Microstructural differences in migraine: A diffusion-tensor imaging study.

BACKGROUND: Diffusion-tensor imaging can be applied to describe the microstructural integrity of the whole brain. As findings about microstructural alterations in migraine are inconsistent, we aimed to replicate the most frequent results and assess a relationship between migraine parameters and changes in microstructure. METHODS: Diffusion-weighted MRI data of 37 migraine patients and 40 controls were collected. Two indices of diffusion of water molecules, fractional anisotropy and mean diffusivity were used in a voxel-wise analysis. Group comparisons were carried out in SPM12 using age and sex as covariates. Statistically significant results survived family-wise error correction (pFWE < 0.05). Migraine intensity, frequency, and duration were self-reported and correlated with mean fractional anisotropy and mean diffusivity values across clusters. RESULTS: Migraine patients showed significantly lower fractional anisotropy in occipital regions, and significantly higher fractional anisotropy in thirteen clusters across the brain. Mean diffusivity of migraine patients was significantly decreased in the cerebellum and pons, but it was not increased in any area. Correlation between migraine duration and fractional anisotropy was significantly positive in the frontal cortex and significantly negative in the superior parietal lobule. CONCLUSION: We suggest that microstructural integrity of the migraine brain is impaired in visual areas and shows duration-related alterations in regions of the default mode network.

[The importance of MR imaging in the diagnosis and management of acute stroke]. / Az MR-képalkotás jelentosége az akut stroke diagnosztikájában és ellátásában ­ Az MRI FIRST! Projekt.

Background and purpose:

In our collaborative project, called MRI First!, every patient arriving with neurological symptoms of acute stroke and without contraindications was examined by MRI. Our aim was to detect the symptomatic lesions, to obtain appropriate information about the brain parenchyma and to analyse parenchymal perfusion and brain vasculature.

The examinations were conduc­ted on a Philips Ingenia 1.5 Tesla scanner with the following protocol: DWI-ADC, FLAIR, T2 FFE/SWI, PWI, and contrast-enhanced MRA. 415 patients were examined between January 2020 and May 2021. 179 patients arrived within-, and 136 patients after 4.5 hours symptoms onset time, while 100 patients had “wake-up” stroke.

Within the 4.5 hours group, 81 cases had acute ischemic lesion, 48 of them received reperfusion therapy. Acute ische­mic lesion was found in 64 patients in the wake-up stroke group and in 64 in the 4.5-24 hours group. In these groups 10 and 12 patients obtained reperfusion therapy, respectively. Further 117 cases were considered as stroke mimics, in which cases unnecessary intravenous thrombolysis was avoidable.

MRI is accepted as a sensitive diagnostic modality providing detailed information regarding the brain parenchyma, its perfusion and vasculature. Nonetheless, its worldwide utilization in acute stroke is low and further information should be collected on which patient groups would gain the most benefit from acute MR imaging. Our continuous work is aimed at that goal.

Comparative in vitro and in vivo Evaluation of Different Iron Oxide-Based Contrast Agents to Promote Clinical Translation in Compliance with Patient Safety.

Introduction: One of the major challenges in the clinical translation of nanoparticles is the development of formulations combining favorable efficacy and optimal safety. In the past, iron oxide nanoparticles have been introduced as an alternative for gadolinium-containing contrast agents; however, candidates available at the time were not free from adverse effects. Methods: Following the development of a potent iron oxide-based contrast agent SPIONDex, we now performed a systematic comparison of this formulation with the conventional contrast agent ferucarbotran and with ferumoxytol, taking into consideration their physicochemical characteristics, bio- and hemocompatibility in vitro and in vivo, as well as their liver imaging properties in rats. Results: The results demonstrated superior in vitro cyto-, hemo- and immunocompatibility of SPIONDex in comparison to the other two formulations. Intravenous administration of ferucarbotran or ferumoxytol induced strong complement activation-related pseudoallergy in pigs. In contrast, SPIONDex did not elicit any hypersensitivity reactions in the experimental animals. In a rat model, comparable liver imaging properties, but a faster clearance was demonstrated for SPIONDex. Conclusion: The results indicate that SPIONDex possess an exceptional safety compared to the other two formulations, making them a promising candidate for further clinical translation.

Microstructural alterations measured by diffusion tensor imaging following transcatheter aortic valve replacement and their association with cerebral ischemic injury and cognitive function - a prospective study.

PURPOSE: We assessed diffusion tensor imaging (DTI) metric changes of the corpus callosum and cingulum correlated to postprocedural ischemic lesion load (ILL) and cognitive performance in transcatheter aortic valve replacement (TAVR). METHODS: TAVR subjects had DTI post-TAVR (≤ 8 days) and at 6 months (78 participants, males 56%, age 78.8 years ± 6.3) and four neurocognitive tests (pre-TAVR, post-TAVR, 6 months, 1 year). DTI metrics (fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD)) were calculated for 7 regions: corpus callosum (genu, body, splenium) and cingulum (cingulate gyrus, parahippocampal cingulum bilaterally). DTI metrics post-TAVR and at 6 months were compared with Student's t-test (p < 0.0071) and ANOVA covarying for sex, ILL (p < 0.05) with post hoc analysis of ILL groups (p < 0.0167). Repeated-measures linear mixed-effect model (p < 0.05) was performed to investigate the effect of time and ILL on cognition. RESULTS: At 6 months, significant decrease of the following DTI metrics was detected: AD (genu, body, splenium, right parahippocampal cingulum: p ≤ 0.0046); MD (body, both cingulate gyri: p ≤ 0.0050); RD (left cingulate gyrus: p = 0.0021); FA (splenium: p < 0.0001). ANOVA confirmed significant effect of female sex on AD + MD reduction (body, right cingulate gyrus) and AD reduction (left cingulate gyrus) (p ≤ 0.0254). Significant negative effect of ILL on some DTI metric changes was found (AD + MD-body: p ≤ 0.0050; MD-left cingulate gyrus: p = 0.0087). Cognitive performance remained stable with significant negative correlation of ILL and retrograde memory and visual scores (p ≤ 0.0483). CONCLUSION: Significant effect of TAVR on cerebral microstructural integrity was found with reduced diffusivities opposite to the trends reported in various neurodegenerative conditions/ageing, notably in women and lower ILL, and with preserved/improved cognition. TRIAL REGISTRATION NUMBER: NCT02826200 at ClinicalTrials.gov; date of registration: 07. July 2016.

Long-term neurodevelopmental outcome of neonates born at term with perinatal haemorrhagic stroke: A population-based study.

AIM: To assess the long-term neurodevelopmental outcome of neonates born at term diagnosed with perinatal haemorrhagic stroke (PHS) and investigate the associations among brain territorial involvement, clinical risk factors, and neurodevelopmental outcomes. METHOD: We conducted a population-based study enrolling 55 neonates born at term with PHS confirmed by magnetic resonance imaging born between 2007 and 2017. Long-term neurodevelopmental outcome was assessed using the Bayley Scales of Infant Development, Second Edition, the Brunet-Lézine test, and the Stanford-Binet Intelligence Scales, Fifth Edition. RESULTS: Follow-up was available in 50 (91%) of the infants, at a median age of 60 months (interquartile range 35-88). Forty per cent of the infants developed according to population norms, and developmental disabilities were diagnosed less frequently among neonates with frontal lobe PHS. In a multivariable model, parietal lobe PHS increased the risk for cerebral palsy (odds ratio [OR] 6.7; 95% confidence interval [CI] 1.1-41.4) and cognitive impairment (OR: 23.6; 95% CI: 2.9-194.9), while the involvement of the thalamus and/or basal ganglia was associated with epilepsy (OR: 7.0; 95% CI: 1.3-37.7). Seizures on admission were associated with epilepsy (OR: 10.8; 95% CI: 1.8-64.3). Patients with PHS affecting multiple lobes had poor prognosis. INTERPRETATION: Parietal lobe haemorrhage, the involvement of the thalamus/basal ganglia, PHS affecting multiple lobes, and seizures were independent predictors of chronic neurodevelopmental sequelae, suggesting that the stroke territorial involvement and clinical risk factors influence the outcome of PHS.

Fronto-thalamic structural and effective connectivity and delusions in schizophrenia: a combined DTI/DCM study.

BACKGROUND: Schizophrenia (SZ) is a complex disorder characterized by a range of behavioral and cognitive symptoms as well as structural and functional alterations in multiple cortical and subcortical structures. SZ is associated with reduced functional network connectivity involving core regions such as the anterior cingulate cortex (ACC) and the thalamus. However, little is known whether effective coupling, the directed influence of one structure over the other, is altered during rest in the ACC-thalamus network. METHODS: We collected resting-state fMRI and diffusion-weighted MRI data from 18 patients and 20 healthy controls. We analyzed fronto-thalamic effective connectivity using dynamic causal modeling for cross-spectral densities in a network consisting of the ACC and the left and right medio-dorsal thalamic regions. We studied structural connectivity using fractional anisotropy (FA). RESULTS: We found decreased coupling strength from the right thalamus to the ACC and from the right thalamus to the left thalamus, as well as increased inhibitory intrinsic connectivity in the right thalamus in patients relative to controls. ACC-to-left thalamus coupling strength correlated with the Positive and Negative Syndrome Scale (PANSS) total positive syndrome score and with delusion score. Whole-brain structural analysis revealed several tracts with reduced FA in patients, with a maximum decrease in white matter tracts containing fronto-thalamic and cingulo-thalamic fibers. CONCLUSIONS: We found altered effective and structural connectivity within the ACC-thalamus network in SZ. Our results indicate that ACC-thalamus network activity at rest is characterized by reduced thalamus-to-ACC coupling. We suggest that positive symptoms may arise as a consequence of compensatory measures to imbalanced fronto-thalamic coupling.

Neurodevelopmental effect of intracranial hemorrhage observed in hypoxic ischemic brain injury in hypothermia-treated asphyxiated neonates - an MRI study.

BACKGROUND: Identification of early signs of hypoxic ischemic encephalopathy (HIE) with magnetic resonance imaging (MRI) has proven of prognostic significance. Yet, the importance of intracranial hemorrhage (ICH), being present concomitantly had not been investigated yet, despite the known influence of hypothermia on hemostasis. We aimed to determine whether presence of ICH on MRI alongside the signs of HIE have an impact on prognosis in neonates with the clinical diagnosis of HIE. METHODS: A retrospective study of consecutively sampled 108 asphyxiated term infants admitted to a tertiary neonatal intensive care unit (between 2007 and 2016), treated with whole body hypothermia and having brain MRI within 1 week of life was conducted. Presence or absence of HIE signs on MRI (basal ganglia-thalamus, watershed pattern and total brain injury) and on MR spectroscopy (lactate peak with decreased normal metabolites measured by Lac/NAA ratio) and/or of the five major types of ICH were recorded. Neurodevelopmental outcome was measured with Bayley Scales of Infant Development-II (BSID-II) test. Death or abnormal neurodevelopment (BSID-II score < 85) was defined as poor outcome in Chi-square test. Multivariate logistic regression analysis was performed on survivors. RESULTS: MRI and MR-spectroscopy (MRS) signs of HIE were present in 72% (n = 78). 36% (n = 39) of neonates had ICH, being mainly small in size. Chi-square test showed a relationship between neurodevelopmental outcome and initial MRI. Unadjusted logistic regression showed that neonates presenting MRI and MRS signs of HIE have 6.23 times higher odds for delayed mental development (OR = 6.2292; CI95% = [1.2642; 30.6934], p = 0.0246), than infants without imaging alterations; with no ICH effect on outcome. Adjustment for clinical and imaging parameters did not change the pattern of results, i.e. HIE remained an independent risk factor for delayed neurodevelopment (OR = 6.2496; CI95% = [1.2018; 32.4983], p = 0.0294), while ICH remained to have no significant effect. CONCLUSION: HIE related MRI abnormalities proved to be important prognostic factors of poor outcome in cooled asphyxiated infants when present, suggesting that early MRI with MRS is beneficial for prognostication. Interestingly, ICHs present in about one third of all cases had no significant effect on neurodevelopmental outcome, despite the known hemostasis altering effects of hypothermia.

Personalized microstructural evaluation using a Mahalanobis-distance based outlier detection strategy on epilepsy patients' DTI data - Theory, simulations and example cases.

Quantitative MRI methods have recently gained extensive interest and are seeing substantial developments; however, their application in single patient vs control group comparisons is often limited by inherent statistical difficulties. One such application is detecting malformations of cortical development (MCDs) behind drug resistant epilepsies, a task that, especially when based solely on conventional MR images, may represent a serious challenge. We aimed to develop a novel straightforward voxel-wise evaluation method based on the Mahalanobis-distance, combining quantitative MRI data into a multidimensional parameter space and detecting lesion voxels as outliers. Simulations with standard multivariate Gaussian distribution and resampled DTI-eigenvalue data of 45 healthy control subjects determined the optimal critical value, cluster size threshold, and the expectable lesion detection performance through ROC-analyses. To reduce the effect of false positives emanating from registration artefacts and gyrification differences, an automatic classification method was applied, fine-tuned using a leave-one-out strategy based on diffusion and T1-weighted data of the controls. DWI processing, including thorough corrections and robust tensor fitting was performed with ExploreDTI, spatial coregistration was achieved with the DARTEL tools of SPM12. Additional to simulations, clusters of outlying diffusion profile, concordant with neuroradiological evaluation and independent calculations with the MAP07 toolbox were identified in 12 cases of a 13 patient example population with various types of MCDs. The multidimensional approach proved sufficiently sensitive in pinpointing regions of abnormal tissue microstructure using DTI data both in simulations and in the heterogeneous example population. Inherent limitations posed by registration artefacts, age-related differences, and the different or mixed pathologies limit the generalization of specificity estimation. Nevertheless, the proposed statistical method may aid the everyday examination of individual subjects, ever so more upon extending the framework with quantitative information from other modalities, e.g. susceptibility mapping, relaxometry, or perfusion.

What can DTI tell about early cognitive impairment? - Differentiation between MCI subtypes and healthy controls by diffusion tensor imaging.

Mild cognitive impairment (MCI) gained a lot of interest recently, especially that the conversion rate to Alzheimer Disease (AD) in the amnestic subtype (aMCI) is higher than in the non-amnestic subtype (naMCI). We aimed to determine whether and how diffusion-weighted MRI (DWI) using the diffusion tensor model (DTI) can differentiate MCI subtypes from healthy subjects. High resolution 3D T1W and DWI images of patients (aMCI, n = 18; naMCI, n = 20; according to Petersen criteria) and controls (n = 27) were acquired at 3T and processed using ExploreDTI and SPM. Voxel-wise and region of interest (ROI) analyses of fractional anisotropy (FA) and mean diffusivity (MD) were performed with ANCOVA; MD was higher in aMCI compared to controls or naMCI in several grey and white matter (GM, WM) regions (especially in the temporal pole and the inferior temporal lobes), while FA was lower in WM ROI-s (e.g. left Cingulum). Moreover, significant correlations were identified between verbal fluency, visual and verbal memory performance and DTI metrics. Logistic regression showed that measuring FA of the crus of fornix along GM volumetry improves the discrimination of aMCI from naMCI. Additional information from DWI/DTI aids preclinical detection of AD and may help detecting early non-Alzheimer type dementia, too.