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BackgroundIn 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.ObjectiveWe 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.MethodsOn 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.ResultsOver 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.ConclusionDespite 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.

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.

Previous diffusion tensor imaging (DTI) studies indicate that impaired microstructural integrity of the normal-appearing white matter (NAWM) is related to cognitive impairment in cerebral small vessel disease (SVD). This study aimed to investigate whether quantitative T2 relaxometry is a suitable imaging biomarker for the assessment of tissue changes related to cognitive abnormalities in patients with SVD. 39 patients and 18 age-matched healthy control subjects underwent 3 T magnetic resonance imaging (MRI) with T2-weighted multiple spin echo sequences for T2 relaxometry and DTI sequences, as well as comprehensive cognitive assessment. Averaged quantitative T2, fractional anisotropy (FA) and mean diffusivity (MD) were determined in the NAWM and related to cognitive parameters controlling for age, normalized brain volume, white matter hyperintensity volume and other conventional SVD markers. In SVD patients, quantitative T2 values were significantly increased compared to controls (p = 0.002) and significantly negatively correlated with the global cognitive performance (r= –0.410, p = 0.014) and executive function (r= –0.399, p = 0.016). DTI parameters did not correlate with cognitive function. T2 relaxometry of the NAWM seems to be sensitive to microstructural tissue damage associated with cognitive impairment in SVD and might be a promising imaging biomarker for evaluation of disease progression and possible effects of therapeutic interventions.

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.

Understanding the microstructural changes related to physiological aging of the cerebral cortex is pivotal to differentiate healthy aging from neurodegenerative processes. The aim of this study was to investigate the age-related global changes of cortical microstructure and regional patterns using multiparametric quantitative MRI (qMRI) in healthy subjects with a wide age range. 40 healthy participants (age range: 2nd to 8th decade) underwent high-resolution qMRI including T1, PD as well as T2, T2* and T2′ mapping at 3 Tesla. Cortical reconstruction was performed with the FreeSurfer toolbox, followed by tests for correlations between qMRI parameters and age. Cortical T1 values were negatively correlated with age (p=0.007) and there was a widespread age-related decrease of cortical T1 involving the frontal and the parietotemporal cortex, while T2 was correlated positively with age, both in frontoparietal areas and globally (p=0.004). Cortical T2′ values showed the most widespread associations across the cortex and strongest correlation with age (r= -0.724, p=0.0001). PD and T2* did not correlate with age. Multiparametric qMRI allows to characterize cortical aging, unveiling parameter-specific patterns. Quantitative T2′ mapping seems to be a promising imaging biomarker of cortical age-related changes, suggesting that global cortical iron deposition is a prominent process in healthy aging.

BACKGROUND In epilepsy patients with focal cortical dysplasia (FCD) as the epileptogenic focus, global cortical signal changes are generally not visible on conventional MRI. However, epileptic seizures or antiepileptic medication might affect normal-appearing cerebral cortex and lead to subtle damage. PURPOSE To investigate cortical properties outside FCD regions with T2 -relaxometry. STUDY TYPE Prospective study. SUBJECTS Sixteen patients with epilepsy and FCD and 16 age-/sex-matched healthy controls. FIELD STRENGTH/SEQUENCE 3T, fast spin-echo T2 -mapping, fluid-attenuated inversion recovery (FLAIR), and synthetic T1 -weighted magnetization-prepared rapid acquisition of gradient-echoes (MP-RAGE) datasets derived from T1 -maps. ASSESSMENT Reconstruction of the white matter and cortical surfaces based on MP-RAGE structural images was performed to extract cortical T2 values, excluding lesion areas. Three independent raters confirmed that morphological cortical/juxtacortical changes in the conventional FLAIR datasets outside the FCD areas were definitely absent for all patients. Averaged global cortical T2 values were compared between groups. Furthermore, group comparisons of regional cortical T2 values were performed using a surface-based approach. Tests for correlations with clinical parameters were carried out. STATISTICAL TESTS General linear model analysis, permutation simulations, paired and unpaired t-tests, and Pearson correlations. RESULTS Cortical T2 values were increased outside FCD regions in patients (83.4 ± 2.1 msec, control group 81.4 ± 2.1 msec, P = 0.01). T2 increases were widespread, affecting mainly frontal, but also parietal and temporal regions of both hemispheres. Significant correlations were not observed (P ≥ 0.55) between cortical T2 values in the patient group and the number of seizures in the last 3 months or the number of anticonvulsive drugs in the medical history. DATA CONCLUSION Widespread increases in cortical T2 in FCD-associated epilepsy patients were found, suggesting that structural epilepsy in patients with FCD is not only a symptom of a focal cerebral lesion, but also leads to global cortical damage not visible on conventional MRI. EVIDENCE LEVEL 21 TECHNICAL EFFICACY STAGE: 3 J. MAGN. RESON. IMAGING 2020;52:1783-1789.

Simple Summary MRI plays an important role in the classification of structural brain changes and quantitative MRI can provide more and different information than conventional MRI. A comparison with neuropathological parameters helps to expand the understanding of (patho)physiological concepts but has hardly been carried out so far. In this prospective study, we correlated quantitative MRI data with histological features of 25 patients with isocitrate dehydrogenase (IDH) wild-type glioma. We found that the relative shortening of T1 relaxation time after the application of contrast agent was pronounced in the presence of tumor cells and vascular proliferates, indicating a disruption of the blood brain barrier (BBB). T2′ relaxation time, depending on local deoxyhemoglobin concentration, correlated with the vessel density but not with immunopositivity for endogenous markers of hypoxia. Abstract Quantitative MRI allows to probe tissue properties by measuring relaxation times and may thus detect subtle changes in tissue composition. In this work we analyzed different relaxation times (T1, T2, T2* and T2′) and histological features in 321 samples that were acquired from 25 patients with newly diagnosed IDH wild-type glioma. Quantitative relaxation times before intravenous application of gadolinium-based contrast agent (GBCA), T1 relaxation time after GBCA as well as the relative difference between T1 relaxation times pre-to-post GBCA (T1rel) were compared with histopathologic features such as the presence of tumor cells, cell and vessel density, endogenous markers for hypoxia and cell proliferation. Image-guided stereotactic biopsy allowed for the attribution of each tissue specimen to its corresponding position in the respective relaxation time map. Compared to normal tissue, T1 and T2 relaxation times and T1rel were prolonged in samples containing tumor cells. The presence of vascular proliferates was associated with higher T1rel values. Immunopositivity for lactate dehydrogenase A (LDHA) involved slightly longer T1 relaxation times. However, low T2′ values, suggesting high amounts of deoxyhemoglobin, were found in samples with elevated vessel densities, but not in samples with increased immunopositivity for LDHA. Taken together, some of our observations were consistent with previous findings but the correlation of quantitative MRI and histologic parameters did not confirm all our pathophysiology-based assumptions.

Exercise has been shown to counteract age-related volume decreases in the human brain, and in this imaging study, we ask whether the same holds true for the microstructure of the cortex. Healthy older adults (n = 47, 65-90 years old) either exercised three times a week on a stationary bike or maintained their usual physical routine over a 12-week period. Quantitative longitudinal relaxation rate (R1 ) magnetic resonance imaging (MRI) maps were made at baseline and after the 12-week intervention. R1 is commonly taken to reflect cortical myelin density. The change in R1 (ΔR1 ) was significantly increased in a region of interest (ROI) in the primary motor cortex containing motor outputs to the leg musculature in the exercise group relative to the control group (p = .04). The change in R1 in this ROI correlated with an increase in oxygen consumption at the first ventilatory threshold (VT1) (p = .04), a marker of improvement in submaximal aerobic performance. An exploratory analysis across the cortex suggested that the correlation was predominately confined to the leg representation in the motor cortex. This study suggests that microstructural declines in the cortex of older adults may be staved off by exercise.

We aimed to assess cortical damage in patients with relapsing-remitting multiple sclerosis (RRMS)/clinically isolated syndrome (CIS) with a multiparametric, surface-based quantitative MRI (qMRI) approach and to evaluate the correlation of imaging-derived parameters with cognitive scores, hypothesizing that qMRI parameters are correlated with cognitive abilities. Multiparametric qMRI-data (T1, T2 and T2* relaxation times and proton density (PD)) were obtained from 34 patients/24 matched healthy control subjects. Cortical qMRI values were analyzed on the reconstructed cortical surface with Freesurfer. We tested for group differences of cortical microstructural parameters between the healthy and patient collectives and for partial Pearson correlations of qMRI parameters with cognitive scores, correcting for age. Cortical T2-/T2*-/PD values and four cognitive parameters differed between groups (p ≤ 0.046). These cognitive scores, reflecting information processing speed, verbal memory, visuospatial abilities, and attention, were correlated with cortical T2 (p ≤ 0.02) and T2* (p ≤ 0.03). Cortical changes appeared heterogeneous across the cortex and their distribution differed between the parameters. Vertex-wise correlation of T2 with neuropsychological parameters revealed specific patterns of cortical damage being related to distinct cognitive deficits. Microstructural changes are distributed heterogeneously across the cortex in RRMS/CIS. QMRI has the potential to provide surrogate parameters for the assessment of cognitive impairment in these patients for clinical studies. The characteristics of cognitive impairment in RRMS might depend on the distribution of cortical changes. • The goal of the presented study was to investigate cortical changes in RRMS/CIS and their relation to the cognitive status, using multiparametric quantitative MRI. • Cortical T2, T2*, and PD increases observed in patients appeared heterogeneous across the cortex and their distribution differed between the parameters. • Vertex-wise correlation of T2 with neuropsychological scores revealed specific patterns of cortical changes being related to distinct cognitive deficits.

Structural cerebral MRI analysis in patients with neurological diseases usually requires T1-weighted datasets for tissue segmentation. For this purpose, synthetic T1-weighted images which are constructed from quantitative maps of the underlying tissue parameters such as the T1 relaxation time and the proton density (PD) may provide advantages over conventional datasets. However, in some cases synthetic images may suffer from specific artifacts, hampering accurate tissue segmentation. The goal was to improve a previously described method for the calculation of synthetic magnetization-prepared rapid gradient-echo (MP-RAGE) datasets from quantitative T1 and PD maps. Improvements comprise a B0-correction for the water-selective excitation pulses employed in T1-mapping and the use of T1-based pseudo-PD maps. Synthetic T1-weighted MP-RAGE datasets were calculated, using the standard and the improved algorithm, for 10 patients with focal epilepsy (caused by focal cortical dysplasia in 9), 10 patients with multiple sclerosis and 10 healthy control subjects and segmented with the Freesurfer toolbox. Visual inspection disclosed that segmentation of the standard synthetic datasets was inaccurate in 6 out of 10 patients with epilepsy, 7 out of 10 patients with multiple sclerosis and 7 out of 10 healthy control subjects, while the improved synthetic datasets resulted in adequate segmentation outcomes in the majority of cases. Only for one patient with multiple sclerosis and one with epilepsy, segmentation in basal temporal regions was not sufficient. Furthermore, data based on the standard algorithm showed strong signal non-uniformities in basal regions. This effect was not present in the improved synthetic datasets.

Background and Purpose— Chronic cerebral hemodynamic impairment due to high-grade occlusive carotid disease may lead to compromised energy metabolism. This might result in chronic subtle tissue damage, even in patients without overt brain infarction. The aim of this study was to investigate hypoperfusion-related changes of cerebral energy metabolism and their potential restitution after revascularization. For this purpose, 3-dimensional 31 P magnetic resonance spectroscopy and oxygenation-sensitive T2′ magnetic resonance imaging were used (with 1/T2′=1/T2*−1/T2), which were expected to cross-validate each other. Methods— Ten patients with unilateral high-grade carotid artery stenosis resulting in a transient ischemic attack or a nondisabling cerebral ischemia were included. Then, high-energy metabolites, intracellular pH, and oxygenation-sensitive quantitative (q)T2′ values were determined in noninfarcted hypoperfused areas delineated on time-to-peak maps from perfusion-weighted imaging and in unaffected contralateral areas before and shortly after carotid stenting/endarterectomy. Repeated measures ANOVA was used to test for intervention effects. Results— Within dependent hypoperfused areas ipsilateral to the stenosis, qT2′ was significantly decreased ( P P P =0.005) irrespective of time point and hemisphere. Conclusions— After revascularization of unilateral high-grade carotid stenosis, previously decreased qT2′ in the dependent hypoperfused territory as marker of hypoxia reincreases not only in the dependent territory but also in corresponding contralateral brain tissue. This might indicate a restriction of the whole-brain oxygen metabolism in case of unilateral high-grade carotid stenosis and an improvement of whole-brain oxygenation after revascularization that goes beyond acute clinically apparent affection of the dependent territory. Furthermore, tissue oxygen supply seems to be closely linked to intracellular pH.

The present study validates the results of automated hippocampal subfield segmentation with histopathology in epilepsy patients undergoing epilepsy surgery.We performed an automated hippocampal subfield segmentation on presurgical three-dimensional, T1-weighted magnetization Prepared Rapid Acquisition of Gradient Echoes Magnetic Resonance Imaging (MRI) data of 25 patients with unilateral mesial temporal lobe epilepsy due to hippocampal sclerosis (HS), using Freesurfer Version 6.0. The resulting volumes of cornu ammonis (CA) subfields CA1, CA2/3, CA4 and the dentate gyrus (DG) were compared to the histopathological cell count.We found a significant correlation between histopathology in subregion CA2 and automated segmentation of subregion CA1 (p = 0.0062), CA2/3 (p = 0.004), CA4 (p = 0.0062) and the DG (p = 0.0054), between histopathology in CA3 and automated segmentation of CA1 (p = 0.0132), CA2/3 (p = 0.0004), CA4 (p = 0.0032) and the DG (p = 0.0037), as well as between histopathology in the DG and automated segmentation of CA1 (p = 0.0115), CA2/3 (p0.0001), CA4 (p0.0001) and the DG (p = 0.0001). The histopathological finding of HS type 1 could correctly be classified in all cases on MRI.The present study shows significant correlations between histopathological evaluation and results of the automated segmentation of the hippocampus, thereby validating the automated segmentation method. As the differential involvement of different hippocampal subfields may be associated with clinical parameters and the outcome after epilepsy surgery, the automated segmentation is also promising for prognostic purposes.

Purpose In diffusion MRI, the actual b‐value played out on the scanner may deviate from the nominal value due to magnetic field imperfections. A simple image‐based correction method for this problem is presented. Methods The apparent diffusion constant (ADC) of a water phantom was measured voxel‐wise along 64 diffusion directions at b = 1000 s/mm2. The true diffusion constant of water was estimated, considering the phantom temperature. A voxel‐wise correction factor, providing an effective b‐value including any magnetic field deviations, was determined for each diffusion direction by relating the measured ADC to the true diffusion constant. To test the method, the measured b‐value map was used to calculate the corrected voxel‐wise ADC for additionally acquired diffusion data sets on the same water phantom and data sets acquired on a small water phantom at three different positions. Diffusion tensor was estimated by applying the measured b‐value map to phantom and in vivo data sets. Results The b‐value‐corrected ADC maps of the phantom showed the expected spatial uniformity as well as a marked improvement in consistency across diffusion directions. The b‐value correction for the brain data resulted in a 5.8% and 5.5% decrease in mean diffusivity and angular differences of the primary diffusion direction of 2.71° and 0.73° inside gray and white matter, respectively. Conclusion The actual b‐value deviates significantly from its nominal setting, leading to a spatially variable error in the common diffusion outcome measures. The suggested method measures and corrects these artifacts. ISSN:0740-3194 ISSN:1522-2594

Purpose: Auditory functional MRI (fMRI) often uses silent inter-volume delays for stimulus presentation. However, maintaining the steady-state of the magnetization usually requires constant delays. Here, a novel acquisition scheme dubbed “pre-Saturated EPI using Multiple delays in Steady-state” (SEPIMS) is proposed, using spin saturation at a fixed delay before each volume to maintain steady-state conditions, independent of previous spin history. This concept allows for variable inter-volume delays and thus for flexible stimulus design in auditory fMRI. The purpose was to compare the signal stability of SEPIMS and conventional sparse EPI (CS-EPI). Methods: The saturation module comprises two non-selective adiabatic saturation pulses. The efficiency of the saturation and its effect on the SEPIMS signal stability is tested in vitro and in vivo. Results: Data show that SEPIMS yields the same signal stability as CS-EPI, even for extreme variations between inter-volume delay durations. However, dual saturation pulses are required to achieve sufficiently high saturation efficiency in compartments with long T1 values. Importantly, spoiler gradient pulses after the EPI readout have to be optimized to avoid eddy-current-induced image distortions. Conclusion: The proposed SEPIMS sequence maintains high signal stability in the presence of variable inter-volume durations, thus allowing for flexible stimulus design.

In epilepsy patients with focal cortical dysplasia (FCD) as the epileptogenic focus, global cortical signal changes are generally not visible on conventional MRI. However, epileptic seizures or antiepileptic medication might affect normal-appearing cerebral cortex and lead to subtle damage.To investigate cortical properties outside FCD regions with TProspective study.Sixteen patients with epilepsy and FCD and 16 age-/sex-matched healthy controls.3T, fast spin-echo TReconstruction of the white matter and cortical surfaces based on MP-RAGE structural images was performed to extract cortical TGeneral linear model analysis, permutation simulations, paired and unpaired t-tests, and Pearson correlations.Cortical TWidespread increases in cortical T21 TECHNICAL EFFICACY STAGE: 3 J. MAGN. RESON. IMAGING 2020;52:1783-1789.

Purpose To investigate cortical thickness and cortical quantitative T2 values as imaging markers of microstructural tissue damage in patients with unilateral high-grade internal carotid artery occlusive disease (ICAOD). Methods A total of 22 patients with ≥70% stenosis (mean age 64.8 years) and 20 older healthy control subjects (mean age 70.8 years) underwent structural magnetic resonance imaging (MRI) and high-resolution quantitative (q)T2 mapping. Generalized linear mixed models (GLMM) controlling for age and white matter lesion volume were employed to investigate the effect of ICAOD on imaging parameters of cortical microstructural integrity in multivariate analyses. Results There was a significant main effect (p p = 0.01) leading to increased qT2 in the poststenotic hemisphere, which was not found for cortical thickness. The GLMM showed that in general cortical thickness was decreased and cortical qT2 values were increased with increasing age (p Conclusion Unilateral high-grade carotid occlusive disease is associated with widespread cortical thinning and prolongation of cortical qT2, presumably reflecting hypoperfusion-related microstructural cortical damage similar to accelerated aging of the cerebral cortex. Cortical thinning and increase of cortical qT2 seem to reflect different aspects and different pathophysiological states of cortical degeneration. Quantitative T2 mapping might be a sensitive imaging biomarker for early cortical microstructural damage.

Supplemental Digital Content is Available in the Text. Inactivating paired continuous theta-burst stimulation of the primary motor cortex but not on the secondary somatosensory area flattened the relationship between brain activation and stimulus strength while not impacting on the subjective perceptions., Noninvasive modulation of the activity of pain-related brain regions by means of transcranial magnetic stimulation promises an innovative approach at analgesic treatments. However, heterogeneous successes in pain modulation by setting reversible “virtual lesions” at different brain areas point at unresolved problems including the optimum stimulation site. The secondary somatosensory cortex (S2) has been previously identified to be involved in the perception of pain-intensity differences. Therefore, impeding its activity should impede the coding of the sensory component of pain intensity, resulting in a flattening of the relationship between pain intensity and physical stimulus strength. This was assessed using inactivating spaced continuous theta-burst stimulation (cTBS) in 18 healthy volunteers. In addition, cTBS was applied on the primary motor cortex (M1) shown previously to yield moderate and variable analgesic effects, whereas sham stimulation at both sites served as placebo condition. Continuous theta-burst stimulation flattened the relationship between brain activation and stimulus strength, mainly at S2, the insular cortex, and the postcentral gyrus (16 subjects analyzed). However, these effects were observed after inactivation of M1 while this effect was not observed after inactivation of S2. Nevertheless, both the M1 and the S2-spaced cTBS treatment were not reflected in the ratings of the nociceptive stimuli of different strengths (17 subjects analyzed), contrasting with the clear coding of stimulus strength by these data. Hence, while modulating the central processing of nociceptive input, cTBS failed to produce subjectively relevant changes in pain perception, indicating that the method in the present implementation is still unsuitable for clinical application.

The aim of this cross-sectional study was to determine the associations of objectively assessed habitual physical activity and physical performance with brain plasticity outcomes and brain-derived neurotrophic factor (BDNF) levels in cognitively healthy older adults. Physical performance was analyzed based on cardiopulmonary exercise-testing data and accelerometer-based physical activity was analyzed as total activity counts, sedentary time, light physical activity and moderate to vigorous physical activity. Brain plasticity outcomes included magnetic resonance spectroscopy (MRS)-based markers, quantitative imaging-based hippocampal volume and BDNF serum levels. The association between physical performance and hippocampal volume was strongly influenced by participants' education, sex, age and BMI. Confounder-controlled correlation revealed significant associations of brain plasticity outcomes with physical activity but not with performance. MRS-based adenosine triphosphate to phosphocreatine and glycerophosphocholine to phosphocreatine ratios were significantly associated with accelerometer total activity counts. BDNF was detrimentally associated with sedentary time but beneficially related to accelerometer total activity counts and moderate to vigorous physical activity. Exceeding the current moderate to vigorous physical activity recommendations led to significantly higher BDNF levels. Our results indicate that regular physical activity might be beneficial for preserving brain plasticity in higher age. In this study these associations were not mediated significantly by physical performance. Overall physical activity and exceeding current moderate to vigorous physical activity recommendations were positively associated with BDNF. Sedentary behavior, however, seems to be negatively related to neurotrophic factor bioavailability in the elderly.

The aim of this study was to evaluate whether maps of quantitative T1 (qT1) differences induced by a gadolinium-based contrast agent (CA) are better suited than conventional T1-weighted (T1w) MR images for detecting infiltration inside and beyond the peritumoral edema of glioblastomas. Conventional T1w images and qT1 maps were obtained before and after gadolinium-based CA administration in 33 patients with glioblastoma before therapy. The following data were calculated: (i) absolute qT1-difference maps (qT1 pre-CA - qT1 post-CA), (ii) relative qT1-difference maps, (iii) absolute and (iv) relative differences of conventional T1w images acquired pre- and post-CA. The values of these four datasets were compared in four different regions: (a) the enhancing tumor, (b) the peritumoral edema, (c) a 5 mm zone around the pathology (defined as the sum of regions a and b), and (d) the contralateral normal appearing brain tissue. Additionally, absolute qT1-difference maps (displayed with linear gray scaling) were visually compared with respective conventional difference images. The enhancing tumor was visible both in the difference of conventional pre- and post-CA T1w images and in the absolute qT1-difference maps, whereas only the latter showed elevated values in the peritumoral edema and in some cases even beyond. Mean absolute qT1-difference values were significantly higher (P < 0.01) in the enhancing tumor (838 ± 210 ms), the peritumoral edema (123 ± 74 ms) and in the 5 mm zone around the pathology (81 ± 31 ms) than in normal appearing tissue (32 ± 35 ms). In summary, absolute qT1-difference maps-in contrast to the difference of T1w images-of untreated glioblastomas appear to be able to visualize CA leakage, and thus might indicate tumor cell infiltration in the edema region and beyond. Therefore, the absolute qT1-difference maps are potentially useful for treatment planning.

The detection of cortical malformations in conventional MR images can be challenging. Prominent examples are focal cortical dysplasias (FCD), the most common cause of drug-resistant focal epilepsy. The two main MRI hallmarks of cortical malformations are increased cortical thickness and blurring of the gray (GM) and white matter (WM) junction. The purpose of this study was to derive synthetic anatomies from quantitative T1 maps for the improved display of the above imaging characteristics in individual patients. On the basis of a T1 map, a mask comprising pixels with T1 values characteristic for GM is created from which the local cortical extent (CE) is determined. The local smoothness (SM) of the GM-WM junctions is derived from the T1 gradient. For display of cortical malformations, the resulting CE and SM maps serve to enhance local intensities in synthetic double inversion recovery (DIR) images calculated from the T1 map. The resulting CE- and/or SM-enhanced DIR images appear hyperintense at the site of cortical malformations, thus facilitating FCD detection in epilepsy patients. However, false positives may arise in areas with naturally elevated CE and/or SM, such as large GM structures and perivascular spaces. In summary, the proposed method facilitates the detection of cortical abnormalities such as cortical thickening and blurring of the GM-WM junction which are typical FCD markers. Still, subject motion artifacts, perivascular spaces, and large normal GM structures may also yield signal hyperintensity in the enhanced synthetic DIR images, requiring careful comparison with clinical MR images by an experienced neuroradiologist to exclude false positives.

BACKGROUND AND PURPOSE: Chronic hemodynamic impairment in high-grade carotid occlusive disease is thought to cause microstructural abnormalities that might be subclinical or lead to subtle symptoms including cognitive impairment. Quantitative MR imaging allows assessing pathologic structural changes beyond macroscopically visible tissue damage. In this study, high-resolution quantitative T2 mapping combined with DSC-based PWI was used to investigate quantitative T2 changes as a potential marker of microstructural damage in relation to hemodynamic impairment in patients with unilateral high-grade carotid occlusive disease. MATERIALS AND METHODS: Eighteen patients with unilateral high-grade ICA or MCA stenosis/occlusion were included in the study. T2 values and deconvolved perfusion parameters, including relative CBF, relative CBV, and the relative CBF/relative CBV ratio as a potential indicator of local cerebral perfusion pressure, were determined within areas with delayed TTP and compared with values from contralateral unaffected areas after segmentation of normal-appearing hypoperfused WM and cortical regions. Hemispheric asymmetry indices were calculated for all parameters. RESULTS: Quantitative T2 was significantly prolonged (P < .01) in hypoperfused tissue and correlated significantly (P < .01) with TTP delay and relative CBF/relative CBV reduction in WM. Significant correlations (P < .001) between TTP delay and the relative CBF/relative CBV ratio were found both in WM and in cortical areas. CONCLUSIONS: Quantitative T2 can be used as a marker of microstructural tissue damage even in normal-appearing GM and WM within a vascular territory affected by high-grade carotid occlusive disease. Furthermore, the extent of damage correlates with the degree of hemodynamic failure measured by DSC perfusion parameters.

The purpose of this work was to optimize the acquisition of diffusion-weighted (DW) single-refocused spin-echo (srSE) data without intrinsic eddy-current compensation (ECC) for an improved performance of ECC postprocessing. The rationale is that srSE sequences without ECC may yield shorter echo times (TE) and thus higher signal-to-noise ratios (SNR) than srSE or twice-refocused spin-echo (trSE) schemes with intrinsic ECC. The proposed method employs dummy scans with DW gradients to drive eddy currents into a steady state before data acquisition. Parameters of the ECC postprocessing algorithm were also optimized. Simulations were performed to obtain minimum TE values for the proposed sequence and sequences with intrinsic ECC. Experimentally, the proposed method was compared with standard DW-trSE imaging, both in vitro and in vivo. Simulations showed substantially shorter TE for the proposed method than for methods with intrinsic ECC when using shortened echo readouts. Data of the proposed method showed a marked increase in SNR. A dummy scan duration of at least 1.5 s improved performance of the ECC postprocessing algorithm. Changes proposed for the DW-srSE sequence and for the parameter setting of the postprocessing ECC algorithm considerably reduced eddy-current artifacts and provided a higher SNR.

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. This Part II includes the experimental and translational approaches and a discussion of the future perspectives, while the diagnostic methods, EEG network analysis, biomarkers, and personalized treatment approaches were addressed in Part I [1].

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. Part I includes the clinical phenotyping and diagnostic methods, EEG network-analysis, biomarkers, and personalized treatment approaches. In Part II, experimental and translational approaches will be discussed (Bauer et al., 2017) [1].

Purpose The variable flip angle method derives T1 maps from radiofrequency-spoiled gradient-echo data sets, acquired with different flip angles α. Because the method assumes validity of the Ernst equation, insufficient spoiling of transverse magnetization yields errors in T1 estimation, depending on the chosen radiofrequency-spoiling phase increment (Δϕ). This paper presents a versatile correction method that uses modified flip angles α' to restore the validity of the Ernst equation. Methods Spoiled gradient-echo signals were simulated for three commonly used phase increments Δϕ (50°/117°/150°), different values of α, repetition time (TR), T1, and a T2 of 85 ms. For each parameter combination, α′ (for which the Ernst equation yielded the same signal) and a correction factor CΔϕ(α, TR, T1) = α′/α were determined. CΔϕ was found to be independent of T1 and fitted as polynomial CΔϕ(α, TR), allowing to calculate α′ for any protocol using this Δϕ. The accuracy of the correction method for T2 values deviating from 85 ms was also determined. The method was tested in vitro and in vivo for variable flip angle scans with different acquisition parameters. Results The technique considerably improved the accuracy of variable flip angle–based T1 maps in vitro and in vivo. Conclusions The proposed method allows for a simple correction of insufficient spoiling in gradient-echo data. The required polynomial parameters are supplied for three common Δϕ. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Oxygenation-sensitive spin relaxation time T2′ and relaxation rate R2′ (1/T2′) are presumed to be markers of the cerebral oxygen extraction fraction (OEF) in acute ischemic stroke. In this study, we investigate the relationship of T2′/R2′ with dynamic susceptibility contrast-based relative cerebral blood flow (rCBF) in acute ischemic stroke to assess their plausibility as surrogate markers of the ischemic penumbra. Twenty-one consecutive patients with internal carotid artery and/or middle cerebral artery occlusion were studied at 3.0 T. A physiological model of the cerebral vasculature (VM) was used to process PWI raw data in addition to a conventional deconvolution technique. T2′, R2′, and rCBF values were extracted from the ischemic core and hypoperfused areas. Within hypoperfused tissue, no correlation was found between deconvolved rCBF and T2′ ( r = −0.05, p = 0.788), or R2′ ( r = 0.039, p = 0.836). In contrast, we found a strong positive correlation with T2′ ( r = 0.444, p = 0.006) and negative correlation with R2′ ( r = −0.494, p = 0.0025) for rCBFVM, indicating increasing OEF with decreasing CBF and that rCBF based on the vascular model may be more closely related to metabolic disturbances. Further research to refine and validate these techniques may enable their use as MRI-based surrogate markers of the ischemic penumbra for selecting stroke patients for interventional treatment strategies.

Considering the increasing acknowledgment of the human sense of smell as a significant component of the quality of life, olfactory drug effects gain potential clinical importance. A recent observation in a human experimental context indicated that Δ9-tetrahydrocannabinol (THC) impaired the subject’s performance in olfactory tests. To further analyze the role of THC in human olfaction, the present report addresses its effects on the central processing of olfactory stimuli. Employing a placebo-controlled randomized crossover design, an oral dose of 20 mg THC was administered in 15 healthy volunteers. The central processing of olfactory input, consisting of short pulses of gaseous vanillin or hydrogen sulfide, and for comparison, of non-odorous but painful carbon dioxide, were investigated before and after administration of THC or placebo in a pharmacological functional magnet resonance imaging study. Following THC administration, the vanillin stimuli lost their pleasantness and became hedonically inert. This observation had its functional correlate in reduced stimulus-associated brain activations located in the left amygdala, the hippocampus and superior temporal pole (peak MNI coordinates x = − 27, y = − 1, z = − 26 mm p = 0.039). Differences in amygdala activations were significantly correlated with the corresponding differences in vanillin pleasantness (p = 0.025). By contrast, no effects were observed on the perception of processing of H2S stimuli. The results support that THC induced a modulation of the central processing of olfactory input. The THC-induced reduction in the pleasantness of a pleasurable odor was accompanied by reduced activations in the limbic system. Results agree with previous observation of negative effects of cannabinoids on the human sense of smell and strengthen the evidence that THC-based medications will be among drugs with olfactory side effects.

A method is presented for correcting the effects of stimulated and indirect echoes on quantitative T2 mapping data acquired with multiple spin echo techniques, such as turbo spin echo. In contrast to similar correction techniques proposed in the literature, the method does not require a priori knowledge of the radio frequency (RF) pulse profiles. In a first step, for the T2 mapping protocol under investigation, signal decay curves S(TE) are simulated for a range of different RF pulse profiles. The actual signal decay S(TE) is then measured on a phantom with known T2, so the approximate RF pulse profiles can be derived via comparison with the simulated decay curves. In a second step, with the RF pulses obtained from step one, signal decay curves S(TE) are simulated for different T2 values and fitted mono-exponentially, thus allowing to deduce the relationship between true T2 and the apparent T2 (T2app) values. Results show that this relationship is approximately linear, allowing for a direct correction of T2app maps. If the amplitude of the transmitted RF field (B1) does not exceed the nominal value by more than 10%, it is shown that a B1-independent correction of T2app maps yields sufficiently accurate results for T2. A B1-dependent version is also presented. The method is tested in vitro on a phantom with different T2 values and in vivo on healthy subjects.