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1. Evaluating the relationship between magnetic resonance image quality metrics and deep learning‐based segmentation accuracy of brain tumors

   https://doi.org/10.1002/mp.17059  

   Muthusivarajan, Rajarajeswari ; Celaya, Adrian ; Yung, Joshua P. ; Long, James P. ; Viswanath, Satish E. ; Marcus, Daniel S. ; Chung, Caroline ; Fuentes, David ( April 2024 , Medical Physics)

   Magnetic resonance imaging (MRI) scans are known to suffer from a variety of acquisition artifacts as well as equipment‐based variations that impact image appearance and segmentation performance. It is still unclear whether a direct relationship exists between magnetic resonance (MR) image quality metrics (IQMs) (e.g., signal‐to‐noise, contrast‐to‐noise) and segmentation accuracy.

   Deep learning (DL) approaches have shown significant promise for automated segmentation of brain tumors on MRI but depend on the quality of input training images. We sought to evaluate the relationship between IQMs of input training images and DL‐based brain tumor segmentation accuracy toward developing more generalizable models for multi‐institutional data.

   We trained a 3D DenseNet model on the BraTS 2020 cohorts for segmentation of tumor subregions enhancing tumor (ET), peritumoral edematous, and necrotic and non‐ET on MRI; with performance quantified via a 5‐fold cross‐validated Dice coefficient. MRI scans were evaluated through the open‐source quality control tool MRQy, to yield 13 IQMs per scan. The Pearson correlation coefficient was computed between whole tumor (WT) dice values and IQM measures in the training cohorts to identify quality measures most correlated with segmentation performance. Each selected IQM was used to group MRI scans as “better” quality (BQ) or “worse” quality (WQ), via relative thresholding. Segmentation performance was re‐evaluated for the DenseNet model when (i) training on BQ MRI images with validation on WQ images, as well as (ii) training on WQ images, and validation on BQ images. Trends were further validated on independent test sets derived from the BraTS 2021 training cohorts.

   For this study, multimodal MRI scans from the BraTS 2020 training cohorts were used to train the segmentation model and validated on independent test sets derived from the BraTS 2021 cohort. Among the selected IQMs, models trained on BQ images based on inhomogeneity measurements (coefficient of variance, coefficient of joint variation, coefficient of variation of the foreground patch) and the models trained on WQ images based on noise measurement peak signal‐to‐noise ratio (SNR) yielded significantly improved tumor segmentation accuracy compared to their inverse models.

   Our results suggest that a significant correlation may exist between specific MR IQMs and DenseNet‐based brain tumor segmentation performance. The selection of MRI scans for model training based on IQMs may yield more accurate and generalizable models in unseen validation.

    

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2. A Deep Learning Framework for Sickle Cell Disease Microfluidic Biomarker Assays

   https://doi.org/10.1182/blood-2020-141693  

   Praljak, Niksa ; Shipley, Brandon ; Gonzales, Ayesha ; Goreke, Utku ; Iram, Shamreen ; Singh, Gundeep ; Hill, Ailis ; Gurkan, Umut A. ; Hinczewski, Michael ( November 2020 , Blood)

   null (Ed.)

   Introduction: Vaso-occlusive crises (VOCs) are a leading cause of morbidity and early mortality in individuals with sickle cell disease (SCD). These crises are triggered by sickle red blood cell (sRBC) aggregation in blood vessels and are influenced by factors such as enhanced sRBC and white blood cell (WBC) adhesion to inflamed endothelium. Advances in microfluidic biomarker assays (i.e., SCD Biochip systems) have led to clinical studies of blood cell adhesion onto endothelial proteins, including, fibronectin, laminin, P-selectin, ICAM-1, functionalized in microchannels. These microfluidic assays allow mimicking the physiological aspects of human microvasculature and help characterize biomechanical properties of adhered sRBCs under flow. However, analysis of the microfluidic biomarker assay data has so far relied on manual cell counting and exhaustive visual morphological characterization of cells by trained personnel. Integrating deep learning algorithms with microscopic imaging of adhesion protein functionalized microfluidic channels can accelerate and standardize accurate classification of blood cells in microfluidic biomarker assays. Here we present a deep learning approach into a general-purpose analytical tool covering a wide range of conditions: channels functionalized with different proteins (laminin or P-selectin), with varying degrees of adhesion by both sRBCs and WBCs, and in both normoxic and hypoxic environments. Methods: Our neural networks were trained on a repository of manually labeled SCD Biochip microfluidic biomarker assay whole channel images. Each channel contained adhered cells pertaining to clinical whole blood under constant shear stress of 0.1 Pa, mimicking physiological levels in post-capillary venules. The machine learning (ML) framework consists of two phases: Phase I segments pixels belonging to blood cells adhered to the microfluidic channel surface, while Phase II associates pixel clusters with specific cell types (sRBCs or WBCs). Phase I is implemented through an ensemble of seven generative fully convolutional neural networks, and Phase II is an ensemble of five neural networks based on a Resnet50 backbone. Each pixel cluster is given a probability of belonging to one of three classes: adhered sRBC, adhered WBC, or non-adhered / other. Results and Discussion: We applied our trained ML framework to 107 novel whole channel images not used during training and compared the results against counts from human experts. As seen in Fig. 1A, there was excellent agreement in counts across all protein and cell types investigated: sRBCs adhered to laminin, sRBCs adhered to P-selectin, and WBCs adhered to P-selectin. Not only was the approach able to handle surfaces functionalized with different proteins, but it also performed well for high cell density images (up to 5000 cells per image) in both normoxic and hypoxic conditions (Fig. 1B). The average uncertainty for the ML counts, obtained from accuracy metrics on the test dataset, was 3%. This uncertainty is a significant improvement on the 20% average uncertainty of the human counts, estimated from the variance in repeated manual analyses of the images. Moreover, manual classification of each image may take up to 2 hours, versus about 6 minutes per image for the ML analysis. Thus, ML provides greater consistency in the classification at a fraction of the processing time. To assess which features the network used to distinguish adhered cells, we generated class activation maps (Fig. 1C-E). These heat maps indicate the regions of focus for the algorithm in making each classification decision. Intriguingly, the highlighted features were similar to those used by human experts: the dimple in partially sickled RBCs, the sharp endpoints for highly sickled RBCs, and the uniform curvature of the WBCs. Overall the robust performance of the ML approach in our study sets the stage for generalizing it to other endothelial proteins and experimental conditions, a first step toward a universal microfluidic ML framework targeting blood disorders. Such a framework would not only be able to integrate advanced biophysical characterization into fast, point-of-care diagnostic devices, but also provide a standardized and reliable way of monitoring patients undergoing targeted therapies and curative interventions, including, stem cell and gene-based therapies for SCD. Disclosures Gurkan: Dx Now Inc.: Patents & Royalties; Xatek Inc.: Patents & Royalties; BioChip Labs: Patents & Royalties; Hemex Health, Inc.: Consultancy, Current Employment, Patents & Royalties, Research Funding. 

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3. Cryo-shift: reducing domain shift in cryo-electron subtomograms with unsupervised domain adaptation and randomization

   https://doi.org/10.1093/bioinformatics/btab794  

   Bandyopadhyay, Hmrishav ; Deng, Zihao ; Ding, Leiting ; Liu, Sinuo ; Uddin, Mostofa Rafid ; Zeng, Xiangrui ; Behpour, Sima ; Xu, Min ; Xu, ed., Jinbo ( November 2021 , Bioinformatics)

   Cryo-Electron Tomography (cryo-ET) is a 3D imaging technology that enables the visualization of subcellular structures in situ at near-atomic resolution. Cellular cryo-ET images help in resolving the structures of macromolecules and determining their spatial relationship in a single cell, which has broad significance in cell and structural biology. Subtomogram classification and recognition constitute a primary step in the systematic recovery of these macromolecular structures. Supervised deep learning methods have been proven to be highly accurate and efficient for subtomogram classification, but suffer from limited applicability due to scarcity of annotated data. While generating simulated data for training supervised models is a potential solution, a sizeable difference in the image intensity distribution in generated data as compared with real experimental data will cause the trained models to perform poorly in predicting classes on real subtomograms.

   In this work, we present Cryo-Shift, a fully unsupervised domain adaptation and randomization framework for deep learning-based cross-domain subtomogram classification. We use unsupervised multi-adversarial domain adaption to reduce the domain shift between features of simulated and experimental data. We develop a network-driven domain randomization procedure with ‘warp’ modules to alter the simulated data and help the classifier generalize better on experimental data. We do not use any labeled experimental data to train our model, whereas some of the existing alternative approaches require labeled experimental samples for cross-domain classification. Nevertheless, Cryo-Shift outperforms the existing alternative approaches in cross-domain subtomogram classification in extensive evaluation studies demonstrated herein using both simulated and experimental data.

   https://github.com/xulabs/aitom.

   Supplementary data are available at Bioinformatics online.

    

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4. Evaluation of methods for generative modeling of cell and nuclear shape

   https://doi.org/10.1093/bioinformatics/bty983  

   Ruan, Xiongtao ; Murphy, Robert F. ; Wren, ed., Jonathan ( December 2018 , Bioinformatics)

   Cell shape provides both geometry for, and a reflection of, cell function. Numerous methods for describing and modeling cell shape have been described, but previous evaluation of these methods in terms of the accuracy of generative models has been limited.

   Here we compare traditional methods and deep autoencoders to build generative models for cell shapes in terms of the accuracy with which shapes can be reconstructed from models. We evaluated the methods on different collections of 2D and 3D cell images, and found that none of the methods gave accurate reconstructions using low dimensional encodings. As expected, much higher accuracies were observed using high dimensional encodings, with outline-based methods significantly outperforming image-based autoencoders. The latter tended to encode all cells as having smooth shapes, even for high dimensions. For complex 3D cell shapes, we developed a significant improvement of a method based on the spherical harmonic transform that performs significantly better than other methods. We obtained similar results for the joint modeling of cell and nuclear shape. Finally, we evaluated the modeling of shape dynamics by interpolation in the shape space. We found that our modified method provided lower deformation energies along linear interpolation paths than other methods. This allows practical shape evolution in high dimensional shape spaces. We conclude that our improved spherical harmonic based methods are preferable for cell and nuclear shape modeling, providing better representations, higher computational efficiency and requiring fewer training images than deep learning methods.

   All software and data is available at http://murphylab.cbd.cmu.edu/software.

   Supplementary data are available at Bioinformatics online.

    

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5. Machine Learning Estimation of Maximum Vertical Velocity from Radar

   https://doi.org/10.1175/AIES-D-23-0095.1  

   Chase, Randy J. ; McGovern, Amy ; Homeyer, Cameron R. ; Marinescu, Peter J. ; Potvin, Corey K. ( April 2024 , Artificial Intelligence for the Earth Systems)

   The quantification of storm updrafts remains unavailable for operational forecasting despite their inherent importance to convection and its associated severe weather hazards. Updraft proxies, like overshooting top area from satellite images, have been linked to severe weather hazards but only relate to a limited portion of the total storm updraft. This study investigates if a machine learning model, namely, U-Nets, can skillfully retrieve maximum vertical velocity and its areal extent from three-dimensional gridded radar reflectivity alone. The machine learning model is trained using simulated radar reflectivity and vertical velocity from the National Severe Storm Laboratory’s convection permitting Warn-on-Forecast System (WoFS). A parametric regression technique using the sinh–arcsinh–normal distribution is adapted to run with U-Nets, allowing for both deterministic and probabilistic predictions of maximum vertical velocity. The best models after hyperparameter search provided less than 50% root mean squared error, a coefficient of determination greater than 0.65, and an intersection over union (IoU) of more than 0.45 on the independent test set composed of WoFS data. Beyond the WoFS analysis, a case study was conducted using real radar data and corresponding dual-Doppler analyses of vertical velocity within a supercell. The U-Net consistently underestimates the dual-Doppler updraft speed estimates by 50%. Meanwhile, the area of the 5 and 10 m s⁻¹updraft cores shows an IoU of 0.25. While the above statistics are not exceptional, the machine learning model enables quick distillation of 3D radar data that is related to the maximum vertical velocity, which could be useful in assessing a storm’s severe potential.

   All convective storm hazards (tornadoes, hail, heavy rain, straight line winds) can be related to a storm’s updraft. Yet, there is no direct measurement of updraft speed or area available for forecasters to make their warning decisions from. This paper addresses the lack of observational data by providing a machine learning solution that skillfully estimates the maximum updraft speed within storms from only the radar reflectivity 3D structure. After further vetting the machine learning solutions on additional real-world examples, the estimated storm updrafts will hopefully provide forecasters with an added tool to help diagnose a storm’s hazard potential more accurately.

    

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