Ablative margin quantification using deformable versus rigid image registration in colorectal liver metastasis thermal ablation: a retrospective single-center study.

PURPOSE: To investigate the correlation of minimal ablative margin (MAM) quantification using biomechanical deformable (DIR) versus intensity-based rigid image registration (RIR) with local outcomes following colorectal liver metastasis (CLM) thermal ablation. METHODS: This retrospective single-institution study included consecutive patients undergoing thermal ablation between May 2016 and October 2021. Patients who did not have intraprocedural pre- and post-ablation contrast-enhanced CT images for MAM quantification or follow-up period less than 1 year without residual tumor or local tumor progression (LTP) were excluded. DIR and RIR methods were used to quantify the MAM. The registration accuracy was compared using Dice similarity coefficient (DSC). Area under the receiver operating characteristic curve (AUC) was used to test MAM in predicting local tumor outcomes. RESULTS: A total of 72 patients (mean age 57; 44 men) with 139 tumors (mean diameter 1.5 cm ± 0.8 (SD)) were included. During a median follow-up of 29.4 months, there was one residual unablated tumor and the LTP rate was 17% (24/138). The ranges of DSC were 0.96-0.98 and 0.67-0.98 for DIR and RIR, respectively (p < 0.001). When using DIR, 27 (19%) tumors were partially or totally registered outside the liver, compared to 46 (33%) with RIR. Using DIR versus RIR, the corresponding median MAM was 4.7 mm versus 4.0 mm, respectively (p = 0.5). The AUC in predicting residual tumor and 1-year LTP for DIR versus RIR was 0.89 versus 0.72, respectively (p < 0.001). CONCLUSION: Ablative margin quantified on intra-procedural CT imaging using DIR method outperformed RIR for predicting local outcomes of CLM thermal ablation. CLINICAL RELEVANCE STATEMENT: The study supports the role of biomechanical deformable image registration as the preferred image registration method over rigid image registration for quantifying minimal ablative margins using intraprocedural contrast-enhanced CT images. KEY POINTS: • Accurate and reproducible image registration is a prerequisite for clinical application of image-based ablation confirmation methods. • When compared to intensity-based rigid image registration, biomechanical deformable image registration for minimal ablative margin quantification was more accurate for liver registration using intraprocedural contrast-enhanced CT images. • Biomechanical deformable image registration outperformed intensity-based rigid image registration for predicting local tumor outcomes following colorectal liver metastasis thermal ablation.

Targeted exome-based predictors of patterns of progression of colorectal liver metastasis after percutaneous thermal ablation.

BACKGROUND: Percutaneous thermal ablation is a curative-intent locoregional therapy (LRT) for selected patients with unresectable colorectal liver metastasis (CLM). Several factors have been identified that contribute to local tumour control after ablation. However, factors contributing to disease progression outside the ablation zone after ablation are poorly understood. METHODS: In this retrospective study, using next-generation sequencing, we identified genetic biomarkers associated with different patterns of progression following thermal ablation of CLM. RESULTS: A total of 191 ablation naïve patients between January 2011 and March 2020 were included in the analysis, and 101 had genomic profiling available. Alterations in the TGFß pathway were associated with increased risk of development of new intrahepatic tumours (hazard ratio [HR], 2.75, 95% confidence interval [95% CI] 1.39-5.45, P = 0.004); and alterations in the Wnt pathway were associated with increased probability of receiving salvage LRT for any intrahepatic progression (HR, 5.8, 95% CI 1.94-19.5, P = 0.003). CONCLUSIONS: Our findings indicate that genomic alterations in cancer-related signalling pathways can predict different progression patterns and the likelihood of receiving salvage LRT following percutaneous thermal ablation of CLM.

Imaging in Interventional Radiology: 2043 and Beyond.

Since its inception in the early 20th century, interventional radiology (IR) has evolved tremendously and is now a distinct clinical discipline with its own training pathway. The arsenal of modalities at work in IR includes x-ray radiography and fluoroscopy, CT, MRI, US, and molecular and multimodality imaging within hybrid interventional environments. This article briefly reviews the major developments in imaging technology in IR over the past century, summarizes technologies now representative of the standard of care, and reflects on emerging advances in imaging technology that could shape the field in the century ahead. The role of emergent imaging technologies in enabling high-precision interventions is also briefly reviewed, including image-guided ablative therapies.

Ablative Margins of Colorectal Liver Metastases Using Deformable CT Image Registration and Autosegmentation.

Background Confirming ablation completeness with sufficient ablative margin is critical for local tumor control following colorectal liver metastasis (CLM) ablation. An image-based confirmation method considering patient- and ablation-related biomechanical deformation is an unmet need. Purpose To evaluate a biomechanical deformable image registration (DIR) method for three-dimensional (3D) minimal ablative margin (MAM) quantification and the association with local disease progression following CT-guided CLM ablation. Materials and Methods This single-institution retrospective study included patients with CLM treated with CT-guided microwave or radiofrequency ablation from October 2015 to March 2020. A biomechanical DIR method with AI-based autosegmentation of liver, tumors, and ablation zones on CT images was applied for MAM quantification retrospectively. The per-tumor incidence of local disease progression was defined as residual tumor or local tumor progression. Factors associated with local disease progression were evaluated using the multivariable Fine-Gray subdistribution hazard model. Local disease progression sites were spatially localized with the tissue at risk for tumor progression (<5 mm) using a 3D ray-tracing method. Results Overall, 213 ablated CLMs (mean diameter, 1.4 cm) in 124 consecutive patients (mean age, 57 years ± 12 [SD]; 69 women) were evaluated, with a median follow-up interval of 25.8 months. In ablated CLMs, an MAM of 0 mm was depicted in 14.6% (31 of 213), from greater than 0 to less than 5 mm in 40.4% (86 of 213), and greater than or equal to 5 mm in 45.1% (96 of 213). The 2-year cumulative incidence of local disease progression was 72% for 0 mm and 12% for greater than 0 to less than 5 mm. No local disease progression was observed for an MAM greater than or equal to 5 mm. Among 117 tumors with an MAM less than 5 mm, 36 had local disease progression and 30 were spatially localized within the tissue at risk for tumor progression. On multivariable analysis, an MAM of 0 mm (subdistribution hazard ratio, 23.3; 95% CI: 10.8, 50.5; P < .001) was independently associated with local disease progression. Conclusion Biomechanical deformable image registration and autosegmentation on CT images enabled identification and spatial localization of colorectal liver metastases at risk for local disease progression following ablation, with a minimal ablative margin greater than or equal to 5 mm as the optimal end point. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Sofocleous in this issue.

Bayesian parametric models for survival prediction in medical applications.

BACKGROUND: Evidence-based treatment decisions in medicine are made founded on population-level evidence obtained during randomized clinical trials. In an era of personalized medicine, these decisions should be based on the predicted benefit of a treatment on a patient-level. Survival prediction models play a central role as they incorporate the time-to-event and censoring. In medical applications uncertainty is critical especially when treatments differ in their side effect profiles or costs. Additionally, models must be adapted to local populations without diminishing performance and often without the original training data available due to privacy concern. Both points are supported by Bayesian models-yet they are rarely used. The aim of this work is to evaluate Bayesian parametric survival models on public datasets including cardiology, infectious diseases, and oncology. MATERIALS AND METHODS: Bayesian parametric survival models based on the Exponential and Weibull distribution were implemented as a Python package. A linear combination and a neural network were used for predicting the parameters of the distributions. A superiority design was used to assess whether Bayesian models are better than commonly used models such as Cox Proportional Hazards, Random Survival Forest, and Neural Network-based Cox Proportional Hazards. In a secondary analysis, overfitting was compared between these models. An equivalence design was used to assess whether the prediction performance of Bayesian models after model updating using Bayes rule is equivalent to retraining on the full dataset. RESULTS: In this study, we found that Bayesian parametric survival models perform as good as state-of-the art models while requiring less hyperparameters to be tuned and providing a measure of the uncertainty of the predictions. In addition, these models were less prone to overfitting. Furthermore, we show that updating these models using Bayes rule yields equivalent performance compared to models trained on combined original and new datasets. CONCLUSIONS: Bayesian parametric survival models are non-inferior to conventional survival models while requiring less hyperparameter tuning, being less prone to overfitting, and allowing model updating using Bayes rule. Further, the Bayesian models provide a measure of the uncertainty on the statistical inference, and, in particular, on the prediction.

Contemporary evidence on colorectal liver metastases ablation: toward a paradigm shift in locoregional treatment.

Image-guided percutaneous ablation techniques represent an attractive local therapy for the treatment of colorectal liver metastases (CLM) given its low risk of severe complications, which allows for early initiation of adjuvant therapies and spare functional liver parenchyma, allowing repeated treatments at the time of recurrence. However, ablation does not consistently achieve similar oncological outcomes to surgery, with the latter being currently considered the first-line local treatment modality in international guidelines. Recent application of computer-assisted ablation planning, guidance, and intra-procedural response assessment has improved percutaneous ablation outcomes. In addition, the evolving understanding of tumor molecular profiling has brought to light several biological factors associated with oncological outcomes following local therapies. The standardization of ablation procedures, the understanding of previously unknown biological factors affecting ablation outcomes, and the evidence by ongoing prospective clinical trials are poised to change the current perspective and indications on the use of ablation for CLM.

Automatic contouring QA method using a deep learning-based autocontouring system.

PURPOSE: To determine the most accurate similarity metric when using an independent system to verify automatically generated contours. METHODS: A reference autocontouring system (primary system to create clinical contours) and a verification autocontouring system (secondary system to test the primary contours) were used to generate a pair of 6 female pelvic structures (UteroCervix [uterus + cervix], CTVn [nodal clinical target volume (CTV)], PAN [para-aortic lymph nodes], bladder, rectum, and kidneys) on 49 CT scans from our institution and 38 from other institutions. Additionally, clinically acceptable and unacceptable contours were manually generated using the 49 internal CT scans. Eleven similarity metrics (volumetric Dice similarity coefficient (DSC), Hausdorff distance, 95% Hausdorff distance, mean surface distance, and surface DSC with tolerances from 1 to 10 mm) were calculated between the reference and the verification autocontours, and between the manually generated and the verification autocontours. A support vector machine (SVM) was used to determine the threshold that separates clinically acceptable and unacceptable contours for each structure. The 11 metrics were investigated individually and in certain combinations. Linear, radial basis function, sigmoid, and polynomial kernels were tested using the combinations of metrics as inputs for the SVM. RESULTS: The highest contouring error detection accuracies were 0.91 for the UteroCervix, 0.90 for the CTVn, 0.89 for the PAN, 0.92 for the bladder, 0.95 for the rectum, and 0.97 for the kidneys and were achieved using surface DSCs with a thickness of 1, 2, or 3 mm. The linear kernel was the most accurate and consistent when a combination of metrics was used as an input for the SVM. However, the best model accuracy from the combinations of metrics was not better than the best model accuracy from a surface DSC as an input. CONCLUSIONS: We distinguished clinically acceptable contours from clinically unacceptable contours with an accuracy higher than 0.9 for the targets and critical structures in patients with cervical cancer; the most accurate similarity metric was surface DSC with a thickness of 1, 2, or 3 mm.

MRI evaluation of normal tissue deformation and breathing motion under an abdominal compression device.

PURPOSE: Abdominal compression can minimize breathing motion in stereotactic radiotherapy, though it may impact the positioning of dose-limiting normal tissues. This study quantified the reproducibility of abdominal normal tissues and respiratory motion with the use of an abdominal compression device using MR imaging. METHODS: Twenty healthy volunteers had repeat MR over 3 days under an abdominal compression plate device. Normal tissues were delineated on daily axial T2-weighted MR and compared on days 2 and 3 relative to day 1, after adjusting for baseline shifts relative to bony anatomy. Inter-fraction organ deformation was computed using deformable registration of axial T2 images. Deformation > 5 mm was assumed to be clinically relevant. Inter-fraction respiratory amplitude changes and intra-fraction baseline drifts during imaging were quantified on daily orthogonal cine-MR (70 s each), and changes > 3 mm were assumed to be relevant. RESULTS: On axial MR, the mean inter-fraction normal tissue deformation was > 5 mm for all organs (range 5.1-13.4 mm). Inter-fraction compression device misplacements > 5 mm and changes in stomach volume > 50% occurred at a rate of 93% and 38%, respectively, in one or more directions and were associated with larger adjacent organ deformation, in particular for the duodenum. On cine-MR, inter-fraction amplitude changes > 3 mm on day 2 and 3 relative to day 1 occurred at a rate of < 12.5% (mean superior-inferior change was 1.6 mm). Intra-fraction baseline drifts > 3 mm during any cine-MR acquisition occurred at a rate of 23% (mean superior-inferior changes was 2.4 mm). CONCLUSIONS: Respiratory motion under abdominal compression is reproducible in most subjects within 3 mm. However, inter-fraction deformations greater than 5 mm in normal tissues were common and larger than inter- and intra-fraction respiratory changes. Deformations were driven mostly by variable stomach contents and device positioning. The magnitude of this motion may impact normal tissue dosimetry during stereotactic radiotherapy.

MR-guided prostate biopsy for planning of focal salvage after radiation therapy.

PURPOSE: To determine if the integration of diagnostic magnetic resonance (MR) imaging and MR-guided biopsy would improve target delineation for focal salvage therapy in men with prostate cancer. MATERIALS AND METHODS: Between September 2008 and March 2011, 30 men with biochemical failure after radiation therapy for prostate cancer provided written informed consent and were enrolled in a prospective clinical trial approved by the institutional research ethics board. An integrated diagnostic MR imaging and interventional biopsy procedure was performed with a 1.5-T MR imager by using a prototype table and stereotactic transperineal template. Multiparametric MR imaging (T2-weighted, dynamic contrast material-enhanced, and diffusion-weighted sequences) was followed by targeted biopsy of suspicious regions and systematic sextant sampling. Biopsy needle locations were imaged and registered to diagnostic images. Two observers blinded to clinical data and the results of prior imaging studies delineated tumor boundaries. Area under the receiver operating characteristic curve (Az) was calculated based on generalized linear models by using biopsy as the reference standard to distinguish benign from malignant lesions. RESULTS: Twenty-eight patients were analyzed. Most patients (n = 22) had local recurrence, with 82% (18 of 22) having unifocal disease. When multiparametric volumes from two observers were combined, it increased the apparent overall tumor volume by 30%; however, volumes remained small (mean, 2.9 mL; range, 0.5-8.3 mL). Tumor target boundaries differed between T2-weighted, dynamic contrast-enhanced, and diffusion-weighted sequences (mean Dice coefficient, 0.13-0.35). Diagnostic accuracy in the identification of tumors improved with a multiparametric approach versus a strictly T2-weighted or dynamic contrast-enhanced approach through an improvement in sensitivity (observer 1, 0.65 vs 0.35 and 0.44, respectively; observer 2, 0.82 vs 0.64 and 0.53, respectively; P < .05) and improved further with a 5-mm expansion margin (Az = 0.85 vs 0.91 for observer 2). After excluding three patients with fewer than six informative biopsy cores and six patients with inadequately stained margins, MR-guided biopsy enabled more accurate delineation of the tumor target volume be means of exclusion of false-positive results in 26% (five of 19 patients), false-negative results in 11% (two of 19 patients) and by guiding extension of tumor boundaries in 16% (three of 19 patients). CONCLUSION: The integration of guided biopsy with diagnostic MR imaging is feasible and alters delineation of the tumor target boundary in a substantial proportion of patients considering focal salvage.

Incidental Ring-hyperenhancing Liver Micronodules at CT Hepatic Arteriography-guided Percutaneous Thermal Ablation of Colorectal Liver Metastases.

CT during hepatic arteriography (CTHA) is a highly sensitive imaging method for detecting colorectal liver metastases (CLMs), which supports its use during percutaneous thermal liver ablation. In contrast to its high sensitivity, its specificity for incidental small CLMs not detected at preablation cross-sectional imaging is believed to be low given the absence of specific imaging signatures and the common presence of pseudolesions. In this retrospective study of 22 patients (mean age, 55 years ± 10.6 [SD]; 63.6% male, 36.4% female) with CLMs undergoing CTHA-guided microwave percutaneous thermal ablation between November 2017 and October 2022, the authors provided a definition of incidental ring-hyperenhancing liver micronodules (RHLMs) and investigated whether there is a correlation of RHLMs with histologic analysis or intrahepatic tumor progression at imaging follow-up after applying a biomechanical deformable image registration method. The analysis revealed 25 incidental RHLMs in 41.7% (10 of 24) of the CTHA images from the respective guided ablation sessions. Of those, four RHLMs were ablated. Among the remaining 21 RHLMs, 71.4% (15 of 21) were confirmed to be CLM with either histology (n = 3) or imaging follow-up (n = 12). The remaining 28.6% (six of 21) of RHLMs were not observed at follow-up imaging. This suggests that RHLMs at CTHA may be an early indicator of incidental small CLMs. Keywords: Colorectal Neoplasms, Liver, Angiography, CT, Incidental Findings, Ablation Supplemental material is available for this article. © RSNA, 2024.

Using Patient-Specific 3D Modeling and Simulations to Optimize Microwave Ablation Therapy for Liver Cancer.

Microwave ablation (MWA) of liver tumors presents challenges like under- and over-ablation, potentially leading to inadequate tumor destruction and damage to healthy tissue. This study aims to develop personalized three-dimensional (3D) models to simulate MWA for liver tumors, incorporating patient-specific characteristics. The primary objective is to validate the predicted ablation zones compared to clinical outcomes, offering insights into MWA before therapy to facilitate accurate treatment planning. Contrast-enhanced CT images from three patients were used to create 3D models. The simulations used coupled electromagnetic wave propagation and bioheat transfer to estimate the temperature distribution, predicting tumor destruction and ablation margins. The findings indicate that prolonged ablation does not significantly improve tumor destruction once an adequate margin is achieved, although it increases tissue damage. There was a substantial overlap between the clinical ablation zones and the predicted ablation zones. For patient 1, the Dice score was 0.73, indicating high accuracy, with a sensitivity of 0.72 and a specificity of 0.76. For patient 2, the Dice score was 0.86, with a sensitivity of 0.79 and a specificity of 0.96. For patient 3, the Dice score was 0.8, with a sensitivity of 0.85 and a specificity of 0.74. Patient-specific 3D models demonstrate potential in accurately predicting ablation zones and optimizing MWA treatment strategies.

Intraprocedural Versus Initial Follow-up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?

OBJECTIVES: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation. MATERIALS AND METHODS: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation CT and ablation zones on intraprocedural postablation and initial follow-up CT. Prognostic value of MAM to predict LTP was tested using area under the curve and competing-risk regression model. RESULTS: A total of 68 patients (mean age ± standard deviation, 57 ± 12 years; 43 men) with 133 CLMs were included. During a median follow-up of 30.3 months, LTP rate was 17% (22/133). The median volume of ablation zone was 27 mL and 16 mL segmented on intraprocedural and initial follow-up CT, respectively ( P < 0.001), with corresponding median MAM of 4.7 mm and 0 mm, respectively ( P < 0.001). The area under the curve was higher for MAM quantified on intraprocedural CT (0.89; 95% confidence interval [CI], 0.83-0.94) compared with initial follow-up CT (0.66; 95% CI, 0.54-0.76) in predicting 1-year LTP ( P < 0.001). An MAM of 0 mm on intraprocedural CT was an independent predictor of LTP with a subdistribution hazards ratio of 11.9 (95% CI, 4.9-28.9; P < 0.001), compared with 2.4 (95% CI, 0.9-6.0; P = 0.07) on initial follow-up CT. CONCLUSIONS: Ablative margin quantified on intraprocedural CT significantly outperformed initial follow-up CT in predicting LTP and should be used for ablation endpoint assessment.

A joint ESTRO and AAPM guideline for development, clinical validation and reporting of artificial intelligence models in radiation therapy.

BACKGROUND AND PURPOSE: Artificial Intelligence (AI) models in radiation therapy are being developed with increasing pace. Despite this, the radiation therapy community has not widely adopted these models in clinical practice. A cohesive guideline on how to develop, report and clinically validate AI algorithms might help bridge this gap. METHODS AND MATERIALS: A Delphi process with all co-authors was followed to determine which topics should be addressed in this comprehensive guideline. Separate sections of the guideline, including Statements, were written by subgroups of the authors and discussed with the whole group at several meetings. Statements were formulated and scored as highly recommended or recommended. RESULTS: The following topics were found most relevant: Decision making, image analysis, volume segmentation, treatment planning, patient specific quality assurance of treatment delivery, adaptive treatment, outcome prediction, training, validation and testing of AI model parameters, model availability for others to verify, model quality assurance/updates and upgrades, ethics. Key references were given together with an outlook on current hurdles and possibilities to overcome these. 19 Statements were formulated. CONCLUSION: A cohesive guideline has been written which addresses main topics regarding AI in radiation therapy. It will help to guide development, as well as transparent and consistent reporting and validation of new AI tools and facilitate adoption.

Fully automated deep learning based auto-contouring of liver segments and spleen on contrast-enhanced CT images.

Manual delineation of liver segments on computed tomography (CT) images for primary/secondary liver cancer (LC) patients is time-intensive and prone to inter/intra-observer variability. Therefore, we developed a deep-learning-based model to auto-contour liver segments and spleen on contrast-enhanced CT (CECT) images. We trained two models using 3d patch-based attention U-Net ([Formula: see text] and 3d full resolution of nnU-Net ([Formula: see text] to determine the best architecture ([Formula: see text]. BA was used with vessels ([Formula: see text] and spleen ([Formula: see text] to assess the impact on segment contouring. Models were trained, validated, and tested on 160 ([Formula: see text]), 40 ([Formula: see text]), 33 ([Formula: see text]), 25 (CCH) and 20 (CPVE) CECT of LC patients. [Formula: see text] outperformed [Formula: see text] across all segments with median differences in Dice similarity coefficients (DSC) ranging 0.03-0.05 (p < 0.05). [Formula: see text], and [Formula: see text] were not statistically different (p > 0.05), however, both were slightly better than [Formula: see text] by DSC up to 0.02. The final model, [Formula: see text], showed a mean DSC of 0.89, 0.82, 0.88, 0.87, 0.96, and 0.95 for segments 1, 2, 3, 4, 5-8, and spleen, respectively on entire test sets. Qualitatively, more than 85% of cases showed a Likert score [Formula: see text] 3 on test sets. Our final model provides clinically acceptable contours of liver segments and spleen which are usable in treatment planning.

Investigation of autosegmentation techniques on T2-weighted MRI for off-line dose reconstruction in MR-linac workflow for head and neck cancers.

BACKGROUND: In order to accurately accumulate delivered dose for head and neck cancer patients treated with the Adapt to Position workflow on the 1.5T magnetic resonance imaging (MRI)-linear accelerator (MR-linac), the low-resolution T2-weighted MRIs used for daily setup must be segmented to enable reconstruction of the delivered dose at each fraction. PURPOSE: In this pilot study, we evaluate various autosegmentation methods for head and neck organs at risk (OARs) on on-board setup MRIs from the MR-linac for off-line reconstruction of delivered dose. METHODS: Seven OARs (parotid glands, submandibular glands, mandible, spinal cord, and brainstem) were contoured on 43 images by seven observers each. Ground truth contours were generated using a simultaneous truth and performance level estimation (STAPLE) algorithm. Twenty total autosegmentation methods were evaluated in ADMIRE: 1-9) atlas-based autosegmentation using a population atlas library (PAL) of 5/10/15 patients with STAPLE, patch fusion (PF), random forest (RF) for label fusion; 10-19) autosegmentation using images from a patient's 1-4 prior fractions (individualized patient prior [IPP]) using STAPLE/PF/RF; 20) deep learning (DL) (3D ResUNet trained on 43 ground truth structure sets plus 45 contoured by one observer). Execution time was measured for each method. Autosegmented structures were compared to ground truth structures using the Dice similarity coefficient, mean surface distance (MSD), Hausdorff distance (HD), and Jaccard index (JI). For each metric and OAR, performance was compared to the inter-observer variability using Dunn's test with control. Methods were compared pairwise using the Steel-Dwass test for each metric pooled across all OARs. Further dosimetric analysis was performed on three high-performing autosegmentation methods (DL, IPP with RF and 4 fractions [IPP_RF_4], IPP with 1 fraction [IPP_1]), and one low-performing (PAL with STAPLE and 5 atlases [PAL_ST_5]). For five patients, delivered doses from clinical plans were recalculated on setup images with ground truth and autosegmented structure sets. Differences in maximum and mean dose to each structure between the ground truth and autosegmented structures were calculated and correlated with geometric metrics. RESULTS: DL and IPP methods performed best overall, all significantly outperforming inter-observer variability and with no significant difference between methods in pairwise comparison. PAL methods performed worst overall; most were not significantly different from the inter-observer variability or from each other. DL was the fastest method (33 s per case) and PAL methods the slowest (3.7-13.8 min per case). Execution time increased with a number of prior fractions/atlases for IPP and PAL. For DL, IPP_1, and IPP_RF_4, the majority (95%) of dose differences were within ± 250 cGy from ground truth, but outlier differences up to 785 cGy occurred. Dose differences were much higher for PAL_ST_5, with outlier differences up to 1920 cGy. Dose differences showed weak but significant correlations with all geometric metrics (R2 between 0.030 and 0.314). CONCLUSIONS: The autosegmentation methods offering the best combination of performance and execution time are DL and IPP_1. Dose reconstruction on on-board T2-weighted MRIs is feasible with autosegmented structures with minimal dosimetric variation from ground truth, but contours should be visually inspected prior to dose reconstruction in an end-to-end dose accumulation workflow.

Use of Contrast Media During CT-guided Thermal Ablation of Colorectal Liver Metastasis for Procedure Planning is Associated with Improved Immediate Outcomes.

PURPOSE: The aim of this study was to analyze the impact of using intra-procedural pre-ablation contrast-enhanced CT prior to percutaneous thermal ablation (pre-ablation CECT) of colorectal liver metastases (CLM) on local outcomes. MATERIALS AND METHODS: This retrospective analysis of a prospectively collected liver ablation registry included 144 consecutive patients (median age 57 years IQR [49, 65], 60% men) who underwent 173 CT-guided ablation sessions for 250 CLM between October 2015 and March 2020. In addition to oncologic outcomes, technical success was retrospectively evaluated using a biomechanical deformable image registration software for 3D-minimal ablative margin (3D-MAM) quantification. Bayesian regression was used to estimate effects of pre-ablation CECT on residual unablated tumor, 3D-MAM, and local tumor progression-free survival (LTPFS). RESULTS: Pre-ablation CECT was acquired in 71/173 (41%) sessions. Residual unablated tumor was present in one (0.9%) versus nine tumors (6.6%) ablated with versus without using pre-ablation CECT, respectively (p = 0.024). Pre-ablation CECT use decreased the odds of residual disease on first follow-up by 78% (CI95% [5, 86]) and incomplete ablation (3D-MAM ≤ 0 mm) by 58% (CI95% [13, 122]). The odds ratio for residual unablated tumor for larger CLM was lower when pre-ablation CECT was used (odds ratio 1.0 with pre-ablation CECT vs. 2.52 without). Pre-ablation CECT use was not associated with improvements on LTPFS. CONCLUSIONS: Pre-ablation CECT is associated with improved immediate outcomes by significantly reducing the incidence of residual unablated tumor and by mitigating the risk of incomplete ablation for larger CLM. We recommend performing baseline intra-procedural pre-ablation CECT as a standard imaging protocol. LEVEL OF EVIDENCE: Level 3 (retrospective cohort study).

Analysis and prediction of liver volume change maps derived from computational tomography scans acquired pre- and post-radiation therapy.

External beam radiation therapy (EBRT) of liver cancers can cause local liver atrophy as a result of tissue damage or hypertrophy as a result of liver regeneration. Predicting those volumetric changes would enable new strategies for liver function preservation during treatment planning. However, understanding of the spatial dose/volume relationship is still limited. This study leverages the use of deep learning-based segmentation and biomechanical deformable image registration (DIR) to analyze and predict this relationship. Pre- and Post-EBRT imaging data were collected for 100 patients treated for hepatocellular carcinomas, cholangiocarcinoma or CRC with intensity-modulated radiotherapy (IMRT) with prescription doses ranging from 50 to 100 Gy delivered in 10-28 fractions. For each patient, DIR between the portal and venous (PV) phase of a diagnostic computed tomography (CT) scan acquired before radiation therapy (RT) planning, and a PV phase of a diagnostic CT scan acquired after the end of RT (on average 147 ± 36 d) was performed to calculate Jacobian maps representing volume changes in the liver. These volume change maps were used: (i): to analyze the dose/volume relationship in the whole liver and individual Couinaud's segments; and (ii): to investigate the use of deep-learning to predict a Jacobian map solely based on the pre-RT diagnostic CT and planned dose distribution. Moderate correlations between mean equivalent dose in 2 Gy fractions (EQD2) and volume change was observed for all liver sub-regions analyzed individually with Pearson correlationrranging from -0.36 to -067. The predicted volume change maps showed a significantly stronger voxel-wise correlation with the DIR-based volume change maps than when considering the original EQD2 distribution (0.63 ± 0.24 versus 0.55 ± 23, respectively), demonstrating the ability of the proposed approach to establish complex relationships between planned dose and liver volume response months after treatment, which represents a promising prediction tool for the development of future adaptive and personalized liver radiation therapy strategies.

Applicability and usage of dose mapping/accumulation in radiotherapy.

Dose mapping/accumulation (DMA) is a topic in radiotherapy (RT) for years, but has not yet found its widespread way into clinical RT routine. During the ESTRO Physics workshop 2021 on "commissioning and quality assurance of deformable image registration (DIR) for current and future RT applications", we built a working group on DMA from which we present the results of our discussions in this article. Our aim in this manuscript is to shed light on the current situation of DMA in RT and to highlight the issues that hinder consciously integrating it into clinical RT routine. As a first outcome of our discussions, we present a scheme where representative RT use cases are positioned, considering expected anatomical variations and the impact of dose mapping uncertainties on patient safety, which we have named the DMA landscape (DMAL). This tool is useful for future reference when DMA applications get closer to clinical day-to-day use. Secondly, we discussed current challenges, lightly touching on first-order effects (related to the impact of DIR uncertainties in dose mapping), and focusing in detail on second-order effects often dismissed in the current literature (as resampling and interpolation, quality assurance considerations, and radiobiological issues). Finally, we developed recommendations, and guidelines for vendors and users. Our main point include: Strive for context-driven DIR (by considering their impact on clinical decisions/judgements) rather than perfect DIR; be conscious of the limitations of the implemented DIR algorithm; and consider when dose mapping (with properly quantified uncertainties) is a better alternative than no mapping.

Feasibility of quantitative diffusion-weighted imaging during intra-procedural MRI-guided brachytherapy of locally advanced cervical and vaginal cancers.

PURPOSE: To determine the feasibility of quantitative apparent diffusion coefficient (ADC) acquisition during magnetic resonance imaging-guided brachytherapy (MRgBT) using reduced field-of-view (rFOV) diffusion-weighted imaging (DWI). METHODS AND MATERIALS: T2-weighted (T2w) MR and full-FOV single-shot echo planar (ssEPI) DWI were acquired in 7 patients with cervical or vaginal malignancy at baseline and prior to brachytherapy, while rFOV-DWI was acquired during MRgBT following brachytherapy applicator placement. The gross target volume (GTV) was contoured on the T2w images and registered to the ADC map. Voxels at the GTV's maximum Maurer distance comprised a central sub-volume (GTVcenter). Contour ADC mean and standard deviation were compared between timepoints using repeated measures ANOVA. RESULTS: ssEPI-DWI mean ADC increased between baseline and prebrachytherapy from 1.03 ± 0.18 10-3 mm2/s to 1.34 ± 0.28 10-3 mm2/s for the GTV (p = 0.06) and from 0.84 ± 0.13 10-3 mm2/s to 1.26 ± 0.25 10-3 mm2/s at the level of the GTVcenter (p = 0.03), consistent with early treatment response. rFOV-DWI during MRgBT demonstrated mean ADC values of 1.28 ± 0.14 10-3 mm2/s and 1.28 ± 0.19 10-3 mm2/s for the GTV and GTVcenter, respectively (p = 0.02 and p = 0.03 relative to baseline). No significant differences were observed between ssEPI-DWI and rFOV-DWI ADC measurements. CONCLUSIONS: Quantitative ADC measurement in the setting of MRI guided brachytherapy implant placement for cervical and vaginal cancers is feasible using rFOV-DWI, with comparable mean ADC comparable to prebrachytherapy ssEPI-DWI, and may enable MRI-guided radiotherapy targeting of low ADC, radiation resistant sub-volumes of tumor.

Optimization of mesh generation for geometric accuracy, robustness, and efficiency of biomechanical-model-based deformable image registration.

BACKGROUND: Successful generation of biomechanical-model-based deformable image registration (BM-DIR) relies on user-defined parameters that dictate surface mesh quality. The trial-and-error process to determine the optimal parameters can be labor-intensive and hinder DIR efficiency and clinical workflow. PURPOSE: To identify optimal parameters in surface mesh generation as boundary conditions for a BM-DIR in longitudinal liver and lung CT images to facilitate streamlined image registration processes. METHODS: Contrast-enhanced CT images of 29 colorectal liver cancer patients and end-exhale four-dimensional CT images of 26 locally advanced non-small cell lung cancer patients were collected. Different combinations of parameters that determine the triangle mesh quality (voxel side length and triangle edge length) were investigated. The quality of DIRs generated using these parameters was evaluated with metrics for geometric accuracy, robustness, and efficiency. Metrics for geometric accuracy included target registration error (TRE) of internal vessel bifurcations, dice similar coefficient (DSC), mean distance to agreement (MDA), Hausdorff distance (HD) for organ contours, and number of vertices in the triangle mesh. American Association of Physicists in Medicine Task Group 132 was used to ensure parameters met TRE, DSC, MDA recommendations before the comparison among the parameters. Robustness was evaluated as the success rate of DIR generation, and efficiency was evaluated as the total time to generate boundary conditions and compute finite element analysis. RESULTS: Voxel side length of 0.2 cm and triangle edge length of 3 were found to be the optimal parameters for both liver and lung, with success rate of 1.00 and 0.98 and average DIR computation time of 100 and 143 s, respectively. For this combination, the average TRE, DSC, MDA, and HD were 0.38-0.40, 0.96-0.97, 0.09-0.12, and 0.87-1.17 mm, respectively. CONCLUSION: The optimal parameters were found for the analyzed patients. The decision-making process described in this study serves as a recommendation for BM-DIR algorithms to be used for liver and lung. These parameters can facilitate consistence in the evaluation of published studies and more widespread utilization of BM-DIR in clinical practice.