FastMRI Prostate: A public, biparametric MRI dataset to advance machine learning for prostate cancer imaging.

Magnetic resonance imaging (MRI) has experienced remarkable advancements in the integration of artificial intelligence (AI) for image acquisition and reconstruction. The availability of raw k-space data is crucial for training AI models in such tasks, but public MRI datasets are mostly restricted to DICOM images only. To address this limitation, the fastMRI initiative released brain and knee k-space datasets, which have since seen vigorous use. In May 2023, fastMRI was expanded to include biparametric (T2- and diffusion-weighted) prostate MRI data from a clinical population. Biparametric MRI plays a vital role in the diagnosis and management of prostate cancer. Advances in imaging methods, such as reconstructing under-sampled data from accelerated acquisitions, can improve cost-effectiveness and accessibility of prostate MRI. Raw k-space data, reconstructed images and slice, volume and exam level annotations for likelihood of prostate cancer are provided in this dataset for 47468 slices corresponding to 1560 volumes from 312 patients. This dataset facilitates AI and algorithm development for prostate image reconstruction, with the ultimate goal of enhancing prostate cancer diagnosis.

Improved reconstruction of crossing fibers in the mouse optic pathways with orientation distribution function fingerprinting.

PURPOSE: The accuracy of diffusion MRI tractography reconstruction decreases in the white matter regions with crossing fibers. The optic pathways in rodents provide a challenging structure to test new diffusion tractography approaches because of the small crossing volume within the optic chiasm and the unbalanced 9:1 proportion between the contra- and ipsilateral neural projections from the retina to the lateral geniculate nucleus, respectively. METHODS: Common approaches based on Orientation Distribution Function (ODF) peak finding or statistical inference were compared qualitatively and quantitatively to ODF Fingerprinting (ODF-FP) for reconstruction of crossing fibers within the optic chiasm using in vivo diffusion MRI ( n = 18 $$ n=18 $$ healthy C57BL/6 mice). Manganese-Enhanced MRI (MEMRI) was obtained after intravitreal injection of manganese chloride and used as a reference standard for the optic pathway anatomy. RESULTS: ODF-FP outperformed by over 100% all the tested methods in terms of the ratios between the contra- and ipsilateral segments of the reconstructed optic pathways as well as the spatial overlap between tractography and MEMRI. CONCLUSION: In this challenging model system, ODF-Fingerprinting reduced uncertainty of diffusion tractography for complex structural formations of fiber bundles.

Validation of deep learning techniques for quality augmentation in diffusion MRI for clinical studies.

The objective of this study is to evaluate the efficacy of deep learning (DL) techniques in improving the quality of diffusion MRI (dMRI) data in clinical applications. The study aims to determine whether the use of artificial intelligence (AI) methods in medical images may result in the loss of critical clinical information and/or the appearance of false information. To assess this, the focus was on the angular resolution of dMRI and a clinical trial was conducted on migraine, specifically between episodic and chronic migraine patients. The number of gradient directions had an impact on white matter analysis results, with statistically significant differences between groups being drastically reduced when using 21 gradient directions instead of the original 61. Fourteen teams from different institutions were tasked to use DL to enhance three diffusion metrics (FA, AD and MD) calculated from data acquired with 21 gradient directions and a b-value of 1000 s/mm2. The goal was to produce results that were comparable to those calculated from 61 gradient directions. The results were evaluated using both standard image quality metrics and Tract-Based Spatial Statistics (TBSS) to compare episodic and chronic migraine patients. The study results suggest that while most DL techniques improved the ability to detect statistical differences between groups, they also led to an increase in false positive. The results showed that there was a constant growth rate of false positives linearly proportional to the new true positives, which highlights the risk of generalization of AI-based tasks when assessing diverse clinical cohorts and training using data from a single group. The methods also showed divergent performance when replicating the original distribution of the data and some exhibited significant bias. In conclusion, extreme caution should be exercised when using AI methods for harmonization or synthesis in clinical studies when processing heterogeneous data in clinical studies, as important information may be altered, even when global metrics such as structural similarity or peak signal-to-noise ratio appear to suggest otherwise.

Tractography passes the test: Results from the diffusion-simulated connectivity (disco) challenge.

Estimating structural connectivity from diffusion-weighted magnetic resonance imaging is a challenging task, partly due to the presence of false-positive connections and the misestimation of connection weights. Building on previous efforts, the MICCAI-CDMRI Diffusion-Simulated Connectivity (DiSCo) challenge was carried out to evaluate state-of-the-art connectivity methods using novel large-scale numerical phantoms. The diffusion signal for the phantoms was obtained from Monte Carlo simulations. The results of the challenge suggest that methods selected by the 14 teams participating in the challenge can provide high correlations between estimated and ground-truth connectivity weights, in complex numerical environments. Additionally, the methods used by the participating teams were able to accurately identify the binary connectivity of the numerical dataset. However, specific false positive and false negative connections were consistently estimated across all methods. Although the challenge dataset doesn't capture the complexity of a real brain, it provided unique data with known macrostructure and microstructure ground-truth properties to facilitate the development of connectivity estimation methods.

FastMRI Prostate: A Publicly Available, Biparametric MRI Dataset to Advance Machine Learning for Prostate Cancer Imaging.

The fastMRI brain and knee dataset has enabled significant advances in exploring reconstruction methods for improving speed and image quality for Magnetic Resonance Imaging (MRI) via novel, clinically relevant reconstruction approaches. In this study, we describe the April 2023 expansion of the fastMRI dataset to include biparametric prostate MRI data acquired on a clinical population. The dataset consists of raw k-space and reconstructed images for T2-weighted and diffusion-weighted sequences along with slice-level labels that indicate the presence and grade of prostate cancer. As has been the case with fastMRI, increasing accessibility to raw prostate MRI data will further facilitate research in MR image reconstruction and evaluation with the larger goal of improving the utility of MRI for prostate cancer detection and evaluation. The dataset is available at https://fastmri.med.nyu.edu.

Time-dependent diffusivity and kurtosis in phantoms and patients with head and neck cancer.

PURPOSE: To assess the reliability of measuring diffusivity, diffusional kurtosis, and cellular-interstitial water exchange time with long diffusion times (100-800 ms) using stimulated-echo DWI. METHODS: Time-dependent diffusion MRI was tested on two well-established diffusion phantoms and in 5 patients with head and neck cancer. Measurements were conducted using an in-house diffusion-weighted STEAM-EPI pulse sequence with multiple diffusion times at a fixed TE on three scanners. We used the weighted linear least-squares fit method to estimate time-dependent diffusivity, D ( t ) $$ D(t) $$ , and diffusional kurtosis, K ( t ) $$ K(t) $$ . Additionally, the Kärger model was used to estimate cellular-interstitial water exchange time ( τ ex $$ {\tau}_{ex} $$ ) from K ( t ) $$ K(t) $$ . RESULTS: Diffusivity measured by time-dependent STEAM-EPI measurements and commercial SE-EPI showed comparable results with R2 above 0.98 and overall 5.4 ± 3.0% deviation across diffusion times. Diffusional kurtosis phantom data showed expected patterns: constant D $$ D $$ and K $$ K $$  = 0 for negative controls and slow varying D $$ D $$ and K $$ K $$ for samples made of nanoscopic vesicles. Time-dependent diffusion MRI in patients with head and neck cancer found that the Kärger model could be considered valid in 72% ± 23% of the voxels in the metastatic lymph nodes. The median cellular-interstitial water exchange time estimated for lesions was between 58.5 ms and 70.6 ms. CONCLUSIONS: Based on two well-established diffusion phantoms, we found that time-dependent diffusion MRI measurements can provide stable diffusion and kurtosis values over a wide range of diffusion times and across multiple MRI systems. Moreover, estimation of cellular-interstitial water exchange time can be achieved using the Kärger model for the metastatic lymph nodes in patients with head and neck cancer.

Reproducibility of the Standard Model of diffusion in white matter on clinical MRI systems.

Estimating intra- and extra-axonal microstructure parameters, such as volume fractions and diffusivities, has been one of the major efforts in brain microstructure imaging with MRI. The Standard Model (SM) of diffusion in white matter has unified various modeling approaches based on impermeable narrow cylinders embedded in locally anisotropic extra-axonal space. However, estimating the SM parameters from a set of conventional diffusion MRI (dMRI) measurements is ill-conditioned. Multidimensional dMRI helps resolve the estimation degeneracies, but there remains a need for clinically feasible acquisitions that yield robust parameter maps. Here we find optimal multidimensional protocols by minimizing the mean-squared error of machine learning-based SM parameter estimates for two 3T scanners with corresponding gradient strengths of 40and80mT/m. We assess intra-scanner and inter-scanner repeatability for 15-minute optimal protocols by scanning 20 healthy volunteers twice on both scanners. The coefficients of variation all SM parameters except free water fraction are ≲10% voxelwise and 1-4% for their region-averaged values. As the achieved SM reproducibility outcomes are similar to those of conventional diffusion tensor imaging, our results enable robust in vivo mapping of white matter microstructure in neuroscience research and in the clinic.

Insights from the IronTract challenge: Optimal methods for mapping brain pathways from multi-shell diffusion MRI.

Limitations in the accuracy of brain pathways reconstructed by diffusion MRI (dMRI) tractography have received considerable attention. While the technical advances spearheaded by the Human Connectome Project (HCP) led to significant improvements in dMRI data quality, it remains unclear how these data should be analyzed to maximize tractography accuracy. Over a period of two years, we have engaged the dMRI community in the IronTract Challenge, which aims to answer this question by leveraging a unique dataset. Macaque brains that have received both tracer injections and ex vivo dMRI at high spatial and angular resolution allow a comprehensive, quantitative assessment of tractography accuracy on state-of-the-art dMRI acquisition schemes. We find that, when analysis methods are carefully optimized, the HCP scheme can achieve similar accuracy as a more time-consuming, Cartesian-grid scheme. Importantly, we show that simple pre- and post-processing strategies can improve the accuracy and robustness of many tractography methods. Finally, we find that fiber configurations that go beyond crossing (e.g., fanning, branching) are the most challenging for tractography. The IronTract Challenge remains open and we hope that it can serve as a valuable validation tool for both users and developers of dMRI analysis methods.

Performance of orientation distribution function-fingerprinting with a biophysical multicompartment diffusion model.

PURPOSE: Orientation Distribution Function (ODF) peak finding methods typically fail to reconstruct fibers crossing at shallow angles below 40°, leading to errors in tractography. ODF-Fingerprinting (ODF-FP) with the biophysical multicompartment diffusion model allows for breaking this barrier. METHODS: A randomized mechanism to generate a multidimensional ODF-dictionary that covers biologically plausible ranges of intra- and extra-axonal diffusivities and fraction volumes is introduced. This enables ODF-FP to address the high variability of brain tissue. The performance of the proposed approach is evaluated on both numerical simulations and a reconstruction of major fascicles from high- and low-resolution in vivo diffusion images. RESULTS: ODF-FP with the suggested modifications correctly identifies fibers crossing at angles as shallow as 10 degrees in the simulated data. In vivo, our approach reaches 56% of true positives in determining fiber directions, resulting in visibly more accurate reconstruction of pyramidal tracts, arcuate fasciculus, and optic radiations than the state-of-the-art techniques. Moreover, the estimated diffusivity values and fraction volumes in corpus callosum conform with the values reported in the literature. CONCLUSION: The modified ODF-FP outperforms commonly used fiber reconstruction methods at shallow angles, which improves deterministic tractography outcomes of major fascicles. In addition, the proposed approach allows for linearization of the microstructure parameters fitting problem.

Stepwise Stochastic Dictionary Adaptation Improves Microstructure Reconstruction with Orientation Distribution Function Fingerprinting.

Fitting of the multicompartment biophysical model of white matter is an ill-posed optimization problem. One approach to make it computationally tractable is through Orientation Distribution Function (ODF) Fingerprinting. However, the accuracy of this method relies solely on ODF dictionary generation mechanisms which either sample the microstructure parameters on a multidimensional grid or draw them randomly with a uniform distribution. In this paper, we propose a stepwise stochastic adaptation mechanism to generate ODF dictionaries tailored specifically to the diffusion-weighted images in hand. The results we obtained on a diffusion phantom and in vivo human brain images show that our reconstructed diffusivities are less noisy and the separation of a free water fraction is more pronounced than for the prior (uniform) distribution of ODF dictionaries.

T1 and T2 quantification using magnetic resonance fingerprinting in mild traumatic brain injury.

OBJECTIVES: To assess whether MR fingerprinting (MRF)-based relaxation properties exhibit cross-sectional and prospective correlations with patient outcome and compare the results with those from DTI. METHODS: Clinical imaging, MRF, and DTI were acquired in patients (24 ± 10 days after injury (timepoint 1) and 90 ± 17 days after injury (timepoint 2)) and once in controls. Patient outcome was assessed with global functioning, symptom profile, and neuropsychological testing. ADC and fractional anisotropy (FA) from DTI and T1 and T2 from MRF were compared in 12 gray and white matter regions with Mann-Whitney tests. Bivariate associations between MR measures and outcome were assessed using the Spearman correlation and logistic regression. RESULTS: Data from 22 patients (38 ± 12 years; 17 women) and 18 controls (32 ± 8 years; 12 women) were analyzed. Fourteen patients (37 ± 12 years; 11 women) returned for timepoint 2, while two patients provided only timepoint 2 clinical outcome data. At timepoint 1, there were no differences between patients and controls in T1, T2, and ADC, while FA was lower in mTBI frontal white matter. T1 at timepoint 1 and the change in T1 exhibited more (n = 18) moderate to strong correlations (|r|= 0.6-0.85) with clinical outcome at timepoint 2 than T2 (n = 3), FA (n = 7), and ADC (n = 2). High T1 at timepoint 1, and serially increasing T1, accounted for five of the six MR measures with the highest utility for identification of non-recovered patients at timepoint 2 (AUC > 0.80). CONCLUSION: T1 derived from MRF was found to have higher utility than T2, FA, and ADC for predicting 3-month outcome after mTBI. KEY POINTS: • In a region-of-interest approach, FA, ADC, and T1 and T2 all showed limited utility in differentiating patients from controls at an average of 24 and 90 days post-mild traumatic brain injury. • T1 at 24 days, and the serial change in T1, revealed more and stronger predictive correlations with clinical outcome at 90 days than did T2, ADC, or FA. • T1 showed better prospective identification of non-recovered patients at 90 days than ADC, T2, and FA.

Three-Dimensional Printed Anatomic Models Derived From Magnetic Resonance Imaging Data: Current State and Image Acquisition Recommendations for Appropriate Clinical Scenarios.

Three-dimensional (3D) printing technologies have been increasingly utilized in medicine over the past several years and can greatly facilitate surgical planning thereby improving patient outcomes. Although still much less utilized compared to computed tomography (CT), magnetic resonance imaging (MRI) is gaining traction in medical 3D printing. The purpose of this study was two-fold: 1) to determine the prevalence in the existing literature of using MRI to create 3D printed anatomic models for surgical planning and 2) to provide image acquisition recommendations for appropriate clinical scenarios where MRI is the most suitable imaging modality. The workflow for creating 3D printed anatomic models from medical imaging data is complex and involves image segmentation of the regions of interest and conversion of that data into 3D surface meshes, which are compatible with printing technologies. CT is most commonly used to create 3D printed anatomic models due to the high image quality and relative ease of performing image segmentation from CT data. As compared to CT datasets, 3D printing using MRI data offers advantages since it provides exquisite soft tissue contrast needed for accurate organ segmentation and it does not expose patients to unnecessary ionizing radiation. MRI, however, often requires complicated imaging techniques and time-consuming postprocessing procedures to generate high-resolution 3D anatomic models needed for 3D printing. Despite these challenges, 3D modeling and printing from MRI data holds great clinical promises thanks to emerging innovations in both advanced MRI imaging and postprocessing techniques. EVIDENCE LEVEL: 2 TECHNICAL EFFICATCY: 5.

Lower extremity MRI following 10-week supervised exercise intervention in patients with diabetic peripheral neuropathy.

INTRODUCTION: The purpose of this study was to characterize using MRI the effects of a 10-week supervised exercise program on lower extremity skeletal muscle composition, nerve microarchitecture, and metabolic function in individuals with diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS: Twenty participants with DPN completed a longitudinal trial consisting of a 30-day control period, during which subjects made no change to their lifestyle, followed by a 10-week intervention program that included three supervised aerobic and resistance exercise sessions per week targeting the upper and lower extremities. The participants' midcalves were scanned with multinuclear MRI two times prior to intervention (baseline1 and baseline2) and once following intervention to measure relaxation times (T1, T1ρ, and T2), phosphocreatine recovery, fat fraction, and diffusion parameters. RESULTS: There were no changes between baseline1 and baseline2 MRI metrics (p>0.2). Significant changes (p<0.05) between baseline2 and postintervention MRI metrics were: gastrocnemius medialis (GM) T1 -2.3%±3.0% and soleus T2 -3.2%±3.1%. Trends toward significant changes (0.050.3) and tibial nerve fractional anisotropy (p>0.6) and apparent diffusion coefficient (p>0.4). CONCLUSIONS: The 10-week supervised exercise intervention program successfully reduced adiposity and altered resting tissue properties in the lower leg in DPN. Gastrocnemius mitochondrial oxidative capacity and tibial nerve microarchitecture changes were not observed, either due to lack of response to therapy or to lack of measurement sensitivity.

Cortical and subcortical signatures of conscious object recognition.

The neural mechanisms underlying conscious recognition remain unclear, particularly the roles played by the prefrontal cortex, deactivated brain areas and subcortical regions. We investigated neural activity during conscious object recognition using 7 Tesla fMRI while human participants viewed object images presented at liminal contrasts. Here, we show both recognized and unrecognized images recruit widely distributed cortical and subcortical regions; however, recognized images elicit enhanced activation of visual, frontoparietal, and subcortical networks and stronger deactivation of the default-mode network. For recognized images, object category information can be decoded from all of the involved cortical networks but not from subcortical regions. Phase-scrambled images trigger strong involvement of inferior frontal junction, anterior cingulate cortex and default-mode network, implicating these regions in inferential processing under increased uncertainty. Our results indicate that content-specific activity in both activated and deactivated cortical networks and non-content-specific subcortical activity support conscious recognition.

Global decrease in brain sodium concentration after mild traumatic brain injury.

The pathological cascade of tissue damage in mild traumatic brain injury is set forth by a perturbation in ionic homeostasis. However, whether this class of injury can be detected in vivo and serve as a surrogate marker of clinical outcome is unknown. We employ sodium MRI to test the hypotheses that regional and global total sodium concentrations: (i) are higher in patients than in controls and (ii) correlate with clinical presentation and neuropsychological function. Given the novelty of sodium imaging in traumatic brain injury, effect sizes from (i), and correlation types and strength from (ii), were compared to those obtained using standard diffusion imaging metrics. Twenty-seven patients (20 female, age 35.9 ± 12.2 years) within 2 months after injury and 19 controls were scanned with proton and sodium MRI at 3 Tesla. Total sodium concentration, fractional anisotropy and apparent diffusion coefficient were obtained with voxel averaging across 12 grey and white matter regions. Linear regression was used to obtain global grey and white matter total sodium concentrations. Patient outcome was assessed with global functioning, symptom profiles and neuropsychological function assessments. In the regional analysis, there were no statistically significant differences between patients and controls in apparent diffusion coefficient, while differences in sodium concentration and fractional anisotropy were found only in single regions. However, for each of the 12 regions, sodium concentration effect sizes were uni-directional, due to lower mean sodium concentration in patients compared to controls. Consequently, linear regression analysis found statistically significant lower global grey and white matter sodium concentrations in patients compared to controls. The strongest correlation with outcome was between global grey matter sodium concentration and the composite z-score from the neuropsychological testing. In conclusion, both sodium concentration and diffusion showed poor utility in differentiating patients from controls, and weak correlations with clinical presentation, when using a region-based approach. In contrast, sodium linear regression, capitalizing on partial volume correction and high sensitivity to global changes, revealed high effect sizes and associations with patient outcome. This suggests that well-recognized sodium imbalances in traumatic brain injury are (i) detectable non-invasively; (ii) non-focal; (iii) occur even when the antecedent injury is clinically mild. Finally, in contrast to our principle hypothesis, patients' sodium concentrations were lower than controls, indicating that the biological effect of traumatic brain injury on the sodium homeostasis may differ from that in other neurological disorders. Note: This figure has been annotated.

CG-SENSE revisited: Results from the first ISMRM reproducibility challenge.

PURPOSE: The aim of this work is to shed light on the issue of reproducibility in MR image reconstruction in the context of a challenge. Participants had to recreate the results of "Advances in sensitivity encoding with arbitrary k-space trajectories" by Pruessmann et al. METHODS: The task of the challenge was to reconstruct radially acquired multicoil k-space data (brain/heart) following the method in the original paper, reproducing its key figures. Results were compared to consolidated reference implementations created after the challenge, accounting for the two most common programming languages used in the submissions (Matlab/Python). RESULTS: Visually, differences between submissions were small. Pixel-wise differences originated from image orientation, assumed field-of-view, or resolution. The reference implementations were in good agreement, both visually and in terms of image similarity metrics. DISCUSSION AND CONCLUSION: While the description level of the published algorithm enabled participants to reproduce CG-SENSE in general, details of the implementation varied, for example, density compensation or Tikhonov regularization. Implicit assumptions about the data lead to further differences, emphasizing the importance of sufficient metadata accompanying open datasets. Defining reproducibility quantitatively turned out to be nontrivial for this image reconstruction challenge, in the absence of ground-truth results. Typical similarity measures like NMSE of SSIM were misled by image intensity scaling and outlier pixels. Thus, to facilitate reproducibility, researchers are encouraged to publish code and data alongside the original paper. Future methodological papers on MR image reconstruction might benefit from the consolidated reference implementations of CG-SENSE presented here, as a benchmark for methods comparison.

Mapping brain-behavior networks using functional and structural connectome fingerprinting in the HCP dataset.

INTRODUCTION: Connectome analysis of the human brain's structural and functional architecture provides a unique opportunity to understand the organization of the brain's functional architecture. In previous studies, connectome fingerprinting using brain functional connectivity profiles as an individualized trait was able to predict an individual's neurocognitive performance from the Human Connectome Project (HCP) neurocognitive datasets. MATERIALS AND METHODS: In the present study, we extend connectome fingerprinting from functional connectivity (FC) to structural connectivity (SC), identifying multiple relationships between behavioral traits and brain connectivity. Higher-order neurocognitive tasks were found to have a weaker association with structural connectivity than its functional connectivity counterparts. RESULTS: Neurocognitive tasks with a higher sensory footprint were, however, found to have a stronger association with structural connectivity than their functional connectivity counterparts. Language behavioral measurements had a particularly stronger correlation, especially between performance on the picture language test (Pic Vocab) and both FC (r = .28, p < .003) and SC (r = 0.27, p < .00077). CONCLUSIONS: At the neural level, we found that the pattern of structural brain connectivity related to high-level language performance is consistent with the language white matter regions identified in presurgical mapping. We illustrate how this approach can be used to generalize the connectome fingerprinting framework to structural connectivity and how this can help understand the connections between cognitive behavior and the white matter connectome of the brain.

Fingerprinting Orientation Distribution Functions in diffusion MRI detects smaller crossing angles.

Diffusion tractography is routinely used to study white matter architecture and brain connectivity in vivo. A key step for successful tractography of neuronal tracts is the correct identification of tract directions in each voxel. Here we propose a fingerprinting-based methodology to identify these fiber directions in Orientation Distribution Functions, dubbed ODF-Fingerprinting (ODF-FP). In ODF-FP, fiber configurations are selected based on the similarity between measured ODFs and elements in a pre-computed library. In noisy ODFs, the library matching algorithm penalizes the more complex fiber configurations. ODF simulations and analysis of bootstrapped partial and whole-brain in vivo datasets show that the ODF-FP approach improves the detection of fiber pairs with small crossing angles while maintaining fiber direction precision, which leads to better tractography results. Rather than focusing on the ODF maxima, the ODF-FP approach uses the whole ODF shape to infer fiber directions to improve the detection of fiber bundles with small crossing angle. The resulting fiber directions aid tractography algorithms in accurately displaying neuronal tracts and calculating brain connectivity.

Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder.

A mechanistic understanding of the pathology of psychiatric disorders has been hampered by extensive heterogeneity in biology, symptoms, and behavior within diagnostic categories that are defined subjectively. We investigated whether leveraging individual differences in information-processing impairments in patients with post-traumatic stress disorder (PTSD) could reveal phenotypes within the disorder. We found that a subgroup of patients with PTSD from two independent cohorts displayed both aberrant functional connectivity within the ventral attention network (VAN) as revealed by functional magnetic resonance imaging (fMRI) neuroimaging and impaired verbal memory on a word list learning task. This combined phenotype was not associated with differences in symptoms or comorbidities, but nonetheless could be used to predict a poor response to psychotherapy, the best-validated treatment for PTSD. Using concurrent focal noninvasive transcranial magnetic stimulation and electroencephalography, we then identified alterations in neural signal flow in the VAN that were evoked by direct stimulation of that network. These alterations were associated with individual differences in functional fMRI connectivity within the VAN. Our findings define specific neurobiological mechanisms in a subgroup of patients with PTSD that could contribute to the poor response to psychotherapy.

Low Rank plus Sparse decomposition of ODFs for improved detection of group-level differences and variable correlations in white matter.

A novel approach is presented for group statistical analysis of diffusion weighted MRI datasets through voxelwise Orientation Distribution Functions (ODF). Recent advances in MRI acquisition make it possible to use high quality diffusion weighted protocols (multi-shell, large number of gradient directions) for routine in vivo study of white matter architecture. The dimensionality of these data sets is however often reduced to simplify statistical analysis. While these approaches may detect large group differences, they do not fully capitalize on all acquired image volumes. Incorporation of all available diffusion information in the analysis however risks biasing the outcome by outliers. Here we propose a statistical analysis method operating on the ODF, either the diffusion ODF or fiber ODF. To avoid outlier bias and reliably detect voxelwise group differences and correlations with demographic or behavioral variables, we apply the Low-Rank plus Sparse (L+S) matrix decomposition on the voxelwise ODFs which separates the sparse individual variability in the sparse matrix S whilst recovering the essential ODF features in the low-rank matrix L. We demonstrate the performance of this ODF L+S approach by replicating the established negative association between global white matter integrity and physical obesity in the Human Connectome dataset. The volume of positive findings p<0.01,227cm3, agrees with and expands on the volume found by TBSS (17 cm3), Connectivity based fixel enhancement (15 cm3) and Connectometry (212 cm3). In the same dataset we further localize the correlations of brain structure with neurocognitive measures such as fluid intelligence and episodic memory. The presented ODF L+S approach will aid in the full utilization of all acquired diffusion weightings leading to the detection of smaller group differences in clinically relevant settings as well as in neuroscience applications.