No ultrasounds detected from fungi when dehydrated.

Many organisms (including certain plant species) can be observed to emit sounds, potentially signifying threat alerts. Sensitivity to such sounds and vibrations may also play an important role in the lives of fungi. In this work, we explore the potential of ultrasound activity in dehydrating fungi, and discover that several species of fungi do not emit sounds (detectable with conventional instrumentation) in the frequency range of 10kHz to 210kHz upon dehydration. Over 5 terabytes of ultrasound recordings were collected and analysed. We conjecture that fungi interact via non-sound means, such as electrical or chemical.

ESPRESO: An algorithm to estimate the slice profile of a single magnetic resonance image.

To reduce scan time, magnetic resonance (MR) images are often acquired using 2D multi-slice protocols with thick slices that may also have gaps between them. The resulting image volumes have lower resolution in the through-plane direction than in the in-plane direction, and the through-plane resolution is in part characterized by the protocol's slice profile which acts as a through-plane point spread function (PSF). Although super-resolution (SR) has been shown to improve the visualization and down-stream processing of 2D multi-slice MR acquisitions, previous algorithms are usually unaware of the true slice profile, which may lead to sub-optimal SR performance. In this work, we present an algorithm to estimate the slice profile of a 2D multi-slice acquisition given only its own image volume without any external training data. We assume that an anatomical image is isotropic in the sense that, after accounting for a correctly estimated slice profile, the image patches along different orientations have the same probability distribution. Our proposed algorithm uses a modified generative adversarial network (GAN) where the generator network estimates the slice profile to reduce the resolution of the in-plane direction, and the discriminator network determines whether a direction is generated or real low resolution. The proposed algorithm, ESPRESO, which stands for "estimating the slice profile for resolution enhancement of a single image only", was tested with a state-of-the-art internally supervised SR algorithm. Specifically, ESPRESO is used to create training data for this SR algorithm, and results show improvements when ESPRESO is used over commonly-used PSFs.

HACA3: A unified approach for multi-site MR image harmonization.

The lack of standardization and consistency of acquisition is a prominent issue in magnetic resonance (MR) imaging. This often causes undesired contrast variations in the acquired images due to differences in hardware and acquisition parameters. In recent years, image synthesis-based MR harmonization with disentanglement has been proposed to compensate for the undesired contrast variations. The general idea is to disentangle anatomy and contrast information from MR images to achieve cross-site harmonization. Despite the success of existing methods, we argue that major improvements can be made from three aspects. First, most existing methods are built upon the assumption that multi-contrast MR images of the same subject share the same anatomy. This assumption is questionable, since different MR contrasts are specialized to highlight different anatomical features. Second, these methods often require a fixed set of MR contrasts for training (e.g., both T1-weighted and T2-weighted images), limiting their applicability. Lastly, existing methods are generally sensitive to imaging artifacts. In this paper, we present Harmonization with Attention-based Contrast, Anatomy, and Artifact Awareness (HACA3), a novel approach to address these three issues. HACA3 incorporates an anatomy fusion module that accounts for the inherent anatomical differences between MR contrasts. Furthermore, HACA3 can be trained and applied to any combination of MR contrasts and is robust to imaging artifacts. HACA3 is developed and evaluated on diverse MR datasets acquired from 21 sites with varying field strengths, scanner platforms, and acquisition protocols. Experiments show that HACA3 achieves state-of-the-art harmonization performance under multiple image quality metrics. We also demonstrate the versatility and potential clinical impact of HACA3 on downstream tasks including white matter lesion segmentation for people with multiple sclerosis and longitudinal volumetric analyses for normal aging subjects. Code is available at https://github.com/lianruizuo/haca3.

Enlarged perivascular space burden associations with arterial stiffness and cognition.

Enlarged perivascular spaces (ePVS) are difficult to quantify, and their etiologies and consequences are poorly understood. Vanderbilt Memory and Aging Project participants (n = 327, 73 ± 7 years) completed 3T brain MRI to quantify ePVS volume and count, longitudinal neuropsychological assessment, and cardiac MRI to quantify aortic stiffness. Linear regressions related (1) PWV to ePVS burden and (2) ePVS burden to cross-sectional and longitudinal neuropsychological performance adjusting for key demographic and medical factors. Higher aortic stiffness related to greater basal ganglia ePVS volume (ß = 7.0×10-5, p = 0.04). Higher baseline ePVS volume was associated with worse baseline information processing (ß = -974, p = 0.003), executive function (ß = -81.9, p < 0.001), and visuospatial performances (ß = -192, p = 0.02) and worse longitudinal language (ß = -54.9, p = 0.05), information processing (ß = -147, p = 0.03), executive function (ß = -10.9, p = 0.03), and episodic memory performances (ß = -10.6, p = 0.02). Results were similar for ePVS count. Greater arterial stiffness relates to worse basal ganglia ePVS burden, suggesting cardiovascular aging as an etiology. ePVS burden is associated with adverse cognitive trajectory, emphasizing the clinical relevance of ePVS.

Automated Classification of Resting-State fMRI ICA Components Using a Deep Siamese Network.

Manual classification of functional resting state networks (RSNs) derived from Independent Component Analysis (ICA) decomposition can be labor intensive and requires expertise, particularly in large multi-subject analyses. Hence, a fully automatic algorithm that can reliably classify these RSNs is desirable. In this paper, we present a deep learning approach based on a Siamese Network to learn a discriminative feature representation for single-subject ICA component classification. Advantages of this supervised framework are that it requires relatively few training data examples and it does not require the number of ICA components to be specified. In addition, our approach permits one-shot learning, which allows generalization to new classes not seen in the training set with only one example of each new class. The proposed method is shown to out-perform traditional convolutional neural network (CNN) and template matching methods in identifying eleven subject-specific RSNs, achieving 100% accuracy on a holdout data set and over 99% accuracy on an outside data set. We also demonstrate that the method is robust to scan-rescan variation. Finally, we show that the functional connectivity of default mode and salience networks identified by the proposed technique is altered in a group analysis of mild traumatic brain injury (TBI), severe TBI, and healthy subjects.

Efficient Quality Control with Mixed CT and CTA Datasets.

Deep learning promises the extraction of valuable information from traumatic brain injury (TBI) datasets and depends on efficient navigation when using large-scale mixed computed tomography (CT) datasets from clinical systems. To ensure a cleaner signal while training deep learning models, removal of computed tomography angiography (CTA) and scans with streaking artifacts is sensible. On massive datasets of heterogeneously sized scans, time-consuming manual quality assurance (QA) by visual inspection is still often necessary, despite the expectation of CTA annotation (artifact annotation is not expected). We propose an automatic QA approach for retrieving CT scans without artifacts by representing 3D scans as 2D axial slice montages and using a multi-headed convolutional neural network to detect CT vs CTA and artifact vs no artifact. We sampled 848 scans from a mixed CT dataset of TBI patients and performed 4-fold stratified cross-validation on 698 montages followed by an ablation experiment-150 stratified montages were withheld for external validation evaluation. Aggregate AUC for our main model was 0.978 for CT detection, 0.675 for artifact detection during cross-validation and 0.965 for CT detection, 0.698 for artifact detection on the external validation set, while the ablated model showed 0.946 for CT detection, 0.735 for artifact detection during cross-validation and 0.937 for CT detection, 0.708 for artifact detection on the external validation set. While our approach is successful for CT detection, artifact detection performance is potentially depressed due to the heterogeneity of present streaking artifacts and a suboptimal number of artifact scans in our training data.

Bi-directional Synthesis of Pre- and Post-contrast MRI via Guided Feature Disentanglement.

Magnetic resonance imaging (MRI) with gadolinium contrast is widely used for tissue enhancement and better identification of active lesions and tumors. Recent studies have shown that gadolinium deposition can accumulate in tissues including the brain, which raises safety concerns. Prior works have tried to synthesize post-contrast T1-weighted MRIs from pre-contrast MRIs to avoid the use of gadolinium. However, contrast and image representations are often entangled during the synthesis process, resulting in synthetic post-contrast MRIs with undesirable contrast enhancements. Moreover, the synthesis of pre-contrast MRIs from post-contrast MRIs which can be useful for volumetric analysis is rarely investigated in the literature. To tackle pre- and post- contrast MRI synthesis, we propose a BI-directional Contrast Enhancement Prediction and Synthesis (BICEPS) network that enables disentanglement of contrast and image representations via a bi-directional image-to-image translation(I2I)model. Our proposed model can perform both pre-to-post and post-to-pre contrast synthesis, and provides an interpretable synthesis process by predicting contrast enhancement maps from the learned contrast embedding. Extensive experiments on a multiple sclerosis dataset demonstrate the feasibility of applying our bidirectional synthesis and show that BICEPS outperforms current methods.

Comparison of convolutional neural networks for detecting large vessel occlusion on computed tomography angiography.

PURPOSE: Artificial intelligence diagnosis and triage of large vessel occlusion may quicken clinical response for a subset of time-sensitive acute ischemic stroke patients, improving outcomes. Differences in architectural elements within data-driven convolutional neural network (CNN) models impact performance. Foreknowledge of effective model architectural elements for domain-specific problems can narrow the search for candidate models and inform strategic model design and adaptation to optimize performance on available data. Here, we study CNN architectures with a range of learnable parameters and which span the inclusion of architectural elements, such as parallel processing branches and residual connections with varying methods of recombining residual information. METHODS: We compare five CNNs: ResNet-50, DenseNet-121, EfficientNet-B0, PhiNet, and an Inception module-based network, on a computed tomography angiography large vessel occlusion detection task. The models were trained and preliminarily evaluated with 10-fold cross-validation on preprocessed scans (n = 240). An ablation study was performed on PhiNet due to superior cross-validated test performance across accuracy, precision, recall, specificity, and F1 score. The final evaluation of all models was performed on a withheld external validation set (n = 60) and these predictions were subsequently calibrated with sigmoid curves. RESULTS: Uncalibrated results on the withheld external validation set show that DenseNet-121 had the best average performance on accuracy, precision, recall, specificity, and F1 score. After calibration DenseNet-121 maintained superior performance on all metrics except recall. CONCLUSIONS: The number of learnable parameters in our five models and best-ablated PhiNet directly related to cross-validated test performance-the smaller the model the better. However, this pattern did not hold when looking at generalization on the withheld external validation set. DenseNet-121 generalized the best; we posit this was due to its heavy use of residual connections utilizing concatenation, which causes feature maps from earlier layers to be used deeper in the network, while aiding in gradient flow and regularization.

Joint Image and Label Self-Super-Resolution.

We propose a method to jointly super-resolve an anisotropic image volume along with its corresponding voxel labels without external training data. Our method is inspired by internally trained superresolution, or self-super-resolution (SSR) techniques that target anisotropic, low-resolution (LR) magnetic resonance (MR) images. While resulting images from such methods are quite useful, their corresponding LR labels-derived from either automatic algorithms or human raters-are no longer in correspondence with the super-resolved volume. To address this, we develop an SSR deep network that takes both an anisotropic LR MR image and its corresponding LR labels as input and produces both a super-resolved MR image and its super-resolved labels as output. We evaluated our method with 50 T 1-weighted brain MR images 4× down-sampled with 10 automatically generated labels. In comparison to other methods, our method had superior Dice across all labels and competitive metrics on the MR image. Our approach is the first reported method for SSR of paired anisotropic image and label volumes.

Federated Gradient Averaging for Multi-Site Training with Momentum-Based Optimizers.

Multi-site training methods for artificial neural networks are of particular interest to the medical machine learning community primarily due to the difficulty of data sharing between institutions. However, contemporary multi-site techniques such as weight averaging and cyclic weight transfer make theoretical sacrifices to simplify implementation. In this paper, we implement federated gradient averaging (FGA), a variant of federated learning without data transfer that is mathematically equivalent to single site training with centralized data. We evaluate two scenarios: a simulated multi-site dataset for handwritten digit classification with MNIST and a real multi-site dataset with head CT hemorrhage segmentation. We compare federated gradient averaging to single site training, federated weight averaging (FWA), and cyclic weight transfer. In the MNIST task, we show that training with FGA results in a weight set equivalent to centralized single site training. In the hemorrhage segmentation task, we show that FGA achieves on average superior results to both FWA and cyclic weight transfer due to its ability to leverage momentum-based optimization.

Brain connections derived from diffusion MRI tractography can be highly anatomically accurate-if we know where white matter pathways start, where they end, and where they do not go.

MR Tractography, which is based on MRI measures of water diffusivity, is currently the only method available for noninvasive reconstruction of fiber pathways in the brain. However, it has several fundamental limitations that call into question its accuracy in many applications. Therefore, there has been intense interest in defining and mitigating the intrinsic limitations of the method. Recent studies have reported that tractography is inherently limited in its ability to accurately reconstruct the connections of the brain, when based on voxel-averaged estimates of local fiber orientation alone. Several validation studies have confirmed that tractography techniques are plagued by both false-positive and false-negative connections. However, these validation studies which quantify sensitivity and specificity, particularly in animal models, have not utilized prior anatomical knowledge, as is done in the human literature, for virtual dissection of white matter pathways, instead assessing tractography implemented in a relatively unconstrained manner. Thus, they represent a worse-case scenario for bundle-segmentation techniques and may not be indicative of the anatomical accuracy in the process of bundle segmentation, where streamline filtering using inclusion and exclusion regions-of-interest is common. With this in mind, the aim of the current study is to investigate and quantify the upper bounds of accuracy using current tractography methods. Making use of the same dataset utilized in two seminal validation papers, we show that prior anatomical knowledge in the form of manually placed or template-driven constraints can significantly improve the anatomical accuracy of estimated brain connections. Thus, we show that it is possible to achieve a high sensitivity and high specificity simultaneously, and conclude that current tractography algorithms, in combination with anatomically driven constraints, can result in reconstructions which very accurately reflect the ground truth white matter connections.

Generalizing Deep Whole Brain Segmentation for Pediatric and Post- Contrast MRI with Augmented Transfer Learning.

Generalizability is an important problem in deep neural networks, especially in the context of the variability of data acquisition in clinical magnetic resonance imaging (MRI). Recently, the Spatially Localized Atlas Network Tiles (SLANT) approach has been shown to effectively segment whole brain non-contrast T1w MRI with 132 volumetric labels. Enhancing generalizability of SLANT would enable broader application of volumetric assessment in multi-site studies. Transfer learning (TL) is commonly to update neural network weights for local factors; yet, it is commonly recognized to risk degradation of performance on the original validation/test cohorts. Here, we explore TL by data augmentation to address these concerns in the context of adapting SLANT to anatomical variation (e.g., adults versus children) and scanning protocol (e.g., non-contrast research T1w MRI versus contrast-enhanced clinical T1w MRI). We consider two datasets: First, 30 T1w MRI of young children with manually corrected volumetric labels, and accuracy of automated segmentation defined relative to the manually provided truth. Second, 36 paired datasets of pre- and post-contrast clinically acquired T1w MRI, and accuracy of the post-contrast segmentations assessed relative to the pre-contrast automated assessment. For both studies, we augment the original TL step of SLANT with either only the new data or with both original and new data. Over baseline SLANT, both approaches yielded significantly improved performance (pediatric: 0.89 vs. 0.82 DSC, p<0.001; contrast: 0.80 vs 0.76, p<0.001). The performance on the original test set decreased with the new-data only transfer learning approach, so data augmentation was superior to strict transfer learning.

Generalizing deep whole-brain segmentation for post-contrast MRI with transfer learning.

Purpose: Generalizability is an important problem in deep neural networks, especially with variability of data acquisition in clinical magnetic resonance imaging (MRI). Recently, the spatially localized atlas network tiles (SLANT) can effectively segment whole brain, non-contrast T1w MRI with 132 volumetric labels. Transfer learning (TL) is a commonly used domain adaptation tool to update the neural network weights for local factors, yet risks degradation of performance on the original validation/test cohorts. Approach: We explore TL using unlabeled clinical data to address these concerns in the context of adapting SLANT to scanning protocol variations. We optimize whole-brain segmentation on heterogeneous clinical data by leveraging 480 unlabeled pairs of clinically acquired T1w MRI with and without intravenous contrast. We use labels generated on the pre-contrast image to train on the post-contrast image in a five-fold cross-validation framework. We further validated on a withheld test set of 29 paired scans over a different acquisition domain. Results: Using TL, we improve reproducibility across imaging pairs measured by the reproducibility Dice coefficient (rDSC) between the pre- and post-contrast image. We showed an increase over the original SLANT algorithm (rDSC 0.82 versus 0.72) and the FreeSurfer v6.0.1 segmentation pipeline ( rDSC = 0.53 ). We demonstrate the impact of this work decreasing the root-mean-squared error of volumetric estimates of the hippocampus between paired images of the same subject by 67%. Conclusion: This work demonstrates a pipeline for unlabeled clinical data to translate algorithms optimized for research data to generalize toward heterogeneous clinical acquisitions.

Distributed deep learning across multisite datasets for generalized CT hemorrhage segmentation.

PURPOSE: As deep neural networks achieve more success in the wide field of computer vision, greater emphasis is being placed on the generalizations of these models for production deployment. With sufficiently large training datasets, models can typically avoid overfitting their data; however, for medical imaging it is often difficult to obtain enough data from a single site. Sharing data between institutions is also frequently nonviable or prohibited due to security measures and research compliance constraints, enforced to guard protected health information (PHI) and patient anonymity. METHODS: In this paper, we implement cyclic weight transfer with independent datasets from multiple geographically disparate sites without compromising PHI. We compare results between single-site learning (SSL) and multisite learning (MSL) models on testing data drawn from each of the training sites as well as two other institutions. RESULTS: The MSL model attains an average dice similarity coefficient (DSC) of 0.690 on the holdout institution datasets with a volume correlation of 0.914, respectively corresponding to a 7% and 5% statistically significant improvement over the average of both SSL models, which attained an average DSC of 0.646 and average correlation of 0.871. CONCLUSIONS: We show that a neural network can be efficiently trained on data from two physically remote sites without consolidating patient data to a single location. The resulting network improves model generalization and achieves higher average DSCs on external datasets than neural networks trained on data from a single source.

Extracting 2D weak labels from volume labels using multiple instance learning in CT hemorrhage detection.

Multiple instance learning (MIL) is a supervised learning methodology that aims to allow models to learn instance class labels from bag class labels, where a bag is defined to contain multiple instances. MIL is gaining traction for learning from weak labels but has not been widely applied to 3D medical imaging. MIL is well-suited to clinical CT acquisitions since (1) the highly anisotropic voxels hinder application of traditional 3D networks and (2) patch-based networks have limited ability to learn whole volume labels. In this work, we apply MIL with a deep convolutional neural network to identify whether clinical CT head image volumes possess one or more large hemorrhages (> 20cm3), resulting in a learned 2D model without the need for 2D slice annotations. Individual image volumes are considered separate bags, and the slices in each volume are instances. Such a framework sets the stage for incorporating information obtained in clinical reports to help train a 2D segmentation approach. Within this context, we evaluate the data requirements to enable generalization of MIL by varying the amount of training data. Our results show that a training size of at least 400 patient image volumes was needed to achieve accurate per-slice hemorrhage detection. Over a five-fold cross-validation, the leading model, which made use of the maximum number of training volumes, had an average true positive rate of 98.10%, an average true negative rate of 99.36%, and an average precision of 0.9698. The models have been made available along with source code1 to enabled continued exploration and adaption of MIL in CT neuroimaging.

Distributed deep learning for robust multi-site segmentation of CT imaging after traumatic brain injury.

Machine learning models are becoming commonplace in the domain of medical imaging, and with these methods comes an ever-increasing need for more data. However, to preserve patient anonymity it is frequently impractical or prohibited to transfer protected health information (PHI) between institutions. Additionally, due to the nature of some studies, there may not be a large public dataset available on which to train models. To address this conundrum, we analyze the efficacy of transferring the model itself in lieu of data between different sites. By doing so we accomplish two goals: 1) the model gains access to training on a larger dataset that it could not normally obtain and 2) the model better generalizes, having trained on data from separate locations. In this paper, we implement multi-site learning with disparate datasets from the National Institutes of Health (NIH) and Vanderbilt University Medical Center (VUMC) without compromising PHI. Three neural networks are trained to convergence on a computed tomography (CT) brain hematoma segmentation task: one only with NIH data, one only with VUMC data, and one multi-site model alternating between NIH and VUMC data. Resultant lesion masks with the multi-site model attain an average Dice similarity coefficient of 0.64 and the automatically segmented hematoma volumes correlate to those done manually with a Pearson correlation coefficient of 0.87, corresponding to an 8% and 5% improvement, respectively, over the single-site model counterparts.

LEARNING 3D WHITE MATTER MICROSTRUCTURE FROM 2D HISTOLOGY.

Histological analysis is typically the gold standard for validating measures of tissue microstructure derived from magnetic resonance imaging (MRI) contrasts. However, most histological investigations are inherently 2-dimensional (2D), due to increased field-of-view, higher in-plane resolutions, ease of acquisition, decreased costs, and a large number of available contrasts compared to 3-dimensional (3D) analysis. Because of this, it would be of great interest to be able to learn the 3D tissue microstructure from 2D histology. In this study, we use diffusion MRI (dMRI) of a squirrel monkey brain and corresponding myelin stained sections in combination with a convolution neural network to learn the relationship between the 3D diffusion estimated axonal fiber orientation distributions and the 2D myelin stain. We find that we are able to estimate the 3D fiber distribution with moderate to high angular agreement with the ground truth (median angular correlation coefficients of 0.48 across the unseen slices). This network could be used to validate dMRI neuronal structural measurements in 3D, even if only 2D histology is available for validation. Generalization is possible to transfer this network to human stained sections to infer the 3D fiber distribution at resolutions currently unachievable with dMRI, which would allow diffusion fiber tractography at unprecedented resolutions. We envision the use of similar networks to learn other 3D microstructural measures from an array of potential common 2D histology contrasts.

Inter-Scanner Harmonization of High Angular Resolution DW-MRI using Null Space Deep Learning.

Diffusion-weighted magnetic resonance imaging (DW-MRI) allows for non-invasive imaging of the local fiber architecture of the human brain at a millimetric scale. Multiple classical approaches have been proposed to detect both single (e.g., tensors) and multiple (e.g., constrained spherical deconvolution, CSD) fiber population orientations per voxel. However, existing techniques generally exhibit low reproducibility across MRI scanners. Herein, we propose a data-driven technique using a neural network design which exploits two categories of data. First, training data were acquired on three squirrel monkey brains using ex-vivo DW-MRI and histology of the brain. Second, repeated scans of human subjects were acquired on two different scanners to augment the learning of the network proposed. To use these data, we propose a new network architecture, the null space deep network (NSDN), to simultaneously learn on traditional observed/truth pairs (e.g., MRI-histology voxels) along with repeated observations without a known truth (e.g., scan-rescan MRI). The NSDN was tested on twenty percent of the histology voxels that were kept completely blind to the network. NSDN significantly improved absolute performance relative to histology by 3.87% over CSD and 1.42% over a recently proposed deep neural network approach. Moreover, it improved reproducibility on the paired data by 21.19% over CSD and 10.09% over a recently proposed deep approach. Finally, NSDN improved generalizability of the model to a third in vivo human scanner (which was not used in training) by 16.08% over CSD and 10.41% over a recently proposed deep learning approach. This work suggests that data-driven approaches for local fiber reconstruction are more reproducible, informative and precise and offers a novel, practical method for determining these models.

Harmonizing 1.5T/3T Diffusion Weighted MRI through Development of Deep Learning Stabilized Microarchitecture Estimators.

Diffusion weighted magnetic resonance imaging (DW-MRI) is interpreted as a quantitative method that is sensitive to tissue microarchitecture at a millimeter scale. However, the sensitization is dependent on acquisition sequences (e.g., diffusion time, gradient strength, etc.) and susceptible to imaging artifacts. Hence, comparison of quantitative DW-MRI biomarkers across field strengths (including different scanners, hardware performance, and sequence design considerations) is a challenging area of research. We propose a novel method to estimate microstructure using DW-MRI that is robust to scanner difference between 1.5T and 3T imaging. We propose to use a null space deep network (NSDN) architecture to model DW-MRI signal as fiber orientation distributions (FOD) to represent tissue microstructure. The NSDN approach is consistent with histologically observed microstructure (on previously acquired ex vivo squirrel monkey dataset) and scan-rescan data. The contribution of this work is that we incorporate identical dual networks (IDN) to minimize the influence of scanner effects via scan-rescan data. Briefly, our estimator is trained on two datasets. First, a histology dataset was acquired on three squirrel monkeys with corresponding DW-MRI and confocal histology (512 independent voxels). Second, 37 control subjects from the Baltimore Longitudinal Study of Aging (67-95 y/o) were identified who had been scanned at 1.5T and 3T scanners (b-value of 700 s/mm2, voxel resolution at 2.2mm, 30-32 gradient volumes) with an average interval of 4 years (standard deviation 1.3 years). After image registration, we used paired white matter (WM) voxels for 17 subjects and 440 histology voxels for training and 20 subjects and 72 histology voxels for testing. We compare the proposed estimator with super-resolved constrained spherical deconvolution (CSD) and a previously presented regression deep neural network (DNN). NSDN outperformed CSD and DNN in angular correlation coefficient (ACC) 0.81 versus 0.28 and 0.46, mean squared error (MSE) 0.001 versus 0.003 and 0.03, and general fractional anisotropy (GFA) 0.05 versus 0.05 and 0.09. Further validation and evaluation with contemporaneous imaging are necessary, but the NSDN is promising avenue for building understanding of microarchitecture in a consistent and device-independent manner.