Cortical microstructural involvement in cerebral small vessel disease.

Background: In 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 Methods: 33 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. Results: Cortical 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). Conclusions: Cortical 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.

Focal epilepsy without overt epileptogenic lesions: no evidence of microstructural brain tissue damage in multi-parametric quantitative MRI.

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.

Multiparametric quantitative MRI reveals progressive cortical damage over time in clinically stable relapsing-remitting MS.

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.

B1 mapping using an EPI-based double angle approach: A practical guide for correcting slice profile and B0 distortion effects.

PURPOSE: Aim 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. METHODS: The 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. RESULTS: The 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. CONCLUSION: Double 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.

Impaired oxygen extraction and adaptation of intracellular energy metabolism in cerebral small vessel disease.

Background: We aimed to investigate whether combined phosphorous (31P) 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 3-dimensional 31P MRSI and oxygenation-sensitive quantitative T 2 ' mapping (1/ T 2 '  = 1/T2* - 1/T2) 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 (ρ=0.441, p = 0.006). Increased T 2 ' was significantly associated with more alkaline pHi (ρ=0.299, p < 0.05). Both T 2 ' and pHi were significantly positively correlated with vascular pulsatility in the distal carotid arteries (ρ=0.596, p = 0.001 and ρ=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.

Matching Quantitative MRI Parameters with Histological Features of Treatment-Naïve IDH Wild-Type Glioma.

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.

Multiparametric Quantitative MRI in Neurological Diseases.

Magnetic resonance imaging (MRI) is the gold standard imaging technique for diagnosis and monitoring of many neurological diseases. However, the application of conventional MRI in clinical routine is mainly limited to the visual detection of macroscopic tissue pathology since mixed tissue contrasts depending on hardware and protocol parameters hamper its application for the assessment of subtle or diffuse impairment of the structural tissue integrity. Multiparametric quantitative (q)MRI determines tissue parameters quantitatively, enabling the detection of microstructural processes related to tissue remodeling in aging and neurological diseases. In contrast to measuring tissue atrophy via structural imaging, multiparametric qMRI allows for investigating biologically distinct microstructural processes, which precede changes of the tissue volume. This facilitates a more comprehensive characterization of tissue alterations by revealing early impairment of the microstructural integrity and specific disease-related patterns. So far, qMRI techniques have been employed in a wide range of neurological diseases, including in particular conditions with inflammatory, cerebrovascular and neurodegenerative pathology. Numerous studies suggest that qMRI might add valuable information, including the detection of microstructural tissue damage in areas appearing normal on conventional MRI and unveiling the microstructural correlates of clinical manifestations. This review will give an overview of current qMRI techniques, the most relevant tissue parameters and potential applications in neurological diseases, such as early (differential) diagnosis, monitoring of disease progression, and evaluating effects of therapeutic interventions.

Microstructural Alterations Analogous to Accelerated Aging of the Cerebral Cortex in Carotid Occlusive Disease.

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 < 0.05) of the group (patients/controls) on both cortical thickness and cortical qT2 values with cortical thinning and increased cortical qT2 in patients compared to controls, irrespective of the hemisphere. The presence of upstream carotid stenosis had a significant main effect on cortical qT2 values (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 < 0.05). 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.

A novel sequence to improve auditory functional MRI with variable silent delays.

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.

DSC perfusion-based collateral imaging and quantitative T2 mapping to assess regional recruitment of leptomeningeal collaterals and microstructural cortical tissue damage in unilateral steno-occlusive vasculopathy.

Leptomeningeal collateral supply is considered pivotal in steno-occlusive vasculopathy to prevent chronic microstructural ischaemic tissue damage. The aim of this study was to assess the alleged protective role of leptomeningeal collaterals in patients with unilateral high-grade steno-occlusive vasculopathy using quantitative (q)T2 mapping and perfusion-weighted imaging (PWI)-based collateral abundance. High-resolution qT2 was used to estimate microstructural damage of the segmented normal-appearing cortex. Volumetric abundance of collaterals was assessed based on PWI source data. The ratio relative cerebral blood flow/relative cerebral blood volume (rCBF/rCBV) as a surrogate of relative cerebral perfusion pressure (rCPP) was used to investigate the intravascular hemodynamic competency of pial collateral vessels and the hemodynamic state of brain parenchyma. Within the dependent vascular territory with increased cortical qT2 values (P = 0.0001) compared to the contralateral side, parenchymal rCPP was decreased (P = 0.0001) and correlated negatively with increase of qT2 (P < 0.05). Furthermore, volumetric abundance of adjacent leptomeningeal collaterals was significantly increased (P < 0.01) and negatively correlated with changes of parenchymal rCPP (P = 0.01). Microstructural cortical damage is closely related to restrictions of antegrade blood flow despite increased pial collateral vessel abundance. Therefore, increased leptomeningeal collateral supply cannot necessarily be regarded as a sign of effective compensation in patients with high-grade steno-occlusive vasculopathy.

T2 relaxation time of the normal-appearing white matter is related to the cognitive status in cerebral small vessel disease.

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.

Central encoding of the strength of intranasal chemosensory trigeminal stimuli in a human experimental pain setting.

An important measure in pain research is the intensity of nociceptive stimuli and their cortical representation. However, there is evidence of different cerebral representations of nociceptive stimuli, including the fact that cortical areas recruited during processing of intranasal nociceptive chemical stimuli included those outside the traditional trigeminal areas. Therefore, the aim of this study was to investigate the major cerebral representations of stimulus intensity associated with intranasal chemical trigeminal stimulation. Trigeminal stimulation was achieved with carbon dioxide presented to the nasal mucosa. Using a single-blinded, randomized crossover design, 24 subjects received nociceptive stimuli with two different stimulation paradigms, depending on the just noticeable differences in the stimulus strengths applied. Stimulus-related brain activations were recorded using functional magnetic resonance imaging with event-related design. Brain activations increased significantly with increasing stimulus intensity, with the largest cluster at the right Rolandic operculum and a global maximum in a smaller cluster at the left lower frontal orbital lobe. Region of interest analyses additionally supported an activation pattern correlated with the stimulus intensity at the piriform cortex as an area of special interest with the trigeminal input. The results support the piriform cortex, in addition to the secondary somatosensory cortex, as a major area of interest for stimulus strength-related brain activation in pain models using trigeminal stimuli. This makes both areas a primary objective to be observed in human experimental pain settings where trigeminal input is used to study effects of analgesics.

Cortical aging - new insights with multiparametric quantitative MRI.

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.

Improved Visualization of Focal Cortical Dysplasia With Surface-Based Multiparametric Quantitative MRI.

PURPOSE: In the clinical routine, detection of focal cortical dysplasia (FCD) by visual inspection is challenging. Still, information about the presence and location of FCD is highly relevant for prognostication and treatment decisions. Therefore, this study aimed to develop, describe and test a method for the calculation of synthetic anatomies using multiparametric quantitative MRI (qMRI) data and surface-based analysis, which allows for an improved visualization of FCD. MATERIALS AND METHODS: Quantitative T1-, T2- and PD-maps and conventional clinical datasets of patients with FCD and epilepsy were acquired. Tissue segmentation and delineation of the border between white matter and cortex was performed. In order to detect blurring at this border, a surface-based calculation of the standard deviation of each quantitative parameter (T1, T2, and PD) was performed across the cortex and the neighboring white matter for each cortical vertex. The resulting standard deviations combined with measures of the cortical thickness were used to enhance the signal of conventional FLAIR-datasets. The resulting synthetically enhanced FLAIR-anatomies were compared with conventional MRI-data utilizing regions of interest based analysis techniques. RESULTS: The synthetically enhanced FLAIR-anatomies showed higher signal levels than conventional FLAIR-data at the FCD sites (p = 0.005). In addition, the enhanced FLAIR-anatomies exhibited higher signal levels at the FCD sites than in the corresponding contralateral regions (p = 0.005). However, false positive findings occurred, so careful comparison with conventional datasets is mandatory. CONCLUSION: Synthetically enhanced FLAIR-anatomies resulting from surface-based multiparametric qMRI-analyses have the potential to improve the visualization of FCD and, accordingly, the treatment of the respective patients.

Cortical Changes in Epilepsy Patients With Focal Cortical Dysplasia: New Insights With T2 Mapping.

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.

Signal variance-based collateral index in DSC perfusion: A novel method to assess leptomeningeal collateralization in acute ischaemic stroke.

As a determinant of the progression rate of the ischaemic process in acute large-vessel stroke, the degree of collateralization is a strong predictor of the clinical outcome after reperfusion therapy and may influence clinical decision-making. Therefore, the assessment of leptomeningeal collateralization is of major importance. The purpose of this study was to develop and evaluate a quantitative and observer-independent method for assessing leptomeningeal collateralization in acute large-vessel stroke based on signal variance characteristics in T2*-weighted dynamic susceptibility contrast (DSC) perfusion-weighted MR imaging (PWI). Voxels representing leptomeningeal collateral vessels were extracted according to the magnitude of signal variance in the PWI raw data time series in 55 patients with proximal large-artery occlusion and an intra-individual collateral vessel index (CVIPWI) was calculated. CVIPWI correlated significantly with the initial ischaemic core volume (rho = -0.459, p = 0.0001) and the PWI/DWI mismatch ratio (rho = 0.494, p = 0.0001) as an indicator of the amount of salvageable tissue. Furthermore, CVIPWI was significantly negatively correlated with NIHSS and mRS at discharge (rho = -0.341, p = 0.015 and rho = -0.305, p = 0.023). In multivariate logistic regression, CVIPWI was an independent predictor of favourable functional outcome (mRS 0-2) (OR = 16.39, 95% CI 1.42-188.7, p = 0.025). CVIPWI provides useful rater-independent information on the leptomeningeal collateral supply in acute stroke.

How stable is quantitative MRI? - Assessment of intra- and inter-scanner-model reproducibility using identical acquisition sequences and data analysis programs.

BACKGROUND: Quantitative MRI (qMRI) techniques allow assessing cerebral tissue properties. However, previous studies on the accuracy of quantitative T1 and T2 mapping reported a scanner model bias of up to 10% for T1 and up to 23% for T2. Such differences would render multi-centre qMRI studies difficult and raise fundamental questions about the general precision of qMRI. A problem in previous studies was that different methods were used for qMRI parameter mapping or for measuring the transmitted radio frequency field B1 which is critical for qMRI techniques requiring corrections for B1 non-uniformities. AIMS: The goal was to assess the intra- and inter-scanner reproducibility of qMRI data at 3 â€‹T, using two different scanner models from the same vendor with exactly the same multiparametric acquisition protocol. METHODS: Proton density (PD), T1, T2* and T2 mapping was performed on healthy subjects and on a phantom, performing each measurement twice for each of two scanner models. Although the scanners had different hardware and software versions, identical imaging sequences were used for PD, T1 and T2* mapping, adapting the codes of an existing protocol on the older system line by line to match the software version of the newer scanner. For T2-mapping, the respective manufacturer's sequence was used which depended on the software version. However, system-dependent corrections were carried out in this case. Reproducibility was assessed by average values in regions of interest. RESULTS: Mean scan-rescan variations were not exceeding 2.14%, with average values of 1.23% and 1.56% for the new and old system, respectively. Inter-scanner model deviations were not exceeding 5.21% with average values of about 2.2-3.8% for PD, 2.5-3.0% for T2*, 1.6-3.1% for T1 and 3.3-5.2% for T2. CONCLUSIONS: Provided that identical acquisition sequences are used, discrepancies between qMRI data acquired with different scanner models are low. The level of systematic differences reported in this work may help to interpret multi-centre data.

Quantitative T1 mapping indicates tumor infiltration beyond the enhancing part of glioblastomas.

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.

Detection of cortical malformations using enhanced synthetic contrast images derived from quantitative T1 maps.

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.

Delta-9-tetrahydrocannabinol reduces the performance in sensory delayed discrimination tasks. A pharmacological-fMRI study in healthy volunteers.

BACKGROUND: Cannabis proofed to be effective in pain relief, but one major side effect is its influence on memory in humans. Therefore, the role of memory on central processing of nociceptive information was investigated in healthy volunteers. METHODS: In a placebo-controlled cross-over study including 22 healthy subjects, the effect of 20 mg oral Δ9-tetrahydrocannabinol (THC) on memory involving nociceptive sensations was studied, using a delayed stimulus discrimination task (DSDT). To control for nociceptive specificity, a similar DSDT-based study was performed in a subgroup of thirteen subjects, using visual stimuli. RESULTS: For each nociceptive stimulus pair, the second stimulus was associated with stronger and more extended brain activations than the first stimulus. These differences disappeared after THC administration. The THC effects were mainly located in two clusters comprising the insula and inferior frontal cortex in the right hemisphere, and the caudate nucleus and putamen bilaterally. These cerebral effects were accompanied in the DSDT by a significant reduction of correct ratings from 41.61% to 37.05% after THC administration (rm-ANOVA interaction "drug" by "measurement": F (1,21) = 4.685, p = 0.042). Rating performance was also reduced for the visual DSDT (69.87% to 54.35%; rm-ANOVA interaction of "drug" by "measurement": F (1,12) = 13.478, p = 0.003) and reflected in a reduction of stimulus-related brain deactivations in the bilateral angular gyrus. CONCLUSIONS: Results suggest that part of the effect of THC on pain may be related to memory effects. THC reduced the performance in DSDT of nociceptive and visual stimuli, which was accompanied by significant effects on brain activations. However, a pain specificity of these effects cannot be deduced from the data presented.