A Deep Learning Approach to Predict Recanalization First-Pass Effect following Mechanical Thrombectomy in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Following endovascular thrombectomy in patients with large-vessel occlusion stroke, successful recanalization from 1 attempt, known as the first-pass effect, has correlated favorably with long-term outcomes. Pretreatment imaging may contain information that can be used to predict the first-pass effect. Recently, applications of machine learning models have shown promising results in predicting recanalization outcomes, albeit requiring manual segmentation. In this study, we sought to construct completely automated methods using deep learning to predict the first-pass effect from pretreatment CT and MR imaging. MATERIALS AND METHODS: Our models were developed and evaluated using a cohort of 326 patients who underwent endovascular thrombectomy at UCLA Ronald Reagan Medical Center from 2014 to 2021. We designed a hybrid transformer model with nonlocal and cross-attention modules to predict the first-pass effect on MR imaging and CT series. RESULTS: The proposed method achieved a mean 0.8506 (SD, 0.0712) for cross-validation receiver operating characteristic area under the curve (ROC-AUC) on MR imaging and 0.8719 (SD, 0.0831) for cross-validation ROC-AUC on CT. When evaluated on the prospective test sets, our proposed model achieved a mean ROC-AUC of 0.7967 (SD, 0.0335) with a mean sensitivity of 0.7286 (SD, 0.1849) and specificity of 0.8462 (SD, 0.1216) for MR imaging and a mean ROC-AUC of 0.8051 (SD, 0.0377) with a mean sensitivity of 0.8615 (SD, 0.1131) and specificity 0.7500 (SD, 0.1054) for CT, respectively, representing the first classification of the first-pass effect from MR imaging alone and the first automated first-pass effect classification method in CT. CONCLUSIONS: Results illustrate that both nonperfusion MR imaging and CT from admission contain signals that can predict a successful first-pass effect following endovascular thrombectomy using our deep learning methods without requiring time-intensive manual segmentation.

Integrating Battlefield Documentation into Virtual Reality Medical Simulation Training: Virtual Battlefield Assisted Trauma Distributed Observation Kit (BATDOK).

INTRODUCTION: Clinical documentation is an essential component of the provision of medical care, enabling continuity of information across provider and site handoffs. This is particularly important in the combat casualty care setting when a single casualty may be treated by four or more or five completely disparate teams across the roles of care. The Battlefield Assisted Trauma Distributed Observation Kit (BATDOK) is a digital battlefield clinical documentation system developed by the Air Force Research Laboratory to address this need. To support the deployment of this tool, we integrated BATDOK into a commercially available virtual reality (VR) medical simulation platform used by the U.S. Air Force and Defense Health Agency personnel in order to provide an immersive simulation training experience which included battlefield documentation. METHODS: A multidisciplinary team consisting of medical educators, VR simulation engineers, emergency physicians and pararescuemen, and BATDOK developers first developed a specification for a virtual BATDOK capability, including a detailed listing of learning objectives, critical interfaces and task plans, and sensor integrations. These specifications were then implemented into the commercially available Virtual Advancement of Learning for Operational Readiness VR Medical Simulation System and underwent developmental testing and evaluation during pararescueman training exercises at the Air Force Special Operations Command Special Operations Center for Medical Integration and Development. RESULTS AND CONCLUSIONS: The BATDOK capability was successfully implemented within the VR Medical Simulation System. The capability consisted of a virtual tablet with replicated interfaces and capabilities based on the developed specifications. These capabilities included integrated point-of-care ultrasound capability, multi-patient management, vitals sign monitoring with sensor pairing and continuous monitoring, mechanism of injury documentation (including injury pattern documentation), intervention logging (including tourniquets, dressing, airways, lines, tubes and drains, splints, fluids, and medications), and event logging. The capability was found to be operational and in alignment with learning objectives and user acceptance goals.

Perfusion Collateral Index versus Hypoperfusion Intensity Ratio in Assessment of Collaterals in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Perfusion-based collateral indices such as the perfusion collateral index and the hypoperfusion intensity ratio have shown promise in the assessment of collaterals in patients with acute ischemic stroke. We aimed to compare the diagnostic performance of the perfusion collateral index and the hypoperfusion intensity ratio in collateral assessment compared with angiographic collaterals and outcome measures, including final infarct volume, infarct growth, and functional independence. MATERIALS AND METHODS: Consecutive patients with acute ischemic stroke with anterior circulation proximal arterial occlusion who underwent endovascular thrombectomy and had pre- and posttreatment MRI were included. Using pretreatment MR perfusion, we calculated the perfusion collateral index and the hypoperfusion intensity ratio for each patient. The angiographic collaterals obtained from DSA were dichotomized to sufficient (American Society of Interventional and Therapeutic Neuroradiology [ASITN] scale 3-4) versus insufficient (ASITN scale 0-2). The association of collateral status determined by the perfusion collateral index and the hypoperfusion intensity ratio was assessed against angiographic collaterals and outcome measures. RESULTS: A total of 98 patients met the inclusion criteria. Perfusion collateral index values were significantly higher in patients with sufficient angiographic collaterals (P < .001), while there was no significant (P = .46) difference in hypoperfusion intensity ratio values. Among patients with good (mRS 0-2) versus poor (mRS 3-6) functional outcome, the perfusion collateral index of ≥ 62 was present in 72% versus 31% (P = .003), while the hypoperfusion intensity ratio of ≤0.4 was present in 69% versus 56% (P = .52). The perfusion collateral index and the hypoperfusion intensity ratio were both significantly predictive of final infarct volume, but only the perfusion collateral index was significantly (P = .03) associated with infarct growth. CONCLUSIONS: Results show that the perfusion collateral index outperforms the hypoperfusion intensity ratio in the assessment of collateral status, infarct growth, and determination of functional outcomes.

Multi-Parametric Radiomic Model to Predict 1p/19q Co-Deletion in Patients with IDH-1 Mutant Glioma: Added Value to the T2-FLAIR Mismatch Sign.

PURPOSE: The T2-FLAIR mismatch sign has shown promise in determining IDH mutant 1p/19q non-co-deleted gliomas with a high specificity and modest sensitivity. To develop a multi-parametric radiomic model using MRI to predict 1p/19q co-deletion status in patients with newly diagnosed IDH1 mutant glioma and to perform a comparative analysis to T2-FLAIR mismatch sign+. METHODS: In this retrospective study, patients with diagnosis of IDH1 mutant gliomas with known 1p/19q status who had preoperative MRI were included. T2-FLAIR mismatch was evaluated independently by two board-certified neuroradiologists. Texture features were extracted from glioma segmentation of FLAIR images. eXtremeGradient Boosting (XGboost) classifiers were used for model development. Leave-one-out-cross-validation (LOOCV) and external validation performances were reported for both the training and external validation sets. RESULTS: A total of 103 patients were included for model development and 18 patients for external testing validation. The diagnostic performance (sensitivity/specificity/accuracy) in the determination of the 1p/19q co-deletion status was 59%/83%/67% (training) and 62.5%/70.0%/66.3% (testing) for the T2-FLAIR mismatch sign. This was significantly improved (p = 0.04) using the radiomics model to 77.9%/82.8%/80.3% (training) and 87.5%/89.9%/88.8% (testing), respectively. The addition of radiomics as a computer-assisted tool resulted in significant (p = 0.02) improvement in the performance of the neuroradiologist with 13 additional corrected cases in comparison to just using the T2-FLAIR mismatch sign. CONCLUSION: The proposed radiomic model provides much needed sensitivity to the highly specific T2-FLAIR mismatch sign in the determination of the 1p/19q non-co-deletion status and improves the overall diagnostic performance of neuroradiologists when used as an assistive tool.

Automated estimation of ischemic core volume on noncontrast-enhanced CT via machine learning.

BACKGROUND: Accurate estimation of ischemic core on baseline imaging has treatment implications in patients with acute ischemic stroke (AIS). Machine learning (ML) algorithms have shown promising results in estimating ischemic core using routine noncontrast computed tomography (NCCT). OBJECTIVE: We used an ML-trained algorithm to quantify ischemic core volume on NCCT in a comparative analysis to pretreatment magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) in patients with AIS. METHODS: Patients with AIS who had both pretreatment NCCT and MRI were enrolled. An automatic segmentation ML approach was applied using Brainomix software (Oxford, UK) to segment the ischemic voxels and calculate ischemic core volume on NCCT. Ischemic core volume was also calculated on baseline MRI DWI. Comparative analysis was performed using Bland-Altman plots and Pearson correlation. RESULTS: A total of 72 patients were included. The time-to-stroke onset time was 134.2/89.5 minutes (mean/median). The time difference between NCCT and MRI was 64.8/44.5 minutes (mean/median). In patients who presented within 1 hour from stroke onset, the ischemic core volumes were significantly (p = 0.005) underestimated by ML-NCCT. In patients presented beyond 1 hour, the ML-NCCT estimated ischemic core volumes approximated those obtained by MRI-DWI and with significant correlation (r = 0.56, p < 0.001). CONCLUSION: The ischemic core volumes calculated by the described ML approach on NCCT approximate those obtained by MRI in patients with AIS who present beyond 1 hour from stroke onset.

Identifying acute ischemic stroke patients within the thrombolytic treatment window using deep learning.

BACKGROUND AND PURPOSE: Treatment of acute ischemic stroke is heavily contingent upon time, as there is a strong relationship between time clock and tissue progression. Work has established imaging biomarker assessments as surrogates for time since stroke (TSS), namely, by comparing signal mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) imaging. Our goal was to develop an automatic technique for determining TSS from imaging that does not require subspecialist radiology expertise. METHODS: Using 772 patients (66 ± 9 years, 319 women), we developed and externally evaluated a deep learning network for classifying TSS from MR images and compared algorithm predictions to neuroradiologist assessments of DWI-FLAIR mismatch. Models were trained to classify TSS within 4.5 hours and performance metrics with confidence intervals were reported on both internal and external evaluation sets. RESULTS: Three board-certified neuroradiologists' DWI-FLAIR mismatch assessments, based on majority vote, yielded a sensitivity of .62, a specificity of .86, and a Fleiss' kappa of .46 when used to classify TSS. The deep learning method performed similarly to radiologists and outperformed previously reported methods, with the best model achieving an average evaluation accuracy, sensitivity, and specificity of .726, .712, and .741, respectively, on an internal cohort and .724, .757, and .679, respectively, on an external cohort. CONCLUSION: Our model achieved higher generalization performance on external evaluation datasets than the current state-of-the-art for TSS classification. These results demonstrate the potential of automatic assessment of onset time from imaging without the need for expertly trained radiologists.

High resolution histopathology image generation and segmentation through adversarial training.

Semantic segmentation of histopathology images can be a vital aspect of computer-aided diagnosis, and deep learning models have been effectively applied to this task with varying levels of success. However, their impact has been limited due to the small size of fully annotated datasets. Data augmentation is one avenue to address this limitation. Generative Adversarial Networks (GANs) have shown promise in this respect, but previous work has focused mostly on classification tasks applied to MR and CT images, both of which have lower resolution and scale than histopathology images. There is limited research that applies GANs as a data augmentation approach for large-scale image semantic segmentation, which requires high-quality image-mask pairs. In this work, we propose a multi-scale conditional GAN for high-resolution, large-scale histopathology image generation and segmentation. Our model consists of a pyramid of GAN structures, each responsible for generating and segmenting images at a different scale. Using semantic masks, the generative component of our model is able to synthesize histopathology images that are visually realistic. We demonstrate that these synthesized images along with their masks can be used to boost segmentation performance, especially in the semi-supervised scenario.

PathAL: An Active Learning Framework for Histopathology Image Analysis.

Deep neural networks, in particular convolutional networks, have rapidly become a popular choice for analyzing histopathology images. However, training these models relies heavily on a large number of samples manually annotated by experts, which is cumbersome and expensive. In addition, it is difficult to obtain a perfect set of labels due to the variability between expert annotations. This paper presents a novel active learning (AL) framework for histopathology image analysis, named PathAL. To reduce the required number of expert annotations, PathAL selects two groups of unlabeled data in each training iteration: one "informative" sample that requires additional expert annotation, and one "confident predictive" sample that is automatically added to the training set using the model's pseudo-labels. To reduce the impact of the noisy-labeled samples in the training set, PathAL systematically identifies noisy samples and excludes them to improve the generalization of the model. Our model advances the existing AL method for medical image analysis in two ways. First, we present a selection strategy to improve classification performance with fewer manual annotations. Unlike traditional methods focusing only on finding the most uncertain samples with low prediction confidence, we discover a large number of high confidence samples from the unlabeled set and automatically add them for training with assigned pseudo-labels. Second, we design a method to distinguish between noisy samples and hard samples using a heuristic approach. We exclude the noisy samples while preserving the hard samples to improve model performance. Extensive experiments demonstrate that our proposed PathAL framework achieves promising results on a prostate cancer Gleason grading task, obtaining similar performance with 40% fewer annotations compared to the fully supervised learning scenario. An ablation study is provided to analyze the effectiveness of each component in PathAL, and a pathologist reader study is conducted to validate our proposed algorithm.

A Semi-Supervised Learning Framework to Leverage Proxy Information for Stroke MRI Analysis.

Treating acute ischemic stroke (AIS) patients is a time-sensitive endeavor, as therapies target areas experiencing ischemia to prevent irreversible damage to brain tissue. Depending on how an AIS is progressing, thrombolytics such as tissue-plasminogen activator (tPA) may be administered within a short therapeutic window. The underlying conditions for optimal treatment are varied. While previous clinical guidelines only permitted tPA to be administered to patients with a known onset within 4.5 hours, clinical trials demonstrated that patients with signal intensity differences between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences in an MRI study can benefit from thrombolytic therapy. This intensity difference, known as DWI-FLAIR mismatch, is prone to high inter-reader variability. Thus, a paradigm exists where onset time serves as a weak proxy for DWI-FLAIR mismatch. In this study, we sought to detect DWI-FLAIR mismatch in an automated fashion, and we compared this to assessments done by three expert neuroradiologists. Our approach involved training a deep learning model on MRI to classify tissue clock and leveraging time clock as a weak proxy label to supplement training in a semi-supervised learning (SSL) framework. We evaluate our deep learning model by testing it on an unseen dataset from an external institution. In total, our proposed framework was able to improve detection of DWI-FLAIR mismatch, achieving a top ROC-AUC of 74.30%. Our study illustrated that incorporating clinical proxy information into SSL can improve model optimization by increasing the fidelity of unlabeled samples included in the training process.

Intra-domain task-adaptive transfer learning to determine acute ischemic stroke onset time.

Treatment of acute ischemic strokes (AIS) is largely contingent upon the time since stroke onset (TSS). However, TSS may not be readily available in up to 25% of patients with unwitnessed AIS. Current clinical guidelines for patients with unknown TSS recommend the use of MRI to determine eligibility for thrombolysis, but radiology assessments have high inter-reader variability. In this work, we present deep learning models that leverage MRI diffusion series to classify TSS based on clinically validated thresholds. We propose an intra-domain task-adaptive transfer learning method, which involves training a model on an easier clinical task (stroke detection) and then refining the model with different binary thresholds of TSS. We apply this approach to both 2D and 3D CNN architectures with our top model achieving an ROC-AUC value of 0.74, with a sensitivity of 0.70 and a specificity of 0.81 for classifying TSS < 4.5 h. Our pretrained models achieve better classification metrics than the models trained from scratch, and these metrics exceed those of previously published models applied to our dataset. Furthermore, our pipeline accommodates a more inclusive patient cohort than previous work, as we did not exclude imaging studies based on clinical, demographic, or image processing criteria. When applied to this broad spectrum of patients, our deep learning model achieves an overall accuracy of 75.78% when classifying TSS < 4.5 h, carrying potential therapeutic implications for patients with unknown TSS.

A Machine Learning Approach to Predict Acute Ischemic Stroke Thrombectomy Reperfusion using Discriminative MR Image Features.

Mechanical thrombectomy (MTB) is one of the two standard treatment options for Acute Ischemic Stroke (AIS) patients. Current clinical guidelines instruct the use of pretreatment imaging to characterize a patient's cerebrovascular flow, as there are many factors that may underlie a patient's successful response to treatment. There is a critical need to leverage pretreatment imaging, taken at admission, to guide potential treatment avenues in an automated fashion. The aim of this study is to develop and validate a fully automated machine learning algorithm to predict the final modified thrombolysis in cerebral infarction (mTICI) score following MTB. A total 321 radiomics features were computed from segmented pretreatment MRI scans for 141 patients. Successful recanalization was defined as mTICI score >= 2c. Different feature selection methods and classification models were examined in this study. Our best performance model achieved 74.42±2.52% AUC, 75.56±4.44% sensitivity, and 76.75±4.55% specificity, showing a good prediction of reperfusion quality using pretreatment MRI. Results suggest that MR images can be informative to predicting patient response to MTB, and further validation with a larger cohort can determine the clinical utility.

Biomedical Informatics on the Cloud: A Treasure Hunt for Advancing Cardiovascular Medicine.

In the digital age of cardiovascular medicine, the rate of biomedical discovery can be greatly accelerated by the guidance and resources required to unearth potential collections of knowledge. A unified computational platform leverages metadata to not only provide direction but also empower researchers to mine a wealth of biomedical information and forge novel mechanistic insights. This review takes the opportunity to present an overview of the cloud-based computational environment, including the functional roles of metadata, the architecture schema of indexing and search, and the practical scenarios of machine learning-supported molecular signature extraction. By introducing several established resources and state-of-the-art workflows, we share with our readers a broadly defined informatics framework to phenotype cardiovascular health and disease.

Equipping Physiologists with an Informatics Tool Chest: Toward an Integerated Mitochondrial Phenome.

Understanding the complex involvement of mitochondrial biology in disease development often requires the acquisition, analysis, and integration of large-scale molecular and phenotypic data. An increasing number of bioinformatics tools are currently employed to aid in mitochondrial investigations, most notably in predicting or corroborating the spatial and temporal dynamics of mitochondrial molecules, in retrieving structural data of mitochondrial components, and in aggregating as well as transforming mitochondrial centric biomedical knowledge. With the increasing prevalence of complex Big Data from omics experiments and clinical cohorts, informatics tools have become indispensable in our quest to understand mitochondrial physiology and pathology. Here we present an overview of the various informatics resources that are helping researchers explore this vital organelle and gain insights into its form, function, and dynamics.