Neurite Orientation Dispersion and Density Imaging in Multiple Sclerosis: A Systematic Review.

Diffusion-weighted imaging has been applied to investigate alterations in multiple sclerosis (MS). In the last years, advanced diffusion models were used to identify subtle changes and early lesions in MS. Among these models, neurite orientation dispersion and density imaging (NODDI) is an emerging approach, quantifying specific neurite morphology in both grey (GM) and white matter (WM) tissue and increasing the specificity of diffusion imaging. In this systematic review, we summarized the NODDI findings in MS. A search was conducted on PubMed, Scopus, and Embase, which yielded a total number of 24 eligible studies. Compared to healthy tissue, these studies identified consistent alterations in NODDI metrics involving WM (neurite density index), and GM lesions (neurite density index), or normal-appearing WM tissue (isotropic volume fraction and neurite density index). Despite some limitations, we pointed out the potential of NODDI in MS to unravel microstructural alterations. These results might pave the way to a deeper understanding of the pathophysiological mechanism of MS. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.

Cerebellar Microstructural Abnormalities in Parkinson's Disease: a Systematic Review of Diffusion Tensor Imaging Studies.

Diffusion tensor imaging (DTI) is now having a strong momentum in research to evaluate the neural fibers of the CNS. This technique can study white matter (WM) microstructure in neurodegenerative disorders, including Parkinson's disease (PD). Previous neuroimaging studies have suggested cerebellar involvement in the pathogenesis of PD, and these cerebellum alterations can correlate with PD symptoms and stages. Using the PRISMA 2020 framework, PubMed and EMBASE were searched to retrieve relevant articles. Our search revealed 472 articles. After screening titles and abstracts, and full-text review, and implementing the inclusion criteria, 68 papers were selected for synthesis. Reviewing the selected studies revealed that the patterns of reduction in cerebellum WM integrity, assessed by fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity measures can differ symptoms and stages of PD. Cerebellar diffusion tensor imaging (DTI) changes in PD patients with "postural instability and gait difficulty" are significantly different from "tremor dominant" PD patients. Freezing of the gate is strongly related to cerebellar involvement depicted by DTI. The "reduced cognition," "visual disturbances," "sleep disorders," "depression," and "olfactory dysfunction" are not related to cerebellum microstructural changes on DTI, while "impulsive-compulsive behavior" can be linked to cerebellar WM alteration. Finally, higher PD stages and longer disease duration are associated with cerebellum white matter alteration depicted by DTI. Depiction of cerebellar white matter involvement in PD is feasible by DTI. There is an association with disease duration and severity and several clinical presentations with DTI findings. This clinical-imaging association may eventually improve disease management.

White Matter Microstructure Associated with the Antidepressant Effects of Deep Brain Stimulation in Treatment-Resistant Depression: A Review of Diffusion Tensor Imaging Studies.

Treatment-resistant depression (TRD) is a severe disorder characterized by high relapse rates and decreased quality of life. An effective strategy in the management of TRD is deep brain stimulation (DBS), a technique consisting of the implantation of electrodes that receive a stimulation via a pacemaker-like stimulator into specific brain areas, detected through neuroimaging investigations, which include the subgenual cingulate cortex (sgCC), basal ganglia, and forebrain bundles. In this context, to improve our understanding of the mechanism underlying the antidepressant effects of DBS in TRD, we collected the results of diffusion tensor imaging (DTI) studies exploring how WM microstructure is associated with the therapeutic effects of DBS in TRD. A search on PubMed, Web of Science, and Scopus identified 11 investigations assessing WM microstructure in responders and non-responders to DBS. Altered WM microstructure, particularly in the sgCC, medial forebrain bundle, cingulum bundle, forceps minor, and uncinate fasciculus, was associated with the antidepressant effect of DBS in TRD. Overall, the results show that DBS targeting selective brain regions, including the sgCC, forebrain bundle, cingulum bundle, rectus gyrus, anterior limb of the internal capsule, forceps minor, and uncinate fasciculus, seem to be effective for the treatment of TRD.

Distinct patterns of hippocampal subfield volume loss in left and right mesial temporal lobe epilepsy.

OBJECTIVE: To investigate the pattern and severity of hippocampal subfield volume loss in patients with left and right mesial temporal lobe epilepsy (mTLE) using quantitative MRI volumetric analysis. METHODS: A total of 21 left and 14 right mTLE subjects, as well as 15 healthy controls, were enrolled in this cross-sectional study. A publically available magnetic resonance imaging (MRI) brain volumetry system (volBrain) was used for volumetric analysis of hippocampal subfields. The T1-weighted images were processed with a HIPS pipeline. RESULTS: A distinct pattern of hippocampal subfield atrophy was found between left and right mTLE patients when compared with controls. Patients with left mTLE exhibited ipsilateral hippocampal atrophy and segmental volume depletion of the Cornu Ammonis (CA) 2/CA3, CA4/dentate gyrus (DG), and strata radiatum-lacunosum-moleculare (SR-SL-SM). Those with right mTLE exhibited similar ipsilateral hippocampal atrophy but with additional segmental CA1 volume depletion. More extensive bilateral subfield volume loss was apparent with right mTLE patients. CONCLUSION: We demonstrate that left and right mTLE patients show a dissimilar pattern of hippocampal subfield atrophy, suggesting the pathophysiology of epileptogenesis in left and right mTLE to be different.

Brain microstructural abnormalities in type 2 diabetes mellitus: A systematic review of diffusion tensor imaging studies.

Type 2 diabetes mellitus (T2DM) is associated with deficits in the structure and function of the brain. Diffusion tensor imaging (DTI) is a highly sensitive method for characterizing cerebral tissue microstructure. Using PRISMA guidelines, we identified 29 studies which have demonstrated widespread brain microstructural impairment and topological network disorganization in patients with T2DM. Most consistently reported structures with microstructural abnormalities were frontal, temporal, and parietal lobes in the lobar cluster; corpus callosum, cingulum, uncinate fasciculus, corona radiata, and internal and external capsules in the white matter cluster; thalamus in the subcortical cluster; and cerebellum. Microstructural abnormalities were correlated with pathological derangements in the endocrine profile as well as deficits in cognitive performance in the domains of memory, information-processing speed, executive function, and attention. Altogether, the findings suggest that the detrimental effects of T2DM on cognitive functions might be due to microstructural disruptions in the central neural structures.

Structural white matter alterations as compensatory mechanisms in Parkinson's disease: A systematic review of diffusion tensor imaging studies.

Compensation is described as normal or near to normal performance in Parkinson's disease (PD), despite the ongoing neural loss. Functional compensation typically proceeds in an inverse U-shaped manner: compensation initiates in the prodromal phase, followed by an increasing episode until plateauing and diminishes in the advanced stages of the disease. The first evidence of the structural compensation was reported by functional magnetic resonance imaging studies. Recent studies, which have used diffusion tensor imaging (DTI) as the basis for their investigation, have shown improved white matter diffusional properties both in motor- and non-motor-related structures in association with improved clinical scores in patients with PD. The majority of DTI studies have demonstrated microstructural compensation in the prodromal/early stages of PD at the regional scale. However, there have been reports of compensation in later stages of the disease and the whole-brain/network scale that are probably due to the heterogeneous nature of PD. Although serving as a promising beginning to characterize compensation, lots remain to be clarified in understanding the underlying mechanisms of compensation and its structural pattern in PD. The existing knowledge gap necessitates studies that their main research questions are focused on structural compensation. This requirement becomes more apparent because structural compensation evidence has mostly emerged from the post hoc analysis of data and incidental findings of studies. Thus, future studies are required to investigate compensatory microstructural changes in PD to clarify the exact underlying mechanisms. These studies would also provide a basis to develop clinical improvements in the early diagnosis and management of PD.

White matter microstructure in fetal alcohol spectrum disorders: A systematic review of diffusion tensor imaging studies.

Diffusion tensor imaging (DTI) has revolutionized our understanding of the neural underpinnings of alcohol teratogenesis. This technique can detect alterations in white matter in neurodevelopmental disorders, such as fetal alcohol spectrum disorder (FASD). Using Prisma guidelines, we identified 23 DTI studies conducted on individuals with prenatal alcohol exposure (PAE). These studies confirm the widespread nature of brain damage in PAE by reporting diffusivity alterations in commissural, association, and projection fibers; and in relation to increasing cognitive impairment. Reduced integrity in terms of lower fractional anisotropy (FA) and higher mean diffusivity (MD) and radial diffusivity (RD) is reported more consistently in the corpus callosum, cerebellar peduncles, cingulum, and longitudinal fasciculi connecting frontal and temporoparietal regions. Although these interesting results provide insight into FASD neuropathology, it is important to investigate the clinical diversity of this disorder for better treatment options and prediction of progression. The aim of this review is to provide a summary of different patterns of neural structure between PAE and typically developed individuals. We further discuss the association of alterations in diffusivity with demographic features and symptomatology of PAE. With the accumulated knowledge of the neural correlates of FASD presenting symptoms, a comprehensive understanding of the heterogeneity in FASD will potentially improve the disease management and will highlight the diagnostic challenges and potential areas of future research avenues, where neural markers may be beneficial.

Association of olfaction dysfunction with brain microstructure in prodromal Parkinson disease.

OBJECTIVE: Although olfaction dysfunction is now considered as an established clinical marker of prodromal Parkinson disease (PD), little is known about the neural underpinnings of olfaction dysfunction in the prodromal phase of PD. The aim of this study was to examine the microstructural association of olfaction in prodromal PD compared to early stage drug-naïve PD patients. METHODS: Diffusion MRI connectometry was conducted on 18 early PD and 17 prodromal PD patients to investigate the differences in group in terms of altered connectivity, i.e., integrity of white matter tracts, and subsequently to study the correlation of University of Pennsylvania Smell Identification Test (UPSIT) score to white matter integrity in each group using a multiple regression model considering age, sex, RBD, and MoCA, as covariates. RESULTS: Individuals with prodromal PD had significantly higher quantitative anisotropy (QA) comparing with PD patients in bilateral middle cerebellar peduncles and right arcuate fasciculus. Multiple regression analysis in prodromal PD demonstrated positive association between UPSIT score and connectivity in left and right subgenual cingulum, right inferior fronto-occipital fasciculus, left corticospinal tract, left parietopontine, left corticothalamic tract, and the body and the splenium of corpus callosum. CONCLUSION: These results indicate that PD and prodromal PD patients, which were matched for sex, UPSIT, and MoCA scores, have different white matter fiber architecture. Thus, it is postulated that olfaction dysfunction in prodromal and early clinical phases of PD may involve distinct pathogenesis. Increased network connectivity in prodromal and early PD may suggest the neural compensation.

White matter correlates of disease duration in patients with temporal lobe epilepsy: updated review of literature.

BACKGROUND: Medial temporal lobe epilepsy (mTLE) has been associated with widespread white mater (WM) alternations in addition to mesial temporal sclerosis (MTS). Herein, we aimed to investigate the correlation between disease duration and WM structural abnormalities in mTLE using diffusion MRI (DMRI) connectometry approach. METHOD: DMRI connectometry was conducted on 24 patients with mTLE. A multiple regression model was used to investigate white matter tracts with microstructural correlates to disease duration, controlling for age and sex. DMRI data were processed in the MNI space using q-space diffeomorphic reconstruction to obtain the spin distribution function (SDF). The SDF values were converted to quantitative anisotropy (QA) and used in further analyses. RESULTS: Connectometry analysis identified impaired white matter QA of the following fibers to be correlated with disease duration: bilateral retrosplenial cingulum, bilateral fornix, right inferior longitudinal fasciculus (ILF), and genu of corpus callosum (CC) (FDR = 0.009). CONCLUSION: Our results were obtained from DMRI connectometry, which indicates the connectivity and the level of diffusion in nerve fibers rather just the direction of diffusion. Compared to previous studies investigating the correlation between duration of epilepsy and white matter integrity in mTLE patients, we detected broader and somewhat different associations in midline structures and component of limbic system. However, further studies with larger sample sizes are required to elucidate previous and current results.

Comparison of structural connectivity in Parkinson's disease with depressive symptoms versus non-depressed: a diffusion MRI connectometry study.

ABSTRACTObjective:Research on psychobiological markers of Parkinson's disease (PD) remains a hot topic. Non-motor symptoms such as depression and REM sleep behavior disorder (RBD) each attribute to a particular neurodegenerative cluster in PD, and might enlighten the way for early prediction/detection of PD. The neuropathology of mood disturbances remains unclear. In fact, a few studies have investigated depression using diffusion magnetic resonance imaging (diffusion MRI). METHOD: Diffusion MRI of PD patients without comorbid RBD was used to assess whether microstructural abnormalities are detectable in the brain of 40 PD patients with depression compared to 19 patients without depression. Diffusion MRI connectometry was used to carry out group analysis between age- and gender-matched PD patients with and without depressive symptoms. Diffusion MRI connectometry is based on spin distribution function, which quantifies the density of diffusing water and is a sensitive and specific analytical method to psychological differences between groups. RESULTS: A significant difference (FDR = 0.016129) was observed in the left and right uncinate fasciculi, left and right inferior longitudinal fasciculi, left and right fornices, left inferior fronto-occipital fasciculus, right corticospinal tract, genu of corpus callosum, and middle cerebellar peduncle. CONCLUSION: These results suggest the prominent circuits involved in emotion recognition, particularly negative emotions, might be impaired in comorbid depressive symptoms in PD.

Sequential language learning and language immersion in bilingualism: diffusion MRI connectometry reveals microstructural evidence.

Study of bilingual brain has provided evidence for probable advantageous outcomes of early second language learning and brain structural correlates to these outcomes. DMRI connectometry is a novel approach that tracts fibers based on correlation of the adjacent voxels with a variable of interest or group differences. Using the data deposited by Pliatsikas et al., we investigated through diffusion MRI connectometry and correlation analysis, the structural differences in white matter tracts of 20 healthy sequential bilingual adults who used English as a second language on a daily basis, compared to 25 age matched in fiber differentiation analyses. Connectometry results revealed increased connectivity in corpus callosum (CC), bilateral cingulum, arcuate fasciculus (AF), and left IFOF of sequential bilingual adults. All the above fibers except cingulum had positive association with language immersion period. We introduce cingulum as a tract with increased connectivity in late bilingual adults. We also found an increase in white matter connectivity conventional language-related fibers such as AF, and areas that had been shown in previous studies addressing WM differences between early or late bilinguals and monolinguals, inferior frontooccipital fasciculus, and CC. Pliatsikas reported a confounding effect for the immersion period, as a regressor in TBSS model. Through DMRI connectometry and correlation analysis, we showed that quantitative anisotropy of all of the significant fibers from connectometry analysis, except cingulum, had direct correlation with the duration of immersion period of the bilingual group into the second language.

Brain pathway differences between Parkinson's disease patients with and without REM sleep behavior disorder.

PURPOSE: REM (rapid eye movement) sleep behavior disorder (RBD) is characterized by increased muscle tone and violent limb movements and is a usual symptom of the early stages of Parkinson's disease (PD). PD patients with RBD represent faster motor and cognitive dysfunction progression. However, there are limited studies on possible structural brain changes underpinning this disorder. METHODS: Diffusion magnetic resonance imaging (DMRI) was used to assess whether microstructural abnormalities in the brain of 23 RBD positive PD are detectable compared to 31 RBD negative PD. DMRI scans were analyzed without a prior hypothesis. Diffusion MRI connectometry was used to carry out group analysis between age and gender matched PD patients with and without RBD. Diffusion MRI connectometry is based on spin distribution function (SDF) which quantifies the density of diffusing water and is more sensitive to psychological differences between groups. RESULTS: Patients with RBD positive showed microstructural white matter changes in the left and right cingulum, inferior front occipital fasciculus (IFOF), bilateral corticospinal tracts (CST), and middle cerebellar peduncles (MCPs), compared to patients without RBD. CONCLUSIONS: White matter alterations in the cingulum, IFOF regions, and corpus callosum might explain faster cognitive deterioration in PD patients with RBD, in terms of visual recognition and visuospatial dysfunction and executive function. Disturbed brain structural tissue markers in CST in PD + RBD patients, could be justified in the light of faster motor progression in these patients.

Behavioral and dysexecutive variant of Alzheimer's disease: Insights from structural and molecular imaging studies.

Frontal variant Alzheimer's disease (AD) manifests with either behavioral or dysexecutive syndromes. Recent efforts to gain a deeper understanding of this phenotype have led to a re-conceptualization of frontal AD. Behavioral (bAD) and dysexecutive (dAD) phenotypes could be considered subtypes, as suggested by both clinical and neuroimaging studies. In this review, we focused on imaging studies to highlight specific brain patterns in these two uncommon clinical AD phenotypes. Although studies did not compare directly these two variants, a common epicenter located in the frontal cortex could be inferred. On the contrary, 18F-FDG-PET findings suggested differing metabolic patterns, with bAD showing specific involvement of frontal regions and dAD exhibiting widespread alterations. Structural MRI findings confirmed this pattern, suggesting that degeneration might involve neural circuits associated with behavioral control in bAD and attentional networks in dAD. Furthermore, molecular imaging has identified different neocortical tau distribution in bAD and dAD patients compared to typical AD patients, although the distribution is remarkably heterogeneous. In contrast, Aß deposition patterns are less differentiated between these atypical variants and typical AD. Although preliminary, these findings underscore the complexity of AD frontal phenotypes and suggest that they represent distinct entities. Further research is essential to refine our understanding of the pathophysiological mechanisms in frontal AD.

White matter alterations in affective and non-affective early psychosis: A diffusion MRI study.

BACKGROUND: The early years after the onset of psychotic disorders, known as "early psychosis" (EP) are critical to determining the path of psychosis trajectory. We used a Diffusion Magnetic Resonance Imaging (DMRI) connectometry approach to assess the microstructural changes of white matter (WM) associated with EP. METHODS: We used the Human Connectome Project in Early Psychosis (HCP-EP) dataset to collect DMRI data from patients with EP. The imaging data were processed in the Montreal Neuroimaging Initiative space and transformed into quantitative anisotropy (QA). The QA value was translated into the WM connectivity of each tract and used in the subsequent analysis. RESULTS: 121 patients with EP (94 non-affective/27 affective) and 56 healthy controls were recruited. EP was associated with increased QA in the body and tapetum of corpus callosum (CC) and decreased QA in the bilateral cerebellum, and middle cerebellar peduncle. Compared to non-affective psychosis, affective psychosis showed increased QA in the bilateral cerebellum and vermis and decreased QA in the forceps minor, body of CC, right cingulum, and bilateral inferior fronto-occipital fasciculus. Furthermore, QA changes in several WM tracts were correlated with positive and negative symptom scale scores. LIMITATIONS: DMRI intrinsic limitations, limited sample size, and neurobiological effects of psychotropic treatment. CONCLUSIONS: EP is associated with alterations in WM connectivity primarily in the CC and cerebellar regions. Also, affective and non-affective psychosis have distinct alterations in WM connectivity. These results can be used for the early diagnosis and differentiation of psychotic disorders.

Effect of spaceflight experience on human brain structure, microstructure, and function: systematic review of neuroimaging studies.

Spaceflight-induced brain changes have been commonly reported in astronauts. The role of microgravity in the alteration of the brain structure, microstructure, and function can be tested with magnetic resonance imaging (MRI) techniques. Here, we aim to provide a comprehensive overview of Spaceflight studies exploring the potential role of brain alterations identified by MRI in astronauts. We conducted a search on PubMed, Web of Science, and Scopus to find neuroimaging correlates of spaceflight experience using MRI. A total of 20 studies (structural MRI n = 8, diffusion-based MRI n = 2, functional MRI n = 1, structural MRI and diffusion-weighted MRI n = 6, structural MRI and functional MRI n = 3) met our inclusion criteria. Overall, the studies showed that regardless of the MRI techniques, mission duration significantly impacts the human brain, prompting the inclusion of various brain regions as features in the analyses. After spaceflight, notable alterations were also observed in the superior occipital gyrus and the precentral gyrus which show alterations in connectivity and activation during spaceflight. The results provided highlight the alterations in brain structure after spaceflight, the unique patterns of brain remodeling, the challenges in drawing unified conclusions, and the impact of microgravity on intracranial cerebrospinal fluid volume.

Functional and structural lesion network mapping in neurological and psychiatric disorders: a systematic review.

Background: The traditional approach to studying the neurobiological mechanisms of brain disorders and localizing brain function involves identifying brain abnormalities and comparing them to matched controls. This method has been instrumental in clinical neurology, providing insight into the functional roles of different brain regions. However, it becomes challenging when lesions in diverse regions produce similar symptoms. To address this, researchers have begun mapping brain lesions to functional or structural networks, a process known as lesion network mapping (LNM). This approach seeks to identify common brain circuits associated with lesions in various areas. In this review, we focus on recent studies that have utilized LNM to map neurological and psychiatric symptoms, shedding light on how this method enhances our understanding of brain network functions. Methods: We conducted a systematic search of four databases: PubMed, Scopus, and Web of Science, using the term "Lesion network mapping." Our focus was on observational studies that applied lesion network mapping in the context of neurological and psychiatric disorders. Results: Following our screening process, we included 52 studies, comprising a total of 6,814 subjects, in our systematic review. These studies, which utilized functional connectivity, revealed several regions and network overlaps across various movement and psychiatric disorders. For instance, the cerebellum was found to be part of a common network for conditions such as essential tremor relief, parkinsonism, Holmes tremor, freezing of gait, cervical dystonia, infantile spasms, and tics. Additionally, the thalamus was identified as part of a common network for essential tremor relief, Holmes tremor, and executive function deficits. The dorsal attention network was significantly associated with fall risk in elderly individuals and parkinsonism. Conclusion: LNM has proven to be a powerful tool in localizing a broad range of neuropsychiatric, behavioral, and movement disorders. It holds promise in identifying new treatment targets through symptom mapping. Nonetheless, the validity of these approaches should be confirmed by more comprehensive prospective studies.

Deep Learning Methods for Identification of White Matter Fiber Tracts: Review of State-of-the-Art and Future Prospective.

Quantitative analysis of white matter fiber tracts from diffusion Magnetic Resonance Imaging (dMRI) data is of great significance in health and disease. For example, analysis of fiber tracts related to anatomically meaningful fiber bundles is highly demanded in pre-surgical and treatment planning, and the surgery outcome depends on accurate segmentation of the desired tracts. Currently, this process is mainly done through time-consuming manual identification performed by neuro-anatomical experts. However, there is a broad interest in automating the pipeline such that it is fast, accurate, and easy to apply in clinical settings and also eliminates the intra-reader variabilities. Following the advancements in medical image analysis using deep learning techniques, there has been a growing interest in using these techniques for the task of tract identification as well. Recent reports on this application show that deep learning-based tract identification approaches outperform existing state-of-the-art methods. This paper presents a review of current tract identification approaches based on deep neural networks. First, we review the recent deep learning methods for tract identification. Next, we compare them with respect to their performance, training process, and network properties. Finally, we end with a critical discussion of open challenges and possible directions for future works.