Segmentation Of Magnetic Resonance Images Research Articles

Potential roles of transformers in brain tumor diagnosis and treatment

AbstractBrain tumor (BT) is one of many malignancies that have substantially enhanced global human morbidity and mortality rates. Early detection and characterization of glioma are essential for effective preventive strategies. Currently, the use of Transformers, a deep learning model for BT diagnosis and treatment, is attracting significant attention. The transformer self‐attention mechanism automatically learns the associations between input data for efficient processing and analysis. Research indicates that Transformers could play an essential role in the BT segmentation of magnetic resonance imaging (MRI) images, the MRI and histopathology‐based grading of brain cancer, BT molecular expression prediction, the classification of primary brain metastasis sites, voxel‐level dose and BT radiotherapy outcome prediction, synergistic prediction, and the pathway deconvolution of drug combinations. In this review, the feasibility, accuracy, and applicability of various algorithms are systematically analyzed and their prospects are discussed. Overall, this review aimed to discuss and provide an overview of the increasing applications of Transformers in real‐time BT detection and therapy, indicating their broad prospects and potential. In the future, Transformers are expected to be increasingly used for the diagnosis and subsequent treatment of BT because of the continuous development and improvement of Transformer‐based deep learning technology. However, more work is required to investigate their properties for anomaly detection, medical image classification, network design development, and application to other medical data.

Estimating Uncertainty in Neural Networks for Cardiac MRI Segmentation: A Benchmark Study.

Convolutional neural networks (CNNs) have demonstrated promise in automated cardiac magnetic resonance image segmentation. However, when using CNNs in a large real-world dataset, it is important to quantify segmentation uncertainty and identify segmentations which could be problematic. In this work, we performed a systematic study of Bayesian and non-Bayesian methods for estimating uncertainty in segmentation neural networks. We evaluated Bayes by Backprop, Monte Carlo Dropout, Deep Ensembles, and Stochastic Segmentation Networks in terms of segmentation accuracy, probability calibration, uncertainty on out-of-distribution images, and segmentation quality control. We observed that Deep Ensembles outperformed the other methods except for images with heavy noise and blurring distortions. We showed that Bayes by Backprop is more robust to noise distortions while Stochastic Segmentation Networks are more resistant to blurring distortions. For segmentation quality control, we showed that segmentation uncertainty is correlated with segmentation accuracy for all the methods. With the incorporation of uncertainty estimates, we were able to reduce the percentage of poor segmentation to 5% by flagging 31-48% of the most uncertain segmentations for manual review, substantially lower than random review without using neural network uncertainty (reviewing 75-78% of all images). This work provides a comprehensive evaluation of uncertainty estimation methods and showed that Deep Ensembles outperformed other methods in most cases. Neural network uncertainty measures can help identify potentially inaccurate segmentations and alert users for manual review.

A Qualitative Study on Segmentation of MR Images of Brain for Neuro Disorder Analysis

A Qualitative Study on Segmentation of MR Images of Brain for Neuro Disorder Analysis

Predicting Breast Cancer Subtypes Using Magnetic Resonance Imaging Based Radiomics With Automatic Segmentation.

The aim of the study is to demonstrate whether radiomics based on an automatic segmentation method is feasible for predicting molecular subtypes. This retrospective study included 516 patients with confirmed breast cancer. An automatic segmentation-3-dimensional UNet-based Convolutional Neural Networks, trained on our in-house data set-was applied to segment the regions of interest. A set of 1316 radiomics features per region of interest was extracted. Eighteen cross-combination radiomics methods-with 6 feature selection methods and 3 classifiers-were used for model selection. Model classification performance was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. The average dice similarity coefficient value of the automatic segmentation was 0.89. The radiomics models were predictive of 4 molecular subtypes with the best average: AUC = 0.8623, accuracy = 0.6596, sensitivity = 0.6383, and specificity = 0.8775. For luminal versus nonluminal subtypes, AUC = 0.8788 (95% confidence interval [CI], 0.8505-0.9071), accuracy = 0.7756, sensitivity = 0.7973, and specificity = 0.7466. For human epidermal growth factor receptor 2 (HER2)-enriched versus non-HER2-enriched subtypes, AUC = 0.8676 (95% CI, 0.8370-0.8982), accuracy = 0.7737, sensitivity = 0.8859, and specificity = 0.7283. For triple-negative breast cancer versus non-triple-negative breast cancer subtypes, AUC = 0.9335 (95% CI, 0.9027-0.9643), accuracy = 0.9110, sensitivity = 0.4444, and specificity = 0.9865. Radiomics based on automatic segmentation of magnetic resonance imaging can predict breast cancer of 4 molecular subtypes noninvasively and is potentially applicable in large samples.

MSCDA: Multi-level semantic-guided contrast improves unsupervised domain adaptation for breast MRI segmentation in small datasets

Deep learning (DL) applied to breast tissue segmentation in magnetic resonance imaging (MRI) has received increased attention in the last decade, however, the domain shift which arises from different vendors, acquisition protocols, and biological heterogeneity, remains an important but challenging obstacle on the path towards clinical implementation. In this paper, we propose a novel Multi-level Semantic-guided Contrastive Domain Adaptation (MSCDA) framework to address this issue in an unsupervised manner. Our approach incorporates self-training with contrastive learning to align feature representations between domains. In particular, we extend the contrastive loss by incorporating pixel-to-pixel, pixel-to-centroid, and centroid-to-centroid contrasts to better exploit the underlying semantic information of the image at different levels. To resolve the data imbalance problem, we utilize a category-wise cross-domain sampling strategy to sample anchors from target images and build a hybrid memory bank to store samples from source images. We have validated MSCDA with a challenging task of cross-domain breast MRI segmentation between datasets of healthy volunteers and invasive breast cancer patients. Extensive experiments show that MSCDA effectively improves the model’s feature alignment capabilities between domains, outperforming state-of-the-art methods. Furthermore, the framework is shown to be label-efficient, achieving good performance with a smaller source dataset. The code is publicly available at https://github.com/ShengKuangCN/MSCDA.

Automated 3-dimensional MRI segmentation for the posterosuperior rotator cuff tear lesion using deep learning algorithm.

Rotator cuff tear (RCT) is a challenging and common musculoskeletal disease. Magnetic resonance imaging (MRI) is a commonly used diagnostic modality for RCT, but the interpretation of the results is tedious and has some reliability issues. In this study, we aimed to evaluate the accuracy and efficacy of the 3-dimensional (3D) MRI segmentation for RCT using a deep learning algorithm. A 3D U-Net convolutional neural network (CNN) was developed to detect, segment, and visualize RCT lesions in 3D, using MRI data from 303 patients with RCTs. The RCT lesions were labeled by two shoulder specialists in the entire MR image using in-house developed software. The MRI-based 3D U-Net CNN was trained after the augmentation of a training dataset and tested using randomly selected test data (training: validation: test data ratio was 6:2:2). The segmented RCT lesion was visualized in a three-dimensional reconstructed image, and the performance of the 3D U-Net CNN was evaluated using the Dice coefficient, sensitivity, specificity, precision, F1-score, and Youden index. A deep learning algorithm using a 3D U-Net CNN successfully detected, segmented, and visualized the area of RCT in 3D. The model's performance reached a 94.3% of Dice coefficient score, 97.1% of sensitivity, 95.0% of specificity, 84.9% of precision, 90.5% of F1-score, and Youden index of 91.8%. The proposed model for 3D segmentation of RCT lesions using MRI data showed overall high accuracy and successful 3D visualization. Further studies are necessary to determine the feasibility of its clinical application and whether its use could improve care and outcomes.

An advanced fuzzy C-Means algorithm for the tissue segmentation from brain magnetic resonance images in the presence of noise and intensity inhomogeneity

ABSTRACT Segmentation of brain Magnetic Resonance Images (MRIs) into various brain tissues such as white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) is very important to detect and diagnose different brain-related disorders at the primitive level. Accurate segmentation of brain MRIs is very difficult because of the intricate anatomical structure of the tissues, the existence of Intensity Inhomogeneity (IIH), noise, and Partial Volume Effects (PVE). Clustering-based methods are generally used to segment brain images. This work proposes a Chaotic based Enhanced Firefly Algorithm Integrated with Fuzzy C-Means (CEFAFCM) for the segmentation of brain tissues WM, GM, and CSF from brain MRIs. The proposed method can handle IIH, PVE, and noise. CEFAFCM is a spatially modified FCM algorithm combined with the Firefly Algorithm (FA) along with a chaotic map for the initialization of the population of fireflies. The algorithm is tested with brain MRIs acquired from the BrainWeb database. The experimental results demonstrate that the proposed technique is producing better results in comparison with some existing brain MRI segmentation methods such as FCM, BCFCM, FAFCM, and En-FAFCM.

Semiautomated segmentation of lower extremity MRI reveals distinctive subcutaneous adipose tissue in lipedema: a pilot study.

Lipedema is a painful subcutaneous adipose tissue (SAT) disease involving disproportionate SAT accumulation in the lower extremities that is frequently misdiagnosed as obesity. We developed a semiautomatic segmentation pipeline to quantify the unique lower-extremity SAT quantity in lipedema from multislice chemical-shift-encoded (CSE) magnetic resonance imaging (MRI). Patients with lipedema () and controls () matched for age and body mass index (BMI) underwent CSE-MRI acquired from the thighs to ankles. Images were segmented to partition SAT and skeletal muscle with a semiautomated algorithm incorporating classical image processing techniques (thresholding, active contours, Boolean operations, and morphological operations). The Dice similarity coefficient (DSC) was computed for SAT and muscle automated versus ground truth segmentations in the calf and thigh. SAT and muscle volumes and the SAT-to-muscle volume ratio were calculated across slices for decades containing 10% of total slices per participant. The effect size was calculated, and Mann-Whitney test applied to compare metrics in each decade between groups (significance: two-sided ). Mean DSC for SAT segmentations was 0.96 in the calf and 0.98 in the thigh, and for muscle was 0.97 in the calf and 0.97 in the thigh. In all decades, mean SAT volume was significantly elevated in participants with versus without lipedema (), whereas muscle volume did not differ. Mean SAT-to-muscle volume ratio was significantly elevated () in all decades, where the greatest effect size for distinguishing lipedema was in the seventh decade approximately midthigh (). The semiautomated segmentation of lower-extremity SAT and muscle from CSE-MRI could enable fast multislice analysis of SAT deposition throughout the legs relevant to distinguishing patients with lipedema from females with similar BMI but without SAT disease.

An Improved Soft Subspace Clustering Algorithm Based on Particle Swarm Optimization for MR Image Segmentation.

Soft subspace clustering (SSC), which analyzes high-dimensional data and applies various weights to each cluster class to assess the membership degree of each cluster to the space, has shown promising results in recent years. This method of clustering assigns distinct weights to each cluster class. By introducing spatial information, enhanced SSC algorithms improve the degree to which intraclass compactness and interclass separation are achieved. However, these algorithms are sensitive to noisy data and have a tendency to fall into local optima. In addition, the segmentation accuracy is poor because of the influence of noisy data. In this study, an SSC approach that is based on particle swarm optimization is suggested with the intention of reducing the interference caused by noisy data. The particle swarm optimization method is used to locate the best possible clustering center. Second, increasing the amount of geographical membership makes it possible to utilize the spatial information to quantify the link between different clusters in a more precise manner. In conclusion, the extended noise clustering method is implemented in order to maximize the weight. Additionally, the constraint condition of the weight is changed from the equality constraint to the boundary constraint in order to reduce the impact of noise. The methodology presented in this research works to reduce the amount of sensitivity the SSC algorithm has to noisy data. It is possible to demonstrate the efficacy of this algorithm by using photos with noise already present or by introducing noise to existing photographs. The revised SSC approach based on particle swarm optimization (PSO) is demonstrated to have superior segmentation accuracy through a number of trials; as a result, this work gives a novel method for the segmentation of noisy images.

Domain-Aware Dual Attention for Generalized Medical Image Segmentation on Unseen Domains.

Recently, there has been significant progress in medical image segmentation utilizing deep learning techniques. However, these achievements largely rely on the supposition that the source and target domain data are identically distributed, and the direct application of related methods without addressing the distribution shift results in dramatic degradation in realistic clinical environments. Current approaches concerning the distribution shift either require the target domain data in advance for adaptation, or focus only on the distribution shift across domains while ignoring the intra-domain data variation. This paper proposes a domain-aware dual attention network for the generalized medical image segmentation task on unseen target domains. To alleviate the severe distribution shift between the source and target domains, an Extrinsic Attention (EA) module is designed to learn image features with knowledge originating from multi-source domains. Moreover, an Intrinsic Attention (IA) module is also proposed to handle the intra-domain variation by individually modeling the pixel-region relations derived from an image. The EA and IA modules complement each other well in terms of modeling the extrinsic and intrinsic domain relationships, respectively. To validate the model effectiveness, comprehensive experiments are conducted on various benchmark datasets, including the prostate segmentation in magnetic resonance imaging (MRI) scans and the optic cup/disc segmentation in fundus images. The experimental results demonstrate that our proposed model effectively generalizes to unseen domains and exceeds the existing advanced approaches.

Clinically Relevant Myocardium Segmentation in Cardiac Magnetic Resonance Images.

Deep learning approaches have shown great success in myocardium region segmentation in Cardiac MR (CMR) images. However, most of these often ignore irregularities such as protrusions, breaks in contour, etc. As a result, the common practice by clinicians is to manually correct the obtained outputs for the evaluation of myocardium condition. This paper aims to make the deep learning systems capable of handling the aforementioned irregularities and satisfy desired clinical constraints, necessary for various downstream clinical analysis. We propose a refinement model which imposes structural constraints on the outputs of the existing deep learning-based myocardium segmentation methods. The complete system is a pipeline of deep neural networks where an initial network performs myocardium segmentation as accurate as possible and the refinement network removes defects from the initial output to make it suitable for clinical decision support systems. We experiment with datasets collected from four different sources and observe consistent final segmentation outputs with improvement up to 8% in Dice Coefficient and up to 18 pixels in Hausdorff Distance due to the proposed refinement model. The proposed refinement strategy leads to qualitative and quantitative improvements in the performances of all the considered segmentation networks. Our work is an important step towards the development of a fully automatic myocardium segmentation system. It can also be generalized for other tasks where the object of interest has regular structure and the defects can be modelled statistically.

Improvement of semantic segmentation through transfer learning of multi-class regions with convolutional neural networks on supine and prone breast MRI images

Semantic segmentation of breast and surrounding tissues in supine and prone breast magnetic resonance imaging (MRI) is required for various kinds of computer-assisted diagnoses for surgical applications. Variability of breast shape in supine and prone poses along with various MRI artifacts makes it difficult to determine robust breast and surrounding tissue segmentation. Therefore, we evaluated semantic segmentation with transfer learning of convolutional neural networks to create robust breast segmentation in supine breast MRI without considering supine or prone positions. Total 29 patients with T1-weighted contrast-enhanced images were collected at Asan Medical Center and two types of breast MRI were performed in the prone position and the supine position. The four classes, including lungs and heart, muscles and bones, parenchyma with cancer, and skin and fat, were manually drawn by an expert. Semantic segmentation on breast MRI scans with supine, prone, transferred from prone to supine, and pooled supine and prone MRI were trained and compared using 2D U-Net, 3D U-Net, 2D nnU-Net and 3D nnU-Net. The best performance was 2D models with transfer learning. Our results showed excellent performance and could be used for clinical purposes such as breast registration and computer-aided diagnosis.

Automatic semantic segmentation of the lumbar spine: Clinical applicability in a multi-parametric and multi-center study on magnetic resonance images

Significant difficulties in medical image segmentation include the high variability of images caused by their origin (multi-center), the acquisition protocols (multi-parametric), the variability of human anatomy, illness severity, the effect of age and gender, and notable other factors. This work addresses problems associated with the automatic semantic segmentation of lumbar spine magnetic resonance images using convolutional neural networks. We aimed to assign a class label to each pixel of an image, with classes defined by radiologists corresponding to structural elements such as vertebrae, intervertebral discs, nerves, blood vessels, and other tissues. The proposed network topologies represent variants of the U-Net architecture, and we used several complementary blocks to define the variants: three types of convolutional blocks, spatial attention models, deep supervision, and multilevel feature extractor. Here, we describe the topologies and analyze the results of the neural network designs that obtained the most accurate segmentation. Several proposed designs outperform the standard U-Net used as a baseline, primarily when used in ensembles, where the outputs of multiple neural networks are combined according to different strategies.

Reducing segmentation failures in cardiac MRI via late feature fusion and GAN-based augmentation

Cardiac magnetic resonance (CMR) image segmentation is an integral step in the analysis of cardiac function and diagnosis of heart related diseases. While recent deep learning-based approaches in automatic segmentation have shown great promise to alleviate the need for manual segmentation, most of these are not applicable to realistic clinical scenarios. This is largely due to training on mainly homogeneous datasets, without variation in acquisition, which typically occurs in multi-vendor and multi-site settings, as well as pathological data. Such approaches frequently exhibit a degradation in prediction performance, particularly on outlier cases commonly associated with difficult pathologies, artifacts and extensive changes in tissue shape and appearance. In this work, we present a model aimed at segmenting all three cardiac structures in a multi-center, multi-disease and multi-view scenario. We propose a pipeline, addressing different challenges with segmentation of such heterogeneous data, consisting of heart region detection, augmentation through image synthesis and a late-fusion segmentation approach. Extensive experiments and analysis demonstrate the ability of the proposed approach to tackle the presence of outlier cases during both training and testing, allowing for better adaptation to unseen and difficult examples. Overall, we show that the effective reduction of segmentation failures on outlier cases has a positive impact on not only the average segmentation performance, but also on the estimation of clinical parameters, leading to a better consistency in derived metrics.

A meta-learning based method for segmentation of few-shot magnetic resonance images

When applying deep learning algorithms to magnetic resonance (MR) image segmentation, a large number of annotated images are required as data support. However, the specificity of MR images makes it difficult and costly to acquire large amounts of annotated image data. To reduce the dependence of MR image segmentation on a large amount of annotated data, this paper proposes a meta-learning U-shaped network (Meta-UNet) for few-shot MR image segmentation. Meta-UNet can use a small amount of annotated image data to complete the task of MR image segmentation and obtain good segmentation results. Meta-UNet improves U-Net by introducing dilated convolution, which can increase the receptive field of the model to improve the sensitivity to targets of different scales. We introduce the attention mechanism to improve the adaptability of the model to different scales. We introduce the meta-learning mechanism, and employ a composite loss function for well-supervised and effective bootstrapping of model training. We use the proposed Meta-UNet model to train on different segmentation tasks, and then use the trained model to evaluate on a new segmentation task, where the Meta-UNet model achieves high-precision segmentation of target images. Meta-UNet has a certain improvement in mean Dice similarity coefficient (DSC) compared with voxel morph network (VoxelMorph), data augmentation using learned transformations (DataAug) and label transfer network (LT-Net). Experiments show that the proposed method can effectively perform MR image segmentation using a small number of samples. It provides a reliable aid for clinical diagnosis and treatment.

Segmentation of prostate region in magnetic resonance images based on improved V-Net

Magnetic resonance (MR) imaging is an important tool for prostate cancer diagnosis, and accurate segmentation of MR prostate regions by computer-aided diagnostic techniques is important for the diagnosis of prostate cancer. In this paper, we propose an improved end-to-end three-dimensional image segmentation network using a deep learning approach to the traditional V-Net network (V-Net) network in order to provide more accurate image segmentation results. Firstly, we fused the soft attention mechanism into the traditional V-Net's jump connection, and combined short jump connection and small convolutional kernel to further improve the network segmentation accuracy. Then the prostate region was segmented using the Prostate MR Image Segmentation 2012 (PROMISE 12) challenge dataset, and the model was evaluated using the dice similarity coefficient (DSC) and Hausdorff distance (HD). The DSC and HD values of the segmented model could reach 0.903 and 3.912 mm, respectively. The experimental results show that the algorithm in this paper can provide more accurate three-dimensional segmentation results, which can accurately and efficiently segment prostate MR images and provide a reliable basis for clinical diagnosis and treatment.

Assessment of Shared Neurologic Radiomic Markers Among Patients Diagnosed with Functional Seizure Disorder Utilizing a Novel Machine Learning Model (P6-12.007)

<h3>Objective:</h3> The objective of this study is to determine if a machine learning model can utilize magnetic resonance imaging (MRI) to differentiate patients with functional seizure disorder (FSD) from those with temporal lobe epilepsy (TLE). <h3>Background:</h3> FSD is a diagnosis associated with significant disability, but that is ultimately poorly understood. Although some studies have suggested anatomic commonalities among FSD patients, consistent MRI markers and underlying anatomic abnormalities have yet to be elucidated. Clear demonstration of these factors would result in easier diagnosis and may even aid in developing novel treatments for the condition. As the literature has yet to conclusively identify MRI markers, a machine learning model trained through MRI segmentation offers a novel method to classify radiographic markers that would not be detectable through traditional analysis methods. <h3>Design/Methods:</h3> After institutional review board approval, we retrospectively identified 64 patients with FSD and 23 with TLE who underwent workup in the epilepsy monitoring unit between 2015 and 2022. Patients were included in the study only if their typical episode was observed during EEG monitoring, thus confirming their diagnosis and study group. MRI for each patient was then pre-processed and systematically fed through a convolution neural network, generating a novel machine-learning model. <h3>Results:</h3> Although analysis and patient selection are still ongoing, our model has already identified several regions of interest. Currently, we have obtained a positive model certainty of 55% and a negative model certainty of 65% when training from the left thalamus, anterior corpus callosum, and left cerebral cortex. <h3>Conclusions:</h3> Our findings demonstrate promise in using machine learning when assessing complex disorders such as functional seizure disorder. Furthermore, continued work with our machine-learning model may aid in identifying anatomic MRI markers shared by patients with FSD. This work may ultimately expand the understanding of the underlying mechanisms and diagnostic methods available for the disorder. <b>Disclosure:</b> Mr. Moss has nothing to disclose. Ms. Schmid has nothing to disclose. An immediate family member of Dr. Bermeo Ovalle has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bioserenity. An immediate family member of Dr. Bermeo Ovalle has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. An immediate family member of Dr. Bermeo Ovalle has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sunovion. An immediate family member of Dr. Bermeo Ovalle has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Greenwich Biosciences. An immediate family member of Dr. Bermeo Ovalle has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for SK Life Science. An immediate family member of Dr. Bermeo Ovalle has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Neurelis. An immediate family member of Dr. Bermeo Ovalle has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal on Clinical Neuropysiology. An immediate family member of Dr. Bermeo Ovalle has received publishing royalties from a publication relating to health care. Travis Stoub has nothing to disclose. Dr. O’Dwyer has nothing to disclose.

INTEGRATING PROSTATE SPECIFIC ANTIGEN DENSITY BIOMARKER INTO DEEP LEARNING PROSTATE MRI LESION SEGMENTATION MODELS.

Prostate cancer lesion segmentation in multi-parametric magnetic resonance imaging (mpMRI) is crucial for pre-biopsy diagnosis and targeted biopsy guidance. Deep convolution neural networks have been widely utilized for lesion segmentation. However, these methods fail to achieve a high Dice coefficient because of the large variations in lesion size and location within the gland. To address this problem, we integrate the clinically-meaningful prostate specific antigen density (PSAD) biomarker into the deep learning model using feature-wise transformations to condition the features in latent space, and thus control the size of lesion prediction. We tested our models on a public dataset with 214 annotated mpMRI scans and compared the segmentation performance to a baseline 3D U-Net model. Results demonstrate that integrating the PSAD biomarker significantly improves segmentation performance in both Dice coefficient and centroid distance metric.

Next generation immuno-oncology tumor profiling using a rapid, non-invasive, computational biophysics biomarker in early-stage breast cancer.

Immuno-oncology (IO) therapies targeting the PD-1/PD-L1 axis, such as immune checkpoint inhibitor (ICI) antibodies, have emerged as promising treatments for early-stage breast cancer (ESBC). Despite immunotherapy's clinical significance, the number of benefiting patients remains small, and the therapy can prompt severe immune-related events. Current pathologic and transcriptomic predictions of IO response are limited in terms of accuracy and rely on single-site biopsies, which cannot fully account for tumor heterogeneity. In addition, transcriptomic analyses are costly and time-consuming. We therefore constructed a computational biomarker coupling biophysical simulations and artificial intelligence-based tissue segmentation of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRIs), enabling IO response prediction across the entire tumor. By analyzing both single-cell and whole-tissue RNA-seq data from non-IO-treated ESBC patients, we associated gene expression levels of the PD-1/PD-L1 axis with local tumor biology. PD-L1 expression was then linked to biophysical features derived from DCE-MRIs to generate spatially- and temporally-resolved atlases (virtual tumors) of tumor biology, as well as the TumorIO biomarker of IO response. We quantified TumorIO within patient virtual tumors (n = 63) using integrative modeling to train and develop a corresponding TumorIO Score. We validated the TumorIO biomarker and TumorIO Score in a small, independent cohort of IO-treated patients (n = 17) and correctly predicted pathologic complete response (pCR) in 15/17 individuals (88.2% accuracy), comprising 10/12 in triple negative breast cancer (TNBC) and 5/5 in HR+/HER2- tumors. We applied the TumorIO Score in a virtual clinical trial (n = 292) simulating ICI administration in an IO-naïve cohort that underwent standard chemotherapy. Using this approach, we predicted pCR rates of 67.1% for TNBC and 17.9% for HR+/HER2- tumors with addition of IO therapy; comparing favorably to empiric pCR rates derived from published trials utilizing ICI in both cancer subtypes. The TumorIO biomarker and TumorIO Score represent a next generation approach using integrative biophysical analysis to assess cancer responsiveness to immunotherapy. This computational biomarker performs as well as PD-L1 transcript levels in identifying a patient's likelihood of pCR following anti-PD-1 IO therapy. The TumorIO biomarker allows for rapid IO profiling of tumors and may confer high clinical decision impact to further enable personalized oncologic care.

Uncertainty parameter weighted entropy-based fuzzy c-means algorithm using complemented membership functions for noisy volumetric brain MR image segmentation

In this paper, we propose an uncertainty parameter weighted entropy-based fuzzy c-means clustering algorithm for noisy volumetric (3D) brain MR image segmentation using complemented global and spatially constraint local membership functions. Due to inherent noise and intensity inhomogeneity (IIH), the acquired MR images have blurry tissue boundaries. This leads to a situation where uncertainty arises while labeling a pixel/voxel into its proper tissue region. Further, it magnifies in the regions of different tissue boundaries. The proposed algorithm addresses this issue by introducing a class-level uncertainty parameter for each voxel and weightedly incorporating in the fuzzy objective function using complemented global and spatially constraint local fuzzy membership functions. It also incorporates total uncertainties in the 3D image domain by means of Shannon entropy. The complemented local fuzzy membership function estimates the degree of non-association, constraint by the local region-level intensity distribution. This framework allows the algorithm to utilize the spatial intensity distribution both in locally and globally within the image domain and produce more accurate cluster prototypes. We validate the proposed algorithm qualitatively and quantitatively with 10 3D simulated brain MR images, contaminated by noise and intensity inhomogeneity, 4 volumes of clinical real patient 3D brain MR images and a synthetic 3D image with added Rician noise. The simulation results in several evaluation indices indicate its superiority over state-of-the-art algorithms developed in recent past.