Biology subjects

Rokem, A.

Publications and source records attributed to Rokem, A..

At least 37 records · Page 2Linked to original sources

bioRxiv2022

An open, analysis-ready, and quality controlled resource for pediatric brain white-matter research

We created resources to facilitate research on the role of human brain microstructure in the development of mental health disorders, based on openly-available diffusion MRI (dMRI) data from the Healthy Brain Network (HBN) study. First, we curated the HBN dMRI data (N=2747) into the Brain Imaging Data Structure and preprocessed it according to best-practices, including denoising and correcting for motion effects, susceptibility-related distortions, and eddy currents. Preprocessed, analysis-ready data was made openly available. Data quality plays a key role in the analysis of dMRI, and we provide automated quality control (QC) scores for every scan, as part of the data release. To scale QC to this large dataset, we trained a neural network through the combination of a small data subset scored by experts and a larger set scored by community scientists. The network performs QC highly concordant with that of experts on a held out set (ROC-AUC = 0.947). A further analysis of the neural network demonstrates that it relies on image features with relevance to QC. Altogether, this work both delivers a resource for transdiagnostic research in brain connectivity and pediatric mental health and serves as a novel tool for automated QC of large datasets.

neuroscience↗

bioRxiv2021

Development of the visual white matter pathways mediates development of electrophysiological responses in visual cortex

The latency of neural responses in the visual cortex changes systematically across the lifespan. Here we test the hypothesis that development of visual white matter pathways mediates maturational changes in the latency of visual signals. Thirty-eight children participated in a cross-sectional study including diffusion MRI and MEG sessions. During the MEG acquisition, participants performed a lexical decision and a fixation task on words presented at varying levels of contrast and noise. For all stimuli and tasks, early evoked fields were observed around 100 ms after stimulus onset (M100), with slower and lower amplitude responses for low as compared to high contrast stimuli. The optic radiations and optic tracts were identified in each individuals brain based on diffusion MRI tractography. The diffusion properties of the optic radiations predicted M100 responses, especially for high contrast stimuli. Higher optic radiation fractional anisotropy (FA) values were associated with faster and larger M100 responses. Over this developmental window, the M100 responses to high contrast stimuli became faster with age and the optic radiation FA mediated this effect. These findings suggest that the maturation of the optic radiations over childhood accounts for individual variations observed in the developmental trajectory of visual cortex responses.

neuroscience↗

bioRxiv2021

Diffusional Kurtosis Imaging in the Diffusion Imaging in Python Project

Diffusion-weighted magnetic resonance imaging (dMRI) measurements and models provide information about brain connectivity and are sensitive to the physical properties of tissue microstructure. Diffusional Kurtosis Imaging (DKI) quantifies the degree of non-Gaussian diffusion in biological tissue from dMRI. These estimates are of interest because they were shown to be more sensitive to microstructural alterations in health and diseases than measures based on the total anisotropy of diffusion which are highly confounded by tissue dispersion and fiber crossings. In this work, we implemented DKI in the Diffusion in Python (DIPY) project - a large collaborative open-source project which aims to provide well-tested, well-documented and comprehensive implementation of different dMRI techniques. We demonstrate the functionality of our methods in numerical simulations with known ground truth parameters and in openly available datasets. A particular strength of our DKI implementations is that it pursues several extensions of the model that connect it explicitly with microstructural models and the reconstruction of 3D white matter fiber bundles (tractography). For instance, our implementations include DKI-based microstructural models that allow the estimation of biophysical parameters, such as axonal water fraction. Moreover, we illustrate how DKI provides more general characterization of non-Gaussian diffusion compatible with complex white matter fiber architectures and grey matter, and we include a novel mean kurtosis index that is invariant to the confounding effects due to tissue dispersion. In summary, DKI in DIPY provides a well-tested, well-documented and comprehensive reference mplementation for DKI. It provides a platform for wider use of DKI in research on brain disorders and cognitive neuroscience research. It will ease the translation of DKI advantages into clinical applications.

neuroscience↗

bioRxiv2021

On the generalizability of diffusion MRI signal representations across acquisition parameters, sequences and tissue types: chronicles of the MEMENTO challenge.

Diffusion MRI (dMRI) has become an invaluable tool to assess the microstructural organization of brain tissue. Depending on the specific acquisition settings, the dMRI signal encodes specific properties of the underlying diffusion process. In the last two decades, several signal representations have been proposed to fit the dMRI signal and decode such properties. Most methods, however, are tested and developed on a limited amount of data, and their applicability to other acquisition schemes remains unknown. With this work, we aimed to shed light on the generalizability of existing dMRI signal representations to different diffusion encoding parameters and brain tissue types. To this end, we organized a community challenge - named MEMENTO, making available the same datasets for fair comparisons across algorithms and techniques. We considered two state-of-the-art diffusion datasets, including single-diffusion-encoding (SDE) spin-echo data from a human brain with over 3820 unique diffusion weightings (the MASSIVE dataset), and double (oscillating) diffusion encoding data (DDE/DODE) of a mouse brain including over 2520 unique data points. A subset of the data sampled in 5 different voxels was openly distributed, and the challenge participants were asked to predict the remaining part of the data. After one year, eight participant teams submitted a total of 80 signal fits. For each submission, we evaluated the mean squared error, the variance of the prediction error and the Bayesian information criteria. Most predictions predicted either multi-shell SDE data (37%) or DODE data (22%), followed by cartesian SDE data (19%) and DDE (18%). Most submissions predicted the signals measured with SDE remarkably well, with the exception of low and very strong diffusion weightings. The prediction of DDE and DODE data seemed more challenging, likely because none of the submissions explicitly accounted for diffusion time and frequency. Next to the choice of the model, decisions on fit procedure and hyperparameters play a major role in the prediction performance, highlighting the importance of optimizing and reporting such choices. This work is a community effort to highlight strength and limitations of the field at representing dMRI acquired with trending encoding schemes, gaining insights into how different models generalize to different tissue types and fiber configurations over a large range of diffusion encodings.

neuroscience↗

bioRxiv2021

Evaluating the reliability of human brain white matter tractometry

The validity of research results depends on the reliability of analysis methods. In recent years, there have been concerns about the validity of research that uses diffusion-weighted MRI (dMRI) to understand human brain white matter connections in vivo, in part based on reliability of the analysis methods used in this field. We defined and assessed three dimensions of reliability in dMRI-based tractometry, an analysis technique that assesses the physical properties of white matter pathways: (1) reproducibility, (2) test-retest reliability and (3) robustness. To facilitate reproducibility, we provide software that automates tractometry (https://yeatmanlab.github.io/pyAFQ). In measurements from the Human Connectome Project, as well as clinical-grade measurements, we find that tractometry has high test-retest reliability that is comparable to most standardized clinical assessment tools. We find that tractometry is also robust: showing high reliability with different choices of analysis algorithms. Taken together, our results suggest that tractometry is a reliable approach to analysis of white matter connections. The overall approach taken here both demonstrates the specific trustworthiness of tractometry analysis and outlines what researchers can do to demonstrate the reliability of computational analysis pipelines in neuroimaging.

neuroscience↗

bioRxiv2020

Numerical Instabilities in Analytical Pipelines Lead to Large and Meaningful Variability in Brain Networks

The analysis of brain-imaging data requires complex processing pipelines to support findings on brain function or pathologies. Recent work has shown that variability in analytical decisions, small amounts of noise, or computational environments can lead to substantial differences in the results, endangering the trust in conclusions1-7. We explored the instability of results by instrumenting a connectome estimation pipeline with Monte Carlo Arithmetic8,9 to introduce random noise throughout. We evaluated the reliability of the connectomes, their features10,11, and the impact on analysis12,13. The stability of results was found to range from perfectly stable to highly unstable. This paper highlights the potential of leveraging induced variance in estimates of brain connectivity to reduce the bias in networks alongside increasing the robustness of their applications in the classification of individual differences. We demonstrate that stability evaluations are necessary for understanding error inherent to brain imaging experiments, and how numerical analysis can be applied to typical analytical workflows both in brain imaging and other domains of computational science. Overall, while the extreme variability in results due to analytical instabilities could severely hamper our understanding of brain organization, it also leads to an increase in the reliability of datasets.

neuroscience↗

bioRxiv2020

QSIPrep: An integrative platform for preprocessing and reconstructing diffusion MRI

Diffusion-weighted magnetic resonance imaging (dMRI) has become the primary method for non-invasively studying the organization of white matter in the human brain. While many dMRI acquisition sequences have been developed, they all sample q-space in order to characterize water diffusion. Numerous software platforms have been developed for processing dMRI data, but most work on only a subset of sampling schemes or implement only parts of the processing workflow. Reproducible research and comparisons across dMRI methods are hindered by incompatible software, diverse file formats, and inconsistent naming conventions. Here we introduce QSIPrep, an integrative software platform for the processing of diffusion images that is compatible with nearly all dMRI sampling schemes. Drawing upon a diverse set of software suites to capitalize upon their complementary strengths, QSIPrep automatically applies best practices for dMRI preprocessing, including denoising, distortion correction, head motion correction, coregistration, and spatial normalization. Throughout, QSIPrep provides both visual and quantitative measures of data quality as well as "glass-box" methods reporting. Taken together, these features facilitate easy implementation of best practices for processing of diffusion images while simultaneously ensuring reproducibility.

bioinformatics↗

bioRxiv2020

Automated detection of glaucoma with interpretable machine learning using clinical data and multi-modal retinal images

Glaucoma, the leading cause of irreversible blindness worldwide, is a disease that damages the optic nerve. Current machine learning (ML) approaches for glaucoma detection rely on features such as retinal thickness maps; however, the high rate of segmentation errors when creating these maps increase the likelihood of faulty diagnoses. This paper proposes a new, comprehensive, and more accurate ML-based approach for population-level glaucoma screening. Our contributions include: (1) a multi-modal model built upon a large data set that includes demographic, systemic and ocular data as well as raw image data taken from color fundus photos (CFPs) and macular Optical Coherence Tomography (OCT) scans, (2) model interpretation to identify and explain data features that lead to accurate model performance, and (3) model validation via comparison of model output with clinician interpretation of CFPs. We also validated the model on a cohort that was not diagnosed with glaucoma at the time of imaging but eventually received a glaucoma diagnosis. Results show that our model is highly accurate (AUC 0.97) and interpretable. It validated biological features known to be related to the disease, such as age, intraocular pressure and optic disc morphology. Our model also points to previously unknown or disputed features, such as pulmonary capacity and retinal outer layers.

bioengineering↗

bioRxiv2019

Multidimensional analysis and detection of informative features in diffusion MRI measurements of human white matter

The white matter contains long-range connections between different brain regions and the organization of these connections holds important implications for brain function in health and disease. Tractometry uses diffusion-weighted magnetic resonance imaging (dMRI) data to quantify tissue properties (e.g. fractional anisotropy (FA), mean diffusivity (MD), etc.), along the trajectories of these connections [1]. Statistical inference from tractometry usually either (a) averages these quantities along the length of each bundle in each individual, or (b) performs analysis point-by-point along each bundle, with group comparisons or regression models computed separately for each point along every one of the bundles. These approaches are limited in their sensitivity, in the former case, or in their statistical power, in the latter. In the present work, we developed a method based on the sparse group lasso (SGL) [2] that takes into account tissue properties measured along all of the bundles, and selects informative features by enforcing sparsity, not only at the level of individual bundles, but also across the entire set of bundles and all of the measured tissue properties. The sparsity penalties for each of these constraints is identified using a nested cross-validation scheme that guards against over-fitting and simultaneously identifies the correct level of sparsity. We demonstrate the accuracy of the method in two settings: i) In a classification setting, patients with amyotrophic lateral sclerosis (ALS) are accurately distinguished from matched controls [3]. Furthermore, SGL automatically identifies FA in the corticospinal tract as important for this classification - correctly finding the parts of the white matter known to be affected by the disease. ii) In a regression setting, dMRI is used to accurately predict "brain age" [4, 5]. In this case, the weights are distributed throughout the white matter indicating that many different regions of the white matter change with development and contribute to the prediction of age. Thus, SGL makes it possible to leverage the multivariate relationship between diffusion properties measured along multiple bundles to make accurate predictions of subject characteristics while simultaneously discovering the most relevant features of the white matter for the characteristic of interest.

neuroscience↗

bioRxiv2019

Diffusion Weighted Image Co-registration: Investigation of Best Practices

1.The registration or alignment of diffusion weighted images (DWI) with other imaging modalities is a critical step in neuroimaging analysis. Within-subject T1-DWI co-registration is particularly instrumental. DWI-derived scalar images are commonly used as intermediates for T1-DWI co-registration, and the resulting registration transforms are applied to all other scalar images for analysis. The ideal registration intermediate should register well to T1 and other multimodal images and be practically easy to obtain. It is however, currently unclear which DWI-derived scalar image serves as the best intermediate. We aim to determine the best, practical, intermediate for image co-registration. T1 and DWI images were acquired from 20 healthy subjects. DWIs were acquired with 60 directions. Six DWI-derived scalar images were compared including: 1) fractional anisotropy (FA); 2) generalized FA (GFA); 3) B0 images; 4) mean DWIs with the B0 image (MDWI); 5) anisotropic power (AP) images. AP showed the smallest variability in registration improvements across all the tested DWI derived scalar images, and show the highest average percent changes with CC registration cost function (CC=1.2%, MI=15%). In contrast, the FA and GFA transforms resulted in significantly poorer registration across DWI types. The AP image was the DWI-derived scalar image that provided the most consistent registration to all other images. Practically, it is generated easily and so could be implemented in basic and clinical research pipelines currently using other intermediates. Given these findings, it is recommended that AP images be used for T1-DWI co-registration, and that FA and GFA images in particular be avoided.

neuroscience↗

bioRxiv2019

Model-based recommendations for optimal surgical placement of epiretinal implants

A major limitation of current electronic retinal implants is that in addition to stimulating the intended retinal ganglion cells, they also stimulate passing axon fibers, producing perceptual streaks that limit the quality of the generated visual experience. Recent evidence suggests a dependence between the shape of the elicited visual percept and the retinal location of the stimulating electrode. However, this knowledge has yet to be incorporated into the surgical placement of retinal implants. Here we systematically explored the space of possible implant configurations to make recommendations for optimal intraocular positioning of the electrode array. Using a psychophysically validated computational model, we demonstrate that better implant placement has the potential to reduce the spatial extent of axonal activation in existing implant users by up to [~]55 %. Importantly, the best implant location, as inferred from a population of simulated virtual patients, is both surgically feasible and is relatively stable across individuals. This study is a first step towards the use of computer simulations in patient-specific planning of retinal implant surgery.

neuroscience↗

bioRxiv2018

A model of ganglion axon pathways accounts for percepts elicited by retinal implants

Retinal prostheses, now implanted in over 250 patients worldwide, electrically stimulate surviving cells in order to evoke neuronal responses that are interpreted by the brain as visual percepts ( phosphenes). However, instead of seeing focal spots of light, current implant users perceive highly distorted phosphenes that vary in shape both across subjects and electrodes. We characterized these distortions by asking users of the Argus retinal prosthesis system (Second Sight Medical Products) to draw elicited percepts on a touchscreen. We found that phosphene shape could be accurately predicted by simulating the topographic organization of nerve fiber bundles in each subjects retina. Our model shows that activation of ganglion axons contributes to a rich repertoire of phosphene shapes, successfully replicating percepts ranging from blobs to oriented streaks and wedges depending on electrode location. This work provides a first step towards future devices that incorporate stimulation strategies tailored to each individual patients retinal neurophysiology.\n\nOne Sentence SummaryWe show that the perceptual experience of retinal implant users can be accurately predicted using a computational model that simulates the topographic organization of each individual patients retinal ganglion axon pathways.

neuroscience↗

bioRxiv2018

Combining citizen science and deep learning to amplify expertise in neuroimaging

Research in many fields has become increasingly reliant on large and complex datasets. \"Big Data\" holds untold promise to rapidly advance science by tackling new questions that cannot be answered with smaller datasets. While powerful, research with Big Data poses unique challenges, as many standard lab protocols rely on experts examining each one of the samples. This is not feasible for large-scale datasets because manual approaches are time-consuming and hence difficult to scale. Meanwhile, automated approaches lack the accuracy of examination by highly trained scientists and this may introduce major errors, sources of noise, and unforeseen biases into these large and complex datasets. Our proposed solution is to 1) start with a small, expertly labelled dataset, 2) amplify labels through web-based tools that engage citizen scientists, and 3) train machine learning on amplified labels to emulate expert decision making. As a proof of concept, we developed a system to quality control a large dataset of three-dimensional magnetic resonance images (MRI) of human brains. An initial dataset of 200 brain images labeled by experts were amplified by citizen scientists to label 722 brains, with over 80,000 ratings done through a simple web interface. A deep learning algorithm was then trained to predict data quality, based on a combination of the citizen scientist labels that accounts for differences in the quality of classification by different citizen scientists. In an ROC analysis (on left out test data), the deep learning network performed as well as a state-of-the-art, specialized algorithm (MRIQC) for quality control of T1-weighted images, each with an area under the curve of 0.99. Finally, as a specific practical application of the method, we explore how brain image quality relates to the replicability of a well established relationship between brain volume and age over development. Combining citizen science and deep learning can generalize and scale expert decision making; this is particularly important in emerging disciplines where specialized, automated tools do not already exist.

neuroscience↗

bioRxiv2018

Applying biophysical models to understand the role of white matter in cognitive development

Diffusion MRI (dMRI) holds great promise for illuminating the biological changes that underpin cognitive development. The diffusion of water molecules probes the cellular structure of brain tissue, and biophysical modeling of the diffusion signal can be used to make inferences about specific tissue properties that vary over development or predict cognitive performance. However, applying these models to study development requires that the parameters can be reliably estimated given the constraints of data collection with children. Here we collect repeated scans using a multi-shell diffusion MRI protocol in a group of children (ages 7-12) and use two popular biophysical models to characterize axonal properties. We first assess the scan-rescan reliability of model parameters and show that axon water faction can be reliably estimated from a relatively fast acquisition, without applying spatial smoothing or de-noising. We then investigate developmental changes in the white matter, and individual differences in white matter that correlate with reading skill. Specifically, we test the hypothesis that previously reported correlations between reading skill and diffusion anisotropy in the corpus callosum reflect increased axon density in poor readers. Both models support this interpretation, highlighting the utility of biophysical models for testing specific hypotheses about cognitive development.

neuroscience↗

bioRxiv2018

Multilabel multiclass classification of OCT images augmented with age, gender and visual acuity data

Optical Coherence Tomography (OCT) imaging of the retina is in widespread clinical use to diagnose a wide range of retinal pathologies and several previous studies have used deep learning to create systems that can accurately classify retinal OCT as indicative of one of these pathologies. However, patients often exhibit multiple pathologies concurrently. Here, we designed a novel neural network algorithm that performs multiclass and multilabel classification of retinal images from OCT images in four common retinal pathologies: epiretinal membrane, diabetic macular edema, dry age-related macular degeneration and neovascular age-related macular degeneration. Furthermore, clinicians often also use additional information about the patient for diagnosis. Second contribution of this study is improvement of multiclass, multilabel classification augmented with information about the patient: age, visual acuity and gender. We compared two training strategies: a network pre-trained with ImageNet was used for transfer learning, or the network was trained from randomly initialized weights. Transfer learning does not perform better in this case, because many of the low-level filters are tuned to colors, and the OCT images are monochromatic. Finally, we provide a transparent and interpretable diagnosis by highlighting the regions recognized by the neural network.

physiology↗

bioRxiv2018

Forecasting Future Humphrey Visual Fields Using Deep Learning

PurposeTo determine if deep learning networks could be trained to forecast a future 24-2 Humphrey Visual Field (HVF).\n\nDesignRetrospective database study.\n\nParticipantsAll patients who obtained a HVF 24-2 at the University of Washington.\n\nMethodsAll datapoints from consecutive 24-2 HVFs from 1998 to 2018 were extracted from a University of Washington database. Ten-fold cross validation with a held out test set was used to develop the three main phases of model development: model architecture selection, dataset combination selection, and time-interval model training with transfer learning, to train a deep learning artificial neural network capable of generating a point-wise visual field prediction.\n\nMain outcome measuresMean absolute error (MAE) and difference in Mean Deviation (MD) between predicted and actual future HVF.\n\nResultsMore than 1.7 million perimetry points were extracted to the hundredth decibel from 32,443 24-2 HVFs. The best performing model with 20 million trainable parameters, CascadeNet-5, was selected. The overall MAE for the test set was 2.47 dB (95% CI: 2.45 dB to 2.48 dB). The 100 fully trained models were able to successfully predict progressive field loss in glaucomatous eyes up to 5.5 years in the future with a correlation of 0.92 between the MD of predicted and actual future HVF (p < 2.2 = 10-16) and an average difference of 0.41 dB.\n\nConclusionsUsing unfiltered real-world datasets, deep learning networks show an impressive ability to not only learn spatio-temporal HVF changes but also to generate predictions for future HVFs up to 5.5 years, given only a single HVF.

bioinformatics↗

bioRxiv2018

MRI2MRI: A deep convolutional network that accurately transforms between brain MRI contrasts

Different brain MRI contrasts represent different tissue properties and are sensitive to different artifacts. The relationship between different contrasts is therefore complex and nonlinear. We developed a deep convolutional network that learns the mapping between different MRI contrasts. Using a publicly available dataset, we demonstrate that this algorithm accurately transforms between T1- and T2-weighted images, proton density images, time-of-flight angiograms, and diffusion MRI images. We demonstrate that these transformed images can be used to improve spatial registration between MR images of different contrasts.

neuroscience↗

bioRxiv2018

White matter plasticity and reading instruction: Widespread anatomical changes track the learning process

White matter tissue properties correlate with childrens performance across domains ranging from reading, to math, to executive function. We use a longitudinal intervention design to examine experience-dependent growth in reading skills and white matter in a group of grade school aged, struggling readers. Diffusion MRI data were collected at regular intervals during an 8-week, intensive reading intervention. These measurements reveal large-scale changes throughout a collection of white matter tracts, in concert with growth in reading skill. Additionally, we identify tracts whose properties predict reading skill but remain fixed throughout the intervention, suggesting that some anatomical properties may stably predict the ease with which a child learns to read, while others dynamically reflect the effects of experience. These results underscore the importance of considering recent experience when interpreting cross-sectional anatomy-behavior correlations. Widespread changes throughout the white matter may be a hallmark of rapid plasticity associated with an intensive learning experience.

neuroscience↗