Sanjiv J. Shah

Adrienne Kline, Vinesh Appadurai, Yuan Luo et al.

Leveraging medical record information in the era of big data and machine learning comes with the caveat that data must be cleaned and de-identified. Facilitating data sharing and harmonization for multi-center collaborations are particularly difficult when protected health information (PHI) is contained or embedded in image meta-data. We propose a novel library in the Python framework, called PyLogik, to help alleviate this issue for ultrasound images, which are particularly challenging because of the frequent inclusion of PHI directly on the images. PyLogik processes the image volumes through a series of text detection/extraction, filtering, thresholding, morphological and contour comparisons. This methodology de-identifies the images, reduces file sizes, and prepares image volumes for applications in deep learning and data sharing. To evaluate its effectiveness in processing ultrasound data, a random sample of 50 cardiac ultrasounds (echocardiograms) were processed through PyLogik, and the outputs were compared with the manual segmentations by an expert user. The Dice coefficient of the two approaches achieved an average value of 0.976. Next, an investigation was conducted to ascertain the degree of information compression achieved using the algorithm. Resultant data was found to be on average ~72% smaller after processing by PyLogik. Our results suggest that PyLogik is a viable methodology for data cleaning and de-identification, determining ROI, and file compression which will facilitate efficient storage, use, and dissemination of ultrasound data. Variants of the pipeline have also been created for use with other medical imaging data types.

Abhishek Kalyan Adupa, Ravi Prakash Garg, Jessica Corona-Cox et al.

To reduce the large amount of time spent screening, identifying, and recruiting patients into clinical trials, we need prescreening systems that are able to automate the data extraction and decision-making tasks that are typically relegated to clinical research study coordinators. However, a major obstacle is the vast amount of patient data available as unstructured free-form text in electronic health records. Here we propose an information extraction-based approach that first automatically converts unstructured text into a structured form. The structured data are then compared against a list of eligibility criteria using a rule-based system to determine which patients qualify for enrollment in a heart failure clinical trial. We show that we can achieve highly accurate results, with recall and precision values of 0.95 and 0.86, respectively. Our system allowed us to significantly reduce the time needed for prescreening patients from a few weeks to a few minutes. Our open-source information extraction modules are available for researchers and could be tested and validated in other cardiovascular trials. An approach such as the one we demonstrate here may decrease costs and expedite clinical trials, and could enhance the reproducibility of trials across institutions and populations.

Yiming Li, Sanjiv J. Shah, Donna Arnett et al.

Hypertension is the leading global cause of cardiovascular disease and premature death. Distinct hypertension subtypes may vary in their prognoses and require different treatments. An individual's risk for hypertension is determined by genetic and environmental factors as well as their interactions. In this work, we studied 911 African Americans and 1,171 European Americans in the Hypertension Genetic Epidemiology Network (HyperGEN) cohort. We built hypertension subtype classification models using both environmental variables and sets of genetic features selected based on different criteria. The fitted prediction models provided insights into the genetic landscape of hypertension subtypes, which may aid personalized diagnosis and treatment of hypertension in the future.

Yuan Luo, Chengsheng Mao, Yiben Yang et al.

Hypertension is a heterogeneous syndrome in need of improved subtyping using phenotypic and genetic measurements so that patients in different subtypes share similar pathophysiologic mechanisms and respond more uniformly to targeted treatments. Existing machine learning approaches often face challenges in integrating phenotype and genotype information and presenting to clinicians an interpretable model. We aim to provide informed patient stratification by introducing Hybrid Non-negative Matrix Factorization (HNMF) on phenotype and genotype matrices. HNMF simultaneously approximates the phenotypic and genetic matrices using different appropriate loss functions, and generates patient subtypes, phenotypic groups and genetic groups. Unlike previous methods, HNMF approximates phenotypic matrix under Frobenius loss, and genetic matrix under Kullback-Leibler (KL) loss. We propose an alternating projected gradient method to solve the approximation problem. Simulation shows HNMF converges fast and accurately to the true factor matrices. On real-world clinical dataset, we used the patient factor matrix as features to predict main cardiac mechanistic outcomes. We compared HNMF with six different models using phenotype or genotype features alone, with or without NMF, or using joint NMF with only one type of loss. HNMF significantly outperforms all comparison models. HNMF also reveals intuitive phenotype-genotype interactions that characterize cardiac abnormalities.

Jeffrey Zhang, Sravani Gajjala, Pulkit Agrawal et al.

Automated cardiac image interpretation has the potential to transform clinical practice in multiple ways including enabling low-cost serial assessment of cardiac function in the primary care and rural setting. We hypothesized that advances in computer vision could enable building a fully automated, scalable analysis pipeline for echocardiogram (echo) interpretation. Our approach entailed: 1) preprocessing; 2) convolutional neural networks (CNN) for view identification, image segmentation, and phasing of the cardiac cycle; 3) quantification of chamber volumes and left ventricular mass; 4) particle tracking to compute longitudinal strain; and 5) targeted disease detection. CNNs accurately identified views (e.g. 99% for apical 4-chamber) and segmented individual cardiac chambers. Cardiac structure measurements agreed with study report values (e.g. mean absolute deviations (MAD) of 7.7 mL/kg/m2 for left ventricular diastolic volume index, 2918 studies). We computed automated ejection fraction and longitudinal strain measurements (within 2 cohorts), which agreed with commercial software-derived values [for ejection fraction, MAD=5.3%, N=3101 studies; for strain, MAD=1.5% (n=197) and 1.6% (n=110)], and demonstrated applicability to serial monitoring of breast cancer patients for trastuzumab cardiotoxicity. Overall, we found that, compared to manual measurements, automated measurements had superior performance across seven internal consistency metrics with an average increase in the Spearman correlation coefficient of 0.05 (p=0.02). Finally, we developed disease detection algorithms for hypertrophic cardiomyopathy and cardiac amyloidosis, with C-statistics of 0.93 and 0.84, respectively. Our pipeline lays the groundwork for using automated interpretation to support point-of-care handheld cardiac ultrasound and large-scale analysis of the millions of echos archived within healthcare systems.

Ravi Garg, Shu Dong, Sanjiv Shah et al.

Rare diseases are very difficult to identify among large number of other possible diagnoses. Better availability of patient data and improvement in machine learning algorithms empower us to tackle this problem computationally. In this paper, we target one such rare disease - cardiac amyloidosis. We aim to automate the process of identifying potential cardiac amyloidosis patients with the help of machine learning algorithms and also learn most predictive factors. With the help of experienced cardiologists, we prepared a gold standard with 73 positive (cardiac amyloidosis) and 197 negative instances. We achieved high average cross-validation F1 score of 0.98 using an ensemble machine learning classifier. Some of the predictive variables were: Age and Diagnosis of cardiac arrest, chest pain, congestive heart failure, hypertension, prim open angle glaucoma, and shoulder arthritis. Further studies are needed to validate the accuracy of the system across an entire health system and its generalizability for other diseases.