Publications by authors named "Matthias Günther"

64 Publications

ExploreASL: An image processing pipeline for multi-center ASL perfusion MRI studies.

Neuroimage 2020 10 8;219:117031. Epub 2020 Jun 8.

Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands; UCL Queen Square Institute of Neurology, University College London, London, UK; Centre for Medical Image Computing (CMIC), Faculty of Engineering Science, University College London, London, UK.

Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners. The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. To facilitate collaboration and data-exchange, the toolbox follows several standards and recommendations for data structure, provenance, and best analysis practice. ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow. ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts which may increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117031DOI Listing
October 2020

Deep learning-based reconstruction of ultrasound images from raw channel data.

Int J Comput Assist Radiol Surg 2020 Sep 3;15(9):1487-1490. Epub 2020 Jun 3.

Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany.

Purpose: We investigate the feasibility of reconstructing ultrasound images directly from raw channel data using a deep learning network. Starting from the raw data, we present the network the full measurement information, allowing for a more generic reconstruction to form, as compared to common reconstructions constrained by physical models using fixed speed of sound assumptions.

Methods: We propose a U-Net-like architecture for the given task. Additional layers with strided convolutions downsample the raw data. Hyperparameter optimization was used to find a suitable learning rate. We train and test our deep learning approach on plane wave ultrasound images with a single insonification angle. The dataset includes phantom as well as in vivo data.

Results: The images produced by our method are visually comparable to ones reconstructed with the conventional delay and sum algorithm. Deviations between prediction and ground truth are likely to be related to speckle noise. For the test set, the mean absolute error is [Formula: see text] for the phantom images and [Formula: see text] for the in vivo data.

Conclusion: The result shows the feasibility of our approach and opens up new research directions regarding information retrieval from raw channel data. As the networks reconstruction performance is limited by the quality of the ground truth images, using other ultrasound reconstruction technique or image types as target data would be of interest.
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http://dx.doi.org/10.1007/s11548-020-02197-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419487PMC
September 2020

[The baseline assessment of the German National Cohort (NAKO Gesundheitsstudie): participation in the examination modules, quality assurance, and the use of secondary data].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Mar;63(3):254-266

Leibniz-Institut für Präventionsforschung und Epidemiologie - BIPS, Bremen, Deutschland.

Background: The German National Cohort (NAKO) is an interdisciplinary health study aimed at elucidating causes for common chronic diseases and detecting their preclinical stages. This article provides an overview of design, methods, participation in the examinations, and their quality assurance based on the midterm baseline dataset (MBD) of the recruitment.

Methods: More than 200,000 women and men aged 20-69 years derived from random samples of the German general population were recruited in 18 study centers (2014-2019). The data collection comprised physical examinations, standardized interviews and questionnaires, and the collection of biomedical samples for all participants (level 1). At least 20% of all participants received additional in-depth examinations (level 2), and 30,000 received whole-body magnet resonance imaging (MRI). Additional information will be collected through secondary data sources such as medical registries, health insurances, and pension funds. This overview is based on the MBD, which included 101,839 participants, of whom 11,371 received an MRI.

Results: The mean response proportion was 18%. The participation in the examinations was high with most of the modules performed by over 95%. Among MRI participants, 96% completed all 12 MRI sequences. More than 90% of the participants agreed to the use of complementary secondary and registry data.

Discussion: Individuals selected for the NAKO were willing to participate in all examinations despite the time-consuming program. The NAKO provides a central resource for population-based epidemiologic research and will contribute to developing innovative strategies for prevention, screening and prediction of chronic diseases.
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http://dx.doi.org/10.1007/s00103-020-03093-zDOI Listing
March 2020

Portable and platform-independent MR pulse sequence programs.

Magn Reson Med 2020 04 21;83(4):1277-1290. Epub 2019 Oct 21.

Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany.

Purpose: To introduce a new sequence description format for vendor-independent MR sequences that include all calculation logic portably. To introduce a new MRI sequence development approach which utilizes flexibly reusable modules.

Methods: The proposed sequence description contains a sequence module hierarchy for loop and group logic, which is enhanced by a novel strategy for performing efficient parameter and pulse shape calculation. These calculations are powered by a flow graph structure. By using the flow graph, all calculations are performed with no redundancy and without requiring preprocessing. The generation of this interpretable structure is a separate step that combines MRI techniques while actively considering their context. The driver interface is slim and highly flexible through scripting support. The sequences do not require any vendor-specific compiling or processing step. A vendor-independent frontend for sequence configuration can be used. Tests that ensure physical feasibility of the sequence are integrated into the calculation logic.

Results: The framework was used to define a set of standard sequences. Resulting images were compared to respective images acquired with sequences provided by the device manufacturer. Images were acquired using a standard commercial MRI system.

Conclusions: The approach produces configurable, vendor-independent sequences, whose configurability enables rapid prototyping. The transparent data structure simplifies the process of sharing reproducible sequences, modules, and techniques.
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http://dx.doi.org/10.1002/mrm.28020DOI Listing
April 2020

Prospective motion correction in functional MRI using simultaneous multislice imaging and multislice-to-volume image registration.

Neuroimage 2019 10 19;200:159-173. Epub 2019 Jun 19.

Imaging Centre of Excellence, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, Scotland, UK.

The sensitivity to subject motion is one of the major challenges in functional MRI (fMRI) studies in which a precise alignment of images from different time points is required to allow reliable quantification of brain activation throughout the scan. Especially the long measurement times and laborious fMRI tasks add to the amount of subject motion found in typical fMRI measurements, even when head restraints are used. In case of moving subjects, prospective motion correction can maintain the relationship between spatial image information and subject anatomy by constantly adapting the image slice positioning to follow the subject in real time. Image-based prospective motion correction is well-established in fMRI studies and typically computes the motion estimates based on a volume-to-volume image registration, resulting in low temporal resolution. This study combines fMRI using simultaneous multislice imaging with multislice-to-volume-based image registration to allow sub-TR motion detection with subsequent real-time adaption of the imaging system. Simultaneous multislice imaging is widely used in fMRI studies and, together with multislice-to-volume-based image registration algorithms, enables computing suitable motion states after only a single readout by registering the simultaneously excited slices to a reference volume acquired at the start of the measurement. The technique is evaluated in three human BOLD fMRI studies (n = 1, 5, and 1) to explore different aspects of the method. It is compared to conventional, volume-to-volume-based prospective motion correction as well as retrospective motion correction methods. Results show a strong reduction in retrospectively computed residual motion parameters of up to 50% when comparing the two prospective motion correction techniques. An analysis of temporal signal-to-noise ratio as well as brain activation results shows high consistency between the results before and after additional retrospective motion correction when using the proposed technique, indicating successful prospective motion correction. The comparison of absolute tSNR values does not show an improvement compared to using retrospective motion correction alone. However, the improved temporal resolution may provide improved tSNR in the presence of more exaggerated intra-volume motion.
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http://dx.doi.org/10.1016/j.neuroimage.2019.06.042DOI Listing
October 2019

Effects of Nilvadipine on Cerebral Blood Flow in Patients With Alzheimer Disease.

Hypertension 2019 08 17;74(2):413-420. Epub 2019 Jun 17.

From the Department of Geriatric Medicine, Donders Institute for Brain Cognition and Behaviour (D.L.K.d.J., R.A.A.d.H., A.R., M.G.M.O.R., J.A.H.R.C.), Radboud University Medical Center, Nijmegen, the Netherlands.

Cerebrovascular changes, including reduced cerebral blood flow (CBF), occur early in the development of Alzheimer disease and may accelerate disease progression. This randomized, double-blind, placebo-controlled study investigated how 6 months of treatment with the calcium antagonist nilvadipine would affect CBF in patients with mild-to-moderate Alzheimer disease. CBF was measured with magnetic resonance arterial spin labeling in whole-brain gray matter and in a priori defined regions of interest including the hippocampus. Fifty-eight patients were randomly assigned (29 in each group), of whom 22 in both groups had no magnetic resonance exclusion criteria and were medication compliant over 6 months. Mean age was 72.8±6.2 years, mean mini-mental state examination was 20.4±3.4. Nilvadipine treatment lowered systolic blood pressure (Δ=-11.5 [95% CI, -19.7 to -3.2] mm Hg; P<0.01), while whole-brain gray-matter CBF remained stable (Δ=5.4 [95% CI, -6.4 to 17.2] mL/100 g per minute; P=0.36). CBF in the hippocampus increased (left: Δ=24.4 [95% CI, 4.3-44.5] mL/100 g per minute; P=0.02; right: Δ=20.1 [95% CI, -0.6 to 40.8] mL/100 g per minute; P=0.06). There was no significant change in CBF in the posterior cingulate cortex (Δ=5.2 [95% CI, -16.5 to 27.0] mL/100 g per minute; P=0.63) or other regions of interest. In conclusion, nilvadipine reduced blood pressure and increased CBF in the hippocampus, whereas other regions showed stable or small nonsignificant increases in CBF. These findings not only indicate preserved cerebral autoregulation in Alzheimer disease but also point toward beneficial cerebrovascular effects of antihypertensive treatment. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02017340.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.12892DOI Listing
August 2019

Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor.

Elife 2019 04 5;8. Epub 2019 Apr 5.

Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.

The immune system distinguishes between self and foreign antigens. The kinetic proofreading (KPR) model proposes that T cells discriminate self from foreign ligands by the different ligand binding half-lives to the T cell receptor (TCR). It is challenging to test KPR as the available experimental systems fall short of only altering the binding half-lives and keeping other parameters of the interaction unchanged. We engineered an optogenetic system using the plant photoreceptor phytochrome B (PhyB) as a ligand to selectively control the dynamics of ligand binding to the TCR by light. This opto-ligand-TCR system was combined with the unique property of PhyB to continuously cycle between the binding and non-binding states under red light, with the light intensity determining the cycling rate and thus the binding duration. Mathematical modeling of our experimental datasets showed that indeed the ligand-TCR interaction half-life is the decisive factor for activating downstream TCR signaling, substantiating KPR.
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http://dx.doi.org/10.7554/eLife.42475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488296PMC
April 2019

Dynamics of brain perfusion and cognitive performance in revascularization of carotid artery stenosis.

Neuroimage Clin 2019 13;22:101779. Epub 2019 Mar 13.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

Introduction: There is evidence suggesting a detrimental effect of asymptomatic carotid artery stenosis on cognitive function even in the absence of ischemic cerebral lesions. Hypoperfusion has been suggested as pathophysiological mechanism causing cognitive impairment. We aimed to assess cognitive performance and cerebral perfusion changes in patients with carotid artery stenosis without ischemic lesions by arterial spin labeling (ASL) and contrast enhanced (CE) perfusion MRI before and after revascularization therapy.

Methods: 17 asymptomatic patients with unilateral high-grade (≥70%) carotid artery stenosis without evidence of structural brain lesions underwent ASL and CE perfusion MRI and cognitive testing (MMSE, DemTect, Clock-Drawing Test, Trail-Making Test, Stroop Test) before and 6-8 weeks after revascularization therapy by endarterectomy or stenting. Multiparametric perfusion maps (ASL: cerebral blood flow (ASL-CBF), bolus arrival time (ASL-BAT); CE: cerebral blood flow (CE-CBF), mean transit time (CE-MTT), cerebral blood volume (CE-CBV)) were calculated and analyzed by vascular territory. Relative perfusion values were calculated.

Results: Multivariate analysis revealed a significant impact of revascularization therapy on all perfusion measures analyzed. At baseline post-hoc testing showed significant hypoperfusion in MCA borderzones as assessed by ASL-CBF, ASL-BAT, CE-MTT and CE-CBV. All perfusion alterations normalized after revascularization. We did not observe any significant correlation of cognitive test results with perfusion parameters. There was no significant change in cognitive performance after revascularization.

Conclusion: We found evidence of traceable perfusion alterations in patients with high grade carotid artery stenosis in the absence of structural brain lesions, which proved fully reversible after revascularization therapy. In this cohort of asymptomatic patients we did not observe an association of hypoperfusion with cognitive performance.
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http://dx.doi.org/10.1016/j.nicl.2019.101779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431743PMC
January 2020

Stem cell homeostasis by integral feedback through the niche.

J Theor Biol 2019 11 20;481:100-109. Epub 2018 Dec 20.

German Cancer Research Center (DKFZ), Division of Theoretical Systems Biology, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany. Electronic address:

Hematopoiesis is a paradigm for tissue development and renewal from stem cells. Experiments show that the maintenance of hematopoietic stem cells (HSCs) relies on signals from niche cells. However, it is not known how the size of the HSC compartment is set. Competition by HSCs for niche access has been suggested, yet niche cells in the bone marrow outnumber HSCs. Here we propose a cooperative model of HSC homeostasis in which stem and niche cells mutually interact such that niche cells function as negative feedback regulators of HSC proliferation. This model explains puzzling experimental findings, including homeostatic recovery of the HSC compartment after irradiation versus apparent lack of recovery after HSC ablation. We show that bidirectional niche-stem cell regulation has properties of a proportional-integral feedback controller. Moreover, we predict that the outflux of differentiated cells from HSCs can be regulated by the affinity of HSCs for niche cells. Much effort has been devoted to elucidating niche cell signaling to stem cells; our theoretical insights indicate that studying the effect of stem cells on the niche may be equally important for understanding stem cell homeostasis.
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http://dx.doi.org/10.1016/j.jtbi.2018.12.029DOI Listing
November 2019

Simultaneous multislice acquisition with multi-contrast segmented EPI for separation of signal contributions in dynamic contrast-enhanced imaging.

PLoS One 2018 28;13(8):e0202673. Epub 2018 Aug 28.

University Bremen, Bermen, Germany.

We present a method to efficiently separate signal in magnetic resonance imaging (MRI) into a base signal S0, representing the mainly T1-weighted component without T2*-relaxation, and its T2*-weighted counterpart by the rapid acquisition of multiple contrasts for advanced pharmacokinetic modelling. This is achieved by incorporating simultaneous multislice (SMS) imaging into a multi-contrast, segmented echo planar imaging (EPI) sequence to allow extended spatial coverage, which covers larger body regions without time penalty. Simultaneous acquisition of four slices was combined with segmented EPI for fast imaging with three gradient echo times in a preclinical perfusion study. Six female domestic pigs, German-landrace or hybrid-form, were scanned for 11 minutes respectively during administration of gadolinium-based contrast agent. Influences of reconstruction methods and training data were investigated. The separation into T1- and T2*-dependent signal contributions was achieved by fitting a standard analytical model to the acquired multi-echo data. The application of SMS yielded sufficient temporal resolution for the detection of the arterial input function in major vessels, while anatomical coverage allowed perfusion analysis of muscle tissue. The separation of the MR signal into T1- and T2*-dependent components allowed the correction of susceptibility related changes. We demonstrate a novel sequence for dynamic contrast-enhanced MRI that meets the requirements of temporal resolution (Δt < 1.5 s) and image quality. The incorporation of SMS into multi-contrast, segmented EPI can overcome existing limitations of dynamic contrast enhancement and dynamic susceptibility contrast methods, when applied separately. The new approach allows both techniques to be combined in a single acquisition with a large spatial coverage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0202673PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112664PMC
February 2019

MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset.

N Engl J Med 2018 08 16;379(7):611-622. Epub 2018 May 16.

From Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf (G.T., B. Cheng, S.G., A.G., C.G.), the Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf (J.F.), and ZytoService Deutschland (E.S.), Hamburg, Universitätsklinik für Neurologie, Medizinische Universität Graz, Graz (F.F.), Centrum für Schlaganfallforschung Berlin (I.G., K.G.H., K.V., M. Ebinger, M. Endres, J.B.F.) and Klinik und Hochschulambulanz für Neurologie (K.G.H., L.N., M. Endres), Charité-Universitätsmedizin Berlin, and Neurologie der Rehaklinik Medical Park Humboldtmühle (M. Ebinger), Berlin, Mediri (J. Gregori, M.G.), the Department of Neurology, Medical Faculty Mannheim, University of Heidelberg (M.H.), and Neurologische Klinik, Universitätsklinikum Heidelberg (P. Ringleb), Heidelberg, Fraunhofer MEVIS and University of Bremen, Bremen (M.G.), and Institut für Neuroradiologie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck (A.K.) - all in Germany; the Department of Neurology, Aarhus University Hospital, Aarhus (C.Z.S., G.A.), the Department of Neurology, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen (J.M.), and Department of Neurology, Stroke Unit, Aalborg University Hospital, Aalborg (B.M.) - all in Denmark; Hospices Civils de Lyon, Service de Biostatistique (F.B., P. Roy), the Neuroradiology Department, Neurological Hospital, University Lyon (Y.B.), and the Department of Stroke Medicine, Université Claude Bernard Lyon 1, and Hospices Civils de Lyon (T.-H.C., N.N.), Lyon, and Université Lyon 1 and Centre National de la Recherche Scientifique, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne (F.B., P. Roy) - all in France; the Institute of Neuroscience and Psychology (B. Cheripelli, K.W.M.) and the Robertson Centre for Biostatistics (I.F.), University of Glasgow, Glasgow, United Kingdom (I.F.); Fundació Salut Empordà Hospital, Figueres (J. Guibernau), Stroke Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Barcelona (N.P.O.), and the Department of Radiology (J.P., S.P.) and the Stroke Unit (J.S.), Hospital Universitari Doctor Josep Trueta, Institut d'Investigació Biomèdica de Girona, Girona - all in Spain; the Department of Neurology, St. Antonius Hospital, Nieuwegein, and University Medical Center Utrecht, Utrecht (W.S.) - both in the Netherlands; the Department of Imaging and Pathology, University of Leuven (S.S.), the Department of Neurology, University Hospitals Leuven (A.W., R.L.), KU Leuven-University of Leuven, Department of Neurosciences, Experimental Neurology (A.W., R.L.), and the VIB-KU Leuven Center for Brain and Disease Research, Laboratory of Neurobiology (A.W., R.L.), Leuven, Belgium; and Florey Institute of Neuroscience and Mental Health, Heidelberg, VIC, Australia (V.T.).

Background: Under current guidelines, intravenous thrombolysis is used to treat acute stroke only if it can be ascertained that the time since the onset of symptoms was less than 4.5 hours. We sought to determine whether patients with stroke with an unknown time of onset and features suggesting recent cerebral infarction on magnetic resonance imaging (MRI) would benefit from thrombolysis with the use of intravenous alteplase.

Methods: In a multicenter trial, we randomly assigned patients who had an unknown time of onset of stroke to receive either intravenous alteplase or placebo. All the patients had an ischemic lesion that was visible on MRI diffusion-weighted imaging but no parenchymal hyperintensity on fluid-attenuated inversion recovery (FLAIR), which indicated that the stroke had occurred approximately within the previous 4.5 hours. We excluded patients for whom thrombectomy was planned. The primary end point was favorable outcome, as defined by a score of 0 or 1 on the modified Rankin scale of neurologic disability (which ranges from 0 [no symptoms] to 6 [death]) at 90 days. A secondary outcome was the likelihood that alteplase would lead to lower ordinal scores on the modified Rankin scale than would placebo (shift analysis).

Results: The trial was stopped early owing to cessation of funding after the enrollment of 503 of an anticipated 800 patients. Of these patients, 254 were randomly assigned to receive alteplase and 249 to receive placebo. A favorable outcome at 90 days was reported in 131 of 246 patients (53.3%) in the alteplase group and in 102 of 244 patients (41.8%) in the placebo group (adjusted odds ratio, 1.61; 95% confidence interval [CI], 1.09 to 2.36; P=0.02). The median score on the modified Rankin scale at 90 days was 1 in the alteplase group and 2 in the placebo group (adjusted common odds ratio, 1.62; 95% CI, 1.17 to 2.23; P=0.003). There were 10 deaths (4.1%) in the alteplase group and 3 (1.2%) in the placebo group (odds ratio, 3.38; 95% CI, 0.92 to 12.52; P=0.07). The rate of symptomatic intracranial hemorrhage was 2.0% in the alteplase group and 0.4% in the placebo group (odds ratio, 4.95; 95% CI, 0.57 to 42.87; P=0.15).

Conclusions: In patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome and numerically more intracranial hemorrhages than placebo at 90 days. (Funded by the European Union Seventh Framework Program; WAKE-UP ClinicalTrials.gov number, NCT01525290; and EudraCT number, 2011-005906-32 .).
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http://dx.doi.org/10.1056/NEJMoa1804355DOI Listing
August 2018

Arterial Spin Labeling Cerebral Perfusion Magnetic Resonance Imaging in Migraine Aura: An Observational Study.

J Stroke Cerebrovasc Dis 2018 May 10;27(5):1262-1266. Epub 2018 Jan 10.

Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany; Department of Neurology, Klinikum Kempten, Kempten, Germany.

Background: Changes in cerebral perfusion during migraine with aura (MA) have been assessed mainly using dynamic susceptibility contrast (DSC) magnetic resonance perfusion imaging. A contrast agent-free method to assess these changes would be desirable. We assessed changes in cerebral perfusion during MA using arterial spin labeling (ASL) perfusion magnetic resonance imaging.

Methods: We investigated 4 patients with a standardized protocol including ASL perfusion imaging during MA (n = 2) or early headache phase (n = 2) and asymptomatic follow-up. Semiquantitative evaluation was done using a region of interest (ROI) within hypoperfused or hyperperfused areas and corresponding ROIs in the contralateral hemisphere. Relative ratios of mean perfusion in the corresponding ROIs were calculated. DSC imaging was done at initial time points and compared visually with ASL findings.

Results: In all patients, regional perfusion changes were detected in the acute phase. These abnormalities did not respect the boundaries of major cerebral vascular territories but overlapped onto adjoining regions. During MA, adjacent hypoperfused and hyperperfused areas were found, whereas during headache, regional hyperperfusion only was observed. Perfusion abnormalities normalized on follow-up.

Conclusions: ASL perfusion imaging is a contrast agent-free method suitable for assessment of reversible perfusion changes during or immediately after MA.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.12.002DOI Listing
May 2018

Using simultaneous PET/MRI to compare the accuracy of diagnosing frontotemporal dementia by arterial spin labelling MRI and FDG-PET.

Neuroimage Clin 2018 31;17:405-414. Epub 2017 Oct 31.

Lawson Health Research Institute, St Joseph's Health Care, 268 Grosvenor St., London, Ontario N6A 4V2, Canada; Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, Medical Sciences Building, Rm M407, London, Ontario N6A 5C1, Canada. Electronic address:

Purpose: The clinical utility of FDG-PET in diagnosing frontotemporal dementia (FTD) has been well demonstrated over the past decades. On the contrary, the diagnostic value of arterial spin labelling (ASL) MRI - a relatively new technique - in clinical diagnosis of FTD has yet to be confirmed. Using simultaneous PET/MRI, we evaluated the diagnostic performance of ASL in identifying pathological abnormalities in FTD (FTD) to determine whether ASL can provide similar diagnostic value as FDG-PET.

Methods: ASL and FDG-PET images were compared in 10 patients with FTD and 10 healthy older adults. Qualitative and quantitative measures of diagnostic equivalency were used to determine the diagnostic utility of ASL compared to FDG-PET. Sensitivity, specificity, and inter-rater reliability were calculated for each modality from scores of subjective visual ratings and from analysis of regional mean values in thirteen a priori regions of interest (ROI). To determine the extent of concordance between modalities in each patient, individual statistical maps generated from comparison of each patient to controls were compared between modalities using the Jaccard similarity index (JI).

Results: Visual assessments revealed lower sensitivity, specificity and inter-rater reliability for ASL (66.67%/62.12%/0.2) compared to FDG-PET (88.43%/90.91%/0.61). Across all regions, ASL performed lower than FDG-PET in discriminating patients from controls (areas under the receiver operating curve: ASL = 0.75 and FDG-PET = 0.87). In all patients, ASL identified patterns of reduced perfusion consistent with FTD, but areas of hypometabolism exceeded hypoperfused areas (group-mean JI = 0.30 ± 0.22).

Conclusion: This pilot study demonstrated that ASL can detect similar spatial patterns of abnormalities in individual FTD patients compared to FDG-PET, but its sensitivity and specificity for discriminant diagnosis of a patient from healthy individuals remained unmatched to FDG-PET. Further studies at the individual level are required to confirm the clinical role of ASL in FTD management.
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http://dx.doi.org/10.1016/j.nicl.2017.10.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683801PMC
June 2018

A focused ultrasound treatment system for moving targets (part I): generic system design and in-silico first-stage evaluation.

J Ther Ultrasound 2017 24;5:20. Epub 2017 Jul 24.

Fraunhofer Institute for Medical Image Computing MEVIS, Am Fallturm 1, Bremen, 28359 Germany.

Background: Focused ultrasound (FUS) is entering clinical routine as a treatment option. Currently, no clinically available FUS treatment system features automated respiratory motion compensation. The required quality standards make developing such a system challenging.

Methods: A novel FUS treatment system with motion compensation is described, developed with the goal of clinical use. The system comprises a clinically available MR device and FUS transducer system. The controller is very generic and could use any suitable MR or FUS device. MR image sequences (echo planar imaging) are acquired for both motion observation and thermometry. Based on anatomical feature tracking, motion predictions are estimated to compensate for processing delays. FUS control parameters are computed repeatedly and sent to the hardware to steer the focus to the (estimated) target position. All involved calculations produce individually known errors, yet their impact on therapy outcome is unclear. This is solved by defining an intuitive quality measure that compares the achieved temperature to the static scenario, resulting in an overall efficiency with respect to temperature rise. To allow for extensive testing of the system over wide ranges of parameters and algorithmic choices, we replace the actual MR and FUS devices by a virtual system. It emulates the hardware and, using numerical simulations of FUS during motion, predicts the local temperature rise in the tissue resulting from the controls it receives.

Results: With a clinically available monitoring image rate of 6.67 Hz and 20 FUS control updates per second, normal respiratory motion is estimated to be compensable with an estimated efficiency of 80%. This reduces to about 70% for motion scaled by 1.5. Extensive testing (6347 simulated sonications) over wide ranges of parameters shows that the main source of error is the temporal motion prediction. A history-based motion prediction method performs better than a simple linear extrapolator.

Conclusions: The estimated efficiency of the new treatment system is already suited for clinical applications. The simulation-based in-silico testing as a first-stage validation reduces the efforts of real-world testing. Due to the extensible modular design, the described approach might lead to faster translations from research to clinical practice.
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http://dx.doi.org/10.1186/s40349-017-0098-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523151PMC
July 2017

Mapping Long-Term Functional Changes in Cerebral Blood Flow by Arterial Spin Labeling.

PLoS One 2016 5;11(10):e0164112. Epub 2016 Oct 5.

Lawson Health Research Institute, London, ON, Canada.

Although arterial spin labeling (ASL) is appealing for mapping long-term changes in functional activity, inter-sessional variations in basal blood flow, arterial transit times (ATTs), and alignment errors, can result in significant false activation when comparing images from separate sessions. By taking steps to reduce these sources of noise, this study assessed the ability of ASL to detect functional CBF changes between sessions. ASL data were collected in three sessions to image ATT, resting CBF and CBF changes associated with motor activation (7 participants). Activation maps were generated using rest and task images acquired in the same session and from sessions separated by up to a month. Good agreement was found when comparing between-session activation maps to within-session activation maps with only a 16% decrease in precision (within-session: 90 ± 7%) and a 13% decrease in the Dice similarity (within-session: 0.75 ± 0.07) coefficient after a month. In addition, voxel-wise reproducibility (within-session: 4.7 ± 4.5%) and reliability (within-session: 0.89 ± 0.20) of resting grey-matter CBF decreased by less than 18% for the between-session analysis relative to within-session values. ATT variability between sessions (5.0 ± 2.7%) was roughly half the between-subject variability, indicating that its effects on longitudinal CBF were minimal. These results demonstrate that conducting voxel-wise analysis on CBF images acquired on different days is feasible with only modest loss in precision, highlighting the potential of ASL for longitudinal studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0164112PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5051683PMC
June 2017

Automated quality assessment in three-dimensional breast ultrasound images.

J Med Imaging (Bellingham) 2016 Apr 25;3(2):027002. Epub 2016 Apr 25.

mediri GmbH, Vangerowstr. 18, Heidelberg 69115, Germany; Fraunhofer MEVIS, Universitätsallee 29, Bremen 28359, Germany.

Automated three-dimensional breast ultrasound (ABUS) is a valuable adjunct to x-ray mammography for breast cancer screening of women with dense breasts. High image quality is essential for proper diagnostics and computer-aided detection. We propose an automated image quality assessment system for ABUS images that detects artifacts at the time of acquisition. Therefore, we study three aspects that can corrupt ABUS images: the nipple position relative to the rest of the breast, the shadow caused by the nipple, and the shape of the breast contour on the image. Image processing and machine learning algorithms are combined to detect these artifacts based on 368 clinical ABUS images that have been rated manually by two experienced clinicians. At a specificity of 0.99, 55% of the images that were rated as low quality are detected by the proposed algorithms. The areas under the ROC curves of the single classifiers are 0.99 for the nipple position, 0.84 for the nipple shadow, and 0.89 for the breast contour shape. The proposed algorithms work fast and reliably, which makes them adequate for online evaluation of image quality during acquisition. The presented concept may be extended to further image modalities and quality aspects.
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http://dx.doi.org/10.1117/1.JMI.3.2.027002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841937PMC
April 2016

Correction for Susceptibility Distortions Increases the Performance of Arterial Spin Labeling in Patients with Cerebrovascular Disease.

J Neuroimaging 2016 07 27;26(4):436-44. Epub 2016 Jan 27.

Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin, Berlin, Germany.

Background And Purpose: Arterial spin labeling (ASL) is an MRI technique to measure cerebral blood flow (CBF) without the need of exogenous contrast agents and is thus a promising alternative to the clinical standard dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion imaging. Latest international guidelines encourage its application in the clinical setting. However, susceptibility-induced image distortions impair ASL with fast readout modules (eg Echo Planar Imaging, EPI; gradient and spin echo, GRASE). In the present study, we investigated the benefit of a distortion correction for ASL compared to DSC.

Methods: A pulsed ASL (PASL) sequence combined with a 3D-GRASE readout at multiple inflow times (multi-TI) was used and was corrected for susceptibility distortions using a FMRIB Software Library (FSL) implemented tool TOPUP. We performed qualitative (three expert raters) and quantitative (volume of interest [VOI]-based) comparisons of ASL and DSC imaging in 13 patients with chronic steno-occlusive disease.

Results: In the qualitative analysis, distortion correction of the images led to a strong increase in diagnostic precision of ASL compared to DSC in the anterior cerebral artery (ACA) perfusion territory, where the susceptibility artifact was most pronounced (specificity 8% vs. 75%). In the quantitative analysis, the correlation between ASL and DSC values increased for all perfusion territories with the best improvement for the ACA territory (for anterior, middle and posterior cerebral artery: ACA: rho -0.22 vs. 0.71; MCA: rho 0.58 vs. 0.76; PCA: rho 0.58 vs. 0.63).

Conclusions: We showed that susceptibility distortion correction strongly improves the comparability of multi-TI ASL 3D-GRASE to DSC in steno-occlusive disease. We suggest it to be implemented in ASL postprocessing routines.
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http://dx.doi.org/10.1111/jon.12331DOI Listing
July 2016

Principles and methods for automatic and semi-automatic tissue segmentation in MRI data.

MAGMA 2016 Apr 11;29(2):95-110. Epub 2016 Jan 11.

Institute for Medical Image Computing, Fraunhofer MEVIS Universitaetsallee 29, 28359, Bremen, Germany.

The development of magnetic resonance imaging (MRI) revolutionized both the medical and scientific worlds. A large variety of MRI options have generated a huge amount of image data to interpret. The investigation of a specific tissue in 3D or 4D MR images can be facilitated by image processing techniques, such as segmentation and registration. In this work, we provide a brief review of the principles and methods that are commonly applied to achieve superior tissue segmentation results in MRI. The impacts of MR image acquisition on segmentation outcome and the principles of selecting and exploiting segmentation techniques tailored for specific tissue identification tasks are discussed. In the end, two exemplary applications, breast and fibroglandular tissue segmentation in MRI and myocardium segmentation in short-axis cine and real-time MRI, are discussed to explain the typical challenges that can be posed in practical segmentation tasks in MRI data. The corresponding solutions that are adopted to deal with these challenges of the two practical segmentation tasks are thoroughly reviewed.
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http://dx.doi.org/10.1007/s10334-015-0520-5DOI Listing
April 2016

Quantitative, Organ-Specific Interscanner and Intrascanner Variability for 3 T Whole-Body Magnetic Resonance Imaging in a Multicenter, Multivendor Study.

Invest Radiol 2016 Apr;51(4):255-65

From the *Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg; †Department of Clinical Radiology, Campus Grosshadern, Ludwig-Maximilians University, Munich; ‡Fraunhofer Institute for Medical Image Computing MEVIS, Bremen; §Institute of Neuroscience and Medicine, Jülich Research Centre, Jülich; ∥Department of Cardiology and Nephrology, HELIOS Clinic Berlin Buch, Berlin; ¶Institute for Community Medicine, Ernst-Moritz-Arndt University, Greifswald; #Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen; **Institute of Diagnostic Radiology, and ††Department of Epidemiology and Preventive Medicine, University Hospital Regensburg, Regensburg; ‡‡Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Aachen; §§Department of Epidemiology, Helmholtz Centre for Infection Research, Braunschweig; ∥∥Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover; ¶¶O. Vogt Institute for Brain Research, Heinrich-Heine-University Düsseldorf, Düsseldorf; ##Department of Diagnostic and Interventional Radiology, University Hospital Klinikum rechts der Isar, Munich; ***Department of Radiology and Neuroradiology,University Medicine Greifswald, Ernst-Moritz-Arndt University, Greifswald; and †††Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen, Germany.

Introduction: Whole-body magnetic resonance (MR) imaging is increasingly implemented in population-based cohorts and clinical settings. However, to quantify the variability introduced by the different scanners is essential to make conclusions about clinical and biological data, and relevant for internal/external validity. Thus, we determined the interscanner and intrascanner variability of different 3 T MR scanners for whole-body imaging.

Methods: Thirty volunteers were enrolled to undergo multicentric, interscanner as well intrascanner imaging as part of the German National Cohort pilot studies. A comprehensive whole-body MR protocol was installed at 9 sites including 7 different MR scanner models by all 4 major vendors. A set of quantitative, organ-specific measures (n = 20; eg, volume of brain's gray/white matter, pulmonary trunk diameter, vertebral body height) were obtained in blinded fashion. Reproducibility was determined using mean weighted relative differences and intraclass correlation coefficients.

Results: All participants (44 ± 14 years, 50% female) successfully completed the imaging protocol except for two because of technical issues. Mean scan time was 2 hours and 32 minutes and differed significantly across scanners (range, 1 hour 59 minutes to 3 hours 12 minutes). A higher reproducibility of obtained measurements was observed for intrascanner than for interscanner comparisons (intraclass correlation coefficients, 0.80 ± 0.17 vs 0.60 ± 0.31, P = 0.005, respectively). In the interscanner comparison, mean relative difference ranged from 1.0% to 53.2%. Conversely, in the intrascanner comparison, mean relative difference ranged from 0.1% to 15.6%. There were no statistical differences for intrascanner and interscanner reproducibility between the different organ foci (all P ≥ 0.24).

Conclusions: While whole-body MR imaging-derived, organ-specific parameters are generally associated with good to excellent reproducibility, smaller differences are obtained when using identical MR scanner models by a single vendor.
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http://dx.doi.org/10.1097/RLI.0000000000000237DOI Listing
April 2016

Prediction of Early Reperfusion From Repeated Arterial Spin Labeling Perfusion Magnetic Resonance Imaging During Intravenous Thrombolysis.

Stroke 2016 Jan 29;47(1):247-50. Epub 2015 Oct 29.

From the Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (S.O., M.G., J.S.-S., M.E.W., A.G., M.G.H., K.S., R.K.); mediri GmbH, Heidelberg, Germany (J.G., M.G.); Institute for Medical Image Computing MEVIS, Fraunhofer MEVIS, Bremen, Germany (M.G.); MR-Imaging and Spectroscopy, Faculty 01 (Physics/Electrical Engineering), University of Bremen, Bremen, Germany (M.G.); and Department of Neurology, Klinikum Kempten, Kempten-Oberallgaeu, Germany (R.K.).

Background And Purpose: There are few in vivo data on the pathophysiology of reperfusion during systemic thrombolysis. We monitored the time course of cerebral perfusion changes in patients during thrombolysis with repeated arterial spin labeling perfusion magnetic resonance imaging.

Methods: Ten patients with proximal arterial occlusion within 4.5 hours after symptom onset were prospectively enrolled. All patients received intravenous thrombolysis during the magnetic resonance imaging examination. Repeated arterial spin labeling perfusion images were acquired during the 60-minute therapy and at follow-up after 24 to 72 hours. Clinical data, magnetic resonance imaging features, and cerebral perfusion changes were analyzed.

Results: Before thrombolysis, arterial spin labeling hypoperfusion and fluid-attenuation inversion recovery vascular hyperintensity in the territory of the occluded arteries were observed in all patients. In 5 patients, extensive arterial transit artifacts (ATA) developed in the hypoperfused area. The ATA corresponded with fluid-attenuation inversion recovery vascular hyperintensities. All 5 patients who developed extensive ATA in the hypoperfused area had complete reperfusion after thrombolysis, whereas the 5 without extensive ATA showed no or only partial reperfusion (P<0.01). The development of ATA preceded the normalization of tissue perfusion.

Conclusions: The development of ATA during thrombolysis is associated with early reperfusion after thrombolysis. arterial spin labeling assessment during intravenous thrombolysis has the potential to guide subsequent therapeutic strategies in patients with acute stroke.
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http://dx.doi.org/10.1161/STROKEAHA.115.011482DOI Listing
January 2016

Ultrahigh-field MPRAGE Magnetic Resonance Angiography at 7.0 T in patients with cerebrovascular disease.

Eur J Radiol 2015 Dec 1;84(12):2613-7. Epub 2015 Oct 1.

Department of Neurology and Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin, Berlin, Germany; Experimental and Clinical Research Center (ECRC), Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.

Objectives: Time-of-flight (TOF) magnetic-resonance-angiography (MRA) identifies vessel pathology in cerebrovascular disease. At 7.0 T, the clinical performance of TOF-MRA is constrained owing to radio frequency power deposition. We studied the diagnostic value of whole-brain MPRAGE-based MRA as an alternative imaging technique in comparison to the clinical standard 3.0 T TOF-MRA.

Methods: Patients with stroke and/or moya-moya disease were included. TOF-MRA was performed at 3.0 T and MPRAGE-MRA at 7.0 T. Two radiologists rated the MRAs independently for overall quality and local arterial segment visualization. The identification of steno-occlusive pathology was reported for each protocol.

Results: In 18 patients (9 females; 6 patients with moya-moya) 7.0 T MPRAGE-MRA provided better overall image quality and better distinction of small structures compared to 3.0 T TOF-MRA. These findings were pronounced in the proximal segments of the anterior cerebral artery (A1), middle cerebral artery (M1, M2), posterior cerebral artery (P1) and the posterior communicating artery. Seven steno-occlusive findings were identified by both imaging protocols.

Conclusions: For clinical studies using ultrahigh field MRI, 7.0 T MPRAGE-MRA provides a suitable alternative to TOF-MRA imaging to identify brain vessel pathology and yields simultaneous structural brain imaging within clinically feasible acquisition times.
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http://dx.doi.org/10.1016/j.ejrad.2015.09.021DOI Listing
December 2015

Measurement of vascular water transport in human subjects using time-resolved pulsed arterial spin labelling.

NMR Biomed 2015 Aug 5;28(8):1059-68. Epub 2015 Jul 5.

Department of Medical Radiation Physics, Lund University, Lund, Sweden.

Most approaches to arterial spin labelling (ASL) data analysis aim to provide a quantitative measure of the cerebral blood flow (CBF). This study, however, focuses on the measurement of the transfer time of blood water through the capillaries to the parenchyma (referred to as the capillary transfer time, CTT) as an alternative parameter to characterise the haemodynamics of the system. The method employed is based on a non-compartmental model, and no measurements need to be added to a common time-resolved ASL experiment. Brownian motion of labelled spins in a potential was described by a one-dimensional general Langevin equation as the starting point, and as a Fokker-Planck differential equation for the averaged distribution of labelled spins at the end point, which takes into account the effects of flow and dispersion of labelled water by the pseudorandom nature of the microvasculature and the transcapillary permeability. Multi-inversion time (multi-TI) ASL data were acquired in 14 healthy subjects on two occasions in a test-retest design, using a pulsed ASL sequence and three-dimensional gradient and spin echo (3D-GRASE) readout. Based on an error analysis to predict the size of a region of interest (ROI) required to obtain reasonably precise parameter estimates, data were analysed in two relatively large ROIs, i.e. the occipital lobe (OC) and the insular cortex (IC). The average values of CTT in OC were 260 ± 60 ms in the first experiment and 270 ± 60 ms in the second experiment. The corresponding IC values were 460 ± 130 ms and 420 ± 139 ms, respectively. Information related to the water transfer time may be important for diagnostics and follow-up of cerebral conditions or diseases characterised by a disrupted blood-brain barrier or disturbed capillary blood flow.
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http://dx.doi.org/10.1002/nbm.3344DOI Listing
August 2015

Whole-Body MR Imaging in the German National Cohort: Rationale, Design, and Technical Background.

Radiology 2015 Oct 19;277(1):206-20. Epub 2015 May 19.

From the German National Cohort (GNC) Consortium, Central Executive Office of the German National Cohort, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen, Germany (F.B.); Department of Clinical Radiology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany (F.B., T.H., M.F.R.); Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany (H.U.K., S.W., C.L.S., M.A.W.); Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany (M.F., S.C.L.); Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany (K.H.G., R.K.); Charité Campus Buch, ECRC Universitätsmedizin Berlin und HELIOS Klinik Berlin-Buch, Klinik für Kardiologie und Nephrologie, Berlin, Germany (J.S.); Berlin Ultrahigh Field Facility (BUFF), Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (T.N.); Epidemiology Research Group, Max-Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany (T.P.); Institute of Neuroscience and Medicine (INM-1), Jülich Research Centre, Jülich, Germany (S.C., K.A.); C. and O. Vogt Institute for Brain Research, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany (K.A.); JARA-BRAIN, Jülich-Aachen Research Alliance, Jülich, Germany (K.A.); Institute of Epidemiology and Social Medicine, University of Muenster, Muenster, Germany (K.B.); Department of Radiology and Neuroradiology, University Medicine Greifswald, Ernst Moritz Arndt University of Greifswald, Greifswald, Germany (R.B., N.H., K.H.); Klinik für Diagnostische und Interventionelle Radiologie und Neuroradiologie, Klinikum Augsburg, Augsburg, Germany (T.K.); Helmholtz Zentrum München-German Research Center for Environmental Health, Munich, Germany (J.L., H.E.W.); Institute of Medical Infor

Purpose: To detail the rationale, design, and future perspective of implementing whole-body magnetic resonance (MR) imaging in the German National Cohort, a large multicentric population-based study.

Materials And Methods: All institutional review boards approved the study, and informed consent is obtained before study enrollment. Participants are enrolled from a random sample of the general population at five dedicated imaging sites among 18 recruitment centers. MR imaging facilities are equipped with identical 3.0-T imager technology and use uniform MR protocols. Imager-specific hardware and software settings remained constant over the study period. On-site and centralized measures of image quality enable monitoring of completeness of the acquisitions and quality of each of the MR sequences. Certified radiologists read all MR imaging studies for presence of incidental findings according to predefined algorithms.

Results: Over a 4-year period, six participants per day are examined at each center, totaling a final imaging cohort of approximately 30 000 participants. The MR imaging protocol is identical for each site and comprises a set of 12 native series to cover neurologic, cardiovascular, thoracoabdominal, and musculoskeletal imaging phenotypes totaling approximately 1 hour of imaging time. A dedicated analysis platform as part of a central imaging core incorporates a thin client-based integrative and modular data handling platform to enable multicentric off-site image reading for incidental findings. Scientific analysis will be pursued on a per-project hypothesis-driven basis.

Conclusion: Population-based whole-body MR imaging as part of the German National Cohort will serve to compile a comprehensive image repository, will provide insight into physiologic variants and subclinical disease burden, and has the potential to enable identification of novel imaging biomarkers of risk.
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http://dx.doi.org/10.1148/radiol.2015142272DOI Listing
October 2015

Multi-vendor reliability of arterial spin labeling perfusion MRI using a near-identical sequence: implications for multi-center studies.

Neuroimage 2015 Jun 24;113:143-52. Epub 2015 Mar 24.

Department of Psychology, Institute of Social Sciences, University of Oslo, Oslo, Norway.

Introduction: A main obstacle that impedes standardized clinical and research applications of arterial spin labeling (ASL), is the substantial differences between the commercial implementations of ASL from major MRI vendors. In this study, we compare a single identical 2D gradient-echo EPI pseudo-continuous ASL (PCASL) sequence implemented on 3T scanners from three vendors (General Electric Healthcare, Philips Healthcare and Siemens Healthcare) within the same center and with the same subjects.

Material And Methods: Fourteen healthy volunteers (50% male, age 26.4±4.7years) were scanned twice on each scanner in an interleaved manner within 3h. Because of differences in gradient and coil specifications, two separate studies were performed with slightly different sequence parameters, with one scanner used across both studies for comparison. Reproducibility was evaluated by means of quantitative cerebral blood flow (CBF) agreement and inter-session variation, both on a region-of-interest (ROI) and voxel level. In addition, a qualitative similarity comparison of the CBF maps was performed by three experienced neuro-radiologists.

Results: There were no CBF differences between vendors in study 1 (p>0.1), but there were CBF differences of 2-19% between vendors in study 2 (p<0.001 in most gray matter ROIs) and 10-22% difference in CBF values obtained with the same vendor between studies (p<0.001 in most gray matter ROIs). The inter-vendor inter-session variation was not significantly larger than the intra-vendor variation in all (p>0.1) but one of the ROIs (p<0.001).

Conclusion: This study demonstrates the possibility to acquire comparable cerebral CBF maps on scanners of different vendors. Small differences in sequence parameters can have a larger effect on the reproducibility of ASL than hardware or software differences between vendors. These results suggest that researchers should strive to employ identical labeling and readout strategies in multi-center ASL studies.
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http://dx.doi.org/10.1016/j.neuroimage.2015.03.043DOI Listing
June 2015

Feasibility of simultaneous whole-brain imaging on an integrated PET-MRI system using an enhanced 2-point Dixon attenuation correction method.

Front Neurosci 2014 5;8:434. Epub 2015 Jan 5.

Lawson Health Research Institute London, ON, Canada ; Medical Biophysics, Western University London, ON, Canada.

Purpose: To evaluate a potential approach for improved attenuation correction (AC) of PET in simultaneous PET and MRI brain imaging, a straightforward approach that adds bone information missing on Dixon AC was explored.

Methods: Bone information derived from individual T1-weighted MRI data using segmentation tools in SPM8, were added to the standard Dixon AC map. Percent relative difference between PET reconstructed with Dixon+bone and with Dixon AC maps were compared across brain regions of 13 oncology patients. The clinical potential of the improved Dixon AC was investigated by comparing relative perfusion (rCBF) measured with arterial spin labeling to relative glucose uptake (rPETdxbone) measured simultaneously with (18)F-flurodexoyglucose in several regions across the brain.

Results: A gradual increase in PET signal from center to the edge of the brain was observed in PET reconstructed with Dixon+bone. A 5-20% reduction in regional PET signals were observed in data corrected with standard Dixon AC maps. These regional underestimations of PET were either reduced or removed when Dixon+bone AC was applied. The mean relative correlation coefficient between rCBF and rPETdxbone was r = 0.53 (p < 0.001). Marked regional variations in rCBF-to-rPET correlation were observed, with the highest associations in the caudate and cingulate and the lowest in limbic structures. All findings were well matched to observations from previous studies conducted with PET data reconstructed with computed tomography derived AC maps.

Conclusion: Adding bone information derived from T1-weighted MRI to Dixon AC maps can improve underestimation of PET activity in hybrid PET-MRI neuroimaging.
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http://dx.doi.org/10.3389/fnins.2014.00434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283546PMC
January 2015

Sodium magnetic resonance imaging using ultra-short echo time sequences with anisotropic resolution and uniform k-space sampling.

Magn Reson Imaging 2015 Apr 16;33(3):319-27. Epub 2014 Dec 16.

Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.

A method for uniform k-space sampling of 3D ultra-short echo time (UTE) techniques with anisotropic resolution in one direction is introduced to increase signal-to-noise ratio (SNR). State-of-the-art acquisition schemes for sodium MRI with radial (projection reconstruction) and twisting (twisted projection imaging (TPI)) trajectories are investigated regarding SNR efficiency, blurring behavior under T2(⁎) decay, and measurement time in case of anisotropic field-of-view and resolution. 3D radial and twisting trajectories are redistributed in k-space for UTE sodium MRI with homogeneous noise distribution and optimal SNR efficiency, if T2(⁎) decay can be neglected. Simulations based on Voronoi tessellations and phantom simulations/measurements were performed to calculate SNR efficiency. Point-spread functions were simulated to demonstrate the influence of T2(⁎) decay on SNR and resolution. Phantom simulations/measurements and in vivo measurements confirm the SNR gain obtained by simulations based on Voronoi cells. An increase in SNR of up to 21% at an anisotropy factor of 10 could be theoretically achieved by TPI with projection adaption compared to the same sequence but without redistribution of projections in k-space. Sodium MRI with anisotropic resolution and uniform k-space sampling is demonstrated by in vivo measurements of human intervertebral disks and heart at 3 T. The SNR gain can be invested in a measurement time reduction of up to 32%, which is important especially for sodium MRI.
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http://dx.doi.org/10.1016/j.mri.2014.12.007DOI Listing
April 2015

3D GRASE pulsed arterial spin labeling at multiple inflow times in patients with long arterial transit times: comparison with dynamic susceptibility-weighted contrast-enhanced MRI at 3 Tesla.

J Cereb Blood Flow Metab 2015 Mar 19;35(3):392-401. Epub 2014 Nov 19.

1] Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin, Berlin, Germany [2] Department of Neurology, Charité-Universtitätsmedizin, Berlin, Germany.

Pulsed arterial spin labeling (PASL) at multiple inflow times (multi-TIs) is advantageous for the measurement of brain perfusion in patients with long arterial transit times (ATTs) as in steno-occlusive disease, because bolus-arrival-time can be measured and blood flow measurements can be corrected accordingly. Owing to its increased signal-to-noise ratio, a combination with a three-dimensional gradient and spin echo (GRASE) readout allows acquiring a sufficient number of multi-TIs within a clinically feasible acquisition time of 5 minutes. We compared this technique with the clinical standard dynamic susceptibility-weighted contrast-enhanced imaging-magnetic resonance imaging in patients with unilateral stenosis >70% of the internal carotid or middle cerebral artery (MCA) at 3 Tesla. We performed qualitative (assessment by three expert raters) and quantitative (region of interest (ROI)/volume of interest (VOI) based) comparisons. In 43 patients, multi-TI PASL-GRASE showed perfusion alterations with moderate accuracy in the qualitative analysis. Quantitatively, moderate correlation coefficients were found for the MCA territory (ROI based: r=0.52, VOI based: r=0.48). In the anterior cerebral artery (ACA) territory, a readout related right-sided susceptibility artifact impaired correlation (ROI based: r=0.29, VOI based: r=0.34). Arterial transit delay artifacts were found only in 12% of patients. In conclusion, multi-TI PASL-GRASE can correct for arterial transit delay in patients with long ATTs. These results are promising for the transfer of ASL to the clinical practice.
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http://dx.doi.org/10.1038/jcbfm.2014.200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348376PMC
March 2015

Assessment of perfusion deficits in ischemic stroke using 3D-GRASE arterial spin labeling magnetic resonance imaging with multiple inflow times.

J Neuroimaging 2014 Sep-Oct;24(5):453-9. Epub 2013 Nov 25.

Background And Purpose: Arterial spin labeling (ASL) MRI provides information on tissue perfusion by consecutive readout of labeled blood captured in arteries or the microvasculature without using contrast agents.

Methods: We used a single-shot 3D acquisition and readout technique for ASL with multiple inflow times (TI) to evaluate hemodynamic compromise and dynamics of arterial blood inflow expressed by the bolus arrival time (BAT). Thirty-six patients with ischemic stroke were examined with a standard multimodal MRI protocol including dynamic susceptibility contrast (DSC) and multi-TI ASL perfusion imaging. Time-to-peak maps were used to classify hemodynamic impairment as either hypo- or hyperperfusion.

Results: Overall there was a good agreement of ASL perfusion maps with DSC perfusion imaging on visual analysis. Correlations were found between ASL-BAT/(DSC-)Mean transit time (MTT) (r = .416; P < .01) and ASL-CBF/MTT (r = -.489; P < .01). Using ASL, BAT in ischemic territory was delayed by 55% (P = .001) in patients with hypoperfusion (n = 28); CBF was reduced by 39% (P<.001). All patients with hyperperfusion (n = 6) had higher CBF on ASL.

Conclusions: The use of ASL with multiple TI allows the contrast-free assessment of hemodynamic impairment in ischemic stroke patients. Quantitative ASL perfusion analysis reliably demonstrates areas of delayed BAT and reduced CBF matching findings of DSC.
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http://dx.doi.org/10.1111/jon.12064DOI Listing
April 2015

Blood tracer kinetics in the arterial tree.

PLoS One 2014 9;9(10):e109230. Epub 2014 Oct 9.

Department of Radiology, Medical Physics, University Medical Center Freiburg, Freiburg, Germany.

Evaluation of blood supply of different organs relies on labeling blood with a suitable tracer. The tracer kinetics is linear: Tracer concentration at an observation site is a linear response to an input somewhere upstream the arterial flow. The corresponding impulse response functions are currently treated empirically without incorporating the relation to the vascular morphology of an organ. In this work we address this relation for the first time. We demonstrate that the form of the response function in the entire arterial tree is reduced to that of individual vessel segments under approximation of good blood mixing at vessel bifurcations. The resulting expression simplifies significantly when the geometric scaling of the vascular tree is taken into account. This suggests a new way to access the vascular morphology in vivo using experimentally determined response functions. However, it is an ill-posed inverse problem as demonstrated by an example using measured arterial spin labeling in large brain arteries. We further analyze transport in individual vessel segments and demonstrate that experimentally accessible tracer concentration in vessel segments depends on the measurement principle. Explicit expressions for the response functions are obtained for the major middle part of the arterial tree in which the blood flow in individual vessel segments can be treated as laminar. When applied to the analysis of regional cerebral blood flow measurements for which the necessary arterial input is evaluated in the carotid arteries, present theory predicts about 20% underestimation, which is in agreement with recent experimental data.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109230PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192126PMC
June 2015

Improving perfusion quantification in arterial spin labeling for delayed arrival times by using optimized acquisition schemes.

Z Med Phys 2015 Sep 11;25(3):221-9. Epub 2014 Aug 11.

Fraunhofer MEVIS-Institute for Medical Image Computing, Bremen, Germany; Faculty of Physics and Electronics, University of Bremen, Germany; mediri GmbH, Heidelberg, Germany.

Objective: The improvement in Arterial Spin Labeling (ASL) perfusion quantification, especially for delayed bolus arrival times (BAT), with an acquisition redistribution scheme mitigating the T1 decay of the label in multi-TI ASL measurements is investigated. A multi inflow time (TI) 3D-GRASE sequence is presented which adapts the distribution of acquisitions accordingly, by keeping the scan time constant.

Material And Methods: The MR sequence increases the number of averages at long TIs and decreases their number at short TIs and thus compensating the T1 decay of the label. The improvement of perfusion quantification is evaluated in simulations as well as in-vivo in healthy volunteers and patients with prolonged BATs due to age or steno-occlusive disease.

Results: The improvement in perfusion quantification depends on BAT. At healthy BATs the differences are small, but become larger for longer BATs typically found in certain diseases. The relative error of perfusion is improved up to 30% at BATs>1500ms in comparison to the standard acquisition scheme.

Conclusion: This adapted acquisition scheme improves the perfusion measurement in comparison to standard multi-TI ASL implementations. It provides relevant benefit in clinical conditions that cause prolonged BATs and is therefore of high clinical relevance for neuroimaging of steno-occlusive diseases.
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http://dx.doi.org/10.1016/j.zemedi.2014.07.003DOI Listing
September 2015