Abstract Background and aims Cerebral small vessel disease (SVD) is a leading cause of vascular dementia and accounts for 25% of ischemic strokes. Despite white matter hyperintensities (WMH) of similar severity, clinical manifestations vary considerably between individuals, suggesting that microstructural changes beyond macroscopic lesions are critical. Quantitative MRI (qMRI) techniques may detect such changes before overt clinical deterioration; even earlier than known diffusion tensor imaging (DTI) markers. Methods EARLYPROG-SVD (DRKS00034274) aims to establish imaging biomarkers for early disease progression by investigating microstructural tissue integrity using qMRI relaxometry and DTI in affected and normal-appearing brain tissue over time. Results In this prospective longitudinal study, 38 patients (mean age 68.5±5.9 years; mean Fazekas score ≥2.5, rated by two blinded raters) and 33 age-matched controls (mean age 70.8±6.9 years; p=n.s.) aged ≥60 at inclusion underwent 3T MRI, comprehensive clinical assessment, and cognitive testing (CERAD-Plus) at three close-interval time points (baseline, 6 months, and ~12-18 months). Automated WMH segmentation and quantitative T1, T2, T2*, and T2' relaxometry are performed to compare values across brain regions and groups. Subsequent analyses will incorporate DTI-based tractography. Conclusions Cardiovascular risk factors differed significantly between groups, with higher prevalence of hypertension (p=0.002), dyslipidemia (p=0.015), and cardiac comorbidity (p=0.045), alongside a non-significant trend for diabetes. Analyses of WMH distribution patterns and quantitative values in white matter lesions and cortex will be presented. Conflict of interest

BACKGROUND AND OBJECTIVES:Post-recovery brain changes following Coronavirus Disease 2019 (COVID-19) have been reported using various imaging techniques. The objective was to identify microstructural abnormalities between groups in specific fiber tracts using tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI), along with region-specific quantitative analysis of T1 relaxation times (qT1) and volumes. METHODS:This single-center, prospective, observational case-control study included adults ≥ 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen positivity, matched by age and gender with seronegative controls, and categorized by initial infection severity and an age cut-off of 40. MRI included: (1) 2 mm DTI generating fractional anisotropy (FA), mean (MD), radial (RD), and axial diffusivity (AD) maps; (2) two 3D 1 mm³ gradient-echo datasets for mapping T1 relaxation times (qT1) and creating synthetic high-resolution T1 images; (3) 3 mm 2D fluid-attenuated inversion recovery (FLAIR) images. Baseline characteristics and neuro(psycho)logical assessments including olfactory function, Beck Depression Inventory, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, EQ-5D, and Montreal cognitive assessment were also recorded. RESULTS:Between November 2020 and December 2021, 145 unvaccinated subjects (median age, 46 years [IQR, 33.5-53]; 73 women) were consecutively evaluated. TBSS showed no significant FA differences between all 69 cases and 76 age- and sex-matched controls. However, participants ≥ 40 years that required hospitalization due to COVID-19 (n = 23) had decreased FA, increased RD, and reduced qT1 values (all P ≤ 0.001) in specific voxels compared to controls ≥ 40 years (n = 47). These microstructural measures appeared in predominantly right-sided lateral orbitofrontal, frontal inferior, anterior insular, and rostral anterior cingulate white matter (WM) regions, without visually detectable abnormalities or region-specific volume loss in WM or cortical gray matter. This subgroup also showed significantly higher presence of fatigue, depressive symptoms, poorer sleep quality and reduced health-related quality of life. DISCUSSION:Advanced MRI revealed microstructural abnormalities along frontoinsular-cingulate WM fiber tracts in unvaccinated participants aged ≥ 40 with a history of COVID-19 requiring hospitalization. These findings may suggest ongoing reduced fiber integrity and persistent oxidative stress within the salience network, potentially contributing to functional sequelae.

Background:Mild cognitive impairment (MCI) represents anearly stage of cognitive decline, often preceding dementia. While hippocampal atrophy is a recognized imaging marker, the role of deep gray matter structures and tissue alterations remains less understood. This study aimed to assess whether quantitative T1 (qT1) relaxometry and volumetric measures derived from synthetic MRI are associated with global cognitive performance, as measured by the Montreal Cognitive Assessment (MoCA). Methods:In this cross-sectional study, 74 healthy adults (mean age 43.7 years, 50% female) underwent 3D-synthetic MRI and MoCA testing. Participants were stratified into cognitively normal (MoCA ≥26) and MCI (MoCA <26) groups. Brain volumes and qT1 values were extracted across regions. Associations with MoCA were assessed using multivariate regression, controlling for demographic and clinical covariates. Results:Left hippocampal volume was significantly reduced in the MCI group (p = 0.019) and was positively associated with MoCA scores (R2 = 0.18). Although qT1 values did not differ significantly between groups, qT1 in the right putamen independently predicted MoCA scores when adjusted for age (combined model R2 = 0.22). Age was also associated with cortical gray matter qT1 (r = -0.33, p = 0.005) and increased CSF volume (r = 0.45, p < 0.0001), indicating age-related structural changes. No significant effects of sex, BMI, vascular risk, or comorbidities were observed. Conclusions:Hippocampal volume and putamen qT1 are independent imaging correlates of cognitive performance. qT1 mapping may detect early subtle tissue changes not captured by conventional volumetry, supporting its potential role as a biomarker in cognitive aging.

Abstract Messenger ribonucleic acid (mRNA)-based vaccines delivered via lipid nanoparticles (LNP) were pivotal in managing the severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic. While mild systemic reactions are common after vaccination, rare neurological complications have raised concerns about potential structural cerebral changes. This prospective pilot study tested the hypothesis that LNP-mRNA-based SARS-CoV-2 vaccination does not induce significant microstructural cerebral changes in healthy adults. Dedicated 3 Tesla brain MRI was performed at three time points: up to one month before the first vaccination (t1), and 1–2 weeks (t2) and 2–3 months (t3) after the second dose of either BNT162b2 or mRNA-1273. Across 85 MRI scans from 29 initially SARS-CoV-2-seronegative adults, 2D T2-weighted fluid-attenuated inversion recovery, synthetic 3D T1 magnetization prepared rapid acquisition of gradient echoes and 3D quantitative T1 mapping were analyzed. Changes in w matter hyperintensities (WMH) were evaluated visually (Prins scale) and semiquantitatively (Longitudinal Brain Imaging). Microstructural changes of deep and cortical gray matter and white matter were analyzed using qT1 values via paired t-tests or Wilcoxon signed-rank tests. No new or progressive WMH nor significant intraindividual qT1 changes were observed. QT1% deviations were small (mean 0.1%, SD 0.9%; maximum 2.08%) and remained within established scan-rescan variability limits at 3 T. Apart from a 1 mm decrease of a preexisting WMH in one participant, no visually detectable structural brain alterations were observed. Our findings provide no evidence for WMH progression or microstructural cerebral changes after LNP-mRNA-based SARS-CoV-2 vaccination in healthy adults in the subacute phase.

Individual differences in attachment classification reflect children's social expectations given early relational experiences with primary caregivers. When experiencing rejection - when affective needs are unmet - children can develop avoidant attachment strategies, including suppression of negative emotions and inhibition of observable reactions to adversity. A key aversive situation is social rejection, but how attachment differences affect neural responses to it is poorly understood. We combined functional MRI and the Cyberball paradigm to investigate responses to social rejection in 38 children (9-11 years) classified using the Child Attachment Interview. BOLD activation in the anterior cingulate cortex and right ventrolateral prefrontal cortex (vlPFC) was increased for events of social exclusion relative to inclusion. Dorsal to this effect, right vlPFC showed a negative correlation between exclusion-related BOLD activity and attachment dismissal, a continuous marker for avoidant attachment, reflecting greater vlPFC responses during inclusion (fair play) for avoidant attachment but unchanged responses to exclusion, suggesting increased regulatory monitoring during fair play in higher-dismissal children, rather than altered exclusion reactivity. This may be related to greater expressed worry about exclusion despite fair play in the inclusion condition. Our results suggest that avoidant attachment in children may be associated with impaired emotion regulation and greater expectation of rejection.

To determine changes in quantitative T1 relaxation times (qT1) in deep gray matter in patients recovered from coronavirus disease 2019 (COVID-19). Unvaccinated COVID-19 participants ≥ 3 months after seropositivity and age- and sex-matched controls were examined using 3-T magnetic resonance imaging. Bilateral measures of thalamus, pallidum, putamen, caudate and accumbens nuclei, and hippocampus were extracted from qT1 maps after automated segmentation. Baseline characteristics and results of tests assessing neurological functions (standardized exam), ability to smell (4-Item Pocket Smell Test), depression (Beck Depression Inventory-II), sleepiness (Epworth Sleepiness Scale), sleep quality (Pittsburgh Sleep Quality Index), health-related quality of life (EQ-5D), and cognitive performance (Montreal Cognitive Assessment) were evaluated. One hundred forty-five subjects (median age, 46 years; 73 females) were included (11/2020–12/2021): 69 recovered after COVID-19 and 76 controls (age, p = 0.532; sex, p = 0.799), without significant differences in qT1 values overall (all p-values > 0.050). Subgroup analysis of participants aged ≥ 40 (age, p = 0.675; sex, p = 0.447) revealed higher qT1 values in previously hospitalized COVID-19 subjects (23/69) compared to controls (47/76) in left and right caudate nuclei (p = 0.009; p = 0.027), left accumbens nucleus (p = 0.017), right putamen (p = 0.041), and right hippocampus (p = 0.020). No correlations were found with macroscopic imaging findings, pre-existing conditions, time since COVID-19 diagnosis, inpatient treatment duration, or test results. T1 mapping revealed microstructural changes in striatal and hippocampal regions of unvaccinated individuals aged ≥ 40 who recovered from moderate-to-severe COVID-19 during the pre-Omicron era. This study elucidates brain involvement following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, underscoring the need for further longitudinal analyses to assess the potential reversibility, stability or deterioration of these findings.

The intracellular pH (pHi) is critical for understanding various pathologies, including brain tumors. While conventional pHi measurement through 31P-MRS suffers from low spatial resolution and long scan times, 1H-based APT-CEST imaging offers higher resolution with shorter scan times. This study aims to directly predict 31P-pHi maps from CEST data by using a fully connected neuronal network. Fifteen tumor patients were scanned on a 3-T Siemens PRISMA scanner and received 1H-based CEST and T1 measurement, as well as 31P-MRS. A neural network was trained voxel-wise on CEST and T1 data to predict 31P-pHi values, using data from 11 patients for training and 4 for testing. The predicted pHi maps were additionally down-sampled to the original the 31P-pHi resolution, to be able to calculate the RMSE and analyze the correlation, while higher resolved predictions were compared with conventional CEST metrics. The results demonstrated a general correspondence between the predicted deepCEST pHi maps and the measured 31P-pHi in test patients. However, slight discrepancies were also observed, with a RMSE of 0.04 pH units in tumor regions. High-resolution predictions revealed tumor heterogeneity and features not visible in conventional CEST data, suggesting the model captures unique pH information and is not simply a T1 segmentation. The deepCEST pHi neural network enables the APT-CEST hidden pH-sensitivity and offers pHi maps with higher spatial resolution in shorter scan time compared with 31P-MRS. Although this approach is constrained by the limitations of the acquired data, it can be extended with additional CEST features for future studies, thereby offering a promising approach for 3D pH imaging in a clinical environment.

Measuring the intracellular pH (pHi) is of interest for brain tumor diagnostics. Common metrics of CEST imaging like the amide proton transfer-weighted (APTw) MTRasym are pHi sensitive and allow differentiating malignant tumor from healthy tissue. Yet, the image contrast also depends on additional magnetization transfer effects and T1. In contrast, the apparent exchange-dependent relaxation (AREX) provides a T1 corrected exchange rate of the amide protons. As AREX still depends on amide proton density, its pHi sensitivity remains ambiguous. Hence, we conducted this study to assess the influence of pathologic tissue changes on the pHi sensitivity of AREX in vivo. Patients with newly diagnosed intra-axial brain tumors were prospectively recruited and underwent conventional MRI, quantitative T1 relaxometry, APT-CEST and 31P-MRS on a 3T MRI scanner. Tumors were segmented into contrast-enhancing tumor (CE), surrounding T2 hyperintensity (T2-H) and contralateral normal appearing white matter (CNAWM). T1 mapping and APT-CEST metrics were correlated with 31P-MRS-derived pHi maps (Pearson's correlation). Without differentiating tissue subtypes, pHi did not only correlate significantly with MTRasym (r = 0.46) but also with T1 (r = 0.49). Conversely, AREX only correlated poorly with pHi (r = 0.17). Analyzing different tissue subtypes separately revealed a tissue dependency of the pHi sensitivity of AREX with a significant correlation (r = 0.6) in CNAWM and no correlation in T2-H or CE (r = -0.11/-0.24). CE showed significantly increased MTRasym, pHi, and T1 compared with CNAWM (p < 0.001). In our study, the pHi sensitivity of AREX was limited to CNAWM. The lack of sensitivity in CE and T2-H is probably attributable to altered amide and water proton concentrations in these tissues. Conversely, the correlation of pHi with MTRasym may be explained by the coincidental contrast increase through increased T1 and amide proton density. Therefore, limited structural deviations from CNAWM might be a perquisite for the use of CEST contrasts as pHi-marker.

OBJECTIVE:Interictal blood-brain barrier dysfunction in chronic epilepsy has been demonstrated in animal models and pathological specimens. Ictal blood-brain barrier dysfunction has been shown in humans in vivo using an experimental quantitative magnetic resonance imaging (MRI) protocol. Here, we hypothesized that interictal blood-brain barrier dysfunction is also present in people with drug-resistant epilepsy.METHODS:Thirty-nine people (21 females, mean age at MRI ± SD = 30 ± 8 years) with drug-resistant epilepsy were prospectively recruited and underwent interictal T1-relaxometry before and after administration of a paramagnetic contrast agent. Likewise, quantitative T1 was acquired in 29 people without epilepsy (12 females, age at MRI = 48 ± 18 years). Quantitative T1 difference maps were calculated and served as a surrogate imaging marker for blood-brain barrier dysfunction. Values of quantitative T1 difference maps inside hemispheres ipsilateral to the presumed seizure onset zone were then compared, on a voxelwise level and within presumed seizure onset zones, to the contralateral side of people with epilepsy and to people without epilepsy.RESULTS:Compared to the contralateral side, ipsilateral T1 difference values were significantly higher in white matter (corrected p < .05), gray matter (uncorrected p < .05), and presumed seizure onset zones (p = .04) in people with epilepsy. Compared to people without epilepsy, significantly higher T1 difference values were found in the anatomical vicinity of presumed seizure onset zones (p = .004). A subgroup of people with hippocampal sclerosis demonstrated significantly higher T1 difference values in the ipsilateral hippocampus and in regions strongly interconnected with the hippocampus compared to people without epilepsy (corrected p < .01). Finally, z-scores reflecting the deviation of T1 difference values within the presumed seizure onset zone were associated with verbal memory performance (p = .02) in people with temporal lobe epilepsy.SIGNIFICANCE:Our results indicate a blood-brain barrier dysfunction in drug-resistant epilepsy that is detectable interictally in vivo, anatomically related to the presumed seizure onset zone, and associated with cognitive deficits.

BACKGROUND AND PURPOSE:In acute ischemic stroke (AIS) due to large-vessel occlusion (LVO), the relationship between cerebral oxygen extraction fraction (OEF) as the hallmark of the ischemic penumbra and leptomeningeal collateral supply is not well established. We aimed to investigate the relationship between pial collateralization and tissue oxygen extraction in patients with LVO using magnetic resonance imaging (MRI). METHODS:Data from 14 patients with anterior circulation LVO who underwent MRI before acute stroke treatment were analyzed. In addition to diffusion-weighted imaging and perfusion-weighted imaging (PWI), the protocol comprised sequences for multiparametric quantitative blood-oxygen-level-dependent imaging for the calculation of relative OEF (rOEF). Pial collateral supply was quantitatively assessed by analyzing the signal variance in T2*-weighted PWI time series. Relationships between collateral supply, infarct volume, rOEF in peri-infarct hypoperfused tissue, and clinical stroke severity were assessed. RESULTS:The PWI-based parameter quantifying collateral supply was negatively correlated with baseline ischemic core volume and rOEF in the hypoperfused peri-infarct area (p < .01). Both reduced collateral supply and increased rOEF correlated significantly with higher scores on the National Institutes of Health Stroke Scale (p < .05). Increased rOEF within hypoperfused tissue was associated with higher baseline (p = .043) and follow-up infarct volume (p = .009). CONCLUSIONS:Signal variance-based mapping of collaterals with PWI depicts pial collateral supply, which is closely tied to tissue pathophysiology and clinical and imaging outcomes. Magnetic-resonance-derived mapping of cerebral rOEF reveals penumbral characteristics of hypoperfused tissue and might provide a promising imaging biomarker in AIS.

AbstractObjectiveThe piriform cortex is considered to be highly epileptogenic. Its resection during epilepsy surgery is a predictor for postoperative seizure freedom in temporal lobe epilepsy. Epilepsy is associated with a dysfunction of the blood–brain barrier. We investigated blood–brain barrier dysfunction in the piriform cortex of people with temporal lobe epilepsy using quantitative T1‐relaxometry.MethodsGadolinium‐based contrast agent was administered ictally and interictally in 37 individuals before undergoing quantitative T1‐relaxometry. Postictal and interictal images were co‐registered, and subtraction maps were created as biomarkers for peri‐ictal (∆qT1interictal‐postictal) and interictal (∆qT1noncontrast‐interictal) blood–brain barrier dysfunction. Values were extracted for the piriform cortex, hippocampus, amygdala, and the whole cortex.ResultsIn temporal lobe epilepsy (n = 14), ∆qT1noncontrast‐interictal was significantly higher in the piriform cortex than in the whole cortex (p = 0.02). In extratemporal lobe epilepsy (n = 23), ∆qT1noncontrast‐interictal was higher in the hippocampus than in the whole cortex (p = 0.05). Across all individuals (n = 37), duration of epilepsy was correlated with ∆qT1noncontrast‐interictal (ß = 0.001, p < 0.001) in all regions, while the association was strongest in the piriform cortex. Impaired verbal memory was associated with ∆qT1noncontrast‐interictal only in the piriform cortex (p = 0.04). ∆qT1interictal‐postictal did not show differences in any region.InterpretationInterictal blood–brain barrier dysfunction occurs in the piriform cortex in temporal lobe epilepsy. This dysfunction is linked to longer disease duration and worse cognitive deficits, emphasizing the central role of the piriform cortex in the epileptogenic network of temporal lobe epilepsy.

Background Multiparametric quantitative MRI (mp-qMRI) provides noninvasive, quantitative measurements sensitive to a variety of tissue properties. In brain tumors (BTs), longitudinal relaxation time (T1), effective transverse relaxation time (T2*), transverse relaxation time (T2), water content (H2O), and quantitative susceptibility (chi) give valuable insights into the microenvironment. To generate large multicenter datasets, protocols need to be short and implementable on any scanner. The goal of this work was to develop and validate an 8-min, 3T mp-qMRI protocol for BT patients solely using generalized pulse sequences (mGRE and EPI).Methods A protocol was developed and tested on a multicompartment phantom, 5 healthy subjects (mean age: 31.64 years), and 4 BT patients (mean age:39.5 years). Phantom and healthy subject longitudinal relaxation time (T1) maps were compared to those obtained using 2 reference methods. The 5 healthy subjects were scanned on 3T MRI scanners at 2 different sites and the reproducibility between scanners was assessed by computing Coefficients of Variance (COV) maps, performing Bland-Altman analysis and t-tests. Clinical feasibility was tested on 4 BT patients.Results T1 values obtained using the proposed mp-qMRI protocol agree with those obtained using the reference methods in volunteers (mean error = 8.94 ms). The qMRI maps (T1, T2*, H2O, and chi) of the volunteers showed good reproducibility between scanners with no significant differences for mean WM and GM qMRI values. WM and GM mean qMRI values agreed well with literature values. H2O gave the lowest COV and chi maps the highest.Conclusion The proposed vendor sequence-based 3T mp-qMRI protocol gives interpolated, high resolution (1 mm isotropic) T1, T2*, H2O, and chi maps in 8 min of acquisition. Patients with brain tumors often need MRIs. New methods, called quantitative-MRI methods, provide very valuable and unique information in brain tumors, but can take up to 30 min of additional MRI scanning. The authors of this study wanted to develop a shorter-duration quantitative-MRI method that could be used in the clinic without affecting the quality of results. To do this they created a new 8-min quantitative-MRI method that measures different properties of brain tissue. They tested the new method on 5 healthy subjects and 4 patients with brain tumors, using different MRI machines. Their results showed that the shorter quantitative-MRI method provided detailed, good quality images of the brain that were consistent between machines.

BackgroundIn cerebral small vessel disease (CSVD), cortical atrophy occurs at a later stage compared to microstructural abnormalities and therefore cannot be used for monitoring short-term disease progression. We aimed to investigate whether cortical diffusion tensor imaging (DTI) and quantitative (q) magnetic resonance imaging (MRI) are able to detect early microstructural involvement of the cerebral cortex in CSVD.Materials and Methods33 CSVD patients without significant cortical or whole-brain atrophy and 16 healthy control subjects were included and underwent structural MRI, DTI and high-resolution qMRI with T2, T2* and T2' mapping at 3 T as well as comprehensive cognitive assessment. After tissue segmentation and reconstruction of the cortical boundaries with the Freesurfer software, DTI and qMRI parameters were saved as surface datasets and averaged across all vertices.ResultsCortical diffusivity and quantitative T2 values were significantly increased in patients compared to controls (p < 0.05). T2 values correlated significantly positively with white matter hyperintensity (WMH) volume (p < 0.01). Both cortical diffusivity and T2 showed significant negative associations with axonal damage to the white matter fiber tracts (p < 0.05).ConclusionsCortical diffusivity and quantitative T2 mapping are suitable to detect microstructural involvement of the cerebral cortex in CSVD and represent promising imaging biomarkers for monitoring disease progression and effects of therapeutical interventions in clinical studies.

Background Collaterals are the main determinants of the severity of cerebral ischemia and control the pace of the ischemic tissue damage in acute ischemic stroke. Assessment of collateral status remains a major challenge in stroke imaging. We evaluated a signal variance–based collateral vessel index in perfusion‐weighted imaging (CVIPWI) in terms of its association with initial stroke severity, presence of a mismatch for endovascular thrombectomy (EVT), and early functional outcome in patients with large‐vessel occlusion. Methods T2*‐weighted time series from dynamic susceptibility contrast perfusion imaging were processed to calculate the CVIPWI. Ischemic cores were segmented automatically on apparent diffusion coefficient maps. The relationship between collateral status and the fulfilment of mismatch criteria for EVT as well as the association between the CVIPWI and functional outcome in patients undergoing EVT were analyzed. Furthermore, spatial patterns of pial collateralization were investigated. Results A total of 156 patients with large‐vessel occlusion were included in the final analysis. Higher CVIPWI and thus better collateral supply was associated with lower baseline National Institutes of Health Stroke Scale and smaller baseline infarct volumes (P=0.022 and P=0.002, respectively), and the CVIPWI varied significantly among groups according to fulfillment of mismatch criteria for EVT (P<0.001). In patients undergoing EVT (n=105), the CVIPWI was an independent predictor of favorable functional outcome (modified Rankin scale score of 0–2) at discharge in multivariate analysis (P=0.031). In patients with EVT who had successful reperfusion (n=79), good collateral status was associated with a higher rate of early neurological improvement (P=0.026) and better functional outcome at discharge (P=0.04) in shift analysis. Conclusion Signal variance–based CVIPWI represents a semiquantitative and objective, thus observer‐independent parameter for direct assessment of collateral status with clinical relevance. Its use may inform clinical decision‐making and may be of interest for clinical stroke trials.

There is emerging evidence that sampling the blood-oxygen-level-dependent (BOLD) response with high temporal resolution opens up new avenues to study the in vivo functioning of the human brain with functional magnetic resonance imaging. Because the speed of sampling and the signal level are intrinsically connected in magnetic resonance imaging via the T1 relaxation time, optimization efforts usually must make a trade-off to increase the temporal sampling rate at the cost of the signal level. We present a method, which combines a sparse event-related stimulus paradigm with subsequent data reshuffling to achieve high temporal resolution while maintaining high signal levels (HiHi). The proof-of-principle is presented by separately measuring the single-voxel time course of the BOLD response in both the primary visual and primary motor cortices with 100-ms temporal resolution.

Background: We aimed to investigate whether combined phosphorous (P-31) magnetic resonance spectroscopic imaging (MRSI) and quantitative T' (2) mapping are able to detect alterations of the cerebral oxygen extraction fraction (OEF) and intracellular pH (pHi) as markers the of cellular energy metabolism in cerebral small vessel disease (SVD). Materials and methods: 32 patients with SVD and 17 age-matched healthy control subjects were examined with 3dimensional P-31 MRSI and oxygenation-sensitive quantitative T'(2) mapping (1/ T'(2) = 1/T-2* - 1/T-2) at 3 Tesla (T). PHi was measured within the white matter hyperintensities (WMH) in SVD patients. Quantitative T'(2) values were averaged across the entire white matter (WM). Furthermore, T'(2) values were extracted from normal-appearing WM (NAWM) and the WMH and compared between patients and controls. Results: Quantitative T' (2) values were significantly increased across the entire WM and in the NAWM in patients compared to control subjects (149.51 +/- 16.94 vs. 138.19 +/- 12.66 ms and 147.45 +/- 18.14 vs. 137.99 +/- 12.19 ms, p < 0.05). WM T'(2) values correlated significantly with the WMH load (.=0.441, p = 0.006). Increased T'2 was significantly associated with more alkaline pHi (.=0.299, p < 0.05). Both T' (2) and pHi were significantly positively correlated with vascular pulsatility in the distal carotid arteries (.=0.596, p = 0.001 and.=0.452, p = 0.016). Conclusions: This exploratory study found evidence of impaired cerebral OEF in SVD, which is associated with intracellular alkalosis as an adaptive mechanism. The employed techniques provide new insights into the pathophysiology of SVD with regard to disease-related consequences on the cellular metabolic state.

Background and purpose In patients with epilepsies of structural origin, brain atrophy and pathological alterations of the tissue microstructure extending beyond the putative epileptogenic lesion have been reported. However, in patients without any evidence of epileptogenic lesions on diagnostic magnetic resonance imaging (MRI), impairment of the brain microstructure has been scarcely elucidated. Using multiparametric quantitative (q) magnetic resonance imaging MRI, we aimed to investigate diffuse impairment of the microstructural tissue integrity in MRI-negative focal epilepsy patients. Methods 27 MRI-negative patients with focal epilepsy (mean age 33.1 ± 14.2 years) and 27 matched healthy control subjects underwent multiparametric qMRI including T1, T2, and PD mapping at 3 T. After tissue segmentation based on synthetic anatomies, mean qMRI parameter values were extracted from the cerebral cortex, the white matter (WM) and the deep gray matter (GM) and compared between patients and control subjects. Apart from calculating mean values for the qMRI parameters across the respective compartments, voxel-wise analyses were performed for each tissue class. Results There were no significant differences for mean values of quantitative T1, T2, and PD obtained from the cortex, the WM and the deep GM between the groups. Furthermore, the voxel-wise analyses did not reveal any clusters indicating significant differences between patients and control subjects for the qMRI parameters in the respective compartments. Conclusions Based on the employed methodology, no indication for an impairment of the cerebral microstructural tissue integrity in MRI-negative patients with focal epilepsy was found in this study. Further research will be necessary to identify relevant factors and mechanisms contributing to microstructural brain tissue damage in various subgroups of patients with epilepsy.

BACKGROUND:In relapsing-remitting multiple sclerosis (RRMS), cortical grey matter pathology relevantly contributes to long-term disability. Still, diffuse cortical inflammation cannot be detected with conventional MRI.OBJECTIVE:We aimed to assess microstructural damage of cortical grey matter over time and the relation to clinical disability as well as relapse activity in patients with RRMS using multiparametric quantitative (q)MRI techniques.METHODS:On 40 patients with RRMS and 33 age-matched and sex-matched healthy controls, quantitative T1, T2, T2* and proton density (PD) mapping was performed at baseline and follow-up after 2 years. Cortical qMRI parameter values were extracted with the FreeSurfer software using a surface-based approach. QMRI parameters, cortical thickness and white matter lesion (WML) load, as well as Expanded Disability Status Scale (EDSS) and relapse rate, were compared between time points.RESULTS:Over 2 years, significant increases of T1 (p≤0.001), PD (p≤0.001) and T2 (p=0.005) values were found in the patient, but not in the control group. At decreased relapse rate over time (p=0.001), cortical thickness, WML volume and EDSS remained unchanged.CONCLUSION:Despite clinical stability, cortical T1, T2 and PD values increased over time, indicating progressive demyelination and increasing water content. These parameters represent promising surrogate parameters of diffuse cortical inflammation in RRMS.

PurposeAim of this study was to develop a reliable B1 mapping method for brain imaging based on vendor MR sequences available on clinical scanners. Correction procedures for B0 distortions and slice profile imperfections are proposed, together with a phantom experiment for deriving the approximate time‐bandwidth‐product (TBP) of the excitation pulse, which is usually not known for vendor sequences.MethodsThe double angle method was used, acquiring two gradient echo echo‐planar imaging data sets with different excitation angles. A correction factor C (B1, TBP, B0) was derived from simulations for converting double angle method signal quotients into bias‐free B1 maps. In vitro and in vivo tests compare results with reference B1 maps based on an established in‐house sequence.ResultsThe simulation shows that C has a negligible B1 dependence, allowing for a polynomial approximation of C (TBP, B0). Signal quotients measured in a phantom experiment with known TBP reconfirm the simulation results. In vitro and in vivo B1 maps based on the proposed method, assuming TBP = 5.8 as derived from a phantom experiment, match closely the reference B1 maps. Analysis without B0 correction shows marked deviations in areas of distorted B0, highlighting the importance of this correction.ConclusionDouble angle method‐based B1 mapping was set up for vendor gradient echo‐echo‐planar imaging sequences, using a correction procedure for slice profile imperfections and B0 distortions. This will help to set up quantitative MRI studies on clinical scanners with release sequences, as the method does not require knowledge of the exact RF‐pulse profiles or the use of in‐house sequences.

Physical separation from caregivers activates attachment-related behaviors. However, neural underpinnings of this biological mechanism in humans and their development are poorly understood. We examined via functional MRI brain responses to pictorial representations of separation as a function of attachment-security, attachment-avoidance, and attachment-anxiety measured using the Child-Attachment-Interview, in 30 typically developing children (9-11 years). Attachment-related stimuli elicited enhanced activation in the precuneus, temporoparietal junction area, and medial superior frontal gyrus (described as mentalization network). More negatively rated attachment stimuli yielded increased activity in the inferior frontal gyrus/anterior insula and dorsal anterior cingulate cortex/ACC. Furthermore, ACC responses to attachment-related as compared to control stimuli were positively correlated with attachment-security and negatively correlated with attachment-avoidance. Our findings suggest that processing of separation cues elicits increased mentalization-related processing in children and activation of the salience network with increased negative valence of stimuli. Avoidant vs. securely attached children differentially activate ACC-dependent processes of affective evaluation.