Inferior Peduncle Research Articles

Microstructural correlates of olfactory dysfunction in Parkinson's Disease: a systematic review of diffusion MRI studies.

Olfactory dysfunction (OD) is a non-motor symptom of Parkinson's Disease, affecting 75-95% of the patients. This symptom usually emerges before the clinical diagnosis, and patients with OD present with more severe forms of PD and need higher doses of therapy. It remains unknown whether OD is just a mere non-motor symptom or if it is a part of a series of pathological changes in different brain regions of the affected patients. We performed a systematic review to find the microstructural correlates of OD in people with PD. The systematic search in PubMed, Scopus, Embase, and Web of Science yielded ten eligible studies. Assessments in most included studies were inconclusive. However, we found variable brain regions and tracts associated with OD. The most repeated areas included the primary olfactory cortex, gyrus rectus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, corticospinal tract, uncinate fasciculus, cingulum, and cerebellar peduncle. Despite some limitations, we pointed out the microstructural correlates of OD, which were also present in areas other than the olfactory system. These findings imply that OD might be a manifestation of an unknown, greater pathology in the brain of patients with PD.

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.

Neural Mechanisms Associated With Postural Control in Collegiate Soccer and Non-Soccer Athletes.

Sport-specific training may improve postural control, while repetitive head acceleration events (RHAEs) may compromise it. Understanding the neural mechanisms underlying postural control may contextualize changes due to training and RHAE. The goal of this study was to determine whether postural sway during the Balance Error Scoring System (BESS) is related to white matter organization (WMO) in collegiate athletes. Collegiate soccer ( N =33) and non-soccer athletes ( N =44) completed BESS and diffusion tensor imaging. Postural sway during each BESS stance, fractional anisotropy (FA), and mean diffusivity (MD) were extracted for each participant. Partial least squares analyses determined group differences in postural sway and WMO and the relationship between postural sway and WMO in soccer and non-soccer athletes separately. Soccer athletes displayed better performance during BESS 6, with lower FA and higher MD in the medial lemniscus (ML) and inferior cerebellar peduncle (ICP), compared to non-soccer athletes. In soccer athletes, lower sway during BESS 2, 5, and 6 was associated with higher FA and lower MD in the corticospinal tract, ML, and ICP. In non-soccer athletes, lower sway during BESS 2 and 4 was associated with higher FA and lower MD in the ML and ICP. BESS 1 was associated with higher FA, and BESS 3 was associated with lower MD in the same tracts in non-soccer athletes. Soccer and non-soccer athletes showed unique relationships between sway and WMO, suggesting that sport-specific exposures are partly responsible for changes in neurological structure and accompanying postural control performance and should be considered when evaluating postural control after injury.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content, available at: http://links.lww.com/JNPT/A472 ).

Microstructural Properties of the Cerebellar Peduncles in Children With Developmental Language Disorder.

Children with developmental language disorder (DLD) struggle to learn their native language for no apparent reason. While research on the neurobiological underpinnings of the disorder has focused on the role of corticostriatal systems, little is known about the role of the cerebellum in DLD. Corticocerebellar circuits might be involved in the disorder as they contribute to complex sensorimotor skill learning, including the acquisition of spoken language. Here, we used diffusion-weighted imaging data from 77 typically developing and 54 children with DLD and performed probabilistic tractography to identify the cerebellum's white matter tracts: the inferior, middle, and superior cerebellar peduncles. Children with DLD showed lower fractional anisotropy (FA) in the inferior cerebellar peduncles (ICP), fiber tracts that carry motor and sensory input via the inferior olive to the cerebellum. Lower FA in DLD was driven by lower axial diffusivity. Probing this further with more sophisticated modeling of diffusion data, we found higher orientation dispersion but no difference in neurite density in the ICP of children with DLD. Reduced FA is therefore unlikely to be reflecting microstructural differences in myelination, rather the organization of axons in these pathways is disrupted. ICP microstructure was not associated with language or motor coordination performance in our sample. We also found no differences in the middle and superior peduncles, the main pathways connecting the cerebellum with the cortex. To conclude, it is not corticocerebellar but atypical olivocerebellar white matter connections that characterize DLD and suggest the involvement of the olivocerebellar system in speech and language acquisition and development.

Understanding the role of cerebellum in early Parkinson’s disease: a structural and functional MRI study

Increasing evidence suggests that the cerebellum may have a role in the pathophysiology of Parkinson’s disease (PD). Hence, the scope of this study was to investigate whether there are structural and functional alterations of the cerebellum and whether they correlate with motor and non-motor symptoms in early PD patients. Seventy-six patients with early PD and thirty-one age and sex-matched healthy subjects (HS) were enrolled and underwent a 3 T magnetic resonance imaging (MRI) protocol. The following MRI analyses were performed: (1) volumes of 5 cerebellar regions of interest (sensorimotor and cognitive cerebellum, dentate, interposed, and fastigial nuclei); (2) microstructural integrity of the cerebellar white matter connections (inferior, middle, and superior cerebellar peduncles); (3) functional connectivity at rest of the 5 regions of interest already described in point 1 with the rest of brain. Compared to controls, early PD patients showed a significant decrease in gray matter volume of the dentate, interposed and fastigial nuclei, bilaterally. They also showed abnormal, bilateral white matter microstructural integrity in all 3 cerebellar peduncles. Functional connectivity of the 5 cerebellar regions of interest with several areas in the midbrain, basal ganglia and cerebral cortex was altered. Finally, there was a positive correlation between abnormal functional connectivity of the fastigial nucleus with the volume of the nucleus itself and a negative correlation with axial symptoms severity. Our results showed that structural and functional alterations of the cerebellum are present in PD patients and these changes contribute to the pathophysiology of PD in the early phase.

IMG-04. ASSOCIATION BETWEEN MICROSTRUCTURAL INTEGRITY OF BRAIN SUBSTRUCTURES AND NEUROCOGNITIVE OUTCOMES: A MULTI-TRAJECTORY ANALYSIS IN CHILDHOOD BRAIN TUMOR SURVIVORS

Abstract BACKGROUND The relationship between the brain’s microstructural integrity and neurocognitive outcomes is not well characterized in childhood brain tumor survivors. In healthy children, mean diffusivity (MD) generally decreases and fractional anisotropy (FA) increases with age as the brain progressively myelinates and develops. Increasing MD and decreasing FA is suggestive of microstructural injury. We investigate the association between longitudinal neurocognitive outcomes and change in MD and FA in childhood brain tumor survivors. METHODS Patients diagnosed with a brain tumor at < 20 years of age with ≥ 2 neurocognitive assessments and paired DTI at each neurocognitive timepoint were retrospectively identified and eligible for inclusion. Multi-trajectory modeling was applied to cluster patients into distinct neurocognitive trajectories based on intelligent quotient, processing speed and working memory. Linear mixed models were used to determine whether the clusters were associated with change in MD and FA over time. RESULTS A total of 61 patients were eligible with 151 neurocognitive assessments paired with DTI. Mean follow-up was 4.8 years. Multi-trajectory modeling identified two clusters of patients with distinct neurocognitive trajectories. Compared to the low-performance group, the high-performance group (45.5%) had higher baseline neurocognitive scores with less decline in all neurocognitive outcomes. The high-performance group was also associated with a greater decrease in MD and greater increase in FA of the hippocampus and several white matter tracts such as the corpus callosum, pontine crossing tract, anterior limb of the internal capsule and inferior cerebellar peduncle, after adjusting for age and sex (all p<0.05). Additionally, the high-performance group was associated with a greater increase in FA in the superior, middle and inferior frontal gyri (all p<0.05). CONCLUSIONS The high-performance neurocognitive group was associated with greater microstructural integrity over time in multiple brain substructures compared to the low-performance group, as measured by change in fractional anisotropy and mean diffusivity.

Retinal structural thicknesses reflect clinically relevant microstructural white matter abnormalities in neuromyelitis optica spectrum disorders

BackgroundThinning of retinal thickness seen on optical coherence tomography (OCT) is frequent in patients with neuromyelitis optica spectrum disorder (NMOSD). We explored the association between OCT metrics, MRI measurements and clinical outcomes in NMOSD. Methods44 NMOSD and 60 controls underwent OCT and MR imaging. Mean peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell complex (GCC) thicknesses were measured. Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) was used to measure the white matter microstructural integrity. In NMOSD patients, Expanded Disability Status Scale (EDSS) was used to quantify disability. Visual acuity (VA) was also performed for all participants. ResultspRNFL thickness was positively associated with mean diffusivity in left posterior thalamic radiation (pp = 0.010) and axial kurtosis in inferior cerebellar peduncle (p = 0.023). Similarly, GCC thickness in NMOSD patients was positively associated with fractional anisotropy in right superior longitudinal fascicules (p = 0. 041) and axial kurtosis of left cerebellar peduncle (p = 0.011). ConclusionsIn NMOSD, pRNFL and GCC reflect integrity of clinically relevant white matter structures underlying the value of OCT metrics as markers of neuronaxonal loss and disability.

The critical role of neuroimaging in hemicrania continua: Asystematic review and case series.

Hemicrania continua is a primary unilateral headache characterized by ipsilateral parasympathetic and sympathetic autonomic features. A key diagnostic criterion is its dramatic response to indomethacin treatment; however, various vascular or structural abnormalities have been reported to cause secondary hemicrania continua, presenting with clinical features similar to those of the primary headache presentation. We reviewed the literature to compile secondary hemicrania continua cases, highlighting the importance of imaging during the evaluation. Additionally, we also contributed our three cases to the existing studies. We conducted a review of articles from the PubMed and EMBASE databases that described reported cases of secondary hemicrania continua, covering the period from 1993 to 2021. Our review included detailed patient information, signs, and symptoms of hemicrania continua, as well as information on indomethacin usage and headache resolution (if pertinent). Secondary hemicrania continua can result from a remarkably diverse range of structural and vascular lesions, yet clinical reports on long-term follow-up are lacking. Notably, cases may exhibit a classical response to indomethacin, emphasizing the importance of neuroimaging in excluding secondary cases. Our search yielded 41 cases meeting our criteria. We excluded six cases that were not treated with indomethacin or were unresponsive to it. Additionally, we present three cases that highlight the necessity of neuroimaging in evaluating hemicrania continua, along with short- and long-term clinical outcomes following indomethacin and lesion-directed treatments. Case 1 presented with daily right-sided headaches and cranial autonomic symptoms. Her pain completely resolved with indomethacin use. Neuroimaging of the brain revealed a laterally directed saccular aneurysm of the right internal carotid artery. Case 2 presented with continuous left-sided unilateral headaches with superimposed exacerbations. She complained of left-sided photophobia with a dull sensation in the left ear. Her symptoms decreased after 2 weeks of indomethacin use. Neuroimaging of the head indicated a benign tumor with mass effect into the left lateral medulla and inferior cerebellar peduncle. Case 3 presented with a right side-locked headache with daily, severe superimposed exacerbations. She had photophobia in the right eye and a right-sided Horner's syndrome, along with tearing during her exacerbations. Neuroimaging of the brain revealed a pituitary tumor and her pain completely resolved with indomethacin. Hemicrania continua is a rare headache disorder that can be either primary or secondary. Importantly, response to indomethacin can still occur in secondary hemicrania continua. Thus, neuroimaging should be considered to rule out underlying structural etiology in all cases, regardless of their clinical responsiveness to indomethacin therapy.

Abnormality of Early White Matter Development in Tuberous Sclerosis Complex and Autism Spectrum Disorder: Longitudinal Analysis of Diffusion Tensor Imaging Measures.

Background: Abnormalities in white matter development may influence development of autism spectrum disorder in tuberous sclerosis complex (TSC). Our goals for this study were as follows: (1) use data from a longitudinal neuroimaging study of tuberous sclerosis complex (TACERN) to develop optimized linear mixed effects models for analyzing longitudinal, repeated diffusion tensor imaging metrics (fractional anisotropy, mean diffusivity) pertaining to select white matter tracts, in relation to positive Autism Diagnostic Observation Schedule-Second Edition classification at 36 months, and (2) perform an exploratory analysis using optimized models applied to all white matter tracts from these data. Methods: Eligible participants (3-12 months) underwent brain magnetic resonance imaging (MRI) at repeated time points from ages 3 to 36 months. Positive Autism Diagnostic Observation Schedule-Second Edition classification at 36 months was used. Linear mixed effects models were fine-tuned separately for fractional anisotropy values (using fractional anisotropy corpus callosum as test outcome) and mean diffusivity values (using mean diffusivity right posterior limb internal capsule as test outcome). Fixed effects included participant age, within-participant longitudinal age, and autism spectrum disorder diagnosis. Results: Analysis included data from n = 78. After selecting separate optimal models for fractional anisotropy and mean diffusivity values, we applied these models to fractional anisotropy and mean diffusivity of all 27 white matter tracts. Fractional anisotropy corpus callosum was related to positive Autism Diagnostic Observation Schedule-Second Edition classification (coefficient = 0.0093, P = .0612), and mean diffusivity right inferior cerebellar peduncle was related to positive Autism Diagnostic Observation Schedule-Second Edition classification (coefficient = -0.00002071, P = .0445), though these findings were not statistically significant after multiple comparisons correction. Conclusion: These optimized linear mixed effects models possibly implicate corpus callosum and cerebellar pathology in development of autism spectrum disorder in tuberous sclerosis complex, but future studies are needed to replicate these findings and explore contributors of heterogeneity in these models.

β-carbolines that enhance GABAA receptor response expressed in oligodendrocytes promote remyelination in an in vivo rat model of focal demyelination.

Demyelination is typically followed by a remyelination process through mature oligodendrocytes (OLs) differentiated from precursor cells (OPCs) recruited into the lesioned areas, however, this event usually results in uncompleted myelination. Potentiation of the remyelination process is an important target for designing effective therapeutic strategies against white matter loss. Here, it was evaluated the remyelinating effect of different β-carbolines that present differential allosteric modulation on the GABAA receptor expressed in OLs. For this, we used a focalized demyelination model in the inferior cerebellar peduncle (i.c.p.) of rats (DRICP model), in which, demyelination by ethidium bromide (0.05%) stereotaxic injection was confirmed histologically by staining with Black-Gold II (BGII) and toluidine blue. In addition, a longitudinal analysis with diffusion-weighted magnetic resonance imaging (dMRI) was made by computing fractional anisotropy (FA), apparent diffusion coefficient (ADC) and diffusivity parameters to infer i.c.p. microstructural changes. First, dMRI analysis revealed FA decreases together with ADC and radial diffusivity (RD) increases after demyelination, which correlates with histological BGII observations. Then, we evaluated the effect produced by three allosteric GABAA receptor modulators, the N-butyl-β-carboline-3-carboxylate (β-CCB), ethyl 9H-pyrido [3,4-b]indole-3-carboxylate (β-CCE), and 4-ethyl-6,7-dimethoxy-9H-pyrido [3,4-b]indole-3-carboxylic acid methyl ester (DMCM). The results indicated that daily systemic β-CCB (1 mg/Kg) or β-CCE (1 mg/Kg) administration for 2 weeks, but not DMCM (0.35 mg/Kg), in lesioned animals increased FA and decreased ADC or RD, suggesting myelination improvement. This was supported by BGII staining analysis that showed a recovery of myelin content. Also, it was quantified by immunohistochemistry both NG2+ and CC1+ cellular population in the different experimental sceneries. Data indicated that either β-CCB or β-CCE, but not DMCM, produced an increase in the population of CC1+ cells in the lesioned area. Finally, it was also calculated the g-ratio of myelinated axons and observed a similar value in those lesioned animals treated with β-CCB or β-CCE compared to controls. Thus, using the DRICP model, it was observed that either β-CCB or β-CCE, positive modulators of the GABAA receptor in OLs, had a potent promyelinating effect.

A Machine Learning Model for Predicting Major Depressive Disorder Using Diffusion-Tensor Imaging Data

IntroductionMajor Depressive Disorder (MDD) stands as a prevalent psychiatric condition within the general population. Despite extensive research efforts, the identification of definitive diagnostic biomarkers for depressive disorders remains elusive. Currently, machine learning methods are gaining prominence in the diagnosis of medical illnesses.ObjectivesThis study aims to construct a machine learning-based prediction model for Major Depressive Disorder (MDD) by harnessing diffusion tensor imaging (DTI) data.MethodsThe DTI datasets comprising MDD (N=83) and Healthy Control (N=70) groups were procured from the cohort study of Anxiety and Depression conducted at the National Center for Mental Health in South Korea. A machine learning method using a decision tree algorithm was employed to select relevant brain regions and establish a robust diagnostic model. Features associated with white matter (WM) tracts were chosen through recursive feature elimination.Results Demographic characteristics, including age, sex, and handedness, displayed no significant differences between the MDD and Healthy Control groups. However, the total score of the Beck Depression Inventory was notably higher in individuals with MDD compared to Healthy Controls. A diagnostic model was crafted using the decision tree algorithms to distinguish between the two groups. The model demonstrated the following classification performance metrics: accuracy (65.6% ± 8.5), sensitivity (66.6% ± 12.5), and specificity (64.7% ± 13.6). Furthermore, through recursive feature elimination, specific neuroanatomical features tied to brain structures such as the inferior cerebellar peduncle, posterior thalamic radiation, cingulum (hippocampus), uncinate fasciculus, and tapetum were identified.ConclusionsDespite of limited performance of classification, a machine learning-based approach could provide insights into the development of a diagnostic model for MDD using neuroimaging data. Furthermore, these features, derived from DTI-derived data, may have implications for understanding the neural underpinnings of major depressive disorder.Disclosure of InterestNone Declared

Neuroimaging Findings in US Government Personnel and Their Family Members Involved in Anomalous Health Incidents

US government personnel stationed internationally have reported anomalous health incidents (AHIs), with some individuals experiencing persistent debilitating symptoms. To assess the potential presence of magnetic resonance imaging (MRI)-detectable brain lesions in participants with AHIs, with respect to a well-matched control group. This exploratory study was conducted at the National Institutes of Health (NIH) Clinical Center and the NIH MRI Research Facility between June 2018 and November 2022. Eighty-one participants with AHIs and 48 age- and sex-matched control participants, 29 of whom had similar employment as the AHI group, were assessed with clinical, volumetric, and functional MRI. A high-quality diffusion MRI scan and a second volumetric scan were also acquired during a different session. The structural MRI acquisition protocol was optimized to achieve high reproducibility. Forty-nine participants with AHIs had at least 1 additional imaging session approximately 6 to 12 months from the first visit. AHIs. Group-level quantitative metrics obtained from multiple modalities: (1) volumetric measurement, voxel-wise and region of interest (ROI)-wise; (2) diffusion MRI-derived metrics, voxel-wise and ROI-wise; and (3) ROI-wise within-network resting-state functional connectivity using functional MRI. Exploratory data analyses used both standard, nonparametric tests and bayesian multilevel modeling. Among the 81 participants with AHIs, the mean (SD) age was 42 (9) years and 49% were female; among the 48 control participants, the mean (SD) age was 43 (11) years and 42% were female. Imaging scans were performed as early as 14 days after experiencing AHIs with a median delay period of 80 (IQR, 36-544) days. After adjustment for multiple comparisons, no significant differences between participants with AHIs and control participants were found for any MRI modality. At an unadjusted threshold (P < .05), compared with control participants, participants with AHIs had lower intranetwork connectivity in the salience networks, a larger corpus callosum, and diffusion MRI differences in the corpus callosum, superior longitudinal fasciculus, cingulum, inferior cerebellar peduncle, and amygdala. The structural MRI measurements were highly reproducible (median coefficient of variation <1% across all global volumetric ROIs and <1.5% for all white matter ROIs for diffusion metrics). Even individuals with large differences from control participants exhibited stable longitudinal results (typically, <±1% across visits), suggesting the absence of evolving lesions. The relationships between the imaging and clinical variables were weak (median Spearman ρ = 0.10). The study did not replicate the results of a previously published investigation of AHIs. In this exploratory neuroimaging study, there were no significant differences in imaging measures of brain structure or function between individuals reporting AHIs and matched control participants after adjustment for multiple comparisons.

Causal relationship between multiparameter brain MRI phenotypes and age: evidence from Mendelian randomization.

To explore the causal relationship between age and brain health (cortical atrophy, white matter integrity, white matter hyperintensities and cerebral microbleeds in various brain regions) related multiparameter imaging features using two-sample Mendelian randomization. Age was determined as chronological age of the subject. Cortical volume, white matter micro-integrity, white matter hyperintensity volume and cerebral microbleeds of each brain region were included as phenotypes for brain health. Age and imaging of brain health related genetic data were analysed to determine the causal relationship using inverse-variance weighted model, validated by heterogeneity and horizontal pleiotropy variables. Age is causally related to increased volumes of white matter hyperintensities (β = 0.151). For white matter micro-integrity, fibres of the inferior cerebellar peduncle (axial diffusivity β = -0.128, orientation dispersion index β = 0.173), cerebral peduncle (axial diffusivity β = -0.136), superior fronto-occipital fasciculus (isotropic volume fraction β = 0.163) and fibres within the limbic system were causally deteriorated. We also detected decreased cortical thickness of multiple frontal and temporal regions (P < 0.05). Microbleeds were not related with aging (P > 0.05). Aging is a threat of brain health, leading to cortical atrophy mainly in the frontal lobes, as well as the white matter degeneration especially abnormal hyperintensity and deteriorated white matter integrity around the hippocampus.

Widening the Spectrum of Neuroradiological Manifestations of B12 Deficiency: Hyperintensities in the Inferior Cerebellar Peduncles on T2 Images.

Widening the Spectrum of Neuroradiological Manifestations of B12 Deficiency: Hyperintensities in the Inferior Cerebellar Peduncles on T2 Images.

Early, low-dose hydrocortisone and near-term brain connectivity in extremely preterm infants.

Postnatal steroids are used to prevent bronchopulmonary dysplasia in extremely preterm infants but may have adverse effects on brain development. We assessed connectivity metrics of major cerebral and cerebellar white matter pathways at near-term gestational age among infants who did or did not receive a standardized regimen of hydrocortisone during the first 10 days of life. Retrospective cohort study. Infants born <28 weeks: Protocol group (n = 33) received at least 50% and not more than 150% of an intended standard dose of 0.5 mg/kg hydrocortisone twice daily for 7 days, then 0.5 mg/kg per day for 3 days; Non-Protocol group (n = 22), did not receive protocol hydrocortisone or completed <50% of the protocol dose. We assessed group differences in near-term diffusion MRI mean fractional anisotropy (FA) and mean diffusivity (MD) across the corticospinal tract, inferior longitudinal fasciculus, corpus callosum and superior cerebellar peduncle. Groups were comparable in gestational age, post-menstrual age at scan, medical complications, bronchopulmonary dysplasia, and necrotizing enterocolitis. No significant large effect group differences were identified in mean FA or MD in any cerebral or cerebellar tract. Low dose, early, postnatal hydrocortisone was not associated with significant differences in white matter tract microstructure at near-term gestational age. This study compared brain microstructural connectivity as a primary outcome among extremely preterm infants who did or did not receive early postnatal hydrocortisone. Low dose hydrocortisone in the first 10 days of life was not associated with significant differences in white matter microstructure in major cerebral and cerebellar pathways. Hydrocortisone did not have a significant effect on early brain white matter circuits.

Free-Water Imaging in Friedreich Ataxia Using Multi-Compartment Models.

The neurological phenotype of Friedreich ataxia (FRDA) is characterized by neurodegeneration and neuroinflammation in the cerebellum and brainstem. Novel neuroimaging approaches quantifying brain free-water using diffusion magnetic resonance imaging (dMRI) are potentially more sensitive to these processes than standard imaging markers. To quantify the extent of free-water and microstructural change in FRDA-relevant brain regions using neurite orientation dispersion and density imaging (NODDI), and bitensor diffusion tensor imaging (btDTI). Multi-shell dMRI was acquired from 14 individuals with FRDA and 14 controls. Free-water measures from NODDI (FISO) and btDTI (FW) were compared between groups in the cerebellar cortex, dentate nuclei, cerebellar peduncles, and brainstem. The relative sensitivity of the free-water measures to group differences was compared to microstructural measures of NODDI intracellular volume, free-water corrected fractional anisotropy, and conventional uncorrected fractional anisotropy. In individuals with FRDA, FW was elevated in the cerebellar cortex, peduncles (excluding middle), dentate, and brainstem (P < 0.005). FISO was elevated primarily in the cerebellar lobules (P < 0.001). On average, FW effect sizes were larger than all other markers (mean ηρ 2 = 0.43), although microstructural measures also had very large effects in the superior and inferior cerebellar peduncles and brainstem (ηρ 2 > 0.37). Across all regions and metrics, effect sizes were largest in the superior cerebellar peduncles (ηρ 2 > 0.46). Multi-compartment diffusion measures of free-water and neurite integrity distinguish FRDA from controls with large effects. Free-water magnitude in the brainstem and cerebellum provided the greatest distinction between groups. This study supports further applications of multi-compartment diffusion modeling, and investigations of free-water as a measure of disease expression and progression in FRDA. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

White matter integrity assessment in spinocerebellar ataxia type 2 (SCA2) patients

To assess the burden of white matter (WM) damage in the cerebrum and cerebellum of spinocerebellar ataxia type 2 (SCA2) patients in an attempt to identify key regions affected by the neurodegenerative processes using diffusion tensor imaging (DTI). Nine SCA2 patients and 16 age-matched healthy controls were examined twice (SCA2 patients 3.6±0.7 years and controls 3.3±1.0 years apart) on the same 1.5 T scanner by acquiring T1-weighted and diffusion-weighted (b-value=1,000 s/mm2) images. Using tract-based spatial statistics, DTI analysis on fractional anisotropy (FA), mean diffusivity (MD), axial (AD)/radial (RD) diffusivity was performed. At baseline magnetic resonance imaging (MRI), FA was significantly decreased in SCA2 patients in the corticospinal tracts, inferior and superior cerebellar peduncles, middle cerebellar peduncles, cerebral peduncles, right superior and posterior corona radiata. RD was only significantly increased in SCA2 patients in the middle cerebellar peduncles. No significant AD and MD changes were observed. Tract-based spatial statistics (TBSS) analysis between SCA2 patients at baseline and at follow-up showed no significant changes in any of the DTI metrics. DTI is a sensitive tool for following the progression of WM neurodegeneration and severity assessment in patients with SCA2. These findings add to a better understanding of the neurological underpinnings of the symptoms experienced by SCA2 patients.

Multishell diffusion MRI reveals whole-brain white matter changes in HIV.

Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) have been previously used to explore white matter related to human immunodeficiency virus (HIV) infection. While DTI and DKI suffer from low specificity, the Combined Hindered and Restricted Model of Diffusion (CHARMED) provides additional microstructural specificity. We used these three models to evaluate microstructural differences between 35 HIV-positive patients without neurological impairment and 20 healthy controls who underwent diffusion-weighted imaging using three b-values. While significant group effects were found in all diffusion metrics, CHARMED and DKI analyses uncovered wider involvement (80% vs. 20%) of all white matter tracts in HIV infection compared with DTI. In restricted fraction (FR) analysis, we found significant differences in the left corticospinal tract, middle cerebellar peduncle, right inferior cerebellar peduncle, right corticospinal tract, splenium of the corpus callosum, left superior cerebellar peduncle, left superior cerebellar peduncle, pontine crossing tract, left posterior limb of the internal capsule, and left/right medial lemniscus. These are involved in language, motor, equilibrium, behavior, and proprioception, supporting the functional integration that is frequently impaired in HIV-positivity. Additionally, we employed a machine learning algorithm (XGBoost) to discriminate HIV-positive patients from healthy controls using DTI and CHARMED metrics on an ROIwise basis, and unique contributions to this discrimination were examined using Shapley Explanation values. The CHARMED and DKI estimates produced the best performance. Our results suggest that biophysical multishell imaging, combining additional sensitivity and built-in specificity, provides further information about the brain microstructural changes in multimodal areas involved in attentive, emotional and memory networks often impaired in HIV patients.

DTI of Opioid-Exposed Fetuses Using ComBat Harmonization: A Bi-Institutional Study.

The underlying mechanisms leading to altered cognitive, behavioral, and vision outcomes in children with prenatal opioid exposure are yet to be fully understood. Some studies suggest WM alterations in infants and children with prenatal opioid exposure; however, the time course of WM changes is unknown. We aimed to evaluate differences in diffusion tensor imaging MRI parameters in the brain between opioid exposed fetuses and normal controls. This is a pilot, prospective cohort study in which subjects in the third trimester of pregnancy underwent fetal DTI of the brain with 20 noncolinear diffusion directions and a b-value of 500 s/mm2 at 2.5-mm isotropic resolution. The study included a total of 26 fetuses, 11 opioid-exposed (mean gestational age, 32.61 [SD, 2.35] weeks) and 15 unexposed controls (mean gestational age, 31.77 [SD, 1.68] weeks). After we adjusted for gestational age, fractional anisotropy values were significantly higher in opioid-exposed fetuses relative to controls in 8 WM tracts: the bilateral lemniscus (left: P = .017; right: P = .020), middle cerebellar peduncle (P = .027), left inferior cerebellar peduncle (P = .026), right sagittal stratum (P = .040), right fornix stria terminalis (P = .022), right inferior fronto-occipital fasciculus (P = .011), and the right uncinate fasciculus (P = .033). Significant alteration was also identified in other DTI indices involving a series of brain regions. Our data demonstrate initial evidence of cerebral WM microstructural differences between opioid-exposed fetuses and unexposed controls. Further studies in larger patient populations will be needed to fully understand these findings.

Cerebellar and cerebral white matter changes in Parkinson's disease with resting tremor.

Cerebellum modulates the amplitude of resting tremor in Parkinson's disease (PD) via cerebello-thalamo-cortical (CTC) circuit. Tremor-related white matter alterations have been identified in PD patients by pathological studies, but in vivo evidence is limited; the influence of such cerebellar white matter alterations on tremor-related brain network, including CTC circuit, is also unclear. In this study, we investigated the cerebral and cerebellar white matter alterations in PD patients with resting tremor using diffusion tensor imaging (DTI). In this study, 30 PD patients with resting tremor (PDWR), 26 PD patients without resting tremor (PDNR), and 30 healthy controls (HCs) from the Parkinson's Progression Markers Initiative (PPMI) cohort were included. Tract-based spatial statistics (TBSS) and region of interest-based analyses were conducted to determine white matter difference. Correlation analysis between DTI measures and clinical characteristics was also performed. In the whole brain, TBSS and region of interest-based analyses identified higher fractional anisotropy (FA) value, lower mean diffusivity (MD) value, and lower radial diffusivity (RD) in multiple fibers. In the cerebellum, TBSS analysis revealed significantly higher FA value, decreased RD value as well as MD value in multiple cerebellar tracts including the inferior cerebellar peduncle (ICP) and middle cerebellar peduncle (MCP) when comparing the PDWR with HC, and higher FA value in the MCP when compared with PDNR. We identified better white matter integrity in the cerebrum and cerebellum in PDWR indicating a potential association between the cerebral and cerebellar white matter and resting tremor in PD.