Fiber tractography bundle segmentation depends on scanner effects, vendor effects, acquisition resolution, diffusion sampling scheme, diffusion sensitization, and bundle segmentation workflow.

When investigating connectivity and microstructure of white matter pathways of the brain using diffusion tractography bundle segmentation, it is important to understand potential confounds and sources of variation in the process. While cross-scanner and cross-protocol effects on diffusion microstructure measures are well described (in particular fractional anisotropy and mean diffusivity), it is unknown how potential sources of variation effect bundle segmentation results, which features of the bundle are most affected, where variability occurs, nor how these sources of variation depend upon the method used to reconstruct and segment bundles. In this study, we investigate six potential sources of variation, or confounds, for bundle segmentation: variation (1) across scan repeats, (2) across scanners, (3) across vendors (4) across acquisition resolution, (5) across diffusion schemes, and (6) across diffusion sensitization. We employ four different bundle segmentation workflows on two benchmark multi-subject cross-scanner and cross-protocol databases, and investigate reproducibility and biases in volume overlap, shape geometry features of fiber pathways, and microstructure features within the pathways. We find that the effects of acquisition protocol, in particular acquisition resolution, result in the lowest reproducibility of tractography and largest variation of features, followed by vendor-effects, scanner-effects, and finally diffusion scheme and b-value effects which had similar reproducibility as scan-rescan variation. However, confounds varied both across pathways and across segmentation workflows, with some bundle segmentation workflows more (or less) robust to sources of variation. Despite variability, bundle dissection is consistently able to recover the same location of pathways in the deep white matter, with variation at the gray matter/ white matter interface. Next, we show that differences due to the choice of bundle segmentation workflows are larger than any other studied confound, with low-to-moderate overlap of the same intended pathway when segmented using different methods. Finally, quantifying microstructure features within a pathway, we show that tractography adds variability over-and-above that which exists due to noise, scanner effects, and acquisition effects. Overall, these confounds need to be considered when harmonizing diffusion datasets, interpreting or combining data across sites, and when attempting to understand the successes and limitations of different methodologies in the design and development of new tractography or bundle segmentation methods.

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.

MASiVar: Multisite, multiscanner, and multisubject acquisitions for studying variability in diffusion weighted MRI.

PURPOSE: Diffusion-weighted imaging allows investigators to identify structural, microstructural, and connectivity-based differences between subjects, but variability due to session and scanner biases is a challenge. METHODS: To investigate DWI variability, we present MASiVar, a multisite data set consisting of 319 diffusion scans acquired at 3 T from b = 1000 to 3000 s/mm2 across 14 healthy adults, 83 healthy children (5 to 8 years), three sites, and four scanners as a publicly available, preprocessed, and de-identified data set. With the adult data, we demonstrate the capacity of MASiVar to simultaneously quantify the intrasession, intersession, interscanner, and intersubject variability of four common DWI processing approaches: (1) a tensor signal representation, (2) a multi-compartment neurite orientation dispersion and density model, (3) white-matter bundle segmentation, and (4) structural connectomics. Respectively, we evaluate region-wise fractional anisotropy, mean diffusivity, and principal eigenvector; region-wise CSF volume fraction, intracellular volume fraction, and orientation dispersion index; bundle-wise shape, volume, fractional anisotropy, and length; and whole connectome correlation and maximized modularity, global efficiency, and characteristic path length. RESULTS: We plot the variability in these measures at each level and find that it consistently increases with intrasession to intersession to interscanner to intersubject effects across all processing approaches and that sometimes interscanner variability can approach intersubject variability. CONCLUSIONS: This study demonstrates the potential of MASiVar to more globally investigate DWI variability across multiple levels and processing approaches simultaneously and suggests harmonization between scanners for multisite analyses should be considered before inference of group differences on subjects.

PreQual: An automated pipeline for integrated preprocessing and quality assurance of diffusion weighted MRI images.

PURPOSE: Diffusion weighted MRI imaging (DWI) is often subject to low signal-to-noise ratios (SNRs) and artifacts. Recent work has produced software tools that can correct individual problems, but these tools have not been combined with each other and with quality assurance (QA). A single integrated pipeline is proposed to perform DWI preprocessing with a spectrum of tools and produce an intuitive QA document. METHODS: The proposed pipeline, built around the FSL, MRTrix3, and ANTs software packages, performs DWI denoising; inter-scan intensity normalization; susceptibility-, eddy current-, and motion-induced artifact correction; and slice-wise signal drop-out imputation. To perform QA on the raw and preprocessed data and each preprocessing operation, the pipeline documents qualitative visualizations, quantitative plots, gradient verifications, and tensor goodness-of-fit and fractional anisotropy analyses. RESULTS: Raw DWI data were preprocessed and quality checked with the proposed pipeline and demonstrated improved SNRs; physiologic intensity ratios; corrected susceptibility-, eddy current-, and motion-induced artifacts; imputed signal-lost slices; and improved tensor fits. The pipeline identified incorrect gradient configurations and file-type conversion errors and was shown to be effective on externally available datasets. CONCLUSIONS: The proposed pipeline is a single integrated pipeline that combines established diffusion preprocessing tools from major MRI-focused software packages with intuitive QA.

Cross-scanner and cross-protocol multi-shell diffusion MRI data harmonization: Algorithms and results.

Cross-scanner and cross-protocol variability of diffusion magnetic resonance imaging (dMRI) data are known to be major obstacles in multi-site clinical studies since they limit the ability to aggregate dMRI data and derived measures. Computational algorithms that harmonize the data and minimize such variability are critical to reliably combine datasets acquired from different scanners and/or protocols, thus improving the statistical power and sensitivity of multi-site studies. Different computational approaches have been proposed to harmonize diffusion MRI data or remove scanner-specific differences. To date, these methods have mostly been developed for or evaluated on single b-value diffusion MRI data. In this work, we present the evaluation results of 19 algorithms that are developed to harmonize the cross-scanner and cross-protocol variability of multi-shell diffusion MRI using a benchmark database. The proposed algorithms rely on various signal representation approaches and computational tools, such as rotational invariant spherical harmonics, deep neural networks and hybrid biophysical and statistical approaches. The benchmark database consists of data acquired from the same subjects on two scanners with different maximum gradient strength (80 and 300 â€‹mT/m) and with two protocols. We evaluated the performance of these algorithms for mapping multi-shell diffusion MRI data across scanners and across protocols using several state-of-the-art imaging measures. The results show that data harmonization algorithms can reduce the cross-scanner and cross-protocol variabilities to a similar level as scan-rescan variability using the same scanner and protocol. In particular, the LinearRISH algorithm based on adaptive linear mapping of rotational invariant spherical harmonics features yields the lowest variability for our data in predicting the fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK) and the rotationally invariant spherical harmonic (RISH) features. But other algorithms, such as DIAMOND, SHResNet, DIQT, CMResNet show further improvement in harmonizing the return-to-origin probability (RTOP). The performance of different approaches provides useful guidelines on data harmonization in future multi-site studies.

Limits to anatomical accuracy of diffusion tractography using modern approaches.

Diffusion MRI fiber tractography is widely used to probe the structural connectivity of the brain, with a range of applications in both clinical and basic neuroscience. Despite widespread use, tractography has well-known pitfalls that limits the anatomical accuracy of this technique. Numerous modern methods have been developed to address these shortcomings through advances in acquisition, modeling, and computation. To test whether these advances improve tractography accuracy, we organized the 3-D Validation of Tractography with Experimental MRI (3D-VoTEM) challenge at the ISBI 2018 conference. We made available three unique independent tractography validation datasets - a physical phantom and two ex vivo brain specimens - resulting in 176 distinct submissions from 9 research groups. By comparing results over a wide range of fiber complexities and algorithmic strategies, this challenge provides a more comprehensive assessment of tractography's inherent limitations than has been reported previously. The central results were consistent across all sub-challenges in that, despite advances in tractography methods, the anatomical accuracy of tractography has not dramatically improved in recent years. Taken together, our results independently confirm findings from decades of tractography validation studies, demonstrate inherent limitations in reconstructing white matter pathways using diffusion MRI data alone, and highlight the need for alternative or combinatorial strategies to accurately map the fiber pathways of the brain.

DETECTION OF MYCOPLASMA SP. IN INDOCHINESE BOX TURTLES (CUORA BOURRETI).

Mycoplasma species are important pathogens of captive and free-ranging chelonians. Bourret's box turtle (Cuora bourreti) is a critically endangered species of Indochinese box turtle in the family Geoemydidae. Four privately owned wild-caught Bourret's box turtles were presented for clinical evaluation for anorexia and lethargy following shipment from a reptile wholesaler 3 wk prior. Choanal-cloacal swabs of two of the turtles were positive for Mycoplasma sp. by polymerase chain reaction. Sequencing of the 16S rRNA gene and 16S-23S rRNA intergenic spacer was 99% homologous to an unclassified Mycoplasma sp. previously documented in free-ranging and captive North American species of the family Emydidae. The potential of Mycoplasma sp. to induce disease in Bourret's box turtles is unknown. Global trade in live reptiles is believed to have facilitated this potential expansion of host range.

109Ag NMR chemical shift as a descriptor for Brønsted acidity from molecules to materials.

Molecular-level understanding of the acid/base properties of heterogeneous catalysts requires the development of selective spectroscopic probes to establish structure-activity relationships. In this work we show that substituting the surface protons in oxide supports by isolobal N-heterocyclic carbene (NHC) Ag cations and measuring their 109Ag nuclear magnetic resonance (NMR) signatures enables to probe the speciation and to evaluate the corresponding Brønsted acidity of the substituted OH surface sites. Specifically, a series of silver N-heterocyclic carbene (NHC) Ag(i) complexes of general formula [(NHC)AgX] are synthesized and characterized, showing that the 109Ag NMR chemical shift of the series correlates with the Brønsted acidity of the conjugate acid of X- (i.e., HX), thus establishing an acidity scale based on 109Ag NMR chemical shift. The methodology is then used to evaluate the Brønsted acidity of the OH sites of representative oxide materials using Dynamic Nuclear Polarization (DNP-)enhanced solid-state NMR spectroscopy.

Establishing the acute physiological and sleep disruption characteristics of wind farm versus road traffic noise disturbances in sleep: a randomized controlled trial protocol.

Study Objectives: Despite the global expansion of wind farms, effects of wind farm noise (WFN) on sleep remain poorly understood. This protocol details a randomized controlled trial designed to compare the sleep disruption characteristics of WFN versus road traffic noise (RTN). Methods: This study was a prospective, seven night within-subjects randomized controlled in-laboratory polysomnography-based trial. Four groups of adults were recruited from; <10 km away from a wind farm, including those with, and another group without, noise-related complaints; an urban RTN exposed group; and a group from a quiet rural area. Following an acclimation night, participants were exposed, in random order, to two separate nights with 20-s or 3-min duration WFN and RTN noise samples reproduced at multiple sound pressure levels during established sleep. Four other nights tested for continuous WFN exposure during wake and/or sleep on sleep outcomes. Results: The primary analyses will assess changes in electroencephalography (EEG) assessed as micro-arousals (EEG shifts to faster frequencies lasting 3-15 s) and awakenings (>15 s events) from sleep by each noise type with acute (20-s) and more sustained (3-min) noise exposures. Secondary analyses will compare dose-response effects of sound pressure level and noise type on EEG K-complex probabilities and quantitative EEG measures, and cardiovascular activation responses. Group effects, self-reported noise sensitivity, and wake versus sleep noise exposure effects will also be examined. Conclusions: This study will help to clarify if wind farm noise has different sleep disruption characteristics compared to road traffic noise.

Beyond traditional wind farm noise characterisation using transfer learning.

This study proposes an approach for the characterisation and assessment of wind farm noise (WFN), which is based on extraction of acoustic features between 125 and 7500 Hz from a pretrained deep learning model (referred to as deep acoustic features). Using data measured at a variety of locations, this study shows that deep acoustic features can be linked to meaningful characteristics of the noise. This study finds that deep acoustic features can reveal an improved spatial and temporal representation of WFN compared to what is revealed using traditional spectral analysis and overall noise descriptors. These results showed that this approach is promising, and thus it could provide the basis for an improved framework for WFN assessment in the future.

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.

Contrastive semi-supervised harmonization of single-shell to multi-shell diffusion MRI.

Diffusion weighted MRI (DW-MRI) harmonization is necessary for multi-site or multi-acquisition studies. Current statistical methods address the need to harmonize from one site to another, but do not simultaneously consider the use of multiple datasets which are comprised of multiple sites, acquisitions protocols, and age demographics. This work explores deep learning methods which can generalize across these variations through semi-supervised and unsupervised learning while also learning to estimate multi-shell data from single-shell data using the Multi-shell Diffusion MRI Harmonization Challenge (MUSHAC) and Baltimore Longitudinal Study on Aging (BLSA) datasets. We compare disentanglement harmonization models, which seek to encode anatomy and acquisition in separate latent spaces, and a CycleGAN harmonization model, which uses generative adversarial networks (GAN) to perform style transfer between sites, to the baseline preprocessing and to SHORE interpolation. We find that the disentanglement models achieve superior performance in harmonizing all data while at the same transforming the input data to a single target space across several diffusion metrics (fractional anisotropy, mean diffusivity, mean kurtosis, primary eigenvector).

Mapping the Impact of Non-Linear Gradient Fields on Diffusion MRI Tensor Estimation.

Non-linear gradients impact diffusion weighted (DW) MRI by corrupting the experimental setup and lead to problems during image encoding including the effects in-plane distortion, in-plane shifts, intensity modulations and phase errors. Recent studies have been shown this may present significant complication in the interpretation of results and conclusion while studying tractography and tissue microstructure in data. To interpret the degree in consequences of gradient non-linearities between the desired and achieved gradients, we introduced empirically derived gradient nonlinear fields at different orientations and different tensor properties. The impact is assessed through diffusion tensor properties including mean diffusivity (MD), fractional anisotropy (FA) and principal eigen vector (PEV). The study shows lower FA are more susceptible to LR fields and LR fields with determinant <1 or >1 corrupt tensor more. The corruption can result in significantly different FA based on true-FA and LR field. Apparent MD decreases for negative determinant, on the other hand positive determinant shows the opposite effect. LR field have a larger impact on PEV when FA value is small. The results are dependent on the underlying orientation, non-linear field corruption can cause both increase and decrease of estimated FA, MD and PEV value. This work provides insight into characterizing the non-linear gradient error and aid in selecting correction techniques to address the inaccuracies in b-values.

Learning white matter subject-specific segmentation from structural MRI.

PURPOSE: Mapping brain white matter (WM) is essential for building an understanding of brain anatomy and function. Tractography-based methods derived from diffusion-weighted MRI (dMRI) are the principal tools for investigating WM. These procedures rely on time-consuming dMRI acquisitions that may not always be available, especially for legacy or time-constrained studies. To address this problem, we aim to generate WM tracts from structural magnetic resonance imaging (MRI) image by deep learning. METHODS: Following recently proposed innovations in structural anatomical segmentation, we evaluate the feasibility of training multiply spatial localized convolution neural networks to learn context from fixed spatial patches from structural MRI on standard template. We focus on six widely used dMRI tractography algorithms (TractSeg, RecoBundles, XTRACT, Tracula, automated fiber quantification (AFQ), and AFQclipped) and train 125 U-Net models to learn these techniques from 3870 T1-weighted images from the Baltimore Longitudinal Study of Aging, the Human Connectome Project S1200 release, and scans acquired at Vanderbilt University. RESULTS: The proposed framework identifies fiber bundles with high agreement against tractography-based pathways with a median Dice coefficient from 0.62 to 0.87 on a test cohort, achieving improved subject-specific accuracy when compared to population atlas-based methods. We demonstrate the generalizability of the proposed framework on three externally available datasets. CONCLUSIONS: We show that patch-wise convolutional neural network can achieve robust bundle segmentation from T1w. We envision the use of this framework for visualizing the expected course of WM pathways when dMRI is not available.

Aging and white matter microstructure and macrostructure: a longitudinal multi-site diffusion MRI study of 1218 participants.

Quantifying the microstructural and macrostructural geometrical features of the human brain's connections is necessary for understanding normal aging and disease. Here, we examine brain white matter diffusion magnetic resonance imaging data from one cross-sectional and two longitudinal data sets totaling in 1218 subjects and 2459 sessions of people aged 50-97 years. Data was drawn from well-established cohorts, including the Baltimore Longitudinal Study of Aging data set, Cambridge Centre for Ageing Neuroscience data set, and the Vanderbilt Memory & Aging Project. Quantifying 4 microstructural features and, for the first time, 11 macrostructure-based features of volume, area, and length across 120 white matter pathways, we apply linear mixed effect modeling to investigate changes in pathway-specific features over time, and document large age associations within white matter. Conventional diffusion tensor microstructure indices are the most age-sensitive measures, with positive age associations for diffusivities and negative age associations with anisotropies, with similar patterns observed across all pathways. Similarly, pathway shape measures also change with age, with negative age associations for most length, surface area, and volume-based features. A particularly novel finding of this study is that while trends were homogeneous throughout the brain for microstructure features, macrostructural features demonstrated heterogeneity across pathways, whereby several projection, thalamic, and commissural tracts exhibited more decline with age compared to association and limbic tracts. The findings from this large-scale study provide a comprehensive overview of the age-related decline in white matter and demonstrate that macrostructural features may be more sensitive to heterogeneous white matter decline. Therefore, leveraging macrostructural features may be useful for studying aging and could facilitate comparisons in a variety of diseases or abnormal conditions.

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.

Architectural Distortion on Screening Digital Breast Tomosynthesis: Pathologic Outcomes and Indicators of Malignancy.

OBJECTIVE: Digital breast tomosynthesis (DBT) has significantly improved cancer detection capabilities through its identification of subtle findings often imperceptible on 2D digital mammography, particularly architectural distortion (AD). The purpose of this study was to analyze of suspicious AD detected on screening DBT to evaluate the incidence of malignancy and to determine other patient or imaging characteristics in these cases as possible predictors of malignancy. METHODS: This was an IRB approved retrospective analysis of subjects with AD detected on DBT screening mammography who were given a biopsy recommendation between January 1, 2016, and June 30, 2018. Univariate analysis of various imaging characteristics and patient high-risk factors was performed for statistical correlation with diagnosis of malignancy. RESULTS: In the 218 DBT-detected AD findings with a final BI-RADS assessment of 4 or 5 on diagnostic workup, 94 (43.1%) yielded malignancy, 57 (26.2%) were classified as high-risk, and 67 (30.7%) were benign. There was a strong statistically significant association with malignancy in the cases with an US correlate (P < 0.0001). There was a statistically significant inverse correlation between malignancy and one-view findings (P = 0.0002). The presence of AD on 2D (P = 0.005) or synthetic 2D views (P = 0.002) showed statistically significant correlations with malignancy, whereas breast density or high-risk factors (P = 0.316) did not. CONCLUSION: AD detected on DBT that persists on further workup and has no explainable cause should be considered suspicious for malignancy. Identification of the AD on both standard mammographic views and the presence of an US correlate significantly increase the probability of malignancy.

Empirical field mapping for gradient nonlinearity correction of multi-site diffusion weighted MRI.

BACKGROUND: Achieving inter-site / inter-scanner reproducibility of diffusion weighted magnetic resonance imaging (DW-MRI) metrics has been challenging given differences in acquisition protocols, analysis models, and hardware factors. PURPOSE: Magnetic field gradients impart scanner-dependent spatial variations in the applied diffusion weighting that can be corrected if the gradient nonlinearities are known. However, retrieving manufacturer nonlinearity specifications is not well supported and may introduce errors in interpretation of units or coordinate systems. We propose an empirical approach to mapping the gradient nonlinearities with sequences that are supported across the major scanner vendors. STUDY TYPE: Prospective observational study. SUBJECTS: A spherical isotropic diffusion phantom, and a single human control volunteer. FIELD STRENGTH/SEQUENCE: 3 T (two scanners). Stejskal-Tanner spin echo sequence with b-values of 1000, 2000 s/mm2 with 12, 32, and 384 diffusion gradient directions per shell. ASSESSMENT: We compare the proposed correction with the prior approach using manufacturer specifications against typical diffusion pre-processing pipelines (i.e., ignoring spatial gradient nonlinearities). In phantom data, we evaluate metrics against the ground truth. In human and phantom data, we evaluate reproducibility across scans, sessions, and hardware. STATISTICAL TESTS: Wilcoxon rank-sum test between uncorrected and corrected data. RESULTS: In phantom data, our correction method reduces variation in mean diffusivity across sessions over uncorrected data (p < 0.05). In human data, we show that this method can also reduce variation in mean diffusivity across scanners (p < 0.05). CONCLUSION: Our method is relatively simple, fast, and can be applied retroactively. We advocate incorporating voxel-specific b-value and b-vector maps should be incorporated in DW-MRI harmonization preprocessing pipelines to improve quantitative accuracy of measured diffusion parameters.

Pandora: 4-D White Matter Bundle Population-Based Atlases Derived from Diffusion MRI Fiber Tractography.

Brain atlases have proven to be valuable neuroscience tools for localizing regions of interest and performing statistical inferences on populations. Although many human brain atlases exist, most do not contain information about white matter structures, often neglecting them completely or labelling all white matter as a single homogenous substrate. While few white matter atlases do exist based on diffusion MRI fiber tractography, they are often limited to descriptions of white matter as spatially separate "regions" rather than as white matter "bundles" or fascicles, which are well-known to overlap throughout the brain. Additional limitations include small sample sizes, few white matter pathways, and the use of outdated diffusion models and techniques. Here, we present a new population-based collection of white matter atlases represented in both volumetric and surface coordinates in a standard space. These atlases are based on 2443 subjects, and include 216 white matter bundles derived from 6 different automated state-of-the-art tractography techniques. This atlas is freely available and will be a useful resource for parcellation and segmentation.

Semi-supervised Machine Learning with MixMatch and Equivalence Classes.

Semi-supervised methods have an increasing impact on computer vision tasks to make use of scarce labels on large datasets, yet these approaches have not been well translated to medical imaging. Of particular interest, the MixMatch method achieves significant performance improvement over popular semi-supervised learning methods with scarce labels in the CIFAR-10 dataset. In a complementary approach, Nullspace Tuning on equivalence classes offers the potential to leverage multiple subject scans when the ground truth for the subject is unknown. This work is the first to (1) explore MixMatch with Nullspace Tuning in the context of medical imaging and (2) characterize the impacts of the methods with diminishing labels. We consider two distinct medical imaging domains: skin lesion diagnosis and lung cancer prediction. In both cases we evaluate models trained with diminishing labeled data using supervised, MixMatch, and Nullspace Tuning methods as well as MixMatch with Nullspace Tuning together. MixMatch with Nullspace Tuning together is able to achieve an AUC of 0.755 in lung cancer diagnosis with only 200 labeled subjects on the National Lung Screening Trial and a balanced multi-class accuracy of 77% with only 779 labeled examples on HAM10000. This performance is similar to that of the fully supervised methods when all labels are available. In advancing data driven methods in medical imaging, it is important to consider the use of current state-of-the-art semi-supervised learning methods from the greater machine learning community and their impact on the limitations of data acquisition and annotation.