Reconstruction of respiratory variation signals from fMRI data.

Functional MRI signals can be heavily influenced by systemic physiological processes in addition to local neural activity. For example, widespread hemodynamic fluctuations across the brain have been found to correlate with natural, low-frequency variations in the depth and rate of breathing over time. Acquiring peripheral measures of respiration during fMRI scanning not only allows for modeling such effects in fMRI analysis, but also provides valuable information for interrogating brain-body physiology. However, physiological recordings are frequently unavailable or have insufficient quality. Here, we propose a computational technique for reconstructing continuous low-frequency respiration volume (RV) fluctuations from fMRI data alone. We evaluate the performance of this approach across different fMRI preprocessing strategies. Further, we demonstrate that the predicted RV signals can account for similar patterns of temporal variation in resting-state fMRI data compared to measured RV fluctuations. These findings indicate that fluctuations in respiration volume can be extracted from fMRI alone, in the common scenario of missing or corrupted respiration recordings. The results have implications for enriching a large volume of existing fMRI datasets through retrospective addition of respiratory variations information.

NeuroGraph: Benchmarks for Graph Machine Learning in Brain Connectomics.

Machine learning provides a valuable tool for analyzing high-dimensional functional neuroimaging data, and is proving effective in predicting various neurological conditions, psychiatric disorders, and cognitive patterns. In functional magnetic resonance imaging (MRI) research, interactions between brain regions are commonly modeled using graph-based representations. The potency of graph machine learning methods has been established across myriad domains, marking a transformative step in data interpretation and predictive modeling. Yet, despite their promise, the transposition of these techniques to the neuroimaging domain has been challenging due to the expansive number of potential preprocessing pipelines and the large parameter search space for graph-based dataset construction. In this paper, we introduce NeuroGraph, a collection of graph-based neuroimaging datasets, and demonstrated its utility for predicting multiple categories of behavioral and cognitive traits. We delve deeply into the dataset generation search space by crafting 35 datasets that encompass static and dynamic brain connectivity, running in excess of 15 baseline methods for benchmarking. Additionally, we provide generic frameworks for learning on both static and dynamic graphs. Our extensive experiments lead to several key observations. Notably, using correlation vectors as node features, incorporating larger number of regions of interest, and employing sparser graphs lead to improved performance. To foster further advancements in graph-based data driven neuroimaging analysis, we offer a comprehensive open-source Python package that includes the benchmark datasets, baseline implementations, model training, and standard evaluation.

TractEM: Evaluation of protocols for deterministic tractography white matter atlas.

Reproducible identification of white matter pathways across subjects is essential for the study of structural connectivity of the human brain. One of the key challenges is anatomical differences between subjects and human rater subjectivity in labeling. Labeling white matter regions of interest presents many challenges due to the need to integrate both local and global information. Clearly communicating the manual processes to capture this information is cumbersome, yet essential to lay a solid foundation for comprehensive atlases. Segmentation protocols must be designed so the interpretation of the requested tasks as well as locating structural landmarks is anatomically accurate, intuitive and reproducible. In this work, we quantified the reproducibility of a first iteration of an open/public multi-bundle segmentation protocol. This allowed us to establish a baseline for its reproducibility as well as to identify the limitations for future iterations. The protocol was tested/evaluated on both typical 3 T research acquisition Baltimore Longitudinal Study of Aging (BLSA) and high-acquisition quality Human Connectome Project (HCP) datasets. The results show that a rudimentary protocol can produce acceptable intra-rater and inter-rater reproducibility. However, this work highlights the difficulty in generalizing reproducible results and the importance of reaching consensus on anatomical description of white matter pathways. The protocol has been made available in open source to improve generalizability and reliability in collaboration. The goal is to improve upon the first iteration and initiate a discussion on the anatomical validity (or lack thereof) of some bundle definitions and the importance of reproducibility of tractography segmentation.

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.

Consideration of Cerebrospinal Fluid Intensity Variation in Diffusion Weighted MRI.

Diffusion weighted MRI (DW-MRI) depends on accurate quantification signal intensities that reflect directional apparent diffusion coefficients (ADC). Signal drift and fluctuations during imaging can cause systematic non-linearities that manifest as ADC changes if not corrected. Here, we present a case study on a large longitudinal dataset of typical diffusion tensor imaging. We investigate observed variation in the cerebral spinal fluid (CSF) regions of the brain, which should represent compartments with isotropic diffusivity. The study contains 3949 DW-MRI acquisitions of the human brain with 918 subjects and 542 with repeated scan sessions. We provide an analysis of the inter-scan, inter-session, and intra-session variation and an analysis of the associations with the applied diffusion gradient directions. We investigate a hypothesis that CSF models could be used in lieu of an interspersed minimally diffusion-weighted image (b0) correction. Variation in CSF signal is not largely attributable to within-scan dynamic anatomical changes (3.6%), but rather has substantial variation across scan sessions (10.6%) and increased variation across individuals (26.6%). Unfortunately, CSF intensity is not solely explained by a main drift model or a gradient model, but rather has statistically significant associations with both possible explanations. Further exploration is necessary for CSF drift to be used as an effective harmonization technique.

Characterization and correlation of signal drift in diffusion weighted MRI.

Diffusion weighted MRI (DWMRI) and the myriad of analysis approaches (from tensors to spherical harmonics and brain tractography to body multi-compartment models) depend on accurate quantification of the apparent diffusion coefficient (ADC). Signal drift during imaging (e.g., due to b0 drift associated with heating) can cause systematic non-linearities that manifest as ADC changes if not corrected. Herein, we present a case study on two phantoms on one scanner. Different scan protocols exhibit different degrees of drift during similar scans and may be sensitive to the order of scans within an exam. Vos et al. recently reviewed the effects of signal drift in DWMRI acquisitions and proposed a temporal model for correction. We propose a novel spatial-temporal model to correct for higher order aspects of the signal drift and derive a statistically robust variant. We evaluate the Vos model and propose a method using two phantoms that mimic the ADC of the relevant brain tissue (0.36-2.2 × 10-3 mm2/s) on a single 3 T scanner. The phantoms are (1) a spherical isotropic sphere consisting of a single concentration of polyvinylpyrrolidone (PVP) and (2) an ice-water phantom with 13 vials of varying PVP concentrations. To characterize the impact of interspersed minimally weighted volumes ("b0's"), image volumes with b-value equal to 0.1 s/mm2 are interspersed every 8, 16, 32, 48, and 96 diffusion weighted volumes in different trials. Signal drift is found to have spatially varying effects that are not accounted for with temporal-only models. The novel model captures drift more accurately (i.e., reduces the overall change per-voxel over the course of a scan) and results in more consistent ADC metrics.

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.