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1.
Nat Methods ; 20(12): 2048-2057, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38012321

ABSTRACT

To increase granularity in human neuroimaging science, we designed and built a next-generation 7 Tesla magnetic resonance imaging scanner to reach ultra-high resolution by implementing several advances in hardware. To improve spatial encoding and increase the image signal-to-noise ratio, we developed a head-only asymmetric gradient coil (200 mT m-1, 900 T m-1s-1) with an additional third layer of windings. We integrated a 128-channel receiver system with 64- and 96-channel receiver coil arrays to boost signal in the cerebral cortex while reducing g-factor noise to enable higher accelerations. A 16-channel transmit system reduced power deposition and improved image uniformity. The scanner routinely performs functional imaging studies at 0.35-0.45 mm isotropic spatial resolution to reveal cortical layer functional activity, achieves high angular resolution in diffusion imaging and reduces acquisition time for both functional and structural imaging.


Subject(s)
Brain , Magnetic Resonance Imaging , Humans , Brain/diagnostic imaging , Brain/pathology , Magnetic Resonance Imaging/methods , Head , Neuroimaging , Signal-To-Noise Ratio
2.
Magn Reson Med ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987985

ABSTRACT

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.

3.
Magn Reson Med ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38988040

ABSTRACT

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.

4.
Magn Reson Med ; 88(5): 2217-2232, 2022 11.
Article in English | MEDLINE | ID: mdl-35877781

ABSTRACT

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.


Subject(s)
Brain Mapping , Magnetic Resonance Imaging , Brain/diagnostic imaging , Brain Mapping/methods , Cross-Sectional Studies , Humans , Magnetic Resonance Imaging/methods , Reproducibility of Results
5.
Magn Reson Med ; 88(6): 2564-2572, 2022 12.
Article in English | MEDLINE | ID: mdl-35942989

ABSTRACT

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.


Subject(s)
Image Processing, Computer-Assisted , Water , Algorithms , Brain , Computer Simulation , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Phantoms, Imaging
6.
Magn Reson Med ; 85(3): 1540-1551, 2021 03.
Article in English | MEDLINE | ID: mdl-32936488

ABSTRACT

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.


Subject(s)
Image Enhancement , Image Interpretation, Computer-Assisted , Algorithms , Brain/diagnostic imaging , Echo-Planar Imaging , Image Processing, Computer-Assisted , Imaging, Three-Dimensional
7.
J Psychiatry Neurosci ; 46(5): E528-E537, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34548387

ABSTRACT

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.


Subject(s)
Attention Deficit Disorder with Hyperactivity/physiopathology , Attention Deficit Disorder with Hyperactivity/psychology , Auditory Perception , Rest , Visual Perception , Adult , Attention Deficit Disorder with Hyperactivity/complications , Autism Spectrum Disorder/complications , Female , Humans , Illusions , Magnetic Resonance Imaging , Male
8.
Magn Reson Med ; 84(5): 2469-2483, 2020 11.
Article in English | MEDLINE | ID: mdl-32385888

ABSTRACT

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.


Subject(s)
Brain , White Matter , Brain/diagnostic imaging , Humans , Magnetic Resonance Imaging , Protons , Reproducibility of Results
9.
Magn Reson Med ; 84(4): 2219-2230, 2020 10.
Article in English | MEDLINE | ID: mdl-32270542

ABSTRACT

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.


Subject(s)
Diffusion Magnetic Resonance Imaging , Diffusion Tensor Imaging , Algorithms , Brain/diagnostic imaging , Image Enhancement
10.
Magn Reson Med ; 82(3): 924-934, 2019 09.
Article in English | MEDLINE | ID: mdl-31038244

ABSTRACT

PURPOSE: Demonstration of a 3D version of the DREAM sequence (3DREAM) for rapid 3D flip angle and B1+ mapping of the human brain. METHODS: A rectangular non-selective STE preparation is followed by a 3D readout with a Cartesian center-out spiral phase encoding order. This enables parallel imaging acceleration in both phase encoding dimensions as well as early capture of the prepared magnetization. RESULTS: B1+ mapping of the whole human head is demonstrated on a 7T system at a nominal resolution of 5 mm with and without parallel imaging acceleration. Artifacts caused by the different signal decay of the FID and STE signal during the long imaging train is suppressed by appropriate filtering of the FID image. Remaining blurring can be controlled by adjusting the echo train length and readout flip angle. CONCLUSIONS: 3DREAM provides a whole-brain flip angle map in a few seconds or individual maps for an 8-channel array in about a minute.


Subject(s)
Brain/diagnostic imaging , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging/methods , Algorithms , Artifacts , Head/diagnostic imaging , Humans , Phantoms, Imaging
11.
Magn Reson Med ; 82(5): 1741-1752, 2019 11.
Article in English | MEDLINE | ID: mdl-31199016

ABSTRACT

PURPOSE: The aim of this work is to develop a fast and robust CEST sequence in order to allow the acquisition of a whole-brain imaging volume after a single preparation block (snapshot acquisition). METHODS: A 3D-CEST sequence with an optimized 3D-EPI readout module was developed, which acquires the complete k-space data following a single CEST preparation for 1 saturation offset. Whole-brain mapping of the Z-spectrum with 2 mm isotropic resolution is achieved at 68 saturation frequencies in 5 minutes (4.33 s per offset). We analyzed the B1 distribution in order to optimize B1 correction and to provide accurate CEST quantification across the whole brain. RESULTS: We obtained maps for 3 different CEST contrasts from 4 healthy subjects. Based on our B1 distribution analysis, we conclude that 3 B1 sampling points allow for sufficient compensation of B1 variations across most of the brain. Two brain regions, the cerebellum and the temporal lobes, are difficult to quantify at 7 T due to very low B1 that was achieved in these regions. CONCLUSIONS: The proposed sequence enables robust acquisition of 2 mm isotropic whole-brain CEST maps at 7 Tesla within a total scan time of 16 minutes.


Subject(s)
Brain Mapping/methods , Echo-Planar Imaging/methods , Imaging, Three-Dimensional/methods , Healthy Volunteers , Humans , Image Enhancement/methods , Image Processing, Computer-Assisted/methods , Phantoms, Imaging , Signal-To-Noise Ratio
12.
NMR Biomed ; 32(3): e4055, 2019 03.
Article in English | MEDLINE | ID: mdl-30637831

ABSTRACT

Time constraints placed on magnetic resonance imaging often restrict the application of advanced diffusion MRI (dMRI) protocols in clinical practice and in high throughput research studies. Therefore, acquisition strategies for accelerated dMRI have been investigated to allow for the collection of versatile and high quality imaging data, even if stringent scan time limits are imposed. Diffusion spectrum imaging (DSI), an advanced acquisition strategy that allows for a high resolution of intra-voxel microstructure, can be sufficiently accelerated by means of compressed sensing (CS) theory. CS theory describes a framework for the efficient collection of fewer samples of a data set than conventionally required followed by robust reconstruction to recover the full data set from sparse measurements. For an accurate recovery of DSI data, a suitable acquisition scheme for sparse q-space sampling and the sensing and sparsifying bases for CS reconstruction need to be selected. In this work we explore three different types of q-space undersampling schemes and two frameworks for CS reconstruction based on either Fourier or SHORE basis functions. After CS recovery, diffusion and microstructural parameters and orientational information are estimated from the reconstructed data by means of state-of-the-art processing techniques for dMRI analysis. By means of simulation, diffusion phantom and in vivo DSI data, an isotropic distribution of q-space samples was found to be optimal for sparse DSI. The CS reconstruction results indicate superior performance of Fourier-based CS-DSI compared to the SHORE-based approach. Based on these findings we outline an experimental design for accelerated DSI and robust CS reconstruction of the sparse measurements that is suitable for the application within time-limited studies.


Subject(s)
Algorithms , Diffusion Magnetic Resonance Imaging , Image Processing, Computer-Assisted , Acceleration , Adult , Computer Simulation , Female , Humans , Phantoms, Imaging
13.
Magn Reson Med ; 80(6): 2475-2484, 2018 12.
Article in English | MEDLINE | ID: mdl-29770492

ABSTRACT

PURPOSE: To investigate the impact of accelerated, single-shot 3D-GRASE acquisition on quantitative arterial spin labeling (ASL) with multiple and single post-labeling delay (PLD) in terms of perfusion-weighted SNR per unit scan time (TSNRPW ) and quantification accuracy. METHODS: Five subjects were scanned on a 3T MRI scanner using the pseudo-continuous arterial spin labeling (PCASL) technique with a 3D-GRASE imaging sequence capable of parallel imaging acceleration. A 3-inversion pulse background suppression was simulated and implemented in the sequence. Three time-matched single PLD measurements, a segmented one without acceleration, 1 with conventional GRAPPA, and 1 with CAIPIRINHA sampling, were used to compare TSNRPW . Three time-matched multiple PLD measurements with the identical imaging parameters were additionally evaluated (no acceleration vs. CAIPIRINHA sampling vs. CAIPIRINHA sampling with doubled number of PLDs). Cerebral blood flow and arterial transit time fit uncertainties were compared and used as a quality measure. RESULTS: The single PLD measurements show an 11% TSNRPW increase using CAIPIRINHA sampling instead of GRAPPA sampling, while the non-accelerated scan exhibits 35% higher TSNRPW compared to the GRAPPA scan. However, taking advantage of the increased number of averages for multiple PLD acquisitions, a 14%/16% (gray matter) and 34%/36% (white matter) reduction of CBF fit uncertainty is observed with CAIPIRINHA sampling (6 PLDs/12 PLDs) compared to no acceleration. CONCLUSION: Accelerated single-shot 3D-GRASE with PCASL allows for smaller quantification uncertainties than time-matched segmented acquisitions. Corresponding single-shot acquisitions with acceptable blurring and no intra-volume motion render state-of-the-art ASL methods in a clinically feasible time possible.


Subject(s)
Arteries/diagnostic imaging , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Spin Labels , Adult , Bayes Theorem , Brain/diagnostic imaging , Brain/physiology , Calibration , Cerebrovascular Circulation , Computer Simulation , Female , Humans , Magnetic Resonance Imaging , Male , Motion , Perfusion , Reproducibility of Results , Signal-To-Noise Ratio
14.
Brain ; 140(6): 1561-1578, 2017 06 01.
Article in English | MEDLINE | ID: mdl-28459997

ABSTRACT

Despite extensive efforts, half of patients with rare movement disorders such as hereditary spastic paraplegias and cerebellar ataxias remain genetically unexplained, implicating novel genes and unrecognized mutations in known genes. Non-coding DNA variants are suspected to account for a substantial part of undiscovered causes of rare diseases. Here we identified mutations located deep in introns of POLR3A to be a frequent cause of hereditary spastic paraplegia and cerebellar ataxia. First, whole-exome sequencing findings in a recessive spastic ataxia family turned our attention to intronic variants in POLR3A, a gene previously associated with hypomyelinating leukodystrophy type 7. Next, we screened a cohort of hereditary spastic paraplegia and cerebellar ataxia cases (n = 618) for mutations in POLR3A and identified compound heterozygous POLR3A mutations in ∼3.1% of index cases. Interestingly, >80% of POLR3A mutation carriers presented the same deep-intronic mutation (c.1909+22G>A), which activates a cryptic splice site in a tissue and stage of development-specific manner and leads to a novel distinct and uniform phenotype. The phenotype is characterized by adolescent-onset progressive spastic ataxia with frequent occurrence of tremor, involvement of the central sensory tracts and dental problems (hypodontia, early onset of severe and aggressive periodontal disease). Instead of the typical hypomyelination magnetic resonance imaging pattern associated with classical POLR3A mutations, cases carrying c.1909+22G>A demonstrated hyperintensities along the superior cerebellar peduncles. These hyperintensities may represent the structural correlate to the cerebellar symptoms observed in these patients. The associated c.1909+22G>A variant was significantly enriched in 1139 cases with spastic ataxia-related phenotypes as compared to unrelated neurological and non-neurological phenotypes and healthy controls (P = 1.3 × 10-4). In this study we demonstrate that (i) autosomal-recessive mutations in POLR3A are a frequent cause of hereditary spastic ataxias, accounting for about 3% of hitherto genetically unclassified autosomal recessive and sporadic cases; and (ii) hypomyelination is frequently absent in POLR3A-related syndromes, especially when intronic mutations are present, and thus can no longer be considered as the unifying feature of POLR3A disease. Furthermore, our results demonstrate that substantial progress in revealing the causes of Mendelian diseases can be made by exploring the non-coding sequences of the human genome.


Subject(s)
Intellectual Disability/genetics , Muscle Spasticity/genetics , Optic Atrophy/genetics , RNA Polymerase III/genetics , Spastic Paraplegia, Hereditary/genetics , Spinocerebellar Ataxias/genetics , Aged , Cell Culture Techniques , Exons/genetics , Female , Genetic Association Studies , Humans , Induced Pluripotent Stem Cells , Intellectual Disability/diagnostic imaging , Intellectual Disability/physiopathology , Introns/genetics , Male , Middle Aged , Muscle Spasticity/diagnostic imaging , Muscle Spasticity/physiopathology , Mutation , Optic Atrophy/diagnostic imaging , Optic Atrophy/physiopathology , Pedigree , Phenotype , Spastic Paraplegia, Hereditary/diagnostic imaging , Spastic Paraplegia, Hereditary/physiopathology , Spinocerebellar Ataxias/diagnostic imaging , Spinocerebellar Ataxias/physiopathology
15.
Neuroimage ; 163: 81-92, 2017 12.
Article in English | MEDLINE | ID: mdl-28923276

ABSTRACT

State-of-the-art simultaneous-multi-slice (SMS-)EPI and 3D-EPI share several properties that benefit functional MRI acquisition. Both sequences employ equivalent parallel imaging undersampling with controlled aliasing to achieve high temporal sampling rates. As a volumetric imaging sequence, 3D-EPI offers additional means of acceleration complementary to 2D-CAIPIRINHA sampling, such as fast water excitation and elliptical sampling. We performed an application-oriented comparison between a tailored, six-fold CAIPIRINHA-accelerated 3D-EPI protocol at 530 ms temporal and 2.4 mm isotropic spatial resolution and an SMS-EPI protocol with identical spatial and temporal resolution for whole-brain resting-state fMRI at 3 T. The latter required eight-fold slice acceleration to compensate for the lack of elliptical sampling and fast water excitation. Both sequences used vendor-supplied on-line image reconstruction. We acquired test/retest resting-state fMRI scans in ten volunteers, with simultaneous acquisition of cardiac and respiration data, subsequently used for optional physiological noise removal (nuisance regression). We found that the 3D-EPI protocol has significantly increased temporal signal-to-noise ratio throughout the brain as compared to the SMS-EPI protocol, especially when employing motion and nuisance regression. Both sequence types reliably identified known functional networks with stronger functional connectivity values for the 3D-EPI protocol. We conclude that the more time-efficient 3D-EPI primarily benefits from reduced parallel imaging noise due to a higher, actual k-space sampling density compared to SMS-EPI. The resultant BOLD sensitivity increase makes 3D-EPI a valuable alternative to SMS-EPI for whole-brain fMRI at 3 T, with voxel sizes well below 3 mm isotropic and sampling rates high enough to separate dominant cardiac signals from BOLD signals in the frequency domain.


Subject(s)
Brain Mapping/methods , Brain/diagnostic imaging , Echo-Planar Imaging/methods , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Female , Humans , Male , Rest , Young Adult
16.
Neuroimage ; 147: 111-120, 2017 02 15.
Article in English | MEDLINE | ID: mdl-27919751

ABSTRACT

Head motion reduces data quality of neuroimaging data. In three functional magnetic resonance imaging (MRI) experiments we demonstrate that people make less head movements under task than resting-state conditions. In Experiment 1, we observed less head motion during a memory encoding task than during the resting-state condition. In Experiment 2, using publicly shared data from the UCLA Consortium for Neuropsychiatric Phenomics LA5c Study, we again found less head motion during several active task conditions than during a resting-state condition, although some task conditions also showed comparable motion. In the healthy controls, we found more head motion in men than in women and more motion with increasing age. When comparing clinical groups, we found that patients with a clinical diagnosis of bipolar disorder, or schizophrenia, move more compared to healthy controls or patients with ADHD. Both these experiments had a fixed acquisition order across participants, and we could not rule out that a first or last scan during a session might be particularly prone to more head motion. Therefore, we conducted Experiment 3, in which we collected several task and resting-state fMRI runs with an acquisition order counter-balanced. The results of Experiment 3 show again less head motion during several task conditions than during rest. Together these experiments demonstrate that small head motions occur during MRI even with careful instruction to remain still and fixation with foam pillows, but that head motion is lower when participants are engaged in a cognitive task. These finding may inform the choice of functional runs when studying difficult-to-scan populations, such as children or certain patient populations. Our findings also indicate that differences in head motion complicate direct comparisons of measures of functional neuronal networks between task and resting-state fMRI because of potential differences in data quality. In practice, a task to reduce head motion might be especially useful when acquiring structural MRI data such as T1/T2-weighted and diffusion MRI in research and clinical settings.


Subject(s)
Artifacts , Head Movements , Magnetic Resonance Imaging/methods , Adult , Aged , Aging , Attention Deficit Disorder with Hyperactivity/psychology , Bipolar Disorder/psychology , Cognition/physiology , Cohort Studies , Female , Humans , Image Processing, Computer-Assisted , Male , Memory/physiology , Middle Aged , Prospective Studies , Rest , Schizophrenic Psychology , Sex Characteristics , Young Adult
17.
Magn Reson Med ; 76(5): 1517-1523, 2016 11.
Article in English | MEDLINE | ID: mdl-26612608

ABSTRACT

PURPOSE: To investigate a method for rapid water excitation with minimal radiofrequency power deposition for efficient functional MRI at ultrahigh fields. THEORY AND METHODS: The suitability of the spectral response of a single rectangular radiofrequency pulse (rect) as a replacement of conventional fat saturation in segmented three-dimensional (3D) echo planar imaging (EPI) is explored. A pulse duration formula for lipid signal nulling independent of the small-tip-angle approximation is derived and tested by means of simulations and experiments at 3 and 7 Tesla (T). RESULTS: Compared with conventional binomial-11 water excitation, the single rect method is more selective and less sensitive to shim imperfections. In functional MRI, a significant measurement speedup (25%) and specific absorption rate reduction (from 44% to 1% at 7T) compared with conventional fat saturation are achieved. Furthermore, magnetization transfer effects are reduced resulting in up to 25% higher brain tissue signal-to-noise ratio. CONCLUSION: The proposed method is well suited for whole-brain functional MRI, not only at ultra-high fields, as it maximizes the sensitivity per unit time and at the same time minimizes radiofrequency power deposition. It requires little implementation effort and may thus be used in other spatially nonselective imaging methods that require fat suppression at minimal specific absorption rate and time requirements. Magn Reson Med 76:1517-1523, 2016. © 2015 International Society for Magnetic Resonance in Medicine.


Subject(s)
Adipose Tissue/diagnostic imaging , Brain/physiology , Echo-Planar Imaging/methods , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging/methods , Subtraction Technique , Absorption, Radiation , Algorithms , Body Water/diagnostic imaging , Brain/diagnostic imaging , Humans , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Sensitivity and Specificity , Signal Processing, Computer-Assisted
18.
MAGMA ; 27(5): 455-62, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24510154

ABSTRACT

OBJECT: Implementation of an accelerated Magnetization Prepared RApid Gradient Echo (MP-RAGE) sequence for T1 weighted neuroimaging; exploiting modern MRI technologies to minimize scan time while preserving the image quality. MATERIALS AND METHODS: A custom MP-RAGE sequence was implemented on a state-of-the-art 3T MR scanner equipped with a 32-channel receiver array head coil. The sequence utilized a shifted CAIPIRINHA k y -k z under-sampling pattern combined with elliptical scanning and a two-dimensional view ordering scheme to achieve high parallel imaging acceleration factors at maintained image contrast. RESULTS: It could be shown that MP-RAGE accelerated in two k-space directions outperforms single direction acceleration, which is the common practice with standard view ordering. Applying the CAIPIRINHA technique in conjunction with elliptical scanning further increased this benefit. CONCLUSION: By combining MP-RAGE with CAIPIRINHA sampling and elliptical scanning, the scan time can be reduced from 4-5 min to 2-3 min with insignificant reduction in image quality.


Subject(s)
Image Enhancement/methods , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Neuroimaging/methods , Artifacts , Humans , Magnetic Resonance Imaging/instrumentation , Signal-To-Noise Ratio , Time Factors
19.
Commun Biol ; 7(1): 271, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38443439

ABSTRACT

Physical exercise studies are generally underrepresented in young adulthood. Seventeen subjects were randomized into an intervention group (24.2 ± 3.9 years; 3 trainings/week) and 10 subjects into a passive control group (23.7 ± 4.2 years), over a duration of 6 months. Every two months, performance diagnostics, computerized spatial memory tests, and 3 Tesla magnetic resonance imaging were conducted. Here we find that the intervention group, compared to controls, showed increased cardiorespiratory fitness, spatial memory performance and subregional hippocampal volumes over time. Time-by-condition interactions occurred in right cornu ammonis 4 body and (trend only) dentate gyrus, left hippocampal tail and left subiculum. Increases in spatial memory performance correlated with hippocampal body volume changes and, subregionally, with left subicular volume changes. In conclusion, findings support earlier reports of exercise-induced subregional hippocampal volume changes. Such exercise-related plasticity may not only be of interest for young adults with clinical disorders of hippocampal function, but also for sedentary normal cohorts.


Subject(s)
Body Composition , Spatial Memory , Young Adult , Humans , Adult , Cognition , Exercise , Hippocampus/diagnostic imaging
20.
Healthcare (Basel) ; 11(5)2023 Feb 26.
Article in English | MEDLINE | ID: mdl-36900693

ABSTRACT

Physical activity (PA) plays an important role in affect processing. Studies describe the orbitofrontal cortex (OFC) as a major hub for emotion processing and the pathophysiology of affective disorders. Subregions of the OFC show diverse functional connectivity (FC) topographies, but the effect of chronic PA on subregional OFC FC still lacks scientific understanding. Therefore, we aimed at investigating the effects of regular PA on the FC topographies of OFC subregions in healthy individuals within a longitudinal randomized controlled exercise study. Participants (age: 18-35 years) were randomly assigned to either an intervention group (IG; N = 18) or a control group (CG; N = 10). Fitness assessments, mood questionnaires, and resting state functional magnetic resonance imaging (rsfMRI) were performed four times over the duration of 6 months. Using a detailed parcellation of the OFC, we created subregional FC topography maps at each time point and applied a linear mixed model to assess the effects of regular PA. The posterior-lateral right OFC showed a group and time interaction, revealing decreased FC with the left dorsolateral prefrontal cortex in the IG, while FC in the CG increased. Group and time interaction in the anterior-lateral right OFC with the right middle frontal gyrus was driven by increased FC in the IG. The posterior-lateral left OFC showed a group and time interaction based on differential change in FC to the left postcentral gyrus and the right occipital gyrus. This study emphasized regionally distinctive FC changes induced by PA within the lateral OFC territory, while providing aspects for further research.

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