Establishing connectivity through microdissections of midbrain stimulation-related neural circuits.

Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomo-functional mechanisms governing human behaviour as well as the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. While the ventral tegmental area has been successfully targeted with deep brain stimulation for different neuropsychiatric diseases, the axonal connectivity of the region has not been fully understood. Here using fiber micro-dissections in human cadaveric hemispheres, population-based high-definition fiber tractography, and previously reported deep brain stimulation hotspots, we find that the ventral tegmental area participates in an intricate network involving the serotonergic pontine nuclei, basal ganglia, limbic system, basal forebrain, and prefrontal cortex, which is implicated in the treatment of obsessive-compulsive disorder, major depressive disorder, Alzheimer's disease, cluster headaches, and aggressive behaviors.

Mapping short association fibre connectivity up to V3 in the human brain in vivo.

Short association fibres (SAF) are the most abundant fibre pathways in the human white matter. Until recently, SAF could not be mapped comprehensively in vivo because diffusion weighted magnetic resonance imaging with sufficiently high spatial resolution needed to map these thin and short pathways was not possible. Recent developments in acquisition hardware and sequences allowed us to create a dedicated in vivo method for mapping the SAF based on sub-millimetre spatial resolution diffusion weighted tractography, which we validated in the human primary (V1) and secondary (V2) visual cortex against the expected SAF retinotopic order. Here, we extended our original study to assess the feasibility of the method to map SAF in higher cortical areas by including SAF up to V3. Our results reproduced the expected retinotopic order of SAF in the V2-V3 and V1-V3 stream, demonstrating greater robustness to the shorter V1-V2 and V2-V3 than the longer V1-V3 connections. The demonstrated ability of the method to map higher-order SAF connectivity patterns in vivo is an important step towards its application across the brain.

Anatomically constrained tractography of the fetal brain.

Diffusion-weighted Magnetic Resonance Imaging (dMRI) is increasingly used to study the fetal brain in utero. An important computation enabled by dMRI is streamline tractography, which has unique applications such as tract-specific analysis of the brain white matter and structural connectivity assessment. However, due to the low fetal dMRI data quality and the challenging nature of tractography, existing methods tend to produce highly inaccurate results. They generate many false streamlines while failing to reconstruct the streamlines that constitute the major white matter tracts. In this paper, we advocate for anatomically constrained tractography based on an accurate segmentation of the fetal brain tissue directly in the dMRI space. We develop a deep learning method to compute the segmentation automatically. Experiments on independent test data show that this method can accurately segment the fetal brain tissue and drastically improve the tractography results. It enables the reconstruction of highly curved tracts such as optic radiations. Importantly, our method infers the tissue segmentation and streamline propagation direction from a diffusion tensor fit to the dMRI data, making it applicable to routine fetal dMRI scans. The proposed method can facilitate the study of fetal brain white matter tracts with dMRI.

Connectome alterations following perinatal deafness in the cat.

Following sensory deprivation, areas and networks in the brain may adapt and reorganize to compensate for the loss of input. These adaptations are manifestations of compensatory crossmodal plasticity, which has been documented in both human and animal models of deafness-including the domestic cat. Although there are abundant examples of structural plasticity in deaf felines from retrograde tracer-based studies, there is a lack of diffusion-based knowledge involving this model compared to the current breadth of human research. The purpose of this study was to explore white matter structural adaptations in the perinatally-deafened cat via tractography, increasing the methodological overlap between species. Plasticity was examined by identifying unique group connections and assessing altered connectional strength throughout the entirety of the brain. Results revealed a largely preserved connectome containing a limited number of group-specific or altered connections focused within and between sensory networks, which is generally corroborated by deaf feline anatomical tracer literature. Furthermore, five hubs of cortical plasticity and altered communication following perinatal deafness were observed. The limited differences found in the present study suggest that deafness-induced crossmodal plasticity is largely built upon intrinsic structural connections, with limited remodeling of underlying white matter.

Individual differences of white matter characteristic along the anterior insula-based fiber tract circuit for pain empathy in healthy women and women with primary dysmenorrhea.

Pain empathy, defined as the ability of one person to understand another person's pain, shows large individual variations. The anterior insula is the core region of the pain empathy network. However, the relationship between white matter (WM) properties of the fiber tracts connecting the anterior insula with other cortical regions and an individual's ability to modulate pain empathy remains largely unclear. In this study, we outline an automatic seed-based fiber streamline (sFS) analysis method and multivariate pattern analysis (MVPA) to predict the levels of pain empathy in healthy women and women with primary dysmenorrhoea (PDM). Using the sFS method, the anterior insula-based fiber tract network was divided into five fiber cluster groups. In healthy women, interindividual differences in pain empathy were predicted only by the WM properties of the five fiber cluster groups, suggesting that interindividual differences in pain empathy may rely on the connectivity of the anterior insula-based fiber tract network. In women with PDM, pain empathy could be predicted by a single cluster group. The mean WM properties along the anterior insular-rostroventral area of the inferior parietal lobule further mediated the effect of pain on empathy in patients with PDM. Our results suggest that chronic periodic pain may lead to maladaptive plastic changes, which could further impair empathy by making women with PDM feel more pain when they see other people experiencing pain. Our study also addresses an important gap in the analysis of the microstructural characteristics of seed-based fiber tract network.

Bundle-specific tractogram distribution estimation using higher-order streamline differential equation.

Streamline tractography locally traces peak directions extracted from fiber orientation distribution (FOD) functions, lacking global information about the trend of the whole fiber bundle. Therefore, it is prone to producing erroneous tracks while missing true positive connections. In this work, we propose a new bundle-specific tractography (BST) method based on a bundle-specific tractogram distribution (BTD) function, which directly reconstructs the fiber trajectory from the start region to the termination region by incorporating the global information in the fiber bundle mask. A unified framework for any higher-order streamline differential equation is presented to describe the fiber bundles with disjoint streamlines defined based on the diffusion vectorial field. At the global level, the tractography process is simplified as the estimation of BTD coefficients by minimizing the energy optimization model, and is used to characterize the relations between BTD and diffusion tensor vector under the prior guidance by introducing the tractogram bundle information to provide anatomic priors. Experiments are performed on simulated Hough, Sine, Circle data, ISMRM 2015 Tractography Challenge data, FiberCup data, and in vivo data from the Human Connectome Project (HCP) for qualitative and quantitative evaluation. Results demonstrate that our approach reconstructs complex fiber geometry more accurately. BTD reduces the error deviation and accumulation at the local level and shows better results in reconstructing long-range, twisting, and large fanning tracts.

Clinical characteristics of post-stroke basal ganglia aphasia and the study of language-related white matter tracts based on diffusion spectrum imaging.

BACKGROUND: Stroke often damages the basal ganglia, leading to atypical and transient aphasia, indicating that post-stroke basal ganglia aphasia (PSBGA) may be related to different anatomical structural damage and functional remodeling rehabilitation mechanisms. The basal ganglia contain dense white matter tracts (WMTs). Hence, damage to the functional tract may be an essential anatomical structural basis for the development of PSBGA. METHODS: We first analyzed the clinical characteristics of PSBGA in 28 patients and 15 healthy controls (HCs) using the Western Aphasia Battery and neuropsychological test batteries. Moreover, we investigated white matter injury during the acute stage using diffusion magnetic resonance imaging scans for differential tractography. Finally, we used multiple regression models in correlation tractography to analyze the relationship between various language functions and quantitative anisotropy (QA) of WMTs. RESULTS: Compared with HCs, patients with PSBGA showed lower scores for fluency, comprehension (auditory word recognition and sequential commands), naming (object naming and word fluency), reading comprehension of sentences, Mini-Mental State Examination, and Montreal Cognitive Assessment, along with increased scores in Hamilton Anxiety Scale-17 and Hamilton Depression Scale-17 within 7 days after stroke onset (P < 0.05). Differential tractography revealed that patients with PSBGA had damaged fibers, including in the body fibers of the corpus callosum, left cingulum bundles, left parietal aslant tracts, bilateral superior longitudinal fasciculus II, bilateral thalamic radiation tracts, left fornix, corpus callosum tapetum, and forceps major, compared with HCs (FDR < 0.02). Correlation tractography highlighted that better comprehension was correlated with a higher QA of the left inferior fronto-occipital fasciculus (IFOF), corpus callosum forceps minor, and left extreme capsule (FDR < 0.0083). Naming was positively associated with the QA of the left IFOF, forceps minor, left arcuate fasciculus, and uncinate fasciculus (UF) (FDR < 0.0083). Word fluency of naming was also positively associated with the QA of the forceps minor, left IFOF, and thalamic radiation tracts (FDR < 0.0083). Furthermore, reading was positively correlated with the QA of the forceps minor, left IFOF, and UF (FDR < 0.0083). CONCLUSION: PSBGA is primarily characterized by significantly impaired word fluency of naming and preserved repetition abilities, as well as emotional and cognitive dysfunction. Damaged limbic pathways, dorsally located tracts in the left hemisphere, and left basal ganglia pathways are involved in PSBGA pathogenesis. The results of connectometry analysis further refine the current functional localization model of higher-order neural networks associated with language functions.

Altered thalamocortical tract trajectory growth with undisrupted thalamic parcellation pattern in human lissencephaly brain at mid-gestational stage.

Proper topographically organized neural connections between the thalamus and the cerebral cortex are mandatory for thalamus function. Thalamocortical (TC) fiber growth begins during the embryonic period and completes by the third trimester of gestation, so that human neonates at birth have a thalamus with a near-facsimile of adult functional parcellation. Whether congenital neocortical anomaly (e.g., lissencephaly) affects TC connection in humans is unknown. Here, via diffusion MRI fiber-tractography analysis of long-term formalin-fixed postmortem fetal brain diagnosed as lissencephaly in comparison with an age-matched normal one, we found similar topological patterns of thalamic subregions and of internal capsule parcellated by TC fibers. However, lissencephaly fetal brain showed white matter structural changes, including fewer/less organized TC fibers and optic radiations, and much less cortical plate invasion by TC fibers - particularly around the shallow central sulcus. Diffusion MRI fiber tractography of normal fetal brains at 15, 23, and 26 gestational weeks (GW) revealed dynamic volumetric change of each parcellated thalamic subregion, suggesting coupled developmental progress of the thalamus with the corresponding cortex. Moreover, from GW23 and GW26 normal fetal brains, TC endings in the cortical plate could be delineated to reflect cumulative progressive TC invasion of cortical plate. By contrast, lissencephaly brain showed a dramatic decrease in TC invasion of the cortical plate. Our study thus shows the feasibility of diffusion MRI fiber tractography in postmortem long-term formalin-fixed fetal brains to disclose the developmental progress of TC tracts coordinating with thalamic and neocortical growth both in normal and lissencephaly fetal brains at mid-gestational stage.

Structural interhemispheric connectivity defects in mouse models of BBSOAS: Insights from high spatial resolution 3D white matter tractography.

White matter (WM) tract formation and axonal pathfinding are major processes in brain development allowing to establish precise connections between targeted structures. Disruptions in axon pathfinding and connectivity impairments will lead to neural circuitry abnormalities, often associated with various neurodevelopmental disorders (NDDs). Among several neuroimaging methodologies, Diffusion Tensor Imaging (DTI) is a magnetic resonance imaging (MRI) technique that has the advantage of visualizing in 3D the WM tractography of the whole brain non-invasively. DTI is particularly valuable in unpinning structural tract connectivity defects of neural networks in NDDs. In this study, we used 3D DTI to unveil brain-specific tract defects in two mouse models lacking the Nr2f1 gene, which mutations in patients have been proven to cause an emerging NDD, called Bosch-Boonstra-Schaaf Optic Atrophy (BBSOAS). We aimed to investigate the impact of the lack of cortical Nr2f1 function on WM morphometry and tract microstructure quantifications. We found in both mutant mice partial loss of fibers and severe misrouting of the two major cortical commissural tracts, the corpus callosum, and the anterior commissure, as well as the two major hippocampal efferent tracts, the post-commissural fornix, and the ventral hippocampal commissure. DTI tract malformations were supported by 2D histology, 3D fluorescent imaging, and behavioral analyses. We propose that these interhemispheric connectivity impairments are consistent in explaining some cognitive defects described in BBSOAS patients, particularly altered information processing between the two brain hemispheres. Finally, our results highlight 3DDTI as a relevant neuroimaging modality that can provide appropriate morphometric biomarkers for further diagnosis of BBSOAS patients.

Comparison of T1-weighted landmark placement and ROI transfer onto diffusion-weighted EPI sequences for targeted tractography tasks in the optic nerve.

Diffusion-based tractography in the optic nerve requires sampling strategies assisted by anatomical landmark information (regions of interest [ROIs]). We aimed to investigate the feasibility of expert-placed, high-resolution T1-weighted ROI-data transfer onto lower spatial resolution diffusion-weighted images. Slab volumes from 20 volunteers were acquired and preprocessed including distortion bias correction and artifact reduction. Constrained spherical deconvolution was used to generate a directional diffusion information grid (fibre orientation distribution-model [FOD]). Three neuroradiologists marked landmarks on both diffusion imaging variants and structural datasets. Structural ROI information (volumetric interpolated breath-hold sequence [VIBE]) was respectively registered (linear with 6/12 degrees of freedom [DOF]) onto single-shot EPI (ss-EPI) and readout-segmented EPI (rs-EPI) volumes, respectively. All eight ROI/FOD-combinations were compared in a targeted tractography task of the optic nerve pathway. Inter-rater reliability for placed ROIs among experts was highest in VIBE images (lower confidence interval 0.84 to 0.97, mean 0.91) and lower in both ss-EPI (0.61 to 0.95, mean 0.79) and rs-EPI (0.59 to 0.86, mean 0.70). Tractography success rate based on streamline selection performance was highest in VIBE-drawn ROIs registered (6-DOF) onto rs-EPI FOD (70.0% over 5%-threshold, capped to failed ratio 39/16) followed by both 12-DOF-registered (67.5%; 41/16) and nonregistered VIBE (67.5%; 40/23). On ss-EPI FOD, VIBE-ROI-datasets obtained fewer streamlines overall with each at 55.0% above 5%-threshold and with lower capped to failed ratio (6-DOF: 35/36; 12-DOF: 34/34, nonregistered 33/36). The combination of VIBE-placed ROIs (highest inter-rater reliability) with 6-DOF registration onto rs-EPI targets (best streamline selection performance) is most suitable for white matter template generation required in group studies.

Unveiling the axonal connectivity between the precuneus and temporal pole: Structural evidence from the cingulum pathways.

Neuroimaging studies have consistently demonstrated concurrent activation of the human precuneus and temporal pole (TP), both during resting-state conditions and various higher-order cognitive functions. However, the precise underlying structural connectivity between these brain regions remains uncertain despite significant advancements in neuroscience research. In this study, we investigated the connectivity of the precuneus and TP by employing parcellation-based fiber micro-dissections in human brains and fiber tractography techniques in a sample of 1065 human subjects and a sample of 41 rhesus macaques. Our results demonstrate the connectivity between the posterior precuneus area POS2 and the areas 35, 36, and TG of the TP via the fifth subcomponent of the cingulum (CB-V) also known as parahippocampal cingulum. This finding contributes to our understanding of the connections within the posteromedial cortices, facilitating a more comprehensive integration of anatomy and function in both normal and pathological brain processes. PRACTITIONER POINTS: Our investigation delves into the intricate architecture and connectivity patterns of subregions within the precuneus and temporal pole, filling a crucial gap in our knowledge. We revealed a direct axonal connection between the posterior precuneus (POS2) and specific areas (35, 35, and TG) of the temporal pole. The direct connections are part of the CB-V pathway and exhibit a significant association with the cingulum, SRF, forceps major, and ILF. Population-based human tractography and rhesus macaque fiber tractography showed consistent results that support micro-dissection outcomes.

Probabilistic coverage of the frontal aslant tract in young adults: Insights into individual variability, lateralization, and language functions.

The frontal aslant tract (FAT) is a crucial neural pathway of language and speech, but little is known about its connectivity and segmentation differences across populations. In this study, we investigate the probabilistic coverage of the FAT in a large sample of 1065 young adults. Our primary goal was to reveal individual variability and lateralization of FAT and its structure-function correlations in language processing. The study utilized diffusion MRI data from 1065 subjects obtained from the Human Connectome Project. Automated tractography using DSI Studio software was employed to map white matter bundles, and the results were examined to study the population variation of the FAT. Additionally, anatomical dissections were performed to validate the fiber tracking results. The tract-to-region connectome, based on Human Connectome Project-MMP parcellations, was utilized to provide population probability of the tract-to-region connections. Our results showed that the left anterior FAT exhibited the most substantial individual differences, particularly in the superior and middle frontal gyrus, with greater variability in the superior than the inferior region. Furthermore, we found left lateralization in FAT, with a greater difference in coverage in the inferior and posterior portions. Additionally, our analysis revealed a significant positive correlation between the left FAT inferior coverage area and the performance on the oral reading recognition (p = .016) and picture vocabulary (p = .0026) tests. In comparison, fractional anisotropy of the right FAT exhibited marginal significance in its correlation (p = .056) with Picture Vocabulary Test. Our findings, combined with the connectivity patterns of the FAT, allowed us to segment its structure into anterior and posterior segments. We found significant variability in FAT coverage among individuals, with left lateralization observed in both macroscopic shape measures and microscopic diffusion metrics. Our findings also suggested a potential link between the size of the left FAT's inferior coverage area and language function tests. These results enhance our understanding of the FAT's role in brain connectivity and its potential implications for language and executive functions.

Connectome spectrum electromagnetic tomography: A method to reconstruct electrical brain source networks at high-spatial resolution.

Connectome spectrum electromagnetic tomography (CSET) combines diffusion MRI-derived structural connectivity data with well-established graph signal processing tools to solve the M/EEG inverse problem. Using simulated EEG signals from fMRI responses, and two EEG datasets on visual-evoked potentials, we provide evidence supporting that (i) CSET captures realistic neurophysiological patterns with better accuracy than state-of-the-art methods, (ii) CSET can reconstruct brain responses more accurately and with more robustness to intrinsic noise in the EEG signal. These results demonstrate that CSET offers high spatio-temporal accuracy, enabling neuroscientists to extend their research beyond the current limitations of low sampling frequency in functional MRI and the poor spatial resolution of M/EEG.

Multimodal cross-examination of progressive apraxia of speech by diffusion tensor imaging-based tractography and Tau-PET scans.

Progressive apraxia of speech (PAOS) is a 4R tauopathy characterized by difficulties with motor speech planning. Neurodegeneration in PAOS targets the premotor cortex, particularly the supplementary motor area (SMA), with degeneration of white matter (WM) tracts connecting premotor and motor cortices and Broca's area observed on diffusion tensor imaging (DTI). We aimed to assess flortaucipir uptake across speech-language-related WM tracts identified using DTI tractography in PAOS. Twenty-two patients with PAOS and 26 matched healthy controls were recruited by the Neurodegenerative Research Group (NRG) and underwent MRI and flortaucipir-PET. The patient population included patients with primary progressive apraxia of speech (PPAOS) and non-fluent variant/agrammatic primary progressive aphasia (agPPA). Flortaucipir PET scans and DTI were coregistered using rigid registration with a mutual information cost function in subject space. Alignments between DTI and flortaucipir PET were inspected in all cases. Whole-brain tractography was calculated using deterministic algorithms by a tractography reconstruction tool (DSI-studio) and specific tracts were identified using an automatic fiber tracking atlas-based method. Fractional anisotropy (FA) and flortaucipir standardized uptake value ratios (SUVRs) were averaged across the frontal aslant tract, arcuate fasciculi, inferior frontal-occipital fasciculus, inferior and middle longitudinal fasciculi, as well as the SMA commissural fibers. Reduced FA (p < .0001) and elevated flortaucipir SUVR (p = .0012) were observed in PAOS cases compared to controls across all combined WM tracts. For flortaucipir SUVR, the greatest differentiation of PAOS from controls was achieved with the SMA commissural fibers (area under the receiver operator characteristic curve [AUROC] = 0.83), followed by the left arcuate fasciculus (AUROC = 0.75) and left frontal aslant tract (AUROC = 0.71). Our findings demonstrate that flortaucipir uptake is increased across WM tracts related to speech/language difficulties in PAOS.

Fibre orientation atlas guided rapid segmentation of white matter tracts.

Fibre tract delineation from diffusion magnetic resonance imaging (MRI) is a valuable clinical tool for neurosurgical planning and navigation, as well as in research neuroimaging pipelines. Several popular methods are used for this task, each with different strengths and weaknesses making them more or less suited to different contexts. For neurosurgical imaging, priorities include ease of use, computational efficiency, robustness to pathology and ability to generalise to new tracts of interest. Many existing methods use streamline tractography, which may require expert neuroimaging operators for setting parameters and delineating anatomical regions of interest, or suffer from as a lack of generalisability to clinical scans involving deforming tumours and other pathologies. More recently, data-driven approaches including deep-learning segmentation models and streamline clustering methods have improved reproducibility and automation, although they can require large amounts of training data and/or computationally intensive image processing at the point of application. We describe an atlas-based direct tract mapping technique called 'tractfinder', utilising tract-specific location and orientation priors. Our aim was to develop a clinically practical method avoiding streamline tractography at the point of application while utilising prior anatomical knowledge derived from only 10-20 training samples. Requiring few training samples allows emphasis to be placed on producing high quality, neuro-anatomically accurate training data, and enables rapid adaptation to new tracts of interest. Avoiding streamline tractography at the point of application reduces computational time, false positives and vulnerabilities to pathology such as tumour deformations or oedema. Carefully filtered training streamlines and track orientation distribution mapping are used to construct tract specific orientation and spatial probability atlases in standard space. Atlases are then transformed to target subject space using affine registration and compared with the subject's voxel-wise fibre orientation distribution data using a mathematical measure of distribution overlap, resulting in a map of the tract's likely spatial distribution. This work includes extensive performance evaluation and comparison with benchmark techniques, including streamline tractography and the deep-learning method TractSeg, in two publicly available healthy diffusion MRI datasets (from TractoInferno and the Human Connectome Project) in addition to a clinical dataset comprising paediatric and adult brain tumour scans. Tract segmentation results display high agreement with established techniques while requiring less than 3 min on average when applied to a new subject. Results also display higher robustness than compared methods when faced with clinical scans featuring brain tumours and resections. As well as describing and evaluating a novel proposed tract delineation technique, this work continues the discussion on the challenges surrounding the white matter segmentation task, including issues of anatomical definitions and the use of quantitative segmentation comparison metrics.

Preoperative diffusion tensor imaging: Fiber-trajectory-distribution-based tractography to identify facial nerve in vestibular schwannoma.

PURPOSE: Tractography of the facial nerve based on diffusion MRI is instrumental before surgery for the resection of vestibular schwannoma, but no excellent methods usable for the suppression of motion and image noise have been proposed. The aim of this study was to effectively suppress noise and provide accurate facial nerve reconstruction by extend a fiber trajectory distribution function based on the fourth-order streamline differential equations. METHODS: Preoperative MRI from 33 patients with vestibular schwannoma who underwent surgical resection were utilized in this study. First, T1WI and T2WI were used to obtain mask images and regions of interest. Second, probabilistic tractography was employed to obtain the fibers representing the approximate facial nerve pathway, and these fibers were subsequently translated into orientation information for each voxel. Last, the voxel orientation information and the peaks of the fiber orientation distribution were combined to generate a fiber trajectory distribution function, which was used to parameterize the anatomical information. The parameters were determined by minimizing the cost between the trajectory of fibers and the estimated directions. RESULTS: Qualitative and visual analyses were used to compare facial nerve reconstruction with intraoperative recordings. Compared with other methods (SD_Stream, iFOD1, iFOD2, unscented Kalman filter, parallel transport tractography), the fiber-trajectory-distribution-based tractography provided the most accurate facial nerve reconstructions. CONCLUSION: The fiber-trajectory-distribution-based tractography can effectively suppress the effect of noise. It is a more valuable aid for surgeons before vestibular schwannoma resection, which may ultimately improve the postsurgical patient's outcome.

Sensitivity analyses of probabilistic and deterministic DTI tractography methodologies for studying arm muscle architecture.

PURPOSE: To determine the sensitivity profiles of probabilistic and deterministic DTI tractography methods in estimating geometric properties in arm muscle anatomy. METHODS: Spin-echo diffusion-weighted MR images were acquired in the dominant arm of 10 participants. Both deterministic and probabilistic tractography were performed in two different muscle architectures of the parallel-structured biceps brachii (and the pennate-structured flexor carpi ulnaris. Muscle fascicle geometry estimates and number of fascicles were evaluated with respect to tractography turning angle, polynomial fitting order, and SNR. The DTI tractography estimated fascicle lengths were compared with measurements obtained from conventional cadaveric dissection and ultrasound modalities. RESULTS: The probabilistic method generally estimated fascicle lengths closer to ranges reported by conventional methods than the deterministic method, most evident in the biceps brachii (p > 0.05), consisting of longer, arc-like fascicles. For both methods, a wide turning angle (50º-90°) generated fascicle lengths that were in close agreement with conventional methods, most evident in the flexor carpi ulnaris (p > 0.05), consisting of shorter, feather-like fascicles. The probabilistic approach produced at least two times more fascicles than the deterministic approach. For both approaches, second-order fitting yielded about double the complete tracts as third-order fitting. In both muscles, as SNR decreased, deterministic tractography produced less fascicles but consistent geometry (p > 0.05), whereas probabilistic tractography produced a consistent number but altered geometry of fascicles (p < 0.001). CONCLUSION: Findings from this study provide best practice recommendations for implementing DTI tractography in skeletal muscle and will inform future in vivo studies of healthy and pathological muscle structure.

Atlas-guided brain projection tracts: From regions of interest to tractography 3D rendering.

The use of diffusion tensor imaging (DTI) has seen significant development over the last two decades, in particular with the development of the tractography of association tracts for preoperative planning of surgery. However, projection tracts are difficult to differentiate from one another and tractography studies have failed to reconstruct these ascending/descending pathways from/to the spinal cord. The present study proposes an atlas of regions of interest (ROIs) designed specifically for projection tracts tractography. Forty-nine healthy subjects were included in this prospective study. Brain DTI was acquired using the same 3 T MRI scanner, with 32 diffusion directions. Distortions were corrected using the FSL software package. ROIs were drawn using the anterior commissure (AC)-posterior commissure (PC) line on the following landmarks: the pyramid for the corticospinal tract, the medio-caudal part of the red nucleus for the rubrospinal tract, the pontine reticular nucleus for corticoreticular tract, the superior and inferior cerebellar peduncles for, respectively, the anterior and posterior spinocerebellar tract, the gracilis and cuneatus nucleus for the dorsal columns, and the ventro-posterolateral nucleus for the spinothalamic tract. Fiber tracking was performed using a deterministic algorithm using DSI Studio software. ROI coordinates, according to AC-PC line, were given for each tract. Tractography was obtained for each tract, allowing tridimensional rendering and comparison of tracking metrics between tracts. The present study reports the accurate design of specific ROIs for tractography of each projection tract. This could be a useful tool in order to differentiate projection tracts at the spinal cord level.

Prospective longitudinal cohort study of quantitative muscle magnetic resonance imaging in a healthy control population.

Quantitative muscle magnetic resonance imaging (qMRI) is a valuable methodology for assessing muscular injuries and neuromuscular disorders. Notably, muscle diffusion tensor imaging (DTI) gives insights into muscle microstructural and macrostructural characteristics. However, the long-term reproducibility and robustness of these measurements remain relatively unexplored. The purpose of this prospective longitudinal cohort study was to assess the long-term robustness and range of variation of qMRI parameters, especially DTI metrics, in the lower extremity muscles of healthy controls under real-life conditions. Twelve volunteers (seven females, age 44.1 ± 12.1 years, body mass index 23.3 ± 2.0 kg/m2) underwent five leg muscle MRI sessions every 20 ± 4 weeks over a total period of 1.5 years. A multiecho gradient-echo Dixon-based sequence, a multiecho spin-echo T2-mapping sequence, and a spin-echo echo planar imaging diffusion-weighted sequence were acquired bilaterally with a Philips 3-T Achieva MR System using a 16-channel torso coil. Fifteen leg muscles were segmented in both lower extremities. qMRI parameters, including fat fraction (FF), water T2 relaxation time, and the diffusion metrics fractional anisotropy (FA) and mean diffusivity (MD), were evaluated. Coefficients of variance (wsCV) and intraclass correlation coefficients (ICCs) were calculated to assess the reproducibility of qMRI parameters. The standard error of measurement (SEM) and the minimal detectable change (MDC) were calculated to determine the range of variation. All tests were applied to all muscles and, subsequently, to each muscle separately. wsCV showed good reproducibility (≤ 10%) for all qMRI parameters in all muscles. The ICCs revealed excellent agreement between time points (FF = 0.980, water T2 = 0.941, FA = 0.952, MD = 0.948). Random measurement errors assessed by SEM and the MDC were low (< 12%). In conclusion, in this study, we showed that qMRI parameters in healthy volunteers living normal lives are stable over 18 months, thereby defining a benchmark for the expected range of variation over time.

Improvement of the thalamocortical white matter network in people with stable treated relapsing-remitting multiple sclerosis over time.

Advanced imaging techniques (tractography) enable the mapping of white matter (WM) pathways and the understanding of brain connectivity patterns. We combined tractography with a network-based approach to examine WM microstructure on a network level in people with relapsing-remitting multiple sclerosis (pw-RRMS) and healthy controls (HCs) over 2 years. Seventy-six pw-RRMS matched with 43 HCs underwent clinical assessments and 3T MRI scans at baseline (BL) and 2-year follow-up (2-YFU). Probabilistic tractography was performed, accounting for the effect of lesions, producing connectomes of 25 million streamlines. Network differences in fibre density across pw-RRMS and HCs at BL and 2-YFU were quantified using network-based statistics (NBS). Longitudinal network differences in fibre density were quantified using NBS in pw-RRMS, and were tested for correlations with disability, cognition and fatigue scores. Widespread network reductions in fibre density were found in pw-RRMS compared with HCs at BL in cortical regions, with more reductions detected at 2-YFU. Pw-RRMS had reduced fibre density at BL in the thalamocortical network compared to 2-YFU. This effect appeared after correction for age, was robust across different thresholds, and did not correlate with lesion volume or disease duration. Pw-RRMS demonstrated a robust and long-distance improvement in the thalamocortical WM network, regardless of age, disease burden, duration or therapy, suggesting a potential locus of neuroplasticity in MS. This network's role over the disease's lifespan and its potential implications in prognosis and treatment warrants further investigation.