Publications by authors named "Lars G Hanson"

31 Publications

On the reconstruction of magnetic resonance current density images of the human brain: Pitfalls and perspectives.

Neuroimage 2021 Sep 1;243:118517. Epub 2021 Sep 1.

Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Copenhagen, Denmark; Section for Magnetic Resonance, DTU Health Tech, Technical University of Denmark, Kgs Lyngby, Denmark. Electronic address:

Magnetic resonance current density imaging (MRCDI) of the human brain aims to reconstruct the current density distribution caused by transcranial electric stimulation from MR-based measurements of the current-induced magnetic fields. So far, the MRCDI data acquisition achieves only a low signal-to-noise ratio, does not provide a full volume coverage and lacks data from the scalp and skull regions. In addition, it is only sensitive to the component of the current-induced magnetic field parallel to the scanner field. The reconstruction problem thus involves coping with noisy and incomplete data, which makes it mathematically challenging. Most existing reconstruction methods have been validated using simulation studies and measurements in phantoms with simplified geometries. Only one reconstruction method, the projected current density algorithm, has been applied to human in-vivo data so far, however resulting in blurred current density estimates even when applied to noise-free simulated data. We analyze the underlying causes for the limited performance of the projected current density algorithm when applied to human brain data. In addition, we compare it with an approach that relies on the optimization of the conductivities of a small number of tissue compartments of anatomically detailed head models reconstructed from structural MR data. Both for simulated ground truth data and human in-vivo MRCDI data, our results indicate that the estimation of current densities benefits more from using a personalized volume conductor model than from applying the projected current density algorithm. In particular, we introduce a hierarchical statistical testing approach as a principled way to test and compare the quality of reconstructed current density images that accounts for the limited signal-to-noise ratio of the human in-vivo MRCDI data and the fact that the ground truth of the current density is unknown for measured data. Our results indicate that the statistical testing approach constitutes a valuable framework for the further development of accurate volume conductor models of the head. Our findings also highlight the importance of tailoring the reconstruction approaches to the quality and specific properties of the available data.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118517DOI Listing
September 2021

Sensitivity and resolution improvement for in vivo magnetic resonance current-density imaging of the human brain.

Magn Reson Med 2021 Aug 1. Epub 2021 Aug 1.

Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital-Amager and Hvidovre, Copenhagen, Denmark.

Purpose: Magnetic resonance current-density imaging (MRCDI) combines MRI with low-intensity transcranial electrical stimulation (TES; 1-2 mA) to map current flow in the brain. However, usage of MRCDI is still hampered by low measurement sensitivity and image quality.

Methods: Recently, a multigradient-echo-based MRCDI approach has been introduced that presently has the best-documented efficiency. This MRCDI approach has now been advanced in three directions and has been validated by phantom and in vivo experiments. First, the importance of optimum spoiling for brain imaging was verified. Second, the sensitivity and spatial resolution were improved by using acquisition weighting. Third, navigators were added as a quality control measure for tracking physiological noise. Combining these advancements, the optimized MRCDI method was tested by using 1 mA TES for two different injection profiles.

Results: For a session duration of 4:20 min, the new MRCDI method was able to detect TES-induced magnetic fields at a sensitivity level of 84 picotesla, representing a twofold efficiency increase against our original method. A comparison between measurements and simulations based on personalized head models showed a consistent increase in the coefficient of determination of ΔR = 0.12 for the current-induced magnetic fields and ΔR = 0.22 for the current flow reconstructions. Interestingly, some of the simulations still clearly deviated from the measurements despite the strongly improved measurement quality. This highlights the utility of MRCDI to improve head models for TES simulations.

Conclusion: The achieved sensitivity improvement is an important step from proof-of-concept studies toward a broader application of MRCDI in clinical and basic neuroscience research.
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http://dx.doi.org/10.1002/mrm.28944DOI Listing
August 2021

Elevated body weight modulates subcortical volume change and associated clinical response following electroconvulsive therapy.

J Psychiatry Neurosci 2021 07 5;46(4):E418-E426. Epub 2021 Jul 5.

From the Institute for Translational Psychiatry, University of Münster, Münster, Germany (Opel, Repple, Dannlowski, Redlich); Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany (Kavakbasi, Baune); the Departments of Neurology, Psychiatry, and Biobehavioral Sciences, University of California, Los Angeles, CA (Narr); the Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, NM (Abbott); the Institute of Behavioral Science, Feintein Institutes for Medical Research, Manhasset, NY (Argyelan); the Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, NY (Argyelan); the Department of Psychiatry, University of California, Los Angeles (Espinoza); the Department of Geriatric Psychiatry, University Psychiatric Center KU Leuven, KU Leuven, Leuven, Belgium (Emsell, Vandenbulcke); the KU Leuven, Leuven Brain Institute, Department of Neurosciences, Neuropsychiatry & Geriatric Psychiatry, University Psychiatric Center KU Leuven, Belgium (Bouckaert); the Academic Center for ECT and Neurostimulation (AcCENT), University Psychiatric Center (UPC)-KU Leuven, Kortenberg, Belgium (Sienaert); the Center for Social and Affective Neuroscience, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden (Nordanskog); the Psychiatric Center Copenhagen (Rigshospitalet), Mental Health Services of the Capital Region of Denmark, Copenhagen, Denmark (Jorgensen); the Neurobiology Research Unit, Rigshospitalet and University of Copenhagen, Denmark (Paulson); the Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Denmark (Hanson); the Center for Magnetic Resonance, Department of Health Technology, Technical University of Denmark, Kgs, Lyngby, Denmark (Hanson); the GGZ in Geest Specialized Mental Health Care, Amsterdam, the Netherlands (Dols, Van Exel, Oudega); the Amsterdam UMC, Vrije Universiteit Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, the Netherlands (Dols, van Exel, Oudega); the Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan (Takamiya, Kishimoto); the Department of Radiology, Haukeland University Hospital, Bergen, Norway (Ousdal); the Department of Biomedicine, University of Bergen, Bergen, Norway (Haavik); the Division of Psychiatry, Haukeland University Hospital, Bergen, Norway (Haavik, Hammar); the Department of Biological and Medical Psychology, University of Bergen, Norway (Hammar); the NORMENT, Department of Psychiatry, Haukeland University Hospital, Bergen, Norway (Oedegaard, Kessler); the Department of Clinical Medicine, University of Bergen, Bergen, Norway (Oedegaard, Kessler, Oltedal); the Department of Radiology, University of California, San Diego, La Jolla, California (Bartsch); the Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway (Bartsch, Oltedal); the Departments of Radiology, Neurosciences, and Psychiatry, University of California, San Diego (Dale); the Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, California (Dale); the Department of Psychiatry, University of Melbourne, Melbourne, Australia (Baune); the The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia (Baune); and the Department of Psychology, University of Halle, Halle, Germany (Redlich).

Background: Obesity is a frequent somatic comorbidity of major depression, and it has been associated with worse clinical outcomes and brain structural abnormalities. Converging evidence suggests that electroconvulsive therapy (ECT) induces both clinical improvements and increased subcortical grey matter volume in patients with depression. However, it remains unknown whether increased body weight modulates the clinical response and structural neuroplasticity that occur with ECT.

Methods: To address this question, we conducted a longitudinal investigation of structural MRI data from the Global ECT-MRI Research Collaboration (GEMRIC) in 223 patients who were experiencing a major depressive episode (10 scanning sites). Structural MRI data were acquired before and after ECT, and we assessed change in subcortical grey matter volume using FreeSurfer and Quarc.

Results: Higher body mass index (BMI) was associated with a significantly lower increase in subcortical grey matter volume following ECT. We observed significant negative associations between BMI and change in subcortical grey matter volume, with pronounced effects in the thalamus and putamen, where obese participants showed increases in grey matter volume that were 43.3% and 49.6%, respectively, of the increases found in participants with normal weight. As well, BMI significantly moderated the association between subcortical grey matter volume change and clinical response to ECT. We observed no significant association between BMI and clinical response to ECT.

Limitations: Because only baseline BMI values were available, we were unable to study BMI changes during ECT and their potential association with clinical and grey matter volume change.

Conclusion: Future studies should take into account the relevance of body weight as a modulator of structural neuroplasticity during ECT treatment and aim to further explore the functional relevance of this novel finding.
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http://dx.doi.org/10.1503/jpn.200176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410473PMC
July 2021

Safety evaluation of a new setup for transcranial electric stimulation during magnetic resonance imaging.

Brain Stimul 2021 May-Jun;14(3):488-497. Epub 2021 Mar 9.

Section for Magnetic Resonance, DTU Health Tech, Technical University of Denmark, Kgs Lyngby, Denmark; Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark. Electronic address:

Background: Transcranial electric stimulation during MR imaging can introduce safety issues due to coupling of the RF field with the stimulation electrodes and leads.

Objective: To optimize the stimulation setup for MR current density imaging (MRCDI) and increase maximum stimulation current, a new low-conductivity (σ = 29.4 S/m) lead wire is designed and tested.

Method: The antenna effect was simulated to investigate the effect of lead conductivity. Subsequently, specific absorption rate (SAR) simulations for realistic lead configurations with low-conductivity leads and two electrode types were performed at 128 MHz and 298 MHz being the Larmor frequencies of protons at 3T and 7T. Temperature measurements were performed during MRI using high power deposition sequences to ensure that the electrodes comply with MRI temperature regulations.

Results: The antenna effect was found for copper leads at ¼ RF wavelength and could be reliably eliminated using low-conductivity leads. Realistic lead configurations increased the head SAR and the local head SAR at the electrodes only minimally. The highest temperatures were measured on the rings of center-surround electrodes, while circular electrodes showed little heating. No temperature increase above the safety limit of 39 °C was observed.

Conclusion: Coupling to the RF field can be reliably prevented by low-conductivity leads, enabling cable paths optimal for MRCDI. Compared to commercial copper leads with safety resistors, the low-conductivity leads had lower total impedance, enabling the application of higher currents without changing stimulator design. Attention must be paid to electrode pads.
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http://dx.doi.org/10.1016/j.brs.2021.02.019DOI Listing
March 2021

Multi-site benchmarking of clinical C RF coils at 3T.

J Magn Reson 2020 09 27;318:106798. Epub 2020 Jul 27.

Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark; GE Healthcare, Brøndby, Denmark. Electronic address:

A quality assurance protocol for RF coils is proposed, which can be used for volume (Tx/Rx) and surface (Rx) coils. Following this protocol, a benchmarking of seven coils (from three different MR sites) dedicated to C MRI at 3T is reported. Coil performance is particularly important for 3T MRI at the C frequency, since the coil-to-sample noise ratio is typically high. The coils are evaluated experimentally using the proposed protocol based on MR spectroscopic imaging performed with two different phantoms: one head-shaped, and one with cylindrical shape and nearly twice the volume of the first one. To achieve an unbiased SNR comparison of volume and array coils, coil combination was done using sensitivity profiles extracted from the data. SNR, noise correlation matrices and example g-factor maps are reported. For globally calibrated, equal excitation angles, the measured SNR shows large differences for the volume coils of up to 115% at the phantom center for a head phantom. The arrays show lower differences in superficial SNR. The sample surface depth at which the volume coils outperform the arrays is estimated to 7 cm, and SNR furthest away from the coil surface is 28% lower for the best array compared to the best volume coil. A broad set of coils for C at 3T have been benchmarked. The results reported, and the method used to benchmark them, should guide the C community to choose the most suitable coil for a given experiment.
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http://dx.doi.org/10.1016/j.jmr.2020.106798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501735PMC
September 2020

Transducer modeling for accurate acoustic simulations of transcranial focused ultrasound stimulation.

J Neural Eng 2020 07 13;17(4):046010. Epub 2020 Jul 13.

Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. Center for Magnetic Resonance, Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark. These authors contributed equally to the work.

Objective: Low-intensity transcranial ultrasound stimulation (TUS) is emerging as a non-invasive brain stimulation technique with superior spatial resolution and the ability to reach deep brain areas. Medical image-based computational modeling could be an important tool for individualized TUS dose control and targeting optimization, but requires further validation. This study aims to assess the impact of the transducer model on the accuracy of the simulations.

Approach: Using hydrophone measurements, the acoustic beam of a single-element focused transducer (SEFT) with a flat piezoelectric disc and an acoustic lens was characterized. The acoustic beam was assessed in a homogeneous water bath and after transmission through obstacles (3D-printed shapes and skull samples). The acoustic simulations employed the finite-difference time-domain method and were informed by computed tomography (CT) images of the obstacles. Transducer models of varying complexity were tested representing the SEFT either as a surface boundary condition with variable curvature or also accounting for its internal geometry. In addition, a back-propagated pressure distribution from the first measurement plane was used as source model. The simulations and measurements were quantitatively compared using key metrics for peak location, focus size, intensity and spatial distribution.

Main Results: While a surface boundary with an adapted, 'effective' curvature radius based on the specifications given by the manufacturer could reproduce the measured focus location and size in a homogeneous water bath, it regularly failed to accurately predict the beam after obstacle transmission. In contrast, models that were based on a one-time calibration to the homogeneous water bath measurements performed substantially better in all cases with obstacles. For one of the 3D-printed obstacles, the simulated intensities deviated substantially from the measured ones, irrespective of the transducer model. We attribute this finding to a standing wave effect, and further studies should clarify its relevance for accurate simulations of skull transmission.

Significance: Validated transducer models are important to ensure accurate simulations of the acoustic beam of SEFTs, in particular in the presence of obstacles such as the skull.
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http://dx.doi.org/10.1088/1741-2552/ab98dcDOI Listing
July 2020

Three-dimensional accelerated acquisition for hyperpolarized C MR  with blipped stack-of-spirals and conjugate-gradient  SENSE.

Magn Reson Med 2020 08 20;84(2):519-534. Epub 2020 Jan 20.

Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.

Purpose: To test a new parallel imaging strategy for acceleration of hyperpolarized C MR acquisitions based on a 3D blipped stack-of-spirals trajectory and conjugate-gradient SENSE reconstruction with precalibrated sensitivities.

Methods: The blipped stack-of-spirals trajectory was developed for an acceleration factor of 4, based on an undersampled stack-of-spirals with gradient blips during spiral readout. The trajectory was developed with volumetric coverage of a large FOV and with high spatial resolution. High temporal resolution was attained through spectral-spatial excitation and 4 excitations per volume. The blipped stack-of-spirals was evaluated in simulations and phantom experiments. Next, the method was evaluated for kidney and cardiac imaging in 2 separate healthy pigs.

Results: Simulation and phantom results showed successful acquisition and reconstruction, but also revealed reconstruction challenges for certain locations and for wide signal sources. For the kidney experiment, the accelerated acquisition showed high similarity to 2 separately acquired fully sampled data sets with matched spatial and temporal resolution, respectively. For the cardiac experiment, the accelerated acquisition proved able to map each metabolite in 3 dimensions within a single cardiac cycle.

Conclusion: The proposed method demonstrated effective mapping of metabolism in both kidneys and the heart of healthy pigs. Limitations seen in phantom experiments, may be irrelevant for most clinical applications, but should be kept in mind as well as reconstruction challenges related to residual aliasing. All in all, we show that the blipped stack-of-spirals is a relevant parallel imaging method for hyperpolarized human imaging, facilitating better insights into metabolism compared with nonaccelerated acquisition.
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http://dx.doi.org/10.1002/mrm.28171DOI Listing
August 2020

Brain Changes Induced by Electroconvulsive Therapy Are Broadly Distributed.

Biol Psychiatry 2020 03 25;87(5):451-461. Epub 2019 Jul 25.

Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, California; Department of Radiology, University of California, San Diego, La Jolla, California.

Background: Electroconvulsive therapy (ECT) is associated with volumetric enlargements of corticolimbic brain regions. However, the pattern of whole-brain structural alterations following ECT remains unresolved. Here, we examined the longitudinal effects of ECT on global and local variations in gray matter, white matter, and ventricle volumes in patients with major depressive disorder as well as predictors of ECT-related clinical response.

Methods: Longitudinal magnetic resonance imaging and clinical data from the Global ECT-MRI Research Collaboration (GEMRIC) were used to investigate changes in white matter, gray matter, and ventricle volumes before and after ECT in 328 patients experiencing a major depressive episode. In addition, 95 nondepressed control subjects were scanned twice. We performed a mega-analysis of single subject data from 14 independent GEMRIC sites.

Results: Volumetric increases occurred in 79 of 84 gray matter regions of interest. In total, the cortical volume increased by mean ± SD of 1.04 ± 1.03% (Cohen's d = 1.01, p < .001) and the subcortical gray matter volume increased by 1.47 ± 1.05% (d = 1.40, p < .001) in patients. The subcortical gray matter increase was negatively associated with total ventricle volume (Spearman's rank correlation ρ = -.44, p < .001), while total white matter volume remained unchanged (d = -0.05, p = .41). The changes were modulated by number of ECTs and mode of electrode placements. However, the gray matter volumetric enlargements were not associated with clinical outcome.

Conclusions: The findings suggest that ECT induces gray matter volumetric increases that are broadly distributed. However, gross volumetric increases of specific anatomically defined regions may not serve as feasible biomarkers of clinical response.
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http://dx.doi.org/10.1016/j.biopsych.2019.07.010DOI Listing
March 2020

Safety of transcranial focused ultrasound stimulation: A systematic review of the state of knowledge from both human and animal studies.

Brain Stimul 2019 Nov - Dec;12(6):1367-1380. Epub 2019 Jul 31.

Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Denmark; Center for Magnetic Resonance, Department of Health Technology, Technical University of Denmark, Kgs, Lyngby, Denmark. Electronic address:

Background: Low-intensity transcranial focused ultrasound stimulation (TFUS) holds great promise as a highly focal technique for transcranial stimulation even for deep brain areas. Yet, knowledge about the safety of this novel technique is still limited.

Objective: To systematically review safety related aspects of TFUS. The review covers the mechanisms-of-action by which TFUS may cause adverse effects and the available data on the possible occurrence of such effects in animal and human studies.

Methods: Initial screening used key term searches in PubMed and bioRxiv, and a review of the literature lists of relevant papers. We included only studies where safety assessment was performed, and this results in 33 studies, both in humans and animals.

Results: Adverse effects of TFUS were very rare. At high stimulation intensity and/or rate, TFUS may cause haemorrhage, cell death or damage, and unintentional blood-brain barrier (BBB) opening. TFUS may also unintentionally affect long-term neural activity and behaviour. A variety of methods was used mainly in rodents to evaluate these adverse effects, including tissue staining, magnetic resonance imaging, temperature measurements and monitoring of neural activity and behaviour. In 30 studies, adverse effects were absent, even though at least one Food and Drug Administration (FDA) safety index was frequently exceeded. Two studies reported microhaemorrhages after long or relatively intense stimulation above safety limits. Another study reported BBB opening and neuronal damage in a control condition, which intentionally and substantially exceeded the safety limits.

Conclusion: Most studies point towards a favourable safety profile of TFUS. Further investigations are warranted to establish a solid safety framework for the therapeutic window of TFUS to reliably avoid adverse effects while ensuring neural effectiveness. The comparability across studies should be improved by a more standardized reporting of TFUS parameters.
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http://dx.doi.org/10.1016/j.brs.2019.07.024DOI Listing
February 2020

Inductive measurement and encoding of k-space trajectories in MR raw data.

MAGMA 2019 Dec 30;32(6):655-667. Epub 2019 Jul 30.

Department of Health Technology, Center for Magnetic Resonance, Technical University of Denmark, Kongens Lyngby, Denmark.

Objectives:  The objective of this study was to concurrently acquire an inductive k-space trajectory measure and corresponding imaging data by an MR scanner.

Materials And Methods:  1D gradient measures were obtained by digital integration, regularized using measured gradient coil currents and recorded individually by the scanner concurrently with raw MR data. Gradient measures were frequency modulated into an RF signal receivable by the scanner, yielding a k-space trajectory measure from the cumulative phase of the acquired data. Generation of the gradient measure and frequency modulation was performed by previously developed custom, versatile circuitry.

Results:  For a normal echo planar imaging (EPI) sequence, the acquired k-space trajectory measure yielded slightly improved image quality compared to that obtained from using the scanner's estimated eddy current-compensated k-space trajectory. For a spiral trajectory, the regularized inductive k-space trajectory measure lead to a 76% decrease in the root-mean-square error of the reconstructed image.

Discussion:  While the proof-of-concept experiments show potential for further improvement, the feasibility of inductively measuring k-space trajectories and increasing the precision through regularization was demonstrated. The approach may offer an inexpensive method to acquire k-space trajectories concurrently with scanning.
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http://dx.doi.org/10.1007/s10334-019-00770-2DOI Listing
December 2019

Coil profile estimation strategies for parallel imaging with hyperpolarized C MRI.

Magn Reson Med 2019 12 11;82(6):2104-2117. Epub 2019 Jul 11.

Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.

Purpose: To investigate auto- and pre-calibration coil profile estimation for parallel imaging reconstruction of hyperpolarized C MRI volumetric data.

Methods: Parallel imaging reconstruction was studied with 3 different approaches for coil profile estimation: auto-calibration, phantom calibration, and theoretic calibration. Acquisition was performed with a 3D stack-of-spirals sequence with spectral-spatial excitation and Cartesian undersampling. Parallel imaging reconstructions were done with conjugate gradient SENSE and 3D gridding with inhomogeneity correction. The approaches were compared in simulations with different SNR, through phantom experiments, and in an in vivo pig study focused on the kidneys. All imaging was done with a rigid home-built 12-channel C receive coil at 3T.

Results: The phantom calibrated and theoretic approaches resulted in the best structural similarities in simulations and demonstrated higher image quality in the phantom experiments compared to the auto-calibrated approach. In vivo mapping of pyruvate uptake and lactate conversion improved for accelerated acquisitions because of a better temporal resolution. From a practical and image quality point of view, use of theoretic coil profiles led to improved results compared to the other approaches.

Conclusion: The success of the theoretic coil profile estimation demonstrates a negligible effect of load on sensitivity profiles at the carbon frequency at 3T. Through theoretic or phantom calibrated parallel imaging, accelerated 3D volumes could be reconstructed with sufficient sensitivity, temporal, and spatial resolution to map the metabolism of kidneys exemplifying abdominal organs. This approach overcomes a critical step in the clinical translation of parallel imaging in hyperpolarized C MR.
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http://dx.doi.org/10.1002/mrm.27892DOI Listing
December 2019

The stray magnetic fields in Magnetic Resonance Current Density Imaging (MRCDI).

Phys Med 2019 Mar 8;59:142-150. Epub 2019 Mar 8.

Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Denmark; Center for Magnetic Resonance, DTU Health Tech, Technical University of Denmark, Kgs Lyngby, Denmark. Electronic address:

Purpose: MR Current Density Imaging (MRCDI) involves weak current-injection into the head. The resulting magnetic field changes are measured by MRI. Stray fields pose major challenges since these can dominate the fields caused by tissue currents. We analyze the sources and influences of stray fields.

Methods: First, we supply validation data for a recently introduced MRCDI method with an unprecedented noise floor of ∼0.1 nT in vivo. Second, we assess the accuracy limit of the method and our corresponding cable current correction in phantoms ensuring high signal-to-noise ratio (SNR). Third, we simulate the influence of stray fields on current flow reconstructions for various realistic experimental set-ups. Fourth, we experimentally determine the physiological field variations. Finally, we explore the consequences of head positioning in an exemplary head coil, since off-center positioning provides space for limiting cable-induced fields.

Results: The cable correction method performs well except near the cables. Unless correcting for cable currents, the reconstructed current flow is easily misestimated by up to 45% for a realistic experimental set-up. Stray fields dominating the fields caused by tissue currents can occur, e.g. due to a wire segment 20 cm away from the imaged region, or due to a slight cable misalignment of 3°. The noise is increased by 40% due to physiological factors. Minor patient movements can cause field changes of ∼40 nT. Off-centered head positioning can locally reduce SNR by e.g. 30%.

Conclusions: Quantification of stray fields showed that MRCDI requires careful field correction. After cable correction, physiological noise is a limiting factor.
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http://dx.doi.org/10.1016/j.ejmp.2019.02.022DOI Listing
March 2019

[Magnetic resonance imaging for the diagnosis of non-alcoholic fatty liver disease].

Ugeskr Laeger 2019 Feb;181(9)

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease with an estimated overall prevalence of 25% in the global adult population. Liver biopsy is the gold standard for the diagnosis of NAFLD. However, the risk of complications and collection of only 1/50,000 of the total liver volume, limits this diagnostic method in an unselected population. Non-invasive diag-nostic methods are warranted, and magnetic resonance imaging of the liver for NAFLD has shown promising results.
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February 2019

Development of a Symmetric Echo-Planar Spectroscopy Imaging Framework for Hyperpolarized C Imaging in a Clinical PET/MR Scanner.

Tomography 2018 Sep;4(3):110-122

Department of Electrical Engineering, Center for Hyperpolarization in Magnetic Resonance, Technical University of Denmark, Denmark.

Here, we developed a symmetric echo-planar spectroscopic imaging (EPSI) sequence for hyperpolarized C imaging on a clinical hybrid positron emission tomography/magnetic resonance imaging system. The pulse sequence uses parallel reconstruction pipelines to separately reconstruct data from odd-and-even gradient echoes to reduce artifacts from gradient imbalances. The ramp-sampled data in the spatiotemporal frequency space are regridded to compensate for the chemical-shift displacements. Unaliasing of nonoverlapping peaks outside of the sampled spectral width was performed to double the effective spectral width. The sequence was compared with conventional phase-encoded chemical-shift imaging (CSI) in phantoms, and it was evaluated in a canine cancer patient with ameloblastoma after injection of hyperpolarized [1-C]pyruvate. The relative signal-to-noise ratio of EPSI with respect to CSI was 0.88, which is consistent with the decrease in sampling efficiency due to ramp sampling. Data regridding in the spatiotemporal frequency space significantly reduced spatial blurring compared with direct fast Fourier transform. EPSI captured the spatial distributions of both metabolites and their temporal dynamics in vivo with an in-plane spatial resolution of 5 × 9 mm and a temporal resolution of 3 seconds. Significantly higher spatial and temporal resolution for delineating anatomical structures in vivo was achieved for EPSI metabolic maps than for CSI maps, which suffered spatiotemporal blurring. The EPSI sequence showed promising results in terms of short acquisition time and sufficient spectral bandwidth of 500 Hz, allowing to adjust the trade-off between signal-to-noise ratio and encoding speed.
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http://dx.doi.org/10.18383/j.tom.2018.00006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173787PMC
September 2018

Gamma-aminobutyric acid edited echo-planar spectroscopic imaging (EPSI) with MEGA-sLASER at 7T.

Magn Reson Med 2019 02 29;81(2):773-780. Epub 2018 Aug 29.

Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.

Purpose: For rapid spatial mapping of gamma-aminobutyric acid (GABA) at the increased sensitivity and spectral separation for ultra-high magnetic field strength (7 tesla [T]), an accelerated edited magnetic resonance spectroscopic imaging technique was developed and optimized for the human brain at 7 T.

Methods: A MEGA-sLASER sequence was used for GABA editing and volume selection to maximize editing efficiency and minimize chemical shift displacement errors. To accommodate the high bandwidth requirements at 7 T, a single-shot echo planar readout was used for rapid simultaneous encoding of the temporal dimension and 1 spatial. B and B field aspects specific for 7 T were studied together with correction procedures, and feasibility of the EPSI MEGA-sLASER technique was tested in vivo in 5 healthy subjects.

Results: Localized edited spectra could be measured in all subjects giving spatial GABA signal distributions over a central brain region, having 45- to 50-Hz spatial intervoxel B field variations and up to 30% B field deviations. MEGA editing was found unaffected by the B inhomogeneities for the optimized sequence. The correction procedures reduced effects of intervoxel B inhomogeneities, corrected for spatial editing efficiency variations, and compensated for GABA resonance phase and frequency shifts from subtle motion and acquisition instabilities. The optimized oscillating echo-planar gradient scheme permitted full spectral acquisition at 7 T and exhibited minimal spectral-spatial ghosting effects for the selected brain region.

Conclusion: The EPSI MEGA-sLASER technique was shown to provide time-efficient mapping of regional variations in cerebral GABA in a central volume of interest with spatial B and B field variations typical for 7 T.
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http://dx.doi.org/10.1002/mrm.27450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646902PMC
February 2019

Volume of the Human Hippocampus and Clinical Response Following Electroconvulsive Therapy.

Biol Psychiatry 2018 10 29;84(8):574-581. Epub 2018 May 29.

Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, California; Department of Radiology, University of California, San Diego, La Jolla, California; Department of Neurosciences, University of California, San Diego, La Jolla, California.

Background: Hippocampal enlargements are commonly reported after electroconvulsive therapy (ECT). To clarify mechanisms, we examined if ECT-induced hippocampal volume change relates to dose (number of ECT sessions and electrode placement) and acts as a biomarker of clinical outcome.

Methods: Longitudinal neuroimaging and clinical data from 10 independent sites participating in the Global ECT-Magnetic Resonance Imaging Research Collaboration (GEMRIC) were obtained for mega-analysis. Hippocampal volumes were extracted from structural magnetic resonance images, acquired before and after patients (n = 281) experiencing a major depressive episode completed an ECT treatment series using right unilateral and bilateral stimulation. Untreated nondepressed control subjects (n = 95) were scanned twice.

Results: The linear component of hippocampal volume change was 0.28% (SE 0.08) per ECT session (p < .001). Volume change varied by electrode placement in the left hippocampus (bilateral, 3.3 ± 2.2%, d = 1.5; right unilateral, 1.6 ± 2.1%, d = 0.8; p < .0001) but not the right hippocampus (bilateral, 3.0 ± 1.7%, d = 1.8; right unilateral, 2.7 ± 2.0%, d = 1.4; p = .36). Volume change for electrode placement per ECT session varied similarly by hemisphere. Individuals with greater treatment-related volume increases had poorer outcomes (Montgomery-Åsberg Depression Rating Scale change -1.0 [SE 0.35], per 1% volume increase, p = .005), although the effects were not significant after controlling for ECT number (slope -0.69 [SE 0.38], p = .069).

Conclusions: The number of ECT sessions and electrode placement impacts the extent and laterality of hippocampal enlargement, but volume change is not positively associated with clinical outcome. The results suggest that the high efficacy of ECT is not explained by hippocampal enlargement, which alone might not serve as a viable biomarker for treatment outcome.
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http://dx.doi.org/10.1016/j.biopsych.2018.05.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697556PMC
October 2018

Human in-vivo brain magnetic resonance current density imaging (MRCDI).

Neuroimage 2018 05 28;171:26-39. Epub 2017 Dec 28.

Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Denmark; Center for Magnetic Resonance, DTU Elektro, Technical University of Denmark, Kgs Lyngby, Denmark; High-Field Magnetic Resonance Center, Max-Planck-Institute for Biological Cybernetics, Tübingen, Germany. Electronic address:

Magnetic resonance current density imaging (MRCDI) and MR electrical impedance tomography (MREIT) are two emerging modalities, which combine weak time-varying currents injected via surface electrodes with magnetic resonance imaging (MRI) to acquire information about the current flow and ohmic conductivity distribution at high spatial resolution. The injected current flow creates a magnetic field in the head, and the component of the induced magnetic field ΔB parallel to the main scanner field causes small shifts in the precession frequency of the magnetization. The measured MRI signal is modulated by these shifts, allowing to determine ΔB for the reconstruction of the current flow and ohmic conductivity. Here, we demonstrate reliable ΔB measurements in-vivo in the human brain based on multi-echo spin echo (MESE) and steady-state free precession free induction decay (SSFP-FID) sequences. In a series of experiments, we optimize their robustness for in-vivo measurements while maintaining a good sensitivity to the current-induced fields. We validate both methods by assessing the linearity of the measured ΔB with respect to the current strength. For the more efficient SSFP-FID measurements, we demonstrate a strong influence of magnetic stray fields on the ΔB images, caused by non-ideal paths of the electrode cables, and validate a correction method. Finally, we perform measurements with two different current injection profiles in five subjects. We demonstrate reliable recordings of ΔB fields as weak as 1 nT, caused by currents of 1 mA strength. Comparison of the ΔB measurements with simulated ΔB images based on FEM calculations and individualized head models reveals significant linear correlations in all subjects, but only for the stray field-corrected data. As final step, we reconstruct current density distributions from the measured and simulated ΔB data. Reconstructions from non-corrected ΔB measurements systematically overestimate the current densities. Comparing the current densities reconstructed from corrected ΔB measurements and from simulated ΔB images reveals an average coefficient of determination R of 71%. In addition, it shows that the simulations underestimated the current strength on average by 24%. Our results open up the possibility of using MRI to systematically validate and optimize numerical field simulations that play an important role in several neuroscience applications, such as transcranial brain stimulation, and electro- and magnetoencephalography.
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http://dx.doi.org/10.1016/j.neuroimage.2017.12.075DOI Listing
May 2018

Sensitivity analysis of magnetic field measurements for magnetic resonance electrical impedance tomography (MREIT).

Magn Reson Med 2018 02 30;79(2):748-760. Epub 2017 May 30.

Danish Research Center for Magnetic Resonance, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.

Purpose: Clinical use of magnetic resonance electrical impedance tomography (MREIT) still requires significant sensitivity improvements. Here, the measurement of the current-induced magnetic field (ΔB ) is improved using systematic efficiency analyses and optimization of multi-echo spin echo (MESE) and steady-state free precession free induction decay (SSFP-FID) sequences.

Theory And Methods: Considering T , T , and T2* relaxation in the signal-to-noise ratios (SNRs) of the MR magnitude images, the efficiency of MESE and SSFP-FID MREIT experiments, and its dependence on the sequence parameters, are analytically analyzed and simulated. The theoretical results are experimentally validated in a saline-filled homogenous spherical phantom with relaxation parameters similar to brain tissue. Measurement of ΔB is also performed in a cylindrical phantom with saline and chicken meat.

Results: The efficiency simulations and experimental results are in good agreement. When using optimal parameters, ΔB can be reliably measured in the phantom even at injected current strengths of 1 mA or lower for both sequence types. The importance of using proper crusher gradient selection on the phase evolution in a MESE experiment is also demonstrated.

Conclusion: The efficiencies observed with the optimized sequence parameters will likely render in-vivo human brain MREIT feasible. Magn Reson Med 79:748-760, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
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http://dx.doi.org/10.1002/mrm.26727DOI Listing
February 2018

Measuring motion-induced B0 -fluctuations in the brain using field probes.

Magn Reson Med 2016 May 15;75(5):2020-30. Epub 2015 Jun 15.

C.J. Gorter Center, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.

Purpose: Fluctuations of the background magnetic field (B0 ) due to body and breathing motion can lead to significant artifacts in brain imaging at ultrahigh field. Corrections based on real-time sensing using external field probes show great potential. This study evaluates different aspects of field interpolation from these probes into the brain which is implicit in such methods. Measurements and simulations were performed to quantify how well B0 -fluctuations in the brain due to body and breathing motion are reflected in external field probe measurements.

Methods: Field probe measurements were compared with scanner acquired B0 -maps from experiments with breathing and shoulder movements. A realistic simulation of B0 -fluctuations caused by breathing was performed, and used for testing different sets of field probe positions.

Results: The B0 -fluctuations were well reflected in the field probe measurements in the shoulder experiments, while the breathing experiments showed only moderate correspondence. The simulations showed the importance of the probe positions, and that performing full 3(rd) order corrections based on 16 field probes is not recommended.

Conclusion: Methods for quantitative assessment of the field interpolation problem were developed and demonstrated. Field corrections based on external field measurements show great potential, although potential pitfalls were identified.
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http://dx.doi.org/10.1002/mrm.25802DOI Listing
May 2016

The effects of the CXCR2 antagonist, MK-7123, on bone marrow functions in healthy subjects.

Cytokine 2015 Apr 4;72(2):197-203. Epub 2015 Feb 4.

PhaseOneTrials A/S Copenhagen, Denmark.

The CXCR2 antagonist MK-7123 causes dose-dependent reductions in absolute neutrophil counts (ANC) and decreases neutrophil tissue responses, but its effects on bone marrow functions are not yet known. We conducted a double-blind, randomized study in 18 healthy subjects comparing the effects of either MK-7123 (30mg, po, daily for 28days) or placebo on peripheral blood counts and bone marrow myeloid cell populations. MK-7123 caused a reversible decrease (approximately 50%) in the ANC as demonstrated on days 1 and 28, the first and last days of the treatment period. Bone marrow aspirate smears and biopsy imprints did not differ in the proportion of mature neutrophils in pretreatment, day 28, day 56 or placebo samples. There were no treatment effects on biopsy or aspirate clot cellularity, myeloid to erythroid or myeloid post-mitotic to mitotic ratios; flow-cytometric analyses of aspirate cells; or bone marrow fat to cell balance as assessed by MRI. MK-7123 was generally well tolerated with neutropenia being the most common adverse event; however, there were no clinical symptoms associated with decreased ANCs. These findings indicate that the CXCR2 antagonist MK-7123 causes rapidly reversible decrease in the ANC without measurable myelosuppressive effects. The results support the development of CXCR2 antagonists as potentially useful anti-inflammatory agents, primarily interrupting neutrophil trafficking.
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http://dx.doi.org/10.1016/j.cyto.2015.01.002DOI Listing
April 2015

Blood-brain barrier permeability of normal appearing white matter in relapsing-remitting multiple sclerosis.

PLoS One 2013 18;8(2):e56375. Epub 2013 Feb 18.

Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.

Background: Multiple sclerosis (MS) affects the integrity of the blood-brain barrier (BBB). Contrast-enhanced T1 weighted magnetic resonance imaging (MRI) is widely used to characterize location and extent of BBB disruptions in focal MS lesions. We employed quantitative T1 measurements before and after the intravenous injection of a paramagnetic contrast agent to assess BBB permeability in the normal appearing white matter (NAWM) in patients with relapsing-remitting MS (RR-MS).

Methodology/principal Findings: Fifty-nine patients (38 females) with RR-MS undergoing immunomodulatory treatment and nine healthy controls (4 females) underwent quantitative T1 measurements at 3 tesla before and after injection of a paramagnetic contrast agent (0.2 mmol/kg Gd-DTPA). Mean T1 values were calculated for NAWM in patients and total cerebral white matter in healthy subjects for the T1 measurements before and after injection of Gd-DTPA. The pre-injection baseline T1 of NAWM (945±55 [SD] ms) was prolonged in RR-MS relative to healthy controls (903±23 ms, p = 0.028). Gd-DTPA injection shortened T1 to a similar extent in both groups. Mean T1 of NAWM was 866±47 ms in the NAWM of RR-MS patients and 824±13 ms in the white matter of healthy controls. The regional variability of T1 values expressed as the coefficient of variation (CV) was comparable between the two groups at baseline, but not after injection of the contrast agent. After intravenous Gd-DTPA injection, T1 values in NAWM were more variable in RR-MS patients (CV = 0.198±0.046) compared to cerebral white matter of healthy controls (CV = 0.166±0.018, p = 0.046).

Conclusions/significance: We found no evidence of a global BBB disruption within the NAWM of RR-MS patients undergoing immunomodulatory treatment. However, the increased variation of T1 values in NAWM after intravenous Gd-DTPA injection points to an increased regional inhomogeneity of BBB function in NAWM in relapsing-remitting MS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056375PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575471PMC
August 2013

Cerebral metabolism, magnetic resonance spectroscopy and cognitive dysfunction in early multiple sclerosis: an exploratory study.

Neurol Res 2012 Jan;34(1):52-8

Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark.

Objectives: Positron emission tomography (PET) studies have shown that cortical cerebral metabolic rate of glucose (CMRglc) is reduced in multiple sclerosis (MS). Quantitative magnetic resonance spectroscopy (MRS) measures of N-acetyl-aspartate (NAA) normalized to creatine (NAA/Cr) assess neuronal deterioration, and several studies have shown reductions in MS. Furthermore, both PET and MRS reductions correlate with cognitive dysfunction in MS. Our aim was to determine if changes in cortical CMRglc in early MS correlate with NAA/Cr measurements of neuronal deterioration, as well as cognitive dysfunction and neurological disability.

Methods: We studied 20 recently diagnosed, clinically definite, relapsing-remitting MS patients. Global and cortical CMRglc was estimated using PET with 18-F-deoxyglucose and NAA/Cr ratio was measured using multislice echo-planar spectroscopic imaging. All subjects were neuro-psychologically tested and a cognitive dysfunction factor (CDF) was calculated.

Results: Cortical CMRglc correlated with cortical NAA/Cr (r = 0.45; P < 0.05), but there were no correlation between CMRglc and other NAA/Cr measurements, conventional magnetic resonance imaging measurements, or CDF. Stepwise regression analysis showed association between cortical NAA/Cr and CMRglc of the left ventrolateral prefrontal cortex (P < 0.001), left putamen (P = 0.010), and left hippocampus (P = 0.011). Furthermore, CDF was related to CMRglc in the left cerebellum (P = 0.001) and the left caudate nucleus (P = 0.013). The results of the statistical analysis should be regarded as exploratory, since we did not correct for multiple comparisons.

Conclusion: Our findings suggest that reductions in cortical CMRglc are associated with reductions in cortical NAA/Cr in early MS. These changes affect cortical and subcortical neural circuits of importance to cognitive function.
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http://dx.doi.org/10.1179/1743132811Y.0000000059DOI Listing
January 2012

Motion correction of single-voxel spectroscopy by independent component analysis applied to spectra from nonanesthetized pediatric subjects.

Magn Reson Med 2009 Nov;62(5):1147-54

Danish Research Centre for Magnetic Resonance, Hvidovre, Denmark.

For single-voxel spectroscopy, the acquisition of the spectrum is typically repeated n times and then combined with a factor sqrt[n] in order to improve the signal-to-noise ratio. In practice, the acquisitions are not only affected by random noise but also by physiologic motion and subject movements. Since the influence of physiologic motion such as cardiac and respiratory motion on the data is limited, it can be compensated for without data loss. Individual acquisitions hampered by subject movements, on the other hand, need to be rejected if no correction or compensation is possible. If the individual acquisitions are stored, it is possible to identify and reject the motion-disturbed acquisitions before averaging. Several automatic algorithms were investigated using a dataset of spectra from nonanesthetized infants with a gestational age of 40 weeks. Median filtering removed most subject movement artifacts, but at the cost of increased sensitivity to random noise. Neither independent component analysis nor outlier identification with multiple comparisons has this problem. These two algorithms are novel in this context. The peak height values of the metabolites were increased compared to the mean of all acquisitions for both methods, although primarily for the ICA method.
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http://dx.doi.org/10.1002/mrm.22129DOI Listing
November 2009

A graphical simulator for teaching basic and advanced MR imaging techniques.

Authors:
Lars G Hanson

Radiographics 2007 Nov-Dec;27(6):e27. Epub 2007 Sep 7.

Danish Research Center for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Dept 340, Kettegård Allé 30, DK-2650 Hvidovre, Denmark.

Teaching of magnetic resonance (MR) imaging techniques typically involves considerable handwaving, literally, to explain concepts such as resonance, rotating frames, dephasing, refocusing, sequences, and imaging. A proper understanding of MR contrast and imaging techniques is crucial for radiologists, radiographers, and technical staff alike, but it is notoriously challenging to explain spin dynamics by using traditional teaching tools. The author developed a freely available graphical simulator based on the Bloch equations to aid in the teaching of topics ranging from precession and relaxation to advanced concepts such as stimulated echoes, spin tagging, and k-space-methods. A graphical user interface provides the user with a three-dimensional view of spin isochromates that can be manipulated by selecting radiofrequency pulses and gradient events. Even complicated sequences can be visualized in an intuitive way. The cross-platform software is primarily designed for use in lectures, but is also useful for self studies and student assignments. Movies available at http://radiographics.rsnajnls.org/cgi/content/full/e27/DC1.
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http://dx.doi.org/10.1148/radiographics.27.6.e27DOI Listing
January 2008

Encoding of electrophysiology and other signals in MR images.

J Magn Reson Imaging 2007 May;25(5):1059-66

Danish Research Center for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark.

Purpose: To develop a gradient insensitive, generic technique for recording of non-MR signals by use of surplus scanner bandwidth.

Materials And Methods: Relatively simple battery driven hardware is used to transform one or more signals into radio waves detectable by the MR scanner. Similar to the "magstripe" technique used for encoding of soundtracks in motion pictures, the electrical signals are in this way encoded as artifacts appearing in the MR images or spectra outside the region of interest. The encoded signals are subsequently reconstructed from the signal recorded by the scanner.

Results: Electrophysiological (EP) eye and heart muscular recording (electrooculography [EOG] and electrocardiography [ECG]) during fast echo planar imaging (EPI) is demonstrated with an expandable, modular 8-channel prototype implementation. The gradient artifacts that would normally be dominating EOG are largely eliminated.

Conclusion: The method provides relatively inexpensive sampling with inherent microsecond synchronization and it reduces gradient artifacts in physiological recordings significantly. When oversampling is employed, the method is compatible with all MR reconstruction and postprocessing techniques.
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http://dx.doi.org/10.1002/jmri.20906DOI Listing
May 2007

The relationship between MRI and PET changes and cognitive disturbances in MS.

J Neurol Sci 2006 Jun 2;245(1-2):99-102. Epub 2006 May 2.

Department of Neurology 2082, Danish MS Research Center, Copenhagen University Hospital, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark.

Cognitive dysfunction in multiple sclerosis (MS) is present in approximately 50% of the patients. Only moderate correlations have been found between cognitive dysfunction and T(2) lesion load, black holes or atrophy. Cognitive dysfunction in MS is probably related to the overall disease burden of the brain including abnormalities in normal appearing white matter (NAWM) and cortical grey matter, which is undetected with conventional magnetic resonance imaging (MRI). Hence, imaging techniques that embrace such abnormalities are needed to achieve better correlation with cognitive dysfunction. MR spectroscopy (MRS) performed with multi-slice echo planar spectroscopic imaging (EPSI) and PET measurements of brain metabolism as the cortical cerebral metabolic rate of glucose are imaging methods that are able to provide information on axonal loss or dysfunction in both MS lesions and in NAWM and cortical grey matter. Measurements of global NAA using multi-slice EPSI is a new promising method for measurement of the global neuron capacity and can be repeated with only little discomfort and without any risk for the patient.
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http://dx.doi.org/10.1016/j.jns.2005.09.020DOI Listing
June 2006

Correlation of global N-acetyl aspartate with cognitive impairment in multiple sclerosis.

Arch Neurol 2006 Apr;63(4):533-6

Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark.

Background: Whole-brain N-acetyl aspartate (NAA), a measure of neuronal function, can be assessed by multislice echo-planar spectroscopic imaging.

Objective: To test the hypothesis that the global brain NAA/creatine (Cr) ratio is a better predictor of cognitive dysfunction in multiple sclerosis than conventional magnetic resonance imaging measures.

Design: Survey.

Setting: Research-oriented hospitals.

Patients: Twenty patients, 16 women and 4 men (mean age, 36 years), with early relapsing-remitting multiple sclerosis (mean Expanded Disability Status Scale score, 2.5).

Main Outcome Measures: Correlation between the global NAA/Cr ratio and a cognitive dysfunction factor comprising 16 measures from an extensive neuropsychological test battery that best distinguished patients with multiple sclerosis from healthy control subjects.

Results: A significant partial correlation between the global NAA/Cr ratio and the cognitive dysfunction factor was found (partial r = 0.62, P = .01), and 9 cognitively impaired patients had significantly lower global NAA/Cr ratios than 11 unimpaired patients (P = .04). No significant correlations were found between the cognitive dysfunction factor and conventional magnetic resonance imaging measures (ie, brain parenchymal fraction and lesion volume).

Conclusions: Multislice echo-planar spectroscopic imaging provides global metabolic measures that distinguish between cognitively impaired and unimpaired patients with multiple sclerosis and correlate with a global cognitive measure. Standardization of the technique is needed, and larger-scale studies that include healthy controls are suggested.
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http://dx.doi.org/10.1001/archneur.63.4.533DOI Listing
April 2006

Magnetic resonance imaging at 3.0 tesla detects more lesions in acute optic neuritis than at 1.5 tesla.

Invest Radiol 2006 Feb;41(2):76-82

Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.

Objective: We sought to assess whether magnetic resonance imaging (MRI) at 3.0 T detects more brain lesions in acute optic neuritis (ON) than MRI at 1.5 T.

Materials And Methods: Twenty-eight patients with acute ON were scanned at both field-strengths using fast-fluid-attenuated inversion recovery (FLAIR), proton density and T2-weighted turbo spin echo, and T1-weighted spin echo after contrast. In addition, magnetization-prepared rapid acquisition gradient echo (MPRAGE) was obtained after contrast at 3.0 T. Lesion number and volumes were assessed by an observer blind to patient identity and field strength.

Results: Scans at 3.0 T showed a significantly increase in number of lesions detected on FLAIR images (P = 0.002) relative to scanning at 1.5 T. MPRAGE proved to be suitable for detecting enhancing lesions in ON.

Conclusion: The MRI protocol at 3.0 T was more sensitive to hyperintense brain lesions in ON than the standard MRI protocol at 1.5 T.
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http://dx.doi.org/10.1097/01.rli.0000188364.76251.28DOI Listing
February 2006

Hyperpolarized 3He MRI and 81mKr SPECT in chronic obstructive pulmonary disease.

Eur J Nucl Med Mol Imaging 2005 Apr 20;32(4):448-57. Epub 2004 Nov 20.

Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, Denmark.

Purpose: During recent years, magnetic resonance imaging (MRI) using hyperpolarised (HP) 3He gas has emerged as a promising new method for the imaging of lung ventilation. However, systematic comparisons with nuclear medicine techniques have not yet been performed. The aim of this study was to compare ventilation imaging methods in 26 patients with chronic obstructive pulmonary disease (COPD) and nine lung healthy volunteers.

Methods: HP 3He MRI, 81mKr single-photon emission computed tomography (SPECT), high-resolution computed tomography (HRCT) and pulmonary function tests were performed. The three scans were scored visually as percentage of non-ventilated/diseased lung, and a computer-based objective measure of the ventilated volume in HP 3He MRI and 81mKr SPECT and an emphysema index in HRCT were calculated.

Results: We found a good correlation between HP 3He MRI and 81mKr SPECT for both visual defect score (r=0.80, p<0.0001) and objective estimate of ventilation (r=0.45, p=0.0157). In addition, both scans were well correlated with reference methods for the diagnosis of emphysema (pulmonary function test and HRCT). The defect scores were largest on 81mKr SPECT (the score on HP 3He MRI was one-third less than that on 81mKr SPECT), but the difference was reduced after normalisation for different breathing depths (HP 3He MRI at total lung capacity; 81mKr SPECT at tidal breathing at functional residual capacity).

Conclusion: HP 3He MRI provides detailed ventilation distribution images and defect scores are comparable on HP 3He MRI and 81mKr SPECT. Additionally, new insights into the regional pulmonary microstructure via the apparent diffusion coefficient measurements are provided by HP 3He MRI. HP 3He MRI is a promising new diagnostic tool for the assessment of ventilation distribution.
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http://dx.doi.org/10.1007/s00259-004-1691-xDOI Listing
April 2005

Multi-slice echo-planar spectroscopic MR imaging provides both global and local metabolite measures in multiple sclerosis.

Magn Reson Med 2005 Apr;53(4):750-9

Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark.

MR spectroscopy (MRS) provides information about neuronal loss or dysfunction by measuring decreases in N-acetyl aspartate (NAA), a metabolite widely believed to be a marker of neuronal viability. In multiple sclerosis (MS), whole-brain NAA (WBNAA) has been suggested as a marker of disease progression and treatment efficacy in treatment trials, and the ability to measure NAA loss in specific brain regions early in the evolution of this disease may have prognostic value. Most spectroscopic studies to date have been limited to single voxels or nonlocalized measurements of WBNAA only, and longitudinal studies have often been hampered by standardization and reproducibility problems. Multi-slice echo-planar spectroscopic imaging (EPSI) is presented as a promising alternative to single-voxel or nonlocalized spectroscopy for obtaining global metabolite estimates in MS. In the same session, measurements of metabolites in specific brain areas chosen after image acquisition (e.g., normal-appearing white matter (NAWM), gray matter (GM), and lesions) can be obtained. The identification and exclusion of regions that are inadequate for spectroscopic evaluation in global assessments can significantly improve quality and reproducibility, as demonstrated by a low within-subject variance in healthy controls. The reproducibility of the technique makes it a promising tool for future longitudinal spectroscopic studies of MS.
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http://dx.doi.org/10.1002/mrm.20407DOI Listing
April 2005
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