In Vivo Measurement of Rat Brain Water Content at 9.4 T MR Using Super-Resolution Reconstruction: Validation With Ex Vivo Experiments.

BACKGROUND: Given that changes in brain water content are often correlated with disease, investigating water content non-invasively and in vivo could lead to a better understanding of the pathogenesis of several neurologic diseases. PURPOSE: To adapt a super-resolution-based technique, previously developed for humans, to the rat brain and report in vivo high-resolution (HR) water content maps in comparison with ex vivo wet/dry methods. STUDY TYPE: Prospective. ANIMAL MODEL: Eight healthy male Wistar rats. FIELD STRENGTH/SEQUENCE: 9.4-T, multi-echo gradient-echo (mGRE) sequence. ASSESSMENT: Using super-resolution reconstruction (SRR), a HR mGRE image (200 µm isotropic) was reconstructed from three low-resolution (LR) orthogonal whole-brain images in each animal, which was followed by water content mapping in vivo. The animals were subsequently sacrificed, the brains excised and divided into five regions (front left, front right, middle left, middle right, and cerebellum-brainstem regions), and the water content was measured ex vivo using wet/dry measurements as the reference standard. The water content values of the in vivo and ex vivo methods were then compared for the whole brain and also for the different regions separately. STATISTICAL TESTS: Friedman's non-parametric test was used to test difference between the five regions, and Pearson's correlation coefficient was used for correlation between in vivo and ex vivo measurements. A P-value <0.05 was considered statistically significant. RESULTS: Water content values derived from in vivo MR measurements showed strong correlations with water content measured ex vivo at a regional level (r = 0.902). Different brain regions showed significantly different water content values. Water content values were highest in the frontal brain, followed by the midbrain, and lowest in the cerebellum and brainstem regions. DATA CONCLUSION: An in vivo technique to achieve HR isotropic water content maps in the rat brain using SRR was adopted in this study. The MRI-derived water content values obtained using the technique showed strong correlations with water content values obtained using ex vivo wet/dry methods. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Primary Multiparametric Quantitative Brain MRI: State-of-the-Art Relaxometric and Proton Density Mapping Techniques.

This review on brain multiparametric quantitative MRI (MP-qMRI) focuses on the primary subset of quantitative MRI (qMRI) parameters that represent the mobile ("free") and bound ("motion-restricted") proton pools. Such primary parameters are the proton densities, relaxation times, and magnetization transfer parameters. Diffusion qMRI is also included because of its wide implementation in complete clinical MP-qMRI application. MP-qMRI advances were reviewed over the past 2 decades, with substantial progress observed toward accelerating image acquisition and increasing mapping accuracy. Areas that need further investigation and refinement are identified as follows: (a) the biologic underpinnings of qMRI parameter values and their changes with age and/or disease and (b) the theoretical limitations implicitly built into most qMRI mapping algorithms that do not distinguish between the different spatial scales of voxels versus spin packets, the central physical object of the Bloch theory. With rapidly improving image processing techniques and continuous advances in computer hardware, MP-qMRI has the potential for implementation in a wide range of clinical applications. Currently, three emerging MP-qMRI applications are synthetic MRI, macrostructural qMRI, and microstructural tissue modeling.

Whole-Brain Water Content Mapping Using Super-Resolution Reconstruction with MRI Acquisition in 3 Orthogonal Orientations.

PURPOSE: Brain water content provides rich tissue contrast comparable to that of longitudinal relaxation time T1 , but mapping is usually performed at modest resolution. In particular, the slice thickness in 2D mapping methods is limited. Here, we combine super-resolution reconstruction techniques with a fast water content mapping method to acquire high and isotropic resolution (0.75 mm) water content maps at 3 Tesla. METHODS: A high-resolution multi-echo gradient echo image is super-resolution-reconstructed from 3 low-resolution, orthogonal multi-echo gradient echo image acquisitions, followed by water content mapping. The mapping accuracy and SNR of the proposed method are assessed using numerical simulations, phantom studies, and in vivo data acquired from 6 healthy volunteers at 3 Tesla. A high-resolution acquisition with an established mapping method is used as a reference. RESULTS: Whole-brain water content maps with 0.75 mm isotropic resolution are demonstrated. No bias in the water content values was seen following super-resolution reconstruction. In the in vivo experiments, a lower SD of the mean water content values was observed with the proposed method compared to the reference method. CONCLUSIONS: Super-resolution reconstruction of multi-echo gradient echo data is demonstrated, enabling whole-brain water content mapping with high and isotropic resolution. The accuracy of the proposed method is shown using phantoms and 6 healthy volunteers and was found to be unchanged compared to the conventional acquisition. The proposed method could increase the sensitivity of water content mapping sufficiently to enable the detection of very small lesions, such as cortical lesions in multiple sclerosis.

Surgery of Motor Eloquent Glioblastoma Guided by TMS-Informed Tractography: Driving Resection Completeness Towards Prolonged Survival.

Background: Surgical treatment of patients with glioblastoma affecting motor eloquent brain regions remains critically discussed given the risk-benefit dilemma of prolonging survival at the cost of motor-functional damage. Tractography informed by navigated transcranial magnetic stimulation (nTMS-informed tractography, TIT) provides a rather robust estimate of the individual location of the corticospinal tract (CST), a highly vulnerable structure with poor functional reorganisation potential. We hypothesised that by a more comprehensive, individualised surgical decision-making using TIT, tumours in close relationship to the CST can be resected with at least equal probability of gross total resection (GTR) than less eloquently located tumours without causing significantly more gross motor function harm. Moreover, we explored whether the completeness of TIT-aided resection translates to longer survival. Methods: A total of 61 patients (median age 63 years, m = 34) with primary glioblastoma neighbouring or involving the CST were operated on between 2010 and 2015. TIT was performed to inform surgical planning in 35 of the patients (group T; vs. 26 control patients). To achieve largely unconfounded group comparisons for each co-primary outcome (i.e., gross-motor functional worsening, GTR, survival), (i) uni- and multivariate regression analyses were performed to identify features of optimal outcome prediction; (ii), optimal propensity score matching (PSM) was applied to balance those features pairwise across groups, followed by (iii) pairwise group comparison. Results: Patients in group T featured a significantly higher lesion-CST overlap compared to controls (8.7 ± 10.7% vs. 3.8 ± 5.7%; p = 0.022). The frequency of gross motor worsening was higher in group T, albeit non-significant (n = 5/35 vs. n = 0/26; p = 0.108). PSM-based paired-sample comparison, controlling for the confounders of preoperative tumour volume and vicinity to the delicate vasculature of the insula, showed higher GTR rates in group T (77% vs. 69%; p = 0.025), particularly in patients with a priori intended GTR (87% vs. 78%; p = 0.003). This translates into a prolonged PFS in the same PSM subgroup (8.9 vs. 5.8 months; p = 0.03), with GTR representing the strongest predictor of PFS (p = 0.001) and OS (p = 0.0003) overall. Conclusion: The benefit of TIT-aided GTR appears to overcome the drawbacks of potentially elevated motor functional risk in motor eloquent tumour localisation, leading to prolonged survival of patients with primary glioblastoma close to the CST.

A novel MRI-based quantitative water content atlas of the human brain.

The measurement of quantitative, tissue-specific MR properties, e.g., water content, longitudinal relaxation time (T1) and effective transverse relaxation time (T2⁎), using quantitative MRI at a clinical field strength (1.5 T to 3T) is a well-explored topic. However, none of the commonly used standard brain atlases, such as MNI or JHU, provide quantitative information. Within the framework of quantitative MRI of the brain, this work reports on the development of the first quantitative brain atlas for tissue water content at 3T. A methodology to create this quantitative atlas of in vivo brain water content based on healthy volunteers is presented, and preliminary, practical examples of its potential applications are also shown. Established methods for the fast and reliable measurement of the absolute water content were used to achieve high precision and accuracy. Water content and T2⁎ were mapped based on two different methods: an intermediate-TR, two-point method and a long-TR, single-scan method. Twenty healthy subjects (age 25.3 ± 2.5 years) were examined with these quantitative imaging protocols. The images were normalised to MNI stereotactic coordinates, and water content atlases of healthy volunteers were created for each method and compared. Regions-of-interest were generated with the help of a standard MNI template, and water content values averaged across the ROIs were compared to water content values from the literature. Finally, in order to demonstrate the strength of quantitative MRI, water content maps from patients with pathological changes in the brain due to stroke, tumour (glioblastoma) and multiple sclerosis were voxel-wise compared to the healthy brain. The water content atlases were largely independent of the method used to acquire the individual water maps. Global grey matter and white matter water content values between the methods agreed with each other to within 0.5 %. The feasibility of detecting abnormal water content in the brains of patients based on comparison to a healthy brain water content atlas was demonstrated. In summary, the first quantitative water content brain atlas in vivo has been developed, and a voxel-wise assessment of pathology-related changes in the brain water content has been performed. These results suggest that qMRI, in combination with a water content atlas, allows for a quantitative interpretation of changes due to disease and could be used for disease monitoring.

MRI Analysis Of the Water Content Change In the Brain During Acute Ethanol Consumption Via Quantitative Water Mapping.

AIMS: Alcohol consumption influences the water balance in the brain. While the impact of chronic alcohol misuse on cerebral water content has been the subject of several studies, less is known about the effects of acute alcohol misuse, with contradictory results in the literature. Therefore, we investigated the effects of acute alcohol intoxication on cerebral water content using a precise quantitative magnetic resonance imaging (MRI) sequence. METHODS: In a prospective study, we measured cerebral water content in 20 healthy volunteers before alcohol consumption and after reaching a breath alcohol concentration of 1 ‰. A quantitative MRI water mapping sequence was conducted on a clinical 3 T system. Non-alcoholic fluid input and output were documented and accounted for. Water content was assessed for whole brain, grey and white matter and more specifically for regions known to be affected by acute or chronic alcohol misuse (occipital and frontal lobes, thalamus and pons). Changes in the volume of grey and white matter as well as the whole brain were examined. RESULTS: Quantitative cerebral water content before and after acute alcohol consumption did not differ significantly (P ≥ 0.07), with changes often being within the range of measurement accuracy. Whole brain, white and grey matter volume did not change significantly (P ≥ 0.12). CONCLUSION: The results of our study show no significant water content or volume change in the brain after recent alcohol intake in healthy volunteers. This accounts for the whole brain, grey and white matter, occipital and frontal lobes, thalamus and pons.

A Fast Protocol for Multiparametric Characterisation of Diffusion in the Brain and Brain Tumours.

Multi-parametric tissue characterisation is demonstrated using a 4-minute protocol based on diffusion trace acquisitions. Three diffusion regimes are covered simultaneously: pseudo-perfusion, Gaussian, and non-Gaussian diffusion. The clinical utility of this method for fast multi-parametric mapping for brain tumours is explored. A cohort of 17 brain tumour patients was measured on a 3T hybrid MR-PET scanner with a standard clinical MRI protocol, to which the proposed multi-parametric diffusion protocol was subsequently added. For comparison purposes, standard perfusion and a full diffusion kurtosis protocol were acquired. Simultaneous amino-acid (18F-FET) PET enabled the identification of active tumour tissue. The metrics derived from the proposed protocol included perfusion fraction, pseudo-diffusivity, apparent diffusivity, and apparent kurtosis. These metrics were compared to the corresponding metrics from the dedicated acquisitions: cerebral blood volume and flow, mean diffusivity and mean kurtosis. Simulations were carried out to assess the influence of fitting methods and noise levels on the estimation of the parameters. The diffusion and kurtosis metrics obtained from the proposed protocol show strong to very strong correlations with those derived from the conventional protocol. However, a bias towards lower values was observed. The pseudo-perfusion parameters showed very weak to weak correlations compared to their perfusion counterparts. In conclusion, we introduce a clinically applicable protocol for measuring multiple parameters and demonstrate its relevance to pathological tissue characterisation.

Invasive versus non-invasive mapping of the motor cortex.

Precise and comprehensive mapping of somatotopic representations in the motor cortex is clinically essential to achieve maximum resection of brain tumours whilst preserving motor function, especially since the current gold standard, that is, intraoperative direct cortical stimulation (DCS), holds limitations linked to the intraoperative setting such as time constraints or anatomical restrictions. Non-invasive techniques are increasingly relevant with regard to pre-operative risk-assessment. Here, we assessed the congruency of neuronavigated transcranial magnetic stimulation (nTMS) and functional magnetic resonance imaging (fMRI) with DCS. The motor representations of the hand, the foot and the tongue regions of 36 patients with intracranial tumours were mapped pre-operatively using nTMS and fMRI and by intraoperative DCS. Euclidean distances (ED) between hotspots/centres of gravity and (relative) overlaps of the maps were compared. We found significantly smaller EDs (11.4 ± 8.3 vs. 16.8 ± 7.0 mm) and better spatial overlaps (64 ± 38% vs. 37 ± 37%) between DCS and nTMS compared with DCS and fMRI. In contrast to DCS, fMRI and nTMS mappings were feasible for all regions and patients without complications. In summary, nTMS seems to be the more promising non-invasive motor cortex mapping technique to approximate the gold standard DCS results.

Increasing body mass index in an elderly cohort: Effects on the quantitative MR parameters of the brain.

BACKGROUND: Body mass index (BMI) is increasing in a large number of elderly persons. This increase in BMI is known to put one at risk for many "diseases of aging," although less is known about how a change in BMI may affect the brains of the elderly. PURPOSE: To investigate the relationship between BMI and quantitative water content, T1 , T2 *, and the semi-quantitative magnetization transfer ratio (MTR) of various structures in elderly brains. STUDY TYPE: Cross-sectional. SUBJECTS: Forty-two adults (BMI range: 19.1-33.5 kg/m2 , age range: 58-80 years). FIELD STRENGTH: 3T MRI (two multi-echo gradient echoes, actual flip angle imaging, magnetization prepared rapid gradient echo, fluid attenuated inversion recovery). ASSESSMENT: The 3D two-point method was used to derive (semi-)quantitative parameters in global white (WM) and gray matter (GM) and their regions as defined by the Johns Hopkins University and the Montreal Neurological Institute atlases. STATISTICAL TESTS: Multivariate linear regression with BMI as principal regressor, corrected for the additional regressors age, gender, and glycated hemoglobin. Spearman correlation between quantitative parameters of the regions showing significant changes and the lipid spectra / C-reactive protein (CRP). Voxel-based morphometry and analysis of covariance (ANCOVA) to explore changes in the GM volume. RESULTS: T1 increased significantly (P < 0.05) in the frontal, temporal, and parietal cortices, while the bilateral corona radiata, right superior longitudinal fasciculus, as well as the corpus callosum showed significant changes in the WM regions. T2 * increased significantly in the global WM and left corona radiata. Changes in MTR and the free water content did not reach significance. No significant correlation between any quantitative parameter and the lipid spectra or CRP could be identified. DATA CONCLUSION: These results suggest that an elevated BMI predominantly affects T1 in WM as well as GM structures in the elderly human brain. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:514-523.

Quantitative MRI of cerebral white matter hyperintensities: A new approach towards understanding the underlying pathology.

Interest in white matter hyperintensities (WMH), a radiological biomarker of small vessel disease, is continuously increasing. This is, in most part, due to our better understanding of their association with various clinical disorders, such as stroke and Alzheimer's disease, and the overlapping pathology of WMH with these afflictions. Although post-mortem histological studies have reported various underlying pathophysiological substrates, in vivo research has not been specific enough to fully corroborate these findings. Furthermore, post-mortem studies are not able to capture which pathological processes are the driving force of the WMH severity. The current study attempts to fill this gap by non-invasively investigating the influence of WMH on brain tissue using quantitative MRI (qMRI) measurements of the water content (H2O), the longitudinal (T1) and effective transverse relaxation times (T2∗), as well as the semi-quantitative magnetization transfer ratio (MTR), and bound proton fraction (ƒbound). In total, seventy subjects (age range 50-80 years) were selected from a population-based aging cohort study, 1000BRAINS. Normal appearing grey (NAGM) and white matter (NAWM), as well as deep (DWMH) and periventricular (PWMH) white matter hyperintensities, were segmented and characterized in terms of their quantitative properties. The subjects were then further divided into four grades according to the Fazekas rating scale of severity. Groupwise analyses of the qMRI values in each tissue class were performed. All five qMRI parameters showed significant differences between WMH and NAWM (p < 0.001). Importantly, the parameters differed between DWMH and PWMH, the latter having higher H2O, T1, T2∗ and lower MTR and ƒbound values (p < 0.001). Following grading according to the Fazekas scale, DWMH showed an increase in the water content, T1 and a decrease in bound proton fraction corresponding to severity, exhibiting significant changes in grade 3 (p < 0.001), while NAWM revealed significantly higher H2O values in grade 3 compared to grade 0 (p < 0.001). PWMH demonstrated an increase in T2∗ values (significant in grade 3, P < 0.001). These results are in agreement with previous histopathological studies and support the interpretation that both edema and myelin loss due to a possible breakdown of the blood-brain barrier and inflammation are the major pathological substrates turning white matter into DWMH. Edema being an earlier contributing factor to the pathology, as expressed in the elevated water content values in NAWM with increasing severity. In the case of PWMH, an altered fluid dynamic and cerebrospinal fluid leakage exacerbate the changes. It was also found that the pathology, as monitored by qMRI, evolves faster in DWMH than in the PWMH following the severity.

Multi-Exponential Relaxometry Using l1 -Regularized Iterative NNLS (MERLIN) With Application to Myelin Water Fraction Imaging.

A new parameter estimation algorithm, MERLIN, is presented for accurate and robust multi-exponential relaxometry using magnetic resonance imaging, a tool that can provide valuable insight into the tissue microstructure of the brain. Multi-exponential relaxometry is used to analyze the myelin water fraction and can help to detect related diseases. However, the underlying problem is ill-conditioned, and as such, is extremely sensitive to noise and measurement imperfections, which can lead to less precise and more biased parameter estimates. MERLIN is a fully automated, multi-voxel approach that incorporates state-of-the-art l1 -regularization to enforce sparsity and spatial consistency of the estimated distributions. The proposed method is validated in simulations and in vivo experiments, using a multi-echo gradient-echo (MEGE) sequence at 3 T. MERLIN is compared to the conventional single-voxel l2 -regularized NNLS (rNNLS) and a multi-voxel extension with spatial priors (rNNLS + SP), where it consistently showed lower root mean squared errors of up to 70 percent for all parameters of interest in these simulations.

An MR technique for simultaneous quantitative imaging of water content, conductivity and susceptibility, with application to brain tumours using a 3T hybrid MR-PET scanner.

Approaches for the quantitative mapping of water content, electrical conductivity and susceptibility have been developed independently. The purpose of this study is to develop a method for simultaneously acquiring quantitative water content, electrical conductivity and susceptibility maps based on a 2D multi-echo gradient echo sequence. Another purpose is to investigate the changes in these properties caused by brain tumours. This was done using a 3T hybrid magnetic resonance imaging and positron emission tomography (MR-PET) scanner. Water content maps were derived after performing T2* and transmit-receive field bias corrections to magnitude images essentially reflecting only the H2O content contrast. Phase evolution during the multi-echo train was used to generate field maps and derive quantitative susceptibility, while the conductivity maps were retrieved from the phase value at zero echo time. Performance of the method is demonstrated on phantoms and two healthy volunteers. In addition, the method was applied to three patients with brain tumours and a comparison to maps obtained from PET using O-(2-[18 F]fluoroethyl)-L-tyrosine and clinical MR images is presented. The combined information of the water content, conductivity and susceptibility may provide additional information about the tissue viability. Future studies can benefit from the evaluation of these contrasts with shortened acquisition times.

A Single-Scan, Rapid Whole-Brain Protocol for Quantitative Water Content Mapping With Neurobiological Implications.

Water concentration is tightly regulated in the healthy human brain and changes only slightly with age and gender in healthy subjects. Consequently, changes in water content are important for the characterization of disease. MRI can be used to measure changes in brain water content, but as these changes are usually in the low percentage range, highly accurate and precise methods are required for detection. The method proposed here is based on a long-TR (10 s) multiple-echo gradient-echo measurement with an acquisition time of 7:21 min. Using such a long TR ensures that there is no T1 weighting, meaning that the image intensity at zero echo time is only proportional to the water content, the transmit field, and to the receive field. The receive and transmit corrections, which are increasingly large at higher field strengths and for highly segmented coil arrays, are multiplicative and can be approached heuristically using a bias field correction. The method was tested on 21 healthy volunteers at 3T field strength. Calibration using cerebral-spinal fluid values (~100% water content) resulted in mean values and standard deviations of the water content distribution in white matter and gray matter of 69.1% (1.7%) and 83.7% (1.2%), respectively. Measured distributions were coil-independent, as seen by using either a 12-channel receiver coil or a 32-channel receiver coil. In a test-retest investigation using 12 scans on one volunteer, the variation in the mean value of water content for different tissue types was ~0.3% and the mean voxel variability was ~1%. Robustness against reduced SNR was assessed by comparing results for 5 additional volunteers at 1.5T and 3T. Furthermore, water content distribution in gray matter is investigated and regional contrast reported for the first time. Clinical applicability is illustrated with data from one stroke patient and one brain tumor patient. It is anticipated that this fast, stable, easy-to-use, high-quality mapping method will facilitate routine quantitative MR imaging of water content.

Correlation of Dynamic O-(2-[18F]Fluoroethyl)-L-Tyrosine Positron Emission Tomography, Conventional Magnetic Resonance Imaging, and Whole-Brain Histopathology in a Pretreated Glioblastoma: A Postmortem Study.

OBJECTIVE: Amino acid positron emission tomography (PET) using O-(2-[18F]fluoroethyl)-L-tyrosine (FET) provides important additional information on the extent of viable tumor tissue of glioblastoma compared with magnetic resonance imaging (MRI). Especially after radiochemotherapy, progression of contrast enhancement in MRI is equivocal and may represent either tumor progression or treatment-related changes. Here, the first case comparing postmortem whole-brain histology of a patient with pretreated glioblastoma with dynamic in vivo FET PET and MRI is presented. METHODS: A 61-year-old patient with glioblastoma initially underwent partial tumor resection and died 11 weeks after completion of chemoradiation with concurrent temozolomide. Three days before the patient died, a follow-up FET PET and MRI scan indicated tumor progression. Autopsy was performed 48 hours after death. After formalin fixation, a 7-cm bihemispherical segment of the brain containing the entire tumor mass was cut into 3500 consecutive 20µm coronal sections. Representative sections were stained with hematoxylin and eosin stain, cresyl violet, and glial fibrillary acidic protein immunohistochemistry. An experienced neuropathologist identified areas of dense and diffuse neoplastic infiltration, astrogliosis, and necrosis. In vivo FET PET, MRI datasets, and postmortem histology were co-registered and compared by 3 experienced physicians. RESULTS: Increased uptake of FET in the area of equivocal contrast enhancement on MRI correlated very well with dense infiltration by vital tumor cells and showed tracer kinetics typical for malignant gliomas. An area of predominantly reactive astrogliosis showed only moderate uptake of FET and tracer kinetics usually observed in benign lesions. CONCLUSIONS: This case report impressively documents the correct imaging of a progressive glioblastoma by FET PET.

A 3D two-point method for whole-brain water content and relaxation time mapping: Comparison with gold standard methods.

Quantitative imaging of the human brain is of great interest in clinical research as it enables the identification of a range of MR biomarkers useful in diagnosis, treatment and prognosis of a wide spectrum of diseases. Here, a 3D two-point method for water content and relaxation time mapping is presented and compared to established gold standard methods. The method determines free water content, H2O, and the longitudinal relaxation time, T1, quantitatively from a two-point fit to the signal equation including corrections of the transmit and receive fields. In addition, the effective transverse relaxation time, T2*, is obtained from an exponential fit to the multi-echo signal train and its influence on H2O values is corrected. The phantom results obtained with the proposed method show good agreement for H2O and T1 values with known and spectroscopically measured values, respectively. The method is compared in vivo to already established gold standard quantitative methods. For H2O and T2* mapping, the 3D two-point results were compared to a measurement conducted with a multiple-echo GRE with long TR and T1 is compared to results from a Look-Locker method, TAPIR. In vivo results show good overall agreement between the methods, but some systematic deviations are present. Besides an expected dependence of T2* on voxel size, T1 values are systematically larger in the 3D approach than those obtained with the gold standard method. This behaviour might be due to imperfect spoiling, influencing each method differently. Results for H2O differ due to differences in the saturation of cerebrospinal fluid and partial volume effects. In addition, ground truth values of in vivo studies are unknown, even when comparing to in vivo gold standard methods. A detailed region-of-interest analysis for H2O and T1 matches well published literature values.

Neuroanatomy of pain-deficiency and cross-modal activation in calcium channel subunit (CACN) α2δ3 knockout mice.

The phenotype of calcium channel subunit (CACN) α2δ3 knockout (KO) mice includes sensory cross-activation and deficient pain perception. Sensory cross-activation defines the activation of a sensory cortical region by input from another modality due to reorganization in the brain such as after sensory loss. To obtain mechanistic insight into both phenomena, we employed a comprehensive battery of neuroanatomical techniques. While CACNα2δ3 was ubiquitously expressed in wild-type mice, it was absent in α2δ3 KO animals. Immunostaining of α1A, α1B, and α1E revealed upregulation of N-type and R-type, but not P/Q-type Cav2 channels in cortical neurons of CACNα2δ3 KO mice. Compared to wild-type mice, axonal processes in somatosensory cortex were enhanced, and dendritic processes reduced, in CACNα2δ3 KO mice. Immunohistochemical and MRI analyses, investigating morphology, thalamocortical and intra-/intercortical trajectories, revealed a disparity between projection and commissural fibers with reduction of the number of spatial specificity of thalamocortical projections. L1cam staining revealed wide-ranging projections of thalamocortical fibers reaching both somatosensory/motor and visual cortical areas. Activation (c-fos+) of excitatory and inhibitory neurons suggested that deficient pain perception in α2δ3 KO mice is unlikely to result from cortical disinhibition. Collectively, our data demonstrate that knock out of CACN α2δ3 results in some structural abnormalities whose functional implications converge to dedifferentiation of sensory activation.

Concerning the matching of magnetic susceptibility differences for the compensation of background gradients in anisotropic diffusion fibre phantoms.

Artificial, anisotropic fibre phantoms are nowadays increasingly used in the field of diffusion-weighted MRI. Such phantoms represent useful tools for, among others, the calibration of pulse sequences and validation of diffusion models since they can mimic well-known structural features of brain tissue on the one hand, but exhibit a reduced complexity, on the other. Among all materials, polyethylene fibres have been widely used due to their excellent properties regarding the restriction of water diffusion and surface relaxation properties. Yet the magnetic susceptibility of polyethylene can be distinctly lower than that of distilled water. This difference produces strong microscopic, background field gradients in the vicinity of fibre bundles which are not parallel to the static magnetic field. This, in turn, modulates the MRI signal behaviour. In the present work we investigate an approach to reduce the susceptibility-induced background gradients via reducing the heterogeneity in the internal magnetic susceptibility. An aqueous solution of magnesium chloride hexahydrate (MgCl2·6H2O) is used for this purpose. Its performance is demonstrated in dedicated anisotropic fibre phantoms with different geometrical configurations.

Functional MRI vs. navigated TMS to optimize M1 seed volume delineation for DTI tractography. A prospective study in patients with brain tumours adjacent to the corticospinal tract.

BACKGROUND: DTI-based tractography is an increasingly important tool for planning brain surgery in patients suffering from brain tumours. However, there is an ongoing debate which tracking approaches yield the most valid results. Especially the use of functional localizer data such as navigated transcranial magnetic stimulation (nTMS) or functional magnetic resonance imaging (fMRI) seem to improve fibre tracking data in conditions where anatomical landmarks are less informative due to tumour-induced distortions of the gyral anatomy. We here compared which of the two localizer techniques yields more plausible results with respect to mapping different functional portions of the corticospinal tract (CST) in brain tumour patients. METHODS: The CSTs of 18 patients with intracranial tumours in the vicinity of the primary motor area (M1) were investigated by means of deterministic DTI. The core zone of the tumour-adjacent hand, foot and/or tongue M1 representation served as cortical regions of interest (ROIs). M1 core zones were defined by both the nTMS hot-spots and the fMRI local activation maxima. In addition, for all patients, a subcortical ROI at the level of the inferior anterior pons was implemented into the tracking algorithm in order to improve the anatomical specificity of CST reconstructions. As intra-individual control, we additionally tracked the CST of the hand motor region of the unaffected, i.e., non-lesional hemisphere, again comparing fMRI and nTMS M1 seeds. The plausibility of the fMRI-ROI- vs. nTMS-ROI-based fibre trajectories was assessed by a-priori defined anatomical criteria. Moreover, the anatomical relationship of different fibre courses was compared regarding their distribution in the anterior-posterior direction as well as their location within the posterior limb of the internal capsule (PLIC). RESULTS: Overall, higher plausibility rates were observed for the use of nTMS- as compared to fMRI-defined cortical ROIs (p < 0.05) in tumour vicinity. On the non-lesional hemisphere, however, equally good plausibility rates (100%) were observed for both localizer techniques. fMRI-originated fibres generally followed a more posterior course relative to the nTMS-based tracts (p < 0.01) in both the lesional and non-lesional hemisphere. CONCLUSION: NTMS achieved better tracking results than fMRI in conditions when the cortical tract origin (M1) was located in close vicinity to a brain tumour, probably influencing neurovascular coupling. Hence, especially in situations with altered BOLD signal physiology, nTMS seems to be the method of choice in order to identify seed regions for CST mapping in patients.

Automatic Segmentation of Human Cortical Layer-Complexes and Architectural Areas Using Ex vivo Diffusion MRI and Its Validation.

Recently, several magnetic resonance imaging contrast mechanisms have been shown to distinguish cortical substructure corresponding to selected cortical layers. Here, we investigate cortical layer and area differentiation by automatized unsupervised clustering of high-resolution diffusion MRI data. Several groups of adjacent layers could be distinguished in human primary motor and premotor cortex. We then used the signature of diffusion MRI signals along cortical depth as a criterion to detect area boundaries and find borders at which the signature changes abruptly. We validate our clustering results by histological analysis of the same tissue. These results confirm earlier studies which show that diffusion MRI can probe layer-specific intracortical fiber organization and, moreover, suggests that it contains enough information to automatically classify architecturally distinct cortical areas. We discuss the strengths and weaknesses of the automatic clustering approach and its appeal for MR-based cortical histology.

Multistage Background Field Removal (MUBAFIRE)-Compensating for B0 Distortions at Ultra-High Field.

The investigation of tissue magnetic susceptibility and the resultant magnetic field offers a new avenue for quantitative tissue characterisation by MRI. One crucial step in mining the phase and field data for relevant tissue information is the correction of externally induced field shifts. This article outlines a multistep approach comprising several methodologies for background field removal. The virtues of B0 long-range variation detection and compensation of more localised external disturbances are unified in a sequential filter chain. The algorithm is tested by means of a numerical Monte Carlo simulation model and applied to in vivo measurements at 3T and 9.4T as well as to a fixed brain tissue measurement at 9.4T. Further, a comparison to conventional filter types has been undertaken.