Including Diffusion Tensor Imaging Research Articles

Rationale and design of the brain magnetic resonance imaging protocol for FutureMS: a longitudinal multi-centre study of newly diagnosed patients with relapsing-remitting multiple sclerosis in Scotland.

Introduction: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease. MS prevalence varies geographically and is notably high in Scotland. Disease trajectory varies significantly between individuals and the causes for this are largely unclear. Biomarkers predictive of disease course are urgently needed to allow improved stratification for current disease modifying therapies and future targeted treatments aimed at neuroprotection and remyelination. Magnetic resonance imaging (MRI) can detect disease activity and underlying damage non-invasively in vivo at the micro and macrostructural level. FutureMS is a prospective Scottish longitudinal multi-centre cohort study, which focuses on deeply phenotyping patients with recently diagnosed relapsing-remitting MS (RRMS). Neuroimaging is a central component of the study and provides two main primary endpoints for disease activity and neurodegeneration. This paper provides an overview of MRI data acquisition, management and processing in FutureMS. FutureMS is registered with the Integrated Research Application System (IRAS, UK) under reference number 169955. Methods and analysis: MRI is performed at baseline (N=431) and 1-year follow-up, in Dundee, Glasgow and Edinburgh (3T Siemens) and in Aberdeen (3T Philips), and managed and processed in Edinburgh. The core structural MRI protocol comprises T1-weighted, T2-weighted, FLAIR and proton density images. Primary imaging outcome measures are new/enlarging white matter lesions (WML) and reduction in brain volume over one year. Secondary imaging outcome measures comprise WML volume as an additional quantitative structural MRI measure, rim lesions on susceptibility-weighted imaging, and microstructural MRI measures, including diffusion tensor imaging and neurite orientation dispersion and density imaging metrics, relaxometry, magnetisation transfer (MT) ratio, MT saturation and derived g-ratio measures. Conclusions: FutureMS aims to reduce uncertainty around disease course and allow for targeted treatment in RRMS by exploring the role of conventional and advanced MRI measures as biomarkers of disease severity and progression in a large population of RRMS patients in Scotland.

Magnetic Resonance Imaging in (Near-)Term Infants with Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a major cause of neurological sequelae in (near-)term newborns. Despite the use of therapeutic hypothermia, a significant number of newborns still experience impaired neurodevelopment. Neuroimaging is the standard of care in infants with HIE to determine the timing and nature of the injury, guide further treatment decisions, and predict neurodevelopmental outcomes. Cranial ultrasonography is a helpful noninvasive tool to assess the brain before initiation of hypothermia to look for abnormalities suggestive of HIE mimics or antenatal onset of injury. Magnetic resonance imaging (MRI) which includes diffusion-weighted imaging has, however, become the gold standard to assess brain injury in infants with HIE, and has an excellent prognostic utility. Magnetic resonance spectroscopy provides complementary metabolic information and has also been shown to be a reliable prognostic biomarker. Advanced imaging modalities, including diffusion tensor imaging and arterial spin labeling, are increasingly being used to gain further information about the etiology and prognosis of brain injury. Over the past decades, tremendous progress has been made in the field of neonatal neuroimaging. In this review, the main brain injury patterns of infants with HIE, the application of conventional and advanced MRI techniques in these newborns, and HIE mimics, will be described.

Diagnosis and Therapy for Idiopathic Intracranial Hypertension

Idiopathic intracranial hypertension is a pathological state of increased intracranial pressure without intracranial mass lesion, vascular lesion, or hydrocephalus. For the diagnosis of this pathology, various secondary and primary headaches, such as migraine and medication overuse headaches should be excluded. Radiological imaging, including diffusion tensor imaging may show secondary findings of intracranial hypertension. These imaging techniques may be useful to diagnose intracranial hypertension, because at present there is no reliable non-invasive method to measure intracranial pressure. The pathophysiology of idiopathic intracranial hypertension has not been revealed; however there are some theories include, the disorder of cerebrospinal fluid circulation, disturbance of intracranial venous circulation, and metabolic disorders. Headache, nausea, and optic disc edema are frequently observed. The disease is frequently seen in obese females of childbearing age. Several therapies, including weight reduction, medication, and surgery have been studied; however the level of evidence for these therapies remains low.

Quantitative MR-Neurography at 3.0T: Inter-Scanner Reproducibility.

BackgroundQuantitative MR-neurography (MRN) is increasingly applied, however, the impact of the MR-scanner on the derived parameters is unknown. Here, we used different 3.0T MR scanners and applied comparable MR-sequences in order to quantify the inter-scanner reproducibility of various MRN parameters of the sciatic nerve.MethodsTen healthy volunteers were prospectively examined at three different 3.0T MR scanners and underwent MRN of their sciatic nerve using comparable imaging protocols including diffusion tensor imaging (DTI) and T2 relaxometry. Subsequently, inter-scanner agreement was assessed for seven different parameters by calculating the intraclass correlation coefficients (ICCs) and the standard error of measurement (SEM).ResultsAssessment of inter-scanner reliability revealed good to excellent agreement for T2 (ICC: 0.846) and the quantitative DTI parameters, such as fractional anisotropy (FA) (ICC: 0.876), whereas moderate agreement was observed for proton spin density (PD) (ICC: 0.51). Analysis of variance identified significant inter-scanner differences for several parameters, such as FA (p < 0.001; p = 0.02), T2 (p < 0.01) and PD (p = 0.02; p < 0.01; p = 0.02). Calculated SEM values were mostly within the range of one standard deviation of the absolute mean values, for example 0.033 for FA, 4.12 ms for T2 and 27.8 for PD.ConclusionThis study quantifies the measurement imprecision for peripheral nerve DTI and T2 relaxometry, which is associated with the use of different MR scanners. The here presented values may serve as an orientation of the possible scanner-associated fluctuations of MRN biomarkers, which can occur under similar conditions.

Quantitative Parameters of Diffusion Spectrum Imaging: HER2 Status Prediction in Patients With Breast Cancer.

ObjectiveTo explore the value of quantitative parameters derived from diffusion spectrum imaging (DSI) in preoperatively predicting human epidermal growth factor receptor 2 (HER2) status in patients with breast cancer.MethodsIn this prospective study, 114 and 56 female patients with invasive ductal carcinoma were consecutively included in a derivation cohort and an independent validation cohort, respectively. Each patient was categorized into HER2-positive or HER2-negative groups based on the pathologic result. All patients underwent DSI and conventional MRI including dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI). The tumor size, type of the time-signal intensity curve (TIC) from DCE-MRI, apparent diffusion coefficient (ADC) from DWI, and quantitative parameters derived from DSI, including diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), mean apparent propagator (MAP), and neurite orientation dispersion and density imaging (NODDI) of primary tumors, were measured and compared between the HER2-positive and HER2-negative groups in the derivation cohort. Univariable and multivariable logistic regression analyses were used to determine the potential independent predictors of HER2 status. The discriminative ability of quantitative parameters was assessed by receiver operating characteristic (ROC) curve analyses and validated in the independent cohort.ResultsIn the derivation cohort, the tumor size, TIC type, and ADC values did not differ between the HER2-positive and HER2-negative groups (p = 0.126–0.961). DSI quantitative parameters including axial kurtosis of DKI (DKI_AK), non-Gaussianity (MAP_NG), axial non-Gaussianity (MAP_NGAx), radial non-Gaussianity (MAP_NGRad), return-to-origin probability (MAP_RTOP), return-to-axis probability of MAP (MAP_RTAP), and intracellular volume fraction of NODDI (NODDI_ICVF) were lower in the HER2-positive group than in the HER2-negative group (p ≤ 0.001–0.035). DSI quantitative parameters including radial diffusivity (DTI_RD), mean diffusivity of DTI (DTI_MD), mean squared diffusion (MAP_MSD), and q-space inverse variance of MAP (MAP_QIV) were higher in the HER2-positive group than in the HER2-negative group (p = 0.016–0.049). The ROC analysis showed that the area under the curve (AUC) of ADC was 0.632 and 0.568, respectively, in the derivation and validation cohorts. The AUC values of DSI quantitative parameters ranged from 0.628 to 0.700 and from 0.673 to 0.721, respectively, in the derivation and validation cohorts. Logistic regression analysis showed that only NODDI_ICVF was an independent predictor of HER2 status (p = 0.001), with an AUC of 0.700 and 0.721, respectively, in the derivation and validation cohorts.ConclusionsDSI could be helpful for preoperative prediction of HER2, but DSI alone may not be sufficient in predicting HER2 status preoperatively in patients with breast cancer.

Magnetic Resonance Imaging in Tauopathy Animal Models.

The microtubule-associated protein tau plays an important role in tauopathic diseases such as Alzheimer’s disease and primary tauopathies such as progressive supranuclear palsy and corticobasal degeneration. Tauopathy animal models, such as transgenic, knock-in mouse and rat models, recapitulating tauopathy have facilitated the understanding of disease mechanisms. Aberrant accumulation of hyperphosphorylated tau contributes to synaptic deficits, neuroinflammation, and neurodegeneration, leading to cognitive impairment in animal models. Recent advances in molecular imaging using positron emission tomography (PET) and magnetic resonance imaging (MRI) have provided valuable insights into the time course of disease pathophysiology in tauopathy animal models. High-field MRI has been applied for in vivo imaging in animal models of tauopathy, including diffusion tensor imaging for white matter integrity, arterial spin labeling for cerebral blood flow, resting-state functional MRI for functional connectivity, volumetric MRI for neurodegeneration, and MR spectroscopy. In addition, MR contrast agents for non-invasive imaging of tau have been developed recently. Many preclinical MRI indicators offer excellent translational value and provide a blueprint for clinical MRI in the brains of patients with tauopathies. In this review, we summarized the recent advances in using MRI to visualize the pathophysiology of tauopathy in small animals. We discussed the outstanding challenges in brain imaging using MRI in small animals and propose a future outlook for visualizing tau-related alterations in the brains of animal models.

Associations between diffusion MRI microstructure and cerebrospinal fluid markers of Alzheimer's disease pathology and neurodegeneration along the Alzheimer's disease continuum.

White matter (WM) degeneration is a critical component of early Alzheimer's disease (AD) pathophysiology. Diffusion-weighted imaging (DWI) models, including diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and mean apparent propagator MRI (MAP-MRI), have the potential to identify early neurodegenerative WM changes associated with AD. We imaged 213 (198 cognitively unimpaired) aging adults with DWI and used tract-based spatial statistics to compare 15 DWI metrics of WM microstructure to 9 cerebrospinal fluid (CSF) markers of AD pathology and neurodegeneration treated as continuous variables. We found widespread WM injury in AD, as indexed by robust associations between DWI metrics and CSF biomarkers. MAP-MRI had more spatially diffuse relationships with Aβ42/40 and pTau, compared with NODDI and DTI. Our results suggest that WM degeneration may be more pervasive in AD than is commonly appreciated and that innovative DWI models such as MAP-MRI may provide clinically viable biomarkers of AD-related neurodegeneration in the earliest stages of AD progression.

Study of renal parenchymal changes by diffusion tensor imaging in diabetic nephropathy.

PurposeTo evaluate differences in diffusion imaging parameters, including fractional anisotropy (FA) and the apparent diffusion coefficient (ADC), in control and diabetic subjects, and to assess changes in these parameters to patient’s urine albumin/protein levels, estimated glomerular filtration rate (eGFR), and glycated haemoglobin (HbA1c).Material and methodsThis is a cross-sectional analytical study involving 100 patients who underwent diffusion imaging including diffusion tensor imaging (DTI) of the kidneys in our hospital from 2019 to 2020. Diffusion imaging parameters (ADC and FA) were obtained from the medulla and cortex of both kidneys using dedicated software. Statistical analysis was done.ResultsOut of 100 subjects, 27 were controls and 73 were diabetics (19 normoalbuminuric, 23 microalbuminuric, and 31 proteinuric). The medullary FA (0.419 ± 0.024 vs. 0.346 ± 0.042), cortical FA (0.194 ± 0.035 vs. 0.303 ± 0.067), and cortical ADC (3.307 ± 0.341 vs. 2.309 ± 0.515) values showed significant differences between controls and diabetics. Medullary FA and cortical ADC values showed a decreasing trend with an increasing amount of albumin/protein in the urine, decreasing renal function (reducing eGFR), and increasing HbA1c, whereas the trend was opposite for cortical FA. In addition, on ROC curve analysis a cut-off value for medullary FA of 0.4 had a sensitivity of 64% and specificity of 80.95% to differentiate healthy volunteers and diabetics with normo-albuminuria.ConclusionsDTI has the potential to be a promising non-invasive test for the detection of early renal parenchymal changes in diabetic nephropathy.

Microstructural Tissue Changes in a Rat Model of Mild Traumatic Brain Injury.

Our study investigates the potential of diffusion MRI (dMRI), including diffusion tensor imaging (DTI), fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI), to detect microstructural tissue abnormalities in rats after mild traumatic brain injury (mTBI). The brains of sham-operated and mTBI rats 35 days after lateral fluid percussion injury were imaged ex vivo in a 11.7-T scanner. Voxel-based analyses of DTI-, fixel- and NODDI-based metrics detected extensive tissue changes in directly affected brain areas close to the primary injury, and more importantly, also in distal areas connected to primary injury and indirectly affected by the secondary injury mechanisms. Histology revealed ongoing axonal abnormalities and inflammation, 35 days after the injury, in the brain areas highlighted in the group analyses. Fractional anisotropy (FA), fiber density (FD) and fiber density and fiber bundle cross-section (FDC) showed similar pattern of significant areas throughout the brain; however, FA showed more significant voxels in gray matter areas, while FD and FDC in white matter areas, and orientation dispersion index (ODI) in areas most damage based on histology. Region-of-interest (ROI)-based analyses on dMRI maps and histology in selected brain regions revealed that the changes in MRI parameters could be attributed to both alterations in myelinated fiber bundles and increased cellularity. This study demonstrates that the combination of dMRI methods can provide a more complete insight into the microstructural alterations in white and gray matter after mTBI, which may aid diagnosis and prognosis following a mild brain injury.

A high temporal/spatial resolution neuro-architecture study of rodent brain by wideband echo planar imaging

Latest simultaneous multi-slice (SMS) methods greatly benefit MR efficiency for recent studies using parallel imaging technique. However, these methods are limited by the requirement of array coils. The proposed Coherent Wideband method, which employs an extended field of view to separate multiple excited slices, can be applied to any existing MRI instrument, even those without array coils. In this study, the Coherent Wideband echo-planar imaging method was implemented on 7 T animal MRI to exhibit comprehensive enhancements in neuro-architecture, including diffusion tensor imaging (DTI) and functional MR studies (fMRI). Under the same scan time, the time-saving effect can be manipulated to increase the number of averages for DTI SNR improvement, reducing fractional anisotropy difference by 56.9% (from 0.072 to 0.041) and the deviation angle by 64% (from 25.3° to 16.2°). In summary, Coherent Wideband Echo Planar Imaging (EPI) will provide faster, higher resolution, thinner slice, or higher SNR imaging for precision neuro-architecture studies.

Brain networks in migraine with and without aura: An exploratory arterial spin labeling MRI study.

The aim of this exploratory study was to investigate the underlying pathomechanisms of migraine with aura (MA) and migraine without aura (MO) in the interictal phase using a connectivity analysis. We prospectively enrolled patients who were newly diagnosed with migraine. All patients underwent brain MRI, including diffusion tensor imaging and arterial spin labeling perfusion MRI. We analyzed the differences between patients with MA and those with MO in structural connectivity based on diffusion tensor imaging and functional connectivity based on arterial spin labeling perfusion MRI using a graph theoretical analysis. We enrolled 58 patients with migraine (11 patients with MA and 47 patients with MO). There were no differences between patients with MA and those with MO in the network measures of global structural connectivity. However, differences in global functional connectivity were found between the two groups. The assortative coefficient was lower in patients with MA than in those with MO (-0.050 vs. -0.012, p=.017). There were no differences in local structural and functional connectivity between patients with MA and those with MO. We found differences in global functional connectivity between patients with MO and those with MA. The study of MA and MO using a connectivity analysis may shed light on migraine pathophysiology. We suggest it is worthwhile to investigate if changes in functional connectivity may serve as novel biomarkers in MA. In this regard, ASL MRI appears to be valuable in the context of network analysis, but further studies are needed to confirm our findings.

Alterations of structural connectivity and structural co-variance network in focal cortical dysplasia

BackgroundThe aim of this study was to investigate alterations in structural connectivity and structural co-variance network in patients with focal cortical dysplasia (FCD).MethodsWe enrolled 37 patients with FCD and 35 healthy controls. All subjects underwent brain MRI with the same scanner and with the same protocol, which included diffusion tensor imaging (DTI) and T1-weighted imaging. We analyzed the structural connectivity based on DTI, and structural co-variance network based on the structural volume with T1-weighted imaging. We created a connectivity matrix and obtained network measures from the matrix using the graph theory. We tested the difference in network measure between patients with FCD and healthy controls.ResultsIn the structural connectivity analysis, we found that the local efficiency in patients with FCD was significantly lower than in healthy controls (2.390 vs. 2.578, p = 0.031). Structural co-variance network analysis revealed that the mean clustering coefficient, global efficiency, local efficiency, and transitivity were significantly decreased in patients with FCD compared to those in healthy controls (0.527 vs. 0.635, p = 0.036; 0.545 vs. 0.648, p = 0.026; 2.699 vs. 3.801, p = 0.019; 0.791 vs. 0.954, p = 0.026, respectively).ConclusionsWe demonstrate that there are significant alterations in structural connectivity, based on DTI, and structural co-variance network, based on the structural volume, in patients with FCD compared to healthy controls. These findings suggest that focal lesions with FCD could affect the whole-brain network and that FCD is a network disease.

The Contribution of White Matter Diffusion and Cortical Perfusion Pathology to Vascular Cognitive Impairment: A Multimode Imaging-Based Machine Learning Study.

Widespread impairments in white matter and cerebrovascular integrity have been consistently implicated in the pathophysiology of patients with small vessel disease (SVD). However, the neural circuit mechanisms that underlie the developing progress of clinical cognitive symptoms remain largely elusive. Here, we conducted cross-modal MRI scanning including diffusion tensor imaging and arterial spin labeling in a cohort of 113 patients with SVD, which included 74 patients with vascular mild cognitive impairment (vMCI) and 39 patients without vMCI symptoms, and hence developed multimode imaging-based machine learning models to identify markers that discriminated SVD subtypes. Diffusion and perfusion features, respectively, extracted from individual white matter and gray matter regions were used to train three sets of classifiers in a nested 10-fold fashion: diffusion-based, perfusion-based, and combined diffusion-perfusion-based classifiers. We found that the diffusion-perfusion combined classifier achieved the highest accuracy of 72.57% with leave-one-out cross-validation, with the diffusion features largely spanning the capsular lateral pathway of the cholinergic tracts, and the perfusion features mainly distributed in the frontal-subcortical-limbic areas. Furthermore, diffusion-based features within vMCI group were associated with performance on executive function tests. We demonstrated the superior accuracy of using diffusion-perfusion combined multimode imaging features for classifying vMCI subtype out of a cohort of patients with SVD. Disruption of white matter integrity might play a critical role in the progression of cognitive impairment in patients with SVD, while malregulation of coritcal perfusion needs further study.

Detection of early changes in the post-radiosurgery vestibular schwannoma microenvironment using multinuclear MRI

Stereotactic radiosurgery (SRS) is an established, effective therapy against vestibular schwannoma (VS). The mechanisms of tumour response are, however, unknown and in this study we sought to evaluate changes in the irradiated VS tumour microenvironment through a multinuclear MRI approach. Five patients with growing sporadic VS underwent a multi-timepoint comprehensive MRI protocol, which included diffusion tensor imaging (DTI), dynamic contrast-enhanced (DCE) MRI and a spiral 23Na-MRI acquisition for total sodium concentration (TSC) quantification. Post-treatment voxelwise changes in TSC, DTI metrics and DCE-MRI derived microvascular biomarkers (Ktrans, ve and vp) were evaluated and compared against pre-treatment values. Changes in tumour TSC and microvascular parameters were observable as early as 2 weeks post-treatment, preceding changes in structural imaging. At 6 months post-treatment there were significant voxelwise increases in tumour TSC (p < 0.001) and mean diffusivity (p < 0.001, repeated-measures ANOVA) with marked decreases in tumour microvascular parameters (p < 0.001, repeated-measures ANOVA). This study presents the first in vivo evaluation of alterations in the VS tumour microenvironment following SRS, demonstrating that changes in tumour sodium homeostasis and microvascular parameters can be imaged as early as 2 weeks following treatment. Future studies should seek to investigate these clinically relevant MRI metrics as early biomarkers of SRS response.

White Matter Microstructural Differences in Youth With Classical Congenital Adrenal Hyperplasia.

Gray matter morphology in the prefrontal cortex and subcortical regions, including the hippocampus and amygdala, are affected in youth with classical congenital adrenal hyperplasia (CAH). It remains unclear if white matter connecting these aforementioned brain regions is compromised in youth with CAH. To examine brain white matter microstructure in youth with CAH compared to controls. A cross-sectional sample of 23 youths with CAH due to 21-hydroxylase deficiency (12.9 ± 3.5 year; 61% female) and 33 healthy controls (13.1 ± 2.8 year; 61% female) with 3T multishell diffusion-weighted magnetic resonance brain scans. Complementary modeling approaches, including diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), to examine in vivo white matter microstructure in six white matter tracts that innervate the prefrontal and subcortical regions. DTI showed CAH youth had lower fractional anisotropy in both the fornix and stria terminalis and higher mean diffusivity in the fornix compared to controls. NODDI modeling revealed that CAH youth have a significantly higher orientation dispersion index in the stria terminalis compared to controls. White matter microstructural integrity was associated with smaller hippocampal and amygdala volumes in CAH youth. These patterns of microstructure reflect less restricted water diffusion likely due to less coherency in oriented microstructure. These results suggest that white matter microstructural integrity in the fornix and stria terminalis is compromised and may be an additional related brain phenotype alongside affected hippocampus and amygdala neurocircuitry in individuals with CAH.

The Neurological Manifestations of Phelan-McDermid Syndrome

Phelan-McDermid syndrome (PMS) is a genetic disorder, caused by haploinsufficiency of the SHANK3 gene on chromosome 22q13.3. PMS is characterized by neurobehavioral symptoms and signs including intellectual disability, speech and language impairment, autism spectrum disorder (ASD), hypotonia, and other motor abnormalities. In the brain, SHANK3 is expressed in neurons, especially in the synapse, and encodes a master scaffolding protein that forms a key framework in the postsynaptic density of glutamatergic synapses. Mutations in SHANK3 have also been identified in individuals with ASD, intellectual deficiency (ID), and schizophrenia. Shank3 deficient mice have defects in basal glutamatergic synaptic transmission in the hippocampus, and in synaptic transmission plasticity, including deficits in long-term potentiation, and show behavioral deficits compatible with the clinical manifestations of PMS. The PMS phenotype varies between affected individuals, but ID and speech and language impairment are present in all cases. ASD is present in a great majority of these individuals. Neurological examination demonstrates hypotonia and abnormalities of motor coordination, visual motor coordination, and gait in the majority of affected individuals. Sleep disturbances and increased pain tolerance are frequent parental complaints. Seizures and epilepsy are common, affecting more than 40% of individuals. Brain magnetic resonance imaging abnormalities include corpus callosum hypoplasia, delayed myelination and white matter abnormalities, dilated ventricles, and arachnoid cysts. Recent advanced imaging anatomic studies including diffusion tensor imaging, point to abnormal brain connectivity. The natural history of the syndrome is not yet fully known, but some individuals with PMS have a later onset of psychiatric illnesses including bipolar disease, accompanied by functional and neurological regression. Individuals with the syndrome are treated symptomatically. Advances in understanding the pathophysiology of this syndrome and the generation of animal models have raised opportunities for a biological cure for PMS. A pilot clinical trial with insulin-like growth factor-1 (IGF-1) showed positive effects on some behavioral core symptoms.

Characterizing white matter alterations subject to clinical laterality in drug-naïve de novo Parkinson's disease.

ABSTRACTParkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by a range of motor and nonmotor symptoms, often with the motor dysfunction initiated unilaterally. Knowledge regarding disease‐related alterations in white matter pathways can effectively help improve the understanding of the disease and propose targeted treatment strategies. Microstructural imaging techniques, including diffusion tensor imaging (DTI), allows inspection of white matter integrity to study the pathogenesis of various neurological conditions. Previous voxel‐based analyses with DTI measures, such as fractional anisotropy and mean diffusivity have uncovered changes in brain regions that are associated with PD, but the conclusions were inconsistent, partially due to small patient cohorts and the lack of consideration for clinical laterality onset, particularly in early PD. Fixel‐based analysis (FBA) is a recent framework that offers tract‐specific insights regarding white matter health, but very few FBA studies on PD exist. We present a study that reveals strengthened and weakened white matter integrity that is subject to symptom laterality in a large drug‐naïve de novo PD cohort using complementary DTI and FBA measures. The findings suggest that the disease gives rise to tissue degeneration and potential re‐organization in the early stage.

Brain Development and Maternal Behavior in Relation to Cognitive and Language Outcomes in Preterm-Born Children

Background: Children born very preterm (<=32 weeks gestational age) show poorer cognitive and language development compared to their term-born peers. The importance of positive maternal-child interactions for promoting neurodevelopment is well-established. However, little is known about whether sensitive maternal behaviors can buffer the association of early brain dysmaturation with cognitive and language performance. Methods: Infants born very preterm were recruited from the neonatal intensive care unit for a prospective, observational cohort study. Chart review was conducted prospectively from birth to discharge. MRI was acquired at ~32 weeks postmenstrual age and again at term-equivalent age, including diffusion tensor imaging. Fractional anisotropy, a quantitative measure of brain maturation, was obtained from 11 bilateral regions of interest in the cortical gray matter. At 3 years corrected age, neurodevelopmental testing (Bayley Scales of Infant & Toddler Development, Third Edition [Bayley-III]) was administered, and parent-child interaction was filmed. One hundred and forty-six infants with neonatal brain imaging and follow-up data were included for analysis. We examined whether maternal sensitivity interacted with mean fractional anisotropy values to predict Cognitive and Language scores at 3 years corrected age. Findings: Higher maternal sensitivity significantly moderated cortical fractional anisotropy values at term-equivalent age to predict higher Bayley-III Cognitive (s=1.72, P=0.05, R2=0.23), and Language Scores (s=1.91, P=0.03, R2=0.25). Interpretation: This suggests that positive parenting following early brain dysmaturation may provide an opportunity to support more optimal neurodevelopment in children born very preterm. Funding Information: Canadian Institutes for Health Research operating grant MOP-79262 (SPM) and MOP-86489 (REG). Declaration of Interests: The authors have no competing interests to disclose. Ethics Approval Statement: This study was approved by the Clinical Research Ethics Board at the University of British Columbia and BC Children’s and Women’s Hospitals. Parent written informed consent was obtained according to the Declaration of Helsinki.

Recent Advances in Parameter Inference for Diffusion MRI Signal Models.

In this paper, fundamentals and recent progress for obtaining biological features quantitatively by using diffusion MRI are reviewed. First, a brief description of diffusion MRI history, application, and development was presented. Then, well-known parametric models including diffusion tensor imaging (DTI), diffusional kurtosis imaging (DKI), and neurite orientation dispersion diffusion imaging (NODDI) are introduced with several classifications in various viewpoints with other modeling schemes. In addition, this review covers mathematical generalization and examples of methodologies for the model parameter inference from conventional fitting to recent machine learning approaches, which is called Q-space learning (QSL). Finally, future perspectives on diffusion MRI parameter inference are discussed with the aspects of imaging modeling and simulation.

Cerebral Visual Impairment Characterized by Abnormal Visual Orienting Behavior With Preserved Visual Cortical Activation.

PurposeChildren with cerebral visual impairment (CVI) often have abnormal visual orienting behaviors due to impaired or damaged visual cortex. Alternatively, visual-cortical function is intact but visual information is not transformed downstream into an appropriate oculomotor output (visuomotor dysfunction). We examined visual, anatomic, and oculomotor assessments to distinguish visuomotor dysfunction from CVI associated with severely reduced visual-cortical response.MethodsWe reviewed the medical records from children with CVI having abnormal visual orienting behaviors, normal ocular examinations, and born near term. Relevant data were visual evoked potentials (VEPs), Teller card acuity, eye movements recorded by video-oculography (VOG), and neuroimaging (magnetic resonance imaging [MRI]) including diffusion tensor imaging (DTI) tractography.ResultsThirty subjects had visuomotor dysfunction based on a normal VEP; of these 33% had a normal MRI and 67% had white matter abnormalities associated with metabolic disease and/or decreased volume of brain parenchyma. VOG recordings showed smooth pursuit gains were uniformly reduced and saccades were dysmetric but followed the main sequence. Ten subjects had severe CVI based on VEPs at noise levels; visual acuities and MRI findings overlapped those of the visuomotor dysfunction group. Developmental delay, seizures, microcephaly, and hypotonia were common across all groups. All subjects with an abnormal conventional MRI had abnormal metrics on DTI tractography from the occipital lobe.ConclusionsA subset of patients with CVI have abnormal visual orienting behaviors despite a normal VEP (visuomotor dysfunction). A majority have abnormal white matter metrics on tractography suggesting a downstream defect in sensorimotor transformation. Clinically, visuomotor dysfunction is indistinguishable from severe CVI.