Advanced diffusion MRI and image texture analysis detect widespread brain structural differences between relapsing-remitting and secondary progressive multiple sclerosis.

Introduction: Disease development in multiple sclerosis (MS) causes dramatic structural changes, but the exact changing patterns are unclear. Our objective is to investigate the differences in brain structure locally and spatially between relapsing-remitting MS (RRMS) and its advanced form, secondary progressive MS (SPMS), through advanced analysis of diffusion magnetic resonance imaging (MRI) and image texture. Methods: A total of 20 patients with RRMS and nine patients with SPMS from two datasets underwent 3T anatomical and diffusion tensor imaging (DTI). The DTI was harmonized, augmented, and then modeled, which generated six voxel- and sub-voxel-scale measures. Texture analysis focused on T2 and FLAIR MRI, which produced two phase-based measures, namely, phase congruency and weighted mean phase. Data analysis was 3-fold, i.e., histogram analysis of whole-brain normal appearing white matter (NAWM); region of interest (ROI) analysis of NAWM and lesions within three critical white matter tracts, namely, corpus callosum, corticospinal tract, and optic radiation; and along-tract statistics. Furthermore, by calculating the z-score of core-rim pathology within lesions based on diffusion measures, we developed a novel method to define chronic active lesions and compared them between cohorts. Results: Histogram features from diffusion and all but one texture measure differentiated between RRMS and SPMS. Within-tract ROI analysis detected cohort differences in both NAWM and lesions of the corpus callosum body in three measures of neurite orientation and anisotropy. Along-tract statistics detected cohort differences from multiple measures, particularly lesion extent, which increased significantly in SPMS in posterior corpus callosum and optic radiations. The number of chronic active lesions were also significantly higher (by 5-20% over z-scores 0.5 and 1.0) in SPMS than RRMS based on diffusion anisotropy, neurite content, and diameter. Conclusion: Advanced diffusion MRI and texture analysis may be promising approaches for thorough understanding of brain structural changes from RRMS to SPMS, thereby providing new insight into disease development mechanisms in MS.

Advanced Analysis of Diffusion Tensor Imaging Along With Machine Learning Provides New Sensitive Measures of Tissue Pathology and Intra-Lesion Activity in Multiple Sclerosis.

Tissue pathology in multiple sclerosis (MS) is highly complex, requiring multi-dimensional analysis. In this study, our goal was to test the feasibility of obtaining high angular resolution diffusion imaging (HARDI) metrics through single-shell modeling of diffusion tensor imaging (DTI) data, and investigate how advanced measures from single-shell HARDI and DTI tractography perform relative to classical DTI metrics in assessing MS pathology. We examined 52 relapsing-remitting MS patients who had 3T anatomical brain MRI and DTI. Single-shell HARDI modeling yielded 5 sub-voxel-based metrics, totalling 11 diffusion measures including 4 DTI and 2 tractography metrics. Based on machine learning of 3-dimensional regions of interest, we evaluated the importance of the measures through several tissue classification tasks. These included two within-subject comparisons: lesion versus normal appearing white matter (NAWM); and lesion core versus shell. Further, by stratifying patients as having high (above 75% ile ) and low (below 25% ile ) number of MS lesions, we also performed 2 classifications between subjects for lesions and NAWM respectively. Results showed that in lesion-NAWM analysis, HARDI orientation distribution function (ODF) energy, DTI fractional anisotropy (FA), and HARDI orientation dispersion index were the top three metrics, which together achieved 65.2% accuracy and 0.71 area under the receiver operating characteristic curve (AUROC). In core-shell analysis, DTI mean diffusivity (MD), radial diffusivity, and FA were the top three metrics, and MD dominated the classification, which achieved 59.3% accuracy and 0.59 AUROC alone. Between patients, FA was the leading feature in lesion comparisons, while ODF energy was the best in NAWM separation. Collectively, single-shell modeling of common diffusion data can provide robust orientation measures of lesion and NAWM pathology, and DTI metrics are most sensitive to intra-lesion abnormality. Combined analysis of both advanced and classical diffusion measures may be critical for improved understanding of MS pathology.

Microstructural Abnormalities of the Dentatorubrothalamic Tract in Cervical Dystonia.

BACKGROUND: The dentatorubrothalamic tract (DRTT) remains understudied in idiopathic cervical dystonia (CD), despite evidence that the pathway is relevant in the pathophysiology of the disorder. OBJECTIVE: The aim of this study was to examine the DRTT in patients with CD using diffusion tensor imaging (DTI)-based tractography. METHODS: Magnetic resonance imaging scans from 67 participants were collected to calculate diffusion tractography metrics using a binary tractography-based DRTT template. Fractional anisotropy and diffusivity measures of left and right DRTT were computed and compared between 32 subjects with CD and 35 age-matched healthy volunteers. RESULTS: Fractional anisotropy of right DRTT and mean and axial diffusivity of left DRTT were significantly reduced in patients with CD. Similar abnormalities were observed in patients with focal CD and patients with CD without tremor. DTI metrics did not correlate with disease duration or severity. CONCLUSIONS: Significant reductions in DTI measures suggest microstructural abnormalities within the DRTT in CD, characterized by a tractography pattern consistent with decreased axonal integrity. © 2021 International Parkinson and Movement Disorder Society.

Identifying craniofacial features associated with prenatal exposure to androgens and testing their relationship with brain development.

We used magnetic resonance (MR) images obtained in same-sex and opposite-sex dizygotic twins (n = 119, 8 years of age) to study possible effects of prenatal androgens on craniofacial features. Using a principal component analysis of 19 craniofacial landmarks placed on the MR images, we identified a principal component capturing craniofacial features that distinguished females with a presumed differential exposure to prenatal androgens by virtue of having a male (vs. a female) co-twin (Cohen's d = 0.76). Subsequently, we tested the possibility that this craniofacial "signature" of prenatal exposure to androgens predicts brain size, a known sexually dimorphic trait. In an independent sample of female adolescents (singletons; n = 462), we found that the facial signature predicts up to 8% of variance in brain size. These findings are consistent with the organizational effects of androgens on brain development and suggest that the facial signature derived in this study could complement other indirect measures of prenatal exposure to androgens.

Evidence for both compensatory plastic and disuse atrophy-related neuroanatomical changes in the blind.

The behavioural and neurofunctional consequences of blindness are becoming increasingly well established, and it has become evident that the amount of reorganization is directly linked to the behavioural adaptations observed in the blind. However investigations of potential neuroanatomical changes resulting from blindness have yielded conflicting results as to the nature of the observed changes, because apparent loss of occipital tissue is difficult to reconcile with observed functional recruitment. To address this issue we used two complementary brain measures of neuroanatomy, voxel-based morphometry and magnetization transfer imaging, with the latter providing insight into myelin concentration through the magnetization transfer ratio. Both early and late blind, as well as sighted control subjects participated in the study and were tested on a series of auditory and tactile tasks to provide behavioural data that we could relate to neuroanatomy. The behavioural findings show that the early blind outperform the sighted in four of five tasks, whereas the late blind do so for only one. Moreover, correlations between the auditory and tactile performance of early blind individuals seem to indicate that they might benefit from some general-purpose compensatory plasticity mechanisms, as opposed to modality-specific ones. Neuroanatomical findings reveal three key findings: (i) occipital regions in the early blind have higher magnetization transfer ratio and grey matter concentration than in the sighted; (ii) behavioural performance of the blind is strongly predicted by magnetization transfer ratio and grey matter concentration in different occipital regions; and (iii) lower grey matter and white matter concentration was also found in other occipital areas in the early blind compared to the sighted. We thus show a clear dissociation between anatomical changes that are direct result of sensory deprivation and consequent atrophy, and those related to compensatory reorganization and behavioural adaptations. Moreover, the magnetization transfer ratio results also suggest that one mechanism for this reorganization may be related to increased myelination of intracortical neurons, or perhaps of fibres conveying information to and from remote locations.

Estimating volumes of the pituitary gland from T1-weighted magnetic-resonance images: effects of age, puberty, testosterone, and estradiol.

The pituitary gland is a key structure in the hypothalamic-pituitary-gonadal (HPG) axis--it plays an important role in sexual maturation during puberty. Despite its small size, its volume can be quantified using magnetic resonance imaging (MRI). Here, we study a cohort of 962 typically developing adolescents from the Saguenay Youth Study and estimate pituitary volumes using a newly developed multi-atlas segmentation method known as the MAGeT Brain algorithm. We found that age and puberty stage (controlled for age) each predicts adjusted pituitary volumes (controlled for total brain volume) in both males and females. Controlling for the effects of age and puberty stage, total testosterone and estradiol levels also predict adjusted pituitary volumes in males and pre-menarche females, respectively. These findings demonstrate that the pituitary gland grows during adolescence, and its volume relates to circulating plasma-levels of sex steroids in both males and females.

Does skull shape mediate the relationship between objective features and subjective impressions about the face?

In our previous work, we described facial features associated with a successful recognition of the sex of the face (Marecková et al., 2011). These features were based on landmarks placed on the surface of faces reconstructed from magnetic resonance (MR) images; their position was therefore influenced by both soft tissue (fat and muscle) and bone structure of the skull. Here, we ask whether bone structure has dissociable influences on observers' identification of the sex of the face. To answer this question, we used a novel method of studying skull morphology using MR images and explored the relationship between skull features, facial features, and sex recognition in a large sample of adolescents (n=876; including 475 adolescents from our original report). To determine whether skull features mediate the relationship between facial features and identification accuracy, we performed mediation analysis using bootstrapping. In males, skull features mediated fully the relationship between facial features and sex judgments. In females, the skull mediated this relationship only after adjusting facial features for the amount of body fat (estimated with bioimpedance). While body fat had a very slight positive influence on correct sex judgments about male faces, there was a robust negative influence of body fat on the correct sex judgments about female faces. Overall, these results suggest that craniofacial bone structure is essential for correct sex judgments about a male face. In females, body fat influences negatively the accuracy of sex judgments, and craniofacial bone structure alone cannot explain the relationship between facial features and identification of a face as female.

Anatomical correlates of dynamic auditory processing: relationship to literacy during early adolescence.

Adults show great variation in their auditory skills, such as being able to discriminate between foreign speech-sounds. Previous research has demonstrated that structural features of auditory cortex can predict auditory abilities; here we are interested in the maturation of 2-Hz frequency-modulation (FM) detection, a task thought to tap into mechanisms underlying language abilities. We hypothesized that an individual's FM threshold will correlate with gray-matter density in left Heschl's gyrus, and that this function-structure relationship will change through adolescence. To test this hypothesis, we collected anatomical magnetic resonance imaging data from participants who were tested and scanned at three time points: at 10, 11.5 and 13 years of age. Participants judged which of two tones contained FM; the modulation depth was adjusted using an adaptive staircase procedure and their threshold was calculated based on the geometric mean of the last eight reversals. Using voxel-based morphometry, we found that FM threshold was significantly correlated with gray-matter density in left Heschl's gyrus at the age of 10 years, but that this correlation weakened with age. While there were no differences between girls and boys at Times 1 and 2, at Time 3 there was a relationship between gray-matter density in left Heschl's gyrus in boys but not in girls. Taken together, our results confirm that the structure of the auditory cortex can predict temporal processing abilities, namely that gray-matter density in left Heschl's gyrus can predict 2-Hz FM detection threshold. This ability is dependent on the processing of sounds changing over time, a skill believed necessary for speech processing. We tested this assumption and found that FM threshold significantly correlated with spelling abilities at Time 1, but that this correlation was found only in boys. This correlation decreased at Time 2, and at Time 3 we found a significant correlation between reading and FM threshold, but again, only in boys. We examined the sex differences in both the imaging and behavioral data taking into account pubertal stages, and found that the correlation between FM threshold and spelling was strongest pre-pubertally, and the correlation between FM threshold and gray-matter density in left Heschl's gyrus was strongest mid-pubertally.