Thalamic connectivity topography in newborns with spina bifida: association with neurological functional level but not developmental outcome at 2 years.

Spina bifida affects spinal cord and cerebral development, leading to motor and cognitive delay. We investigated whether there are associations between thalamocortical connectivity topography, neurological function, and developmental outcomes in open spina bifida. Diffusion tensor MRI was used to assess thalamocortical connectivity in 44 newborns with open spina bifida who underwent prenatal surgical repair. We quantified the volume of clusters formed based on the strongest probabilistic connectivity to the frontal, parietal, and temporal cortex. Developmental outcomes were assessed using the Bayley III Scales, while the functional level of the lesion was assessed by neurological examination at 2 years of age. Higher functional level was associated with smaller thalamo-parietal, while lower functional level was associated with smaller thalamo-temporal connectivity clusters (Bonferroni-corrected P < 0.05). Lower functional levels were associated with weaker thalamic temporal connectivity, particularly in the ventrolateral and ventral anterior nuclei. No associations were found between thalamocortical connectivity and developmental outcomes. Our findings suggest that altered thalamocortical circuitry development in open spina bifida may contribute to impaired lower extremity function, impacting motor function and independent ambulation. We hypothesize that the neurologic function might not merely be caused by the spinal cord lesion, but further impacted by the disruption of cerebral neuronal circuitry.

Cardiac DTI using short-axis PROPELLER: A feasibility study.

PURPOSE: We aimed to develop a free-breathing (FB) cardiac DTI (cDTI) method based on short-axis PROPELLER (SAP) and M2 motion compensated spin-echo EPI (SAP-M2-EPI) to mitigate geometric distortion and eliminate aliasing in acquired diffusion-weighted (DW) images, particularly in patients with a higher body mass index (BMI). THEORY AND METHODS: The study involved 10 healthy volunteers whose BMI values fell into specific categories: BMI <25 (4 volunteers), 25< BMI <28 (5 volunteers), and BMI >30 (1 volunteer). We compared DTI parameters, including fractional anisotropy (FA), mean diffusivity (MD), and helix angle transmurality (HAT), between SAP-M2-EPI and M2-ssEPI. To evaluate the performance of SAP-M2-EPI in reducing geometric distortions in the left ventricle (LV) compared to CINE and M2-ssEPI, we utilized the DICE similarity coefficient (DSC) and assessed misregistration area. RESULTS: In all volunteers, SAP-M2-EPI yielded high-quality LV DWIs without aliasing, demonstrating significantly reduced geometric distortion (with an average DSC of 0.92 and average misregistration area of 90 mm2) and diminished signal loss due to bulk motion when compared to M2-ssEPI. DTI parameter maps exhibited consistent patterns across slices without motion related artifacts. CONCLUSION: SAP-M2-EPI facilitates free-breathing cDTI of the entire LV, effectively eliminating aliasing and minimizing geometric distortion compared to M2-ssEPI. Furthermore, it preserves accurate quantification of myocardial microstructure.

[Perifocal edema and glymphatic system dysfunction: quantitative assessment based on diffusion tensor magnetic resonance imaging]. / Peritumoroznyi otek i disfunktsiya glimfaticheskoi sistemy golovnogo mozga: kolichestvennaya otsenka na osnove diffuzionno-tenzornoi MRT.

BACKGROUND: Pathogenesis of peritumoral cerebral edema is unclear and potentially associated with glymphatic system dysfunction. Diffusion tensor MRI (DT-MRI) with analysis of ALPS (Analysis along the Perivascular Space) index may be valuable for assessment of edema. This approach visualizes fluid flow along perivascular spaces of deep cerebral veins. OBJECTIVE: To assess glymphatic system function in supratentorial tumors and healthy volunteers using DT-MRI. MATERIAL AND METHODS: There were 52 patients (59% men) aged 43 (28-64) years with supratentorial tumors (meningioma - 20, grade 3-4 glioma - 15, metastases - 9, lymphoma - 8). Tumors and perifocal edema did not involve deep cerebral veins. The control group included 6 healthy volunteers aged 34-66 years. MRI protocol (Signa HDxt, 3 T) contained standard T1, T2, T2FLAIR, DWI and post-contrast T1 (3D BRAVO). DT-MRI had the following parameters: TR=10 000 ms, TEmin=102 ms, FOV=240 mm, isotropic voxel size 3×3×3 mm3, 60 directions of diffusion gradients. Measurements were carried out at b-factor 0 and 1000 s/mm2. Analysis was carried out in the ReadyView software. RESULTS: Right- and left-sided ALPS indices were similar in the control group (p=0.917). Perifocal edema (regardless of histological type of tumor) in the ipsilateral hemisphere was accompanied by significantly lower ALPS index (p<0.005), while these values in contralateral (intact) hemisphere were similar in both groups (p=0.7). CONCLUSION: We found significantly lower ALPS index in deep parts of the affected hemisphere in patients with perifocal edema. These data can indicate the role of glymphatic system dysfunction in pathogenesis of this pathology.

[Factors influencing peritumoral edema in meningiomas: CT- and MRI-based quantitative assessment]. / Peritumoroznyi otek pri meningiomakh i faktory, vliyayushchie na ego formirovanie: kolichestvennaya otsenka na osnove KT i MRT.

Background. Meningiomas may be accompanied by peritumoral edema. Incidence and pathogenesis of edema are nor clearly established. Prevalence and severity of edema vary significantly in patients with meningiomas similar in various parameters. OBJECTIVE: To assess peritumoral edema in intracranial meningiomas and factors influencing incidence and severity of this process. MATERIAL AND METHODS: There were 126 patients (69% women) aged 19-76 years (median 53), who were diagnosed with 142 meningiomas. Patients underwent surgery (n=111) and radiotherapy (n=15) in 2016-2018. The MRI protocol included T1, T2, T2-FLAIR, DWI and post-contrast T1-weighted images in three projections, diffusion tensor MRI in 27 cases and MR spectroscopy in 21 patients. RESULTS: Peritumoral edema was detected in 46% (n=66) of cases including 21 (31%) patients with severe edema. The ALPS index was 1.510±0.1931 in meningiomas without edema and 1.308±0.19 in those with edema (p=0.014). There was positive correlation between edema, dimensions and uneven contours of meningioma, as well as negative correlation with CSF cleft sign. Blood flow velocity was higher in atypical and anaplastic meningiomas with edema (p=0.03). Other signs (localization, histological variant, malignancy grade, characteristics of MR signal, peaks of the main metabolites, diffusion and perfusion parameters of tumor) did not significantly affect peritumoral edema in patients with meningiomas (p>0.05). CONCLUSION: Diffusion tensor tomography with ALPS index revealed significant effect of glymphatic system dysfunction on peritumoral edema. Large meningioma with uneven contours increased the risk of peritumoral edema, while CSF cleft sign reduced this risk. Other factors did not affect cerebral edema in meningiomas.

Future of kidney imaging: Functional magnetic resonance imaging and kidney disease progression.

INTRODUCTION: Chronic kidney disease (CKD) which is a common cause of death has an increasing trend, but there is no established approach for predicting CKD progression yet. Functional magnetic resonance imaging (fMRI) studies such as blood oxygenation level-dependent MRI (BOLD-MRI), diffusion-weighted MRI (DWI-MRI), diffusion-tensor MRI (DTI-MRI) and arterial spin labelling MRI (ASL-MRI) are rising methods for the assessment of kidney functions in native and transplanted kidneys as well as the estimation of CKD progression. METHODS: Systematic literature review was performed through the Embase (Elsevier), Cochrane Central Register of Controlled Trials (Wiley), PubMed/Medline and Web of Science databases, and studies investigating the role of fMRI methods assessing kidney functions in native and transplanted kidneys, as well as the value of fMRI methods to predict CKD progression, were included. Working mechanisms, advantages and limitations of the fMRI modalities were reviewed, and three studies investigating the role of fMRI studies in kidney functions were analysed. RESULTS AND CONCLUSION: BOLD-MRI signal was found to be inversely correlated with annual eGFR change, and DWI/ADC (apparent diffusion coefficient map) values were shown to be correlated with annual eGFR decline. fMRI methods which are currently used for other systems can be utilized to provide more detailed information about kidney functions, and doctors should be ready to interpret kidney MRIs.

Free-breathing diffusion tensor MRI of the whole left ventricle using second-order motion compensation and multitasking respiratory motion correction.

PURPOSE: We aimed to develop a novel free-breathing cardiac diffusion tensor MRI (DT-MRI) approach, M2-MT-MOCO, capable of whole left ventricular coverage that leverages second-order motion compensation (M2) diffusion encoding and multitasking (MT) framework to efficiently correct for respiratory motion (MOCO). METHODS: Imaging was performed in 16 healthy volunteers and 3 heart failure patients with symptomatic dyspnea. The healthy volunteers were scanned to compare the accuracy of interleaved multislice coverage of the entire left ventricle with a single-slice acquisition and the accuracy of the free-breathing conventional MOCO and MT-MOCO approaches with reference breath-hold DT-MRI. Mean diffusivity (MD), fractional anisotropy (FA), helix angle transmurality (HAT), and intrascan repeatability were quantified and compared. RESULTS: In all subjects, free-breathing M2-MT-MOCO DT-MRI yielded DWI of the entire left ventricle without bulk motion-induced signal loss. No significant differences were seen in the global values of MD, FA, and HAT in the multislice and single-slice acquisitions. Furthermore, global quantification of MD, FA, and HAT were also not significantly different between the MT-MOCO and breath-hold, whereas conventional MOCO yielded significant differences in MD, FA, and HAT with MT-MOCO and FA with breath-hold. In heart failure patients, M2-MT-MOCO DT-MRI was feasible yielding higher MD, lower FA, and lower HAT compared with healthy volunteers. Substantial agreement was found between repeated scans across all subjects for MT-MOCO. CONCLUSION: M2-MT-MOCO enables free-breathing DT-MRI of the entire left ventricle in 10 min, while preserving quantification of myocardial microstructure compared to breath-held and single-slice acquisitions and is feasible in heart failure patients.

A pan-mammalian map of interhemispheric brain connections predates the evolution of the corpus callosum.

The brain of mammals differs from that of all other vertebrates, in having a six-layered neocortex that is extensively interconnected within and between hemispheres. Interhemispheric connections are conveyed through the anterior commissure in egg-laying monotremes and marsupials, whereas eutherians evolved a separate commissural tract, the corpus callosum. Although the pattern of interhemispheric connectivity via the corpus callosum is broadly shared across eutherian species, it is not known whether this pattern arose as a consequence of callosal evolution or instead corresponds to a more ancient feature of mammalian brain organization. Here we show that, despite cortical axons using an ancestral commissural route, monotremes and marsupials share features of interhemispheric connectivity with eutherians that likely predate the origin of the corpus callosum. Based on ex vivo magnetic resonance imaging and tractography, we found that connections through the anterior commissure in both fat-tailed dunnarts (Marsupialia) and duck-billed platypus (Monotremata) are spatially segregated according to cortical area topography. Moreover, cell-resolution retrograde and anterograde interhemispheric circuit mapping in dunnarts revealed several features shared with callosal circuits of eutherians. These include the layered organization of commissural neurons and terminals, a broad map of connections between similar (homotopic) regions of each hemisphere, and regions connected to different areas (heterotopic), including hyperconnected hubs along the medial and lateral borders of the cortex, such as the cingulate/motor cortex and claustrum/insula. We therefore propose that an interhemispheric connectome originated in early mammalian ancestors, predating the evolution of the corpus callosum. Because these features have been conserved throughout mammalian evolution, they likely represent key aspects of neocortical organization.

Cardiac Diffusion: Technique and Practical Applications.

The 3D microarchitecture of the cardiac muscle underlies the mechanical and electrical properties of the heart. Cardiomyocytes are arranged helically through the depth of the wall, and their shortening leads to macroscopic torsion, twist, and shortening during cardiac contraction. Furthermore, cardiomyocytes are organized in sheetlets separated by shear layers, which reorientate, slip, and shear during macroscopic left ventricle (LV) wall thickening. Cardiac diffusion provides a means for noninvasive interrogation of the 3D microarchitecture of the myocardium. The fundamental principle of MR diffusion is that an MRI signal is attenuated by the self-diffusion of water in the presence of large diffusion-encoding gradients. Since water molecules are constrained by the boundaries in biological tissue (cell membranes, collagen layers, etc.), depicting their diffusion behavior elucidates the shape of the myocardial microarchitecture they are embedded in. Cardiac diffusion therefore provides a noninvasive means to understand not only the dynamic changes in cardiac microstructure of healthy myocardium during cardiac contraction but also the pathophysiological changes in the presence of disease. This unique and innovative technology offers tremendous potential to enable improved clinical diagnosis through novel microstructural and functional assessment. in vivo cardiac diffusion methods are immediately translatable to patients, opening new avenues for diagnostic investigation and treatment evaluation in a range of clinically important cardiac pathologies. This review article describes the 3D microstructure of the LV, explains in vivo and ex vivo cardiac MR diffusion acquisition and postprocessing techniques, as well as clinical applications to date. Level of Evidence: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2020;52:348-368.

MRI in acute muscle tears in athletes: can quantitative T2 and DTI predict return to play better than visual assessment?

OBJECTIVES: To assess the ability of quantitative T2, diffusion tensor imaging (DTI) and radiologist's scores to detect muscle changes following acute muscle tear in soccer and rugby players. To assess the ability of these parameters to predict return to play times. METHODS: In this prospective, longitudinal study, 13 male athletes (age 19 to 34 years; mean 25 years) underwent MRI within 1 week of suffering acute muscle tear. Imaging included measurements of T2 and DTI parameters. Images were also assessed using modified Peetrons and British athletics muscle injury classification (BAMIC) scores. Participants returned for a second scan within 1 week of being determined fit to return to play. MRI measurements were compared between visits. Pearson's correlation between visit 1 measurements and return to play times was assessed. RESULTS: There were significant differences between visits in BAMIC scores (Z = - 2.088; p = 0.037), modified Peetrons (Z = - 2.530; p = 0.011) and quantitative MRI measurements; T2, 13.12 ms (95% CI, 4.82 ms, 21.42 ms; p = 0.01); mean diffusivity (0.22 (0.04, 0.39); p = 0.02) and fractional anisotropy (0.07 (0.01, 0.14); p = 0.03). BAMIC scores showed a significant correlation with return to play time (Rs = 0.64; p = 0.02), but modified Peetrons scores and quantitative parameters did not. CONCLUSIONS: T2 and DTI measurements in muscle can detect changes due to healing following muscle tear. Although BAMIC scores correlated well with return to play times, in this small study, quantitative MRI values did not, suggesting that T2 and DTI measurements are inferior predictors of return to play time compared with visual scoring. KEY POINTS: • Muscle changes following acute muscle tear can be measured using T2 and diffusion measurements on MRI. • Measurements of T2 and diffusion using MRI are not as good as a radiologist's visual report at predicting return to play time after acute muscle tear.

Axonal degeneration as substrate of fractional anisotropy abnormalities in multiple sclerosis cortex.

Cortical microstructural abnormalities are associated with clinical and cognitive deterioration in multiple sclerosis. Using diffusion tensor MRI, a higher fractional anisotropy has been found in cortical lesions versus normal-appearing cortex in multiple sclerosis. The pathological substrates of this finding have yet to be definitively elucidated. By performing a combined post-mortem diffusion tensor MRI and histopathology study, we aimed to define the histopathological substrates of diffusivity abnormalities in multiple sclerosis cortex. Sixteen subjects with multiple sclerosis and 10 age- and sex-matched non-neurological control donors underwent post-mortem in situ at 3 T MRI, followed by brain dissection. One hundred and ten paraffin-embedded tissue blocks (54 from multiple sclerosis patients, 56 from non-neurological controls) were matched to the diffusion tensor sequence to obtain regional diffusivity measures. Using immunohistochemistry and silver staining, cortical density of myelin, microglia, astrocytes and axons, and density and volume of neurons and glial cells were evaluated. Correlates of diffusivity abnormalities with histological markers were assessed through linear mixed-effects models. Cortical lesions (77% subpial) were found in 27/54 (50%) multiple sclerosis cortical regions. Multiple sclerosis normal-appearing cortex had a significantly lower fractional anisotropy compared to cortex from non-neurological controls (P = 0.047), whereas fractional anisotropy in demyelinated cortex was significantly higher than in multiple sclerosis normal-appearing cortex (P = 0.012) but not different from non-neurological control cortex (P = 0.420). Compared to non-neurological control cortex, both multiple sclerosis normal-appearing and demyelinated cortices showed a lower density of axons perpendicular to the cortical surface (P = 0.012 for both) and of total axons (parallel and perpendicular to cortical surface) (P = 0.028 and 0.012). In multiple sclerosis, demyelinated cortex had a lower density of myelin (P = 0.004), parallel (P = 0.018) and total axons (P = 0.029) versus normal-appearing cortex. Regarding the pathological substrate, in non-neurological controls, cortical fractional anisotropy was positively associated with density of perpendicular, parallel, and total axons (P = 0.031 for all). In multiple sclerosis, normal-appearing cortex fractional anisotropy was positively associated with perpendicular and total axon density (P = 0.031 for both), while associations with myelin, glial and total cells and parallel axons did not survive multiple comparison correction. Demyelinated cortex fractional anisotropy was positively associated with density of neurons, and total cells and negatively with microglia density, without surviving multiple comparison correction. Our results suggest that a reduction of perpendicular axons in normal-appearing cortex and of both perpendicular and parallel axons in demyelinated cortex may underlie the substrate influencing cortical microstructural coherence and being responsible for the different patterns of fractional anisotropy changes occurring in multiple sclerosis cortex.

White matter alterations in early Parkinson's disease: role of motor symptom lateralization.

INTRODUCTION: Parkinson's disease (PD) is a motor disorder that initially presents with unilateral symptoms. Widespread white matter (WM) alterations have been reported since the early stages of the disease. The aim of this study was to investigate WM alterations in right-dominant and left-dominant symptom PD patients (RPD and LPD, respectively) with respect to healthy controls (HC) by diffusion-weighted magnetic resonance imaging (MRI). METHODS: Thirty-eight subjects participated in this study: 12 RPD (median H&Y [IQR] = 1.5 [1.1-2], median UPDRS III [IQR] = 23 [7.8-25]), 9 LPD (median H&Y [IQR] = 1.5 [1-2.5], median UPDRS III [IQR] = 17 [12-22]), and 17 HC. All the participants were scanned on a 1.5-T MRI scanner. Maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were computed for all the subjects. Tract-based spatial statistics (TBSS) was performed for each diffusion parameter, to test WM differences between RPD, LPD, and HC (ANCOVA design). Family-wise error (FWE) correction was performed and p values lower than 0.05 were considered significant. RESULTS: No significant FA and RD differences were observed between RPD, LPD, and HC. Significantly increased MD and AD were observed in RPD with respect to HC within widespread WM regions, bilaterally. Conversely, no significant WM alterations were detected in LPD. CONCLUSION: WM integrity was found to be significantly altered in RPD but not in LPD, suggesting that LPD profile may be associated to more favorable prognosis. Since clinical laterality onset may affect the extent of WM integrity changes, it should be taken into account in neuroimaging studies investigating PD.

Diffusion tensor imaging of the human thigh: consideration of DTI-based fiber tracking stop criteria.

OBJECTIVES: To consider the tract-based analysis of DTI parameters in human muscle by assessing different fiber tracking stop criteria settings on diffusion parameters. MATERIALS AND METHODS: 30 healthy volunteers underwent a 3 T MRI. Diffusion-weighted images were acquired to perform DTI and fiber tracking analysis for six thigh muscles. Whole thigh muscles were evaluated by fiber tractography using different fiber tracking stop parameters [FA (0.01-0.15) to (0.4-0.99); angle 10°-30°, step size 0.75 mm, 1.5 mm, 3 mm]. Diffusion and tractography-derived parameters per stop criterion were compared using a repeated measure ANOVA including Bonferroni-corrected post hoc tests. RESULTS: We found significant differences in all examined diffusion parameters between different stop criteria (main effect p < 0.001). We showed different influence of tracking parameters on diffusion parameters in examined muscles (main effect p ≤ 0.001). CONCLUSIONS: Statistically significant differences in fiber tracking results using different stop criteria were shown. Fiber tracking stop criteria do have an important influence on study results and should be considered in the development of study protocols and comparison of studies. We recommend a FA minimum of 0.10 and a step size lower than voxel size, e.g., a half with a constant ratio between step size and angle of 10°/mm.

Brain mapping in multiple sclerosis: Lessons learned about the human brain.

The application of structural and functional magnetic resonance imaging (MRI) techniques in patients with multiple sclerosis (MS) has certainly helped to improve our understanding of the mechanisms responsible for clinical disability and cognitive impairment in this condition. The numerous studies performed in MS patients have also provided many lessons on the structure-function relationships in the human brain, which could be applied to healthy subjects and to patients affected by other neurological conditions. The findings have allowed a better understanding of the processes involved in the loss of function after central nervous system (CNS) damage, and clarified the substrates of specific symptoms (e.g., cognitive impairment and fatigue), which should aid clinical recovery and help in the monitoring of disease progression. In this review, important examples of how the application of different MRI techniques in MS might provide relevant information on the human brain are discussed. These include how damage to strategic white matter tracts can cause symptoms due to a disconnection mechanism and how involvement of a specific brain network, independent of the underlying pathological substrate, might determine certain symptoms. The role of functional and structural plasticity in clinical recovery (following an acute relapse or promoted by rehabilitation) and the mechanisms that might become the target of treatment aimed at function recovery are also considered. The ways in which network- and system-based analysis can reshape current understanding of the brain structure-function relationships are discussed. Finally, there is speculation about the relevance of inherited or acquired factors, such as age, comorbidity, brain reserve and cognitive reserve, which are likely to influence the relation between CNS damage and disease clinical manifestations.

Brain MRI shows white matter sparing in Kennedy's disease and slow-progressing lower motor neuron disease.

The extent of central nervous system involvement in Kennedy's disease (KD) relative to other motor neuron disease (MND) phenotypes still needs to be clarified. In this study, we investigated cortical and white matter (WM) MRI alterations in 25 patients with KD, compared with 24 healthy subjects, 25 patients with sporadic amyotrophic lateral sclerosis (ALS), and 35 cases with lower motor neuron-predominant disease (LMND). LMND patients were clinically differentiated into 24 fast and 11 slow progressors. Whole-brain cortical thickness, WM tract-based spatial statistics and corticospinal tract (CST) tractography analyses were performed. No significant difference in terms of cortical thickness was found between groups. ALS patients showed widespread decreased fractional anisotropy and increased mean (MD) and radial diffusivity (radD) in the CST, corpus callosum and fronto-temporal extra-motor tracts, compared with healthy controls and other patient groups. CST tractography showed significant alterations of DT MRI metrics in ALS and LMND-fast patients whereas KD and LMND-slow patients were comparable with healthy controls. Our study demonstrated the absence of WM abnormalities in patients with KD and LMND-slow, in contrast with diffuse WM damage in ALS and focal CST degeneration in LMND-fast, supporting the use of DT MRI measures as powerful tools to differentiate fast- and slow-progressing MND syndromes, including KD.

Structural network topology correlates of microstructural brain dysmaturation in term infants with congenital heart disease.

Neonates with complex congenital heart disease (CHD) demonstrate microstructural brain dysmaturation, but the relationship with structural network topology is unknown. We performed diffusion tensor imaging (DTI) in term neonates with CHD preoperatively (N = 61) and postoperatively (N = 50) compared with healthy term controls (N = 91). We used network topology (graph) analyses incorporating different weighted and unweighted approaches and subject-specific white matter segmentation to investigate structural topology differences, as well as a voxel-based analysis (VBA) to confirm the presence of microstructural dysmaturation. We demonstrate cost-dependent network inefficiencies in neonatal CHD in the pre- and postoperative period compared with controls, related to microstructural differences. Controlling for cost, we show the presence of increased small-worldness (hierarchical fiber organization) in CHD infants preoperatively, that persists in the postoperative period compared with controls, suggesting the early presence of brain reorganization. Taken together, topological microstructural dysmaturation in CHD infants is accompanied by hierarchical fiber organization during a protracted critical period of early brain development. Our methodology also provides a pipeline for quantitation of network topology changes in neonates and infants with microstructural brain dysmaturation at risk for perinatal brain injury.

Tensor-based morphometry using scalar and directional information of diffusion tensor MRI data (DTBM): Application to hereditary spastic paraplegia.

Tensor-based morphometry (TBM) performed using T1-weighted images (T1WIs) is a well-established method for analyzing local morphological changes occurring in the brain due to normal aging and disease. However, in white matter regions that appear homogeneous on T1WIs, T1W-TBM may be inadequate for detecting changes that affect specific pathways. In these regions, diffusion tensor MRI (DTI) can identify white matter pathways on the basis of their different anisotropy and orientation. In this study, we propose performing TBM using deformation fields constructed using all scalar and directional information provided by the diffusion tensor (DTBM) with the goal of increasing sensitivity in detecting morphological abnormalities of specific white matter pathways. Previously, mostly fractional anisotropy (FA) has been used to drive registration in diffusion MRI-based TBM (FA-TBM). However, FA does not have the directional information that the tensors contain, therefore, the registration based on tensors provides better alignment of brain structures and better localization of volume change. We compare our DTBM method to both T1W-TBM and FA-TBM in investigating differences in brain morphology between patients with complicated hereditary spastic paraplegia of type 11 (SPG11) and a group of healthy controls. Effect size maps of T1W-TBM of SPG11 patients showed diffuse atrophy of white matter. However, DTBM indicated that atrophy was more localized, predominantly affecting several long-range pathways. The results of our study suggest that DTBM could be a powerful tool for detecting morphological changes of specific white matter pathways in normal brain development and aging, as well as in degenerative disorders.

Tracking brain damage in progressive supranuclear palsy: a longitudinal MRI study.

OBJECTIVES: In this prospective, longitudinal, multiparametric MRI study, we investigated clinical as well as brain grey matter and white matter (WM) regional changes in patients with progressive supranuclear palsy-Richardson's syndrome (PSP-RS). METHODS: Twenty-one patients with PSP-RS were evaluated at baseline relative to 36 healthy controls and after a mean follow-up of 1.4 years with clinical rating scales, neuropsychological tests and MRI scans. RESULTS: Relative to controls, patients with PSP-RS showed at baseline a typical pattern of brain damage, including midbrain atrophy, frontal cortical thinning and widespread WM involvement of the main infratentorial and supratentorial tracts that exceeded cortical damage. Longitudinal study showed that PSP-RS exhibited no further changes in cortical thinning, which remained relatively focal, while midbrain atrophy and WM damage significantly progressed. Corpus callosum and frontal WM tract changes correlated with the progression of both disease severity and behavioural dysfunction. CONCLUSIONS: This study demonstrated the feasibility of carrying out longitudinal diffusion tensor MRI in patients with PSP-RS and its sensitivity to identifying the progression of pathology. Longitudinal midbrain volume loss and WM changes are associated with PSP disease course.

Central and non-central networks, cognition, clinical symptoms, and polygenic risk scores in schizophrenia.

Schizophrenia is a complex disorder that may be the result of aberrant connections between specific brain regions rather than focal brain abnormalities. Here, we investigate the relationships between brain structural connectivity as described by network analysis, intelligence, symptoms, and polygenic risk scores (PGRS) for schizophrenia in a group of patients with schizophrenia and a group of healthy controls. Recently, researchers have shown an interest in the role of high centrality networks in the disorder. However, the importance of non-central networks still remains unclear. Thus, we specifically examined network-averaged fractional anisotropy (mean edge weight) in central and non-central subnetworks. Connections with the highest betweenness centrality within the average network (>75% of centrality values) were selected to represent the central subnetwork. The remaining connections were assigned to the non-central subnetwork. Additionally, we calculated graph theory measures from the average network (connections that occur in at least 2/3 of participants). Density, strength, global efficiency, and clustering coefficient were significantly lower in patients compared with healthy controls for the average network (pFDR < 0.05). All metrics across networks were significantly associated with intelligence (pFDR < 0.05). There was a tendency towards significance for a correlation between intelligence and PGRS for schizophrenia (r = -0.508, p = 0.052) that was significantly mediated by central and non-central mean edge weight and every graph metric from the average network. These results are consistent with the hypothesis that intelligence deficits are associated with a genetic risk for schizophrenia, which is mediated via the disruption of distributed brain networks. Hum Brain Mapp 38:5919-5930, 2017. © 2017 Wiley Periodicals, Inc.

Mapping the order and pattern of brain structural MRI changes using change-point analysis in premanifest Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that progressively affects motor, cognitive, and emotional functions. Structural MRI studies have demonstrated brain atrophy beginning many years prior to clinical onset ("premanifest" period), but the order and pattern of brain structural changes have not been fully characterized. In this study, we investigated brain regional volumes and diffusion tensor imaging (DTI) measurements in premanifest HD, and we aim to determine (1) the extent of MRI changes in a large number of structures across the brain by atlas-based analysis, and (2) the initiation points of structural MRI changes in these brain regions. We adopted a novel multivariate linear regression model to detect the inflection points at which the MRI changes begin (namely, "change-points"), with respect to the CAG-age product (CAP, an indicator of extent of exposure to the effects of CAG repeat expansion). We used approximately 300 T1-weighted and DTI data from premanifest HD and control subjects in the PREDICT-HD study, with atlas-based whole brain segmentation and change-point analysis. The results indicated a distinct topology of structural MRI changes: the change-points of the volumetric measurements suggested a central-to-peripheral pattern of atrophy from the striatum to the deep white matter; and the change points of DTI measurements indicated the earliest changes in mean diffusivity in the deep white matter and posterior white matter. While interpretation needs to be cautious given the cross-sectional nature of the data, these findings suggest a spatial and temporal pattern of spread of structural changes within the HD brain. Hum Brain Mapp 38:5035-5050, 2017. © 2017 Wiley Periodicals, Inc.

Diffusion tensor MRI tractography reveals increased fractional anisotropy (FA) in arcuate fasciculus following music-cued motor training.

Auditory cues are frequently used to support movement learning and rehabilitation, but the neural basis of this behavioural effect is not yet clear. We investigated the microstructural neuroplasticity effects of adding musical cues to a motor learning task. We hypothesised that music-cued, left-handed motor training would increase fractional anisotropy (FA) in the contralateral arcuate fasciculus, a fibre tract connecting auditory, pre-motor and motor regions. Thirty right-handed participants were assigned to a motor learning condition either with (Music Group) or without (Control Group) musical cues. Participants completed 20minutes of training three times per week over four weeks. Diffusion tensor MRI and probabilistic neighbourhood tractography identified FA, axial (AD) and radial (RD) diffusivity before and after training. Results revealed that FA increased significantly in the right arcuate fasciculus of the Music group only, as hypothesised, with trends for AD to increase and RD to decrease, a pattern of results consistent with activity-dependent increases in myelination. No significant changes were found in the left ipsilateral arcuate fasciculus of either group. This is the first evidence that adding musical cues to movement learning can induce rapid microstructural change in white matter pathways in adults, with potential implications for therapeutic clinical practice.