Development and Validation of Multiparametric MRI-based Radiomics Models for Preoperative Risk Stratification of Endometrial Cancer.

Background Stratifying high-risk histopathologic features in endometrial carcinoma is important for treatment planning. Radiomics analysis at preoperative MRI holds potential to identify high-risk phenotypes. Purpose To evaluate the performance of multiparametric MRI three-dimensional radiomics-based machine learning models for differentiating low- from high-risk histopathologic markers-deep myometrial invasion (MI), lymphovascular space invasion (LVSI), and high-grade status-and advanced-stage endometrial carcinoma. Materials and Methods This dual-center retrospective study included women with histologically proven endometrial carcinoma who underwent 1.5-T MRI before hysterectomy between January 2011 and July 2015. Exclusion criteria were tumor diameter less than 1 cm, missing MRI sequences or histopathology reports, neoadjuvant therapy, and malignant neoplasms other than endometrial carcinoma. Three-dimensional radiomics features were extracted after tumor segmentation at MRI (T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI). Predictive features were selected in the training set with use of random forest (RF) models for each end point, and trained RF models were applied to the external test set. Five board-certified radiologists conducted MRI-based staging and deep MI assessment in the training set. Areas under the receiver operating characteristic curve (AUCs) were reported with balanced accuracies, and radiologists' readings were compared with radiomics with use of McNemar tests. Results In total, 157 women were included: 94 at the first institution (training set; mean age, 66 years ± 11 [SD]) and 63 at the second institution (test set; 67 years ± 12). RF models dichotomizing deep MI, LVSI, high grade, and International Federation of Gynecology and Obstetrics (FIGO) stage led to AUCs of 0.81 (95% CI: 0.68, 0.88), 0.80 (95% CI: 0.67, 0.93), 0.74 (95% CI: 0.61, 0.86), and 0.84 (95% CI: 0.72, 0.92), respectively, in the test set. In the training set, radiomics provided increased performance compared with radiologists' readings for identifying deep MI (balanced accuracy, 86% vs 79%; P = .03), while no evidence of a difference was observed in performance for advanced FIGO stage (80% vs 78%; P = .27). Conclusion Three-dimensional radiomics can stratify patients by using preoperative MRI according to high-risk histopathologic end points in endometrial carcinoma and provide nonsignificantly different or higher performance than radiologists in identifying advanced stage and deep myometrial invasion, respectively. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kido and Nishio in this issue.

The future of MRI in radiation therapy: Challenges and opportunities for the MR community.

Radiation therapy is a major component of cancer treatment pathways worldwide. The main aim of this treatment is to achieve tumor control through the delivery of ionizing radiation while preserving healthy tissues for minimal radiation toxicity. Because radiation therapy relies on accurate localization of the target and surrounding tissues, imaging plays a crucial role throughout the treatment chain. In the treatment planning phase, radiological images are essential for defining target volumes and organs-at-risk, as well as providing elemental composition (e.g., electron density) information for radiation dose calculations. At treatment, onboard imaging informs patient setup and could be used to guide radiation dose placement for sites affected by motion. Imaging is also an important tool for treatment response assessment and treatment plan adaptation. MRI, with its excellent soft tissue contrast and capacity to probe functional tissue properties, holds great untapped potential for transforming treatment paradigms in radiation therapy. The MR in Radiation Therapy ISMRM Study Group was established to provide a forum within the MR community to discuss the unmet needs and fuel opportunities for further advancement of MRI for radiation therapy applications. During the summer of 2021, the study group organized its first virtual workshop, attended by a diverse international group of clinicians, scientists, and clinical physicists, to explore our predictions for the future of MRI in radiation therapy for the next 25 years. This article reviews the main findings from the event and considers the opportunities and challenges of reaching our vision for the future in this expanding field.

Malignancy risk stratification of cystic renal lesions based on a contrast-enhanced CT-based machine learning model and a clinical decision algorithm.

OBJECTIVE: To distinguish benign from malignant cystic renal lesions (CRL) using a contrast-enhanced CT-based radiomics model and a clinical decision algorithm. METHODS: This dual-center retrospective study included patients over 18 years old with CRL between 2005 and 2018. The reference standard was histopathology or 4-year imaging follow-up. Training and testing datasets were acquired from two institutions. Quantitative 3D radiomics analyses were performed on nephrographic phase CT images. Ten-fold cross-validated LASSO regression was applied to the training dataset to identify the most discriminative features. A logistic regression model was trained to classify malignancy and tested on the independent dataset. Reported metrics included areas under the receiver operating characteristic curves (AUC) and balanced accuracy. Decision curve analysis for stratifying patients for surgery was performed in the testing dataset. A decision algorithm was built by combining consensus radiological readings of Bosniak categories and radiomics-based risks. RESULTS: A total of 149 CRL (139 patients; 65 years [56-72]) were included in the training dataset-35 Bosniak(B)-IIF (8.6% malignancy), 23 B-III (43.5%), and 23 B-IV (87.0%)-and 50 CRL (46 patients; 61 years [51-68]) in the testing dataset-12 B-IIF (8.3%), 10 B-III (60.0%), and 9 B-IV (100%). The machine learning model achieved high diagnostic performance in predicting malignancy in the testing dataset (AUC = 0.96; balanced accuracy = 94%). There was a net benefit across threshold probabilities in using the clinical decision algorithm over management guidelines based on Bosniak categories. CONCLUSION: CT-based radiomics modeling accurately distinguished benign from malignant CRL, outperforming the Bosniak classification. The decision algorithm best stratified lesions for surgery and active surveillance. KEY POINTS: • The radiomics model achieved excellent diagnostic performance in identifying malignant cystic renal lesions in an independent testing dataset (AUC = 0.96). • The machine learning-enhanced decision algorithm outperformed the management guidelines based on the Bosniak classification for stratifying patients to surgical ablation or active surveillance.

Unsupervised Segmentation of 3D Microvascular Photoacoustic Images Using Deep Generative Learning.

Mesoscopic photoacoustic imaging (PAI) enables label-free visualization of vascular networks in tissues with high contrast and resolution. Segmenting these networks from 3D PAI data and interpreting their physiological and pathological significance is crucial yet challenging due to the time-consuming and error-prone nature of current methods. Deep learning offers a potential solution; however, supervised analysis frameworks typically require human-annotated ground-truth labels. To address this, an unsupervised image-to-image translation deep learning model is introduced, the Vessel Segmentation Generative Adversarial Network (VAN-GAN). VAN-GAN integrates synthetic blood vessel networks that closely resemble real-life anatomy into its training process and learns to replicate the underlying physics of the PAI system in order to learn how to segment vasculature from 3D photoacoustic images. Applied to a diverse range of in silico, in vitro, and in vivo data, including patient-derived breast cancer xenograft models and 3D clinical angiograms, VAN-GAN demonstrates its capability to facilitate accurate and unbiased segmentation of 3D vascular networks. By leveraging synthetic data, VAN-GAN reduces the reliance on manual labeling, thus lowering the barrier to entry for high-quality blood vessel segmentation (F1 score: VAN-GAN vs. U-Net = 0.84 vs. 0.87) and enhancing preclinical and clinical research into vascular structure and function.

Inter-visit and inter-reader reproducibility of multi-parametric diffusion-weighted MR imaging in longitudinally imaged patients with metabolic dysfunction-associated fatty liver disease and healthy volunteers.

BACKGROUND: Despite the widespread use of diffusion-weighted imaging (DWI) in metabolic dysfunction-associated fatty liver disease (MAFLD), MRI acquisition and quantification techniques vary in the literature suggesting the need for established and reproducible protocols. The goal of this study was to assess inter-visit and inter-reader reproducibility of DWI- and IVIM-derived parameters in patients with MAFLD and healthy volunteers using extensive sampling of the "fast" compartment, non-rigid registration, and exclusion voxels with poor fit quality. METHODS: From June 2019 to April 2023, 31 subjects (20 patients with biopsy-proven MAFLD and 11 healthy volunteers) were included in this IRB-approved study. Subjects underwent MRI examinations twice within 40 days. 3.0 T DWI was acquired using a respiratory-triggered spin-echo diffusion-weighted echo-planar imaging sequence (b-values of 0, 10, 20, 30, 40, 50, 100, 200, 400, 800 s/mm2). DWI series were co-registered prior to voxel-wise non-linear regression of the IVIM model and voxels with poor fit quality were excluded (normalized root mean squared error ≥ 0.05). IVIM parameters (perfusion fraction, f; diffusion coefficient, D; and pseudo-diffusion coefficient, D*), and apparent diffusion coefficients (ADC) were computed from manual segmentation of the right liver lobe performed by two analysts on two MRI examinations. RESULTS: All results are reported for f, D, D*, and ADC respectively. For inter-reader agreement on the first visit, ICC were of 0.985, 0.994, 0.986, and 0.993 respectively. For intra-reader agreement of analyst 1 assessed on both imaging examinations, ICC between visits were of 0.805, 0.759, 0.511, and 0.850 respectively. For inter-reader agreement on the first visit, mean bias and 95 % limits of agreement were (0.00 ± 0.03), (-0.01 ± 0.03) × 10-3 mm2/s, (0.70 ± 10.40) × 10-3 mm2/s, and (-0.02 ± 0.04) × 10-3 mm2/s respectively. For intra-reader agreement of analyst 1, mean bias and 95 % limits of agreement were (0.01 ± 0.09) × 10-3 mm2/s, (-0.01 ± 0.21) × 10-3 mm2/s, (-13.37 ± 56.19) × 10-3 mm2/s, and (-0.01 ± 0.16) × 10-3 mm2/s respectively. Except for parameter D* that was associated with between-subjects parameter variability (P = 0.009), there was no significant variability between subjects, examinations, or readers. CONCLUSION: With our approach, IVIM parameters f, D, D*, and ADC provided excellent inter-reader agreement and good to very good inter-visit or intra-reader agreement, thus showing the reproducibility of IVIM-DWI of the liver in MAFLD patients and volunteers.

Performance evaluation of image co-registration methods in photoacoustic mesoscopy of the vasculature.

Objective:The formation of functional vasculature in solid tumours enables delivery of oxygen and nutrients, and is vital for effective treatment with chemotherapeutic agents. Longitudinal characterisation of vascular networks can be enabled using mesoscopic photoacoustic imaging, but requires accurate image co-registration to precisely assess local changes across disease development or in response to therapy. Co-registration in photoacoustic imaging is challenging due to the complex nature of the generated signal, including the sparsity of data, artefacts related to the illumination/detection geometry, scan-to-scan technical variability, and biological variability, such as transient changes in perfusion. To better inform the choice of co-registration algorithms, we compared five open-source methods, in physiological and pathological tissues, with the aim of aligning evolving vascular networks in tumours imaged over growth at different time-points.Approach:Co-registration techniques were applied to 3D vascular images acquired with photoacoustic mesoscopy from murine ears and breast cancer patient-derived xenografts, at a fixed time-point and longitudinally. Images were pre-processed and segmented using an unsupervised generative adversarial network. To compare co-registration quality in different settings, pairs of fixed and moving intensity images and/or segmentations were fed into five methods split into the following categories: affine intensity-based using 1)mutual information (MI) or 2)normalised cross-correlation (NCC) as optimisation metrics, affine shape-based using 3)NCC applied to distance-transformed segmentations or 4)iterative closest point algorithm, and deformable weakly supervised deep learning-based using 5)LocalNet co-registration. Percent-changes in Dice coefficients, surface distances, MI, structural similarity index measure and target registration errors were evaluated.Main results:Co-registration using MI or NCC provided similar alignment performance, better than shape-based methods. LocalNet provided accurate co-registration of substructures by optimising subfield deformation throughout the volumes, outperforming other methods, especially in the longitudinal breast cancer xenograft dataset by minimising target registration errors.Significance:We showed the feasibility of co-registering repeatedly or longitudinally imaged vascular networks in photoacoustic mesoscopy, taking a step towards longitudinal quantitative characterisation of these complex structures. These tools open new outlooks for monitoring tumour angiogenesis at the meso-scale and for quantifying treatment-induced co-localised alterations in the vasculature.

Performance evaluation of mesoscopic photoacoustic imaging.

Photoacoustic mesoscopy visualises vascular architecture at high-resolution up to ~3 mm depth. Despite promise in preclinical and clinical imaging studies, with applications in oncology and dermatology, the accuracy and precision of photoacoustic mesoscopy is not well established. Here, we evaluate a commercial photoacoustic mesoscopy system for imaging vascular structures. Typical artefact types are first highlighted and limitations due to non-isotropic illumination and detection are evaluated with respect to rotation, angularity, and depth of the target. Then, using tailored phantoms and mouse models, we investigate system precision, showing coefficients of variation (COV) between repeated scans [short term (1 h): COV= 1.2%; long term (25 days): COV= 9.6%], from target repositioning (without: COV=1.2%, with: COV=4.1%), or from varying in vivo user experience (experienced: COV=15.9%, unexperienced: COV=20.2%). Our findings show robustness of the technique, but also underscore general challenges of limited-view photoacoustic systems in accurately imaging vessel-like structures, thereby guiding users when interpreting biologically-relevant information.

Predicting histopathology markers of endometrial carcinoma with a quantitative image analysis approach based on spherical harmonics in multiparametric MRI.

PURPOSE: Identifying optimal machine learning pipelines for computer-aided diagnosis is key for the development of robust, reproducible, and clinically relevant imaging biomarkers for endometrial carcinoma. The purpose of this study was to introduce the mathematical development of image descriptors computed from spherical harmonics (SPHARM) decompositions as well as the associated machine learning pipeline, and to evaluate their performance in predicting deep myometrial invasion (MI) and histopathological high-grade in preoperative multiparametric magnetic resonance imaging (MRI). PATIENTS AND METHODS: This retrospective study included 128 women with histopathology-confirmed endometrial carcinomas who underwent 1.5-T MRI before hysterectomy between January 2011 and July 2015. SPHARM descriptors of each tumor were computed on multiparametric MRI images (T2-weighted, diffusion-weighted, dynamic contrast-enhanced-MRI and apparent diffusion coefficient maps). Tensor-based logistic regression was used to classify two-dimensional SPHARM rotationally-invariant descriptors. Head-to-head comparisons with radiomics analyses were performed with DeLong tests with Bonferroni-Holm correction to compare diagnostic performances. RESULTS: With all MRI contrasts, SPHARM analysis resulted in area under the curve, sensitivity, specificity, and balanced accuracy values of 0.94 (95% confidence interval [CI]: 0.85, 1.00), 100% (95% CI: 100, 100), 74% (95% CI: 51, 92), 87% (95% CI: 78, 98), respectively, for predicting deep MI. For predicting high-grade tumor histology, the corresponding values for the same diagnostic metrics were 0.81 (95% CI: 0.64, 0.90), 93% (95% CI: 67, 100), 63% (95% CI: 45, 79) and 78% (95% CI: 64, 86). The corresponding values achieved via radiomics were 0.92 (95% CI: 0.82, 0.95), 82% (95% CI: 65, 93), 80% (95% CI: 51, 94), 81% (95% CI: 70, 91) for deep MI and 0.72 (95% CI: 0.58, 0.83), 93% (95% CI: 65, 100), 55% (95% CI: 41, 69), 74% (95% CI: 52, 88) for high-grade histology. The diagnostic performance of the SPHARM analysis was not significantly different (P = 0.62) from that of radiomics for predicting deep MI but was significantly higher (P = 0.044) for predicting high-grade histology. CONCLUSION: The proposed SPHARM analysis yields similar or higher diagnostic performance than radiomics in identifying deep MI and high-grade status in histology-proven endometrial carcinoma.

The Potential of Photoacoustic Imaging in Radiation Oncology.

Radiotherapy is recognized globally as a mainstay of treatment in most solid tumors and is essential in both curative and palliative settings. Ionizing radiation is frequently combined with surgery, either preoperatively or postoperatively, and with systemic chemotherapy. Recent advances in imaging have enabled precise targeting of solid lesions yet substantial intratumoral heterogeneity means that treatment planning and monitoring remains a clinical challenge as therapy response can take weeks to manifest on conventional imaging and early indications of progression can be misleading. Photoacoustic imaging (PAI) is an emerging modality for molecular imaging of cancer, enabling non-invasive assessment of endogenous tissue chromophores with optical contrast at unprecedented spatio-temporal resolution. Preclinical studies in mouse models have shown that PAI could be used to assess response to radiotherapy and chemoradiotherapy based on changes in the tumor vascular architecture and blood oxygen saturation, which are closely linked to tumor hypoxia. Given the strong relationship between hypoxia and radio-resistance, PAI assessment of the tumor microenvironment has the potential to be applied longitudinally during radiotherapy to detect resistance at much earlier time-points than currently achieved by size measurements and tailor treatments based on tumor oxygen availability and vascular heterogeneity. Here, we review the current state-of-the-art in PAI in the context of radiotherapy research. Based on these studies, we identify promising applications of PAI in radiation oncology and discuss the future potential and outstanding challenges in the development of translational PAI biomarkers of early response to radiotherapy.

Quantification of vascular networks in photoacoustic mesoscopy.

Mesoscopic photoacoustic imaging (PAI) enables non-invasive visualisation of tumour vasculature. The visual or semi-quantitative 2D measurements typically applied to mesoscopic PAI data fail to capture the 3D vessel network complexity and lack robust ground truths for assessment of accuracy. Here, we developed a pipeline for quantifying 3D vascular networks captured using mesoscopic PAI and tested the preservation of blood volume and network structure with topological data analysis. Ground truth data of in silico synthetic vasculatures and a string phantom indicated that learning-based segmentation best preserves vessel diameter and blood volume at depth, while rule-based segmentation with vesselness image filtering accurately preserved network structure in superficial vessels. Segmentation of vessels in breast cancer patient-derived xenografts (PDXs) compared favourably to ex vivo immunohistochemistry. Furthermore, our findings underscore the importance of validating segmentation methods when applying mesoscopic PAI as a tool to evaluate vascular networks in vivo.