Structural connectivity of cytoarchitectonically distinct human left temporal pole subregions: a diffusion MRI tractography study.

The temporal pole (TP) is considered one of the major paralimbic cortical regions, and is involved in a variety of functions such as sensory perception, emotion, semantic processing, and social cognition. Based on differences in cytoarchitecture, the TP can be further subdivided into smaller regions (dorsal, ventrolateral and ventromedial), each forming key nodes of distinct functional networks. However, the brain structural connectivity profile of TP subregions is not fully clarified. Using diffusion MRI data in a set of 31 healthy subjects, we aimed to elucidate the comprehensive structural connectivity of three cytoarchitectonically distinct TP subregions. Diffusion tensor imaging (DTI) analysis suggested that major association fiber pathways such as the inferior longitudinal, middle longitudinal, arcuate, and uncinate fasciculi provide structural connectivity to the TP. Further analysis suggested partially overlapping yet still distinct structural connectivity patterns across the TP subregions. Specifically, the dorsal subregion is strongly connected with wide areas in the parietal lobe, the ventrolateral subregion with areas including constituents of the default-semantic network, and the ventromedial subregion with limbic and paralimbic areas. Our results suggest the involvement of the TP in a set of extensive but distinct networks of cortical regions, consistent with its functional roles.

Predicting histopathology markers of endometrial carcinoma with a quantitative image analysis approach based on spherical harmonics in multiparametric MRI.

PURPOSE: Identifying optimal machine learning pipelines for computer-aided diagnosis is key for the development of robust, reproducible, and clinically relevant imaging biomarkers for endometrial carcinoma. The purpose of this study was to introduce the mathematical development of image descriptors computed from spherical harmonics (SPHARM) decompositions as well as the associated machine learning pipeline, and to evaluate their performance in predicting deep myometrial invasion (MI) and histopathological high-grade in preoperative multiparametric magnetic resonance imaging (MRI). PATIENTS AND METHODS: This retrospective study included 128 women with histopathology-confirmed endometrial carcinomas who underwent 1.5-T MRI before hysterectomy between January 2011 and July 2015. SPHARM descriptors of each tumor were computed on multiparametric MRI images (T2-weighted, diffusion-weighted, dynamic contrast-enhanced-MRI and apparent diffusion coefficient maps). Tensor-based logistic regression was used to classify two-dimensional SPHARM rotationally-invariant descriptors. Head-to-head comparisons with radiomics analyses were performed with DeLong tests with Bonferroni-Holm correction to compare diagnostic performances. RESULTS: With all MRI contrasts, SPHARM analysis resulted in area under the curve, sensitivity, specificity, and balanced accuracy values of 0.94 (95% confidence interval [CI]: 0.85, 1.00), 100% (95% CI: 100, 100), 74% (95% CI: 51, 92), 87% (95% CI: 78, 98), respectively, for predicting deep MI. For predicting high-grade tumor histology, the corresponding values for the same diagnostic metrics were 0.81 (95% CI: 0.64, 0.90), 93% (95% CI: 67, 100), 63% (95% CI: 45, 79) and 78% (95% CI: 64, 86). The corresponding values achieved via radiomics were 0.92 (95% CI: 0.82, 0.95), 82% (95% CI: 65, 93), 80% (95% CI: 51, 94), 81% (95% CI: 70, 91) for deep MI and 0.72 (95% CI: 0.58, 0.83), 93% (95% CI: 65, 100), 55% (95% CI: 41, 69), 74% (95% CI: 52, 88) for high-grade histology. The diagnostic performance of the SPHARM analysis was not significantly different (P = 0.62) from that of radiomics for predicting deep MI but was significantly higher (P = 0.044) for predicting high-grade histology. CONCLUSION: The proposed SPHARM analysis yields similar or higher diagnostic performance than radiomics in identifying deep MI and high-grade status in histology-proven endometrial carcinoma.

DECT-CLUST: Dual-Energy CT Image Clustering and Application to Head and Neck Squamous Cell Carcinoma Segmentation.

Dual-energy computed tomography (DECT) is an advanced CT computed tomography scanning technique enabling material characterization not possible with conventional CT scans. It allows the reconstruction of energy decay curves at each 3D image voxel, representing varied image attenuation at different effective scanning energy levels. In this paper, we develop novel unsupervised learning techniques based on mixture models and functional data analysis models to the clustering of DECT images. We design functional mixture models that integrate spatial image context in mixture weights, with mixture component densities being constructed upon the DECT energy decay curves as functional observations. We develop dedicated expectation-maximization algorithms for the maximum likelihood estimation of the model parameters. To our knowledge, this is the first article to develop statistical functional data analysis and model-based clustering techniques to take advantage of the full spectral information provided by DECT. We evaluate the application of DECT to head and neck squamous cell carcinoma. Current image-based evaluation of these tumors in clinical practice is largely qualitative, based on a visual assessment of tumor anatomic extent and basic one- or two-dimensional tumor size measurements. We evaluate our methods on 91 head and neck cancer DECT scans and compare our unsupervised clustering results to tumor contours traced manually by radiologists, as well as to several baseline algorithms. Given the inter-rater variability even among experts at delineating head and neck tumors, and given the potential importance of tissue reactions surrounding the tumor itself, our proposed methodology has the potential to add value in downstream machine learning applications for clinical outcome prediction based on DECT data in head and neck cancer.

Development and Validation of Multiparametric MRI-based Radiomics Models for Preoperative Risk Stratification of Endometrial Cancer.

Background Stratifying high-risk histopathologic features in endometrial carcinoma is important for treatment planning. Radiomics analysis at preoperative MRI holds potential to identify high-risk phenotypes. Purpose To evaluate the performance of multiparametric MRI three-dimensional radiomics-based machine learning models for differentiating low- from high-risk histopathologic markers-deep myometrial invasion (MI), lymphovascular space invasion (LVSI), and high-grade status-and advanced-stage endometrial carcinoma. Materials and Methods This dual-center retrospective study included women with histologically proven endometrial carcinoma who underwent 1.5-T MRI before hysterectomy between January 2011 and July 2015. Exclusion criteria were tumor diameter less than 1 cm, missing MRI sequences or histopathology reports, neoadjuvant therapy, and malignant neoplasms other than endometrial carcinoma. Three-dimensional radiomics features were extracted after tumor segmentation at MRI (T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI). Predictive features were selected in the training set with use of random forest (RF) models for each end point, and trained RF models were applied to the external test set. Five board-certified radiologists conducted MRI-based staging and deep MI assessment in the training set. Areas under the receiver operating characteristic curve (AUCs) were reported with balanced accuracies, and radiologists' readings were compared with radiomics with use of McNemar tests. Results In total, 157 women were included: 94 at the first institution (training set; mean age, 66 years ± 11 [SD]) and 63 at the second institution (test set; 67 years ± 12). RF models dichotomizing deep MI, LVSI, high grade, and International Federation of Gynecology and Obstetrics (FIGO) stage led to AUCs of 0.81 (95% CI: 0.68, 0.88), 0.80 (95% CI: 0.67, 0.93), 0.74 (95% CI: 0.61, 0.86), and 0.84 (95% CI: 0.72, 0.92), respectively, in the test set. In the training set, radiomics provided increased performance compared with radiologists' readings for identifying deep MI (balanced accuracy, 86% vs 79%; P = .03), while no evidence of a difference was observed in performance for advanced FIGO stage (80% vs 78%; P = .27). Conclusion Three-dimensional radiomics can stratify patients by using preoperative MRI according to high-risk histopathologic end points in endometrial carcinoma and provide nonsignificantly different or higher performance than radiologists in identifying advanced stage and deep myometrial invasion, respectively. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kido and Nishio in this issue.

Improved Detection of Chronic Obstructive Pulmonary Disease at Chest CT Using the Mean Curvature of Isophotes.

PURPOSE: To determine if the mean curvature of isophotes (MCI), a standard computer vision technique, can be used to improve detection of chronic obstructive pulmonary disease (COPD) at chest CT. MATERIALS AND METHODS: In this retrospective study, chest CT scans were obtained in 243 patients with COPD and 31 controls (among all 274: 151 women [mean age, 70 years; range, 44-90 years] and 123 men [mean age, 71 years; range, 29-90 years]) from two community practices between 2006 and 2019. A convolutional neural network (CNN) architecture was trained on either CT images or CT images transformed through the MCI algorithm. Separately, a linear classification based on a single feature derived from the MCI computation (called hMCI1) was also evaluated. All three models were evaluated with cross-validation, using precision-macro and recall-macro metrics, that is, the mean of per-class precision and recall values, respectively (the latter being equivalent to balanced accuracy). RESULTS: Linear classification based on hMCI1 resulted in a higher recall-macro relative to the CNN trained and applied on CT images (0.85 [95% CI: 0.84, 0.86] vs 0.77 [95% CI: 0.75, 0.79]) but with a similar reduction in precision-macro (0.66 [95% CI: 0.65, 0.67] vs 0.77 [95% CI: 0.75, 0.79]). The CNN model trained and applied on MCI-transformed images had a higher recall-macro (0.85 [95% CI: 0.83, 0.87] vs 0.77 [95% CI: 0.75, 0.79]) and precision-macro (0.85 [95% CI: 0.83, 0.87] vs 0.77 [95% CI: 0.75, 0.79]) relative to the CNN trained and applied on CT images. CONCLUSION: The MCI algorithm may be valuable toward the automated detection and diagnosis of COPD on chest CT scans as part of a CNN-based pipeline or with stand-alone features.Keywords: Chronic Obstructive Pulmonary Disease, Quantification, Lung, CT Supplemental material is available for this article. See also the invited commentary by Vannier in this issue.© RSNA, 2021.

Malignancy risk stratification of cystic renal lesions based on a contrast-enhanced CT-based machine learning model and a clinical decision algorithm.

OBJECTIVE: To distinguish benign from malignant cystic renal lesions (CRL) using a contrast-enhanced CT-based radiomics model and a clinical decision algorithm. METHODS: This dual-center retrospective study included patients over 18 years old with CRL between 2005 and 2018. The reference standard was histopathology or 4-year imaging follow-up. Training and testing datasets were acquired from two institutions. Quantitative 3D radiomics analyses were performed on nephrographic phase CT images. Ten-fold cross-validated LASSO regression was applied to the training dataset to identify the most discriminative features. A logistic regression model was trained to classify malignancy and tested on the independent dataset. Reported metrics included areas under the receiver operating characteristic curves (AUC) and balanced accuracy. Decision curve analysis for stratifying patients for surgery was performed in the testing dataset. A decision algorithm was built by combining consensus radiological readings of Bosniak categories and radiomics-based risks. RESULTS: A total of 149 CRL (139 patients; 65 years [56-72]) were included in the training dataset-35 Bosniak(B)-IIF (8.6% malignancy), 23 B-III (43.5%), and 23 B-IV (87.0%)-and 50 CRL (46 patients; 61 years [51-68]) in the testing dataset-12 B-IIF (8.3%), 10 B-III (60.0%), and 9 B-IV (100%). The machine learning model achieved high diagnostic performance in predicting malignancy in the testing dataset (AUC = 0.96; balanced accuracy = 94%). There was a net benefit across threshold probabilities in using the clinical decision algorithm over management guidelines based on Bosniak categories. CONCLUSION: CT-based radiomics modeling accurately distinguished benign from malignant CRL, outperforming the Bosniak classification. The decision algorithm best stratified lesions for surgery and active surveillance. KEY POINTS: • The radiomics model achieved excellent diagnostic performance in identifying malignant cystic renal lesions in an independent testing dataset (AUC = 0.96). • The machine learning-enhanced decision algorithm outperformed the management guidelines based on the Bosniak classification for stratifying patients to surgical ablation or active surveillance.

Knowledge Based Versus Data Based: A Historical Perspective on a Continuum of Methodologies for Medical Image Analysis.

The advent of big data and deep learning algorithms has promoted a major shift toward data-driven methods in medical image analysis recently. However, the medical image analysis field has a long and rich history inclusive of both knowledge-driven and data-driven methodologies. In the present article, we provide a historical review of an illustrative sample of medical image analysis methods and locate them along a knowledge-driven versus data-driven continuum. In doing so, we highlight the historical importance as well as current-day relevance of more traditional, knowledge-based artificial intelligence approaches and their complementarity with fully data-driven techniques such as deep learning.

Individual variations of the human corticospinal tract and its hand-related motor fibers using diffusion MRI tractography.

The corticospinal tract (CST) is one of the most well studied tracts in human neuroanatomy. Its clinical significance can be demonstrated in many notable traumatic conditions and diseases such as stroke, spinal cord injury (SCI) or amyotrophic lateral sclerosis (ALS). With the advent of diffusion MRI and tractography the computational representation of the human CST in a 3D model became available. However, the representation of the entire CST and, specifically, the hand motor area has remained elusive. In this paper we propose a novel method, using manually drawn ROIs based on robustly identifiable neuroanatomic structures to delineate the entire CST and isolate its hand motor representation as well as to estimate their variability and generate a database of their volume, length and biophysical parameters. Using 37 healthy human subjects we performed a qualitative and quantitative analysis of the CST and the hand-related motor fiber tracts (HMFTs). Finally, we have created variability heat maps from 37 subjects for both the aforementioned tracts, which could be utilized as a reference for future studies with clinical focus to explore neuropathology in both trauma and disease states.

Radiomics in hepatocellular carcinoma: a quantitative review.

Radiomics is an emerging field which extracts quantitative radiology data from medical images and explores their correlation with clinical outcomes in a non-invasive manner. This review aims to assess whether radiomics is a useful and reproducible method for clinical management of hepatocellular carcinoma (HCC) by reviewing the strengths and weaknesses of current radiomics literature pertaining specifically to HCC. From an initial set of 48 articles recovered through database searches, 23 articles were retained to be included in this review after full screening. Among these 23 studies, 7 used a radiomics approach in magnetic resonance imaging (MRI). Only two studies applied radiomics to positron emission tomography-computed tomography (PET-CT). In the remaining 14 articles, a radiomics analysis was performed on computed tomography (CT). Eight studies dealt with the relationship between biological signatures and imaging findings, and can be classified as radiogenomic studies. For each study included in our review, we computed a Radiomics Quality Score (RQS) as proposed by Lambin et al. We found that the RQS (mean ± standard deviation) was 8.35 ± 5.38 (out of a possible maximum value of 36). Although these scores are fairly low, and radiomics has not yet reached clinical utility in HCC, it is important to underscore the fact that these early studies pave the way for the radiomics field with a focus on HCC. Radiomics is still a very young field, and is far from being mature, but it remains a very promising technology for the future for developing adequate personalized treatment as a non-invasive approach, for complementing or replacing tumor biopsies, as well as for developing novel prognostic biomarkers in HCC patients.

Radiomics and Artificial Intelligence for Biomarker and Prediction Model Development in Oncology.

Unlabelled Image.

Image-based biomarkers for solid tumor quantification.

The last few decades have witnessed tremendous technological developments in image-based biomarkers for tumor quantification and characterization. Initially limited to manual one- and two-dimensional size measurements, image biomarkers have evolved to harness developments not only in image acquisition technology but also in image processing and analysis algorithms. At the same time, clinical validation remains a major challenge for the vast majority of these novel techniques, and there is still a major gap between the latest technological developments and image biomarkers used in everyday clinical practice. Currently, the imaging biomarker field is attracting increasing attention not only because of the tremendous interest in cutting-edge therapeutic developments and personalized medicine but also because of the recent progress in the application of artificial intelligence (AI) algorithms to large-scale datasets. Thus, the goal of the present article is to review the current state of the art for image biomarkers and their use for characterization and predictive quantification of solid tumors. Beginning with an overview of validated imaging biomarkers in current clinical practice, we proceed to a review of AI-based methods for tumor characterization, such as radiomics-based approaches and deep learning.Key Points• Recent years have seen tremendous technological developments in image-based biomarkers for tumor quantification and characterization.• Image-based biomarkers can be used on an ongoing basis, in a non-invasive (or mildly invasive) way, to monitor the development and progression of the disease or its response to therapy.• We review the current state of the art for image biomarkers, as well as the recent developments in artificial intelligence (AI) algorithms for image processing and analysis.

Utilizing Mutual Information Analysis to Explore the Relationship Between Gray and White Matter Structural Pathologies in Schizophrenia.

Schizophrenia has been characterized as a neurodevelopmental disorder, with structural brain abnormalities reported at all stages. However, at present, it remains unclear whether gray and white matter abnormalities represent related or independent pathologies in schizophrenia. In this study, we present findings from an integrative analysis exploring the morphological relationship between gray and white matter in 45 schizophrenia participants and 49 healthy controls. We utilized mutual information (MI), a measure of how much information two variables share, to assess the morphological dependence between gray and white matter in three segments of the corpus callsoum, and the gray matter regions these segments connect: (1) the genu and the left and right rostral middle frontal gyrus (rMFG), (2) the isthmus and the left and right superior temporal gyrus (STG), (3) the splenium and the left and right lateral occipital gyrus (LOG). We report significantly reduced MI between white matter tract dispersion of the right hemispheric callosal connections to the STG and both cortical thickness and area in the right STG in schizophrenia patients, despite a lack of group differences in cortical thickness, surface area, or dispersion. We believe that this reduction in morphological dependence between gray and white matter may reflect a possible decoupling of the developmental processes that shape morphological features of white and gray matter early in life. The present study also demonstrates the importance of studying the relationship between gray and white matter measures, as opposed to restricting analyses to gray and white matter measures independently.

Striato-nigro-striatal tract dispersion abnormalities in patients with chronic schizophrenia.

The white matter connections between the midbrain dopamine neurons and the striatum are part of a neural system involved in reward-based learning, a process that is impaired in patients with schizophrenia. The striato-nigro-striatal (SNS) tract, which participates in this process, has not as yet been explored. The present study aimed to use diffusion MRI (dMRI) to delineate the SNS tract, and to compare the application of two dMRI measures, Tract Dispersion (TD), an index of white matter morphology, and Fractional Anisotropy (FA), an index of white matter integrity, to detect group differences between patients with chronic schizophrenia (CSZ) and healthy controls (HC). dMRI scans were acquired in 22 male patients with CSZ and 23 age-matched HC. Two-tensor tractography was used in addition to manually-delineated regions of interest to extract the SNS tract. A mixed-model analysis of variance was used to investigate differences in TD and FA between CSZ patients and HC. The associations between TD and behavioral measures were also explored. Patients and controls differed significantly in TD (P = 0.04), but not in FA (P = 0.69). The group differences in TD were driven by a higher TD in the right hemisphere in the CSZ group. Higher TD correlated significantly with poorer performance in the Iowa Gambling Task (IGT) when combining the scores of both groups. The findings suggest that dysconnectiviy of the SNS tract which is associated with schizophrenia, could arise from abnormalities in white matter morphology. These abnormalities may potentially reflect irregularities in brain development.

Demystification of AI-driven medical image interpretation: past, present and future.

The recent explosion of 'big data' has ushered in a new era of artificial intelligence (AI) algorithms in every sphere of technological activity, including medicine, and in particular radiology. However, the recent success of AI in certain flagship applications has, to some extent, masked decades-long advances in computational technology development for medical image analysis. In this article, we provide an overview of the history of AI methods for radiological image analysis in order to provide a context for the latest developments. We review the functioning, strengths and limitations of more classical methods as well as of the more recent deep learning techniques. We discuss the unique characteristics of medical data and medical science that set medicine apart from other technological domains in order to highlight not only the potential of AI in radiology but also the very real and often overlooked constraints that may limit the applicability of certain AI methods. Finally, we provide a comprehensive perspective on the potential impact of AI on radiology and on how to evaluate it not only from a technical point of view but also from a clinical one, so that patients can ultimately benefit from it. KEY POINTS: • Artificial intelligence (AI) research in medical imaging has a long history • The functioning, strengths and limitations of more classical AI methods is reviewed, together with that of more recent deep learning methods. • A perspective is provided on the potential impact of AI on radiology and on its evaluation from both technical and clinical points of view.

Genetic load determines atrophy in hand cortico-striatal pathways in presymptomatic Huntington's disease.

Huntington's disease (HD) is an inherited neurodegenerative disorder that causes progressive breakdown of striatal neurons. Standard white matter integrity measures like fractional anisotropy and mean diffusivity derived from diffusion tensor imaging were analyzed in prodromal-HD subjects; however, they studied either a whole brain or specific subcortical white matter structures with connections to cortical motor areas. In this work, we propose a novel analysis of a longitudinal cohort of 243 prodromal-HD individuals and 88 healthy controls who underwent two or more diffusion MRI scans as part of the PREDICT-HD study. We separately trace specific white matter fiber tracts connecting the striatum (caudate and putamen) with four cortical regions corresponding to the hand, face, trunk, and leg motor areas. A multi-tensor tractography algorithm with an isotropic volume fraction compartment allows estimating diffusion of fast-moving extra-cellular water in regions containing crossing fibers and provides quantification of a microstructural property related to tissue atrophy. The tissue atrophy rate is separately analyzed in eight cortico-striatal pathways as a function of CAG-repeats (genetic load) by statistically regressing out age effect from our cohort. The results demonstrate a statistically significant increase in isotropic volume fraction (atrophy) bilaterally in hand fiber connections to the putamen with increasing CAG-repeats, which connects the genetic abnormality (CAG-repeats) to an imaging-based microstructural marker of tissue integrity in specific white matter pathways in HD. Isotropic volume fraction measures in eight cortico-striatal pathways are also correlated significantly with total motor scores and diagnostic confidence levels, providing evidence of their relevance to HD clinical presentation.

Conduction in the Heart Wall: Helicoidal Fibers Minimize Diffusion Bias.

The mammalian heart must function as an efficient pump while simultaneously conducting electrical signals to drive the contraction process. In the ventricles, electrical activation begins at the insertion points of the Purkinje network in the endocardium. How does the diffusion component of the subsequent excitation wave propagate from the endocardium in a healthy heart wall without creating directional biases? We show that this is a consequence of the particular geometric organization of myocytes in the heart wall. Using a generalized helicoid to model fiber orientation, we treat the myocardium as a curved space via Riemannian geometry, and then use stochastic calculus to model local signal diffusion. Our analysis shows that the helicoidal arrangement of myocytes minimizes the directional biases that could lead to aberrant propagation, thereby explaining how electrophysiological principles are consistent with local measurements of cardiac fiber geometry. We discuss our results in the context of the need to balance electrical and mechanical requirements for heart function.

Childhood adversity associated with white matter alteration in the corpus callosum, corona radiata, and uncinate fasciculus of psychiatrically healthy adults.

Diffusion tensor imaging studies report childhood adversity (CA) is associated with reduced fractional anisotropy (FA) in multiple white matter tracts in adults. Reduced FA may result from changes in tissue, suggesting myelin/axonal damage, and/or from increased levels of extracellular free-water, suggesting atrophy or neuroinflammation. Free-water imaging can separately identify FA in tissue (FAT) and the fractional volume of free-water (FW). We tested whether CA was associated with altered FA, FAT, and FW in seven white matter regions of interest (ROI), in which FA changes had been previously linked to CA (corona radiata, corpus callosum, fornix, cingulum bundle: hippocampal projection, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, uncinate fasciculus). Tract-based spatial statistics were performed in 147 psychiatrically healthy adults who had completed a self-report questionnaire on CA primarily stemming from parental maltreatment. ROI were extracted according to the protocol provided by the ENIGMA-DTI working group. Analyses were performed both treating CA as a continuous and a categorical variable. CA was associated with reduced FA in all ROI (although categorical analyses failed to find an association in the fornix). In contrast, CA was only associated with reduced FAT in the corona radiata, corpus callosum, and uncinate fasciculus (with the continuous measure of CA finding evidence of a negative relation between CA and FAT in the fornix). There was no association between CA on FW in any ROI. These results provide preliminary evidence that childhood adversity is associated with changes to the microstructure of white matter itself in adulthood. However, these results should be treated with caution until they can be replicated by future studies which address the limitations of the present study.

Multi-site harmonization of diffusion MRI data in a registration framework.

Diffusion MRI (dMRI) data acquired on different scanners varies significantly in its content throughout the brain even if the acquisition parameters are nearly identical. Thus, proper harmonization of such data sets is necessary to increase the sample size and thereby the statistical power of neuroimaging studies. In this paper, we present a novel approach to harmonize dMRI data (the raw signal, instead of dMRI derived measures such as fractional anisotropy) using rotation invariant spherical harmonic (RISH) features embedded within a multi-modal image registration framework. All dMRI data sets from all sites are registered to a common template and voxel-wise differences in RISH features between sites at a group level are used to harmonize the signal in a subject-specific manner. We validate our method on diffusion data acquired from seven different sites (two GE, three Philips, and two Siemens scanners) on a group of age-matched healthy subjects. We demonstrate the efficacy of our method by statistically comparing diffusion measures such as fractional anisotropy, mean diffusivity and generalized fractional anisotropy across these sites before and after data harmonization. Validation was also done on a group oftest subjects, which were not used to "learn" the harmonization parameters. We also show results using TBSS before and after harmonization for independent validation of the proposed methodology. Using synthetic data, we show that any abnormality in diffusion measures due to disease is preserved during the harmonization process. Our experimental results demonstrate that, for nearly identical acquisition protocol across sites, scanner-specific differences in the signal can be removed using the proposed method in a model independent manner.

Whole brain white matter connectivity analysis using machine learning: An application to autism.

In this paper, we propose an automated white matter connectivity analysis method for machine learning classification and characterization of white matter abnormality via identification of discriminative fiber tracts. The proposed method uses diffusion MRI tractography and a data-driven approach to find fiber clusters corresponding to subdivisions of the white matter anatomy. Features extracted from each fiber cluster describe its diffusion properties and are used for machine learning. The method is demonstrated by application to a pediatric neuroimaging dataset from 149 individuals, including 70 children with autism spectrum disorder (ASD) and 79 typically developing controls (TDC). A classification accuracy of 78.33% is achieved in this cross-validation study. We investigate the discriminative diffusion features based on a two-tensor fiber tracking model. We observe that the mean fractional anisotropy from the second tensor (associated with crossing fibers) is most affected in ASD. We also find that local along-tract (central cores and endpoint regions) differences between ASD and TDC are helpful in differentiating the two groups. These altered diffusion properties in ASD are associated with multiple robustly discriminative fiber clusters, which belong to several major white matter tracts including the corpus callosum, arcuate fasciculus, uncinate fasciculus and aslant tract; and the white matter structures related to the cerebellum, brain stem, and ventral diencephalon. These discriminative fiber clusters, a small part of the whole brain tractography, represent the white matter connections that could be most affected in ASD. Our results indicate the potential of a machine learning pipeline based on white matter fiber clustering.

Characterizing white matter changes in chronic schizophrenia: A free-water imaging multi-site study.

Diffusion tensor imaging (DTI) studies in chronic schizophrenia have found widespread but often inconsistent patterns of white matter abnormalities. These studies have typically used the conventional measure of fractional anisotropy, which can be contaminated by extracellular free-water. A recent free-water imaging study reported reduced free-water corrected fractional anisotropy (FAT) in chronic schizophrenia across several brain regions, but limited changes in the extracellular volume. The present study set out to validate these findings in a substantially larger sample. Tract-based spatial statistics (TBSS) was performed in 188 healthy controls and 281 chronic schizophrenia patients. Forty-two regions of interest (ROIs), as well as average whole-brain FAT and FW were extracted from free-water corrected diffusion tensor maps. Compared to healthy controls, reduced FAT was found in the chronic schizophrenia group in the anterior limb of the internal capsule bilaterally, the posterior thalamic radiation bilaterally, as well as the genu and body of the corpus callosum. While a significant main effect of group was observed for FW, none of the follow-up contrasts survived correction for multiple comparisons. The observed FAT reductions in the absence of extracellular FW changes, in a large, multi-site sample of chronic schizophrenia patients, validate the pattern of findings reported by a previous, smaller free-water imaging study of a similar sample. The limited number of regions in which FAT was reduced in the schizophrenia group suggests that actual white matter tissue degeneration in chronic schizophrenia, independent of extracellular FW, might be more localized than suggested previously.