The Use of Magnetic Resonance Imaging in Radiation Therapy Treatment Simulation and Planning.

Ever since its introduction as a diagnostic imaging tool the potential of magnetic resonance imaging (MRI) in radiation therapy (RT) treatment simulation and planning has been recognized. Recent technical advances have addressed many of the impediments to use of this technology and as a result have resulted in rapid and growing adoption of MRI in RT. The purpose of this article is to provide a broad review of the multiple uses of MR in the RT treatment simulation and planning process, identify several of the most used clinical scenarios in which MR is integral to the simulation and planning process, highlight existing limitations and provide multiple unmet needs thereby highlighting opportunities for the diagnostic MR imaging community to contribute and collaborate with our oncology colleagues. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 5.

Pattern of Radiotherapy Treatment in Low-Risk, Intermediate-Risk, and High-Risk Prostate Cancer Patients: Analysis of National Cancer Database.

Background: In this study, the utilization rates and survival outcomes of different radiotherapy techniques are compared in prostate cancer (PCa) patients stratified by risk group. Methods: We analyzed an extensive data set of N0, M0, non-surgical PCa patients diagnosed between 2004 and 2015 from the National Cancer Database (NCDB). Patients were grouped into six categories based on RT modality: an intensity-modulated radiation therapy (IMRT) group with brachytherapy (BT) boost, IMRT with/without IMRT boost, proton therapy, stereotactic body radiation therapy (SBRT), low-dose-rate brachytherapy (BT LDR), and high-dose-rate brachytherapy (BT HDR). Patients were also stratified by the National Comprehensive Cancer Network (NCCN) guidelines: low-risk (clinical stage T1−T2a, Gleason Score (GS) ≤ 6, and Prostate-Specific Antigen (PSA) < 10), intermediate-risk (clinical stage T2b or T2c, GS of 7, or PSA of 10−20), and high-risk (clinical stage T3−T4, or GS of 8−10, or PSA > 20). Overall survival (OS) probability was determined using a Kaplan−Meier estimator. Univariate and multivariate analyses were performed by risk group for the six treatment modalities. Results: The most utilized treatment modality for all PCa patients was IMRT (53.1%). Over the years, a steady increase in SBRT utilization was observed, whereas BT HDR usage declined. IMRT-treated patient groups exhibited relatively lower survival probability in all risk categories. A slightly better survival probability was observed for the proton therapy group. Hormonal therapy was used for a large number of patients in all risk groups. Conclusion: This study revealed that IMRT was the most common treatment modality for PCa patients. Brachytherapy, SBRT, and IMRT+BT exhibited similar survival rates, whereas proton showed slightly better overall survival across the three risk groups. However, analysis of the demographics indicates that these differences are at least in part due to selection bias.

Abdominopelvic MR to CT registration using a synthetic CT intermediate.

Accurate coregistration of computed tomography (CT) and magnetic resonance (MR) imaging can provide clinically relevant and complementary information and can serve to facilitate multiple clinical tasks including surgical and radiation treatment planning, and generating a virtual Positron Emission Tomography (PET)/MR for the sites that do not have a PET/MR system available. Despite the long-standing interest in multimodality co-registration, a robust, routine clinical solution remains an unmet need. Part of the challenge may be the use of mutual information (MI) maximization and local phase difference (LPD) as similarity metrics, which have limited robustness, efficiency, and are difficult to optimize. Accordingly, we propose registering MR to CT by mapping the MR to a synthetic CT intermediate (sCT) and further using it in a sCT-CT deformable image registration (DIR) that minimizes the sum of squared differences. The resultant deformation field of a sCT-CT DIR is applied to the MRI to register it with the CT. Twenty-five sets of abdominopelvic imaging data are used for evaluation. The proposed method is compared to standard MI- and LPD-based methods, and the multimodality DIR provided by a state of the art, commercially available FDA-cleared clinical software package. The results are compared using global similarity metrics, Modified Hausdorff Distance, and Dice Similarity Index on six structures. Further, four physicians visually assessed and scored registered images for their registration accuracy. As evident from both quantitative and qualitative evaluation, the proposed method achieved registration accuracy superior to LPD- and MI-based methods and can refine the results of the commercial package DIR when using its results as a starting point. Supported by these, this manuscript concludes the proposed registration method is more robust, accurate, and efficient than the MI- and LPD-based methods.

Effect of applicator removal from target volume for cervical cancer patients treated with Venezia high-dose-rate brachytherapy applicator.

Purpose: The volume of Venezia applicator with vaginal caps can be relatively large compared to target volumes. This study investigated the dosimetric and radiobiological effects of applicator volume removal for cervical cancer patients treated with Venezia (VZ) and tandem and split-ring (TSR) applicators used in the clinic. Material and methods: A total of 40 patients (101 plans) with stage IIA-IIIC cervical cancer were retrospectively reviewed. Thirty patients were treated with VZ and ten patients were treated with TSR. Applicators were contoured on planning CTs where target contours were involved. Applicator contours were subtracted from the target contours. External beam radiation therapy (EBRT) and brachytherapy doses were calculated in biologically equivalent doses in 2 Gy fractions (EQD2) and combined using full parameter addition for dose-volume histogram (DVH) parameters of composited dose. D90%, D50%, V100%, V150%, V200%, and tumor control probability (TCP) were evaluated and compared for targets after applicator exclusion. Results: The average volume changes in gross tumor volume (GTV), high-risk clinical target volume (HR-CTV), and intermediate-risk clinical target volume (IR-CTV) after VZ applicator exclusion were 1.4 ±1.5 cm3, 15.7 ±6.6 cm3, and 33.8 ±15.1 cm3, respectively. VZ exclusion resulted in significant changes (p < 0.05) in small volume parameters (D50%) and high-dose parameters (V150% and V200%) for HR-CTV and IR-CTV. Dosimetric impact of TSR exclusion on targets was not significant. There was no significant change in TCP after applicator exclusion. Conclusions: Venezia applicator with vaginal caps has significant impact on small volume and high-dose DVH parameters of the target. Applicator contour exclusion is recommended for dosimetric evaluation when Venezia applicator is used.

Dose uncertainty due to needle-tip localization error in prostate seed implantation.

Purpose: This study quantified the dosimetric uncertainty caused by needle-tip detection errors in ultrasound images due to bevel-tip orientation differences, with respect to the location on template grid. Material and methods: Trans-rectal ultrasound (TRUS) system with physical template grid and 18-gauge bevel-tip brachytherapy needles were used. TRUS was set at 6.5 MHz in water phantom, and measurements were taken with 50% and 100% B-mode TRUS gains. Needle-tip localization errors were then retrospectively applied back to 45 prostate seed implant plans to evaluate the important planning parameters for the prostate (D90, V100, V150, and V200), urethra (D10 and D30), and rectum (V100, D2cc, and D0.1cc), following the ABS and AAPM TG-137 guidelines. Results: The needle-tip detection errors for 50% and 100% TRUS gains were 3.7 mm (max) and 5.2 mm (max), respectively. The observed significant decrease in prostate coverage (mean D90 lower by 12.8%, and V100 lower by 3.9% for smaller prostates) after seed placements were corrected by compensating the needle-tip detection errors. Apex of the prostate was hotter, and the base was cooler. Dosimetric difference for urethral and rectal parameters were not statistically significant. Conclusions: This study revealed that the beveled needle-tip orientation could considerably impact the needle tips detection accuracy, based on which the seeds might be delivered. These errors can lead to significant dosimetric uncertainty in prostate seed implantation.

Focal Prostate Stereotactic Body Radiation Therapy With Correlative Pathological and Radiographic-Based Treatment Planning.

INTRODUCTION: Advances in multiparametric MRI (mpMRI) combining anatomic and functional imaging can accurately identify foci of adenocarcinoma within the prostate, offering the possibility of partial gland therapy. We performed tandem prospective pilot trials to investigate the feasibility of focal prostate SBRT (f-SBRT) based on correlating diagnostic mpMRI and biopsies with confirmatory pathology in treatment planning. MATERIALS AND METHODS: Patients with pathologic focal Gleason 6-7 disease and a corresponding PIRADS 4-5 lesion on mpMRI underwent targeted and comprehensive biopsies using MRI/ultrasound fusion under electromagnetic sensor navigation. After rigorous analysis for imaging biopsy concordance, five of 18 patients were eligible to proceed to f-SBRT. Chi-squared test was used for differences from expected outcomes, and concordance was estimated with binomial distribution theory and Wilson's method. RESULTS: Six patients had Gleason 6 and 12 had Gleason 3 + 4 disease (mean PSA: 5.8 ng/ml, range: 2.2-8.4). Absolute concordance was 43.8% (95% CI: 0.20, 0.64). Patterns of discordance included additional sites of ipsilateral disease, bilateral disease, and negative target. Five were upstaged to a new NCCN risk category necessitating treatment escalation. The five patients with concordant pathology completed three-fraction f-SBRT with sparing of the surrounding normal structures (including contralateral neurovascular bundle), with no reported grade 2+ toxicities and favorable PSA responses (mean: 41% decrease). CONCLUSIONS: On our pilot trials of f-SBRT planning using rigorous imaging and pathology concordance, image-guided confirmatory biopsies frequently revealed additional disease, suggesting the need for caution in partial-gland therapy. For truly focal disease, f-SBRT provided excellent dosimetry, minimal toxicity, and encouraging biochemical response. Clinical Trial Registration: www.clinicaltrials.gov, NCT02681614; NCT02163317.

Synthetic CT Generation of the Pelvis in Patients With Cervical Cancer: A Single Input Approach Using Generative Adversarial Network.

Multi-modality imaging constitutes a foundation of precision medicine, especially in oncology where reliable and rapid imaging techniques are needed in order to insure adequate diagnosis and treatment. In cervical cancer, precision oncology requires the acquisition of 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET), magnetic resonance (MR), and computed tomography (CT) images. Thereafter, images are co-registered to derive electron density attributes required for FDG-PET attenuation correction and radiation therapy planning. Nevertheless, this traditional approach is subject to MR-CT registration defects, expands treatment expenses, and increases the patient's radiation exposure. To overcome these disadvantages, we propose a new framework for cross-modality image synthesis which we apply on MR-CT image translation for cervical cancer diagnosis and treatment. The framework is based on a conditional generative adversarial network (cGAN) and illustrates a novel tactic that addresses, simplistically but efficiently, the paradigm of vanishing gradient vs. feature extraction in deep learning. Its contributions are summarized as follows: 1) The approach -termed sU-cGAN-uses, for the first time, a shallow U-Net (sU-Net) with an encoder/decoder depth of 2 as generator; 2) sU-cGAN's input is the same MR sequence that is used for radiological diagnosis, i.e. T2-weighted, Turbo Spin Echo Single Shot (TSE-SSH) MR images; 3) Despite limited training data and a single input channel approach, sU-cGAN outperforms other state of the art deep learning methods and enables accurate synthetic CT (sCT) generation. In conclusion, the suggested framework should be studied further in the clinical settings. Moreover, the sU-Net model is worth exploring in other computer vision tasks.

Transforming UTE-mDixon MR Abdomen-Pelvis Images Into CT by Jointly Leveraging Prior Knowledge and Partial Supervision.

Computed tomography (CT) provides information for diagnosis, PET attenuation correction (AC), and radiation treatment planning (RTP). Disadvantages of CT include poor soft tissue contrast and exposure to ionizing radiation. While MRI can overcome these disadvantages, it lacks the photon absorption information needed for PET AC and RTP. Thus, an intelligent transformation from MR to CT, i.e., the MR-based synthetic CT generation, is of great interest as it would support PET/MR AC and MR-only RTP. Using an MR pulse sequence that combines ultra-short echo time (UTE) and modified Dixon (mDixon), we propose a novel method for synthetic CT generation jointly leveraging prior knowledge as well as partial supervision (SCT-PK-PS for short) on large-field-of-view images that span abdomen and pelvis. Two key machine learning techniques, i.e., the knowledge-leveraged transfer fuzzy c-means (KL-TFCM) and the Laplacian support vector machine (LapSVM), are used in SCT-PK-PS. The significance of our effort is threefold: 1) Using the prior knowledge-referenced KL-TFCM clustering, SCT-PK-PS is able to group the feature data of MR images into five initial clusters of fat, soft tissue, air, bone, and bone marrow. Via these initial partitions, clusters needing to be refined are observed and for each of them a few additionally labeled examples are given as the partial supervision for the subsequent semi-supervised classification using LapSVM; 2) Partial supervision is usually insufficient for conventional algorithms to learn the insightful classifier. Instead, exploiting not only the given supervision but also the manifold structure embedded primarily in numerous unlabeled data, LapSVM is capable of training multiple desired tissue-recognizers; 3) Benefiting from the joint use of KL-TFCM and LapSVM, and assisted by the edge detector filter based feature extraction, the proposed SCT-PK-PS method features good recognition accuracy of tissue types, which ultimately facilitates the good transformation from MR images to CT images of the abdomen-pelvis. Applying the method on twenty subjects' feature data of UTE-mDixon MR images, the average score of the mean absolute prediction deviation (MAPD) of all subjects is 140.72 ± 30.60 HU which is statistically significantly better than the 241.36 ± 21.79 HU obtained using the all-water method, the 262.77 ± 42.22 HU obtained using the four-cluster-partitioning (FCP, i.e., external-air, internal-air, fat, and soft tissue) method, and the 197.05 ± 76.53 HU obtained via the conventional SVM method. These results demonstrate the effectiveness of our method for the intelligent transformation from MR to CT on the body section of abdomen-pelvis.

Final results of a dose escalation protocol of stereotactic body radiotherapy for poor surgical candidates with localized renal cell carcinoma.

BACKGROUND AND PURPOSE: We previously demonstrated the safety of doses up to 48 Gy in 4 fractions with stereotactic body radiotherapy (SBRT) in poor surgical candidates with localized renal cell carcinoma (RCC). In an additional expansion cohort, we aimed to assess the safety of further dose escalation to 48-60 Gy in 3 fractions. MATERIAL AND METHODS: Patients were required to have localized RCC and be poor surgical candidates due to medical comorbidities. Dose-limiting toxicity (DLT) was defined as acute (<180 days) grade ≥3 gastrointestinal/genitourinary toxicity by CTCAEv4. Tumor response was assessed using RECIST 1.1 criteria measurements every 6 months for 3 years and optional percutaneous biopsy. RESULTS: Groups of 4, 4, and 3 patients received 48, 54, and 60 Gy in 3 fractions, respectively from 2012 to 2016. Median follow-up was 34.3 months. Zero DLTs were observed. Acute toxicities were limited to grade 1 fatigue and nausea in 45.5% and 18.1%. Late grade 2+ and grade 3+ possibly treatment-related events occurred in 18.1% and 9.1%, respectively. Three-year local control was 90% by RECIST 1.1 criteria. Five of 5 post-treatment biopsies in the expansion cohort were positive by Hematoxylin and Eosin staining. Three of the 5 patients with positive biopsies have been observed for 1.2-3.9 years without evidence of progression. CONCLUSION: Dose escalation to 60 Gy in 3 fractions was achieved without DLTs. Favorable local control rates were observed, and the interpretation of post-SBRT biopsies remains uncertain. Further studies comparing SBRT to percutaneous ablation for poor surgical candidates with RCC are warranted.

Feasibility of improving patient's safety with in vivo dose tracking in intracavitary and interstitial HDR brachytherapy.

PURPOSE: The in vivo dosimetric monitoring in HDR brachytherapy is important for improving patient safety. However, there are very limited options available for clinical application. In this study, we present a new in vivo dose measurement system with a plastic scintillating detector (PSD) for GYN HDR brachytherapy. METHODS: An FDA approved PSD system, called OARtrac (AngioDynamics, Latham, NY), was used with various applicators for in vivo dose measurements for GYN patients. An institutional workflow was established for the clinical implementation of the dosimetric system. Action levels were proposed based on the measurement and system uncertainty for measurement deviations. From October 2018 to September 2019, a total of 75 measurements (48 fractions) were acquired from 14 patients who underwent HDR brachytherapy using either a multichannel cylinder, Venezia applicator, or Syed-Neblett template. The PSDs were placed in predetermined catheters/channels. A planning CT was acquired for treatment planning in Oncentra (Elekta, Version-4.5.2) TPS. The PSDs were contoured on the CT images, and the PSD D90% values were used as the expected doses for comparison with the measured doses. RESULTS: The mean difference from patient measurements was -0.22% ± 5.98%, with 26% being the largest deviation from the expected value (Syed case). Large deviations were observed when detectors were placed in the area where dose rates were less than 1 cGy/s. CONCLUSIONS: The establishment of clinical workflow for the in vivo dosimetry for both the intracavitary and interstitial GYN HDR brachytherapy will potentially improve the safety of the patient treatment.

Adjusting to the new reality: Evaluation of early practice pattern adaptations to the COVID-19 pandemic.

OBJECTIVE: We aim to define national practice patterns to assess current clinical practice, anticipated delays and areas of concern that potentially could lead to deviations from the normal standard of care. METHODS: Anonymous surveys were emailed to members of the Society of Gynecologic Oncology (SGO). The spread of COVID-19 and its impact on gynecologic oncology care in terms of alterations to normal treatment patterns and anticipated challenges were assessed. The Wilcoxon rank sum test was performed to determine risk factors for COVID-19 infection. RESULTS: We analyzed the responses of 331 gynecologic oncology providers. COVID-19 is present in 99.1% of surveyed communities with 99.7% reporting mitigation efforts in effect. The infection rate differs significantly between regions (p≪0.001) with the Northeast reporting the highest number of COVID-19 cases. Practice volume has dropped by 61.6% since the start of the pandemic with most cancellations being provider initiated. A majority of responders (52.8%) believed that ovarian cancer will be the most affected cancer by COVID-19. >94% of responders are proceeding with gynecologic cancer surgeries with exception of grade 1, endometrioid endometrial adenocarcinoma (36.3%). Surgical backlog (58.6%), delayed cancer diagnosis (43.2%) and re-establishing normal care with delayed patient (37.8%) were identified as the top 3 challenges after COVID-19 has abated. CONCLUSIONS: COVID-19 is widespread and has radically altered normal practice patterns. Despite COVID-19 related concerns, most gynecologic oncology care is proceeding. However, the steep decline in clinical volume shows there is a large group of patients who are not being diagnosed or are deferring care.

mDixon-Based Synthetic CT Generation for PET Attenuation Correction on Abdomen and Pelvis Jointly Using Transfer Fuzzy Clustering and Active Learning-Based Classification.

We propose a new method for generating synthetic CT images from modified Dixon (mDixon) MR data. The synthetic CT is used for attenuation correction (AC) when reconstructing PET data on abdomen and pelvis. While MR does not intrinsically contain any information about photon attenuation, AC is needed in PET/MR systems in order to be quantitatively accurate and to meet qualification standards required for use in many multi-center trials. Existing MR-based synthetic CT generation methods either use advanced MR sequences that have long acquisition time and limited clinical availability or use matching of the MR images from a newly scanned subject to images in a library of MR-CT pairs which has difficulty in accounting for the diversity of human anatomy especially in patients that have pathologies. To address these deficiencies, we present a five-phase interlinked method that uses mDixon MR acquisition and advanced machine learning methods for synthetic CT generation. Both transfer fuzzy clustering and active learning-based classification (TFC-ALC) are used. The significance of our efforts is fourfold: 1) TFC-ALC is capable of better synthetic CT generation than methods currently in use on the challenging abdomen using only common Dixon-based scanning. 2) TFC partitions MR voxels initially into the four groups regarding fat, bone, air, and soft tissue via transfer learning; ALC can learn insightful classifiers, using as few but informative labeled examples as possible to precisely distinguish bone, air, and soft tissue. Combining them, the TFC-ALC method successfully overcomes the inherent imperfection and potential uncertainty regarding the co-registration between CT and MR images. 3) Compared with existing methods, TFC-ALC features not only preferable synthetic CT generation but also improved parameter robustness, which facilitates its clinical practicability. Applying the proposed approach on mDixon-MR data from ten subjects, the average score of the mean absolute prediction deviation (MAPD) was 89.78±8.76 which is significantly better than the 133.17±9.67 obtained using the all-water (AW) method (p=4.11E-9) and the 104.97±10.03 obtained using the four-cluster-partitioning (FCP, i.e., external-air, internal-air, fat, and soft tissue) method (p=0.002). 4) Experiments in the PET SUV errors of these approaches show that TFC-ALC achieves the highest SUV accuracy and can generally reduce the SUV errors to 5% or less. These experimental results distinctively demonstrate the effectiveness of our proposed TFCALC method for the synthetic CT generation on abdomen and pelvis using only the commonly-available Dixon pulse sequence.

Appropriate Methodology for EBRT and HDR Intracavitary/Interstitial Brachytherapy Dose Composite and Clinical Plan Evaluation for Patients With Cervical Cancer.

PURPOSE: This study assessed the appropriateness of full parameter addition (FPA) methods with respect to the 3-dimensional deformable dose composite method for evaluating combined external beam radiation therapy (EBRT) and intracavitary brachytherapy (ICBT). METHODS AND MATERIALS: A total of 22 patients who received EBRT and high-dose-rate ICBT were retrospectively evaluated. Split-ring and tandem applicators were used for all patients. Additional interstitial needles were used for 5 patients to supplement the implant. Deformable image registrations were performed to deform the secondary EBRT and ICBT planning computed tomography (CT) images onto the reference CT from the third fraction of ICBT. The Dice similarity coefficient was used to evaluate the quality of deformable registration. Doses were transferred to the reference CT, scaled to the equivalent dose in 2-Gy fractions and combined to create the dose composite. Eight dose-accumulation methods were evaluated and compared. D2cc and D0.1cc for organs at risk were investigated. RESULTS: The differences in D2cc for rectum, bladder, sigmoid, and bowel between the FPA method for whole-pelvis EBRT and ICBT, calculated using an old American Brachytherapy Society worksheet (FPA_Eh + I_old) and deformable composite for EBRT with boosts and ICBT (Def_E + B + I) were -2.19 ± 1.37 Gyα/ß = 3, -0.64 ± 1.13 Gyα/ß = 3, -2.06 ± 2.71 Gyα/ß = 3, and -1.59 ± 0.89 Gyα/ß = 3, respectively. The differences in D2cc for rectum, bladder, sigmoid, and bowel between the new ABS worksheet (FPA_Eh + B + I_abs) and the Def_E + B + I method were 1.21 ± 1.22 Gy α/ß = 3, 1.93 ± 1.38 Gyα/ß = 3, 0.72 ± 1.12 Gyα/ß = 3, and 1.19 ± 1.46 Gyα/ß = 3, respectively. Differences in dose-volume histogram parameter values among Def_E + B + I and other FPA methods were not statistically significant (P > .05). CONCLUSIONS: Compared with the FPA-based method, deformable registration-based dose composites demonstrated lower OAR D2cc and D0.1cc values; however, the differences were not statistically significant. The current ABS-recommended FPA-based sheet can serve as an acceptable plan evaluation tool for clinical purposes.

UTE-mDixon-based thorax synthetic CT generation.

PURPOSE: Accurate photon attenuation assessment from MR data remains an unmet challenge in the thorax due to tissue heterogeneity and the difficulty of MR lung imaging. As thoracic tissues encompass the whole physiologic range of photon absorption, large errors can occur when using, for example, a uniform, water-equivalent or a soft-tissue-only approximation. The purpose of this study was to introduce a method for voxel-wise thoracic synthetic CT (sCT) generation from MR data attenuation correction (AC) for PET/MR or for MR-only radiation treatment planning (RTP). METHODS: Acquisition: A radial stack-of-stars combining ultra-short-echo time (UTE) and modified Dixon (mDixon) sequence was optimized for thoracic imaging. The UTE-mDixon pulse sequence collects MR signals at three TE times denoted as UTE, Echo1, and Echo2. Three-point mDixon processing was used to reconstruct water and fat images. Bias field correction was applied in order to avoid artifacts caused by inhomogeneity of the MR magnetic field. ANALYSIS: Water fraction and R2* maps were estimated using the UTE-mDixon data to produce a total of seven MR features, that is UTE, Echo1, Echo2, Dixon water, Dixon fat, Water fraction, and R2*. A feature selection process was performed to determine the optimal feature combination for the proposed automatic, 6-tissue classification for sCT generation. Fuzzy c-means was used for the automatic classification which was followed by voxel-wise attenuation coefficient assignment as a weighted sum of those of the component tissues. Performance evaluation: MR data collected using the proposed pulse sequence were compared to those using a traditional two-point Dixon approach. Image quality measures, including image resolution and uniformity, were evaluated using an MR ACR phantom. Data collected from 25 normal volunteers were used to evaluate the accuracy of the proposed method compared to the template-based approach. Notably, the template approach is applicable here, that is normal volunteers, but may not be robust enough for patients with pathologies. RESULTS: The free breathing UTE-mDixon pulse sequence yielded images with quality comparable to those using the traditional breath holding mDixon sequence. Furthermore, by capturing the signal before T2* decay, the UTE-mDixon image provided lung and bone information which the mDixon image did not. The combination of Dixon water, Dixon fat, and the Water fraction was the most robust for tissue clustering and supported the classification of six tissues, that is, air, lung, fat, soft tissue, low-density bone, and dense bone, used to generate the sCT. The thoracic sCT had a mean absolute difference from the template-based (reference) CT of less than 50 HU and which was better agreement with the reference CT than the results produced using the traditional Dixon-based data. CONCLUSION: MR thoracic acquisition and analyses have been established to automatically provide six distinguishable tissue types to generate sCT for MR-based AC of PET/MR and for MR-only RTP.

Comparison of multiparametric MRI-based and transrectal ultrasound-based preplans with intraoperative ultrasound-based planning for low dose rate interstitial prostate seed implantation.

PURPOSE: Transrectal ultrasound images are routinely acquired for low dose rate (LDR) prostate brachytherapy dosimetric preplanning (pTRUS), although diagnostic multiparametric magnetic resonance imaging (mpMRI) may serve this purpose as well. We compared the predictive abilities of TRUS vs MRI relative to intraoperative TRUS (iTRUS) to assess the role of mpMRI in brachytherapy preplanning. MATERIALS AND METHODS: Retrospective analysis was performed on 32 patients who underwent iTRUS-guided prostate LDR brachytherapy as either mono- or combination therapy. 56.3% had pTRUS-only volume studies and 43.7% had both 3T-mpMRI and pTRUS preplanning. MRI was used for preplanning and its image fusion with iTRUS was also used for intraoperative guidance of seed placement. Differences in gland volume, seed number, and activity and procedure time were examined, as well as the identification of lesions suspicious for tumor foci. Pearson correlation coefficient and Fisher's Z test were used to estimate associations between continuous measures. RESULTS: There was good correlation of planning volumes between iTRUS and either pTRUS or MRI (r = 0.89, r = 0.77), not impacted by the addition of hormonal therapy (P = 0.65, P = 0.33). Both consistently predicted intraoperative seed number (r = 0.87, r = 0.86). MRI/TRUS fusion did not significantly increase surgical or anesthesia time (P = 0.10, P = 0.46). mpMRI revealed suspicious focal lesions in 11 of 14 cases not visible on pTRUS, that when correlated with histopathology, were incorporated into the plan. CONCLUSIONS: Relative to pTRUS, MRI yielded reliable preplanning measures, supporting the role of MRI-only LDR treatment planning. mpMRI carries numerous diagnostic, staging and preplanning advantages that facilitate better patient selection and delivery of novel dose escalation and targeted therapy, with no additional surgical or anesthesia time. Prospective studies assessing its impact on treatment planning and delivery can serve to establish mpMRI as the standard of care in LDR prostate brachytherapy planning.

Abdominal, multi-organ, auto-contouring method for online adaptive magnetic resonance guided radiotherapy: An intelligent, multi-level fusion approach.

BACKGROUND: Manual contouring remains the most laborious task in radiation therapy planning and is a major barrier to implementing routine Magnetic Resonance Imaging (MRI) Guided Adaptive Radiation Therapy (MR-ART). To address this, we propose a new artificial intelligence-based, auto-contouring method for abdominal MR-ART modeled after human brain cognition for manual contouring. METHODS/MATERIALS: Our algorithm is based on two types of information flow, i.e. top-down and bottom-up. Top-down information is derived from simulation MR images. It grossly delineates the object based on its high-level information class by transferring the initial planning contours onto daily images. Bottom-up information is derived from pixel data by a supervised, self-adaptive, active learning based support vector machine. It uses low-level pixel features, such as intensity and location, to distinguish each target boundary from the background. The final result is obtained by fusing top-down and bottom-up outputs in a unified framework through artificial intelligence fusion. For evaluation, we used a dataset of four patients with locally advanced pancreatic cancer treated with MR-ART using a clinical system (MRIdian, Viewray, Oakwood Village, OH, USA). Each set included the simulation MRI and onboard T1 MRI corresponding to a randomly selected treatment session. Each MRI had 144 axial slices of 266 × 266 pixels. Using the Dice Similarity Index (DSI) and the Hausdorff Distance Index (HDI), we compared the manual and automated contours for the liver, left and right kidneys, and the spinal cord. RESULTS: The average auto-segmentation time was two minutes per set. Visually, the automatic and manual contours were similar. Fused results achieved better accuracy than either the bottom-up or top-down method alone. The DSI values were above 0.86. The spinal canal contours yielded a low HDI value. CONCLUSION: With a DSI significantly higher than the usually reported 0.7, our novel algorithm yields a high segmentation accuracy. To our knowledge, this is the first fully automated contouring approach using T1 MRI images for adaptive radiotherapy.

Machine learning-based dual-energy CT parametric mapping.

The aim is to develop and evaluate machine learning methods for generating quantitative parametric maps of effective atomic number (Zeff), relative electron density (ρ e), mean excitation energy (I x ), and relative stopping power (RSP) from clinical dual-energy CT data. The maps could be used for material identification and radiation dose calculation. Machine learning methods of historical centroid (HC), random forest (RF), and artificial neural networks (ANN) were used to learn the relationship between dual-energy CT input data and ideal output parametric maps calculated for phantoms from the known compositions of 13 tissue substitutes. After training and model selection steps, the machine learning predictors were used to generate parametric maps from independent phantom and patient input data. Precision and accuracy were evaluated using the ideal maps. This process was repeated for a range of exposure doses, and performance was compared to that of the clinically-used dual-energy, physics-based method which served as the reference. The machine learning methods generated more accurate and precise parametric maps than those obtained using the reference method. Their performance advantage was particularly evident when using data from the lowest exposure, one-fifth of a typical clinical abdomen CT acquisition. The RF method achieved the greatest accuracy. In comparison, the ANN method was only 1% less accurate but had much better computational efficiency than RF, being able to produce parametric maps in 15 s. Machine learning methods outperformed the reference method in terms of accuracy and noise tolerance when generating parametric maps, encouraging further exploration of the techniques. Among the methods we evaluated, ANN is the most suitable for clinical use due to its combination of accuracy, excellent low-noise performance, and computational efficiency.

Reduction of seed motion using a bio-absorbable polymer coating during permanent prostate brachytherapy using a mick applicator technique.

PURPOSE: The addition of a braided bio-absorbable vicryl coating to the surface of radioactive seeds used for low dose rate (LDR) prostate brachytherapy is intended to reduce the incidence of seed movement and migration. Here, we present a single-institution study of the frequency and severity of seed slippage (initial seed movement) of coated seeds in comparison with uncoated seeds. METHODS: Forty-seven patients received permanent prostate brachytherapy, with either coated (n = 26) or uncoated (n = 21) seeds. AgX100 125 I seeds, coated or uncoated, and uncoated Model 200 103 Pd seeds were used. During the ultrasound-guided implantation procedure, each implanted seed was categorized as having remained in the implanted position after being placed, having moved slightly, or having left the ultrasound field of view. RESULTS: 3.1% of the coated seeds (AgX100 seeds, n = 70) and 6.9% of the uncoated seeds (AgX100 and Model 200 seeds, n = 128) were observed to have moved at least 2 mm from their initial implant positions, respectively. The difference in incidence of this movement was 54.4% (P = 0.0026). Coated AgX100 seeds demonstrated a 66.7% lower rate of movement of at least 2 mm than that for uncoated AgX100 seeds (P = 0.038), and a 49.0% lower rate than that for Model 200 seeds (P = 0.021). While no significant differences were noted in prescription dose coverage of the prostate or the studied dosimetric parameters for the organs at risk between the coated and uncoated seeds (P > 0.05) in the CT-based Day-0 postoperative plans, the limited sample size and differences in energies between the 125 I and 103 Pd seeds make further analysis of postoperative dosimetric coverage difficult without additional data directly comparing the coated and uncoated 125 I seeds. CONCLUSION: When the vicryl coating is used, seeds have a significantly lower propensity to slip from their initial implant locations. This may help maintain dosimetric integrity, warranting further study of postoperative dosimetry.

Comparative analysis for renal stereotactic body radiotherapy using Cyberknife, VMAT and proton therapy based treatment planning.

PURPOSE: We conducted this dosimetric analysis to evaluate the feasibility of a multi-center stereotactic body radiation therapy (SBRT) trial for renal cell carcinoma (RCC) using different SBRT platforms. MATERIALS/METHODS: The computed tomography (CT) simulation images of 10 patients with unilateral RCC previously treated on a Phase 1 trial at Institution 1 were anonymized and shared with Institution 2 after IRB approval. Treatment planning was generated through five different platforms aiming a total dose of 48 Gy in three fractions. These platforms included: Cyberknife and volumetric modulated arc therapy (VMAT) at institution 1, and Cyberknife, VMAT, and pencil beam scanning (PBS) Proton Therapy at institution 2. Dose constraints were based on the Phase 1 approved trial. RESULTS: Compared to Cyberknife, VMAT and PBS plans provided overall an equivalent or superior coverage to the target volume, while limiting dose to the remaining kidney, contralateral kidney, liver, spinal cord, and bowel. CONCLUSION: This dosimetric study supports the feasibility of a multi-center trial for renal SBRT using PBS, VMAT and Cyberknife.

3T multiparametric MRI-guided high-dose-rate combined intracavitary and interstitial adaptive brachytherapy for the treatment of cervical cancer with a novel split-ring applicator.

PURPOSE: To evaluate the role of 3T-MRI-guided adaptive high-dose-rate (HDR) combined intracavitary and interstitial brachytherapy for cervical cancer using a novel intracavitary split-ring (ICSR) applicator adapter. METHODS AND MATERIALS: We retrospectively reviewed all HDR brachytherapy cases from 2013 to 2015 using an ICSR applicator. Initial optimization was performed using 3T multiparametric MRI (mpMRI) series with an applicator in place. The mpMRI series were discretionarily acquired before subsequent fractions for possible target adaptation. When necessary, interstitial needles (ISNs) were inserted through a novel ICSR adapter or freehand. Dosimetric parameters, clinical outcomes, and toxicities were compared between groups. RESULTS: Seventeen patients were included, with a mean followup of 32 months. An mpMRI series preceded each initial fraction and 52.9% of patients underwent ≥1 additional pretreatment mpMRI. Among these subsequent fractions, the high-risk clinical target volume was reduced in 80% vs. 41% without pretreatment mpMRI. Five patients had ISN placement (seven insertions) to improve extracervical target coverage. Mean D90 (Gy) per fraction to the high-risk clinical target volume and intermediate-risk clinical target volume with and without an ISN were 7.51 ± 1.07 vs. 6.14 ± 0.52 (p = 0.028) and 6.35 ± 0.75 vs. 5.21 ± 0.49 (p = 0.007), respectively. Mean fractional D2cc (Gy) for organs at risk was comparable. No Grades 3-4 toxicity was reported. Disease-free survival and local control for the ICSR-ISN and ICSR-alone groups were 29.8 months/80.0% and 31.2 months/83.3%, respectively. CONCLUSIONS: The mpMRI acquisition with ICSR applicator in place immediately before HDR brachytherapy for cervical cancer guided successful adaptive treatment optimization and delivery. Our initial experience with a novel interstitial adapter for the split-ring applicator demonstrated excellent target coverage without compromising organs at risk, resulting in good local control and disease-free survival.