexity is handled using thesequential convex programmingby solving a series of convex approximation problems. We directly integrate two novel convex surrogate metrics to improve plan delivery efficiency and reduce plan complexity by promoting aperture shape regularity and neighboring aperture similarity. The entire workflow is automated using the Eclipse TPS application program interface scripting and provided to users as a plug-in, requiring the users to solely provide the contours and their preferred arcs. Our program provides the optimal machine parameters and does not utilize the Eclipse optimization engine, however, it utilizes the Eclipse final dose calculation engine. We have tested our program on 60 patients of different disease sites and prescriptions for stereotactic body radiotherapy (paraspinal (24 Gy × 1, 9 Gy × 3), oligometastis (9 Gy × 3), lung (18 Gy × 3, 12 Gy × 4)) and retrospectively compared the automated plans with the manual plans used for treatment. The program is currently deployed in our clinic and being used in our daily clinical routine to treat patients.Main results.The automated plans found dosimetrically comparable or superior to the manual plans. For paraspinal (24 Gy × 1), the automated plans especially improved tumor coverage (the average PTV (Planning Target Volume) 95% from 96% to 98% and CTV100% from 95% to 97%) and homogeneity (the average PTV maximum dose from 120% to 116%). For other sites/prescriptions, the automated plans especially improved the duty cycle (23%-39.4%).Significance.This work proposes a fully automated approach to the mathematically challenging VMAT problem. It also shows how the capabilities of the existing (Food and Drug Administration)FDA-approved commercial TPS can be enhanced using an in-house developed optimization algorithm that completely replaces the TPS optimization engine. The code and pertained models along with a sample dataset will be released on our ECHO-VMAT GitHub (https://github.com/PortPy-Project/ECHO-VMAT).

Automated tracking of morphologic changes in weekly magnetic resonance imaging during head and neck radiotherapy.

BACKGROUND AND PURPOSE: Anatomic changes during head and neck radiotherapy can impact dose delivery, necessitate adaptive replanning, and indicate patient-specific response to treatment. We have developed an automated system to track these changes through longitudinal MRI scans to aid identification and clinical intervention. The purpose of this article is to describe this tracking system and present results from an initial cohort of patients. MATERIALS AND METHODS: The Automated Watchdog in Adaptive Radiotherapy Environment (AWARE) was developed to process longitudinal MRI data for radiotherapy patients. AWARE automatically identifies and collects weekly scans, propagates radiotherapy planning structures, computes structure changes over time, and reports important trends to the clinical team. AWARE also incorporates manual structure review and revision from clinical experts and dynamically updates tracking statistics when necessary. AWARE was applied to patients receiving weekly T2-weighted MRI scans during head and neck radiotherapy. Changes in nodal gross tumor volume (GTV) and parotid gland delineations were tracked over time to assess changes during treatment and identify early indicators of treatment response. RESULTS: N = 91 patients were tracked and analyzed in this study. Nodal GTVs and parotids both shrunk considerably throughout treatment (-9.7 ± 7.7% and -3.7 ± 3.3% per week, respectively). Ipsilateral parotids shrunk significantly faster than contralateral (-4.3 ± 3.1% vs. -2.9 ± 3.3% per week, p = 0.005) and increased in distance from GTVs over time (+2.7 ± 7.2% per week, p < 1 × 10-5 ). Automatic structure propagations agreed well with manual revisions (Dice = 0.88 ± 0.09 for parotids and 0.80 ± 0.15 for GTVs), but for GTVs the agreement degraded 4-5 weeks after the start of treatment. Changes in GTV volume observed by AWARE as early as one week into treatment were predictive of large changes later in the course (AUC = 0.79). CONCLUSION: AWARE automatically identified longitudinal changes in GTV and parotid volumes during radiotherapy. Results suggest that this system may be useful for identifying rapidly responding patients as early as one week into treatment.

Quantitative longitudinal mapping of radiation-treated prostate cancer using MR fingerprinting with radial acquisition and subspace reconstruction.

MR fingerprinting (MRF) enables fast multiparametric quantitative imaging with a single acquisition and has been shown to improve diagnosis of prostate cancer. However, most prostate MRF studies were performed with spiral acquisitions that are sensitive to B0 inhomogeneities and consequent blurring. In this work, a radial MRF acquisition with a novel subspace reconstruction technique was developed to enable fast T1/T2 mapping in the prostate in under 4 min. The subspace reconstruction exploits the extensive temporal correlations in the MRF dictionary to pre-compute a low dimensional space for the solution and thus reduce the number of radial spokes to accelerate the acquisition. Iterative reconstruction with the subspace model and additional regularization of the signal representation in the subspace is performed to minimize the number of spokes and maintain matching quality and SNR. Reconstruction accuracy was assessed using the ISMRM NIST phantom. In-vivo validation was performed on two healthy subjects and two prostate cancer patients undergoing radiation therapy. The longitudinal repeatability was quantified using the concordance correlation coefficient (CCC) in one of the healthy subjects by repeated scans over 1 year. One prostate cancer patient was scanned at three time points, before initiating therapy and following brachytherapy and external beam radiation. Changes in the T1/T2 maps obtained with the proposed method were quantified. The prostate, peripheral and transitional zones, and visible dominant lesion were delineated for each study, and the statistics and distribution of the quantitative mapping values were analyzed. Significant image quality improvements compared with standard reconstruction methods were obtained with the proposed subspace reconstruction method. A notable decrease in the spread of the T1/T2 values without biasing the estimated mean values was observed with the subspace reconstruction and agreed with reported literature values. The subspace reconstruction enabled visualization of small differences in T1/T2 values in the tumor region within the peripheral zone. Longitudinal imaging of a volunteer subject yielded CCC of 0.89 for MRF T1, and 0.81 for MRF T2 in the prostate gland. Longitudinal imaging of the prostate patient confirmed the feasibility of capturing radiation treatment related changes. This work is a proof-of-concept for a high resolution and fast quantitative mapping using golden-angle radial MRF combined with a subspace reconstruction technique for longitudinal treatment response assessment in subjects undergoing radiation treatment.

Accuracy and Efficiency of Patient Setup Using Surface Imaging versus Skin Tattoos for Accelerated Partial Breast Irradiation.

Purpose: Skin tattoos represent the standard approach for surface alignment and setup of breast cancer radiation therapy, yet permanent skin markings contribute to adverse cosmesis and patient dissatisfaction. With the advent of contemporary surface-imaging technology, we evaluated setup accuracy and timing between "tattoo-less" and traditional tattoo-based setup techniques. Methods and Materials: Patients receiving accelerated partial breast irradiation (APBI) underwent traditional tattoo-based setup (TTB), alternating daily with a tattoo-less setup via surface imaging using AlignRT (ART). Following initial setup, position was verified via daily kV imaging, with matching on surgical clips representing ground truth. Translational shifts (TS) and rotational shifts (RS) were ascertained, as were setup time and total in-room time. Statistical analyses used the Wilcoxon signed rank test and Pitman-Morgan variance test. Results: A total of 43 patients receiving APBI and 356 treatment fractions were analyzed (174 TTB fractions and 182 using ART). For tattoo-less setup via ART, the median absolute TS were 0.31 cm in the vertical (range, 0.08-0.82), 0.23 cm in the lateral (0.05-0.86), and 0.26 cm in the longitudinal (0.02-0.72) axes. For TTB setup, the corresponding median TS were 0.34 cm (0.05-1.98), 0.31 cm (0.09-1.84), and 0.34 cm (0.08-1.25), respectively. The median magnitude shifts were 0.59 (0.30-1.31) for ART and 0.80 (0.27-2.13) for TTB. ART was not statistically distinguishable from TTB in terms of TS, except in the longitudinal direction (P = .154, .059, and .021, respectively), and was superior to TTB for magnitude shift (P < .001). The variance of each TS variable was significantly narrower for ART compared with TTB (P ≤ .001 vertical, P = .001 lateral, P = .005 longitudinal). The median absolute RS for ART was 0.64° rotation (range, 0.00-1.90), 0.65° roll (0.05-2.90), and 0.30° pitch (0.00-1.50). The corresponding median RS for TTB were 0.80° (0.00-2.50), 0.64° (0.00-3.00), and 0.46° (0.00-2.90), respectively. ART setup was not statistically different from TTB in terms of RS (P = .868, .236, and .079, respectively). ART showed lower variance than TTB in terms of pitch (P = .009). The median total in-room time was shorter for ART than TTB (15.42 vs 17.25 minutes; P = .008), as was the median setup time (11.12 vs 13.00 minutes; P = .001). Moreover, ART had a narrower distribution of setup time with fewer lengthy outliers versus TTB. Conclusions: These findings suggest that a tattoo-less setup approach with AlignRT may be sufficiently accurate and expeditious to supplant surface tattoos for patients receiving APBI. Further analyses with larger cohorts will determine whether tattoo-based approaches can be replaced by noninvasive surface imaging.

Markerless motion tracking with simultaneous MV and kV imaging in spine SBRT treatment-a feasibility study.

Objective. Motion tracking with simultaneous MV-kV imaging has distinct advantages over single kV systems. This research is a feasibility study of utilizing this technique for spine stereotactic body radiotherapy (SBRT) through phantom and patient studies.Approach. A clinical spine SBRT plan was developed using 6xFFF beams and nine sliding-window IMRT fields. The plan was delivered to a chest phantom on a linear accelerator. Simultaneous MV-kV image pairs were acquired during beam delivery. KV images were triggered at predefined intervals, and synthetic MV images showing enlarged MLC apertures were created by combining multiple raw MV frames with corrections for scattering and intensity variation. Digitally reconstructed radiograph (DRR) templates were generated using high-resolution CBCT reconstructions (isotropic voxel size (0.243 mm)3) as the reference for 2D-2D matching. 3D shifts were calculated from triangulation of kV-to-DRR and MV-to-DRR registrations. To evaluate tracking accuracy, detected shifts were compared to known phantom shifts as introduced before treatment. The patient study included a T-spine patient and an L-spine patient. Patient datasets were retrospectively analyzed to demonstrate the performance in clinical settings.Main results. The treatment plan was delivered to the phantom in five scenarios: no shift, 2 mm shift in one of the longitudinal, lateral and vertical directions, and 2 mm shift in all the three directions. The calculated 3D shifts agreed well with the actual couch shifts, and overall, the uncertainty of 3D detection is estimated to be 0.3 mm. The patient study revealed that with clinical patient image quality, the calculated 3D motion agreed with the post-treatment cone beam CT. It is feasible to automate both kV-to-DRR and MV-to-DRR registrations using a mutual information-based method, and the difference from manual registration is generally less than 0.3 mm.Significance. The MV-kV imaging-based markerless motion tracking technique was validated through a feasibility study. It is a step forward toward effective motion tracking and accurate delivery for spinal SBRT.

Seq2Morph: A deep learning deformable image registration algorithm for longitudinal imaging studies and adaptive radiotherapy.

PURPOSE: To simultaneously register all the longitudinal images acquired in a radiotherapy course for analyzing patients' anatomy changes for adaptive radiotherapy (ART). METHODS: To address the unique needs of ART, we designed Seq2Morph, a novel deep learning-based deformable image registration (DIR) network. Seq2Morph was built upon VoxelMorph which is a general-purpose framework for learning-based image registration. The major upgrades are (1) expansion of inputs to all weekly cone-beam computed tomography (CBCTs) acquired for monitoring treatment responses throughout a radiotherapy course, for registration to their planning CT; (2) incorporation of 3D convolutional long short-term memory between the encoder and decoder of VoxelMorph, to parse the temporal patterns of anatomical changes; and (3) addition of bidirectional pathways to calculate and minimize inverse consistency errors (ICEs). Longitudinal image sets from 50 patients, including a planning CT and 6 weekly CBCTs per patient, were utilized for network training and cross-validation. The outputs were deformation vector fields for all the registration pairs. The loss function was composed of a normalized cross-correlation for image intensity similarity, a DICE for contour similarity, an ICE, and a deformation regularization term. For performance evaluation, DICE and Hausdorff distance (HD) for the manual versus predicted contours of tumor and esophagus on weekly basis were quantified and further compared with other state-of-the-art algorithms, including conventional VoxelMorph and large deformation diffeomorphic metric mapping (LDDMM). RESULTS: Visualization of the hidden states of Seq2Morph revealed distinct spatiotemporal anatomy change patterns. Quantitatively, Seq2Morph performed similarly to LDDMM, but significantly outperformed VoxelMorph as measured by GTV DICE: (0.799±0.078, 0.798±0.081, and 0.773±0.078), and 50% HD (mm): (0.80±0.57, 0.88±0.66, and 0.95±0.60). The per-patient inference of Seq2Morph took 22 s, much less than LDDMM (∼30 min). CONCLUSIONS: Seq2Morph can provide accurate and fast DIR for longitudinal image studies by exploiting spatial-temporal patterns. It closely matches the clinical workflow and has the potential to serve both online and offline ART.