Application of machine learning to automated analysis of cerebral edema in large cohorts of ischemic stroke patients

Cerebral edema contributes to neurological deterioration and death after hemispheric stroke but there remains no effective means of preventing or accurately predicting its occurrence. Big data approaches may provide insights into the biologic variability and genetic contributions to severity and time course of cerebral edema. These methods require quantitative analyses of edema severity across large cohorts of stroke patients. We have proposed that changes in cerebrospinal fluid (CSF) volume over time may represent a sensitive and dynamic marker of edema progression that can be measured from routinely available CT scans. To facilitate and scale up such approaches we have created a machine learning algorithm capable of segmenting and measuring CSF volume from serial CT scans of stroke patients. We now present results of our preliminary processing pipeline that was able to efficiently extract CSF volumetrics from an initial cohort of 155 subjects enrolled in a prospective longitudinal stroke study. We demonstrate a high degree of reproducibility in total cranial volume registration between scans (R = 0.982) as well as a strong correlation of baseline CSF volume and patient age (as a surrogate of brain atrophy, R = 0.725). Reduction in CSF volume from baseline to final CT was correlated with infarct volume (R = 0.715) and degree of midline shift (quadratic model, p < 2.2 × 10−16). We utilized generalized estimating equations (GEE) to model CSF volumes over time (using linear and quadratic terms), adjusting for age. This model demonstrated that CSF volume decreases over time (p < 2.2 × 10−13) and is lower in those with cerebral edema (p = 0.0004). We are now fully automating this pipeline to allow rapid analysis of even larger cohorts of stroke patients from multiple sites using an XNAT (eXtensible Neuroimaging Archive Toolkit) platform. Data on kinetics of edema across thousands of patients will facilitate precision approaches to prediction of malignant edema as well as modeling of variability and further understanding of genetic variants that influence edema severity

MicroRNA-300 inhibits the metastasis of prostate cancer through the regulation of TRIM63

Purpose: To investigate the role of microRNA-300 in the tumorigenesis of prostate cancer (PCa), and the relationship between microRNA-300 level and clinical data of PCa patients.Methods: MicroRNA-300 levels in 63 matched PCa and adjacent tissues were determined via quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between microRNA-300 level and the clinical profile of PCa patients was assessed. PCa cell phenotypes influenced by microRNA-300 were evaluated by a series of functional experiments, including CCK-8, colony formation, Transwell and wound healing assays. The role of microRNA-300/TRIM63 axis in the development of PCa was also examined.Results: MicroRNA-300 was more lowly expressed in PCa tissues than in adjacent normal tissues. PCa patients expressing lower levels of microRNA-300 had a higher Gleason score, higher rates of lymphatic metastasis and distant metastasis, and lower survival. Overexpression of microRNA-300 suppressed its proliferative and metastatic potential. Dual-luciferase reporter assay data confirmed that microRNA-300 specifically binds Tripartite Motif-containing Protein 63 (TRIM63). TRIM63 level was downregulated in PCa cells overexpressing microRNA-300.  Moreover, overexpression of TRIM63 abolished the role of microRNA-300 in influencing PCa cell phenotypes.Conclusion: MicroRNA-300 is downregulated in PCa. Its level is related to Gleason score, lymphatic metastasis, distant metastasis and poor prognosis of PCa patients. MicroRNA-300 stimulates proliferative and metastatic abilities in PCa cells by targeting TRIM63. This study may provide new targets for the development of new therapeutics for of PCa as well as its diagnosis

The Stroke Neuro-Imaging Phenotype Repository: An open data science platform for stroke research

Stroke is one of the leading causes of death and disability worldwide. Reducing this disease burden through drug discovery and evaluation of stroke patient outcomes requires broader characterization of stroke pathophysiology, yet the underlying biologic and genetic factors contributing to outcomes are largely unknown. Remedying this critical knowledge gap requires deeper phenotyping, including large-scale integration of demographic, clinical, genomic, and imaging features. Such big data approaches will be facilitated by developing and running processing pipelines to extract stroke-related phenotypes at large scale. Millions of stroke patients undergo routine brain imaging each year, capturing a rich set of data on stroke-related injury and outcomes. The Stroke Neuroimaging Phenotype Repository (SNIPR) was developed as a multi-center centralized imaging repository of clinical computed tomography (CT) and magnetic resonance imaging (MRI) scans from stroke patients worldwide, based on the open source XNAT imaging informatics platform. The aims of this repository are to: (i) store, manage, process, and facilitate sharing of high-value stroke imaging data sets, (ii) implement containerized automated computational methods to extract image characteristics and disease-specific features from contributed images, (iii) facilitate integration of imaging, genomic, and clinical data to perform large-scale analysis of complications after stroke; and (iv) develop SNIPR as a collaborative platform aimed at both data scientists and clinical investigators. Currently, SNIPR hosts research projects encompassing ischemic and hemorrhagic stroke, with data from 2,246 subjects, and 6,149 imaging sessions from Washington University\u27s clinical image archive as well as contributions from collaborators in different countries, including Finland, Poland, and Spain. Moreover, we have extended the XNAT data model to include relevant clinical features, including subject demographics, stroke severity (NIH Stroke Scale), stroke subtype (using TOAST classification), and outcome [modified Rankin Scale (mRS)]. Image processing pipelines are deployed on SNIPR using containerized modules, which facilitate replicability at a large scale. The first such pipeline identifies axial brain CT scans from DICOM header data and image data using a meta deep learning scan classifier, registers serial scans to an atlas, segments tissue compartments, and calculates CSF volume. The resulting volume can be used to quantify the progression of cerebral edema after ischemic stroke. SNIPR thus enables the development and validation of pipelines to automatically extract imaging phenotypes and couple them with clinical data with the overarching aim of enabling a broad understanding of stroke progression and outcomes

Fiber-driven resolution enhancement of diffusion-weighted images

Diffusion-weighted imaging (DWI), while giving rich information about brain circuitry, is often limited by insufficient spatial resolution and low signal-to-noise ratio (SNR). This paper describes an algorithm that will increase the resolution of DW images beyond the scan resolution, allowing for a closer investigation of fiber structures and more accurate assessment of brain connectivity. The algorithm is capable of generating a dense vector-valued field, consisting of diffusion data associated with the full set of diffusion-sensitizing gradients. The fundamental premise is that, to best preserve information, interpolation should always be performed along axonal fibers. To achieve this, at each spatial location, we probe neighboring voxels in various directions to gather diffusion information for data interpolation. Based on the fiber orientation distribution function (ODF), directions that are more likely to be traversed by fibers will be given greater weights during interpolation and vice versa. This ensures that data interpolation is only contributed by diffusion data coming from fibers that are aligned with a specific direction. This approach respects local fiber structures and prevents blurring resulting from averaging of data from significantly misaligned fibers. Evaluations suggest that this algorithm yields results with significantly less blocking artifacts, greater smoothness in anatomical structures, and markedly improved structural visibility

Sub-Character Tokenization for Chinese Pretrained Language Models

Tokenization is fundamental to pretrained language models (PLMs). Existing tokenization methods for Chinese PLMs typically treat each character as an indivisible token. However, they ignore the unique feature of the Chinese writing system where additional linguistic information exists below the character level, i.e., at the sub-character level. To utilize such information, we propose sub-character (SubChar for short) tokenization. Specifically, we first encode the input text by converting each Chinese character into a short sequence based on its glyph or pronunciation, and then construct the vocabulary based on the encoded text with sub-word tokenization. Experimental results show that SubChar tokenizers have two main advantages over existing tokenizers: 1) They can tokenize inputs into much shorter sequences, thus improving the computational efficiency. 2) Pronunciation-based SubChar tokenizers can encode Chinese homophones into the same transliteration sequences and produce the same tokenization output, hence being robust to all homophone typos. At the same time, models trained with SubChar tokenizers perform competitively on downstream tasks. We release our code at https://github.com/thunlp/SubCharTokenization to facilitate future work.Comment: This draft supersedes the previous version named "SHUOWEN-JIEZI: Linguistically Informed Tokenizers For Chinese Language Model Pretraining

CSF Volumetric Analysis for Quantification of Cerebral Edema After Hemispheric Infarction

Malignant cerebral edema (CED) complicates at least 20 % of large hemispheric infarcts (LHI) and may result in neurological deterioration or death. Midline shift (MLS) is a standard but crude measure of edema severity. We propose that volumetric analysis of shifts in cerebrospinal fluid (CSF) over time provides a reliable means of quantifying the spectrum of edema severity after LHI

Self-Supervised Deep Equilibrium Models for Inverse Problems with Theoretical Guarantees

Deep equilibrium models (DEQ) have emerged as a powerful alternative to deep unfolding (DU) for image reconstruction. DEQ models-implicit neural networks with effectively infinite number of layers-were shown to achieve state-of-the-art image reconstruction without the memory complexity associated with DU. While the performance of DEQ has been widely investigated, the existing work has primarily focused on the settings where groundtruth data is available for training. We present self-supervised deep equilibrium model (SelfDEQ) as the first self-supervised reconstruction framework for training model-based implicit networks from undersampled and noisy MRI measurements. Our theoretical results show that SelfDEQ can compensate for unbalanced sampling across multiple acquisitions and match the performance of fully supervised DEQ. Our numerical results on in-vivo MRI data show that SelfDEQ leads to state-of-the-art performance using only undersampled and noisy training data

Reperfusion Beyond 6 Hours Reduces Infarct Probability in Moderately Ischemic Brain Tissue

We aimed to examine perfusion changes between 3 and 6, and 6 and 24 hours after stroke onset and their impact on tissue outcome

Intrinsic Regression Models for Positive-Definite Matrices With Applications to Diffusion Tensor Imaging

The aim of this paper is to develop an intrinsic regression model for the analysis of positive-definite matrices as responses in a Riemannian manifold and their association with a set of covariates, such as age and gender, in a Euclidean space. The primary motivation and application of the proposed methodology is in medical imaging. Because the set of positive-definite matrices do not form a vector space, directly applying classical multivariate regression may be inadequate in establishing the relationship between positive-definite matrices and covariates of interest, such as age and gender, in real applications. Our intrinsic regression model, which is a semiparametric model, uses a link function to map from the Euclidean space of covariates to the Riemannian manifold of positive-definite matrices. We develop an estimation procedure to calculate parameter estimates and establish their limiting distributions. We develop score statistics to test linear hypotheses on unknown parameters and develop a test procedure based on a resampling method to simultaneously assess the statistical significance of linear hypotheses across a large region of interest. Simulation studies are used to demonstrate the methodology and examine the finite sample performance of the test procedure for controlling the family-wise error rate. We apply our methods to the detection of statistical significance of diagnostic effects on the integrity of white matter in a diffusion tensor study of human immunodeficiency virus. Supplemental materials for this article are available online