Higher Validity, Lower Radiation: A New Ictal Single-Photon Emission Computed Tomography Framework.

OBJECTIVE: To assess whether arterial spin labeling perfusion images of healthy controls can enhance ictal single-photon emission computed tomography analysis and whether the acquisition of the interictal image can be omitted. METHODS: We developed 2 pipelines: The first uses ictal and interictal images and compares these to single-photon emission computed tomography and arterial spin labeling of healthy controls. The second pipeline uses only the ictal image and the analogous healthy controls. Both pipelines were compared to the gold standard analysis and evaluated on data of individuals with epilepsy who underwent ictal single-photon emission computed tomography imaging during presurgical evaluation between 2010 and 2022. Fifty healthy controls prospectively underwent arterial spin labeling imaging. The correspondence between the detected hyperperfusion and the postoperative resection cavity or the presumably affected lobe was assessed using Dice score and mean Euclidean distance. Additionally, the outcomes of the pipelines were automatically assigned to 1 of 5 concordance categories. RESULTS: Inclusion criteria were met by 43 individuals who underwent epilepsy surgery and by 73 non-surgical individuals with epilepsy. Compared to the gold standard analysis, both pipelines resulted in significantly higher Dice scores and lower mean distances (p < 0.05). The combination of both provided localizing results in 85/116 cases, compared to 54/116 generated by the current gold standard analysis and the ictal image alone produced localizing results in 60/116 (52%) cases. INTERPRETATION: We propose a new ictal single-photon emission computed tomography protocol; it finds relevantly more ictal hyperperfusion, and halves the radiation dose in about half of the individuals. ANN NEUROL 2024.

Improved gradient echo magnitude- and phase-based mapping of T 2 $$ {\mathrm{T}}_2 $$ using multiple RF spoiling increments at 3T and 7T.

PURPOSE: The transverse relaxation time T 2 $$ {}_2 $$ holds significant relevance in clinical applications and research studies. Conventional T 2 $$ {}_2 $$ mapping approaches rely on spin-echo sequences, which require lengthy acquisition times and involve high radiofrequency (RF) power deposition. An alternative gradient echo (GRE) phase-based T 2 $$ {}_2 $$ mapping method, utilizing steady-state acquisitions at one small RF spoil phase increment, was recently demonstrated. Here, a modified magnitude- and phase-based T 2 $$ {}_2 $$ mapping approach is proposed, which improves T 2 $$ {\mathrm{T}}_2 $$ estimations by simultaneous fitting of T 1 $$ {\mathrm{T}}_1 $$ and signal amplitude ( A ∝ P D $$ A\propto PD $$ ) at three or more RF spoiling phase increments, instead of assuming a fixed T 1 $$ {\mathrm{T}}_1 $$ value. METHODS: The feasibility of the magnitude-phase-based method was assessed by simulations, in phantom and in vivo experiments using skipped-CAIPI three-dimensional-echo-planar imaging (3D-EPI) for rapid GRE imaging. T 2 $$ {\mathrm{T}}_2 $$ , T 1 $$ {\mathrm{T}}_1 $$ and PD estimations obtained by our method were compared to T 2 $$ {\mathrm{T}}_2 $$ of the phase-based method and T 1 $$ {\mathrm{T}}_1 $$ and PD of spoiled GRE-based multi-parameter mapping using a multi-echo version of the same sequence. RESULTS: The agreement of the proposed T 2 $$ {\mathrm{T}}_2 $$ with ground truth and reference T 2 $$ {\mathrm{T}}_2 $$ values was higher than that of phase-based T 2 $$ {\mathrm{T}}_2 $$ in simulations and in phantom data. While phase-based T 2 $$ {\mathrm{T}}_2 $$ overestimation increases with actual T 2 $$ {\mathrm{T}}_2 $$ and T 1 $$ {\mathrm{T}}_1 $$ , the proposed method is accurate over a large range of physiologically meaningful T 2 $$ {\mathrm{T}}_2 $$ and T 1 $$ {\mathrm{T}}_1 $$ values. At the same time, precision is improved. In vivo results were in line with these observations. CONCLUSION: Accurate magnitude-phase-based T 2 $$ {}_2 $$ mapping is feasible in less than 5 min scan time for 1 mm nominal isotropic whole-head coverage at 3T and 7T.

Rapid submillimeter QSM and R2* mapping using interleaved multishot 3D-EPI at 7 and 3 Tesla.

PURPOSE: To explore the high signal-to-noise ratio (SNR) efficiency of interleaved multishot 3D-EPI with standard image reconstruction for fast and robust high-resolution whole-brain quantitative susceptibility (QSM) and R 2 ∗ $$ {R}_2^{\ast } $$ mapping at 7 and 3T. METHODS: Single- and multi-TE segmented 3D-EPI is combined with conventional CAIPIRINHA undersampling for up to 72-fold effective gradient echo (GRE) imaging acceleration. Across multiple averages, scan parameters are varied (e.g., dual-polarity frequency-encoding) to additionally correct for B 0 $$ {\mathrm{B}}_0 $$ -induced artifacts, geometric distortions and motion retrospectively. A comparison to established GRE protocols is made. Resolutions range from 1.4 mm isotropic (1 multi-TE average in 36 s) up to 0.4 mm isotropic (2 single-TE averages in approximately 6 min) with whole-head coverage. RESULTS: Only 1-4 averages are needed for sufficient SNR with 3D-EPI, depending on resolution and field strength. Fast scanning and small voxels together with retrospective corrections result in substantially reduced image artifacts, which improves susceptibility and R 2 ∗ $$ {R}_2^{\ast } $$ mapping. Additionally, much finer details are obtained in susceptibility-weighted image projections through significantly reduced partial voluming. CONCLUSION: Using interleaved multishot 3D-EPI, single-TE and multi-TE data can readily be acquired 10 times faster than with conventional, accelerated GRE imaging. Even 0.4 mm isotropic whole-head QSM within 6 min becomes feasible at 7T. At 3T, motion-robust 0.8 mm isotropic whole-brain QSM and R 2 ∗ $$ {R}_2^{\ast } $$ mapping with no apparent distortion in less than 7 min becomes clinically feasible. Stronger gradient systems may allow for even higher effective acceleration rates through larger EPI factors while maintaining optimal contrast.

Calibration-free whole-brain CEST imaging at 7T with parallel transmit pulse design for saturation homogeneity utilizing universal pulses (PUSHUP).

PURPOSE: Chemical exchange saturation transfer (CEST) measurements at ultra-high field (UHF) suffer from strong saturation inhomogeneity. Retrospective correction of this inhomogeneity is possible to some extent, but requires a time-consuming repetition of the measurement. Here, we propose a calibration-free parallel transmit (pTx)-based saturation scheme that homogenizes the saturation over the imaging volume, which we call PUlse design for Saturation Homogeneity utilizing Universal Pulses (PUSHUP). THEORY: Magnetization transfer effects depend on the saturation B 1 rms $$ {\mathrm{B}}_1^{\mathrm{rms}} $$ . PUSHUP homogenizes the saturation B 1 rms $$ {\mathrm{B}}_1^{\mathrm{rms}} $$ by using multiple saturation pulses with alternating B 1 $$ {\mathrm{B}}_1 $$ -shims. Using a database of B 1 $$ {\mathrm{B}}_1 $$ maps, universal pulses are calculated that remove the necessity of time-consuming, subject-based pulse calculation during the measurement. METHODS: PUSHUP was combined with a whole-brain three-dimensional-echo planar imaging (3D-EPI) readout. Two PUSHUP saturation modules were calculated by either applying whole-brain or cerebellum masks to the database maps. The saturation homogeneity and the group mean CEST amplitudes were calculated for different B 1 $$ {\mathrm{B}}_1 $$ -correction methods and were compared to circular polarized (CP) saturation in five healthy volunteers using an eight-channel transmit coil at 7 Tesla. RESULTS: In contrast to CP saturation, where accurate CEST maps were impossible to obtain in the cerebellum, even with extensive B 1 $$ {\mathrm{B}}_1 $$ -correction, PUSHUP CEST maps were artifact-free throughout the whole brain. A 1-point retrospective B 1 $$ {\mathrm{B}}_1 $$ -correction, that does not need repeated measurements, sufficiently removed the effect of residual saturation inhomogeneity. CONCLUSION: The presented method allows for homogeneous whole-brain CEST imaging at 7 Tesla without the need of a repetition-based B 1 $$ {\mathrm{B}}_1 $$ -correction or online pulse calculation. With the fast 3D-EPI readout, whole-brain CEST imaging with 45 saturation offsets is possible at 1.6 mm resolution in under 4 min.

The possible influence of third-order shim coils on gradient-magnet interactions: an inter-field and inter-site study.

OBJECTIVE: To assess the possible influence of third-order shim coils on the behavior of the gradient field and in gradient-magnet interactions at 7 T and above. MATERIALS AND METHODS: Gradient impulse response function measurements were performed at 5 sites spanning field strengths from 7 to 11.7 T, all of them sharing the same exact whole-body gradient coil design. Mechanical fixation and boundary conditions of the gradient coil were altered in several ways at one site to study the impact of mechanical coupling with the magnet on the field perturbations. Vibrations, power deposition in the He bath, and field dynamics were characterized at 11.7 T with the third-order shim coils connected and disconnected inside the Faraday cage. RESULTS: For the same whole-body gradient coil design, all measurements differed greatly based on the third-order shim coil configuration (connected or not). Vibrations and gradient transfer function peaks could be affected by a factor of 2 or more, depending on the resonances. Disconnecting the third-order shim coils at 11.7 T also suppressed almost completely power deposition peaks at some frequencies. DISCUSSION: Third-order shim coil configurations can have major impact in gradient-magnet interactions with consequences on potential hardware damage, magnet heating, and image quality going beyond EPI acquisitions.

Germany's journey toward 14 Tesla human magnetic resonance.

Multiple sites within Germany operate human MRI systems with magnetic fields either at 7 Tesla or 9.4 Tesla. In 2013, these sites formed a network to facilitate and harmonize the research being conducted at the different sites and make this technology available to a larger community of researchers and clinicians not only within Germany, but also worldwide. The German Ultrahigh Field Imaging (GUFI) network has defined a strategic goal to establish a 14 Tesla whole-body human MRI system as a national research resource in Germany as the next progression in magnetic field strength. This paper summarizes the history of this initiative, the current status, the motivation for pursuing MR imaging and spectroscopy at such a high magnetic field strength, and the technical and funding challenges involved. It focuses on the scientific and science policy process from the perspective in Germany, and is not intended to be a comprehensive systematic review of the benefits and technical challenges of higher field strengths.

Common and dissociable effects of oxytocin and lorazepam on the neurocircuitry of fear.

Benzodiazepines (BZDs) represent the gold standard of anxiolytic pharmacotherapy; however, their clinical benefit is limited by side effects and addictive potential. Consequently, there is an urgent need to develop novel and safe anxiolytics. The peptide hormone oxytocin (OXT) exhibits anxiolytic-like properties in animals and humans, but whether OXT and BZDs share similar effects on the neural circuitry of fear is unclear. Therefore, the rationale of this ultra-high-field functional MRI (fMRI) study was to test OXT against the clinical comparator lorazepam (LZP) with regard to their neuromodulatory effects on local and network responses to fear-related stimuli. One hundred twenty-eight healthy male participants volunteered in this randomized double-blind, placebo-controlled, between-group study. Before scanning using an emotional face-matching paradigm, participants were randomly administered a single dose of OXT (24 IU), LZP (1 mg), or placebo. On the behavioral level, LZP, but not OXT, caused mild sedation, as evidenced by a 19% increase in reaction times. On the neural level, both OXT and LZP inhibited responses to fearful faces vs. neutral faces within the centromedial amygdala (cmA). In contrast, they had different effects on intra-amygdalar connectivity; OXT strengthened the coupling between the cmA and basolateral amygdala, whereas LZP increased the interplay between the cmA and superficial amygdala. Furthermore, OXT, but not LZP, enhanced the coupling between the cmA and the precuneus and dorsomedial prefrontal cortex. These data implicate inhibition of the cmA as a common denominator of anxiolytic action, with only OXT inducing large-scale connectivity changes of potential therapeutic relevance.

Reproducibility of rapid multi-parameter mapping at 3T and 7T with highly segmented and accelerated 3D-EPI.

PURPOSE: Quantitative multi-parameter mapping (MPM) has been shown to provide good longitudinal and cross-sectional reproducibility for clinical research. Unfortunately, acquisition times (TAs) are typically infeasible for routine scanning at high resolutions. METHODS: A fast whole-brain MPM protocol based on interleaved multi-shot 3D-EPI with controlled aliasing (SC-EPI) at 3T and 7T is proposed and compared with MPM using a standard spoiled gradient echo (FLASH) sequence. Four parameters (R1 , PD, R 2 * $$ {R}_2^{\ast } $$ , and MTsat) were measured in less than 3 min at 1 mm isotropic resolution. Five subjects went through the same scanning sessions twice at each scanner. The intra-subject coefficient of variation (scan-rescan) (CoV) was estimated for each protocol and scanner to assess the longitudinal reproducibility. RESULTS: At 3T, the CoV of SC-EPI ranged between 1.2%-4.8% for PD and R1 , 2.8%-10.6% for R 2 * $$ {R}_2^{\ast } $$ and MTsat, which was comparable with FLASH (0.6%-4.9% for PD and R1 , 2.6%-11.3% for R 2 * $$ {R}_2^{\ast } $$ and MTsat). At 7T, where the SC-EPI TA was reduced to ∼2 min, the CoV of SC-EPI (1.4%-10.6% for PD, R1 , and R 2 * $$ {R}_2^{\ast } $$ ) was 1.2-2.4 times larger than the CoV of FLASH (1.0%-15%) and MTsat showed much higher variability across subjects. The SC-EPI-MPM protocol at 3T showed high reproducibility and yielded stable quantitative maps at a clinically feasible resolution and scan time, whereas at 7T, MT saturation homogeneity needs to be improved. CONCLUSION: SC-EPI-based MPM is feasible as an additional MRI modality in clinical or population studies where the parameters offer great potential as biomarkers.

Interleaved binomial kT -points for water-selective imaging at 7T.

PURPOSE: We present a time-efficient water-selective, parallel transmit RF excitation pulse design for ultra-high field applications. METHODS: The proposed pulse design method achieves flip angle homogenization at ultra-high fields by employing spatially nonselective k T $$ {\mathrm{k}}_T $$ -points pulses. In order to introduce water-selection, the concept of binomial pulses is applied. Due to the composite nature of k T $$ {\mathrm{k}}_T $$ -points, the pulse can be split into multiple binomial subpulse blocks shorter than half the precession period of fat, that are played out successively. Additional fat precession turns, that would otherwise impair the spectral response, can thus be avoided. Bloch simulations of the proposed interleaved binomial k T $$ {\mathrm{k}}_T $$ -points pulses were carried out and compared in terms of duration, homogeneity, fat suppression and pulse energy. For validation, in vivo MP-RAGE and 3D-EPI data were acquired. RESULTS: Simulation results show that interleaved binomial k T $$ {\mathrm{k}}_T $$ -points pulses achieve shorter total pulse durations, improved flip angle homogeneity and more robust fat suppression compared to available methods. Interleaved binomial k T $$ {\mathrm{k}}_T $$ -points can be customized by changing the number of k T $$ {\mathrm{k}}_T $$ -points, the subpulse duration and the order of the binomial pulse. Using shorter subpulses, the number of k T $$ {\mathrm{k}}_T $$ -points can be increased and hence better homogeneity is achieved, while still maintaining short total pulse durations. Flip angle homogenization and fat suppression of interleaved binomial k T $$ {\mathrm{k}}_T $$ -points pulses is demonstrated in vivo at 7T, confirming Bloch simulation results. CONCLUSION: In this work, we present a time efficient and robust parallel transmission technique for nonselective water excitation with simultaneous flip angle homogenization at ultra-high field.

Open-source MR imaging and reconstruction workflow.

PURPOSE: This work presents an end-to-end open-source MR imaging workflow. It is highly flexible in rapid prototyping across the whole imaging process and integrates vendor-independent openly available tools. The whole workflow can be shared and executed on different MR platforms. It is also integrated in the JEMRIS simulation framework, which makes it possible to generate simulated data from the same sequence that runs on the MRI scanner using the same pipeline for image reconstruction. METHODS: MRI sequences can be designed in Python or JEMRIS using the Pulseq framework, allowing simplified integration of new sequence design tools. During the sequence design process, acquisition metadata required for reconstruction is stored in the MR raw data format. Data acquisition is possible on MRI scanners supported by Pulseq and in simulations through JEMRIS. An image reconstruction and postprocessing pipeline was implemented into a Python server that allows real-time processing of data as it is being acquired. The Berkeley Advanced Reconstruction Toolbox is integrated into this framework for image reconstruction. The reconstruction pipeline supports online integration through a vendor-dependent interface. RESULTS: The flexibility of the workflow is demonstrated with different examples, containing 3D parallel imaging with controlled aliasing in volumetric parallel imaging (CAIPIRINHA) acceleration, spiral imaging, and B0 mapping. All sequences, data, and the corresponding processing pipelines are publicly available. CONCLUSION: The proposed workflow is highly flexible and allows integration of advanced tools at all stages of the imaging process. All parts of this workflow are open-source, simplifying collaboration across different MR platforms or sites and improving reproducibility of results.

Incidental findings on 3 T neuroimaging: cross-sectional observations from the population-based Rhineland Study.

PURPOSE: Development of best practices for dealing with incidental findings on neuroimaging requires insight in their frequency and clinical relevance. METHODS: Here, we delineate prevalence estimates with 95% confidence intervals and clinical management of incidental findings, based on the first 3589 participants of the population-based Rhineland Study (age range 30-95 years) who underwent 3 Tesla structural neuroimaging (3D, 0.8 mm3 isotropic resolution). Two trained raters independently assessed all scans for abnormalities, with confirmation and adjudication where needed by neuroradiologists. Participants were referred for diagnostic work-up depending on the potential benefit. RESULTS: Of 3589 participants (mean age 55 ± 14 years, 2072 women), 867 had at least one possible incidental finding (24.2%). Most common were pituitary abnormalities (12.3%), arachnoid cysts (4.1%), developmental venous anomalies (2.5%), non-acute infarcts (1.8%), cavernomas (1.0%), and meningiomas (0.7%). Forty-six participants were informed about their findings, which was hitherto unknown in 40 of them (1.1%). Of these, in 19 participants (48%), a wait-and-see policy was applied and nine (23%) received treatment, while lesions in the remainder were benign, could not be confirmed, or the participant refused to inform us about their clinical diagnosis. CONCLUSION: Nearly one-quarter of participants had an incidental finding, but only 5% of those required referral, that mostly remained without direct clinical consequences.

Automated olfactory bulb segmentation on high resolutional T2-weighted MRI.

The neuroimage analysis community has neglected the automated segmentation of the olfactory bulb (OB) despite its crucial role in olfactory function. The lack of an automatic processing method for the OB can be explained by its challenging properties (small size, location, and poor visibility on traditional MRI scans). Nonetheless, recent advances in MRI acquisition techniques and resolution have allowed raters to generate more reliable manual annotations. Furthermore, the high accuracy of deep learning methods for solving semantic segmentation problems provides us with an option to reliably assess even small structures. In this work, we introduce a novel, fast, and fully automated deep learning pipeline to accurately segment OB tissue on sub-millimeter T2-weighted (T2w) whole-brain MR images. To this end, we designed a three-stage pipeline: (1) Localization of a region containing both OBs using FastSurferCNN, (2) Segmentation of OB tissue within the localized region through four independent AttFastSurferCNN - a novel deep learning architecture with a self-attention mechanism to improve modeling of contextual information, and (3) Ensemble of the predicted label maps. For this work, both OBs were manually annotated in a total of 620 T2w images for training (n=357) and testing. The OB pipeline exhibits high performance in terms of boundary delineation, OB localization, and volume estimation across a wide range of ages in 203 participants of the Rhineland Study (Dice Score (Dice): 0.852, Volume Similarity (VS): 0.910, and Average Hausdorff Distance (AVD): 0.215 mm). Moreover, it also generalizes to scans of an independent dataset never encountered during training, the Human Connectome Project (HCP), with different acquisition parameters and demographics, evaluated in 30 cases at the native 0.7 mm HCP resolution (Dice: 0.738, VS: 0.790, and AVD: 0.340 mm), and the default 0.8 mm pipeline resolution (Dice: 0.782, VS: 0.858, and AVD: 0.268 mm). We extensively validated our pipeline not only with respect to segmentation accuracy but also to known OB volume effects, where it can sensitively replicate age effects (ß=-0.232, p<.01). Furthermore, our method can analyze a 3D volume in less than a minute (GPU) in an end-to-end fashion, providing a validated, efficient, and scalable solution for automatically assessing OB volumes.

Insulin resistance accounts for metabolic syndrome-related alterations in brain structure.

Metabolic syndrome (MetS) is a major public health burden worldwide and associated with brain abnormalities. Although insulin resistance is considered a pivotal feature of MetS, its role in the pathogenesis of MetS-related brain alterations in the general population is unclear. Therefore, in 973 participants (mean age 52.5 years) of the population-based Rhineland Study, we assessed brain morphology in relation to MetS and insulin resistance, and evaluated to what extent the pattern of structural brain changes seen in MetS overlap with those associated with insulin resistance. Cortical reconstruction and volumetric segmentation were obtained from high-resolution brain images at 3 Tesla using FreeSurfer. The relations between metabolic measures and brain structure were assessed through (generalized) linear models. Both MetS and insulin resistance were associated with smaller cortical gray matter volume and thickness, but not with white matter or subcortical gray matter volume. Age- and sex-adjusted vertex-based brain morphometry demonstrated that MetS and insulin resistance were related to cortical thinning in a similar spatial pattern. Importantly, no independent effect of MetS on cortical gray matter was observed beyond the effect of insulin resistance. Our findings suggest that addressing insulin resistance is critical in the prevention of MetS-related brain changes in later life.

Segmented K-space blipped-controlled aliasing in parallel imaging for high spatiotemporal resolution EPI.

PURPOSE: A segmented k-space blipped-controlled aliasing in parallel imaging (skipped-CAIPI) sampling strategy for EPI is proposed, which allows for a flexible choice of EPI factor and phase encode bandwidth independent of the controlled aliasing in parallel imaging (CAIPI) sampling pattern. THEORY AND METHODS: With previously proposed approaches, exactly two EPI trajectories were possible given a specific CAIPI pattern, either with slice gradient blips (blipped-CAIPI) or following a shot-selective CAIPI approach (higher resolution). Recently, interleaved multi-shot segmentation along shot-selective CAIPI trajectories has been applied for high-resolution anatomical imaging. For more flexibility and a broader range of applications, we propose segmentation along any blipped-CAIPI trajectory. Thus, all EPI factors and phase encode bandwidths available with traditional segmented EPI can be combined with controlled aliasing. RESULTS: Temporal SNR maps of moderate-to-high-resolution time series acquisitions at varying undersampling factors demonstrate beneficial sampling alternatives to blipped-CAIPI or shot-selective CAIPI. Rapid high-resolution scans furthermore demonstrate SNR-efficient and motion-robust structural imaging with almost arbitrary EPI factor and minimal noise penalty. CONCLUSION: Skipped-CAIPI sampling increases protocol flexibility for high spatiotemporal resolution EPI. In terms of SNR and efficiency, high-resolution functional or structural scans benefit vastly from a free choice of the CAIPI pattern. Even at moderate resolutions, the independence of sampling pattern, TE, and image matrix size is valuable for optimized functional protocol design. Although demonstrated with 3D-EPI, skipped-CAIPI is also applicable with simultaneous multislice EPI.

Disentangling early versus late audiovisual integration in adult ADHD: a combined behavioural and resting-state connectivity study.

BACKGROUND: Studies investigating sensory processing in attention-deficit/hyperactivity disorder (ADHD) have shown altered visual and auditory processing. However, evidence is lacking for audiovisual interplay - namely, multisensory integration. As well, neuronal dysregulation at rest (e.g., aberrant within- or between-network functional connectivity) may account for difficulties with integration across the senses in ADHD. We investigated whether sensory processing was altered at the multimodal level in adult ADHD and included resting-state functional connectivity to illustrate a possible overlap between deficient network connectivity and the ability to integrate stimuli. METHODS: We tested 25 patients with ADHD and 24 healthy controls using 2 illusionary paradigms: the sound-induced flash illusion and the McGurk illusion. We applied the Mann-Whitney U test to assess statistical differences between groups. We acquired resting-state functional MRIs on a 3.0 T Siemens magnetic resonance scanner, using a highly accelerated 3-dimensional echo planar imaging sequence. RESULTS: For the sound-induced flash illusion, susceptibility and reaction time were not different between the 2 groups. For the McGurk illusion, susceptibility was significantly lower for patients with ADHD, and reaction times were significantly longer. At a neuronal level, resting-state functional connectivity in the ADHD group was more highly regulated in polymodal regions that play a role in binding unimodal sensory inputs from different modalities and enabling sensory-to-cognition integration. LIMITATIONS: We did not explicitly screen for autism spectrum disorder, which has high rates of comorbidity with ADHD and also involves impairments in multisensory integration. Although the patients were carefully screened by our outpatient department, we could not rule out the possibility of autism spectrum disorder in some participants. CONCLUSION: Unimodal hypersensitivity seems to have no influence on the integration of basal stimuli, but it might have negative consequences for the multisensory integration of complex stimuli. This finding was supported by observations of higher resting-state functional connectivity between unimodal sensory areas and polymodal multisensory integration convergence zones for complex stimuli.

On the reproducibility of hippocampal MEGA-sLASER GABA MRS at 7T using an optimized analysis pipeline.

OBJECTIVES: GABA is the most important inhibitory neurotransmitter. Thus, variation in its concentration is connected to a wide variety of diseases. However, the low concentration and the overlap of more prominent resonances hamper GABA quantification using MR spectroscopy. The hippocampus plays a pivotal role in neurodegeneration. Susceptibility discontinuities in the vicinity of the hippocampus cause strong B0 inhomogeneities, impeding GABA spectroscopy. The aim of this work is to improve the reproducibility of hippocampal GABA+ MRS. METHODS: The GABA+/total creatine ratio in the hippocampus was measured using a MEGA-sLASER sequence at 7 Tesla. 10 young healthy volunteers participated in the study. A dedicated pre-processing approach was established. Spectral quantification was performed with Tarquin. The quantification parameters were carefully adjusted to ensure optimal quantification. RESULTS: An inter-subject coefficient of variation of the GABA+/total creatine of below 15% was achieved. Additional to spectral registration, which is essential to obtain reproducible GABA measures, eddy current compensation and additional difference artifact suppression improved the reproducibility. The mean FWHM was 23.1 Hz (0.078 ppm). CONCLUSION: The increased spectral dispersion of ultra-high-field spectroscopy allows for reproducible spectral quantification, despite a very broad line width. The achieved reproducibility enables the routine use of hippocampal GABA spectroscopy at 7 Tesla.

Whole brain snapshot CEST at 3T using 3D-EPI: Aiming for speed, volume, and homogeneity.

PURPOSE: CEST MRI enables imaging of distributions of low-concentrated metabolites as well as proteins and peptides and their alterations in diseases. CEST examinations often suffer from low spatial resolution, long acquisition times, and concomitant motion artifacts. This work aims to maximize both resolution and volume coverage with a 3D-EPI snapshot CEST approach at 3T, allowing for fast and robust whole-brain CEST MRI. METHODS: Resolution and temporal SNR of 3D-EPI examinations with nonselective excitation were optimized at a clinical 3T MR scanner in five healthy subjects using a clinical head/neck coil. A CEST presaturation module for low power relayed nuclear Overhauser enhancement and amide proton transfer contrast was applied as an example. The suggested postprocessing included motion correction, dynamic B0 correction, denoising, and B1 correction and was compared to an established 3D-gradient echo-based sequence. RESULTS: CEST examinations were performed at 1.8 mm nominal isotropic resolution in 4.3 s per presaturation offset. In contrast to slab-selective 3D or multislice approaches, the whole brain was covered. Repeated examinations at three different B1 values took 13 minutes for 58 presaturation offsets with temporal SNR around 75. The resulting CEST effects revealed significant gray and white matter contrast and were of similar quality across the whole brain. Coefficient of variation across three healthy subjects was below 9%. CONCLUSION: The suggested protocol enables whole brain coverage at 1.8 mm isotropic resolution and fast acquisition of 4.3 s per presaturation offset. For the fitted CEST amplitudes, high reproducibility was proven, increasing the opportunities of quantitative CEST investigations at 3T significantly.

MAPL1: q-space reconstruction using ℓ1 -regularized mean apparent propagator.

PURPOSE: To improve the quality of mean apparent propagator (MAP) reconstruction from a limited number of q-space samples. METHODS: We implement an ℓ1 -regularised MAP (MAPL1) to consider higher order basis functions and to improve the fit without increasing the number of q-space samples. We compare MAPL1 with the least-squares optimization subject to non-negativity (MAP), and the Laplacian-regularized MAP (MAPL). We use simulations of crossing fibers and compute the normalized mean squared error (NMSE) and the Pearson's correlation coefficient to evaluate the reconstruction quality in q-space. We also compare coefficient-based diffusion indices in the simulations and in in vivo data. RESULTS: Results indicate that MAPL1 improves NMSE in 1 to 3% when compared to MAP or MAPL in a high undersampling regime. Additionally, MAPL1 produces more reproducible and accurate results for all sampling rates when there are enough basis functions to meet the sparsity criterion for the regularizer. These improved reconstructions also produce better coefficient-based diffusion indices for in vivo data. CONCLUSIONS: Adding an ℓ1 regularizer to MAP allows the use of more basis functions and a better fit without increasing the number of q-space samples. The impact of our research is that a complete diffusion spectrum can be reconstructed from an acquisition time very similar to a diffusion tensor imaging protocol.

Blood-brain barrier permeability measurement by biexponentially modeling whole-brain arterial spin labeling data with multiple T2 -weightings.

Blood-brain barrier (BBB) permeability assessment remains of ongoing interest in clinical practice and research. Transitions between intravascular (IV) and extravascular (EV) gray matter (GM) compartments may provide information regarding the microstructural status of the BBB. Due to different transverse relaxation times (T2 ) of water protons in vessels and GM, it is possible to determine the compartment in which these protons are located. This work presents and investigates the feasibility of a simplified analytical approach for compartmentalizing the proportions of magnetically marked water protons into IV and EV GM components by biexponentially modeling T2 -weighted arterial spin labeling (ASL) data. Numerous model assumptions were used to stabilize the fit and achieve in vivo applicability. Particularly, transverse relaxation times of IV and EV water protons were determined from the analysis of two supporting T2 -weighted ASL measurements, utilizing a monoexponential signal model. This stabilized a two-parameter biexponential fit of ASL data with T2 preparation (PLD = 0.9/1.2/1.5/1.8 s, TET2Prep = 0/30/40/60/80/120/160 ms), which thereby robustly provided estimates of the IV and EV compartment fractions. Experiments were conducted with three healthy volunteers in a 3 T scanner. Averaged over all subjects, the labeled water protons inherit T2,IV = 200 ± 18 ms initially and adapt T2,EV = 91 ± 2 ms with a longer retention time in cerebral structures. Accordingly, the EVlocated ASL signal fraction rises with increasing PLD from 0.31 ± 0.11 at the shortest PLD of 0.9 s to 0.73 ± 0.02 at the longest PLD of 1.8s. These results indicate a transition of the water protons from IV to EV space. The findings support the potential of biexponential modeling for compartmentalizing ASL spin fractions between IV and EV space. The novel integration of monoexponential parameter estimates stabilizes the two-compartment model fit, suggesting that this technique is suitable for robustly estimating the BBB permeability in vivo.