Background
Sodium enhancement has been demonstrated in multiple sclerosis (MS) lesions.
Purpose
To investigate sodium MRI with and without an inversion recovery pulse in acute MS lesions in an MS ...relapse and during recovery.
Study Type
Prospective.
Subjects
Twenty‐nine relapsing–remitting MS patients with an acute relapse were included.
Field Strength/Sequence
A 3D density‐adapted radial sodium sequence at 3 T using a dual‐tuned (23Na/1H) head coil.
Assessment
Full‐brain images of the tissue sodium concentration (TSC1, n = 29) and a sodium inversion recovery sequence (SIR1, n = 20) at the beginning of the anti‐inflammatory therapy and on medium‐term follow‐up visits (days 27–99, n = 12 TSC, n = 5 SIR) were measured. Regions of interest (RoIs) with contrast enhancement (T1CE+) and without change in T1‐weighted imaging (FL + T1n) were normalized (nTSC and nSIR). To gain insight on the origin of the TSC enhancement at time point 1, it is investigated whether the nTSC enhancement of the lesions is accompanied by a change of the respective nSIR. Potential prognostic value of nSIR1 is examined referring to the nTSC progression.
Statistical Tests
nTSC and nSIR were compared regarding the type of lesion and the time point using a one‐way ANOVA. Pearson's correlation coefficient was calculated for nTSC over nSIR and for nTSC1‐nTSC2 over nSIR1. A P‐value <0.05 was considered statistically significant.
Results
At the first measurement, all lesion types showed increased nTSC, while nSIR was decreased in the FL + T1n and the T1CE+ lesions in comparison to the normal‐appearing white matter. For acute lesions, the difference between nTSC at baseline and nTSC at time point 2 showed a significant correlation with the baseline nSIR.
Data Conclusion
At time point 1, nTSC is increased, while nSIR is unchanged or decreased in the lesions. The mean sodium IR signal at baseline correlates with recovery or progression of an acute lesion.
Evidence Level
2
Technical Efficacy
Stage 4
•Ninety-seven brain regions segmented using single-voxel multi-spectral MR data.•No atlas used.•Made possible by advanced MR methods: 7T, q-space trajectory (QTI), and chemical exchange saturation ...transfer (CEST) imaging.•Presence of unique MR signals of brain tissues indicated, like cytoarchitectonic and myeloarchitectonic fingerprints.
Since the seminal works by Brodmann and contemporaries, it is well-known that different brain regions exhibit unique cytoarchitectonic and myeloarchitectonic features. Transferring the approach of classifying brain tissues – and other tissues – based on their intrinsic features to the realm of magnetic resonance (MR) is a longstanding endeavor. In the 1990s, atlas-based segmentation replaced earlier multi-spectral classification approaches because of the large overlap between the class distributions. Here, we explored the feasibility of performing global brain classification based on intrinsic MR features, and used several technological advances: ultra-high field MRI, q-space trajectory diffusion imaging revealing voxel-intrinsic diffusion properties, chemical exchange saturation transfer and semi-solid magnetization transfer imaging as a marker of myelination and neurochemistry, and current neural network architectures to analyze the data. In particular, we used the raw image data as well to increase the number of input features. We found that a global brain classification of roughly 97 brain regions was feasible with gross classification accuracy of 60%; and that mapping from voxel-intrinsic MR data to the brain region to which the data belongs is possible. This indicates the presence of unique MR signals of different brain regions, similar to their cytoarchitectonic and myeloarchitectonic fingerprints.
Background:
Due to the absence of robust biomarkers, and the low sensitivity and specificity of routine imaging techniques, the differential diagnosis between Parkinson’s disease (PD) and multiple ...system atrophy (MSA) is challenging. High-field magnetic resonance imaging (MRI) opened up new possibilities regarding the analysis of pathological alterations associated with neurodegenerative processes. Recently, we have shown that quantitative susceptibility mapping (QSM) enables visualization and quantification of two major histopathologic hallmarks observed in MSA: reduced myelin density and iron accumulation in the basal ganglia of a transgenic murine model of MSA. It is therefore emerging as a promising imaging modality on the differential diagnosis of Parkinsonian syndromes.
Objectives:
To assess QSM on high-field MRI for the differential diagnosis of PD and MSA.
Methods:
We assessed 23 patients (nine PDs and 14 MSAs) and nine controls using QSM on 3T and 7T MRI scanners at two academic centers.
Results:
We observed increased susceptibility in MSA at 3T in prototypical subcortical and brainstem regions. Susceptibility measures of putamen, pallidum, and substantia nigra reached excellent diagnostic accuracy to separate both synucleinopathies. Increase toward 100% sensitivity and specificity was achieved using 7T MRI in a subset of patients. Magnetic susceptibility correlated with age in all groups, but not with disease duration in MSA. Sensitivity and specificity were particularly high for possible MSA, and reached 100% in the putamen.
Conclusion:
Putaminal susceptibility measures, in particular on ultra-high-field MRI, may distinguish MSA patients from both, PD and controls, allowing an early and sensitive diagnosis of MSA.
Objective
Functional magnetic resonance imaging (fMRI) visualizes brain structures at increasingly higher resolution and better signal-to-noise ratio (SNR) as field strength increases. Yet, mapping ...the blood oxygen level dependent (BOLD) response to distinct neuronal processes continues to be challenging. Here, we investigated the characteristics of 7 T-fMRI compared to 3 T-fMRI in the human brain beyond the effect of increased SNR and verified the benefits of 7 T-fMRI in the detection of tiny, highly specific modulations of functional connectivity in the resting state following a motor task.
Methods
18 healthy volunteers underwent two resting state and a stimulus driven measurement using a finger tapping motor task at 3 and 7 T, respectively. The SNR for each field strength was adjusted by targeted voxel size variation to minimize the effect of SNR on the field strength specific outcome. Spatial and temporal characteristics of resting state ICA, network graphs, and motor task related activated areas were compared. Finally, a graph theoretical approach was used to detect resting state modulation subsequent to a simple motor task.
Results
Spatial extensions of resting state ICA and motor task related activated areas were consistent between field strengths, but temporal characteristics varied, indicating that 7 T achieved a higher functional specificity of the BOLD response than 3 T-fMRI. Following the motor task, only 7 T-fMRI enabled the detection of highly specific connectivity modulations representing an “offline replay” of previous motor activation. Modulated connections of the motor cortex were directly linked to brain regions associated with memory consolidation.
Conclusion
These findings reveal how memory processing is initiated even after simple motor tasks, and that it begins earlier than previously shown. Thus, the superior capability of 7 T-fMRI to detect subtle functional dynamics promises to improve diagnostics and therapeutic assessment of neurological diseases.
Fatty acid hydroxylase-associated neurodegeneration (FAHN/SPG35) is caused by pathogenic variants in
and has been linked to a continuum of specific motor and non-motor neurological symptoms, leading ...to progressive disability. As an ultra-rare disease, its mutational spectrum has not been fully elucidated. Here, we present the prototypical workup of a novel
variant, including clinical and in silico validation. An 18-year-old male patient presented with a history of childhood-onset progressive cognitive impairment, as well as progressive gait disturbance and lower extremity muscle cramps from the age of 15. Additional symptoms included exotropia, dystonia, and limb ataxia. Trio exome sequencing revealed a novel homozygous c.75C>G (p.Cys25Trp) missense variant in the
gene, which was located in the cytochrome b5 heme-binding domain. Evolutionary conservation, prediction models, and structural protein modeling indicated a pathogenic loss of function. Brain imaging showed characteristic features, thus fulfilling the complete multisystem neurodegenerative phenotype of FAHN/SPG35. In summary, we here present a novel
variant and provide prototypical clinical findings and structural analyses underpinning its pathogenicity.
This study aims to investigate the diffusion metrics of left versus right temporal lobe epilepsy in a well-defined subgroup of patients with mesial temporal lobe epilepsy (mTLE) because of unilateral ...hippocampal sclerosis while taking into account interhemispheric differences. Eighteen patients with TLE nine left temporal lobe epilepsy (LTLE) and nine right temporal lobe epilepsy (RTLE) and a norm group of 36 nonepileptic individuals were scanned with a multiband accelerated diffusion tensor imaging protocol at 3T. The scalar diffusion tensor parameters fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) and, after projection on a symmetric skeleton, their hemispheric difference (dFA, dMD, and dRD) were analyzed using tract-based spatial statistics. In the cluster with significantly (P<0.008) different dFA, dMD, and dRD between right TLE and left TLE, the hemispheric difference in the mean scalar indices (dmFA, dmMD, and dmRD) was assessed and tested for differences using a one-way analysis of variance and for correlation with patient age, seizure onset, or duration of epilepsy using Pearson's correlation. Patients with LTLE showed lower dFA, higher dMD, and higher dRD (P<0.008) compared with patients with RTLE in a cluster including parts of the uncinated and inferior longitudinal fasciculus and the inferior fronto-occipital fasciculus. dmFA, dmMD, and dmRD differed significantly between groups (P<10, corrected) and showed no correlation with patient age, seizure onset, or duration of epilepsy. The exclusion of bilateral interindividual variance through the calculation of the hemispheric difference of the diffusion metrics by the symmetric variant of tract-based spatial statistics allows for a sensitive differentiation of LTLE and RTLE with unilateral hippocampal sclerosis.
Intracerebral hemorrhage (ICH) prognostication during the acute phase is often subjective among physicians and often affects treatment decisions. The present study explores objective imaging ...parameters using quantitative corticospinal tract (CST) fiber reconstruction during the acute phase of ICH and correlates these parameters with functional outcome and patient recovery. We prospectively enrolled nonsurgical spontaneous supratentorial ICH patients and obtained an MRI scan on day 5 ± 1. Q-space diffeomorphic reconstruction was performed using DSI Studio, and quantitative anisotropy (QA) was calculated. The CST was reconstructed based on QA. The dichotomized modified Rankin Scale score on day 90 (favorable outcome = 0–2) and Barthel Index (favorable recovery = 100 on day 90 or improvement between discharge and day 90 > 60%) were assessed. Thirty-three patients, median age 72 years (interquartile range (IQR) 64–83), 21 female (64%), 21 (64%) with lobar hemorrhage, median ICH volume on admission 15.0 (IQR 7.0–27.4) mL, were included. Sixteen patients (48%) had a favorable outcome and 24 (73%) had a favorable recovery. The mean number of ipsilesional reconstructed CST fiber pathways was higher in patients with favorable outcomes (153 (standard deviation (SD) 103) vs. 60 (SD 39),
p
= 0.003) and predicted outcome after adjustment (Exp(B) = 1.016 (95% CI = 1.002–1.030)). QA in the ipsilesional posterior limb of the internal capsule showed a trend towards an association with favorable outcome (Exp(B) = 1.194 (95% CI = 0.991–1.439 (adjusted))). The total (ipsilesional + contralesional) number of reconstructed fiber pathways was associated with favorable recovery (Exp(B) = 1.025 (95% CI = 1.003–1.047 (adjusted))). Quantitative tractography parameters assessed in the acute phase of ICH may represent a promising predictor of long-term outcome and recovery. This might facilitate prognostic evaluation and organization of rehabilitation.
Tract-based spatial statistics (TBSS) has been used to assess the integrity of the visual pathway in glaucoma patients. TBSS uses the subjects' FA data to create a mean FA skeleton of white matter ...tracts before running voxel-wise cross-subject statistics. We compared four different approaches of registration of FA maps to create the skeleton and evaluated alignment and subsequently the impact of the chosen registration on voxel-wise statistics.
Our study comprised 69 subjects, i.e. 46 patients with primary open angle glaucoma (POAG) and a healthy, age-matched control group of 23 subjects. Mean FA skeletons were created using the following registration approaches: registration to a standard template (T), registration to the group mean (GM), registration to a group-wise atlas (GW) and registration to the most typical subject (N). Subsequently, maps of standard deviation of the 4D images were created to assess the alignment. Voxel-wise statistics for each registration approach were performed.
We found distinct differences in voxel-wise statistics depending on the chosen registration approach. Best alignment results were achieved by registration to a study specific template, i.e. to the group mean (GM) or to a group-wise atlas (GW). Overall alignment did not differ between these two approaches. However, voxel-wise statistics showed clusters of significantly decreased FA values in the T and GM approach, which were not significant after GW registration. These voxels of significantly decreased FA values after T and GM registration did not represent white matter tracts and correlated with higher standard deviation in FA maps across subjects, thus implying registration errors, especially in the optic radiation.
Registration to a study-specific template, i.e. to the group mean or a group-wise atlas seems to be the method of choice in TBSS-analysis of glaucoma patients as it shows better alignment of the optic radiation and helps to rule out registration errors due to misalignment.
This study compares the diagnostic performance and image quality of single-shot turbo spin-echo DWI (tseDWI), standard readout-segmented DWI (rsDWI), and a modified rsDWI version (topupDWI) for ...cholesteatoma diagnostics. Thirty-four patients with newly suspected unilateral cholesteatoma were examined on a 1.5 Tesla MRI scanner. Diagnostic performance was evaluated by calculating and comparing the sensitivity and specificity using histopathological results as the standard of reference. Image quality was independently reviewed by two readers using a 5-point Likert scale evaluating image distortions, susceptibility artifacts, image resolution, lesion conspicuity, and diagnostic confidence. Twenty-five cholesteatomas were histologically confirmed after surgery and originated in the study group. TseDWI showed the highest sensitivity with 96% (95% confidence interval (CI): 88-100%), followed by topupDWI with 92% (95% CI: 81-100%) for both readers. The sensitivity for rsDWI was 76% (95% CI: 59-93%) for reader 1 and 84% (95% CI: 70-98%) for reader 2, respectively. Both tseDWI and topupDWI revealed a specificity of 100% (95% CI: 66-100%) and rsDWI of 89% (95% CI: 52-100%). Both tseDWI and topupDWI showed fewer image distortions and susceptibility artifacts compared to rsDWI. Image resolution was consistently rated best for topupDWI, followed by rsDWI, which both outperformed tseDWI. TopupDWI and tseDWI showed comparable results for lesions' conspicuity and diagnostic confidence, both outperforming rsDWI. Modified readout-segmented DWI using the topup-correction method is preferable to standard rsDWI and may be regarded as an accurate alternative to single-shot turbo spin-echo DWI in cholesteatoma diagnostics.
Hippocampal-sparing radiotherapy (HSR) is a promising approach to alleviate cognitive side effects following cranial radiotherapy. Microstructural brain changes after irradiation have been ...demonstrated using Diffusion Tensor Imaging (DTI). However, evidence is conflicting for certain parameters and anatomic structures. This study examines the effects of radiation on white matter and hippocampal microstructure using DTI and evaluates whether these may be mitigated using HSR. A total of 35 tumor patients undergoing a prospective randomized controlled trial receiving either conventional or HSR underwent DTI before as well as 6, 12, 18, 24, and 30 (±3) months after radiotherapy. Fractional Anisotropy (FA), Mean Diffusivity (MD), Axial Diffusivity (AD), and Radial Diffusivity (RD) were measured in the hippocampus (CA), temporal, and frontal lobe white matter (TL, FL), and corpus callosum (CC). Longitudinal analysis was performed using linear mixed models. Analysis of the entire patient collective demonstrated an overall FACC decrease and RDCC increase compared to baseline in all follow-ups; ADCC decreased after 6 months, and MDCC increased after 12 months (p ≤ 0.001, 0.001, 0.007, 0.018). ADTL decreased after 24 and 30 months (p ≤ 0.004, 0.009). Hippocampal FA increased after 6 and 12 months, driven by a distinct increase in ADCA and MDCA, with RDCA not increasing until 30 months after radiotherapy (p ≤ 0.011, 0.039, 0.005, 0.040, 0.019). Mean radiation dose correlated positively with hippocampal FA (p < 0.001). These findings may indicate complex pathophysiological changes in cerebral microstructures after radiation, insufficiently explained by conventional DTI models. Hippocampal microstructure differed between patients undergoing HSR and conventional cranial radiotherapy after 6 months with a higher ADCA in the HSR subgroup (p ≤ 0.034).