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Automated detection and quantification of breast cancer brain metastases in an animal model using democratized machine learning tools.

ABSTRACT: Advances in digital whole-slide imaging and machine learning (ML) provide new opportunities for automated examination and quantification of histopathological slides to support pathologists and biologists. However, implementation of ML tools often requires advanced skills in computer science that may not be immediately available in the traditional wet-lab environment. Here, we propose a simple and accessible workflow to automate detection and quantification of brain epithelial metastases on digitized histological slides. We leverage 100 Hematoxylin & Eosin (H&E)-stained whole slide images (WSIs) from 25 Balb/c mice with various level of brain metastatic tumor burden. A supervised training of the Trainable Weka Segmentation (TWS) from Fiji was achieved from annotated WSIs. Upon comparison with manually drawn regions, it is apparent that the algorithm learned to identify and segment cancer cell-specific nuclei and normal brain tissue. Our approach resulted in a robust and highly concordant correlation between automated metastases quantification of brain metastases and manual human assessment (R²?=?0.8783; P?

SUBMITTER: Sikpa D

PROVIDER: S-EPMC6874643 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Automated detection and quantification of breast cancer brain metastases in an animal model using democratized machine learning tools.

Sikpa Dina D Fouquet Jérémie P JP Lebel Réjean R Diamandis Phedias P Richer Maxime M Lepage Martin M

Scientific reports 20191122 1

Advances in digital whole-slide imaging and machine learning (ML) provide new opportunities for automated examination and quantification of histopathological slides to support pathologists and biologists. However, implementation of ML tools often requires advanced skills in computer science that may not be immediately available in the traditional wet-lab environment. Here, we propose a simple and accessible workflow to automate detection and quantification of brain epithelial metastases on digit ...[more]

PMID: 31758004

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Project description:BackgroundMetastatic complications are a major cause of cancer-related morbidity, with up to 40% of cancer patients experiencing at least one brain metastasis. Earlier detection may significantly improve patient outcomes and overall survival. We investigated machine learning (ML) models for early detection of brain metastases based on diffusion weighted imaging (DWI) radiomics.MethodsLongitudinal diffusion imaging from 116 patients previously treated with stereotactic radiosurgery (SRS) for brain metastases were retrospectively analyzed. Clinical contours from 600 metastases were extracted from radiosurgery planning computed tomography, and rigidly registered to corresponding contrast enhanced-T1 and apparent diffusion coefficient (ADC) maps. Contralateral contours located in healthy brain tissue were used as control. The dataset consisted of (I) radiomic features using ADC maps, (II) radiomic feature change calculated using timepoints before the metastasis manifested on contrast enhanced-T1, (III) primary cancer, and (IV) anatomical location. The dataset was divided into training and internal validation sets using an 80/20 split with stratification. Four classification algorithms [Linear Support Vector Machine (SVM), Random Forest (RF), AdaBoost, and XGBoost] underwent supervised classification training, with contours labeled either 'control' or 'metastasis'. Hyperparameters were optimized towards balanced accuracy. Various model metrics (receiver operating characteristic curve area scores, accuracy, recall, and precision) were calculated to gauge performance.ResultsThe radiomic and clinical data set, feature engineering, and ML models developed were able to identify metastases with an accuracy of up to 87.7% on the training set, and 85.8% on an unseen test set. XGBoost and RF showed superior accuracy (XGBoost: 0.877±0.021 and 0.833±0.47, RF: 0.823±0.024 and 0.858±0.045) for training and validation sets, respectively. XGBoost and RF also showed strong area under the receiver operating characteristic curve (AUC) performance on the validation set (0.910±0.037 and 0.922±0.034, respectively). AdaBoost performed slightly lower in all metrics. SVM model generalized poorly with the internal validation set. Important features involved changes in radiomics months before manifesting on contrast enhanced-T1.ConclusionsThe proposed models using diffusion-based radiomics showed encouraging results in differentiating healthy brain tissue from metastases using clinical imaging data. These findings suggest that longitudinal diffusion imaging and ML may help improve patient care through earlier diagnosis and increased patient monitoring/follow-up. Future work aims to improve model classification metrics, robustness, user-interface, and clinical applicability.

Project description:ObjectivesWe aimed to evaluate whether deep learning-based detection and quantification of brain metastasis (BM) may suggest treatment options for patients with BMs.MethodsThe deep learning system (DLS) for detection and quantification of BM was developed in 193 patients and applied to 112 patients that were newly detected on black-blood contrast-enhanced T1-weighted imaging. Patients were assigned to one of 3 treatment suggestion groups according to the European Association of Neuro-Oncology (EANO)-European Society for Medical Oncology (ESMO) recommendations using number and volume of the BMs detected by the DLS: short-term imaging follow-up without treatment (group A), surgery or stereotactic radiosurgery (limited BM, group B), or whole-brain radiotherapy or systemic chemotherapy (extensive BM, group C). The concordance between the DLS-based groups and clinical decisions was analyzed with or without consideration of targeted agents. The performance of distinguishing high-risk (B + C) was calculated.ResultsAmong 112 patients (mean age 64.3 years, 63 men), group C had the largest number and volume of BM, followed by group B (4.4 and 851.6 mm3) and A (1.5 and 15.5 mm3). The DLS-based groups were concordant with the actual clinical decisions, with an accuracy of 76.8% (86 of 112). Modified accuracy considering targeted agents was 81.3% (91 of 112). The DLS showed 95% (82/86) sensitivity and 81% (21/26) specificity for distinguishing the high risk.ConclusionDLS-based detection and quantification of BM have the potential to be helpful in the determination of treatment options for both low- and high-risk groups of limited and extensive BMs.Clinical relevance statementFor patients with newly diagnosed brain metastasis, deep learning-based detection and quantification may be used in clinical settings where prompt and accurate treatment decisions are required, which can lead to better patient outcomes.Key points• Deep learning-based brain metastasis detection and quantification showed excellent agreement with ground-truth classifications. • By setting an algorithm to suggest treatment based on the number and volume of brain metastases detected by the deep learning system, the concordance was 81.3%. • When dividing patients into low- and high-risk groups, the sensitivity for detecting the latter was 95%.

Project description:BackgroundApproximately one-fourth of all cancer metastases are found in the brain. MRI is the primary technique for detection of brain metastasis, planning of radiotherapy, and the monitoring of treatment response. Progress in tumor treatment now requires detection of new or growing metastases at the small subcentimeter size, when these therapies are most effective.PurposeTo develop a deep-learning-based approach for finding brain metastasis on MRI.Study typeRetrospective.SequenceAxial postcontrast 3D T1 -weighted imaging.Field strength1.5T and 3T.PopulationA total of 361 scans of 121 patients were used to train and test the Faster region-based convolutional neural network (Faster R-CNN): 1565 lesions in 270 scans of 73 patients for training; 488 lesions in 91 scans of 48 patients for testing. From the 48 outputs of Faster R-CNN, 212 lesions in 46 scans of 18 patients were used for training the RUSBoost algorithm (MatLab) and 276 lesions in 45 scans of 30 patients for testing.AssessmentTwo radiologists diagnosed and supervised annotation of metastases on brain MRI as ground truth. This data were used to produce a 2-step pipeline consisting of a Faster R-CNN for detecting abnormal hyperintensity that may represent brain metastasis and a RUSBoost classifier to reduce the number of false-positive foci detected.Statistical testsThe performance of the algorithm was evaluated by using sensitivity, false-positive rate, and receiver's operating characteristic (ROC) curves. The detection performance was assessed both per-metastases and per-slice.ResultsTesting on held-out brain MRI data demonstrated 96% sensitivity and 20 false-positive metastases per scan. The results showed an 87.1% sensitivity and 0.24 false-positive metastases per slice. The area under the ROC curve was 0.79.ConclusionOur results showed that deep-learning-based computer-aided detection (CAD) had the potential of detecting brain metastases with high sensitivity and reasonable specificity.Level of evidence3 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:1227-1236.

Dataset Information

Automated detection and quantification of breast cancer brain metastases in an animal model using democratized machine learning tools.

Publications

Automated detection and quantification of breast cancer brain metastases in an animal model using democratized machine learning tools.

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