Publications by authors named "Julio Acosta-Cabronero"

56 Publications

Associations of Brain Atrophy and Cerebral Iron Accumulation at MRI with Clinical Severity in Wilson Disease.

Radiology 2021 Mar 23:202846. Epub 2021 Mar 23.

From the Department of Radiology (P.D., A.L.), Department of Neurology and Centre of Clinical Neuroscience (P.D., F.R.) and Fourth Department of Internal Medicine (R.B.), First Faculty of Medicine, Charles University and General University Hospital, Katerinska 30, 120 00, Prague 2, Czech Republic; Tenoke, Cambridge, England (J.A.C.); Department of Cybernetics, Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic (T.S.); and Magnetic Resonance Unit, Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic (M.H., M.D.).

Background Abnormal findings at brain MRI in patients with neurologic Wilson disease (WD) are characterized by signal intensity changes and cerebral atrophy. T2 signal hypointensities and atrophy are largely irreversible with treatment; their relationship with permanent disability has not been systematically investigated. Purpose To investigate associations of regional brain atrophy and iron accumulation at MRI with clinical severity in participants with neurologic WD who are undergoing long-term anti-copper treatment. Materials and Methods Participants with WD and controls were compared in a prospective study performed from 2015 to 2019. MRI at 3.0 T included three-dimensional T1-weighted and six-echo multigradient-echo pulse sequences for morphometry and quantitative susceptibility mapping, respectively. Neurologic severity was assessed with the Unified WD Rating Scale (UWDRS). Automated multi-atlas segmentation pipeline with dual contrast (susceptibility and T1) was used for the calculation of volumes and mean susceptibilities in deep gray matter nuclei. Additionally, whole-brain analysis using deformation and surface-based morphometry was performed. Least absolute shrinkage and selection operator regression was used to assess the association of regional volumes and susceptibilities with the UWDRS score. Results Twenty-nine participants with WD (mean age, 47 years ± 9 [standard deviation]; 15 women) and 26 controls (mean age, 45 years ± 12; 14 women) were evaluated. Whole-brain analysis demonstrated atrophy of the deep gray matter nuclei, brainstem, internal capsule, motor cortex and corticospinal pathway, and visual cortex and optic radiation in participants with WD ( < .05 at voxel level, corrected for family-wise error). The UWDRS score was negatively correlated with volumes of putamen ( = -0.63, < .001), red nucleus ( = -0.58, = .001), globus pallidus ( = -0.53, = .003), and substantia nigra ( = -0.50, = .006) but not with susceptibilities. Only the putaminal volume was identified as a stable factor associated with the UWDRS score ( = 0.38, < .001) using least absolute shrinkage and selection operator regression. Conclusion Individuals with Wilson disease (WD) had widespread brain atrophy most pronounced in the central structures. The putaminal volume was associated with the Unified WD Rating Scale score and can be used as a surrogate imaging marker of clinical severity. © RSNA, 2021 See also the editorial by Du and Bydder in this issue.
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http://dx.doi.org/10.1148/radiol.2021202846DOI Listing
March 2021

Regional brain iron and gene expression provide insights into neurodegeneration in Parkinson's disease.

Brain 2021 Mar 11. Epub 2021 Mar 11.

Dementia Research Centre, UCL Institute of Neurology, London, UK.

The mechanisms which are responsible for the selective vulnerability of specific neuronal populations in Parkinson's disease are poorly understood. Oxidative stress secondary to brain iron accumulation is one postulated mechanism. We measured iron deposition in 180 cortical regions in 96 patients with Parkinson's disease and 35 controls using quantitative susceptibility mapping. We estimated the expression of 15 745 genes in the same regions using transcriptomic data from the Allen Human Brain Atlas. Using partial least squares regression, we then identified the profile of gene transcription in the healthy brain that underlies increased cortical iron in patients with Parkinson's disease relative to controls. With gene ontological tools, we investigated the biological processes and cell types associated with this transcriptomic profile. We identified the sets of genes whose spatial expression profiles in control brains correlated significantly with the spatial pattern of cortical iron deposition in Parkinson's disease. Gene ontological analyses revealed that these genes were enriched for biological processes relating to heavy metal detoxification, synaptic function and nervous system development and were predominantly expressed in astrocytes and glutamatergic neurons. We also show that genes found to be differentially expressed in Parkinson's disease play a role in explaining the pattern of cortical expression we identified. Our findings provide mechanistic insights into regional selective vulnerabilities in Parkinson's disease, particularly into processes involving iron accumulation.
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http://dx.doi.org/10.1093/brain/awab084DOI Listing
March 2021

Detection of Cerebral Microbleeds With Venous Connection at 7 Tesla MRI.

Neurology 2021 Mar 2. Epub 2021 Mar 2.

Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany.

Objective: Cerebral microbleeds (MBs) are a common finding in cerebral small vessel disease (CSVD) and Alzheimer's disease patients as well as in healthy elderly people, but their pathophysiology remains unclear. To investigate a possible role of veins in the development of MBs, we performed an exploratory study, assessing in vivo presence of MBs with a direct connection to a vein.

Methods: 7 Tesla (7 T) MRI was conducted and MBs were counted on Quantitative Susceptibility Mapping (QSM). A submillimeter resolution QSM-based venogram allowed identification of MBs with a direct spatial connection to a vein.

Results: 51 subjects (mean age [SD] 70.5[8.6] years, 37% females) participated in the study: 20 were patients with CSVD (cerebral amyloid angiopathy (CAA) with strictly lobar MBs (n=8), hypertensive arteriopathy (HA) with strictly deep MBs (n=5), and mixed lobar and deep MBs (n=7), 72.4 [6.1] years, 30% females) and 31 were healthy controls (69.4 [9.9] years, 42% females). In our cohort, we counted a total of 96 MBs with a venous connection, representing 14% of all detected MBs on 7T QSM. Most venous MBs (86%, n = 83) were observed in lobar locations and all of these were cortical. CAA subjects showed the highest ratio of venous to total MBs (19%) (HA=9%, mixed=18%, controls=5%) CONCLUSIONS: Our findings establish a link between cerebral MBs and the venous vasculature, pointing towards a possible contribution of veins to CSVD in general and to CAA in particular. Pathological studies are needed to confirm our observations.
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http://dx.doi.org/10.1212/WNL.0000000000011790DOI Listing
March 2021

Comparison of parameter optimization methods for quantitative susceptibility mapping.

Magn Reson Med 2021 01 1;85(1):480-494. Epub 2020 Aug 1.

Department of Electrical Engineering, Pontificia Universidad Catolica de Chile, Santiago, Chile.

Purpose: Quantitative Susceptibility Mapping (QSM) is usually performed by minimizing a functional with data fidelity and regularization terms. A weighting parameter controls the balance between these terms. There is a need for techniques to find the proper balance that avoids artifact propagation and loss of details. Finding the point of maximum curvature in the L-curve is a popular choice, although it is slow, often unreliable when using variational penalties, and has a tendency to yield overregularized results.

Methods: We propose 2 alternative approaches to control the balance between the data fidelity and regularization terms: 1) searching for an inflection point in the log-log domain of the L-curve, and 2) comparing frequency components of QSM reconstructions. We compare these methods against the conventional L-curve and U-curve approaches.

Results: Our methods achieve predicted parameters that are better correlated with RMS error, high-frequency error norm, and structural similarity metric-based parameter optimizations than those obtained with traditional methods. The inflection point yields less overregularization and lower errors than traditional alternatives. The frequency analysis yields more visually appealing results, although with larger RMS error.

Conclusion: Our methods provide a robust parameter optimization framework for variational penalties in QSM reconstruction. The L-curve-based zero-curvature search produced almost optimal results for typical QSM acquisition settings. The frequency analysis method may use a 1.5 to 2.0 correction factor to apply it as a stand-alone method for a wider range of signal-to-noise-ratio settings. This approach may also benefit from fast search algorithms such as the binary search to speed up the process.
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http://dx.doi.org/10.1002/mrm.28435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722179PMC
January 2021

Relationship between cortical iron and tau aggregation in Alzheimer's disease.

Brain 2020 05;143(5):1341-1349

Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.

A growing body of evidence suggests that the dysregulation of neuronal iron may play a critical role in Alzheimer's disease. Recent MRI studies have established a relationship between iron accumulation and amyloid-β aggregation. The present study provides further insight demonstrating a relationship between iron and tau accumulation using magnetic resonance-based quantitative susceptibility mapping and tau-PET in n = 236 subjects with amyloid-β pathology (from the Swedish BioFINDER-2 study). Both voxel-wise and regional analyses showed a consistent association between differences in bulk magnetic susceptibility, which can be primarily ascribed to an increase in iron content, and tau-PET signal in regions known to be affected in Alzheimer's disease. Subsequent analyses revealed that quantitative susceptibility specifically mediates the relationship between tau-PET and cortical atrophy measures, thus suggesting a modulatory effect of iron burden on the disease process. We also found evidence suggesting the relationship between quantitative susceptibility and tau-PET is stronger in younger participants (age ≤ 65). Together, these results provide in vivo evidence of an association between iron deposition and both tau aggregation and neurodegeneration, which help advance our understanding of the role of iron dysregulation in the Alzheimer's disease aetiology.
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http://dx.doi.org/10.1093/brain/awaa089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241946PMC
May 2020

Corrigendum to in vivo visualization of age-related differences in the locus coeruleus Neurobiology of Aging Volume 74, February 2019, Pages 101-111.

Neurobiol Aging 2020 07 18;91:172-174. Epub 2020 Apr 18.

Wellcome Centre for Human Neuroimaging, UCL Institute of Neurology, University College London, London, UK; Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany; Institute of Cognitive Neuroscience, University College London, London, UK.

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http://dx.doi.org/10.1016/j.neurobiolaging.2020.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242897PMC
July 2020

The 2016 QSM Challenge: Lessons learned and considerations for a future challenge design.

Magn Reson Med 2020 09 21;84(3):1624-1637. Epub 2020 Feb 21.

Department of Neurology, Medical University of Graz, Graz, Austria.

Purpose: The 4th International Workshop on MRI Phase Contrast and QSM (2016, Graz, Austria) hosted the first QSM Challenge. A single-orientation gradient recalled echo acquisition was provided, along with COSMOS and the χ STI component as ground truths. The submitted solutions differed more than expected depending on the error metric used for optimization and were generally over-regularized. This raised (unanswered) questions about the ground truths and the metrics utilized.

Methods: We investigated the influence of background field remnants by applying additional filters. We also estimated the anisotropic contributions from the STI tensor to the apparent susceptibility to amend the χ ground truth and to investigate the impact on the reconstructions. Lastly, we used forward simulations from the COSMOS reconstruction to investigate the impact noise had on the metric scores.

Results: Reconstructions compared against the amended STI ground truth returned lower errors. We show that the background field remnants had a minor impact in the errors. In the absence of inconsistencies, all metrics converged to the same regularization weights, whereas structural similarity index metric was more insensitive to such inconsistencies.

Conclusion: There was a mismatch between the provided data and the ground truths due to the presence of unaccounted anisotropic susceptibility contributions and noise. Given the lack of reliable ground truths when using in vivo acquisitions, simulations are suggested for future QSM Challenges.
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http://dx.doi.org/10.1002/mrm.28185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526054PMC
September 2020

Brain iron deposition is linked with cognitive severity in Parkinson's disease.

J Neurol Neurosurg Psychiatry 2020 04 20;91(4):418-425. Epub 2020 Feb 20.

Dementia Research Centre, UCL Institute of Neurology, London, UK

Background: Dementia is common in Parkinson's disease (PD) but measures that track cognitive change in PD are lacking. Brain tissue iron accumulates with age and co-localises with pathological proteins linked to PD dementia such as amyloid. We used quantitative susceptibility mapping (QSM) to detect changes related to cognitive change in PD.

Methods: We assessed 100 patients with early-stage to mid-stage PD, and 37 age-matched controls using the Montreal Cognitive Assessment (MoCA), a validated clinical algorithm for risk of cognitive decline in PD, measures of visuoperceptual function and the Movement Disorders Society Unified Parkinson's Disease Rating Scale part 3 (UPDRS-III). We investigated the association between these measures and QSM, an MRI technique sensitive to brain tissue iron content.

Results: We found QSM increases (consistent with higher brain tissue iron content) in PD compared with controls in prefrontal cortex and putamen (p<0.05 corrected for multiple comparisons). Whole brain regression analyses within the PD group identified QSM increases covarying: (1) with lower MoCA scores in the hippocampus and thalamus, (2) with poorer visual function and with higher dementia risk scores in parietal, frontal and medial occipital cortices, (3) with higher UPDRS-III scores in the putamen (all p<0.05 corrected for multiple comparisons). In contrast, atrophy, measured using voxel-based morphometry, showed no differences between groups, or in association with clinical measures.

Conclusions: Brain tissue iron, measured using QSM, can track cognitive involvement in PD. This may be useful to detect signs of early cognitive change to stratify groups for clinical trials and monitor disease progression.
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http://dx.doi.org/10.1136/jnnp-2019-322042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147185PMC
April 2020

Prominent White Matter Involvement in Multiple System Atrophy of Cerebellar Type.

Mov Disord 2020 05 29;35(5):816-824. Epub 2020 Jan 29.

Clinical Research, German Center for Neurodegenerative Diseases, Bonn, Germany.

Background: Sporadic degenerative ataxia patients fall into 2 major groups: multiple system atrophy with predominant cerebellar ataxia (MSA-C) and sporadic adult-onset ataxia (SAOA). Both groups have cerebellar volume loss, but little is known about the differential involvement of gray and white matter in MSA-C when compared with SAOA.

Objectives: The objective of this study was to identify structural differences of brain gray and white matter between both patient groups.

Methods: We used magnetic resonance imaging to acquire T1-weighted images and diffusion tensor images from 12 MSA-C patients, 31 SAOA patients, and 55 healthy controls. Magnetic resonance imaging data were analyzed with voxel-based-morphometry, tract-based spatial statistics, and tractography-based regional diffusion tensor images analysis.

Results: Whole-brain and cerebellar-focused voxel-based-morphometry analysis showed gray matter volume loss in both patient groups when compared with healthy controls, specifically in the cerebellar areas subserving sensorimotor functions. When compared with controls, the SAOA and MSA-C patients showed white matter loss in the cerebellum, whereas brainstem white matter was reduced only in the MSA-C patients. The tract-based spatial statistics revealed reduced fractional anisotropy within the pons and cerebellum in the MSA-C patients both in comparison with the SAOA patients and healthy controls. In addition, tractography-based regional analysis showed reduced fractional anisotropy along the corticospinal tracts in MSA-C, but not SAOA.

Conclusion: Although in our cohort extent and distribution of gray and white matter loss were similar between the MSA-C and SAOA patients, magnetic resonance imaging data showed prominent microstructural white matter involvement in the MSA-C patients that was not present in the SAOA patients. Our findings highlight the significance of microstructural white matter changes in the differentiation between both conditions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27987DOI Listing
May 2020

A multi-contrast MRI approach to thalamus segmentation.

Hum Brain Mapp 2020 06 20;41(8):2104-2120. Epub 2020 Jan 20.

Wellcome Centre for Human Neuroimaging, UCL Institute of Neurology, University College London, London, UK.

Thalamic alterations occur in many neurological disorders including Alzheimer's disease, Parkinson's disease and multiple sclerosis. Routine interventions to improve symptom severity in movement disorders, for example, often consist of surgery or deep brain stimulation to diencephalic nuclei. Therefore, accurate delineation of grey matter thalamic subregions is of the upmost clinical importance. MRI is highly appropriate for structural segmentation as it provides different views of the anatomy from a single scanning session. Though with several contrasts potentially available, it is also of increasing importance to develop new image segmentation techniques that can operate multi-spectrally. We hereby propose a new segmentation method for use with multi-modality data, which we evaluated for automated segmentation of major thalamic subnuclear groups using T -weighted, -weighted and quantitative susceptibility mapping (QSM) information. The proposed method consists of four steps: Highly iterative image co-registration, manual segmentation on the average training-data template, supervised learning for pattern recognition, and a final convex optimisation step imposing further spatial constraints to refine the solution. This led to solutions in greater agreement with manual segmentation than the standard Morel atlas based approach. Furthermore, we show that the multi-contrast approach boosts segmentation performances. We then investigated whether prior knowledge using the training-template contours could further improve convex segmentation accuracy and robustness, which led to highly precise multi-contrast segmentations in single subjects. This approach can be extended to most 3D imaging data types and any region of interest discernible in single scans or multi-subject templates.
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http://dx.doi.org/10.1002/hbm.24933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267924PMC
June 2020

Multiparametric Quantitative Brain MRI in Neurological and Hepatic Forms of Wilson's Disease.

J Magn Reson Imaging 2020 06 11;51(6):1829-1835. Epub 2019 Nov 11.

MR Unit, Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Background: In Wilson's disease (WD), demyelination, rarefaction, gliosis, and iron accumulation in the deep gray matter cause opposing effects on T -weighted MR signal. However, the degree and interplay of these changes in chronically treated WD patients has not been quantitatively studied.

Purpose: To compare differences in brain multiparametric mapping between controls and chronically treated WD patients with neurological (neuro-WD) and hepatic (hep-WD) forms to infer the nature of residual WD neuropathology.

Study Type: Cross-sectional.

Population/subjects: Thirty-eight WD patients (28 neuro-WD, 10 hep-WD); 26 healthy controls.

Field Strength/sequence: 3.0T: susceptibility, T *, T , T relaxometry; 1.5T: T , T relaxometry.

Assessment: The following 3D regions of interest (ROIs) were manually segmented: globus pallidus, putamen, caudate nucleus, and thalamus. Mean bulk magnetic susceptibility, T *, T , and T relaxation times were calculated for each ROI.

Statistical Tests: The effect of group (neuro-WD, hep-WD, controls) and age was assessed using a generalized least squares model with different variance for each ROI and quantitative parameter. A general linear hypothesis test with Tukey adjustment was used for post-hoc between-group analysis; P < 0.05 was considered significant.

Results: Susceptibility values were higher in all ROIs in neuro-WD compared to controls and hep-WD (P < 0.001). In basal ganglia, lower T and T * were found in neuro-WD compared to controls (P < 0.01) and hep-WD (P < 0.05) at 3.0T. Much smaller intergroup differences for T in basal ganglia were observed at 1.5T compared to 3.0T. In the thalamus, increased susceptibility in neuro-WD was accompanied by increased T at both field strengths (P < 0.001 to both groups), and an increased T at 1.5T only (P < 0.001 to both groups).

Data Conclusion: We observed significant residual brain MRI abnormalities in neuro-WD but not in hep-WD patients on chronic anticopper treatment. Patterns of changes were suggestive of iron accumulation in the basal ganglia and demyelination in the thalamus; 3.0T was more sensitive for detection of the former and 1.5T of the latter abnormality.

Level Of Evidence: 2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1829-1835.
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http://dx.doi.org/10.1002/jmri.26984DOI Listing
June 2020

Diffusion Tensor MRI to Distinguish Progressive Supranuclear Palsy from α-Synucleinopathies.

Radiology 2019 12 15;293(3):646-653. Epub 2019 Oct 15.

From the Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Sölvegatan 19, 22100 Lund, Sweden (N.S., S.H., D.v.W., O.H.); Penn Frontotemporal Degeneration Center, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa (N.S., D.J.I., M.G., C.T.M.); Memory Clinic, Skåne University Hospital, Malmö, Sweden (S.H., O.H.); Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa (D.J.I., E.B.L., J.Q.T.); Department of Diagnostic Radiology, Lund University, Lund, Sweden (T.R., D.v.W., M.N.); Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, University College London, London, England (J.A.C.); Parkinson's Disease and Movement Disorders Center, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa (A.F.D., M.A.S.); Alzheimer's Disease Core Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa (E.B.L., J.Q.T.); and Queensland Brain Institute, University of Queensland and Mater Misericordiae, Brisbane, Queensland, Australia (P.J.N.).

Background The differential diagnosis of progressive supranuclear palsy (PSP) and Lewy body disorders, which include Parkinson disease and dementia with Lewy bodies, is often challenging due to the overlapping symptoms. Purpose To develop a diagnostic tool based on diffusion tensor imaging (DTI) to distinguish between PSP and Lewy body disorders at the individual-subject level. Materials and Methods In this retrospective study, skeletonized DTI metrics were extracted from two independent data sets: the discovery cohort from the Swedish BioFINDER study and the validation cohort from the Penn Frontotemporal Degeneration Center (data collected between 2010 and 2018). Based on previous neuroimaging studies and neuropathologic evidence, a combination of regions hypothesized to be sensitive to pathologic features of PSP were identified (ie, the superior cerebellar peduncle and frontal white matter) and fractional anisotropy (FA) was used to compute an FA score for each individual. Classification performances were assessed by using logistic regression and receiver operating characteristic analysis. Results In the discovery cohort, 16 patients with PSP (mean age ± standard deviation, 73 years ± 5; eight women, eight men), 34 patients with Lewy body disorders (mean age, 71 years ± 6; 14 women, 20 men), and 44 healthy control participants (mean age, 66 years ± 8; 26 women, 18 men) were evaluated. The FA score distinguished between clinical PSP and Lewy body disorders with an area under the curve of 0.97 ± 0.04, a specificity of 91% (31 of 34), and a sensitivity of 94% (15 of 16). In the validation cohort 34 patients with PSP (69 years ± 7; 22 women, 12 men), 25 patients with Lewy body disorders (70 years ± 7; nine women, 16 men), and 32 healthy control participants (64 years ± 7; 22 women, 10 men) were evaluated. The accuracy of the FA score was confirmed (area under the curve, 0.96 ± 0.04; specificity, 96% [24 of 25]; and sensitivity, 85% [29 of 34]). Conclusion These cross-validated findings lay the foundation for a clinical test to distinguish progressive supranuclear palsy from Lewy body disorders. © RSNA, 2019 See also the editorial by Shah in this issue.
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http://dx.doi.org/10.1148/radiol.2019190406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889922PMC
December 2019

Brain iron and metabolic abnormalities in C19orf12 mutation carriers: A 7.0 tesla MRI study in mitochondrial membrane protein-associated neurodegeneration.

Mov Disord 2020 01 13;35(1):142-150. Epub 2019 Sep 13.

Neurology Department, Ludwig Maximilians-University of Munich, Germany.

Background: Mitochondrial membrane protein-associated neurodegeneration is an autosomal-recessive disorder caused by C19orf12 mutations and characterized by iron deposits in the basal ganglia.

Objectives: The aim of this study was to quantify iron concentrations in deep gray matter structures using quantitative susceptibility mapping MRI and to characterize metabolic abnormalities in the pyramidal pathway using H MR spectroscopy in clinically manifesting membrane protein-associated neurodegeneration patients and asymptomatic C19orf12 gene mutation heterozygous carriers.

Methods: We present data of 4 clinically affected membrane protein-associated neurodegeneration patients (mean age: 21.0 ± 2.9 years) and 9 heterozygous gene mutation carriers (mean age: 50.4 ± 9.8 years), compared to age-matched healthy controls. MRI assessments were performed on a 7.0 Tesla whole-body system, consisting of whole-brain gradient-echo scans and short echo time, single-volume MR spectroscopy in the white matter of the precentral/postcentral gyrus. Quantitative susceptibility mapping, a surrogate marker for iron concentration, was performed using a state-of-the-art multiscale dipole inversion approach with focus on the globus pallidus, thalamus, putamen, caudate nucleus, and SN.

Results And Conclusion: In membrane protein-associated neurodegeneration patients, magnetic susceptibilities were 2 to 3 times higher in the globus pallidus (P = 0.02) and SN (P = 0.02) compared to controls. In addition, significantly higher magnetic susceptibility was observed in the caudate nucleus (P = 0.02). Non-manifesting heterozygous mutation carriers exhibited significantly increased magnetic susceptibility (relative to controls) in the putamen (P = 0.003) and caudate nucleus (P = 0.001), which may be an endophenotypic marker of genetic heterozygosity. MR spectroscopy revealed significantly increased levels of glutamate, taurine, and the combined concentration of glutamate and glutamine in membrane protein-associated neurodegeneration, which may be a correlate of corticospinal pathway dysfunction frequently observed in membrane protein-associated neurodegeneration patients. © 2019 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27827DOI Listing
January 2020

European Ultrahigh-Field Imaging Network for Neurodegenerative Diseases (EUFIND).

Alzheimers Dement (Amst) 2019 Dec 31;11:538-549. Epub 2019 Jul 31.

German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Magdeburg, Germany.

Introduction: The goal of European Ultrahigh-Field Imaging Network in Neurodegenerative Diseases (EUFIND) is to identify opportunities and challenges of 7 Tesla (7T) MRI for clinical and research applications in neurodegeneration. EUFIND comprises 22 European and one US site, including over 50 MRI and dementia experts as well as neuroscientists.

Methods: EUFIND combined consensus workshops and data sharing for multisite analysis, focusing on 7 core topics: clinical applications/clinical research, highest resolution anatomy, functional imaging, vascular systems/vascular pathology, iron mapping and neuropathology detection, spectroscopy, and quality assurance. Across these topics, EUFIND considered standard operating procedures, safety, and multivendor harmonization.

Results: The clinical and research opportunities and challenges of 7T MRI in each subtopic are set out as a roadmap. Specific MRI sequences for each subtopic were implemented in a pilot study presented in this report. Results show that a large multisite 7T imaging network with highly advanced and harmonized imaging sequences is feasible and may enable future multicentre ultrahigh-field MRI studies and clinical trials.

Discussion: The EUFIND network can be a major driver for advancing clinical neuroimaging research using 7T and for identifying use-cases for clinical applications in neurodegeneration.
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http://dx.doi.org/10.1016/j.dadm.2019.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675944PMC
December 2019

Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases.

Brain 2019 09;142(9):2558-2571

Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.

Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now provide an opportunity to quantify structural features of the locus coeruleus in vivo during disease progression. In combination with neuropathological biomarkers, in vivo locus coeruleus imaging could help to understand the contribution of locus coeruleus neurodegeneration to clinical and pathological manifestations in Alzheimer's disease, atypical neurodegenerative dementias and Parkinson's disease. Moreover, as the functional sensitivity of the noradrenergic system is likely to change with disease progression, in vivo measures of locus coeruleus integrity could provide new pathophysiological insights into cognitive and behavioural symptoms. Locus coeruleus imaging also holds the promise to stratify patients into clinical trials according to noradrenergic dysfunction. In this article, we present a consensus on how non-invasive in vivo assessment of locus coeruleus integrity can be used for clinical research in neurodegenerative diseases. We outline the next steps for in vivo, post-mortem and clinical studies that can lay the groundwork to evaluate the potential of locus coeruleus imaging as a biomarker for neurodegenerative diseases.
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http://dx.doi.org/10.1093/brain/awz193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736046PMC
September 2019

Robust 3D Bloch-Siegert based mapping using multi-echo general linear modeling.

Magn Reson Med 2019 12 18;82(6):2003-2015. Epub 2019 Jul 18.

Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.

Purpose: Quantitative MRI applications, such as mapping the T time of tissue, puts high demands on the accuracy and precision of transmit field ( ) estimation. A candidate approach to satisfy these requirements exploits the difference in phase induced by the Bloch-Siegert frequency shift (BSS) of 2 acquisitions with opposite off-resonance frequency radiofrequency pulses. Interleaving these radiofrequency pulses ensures robustness to motion and scanner drifts; however, here we demonstrate that doing so also introduces a bias in the estimates.

Theory And Methods: It is shown here by means of simulation and experiments that the amplitude of the error depends on MR pulse sequence parameters, such as repetition time and radiofrequency spoiling increment, but more problematically, on the intrinsic properties, T and T , of the investigated tissue. To solve these problems, a new approach to BSS-based estimation that uses a multi-echo acquisition and a general linear model to estimate the correct BSS-induced phase is presented.

Results: In line with simulations, phantom and in vivo experiments confirmed that the general linear model-based method removed the dependency on tissue properties and pulse sequence settings.

Conclusion: The general linear model-based method is recommended as a more accurate approach to BSS-based mapping.
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http://dx.doi.org/10.1002/mrm.27851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771691PMC
December 2019

The choice of embedding media affects image quality, tissue R , and susceptibility behaviors in post-mortem brain MR microscopy at 7.0T.

Magn Reson Med 2019 04 2;81(4):2688-2701. Epub 2018 Dec 2.

NeuroCure Clinical Research Center, Charité-Universitaetsmedizin, Berlin, Germany.

Purpose: The quality and precision of post-mortem MRI microscopy may vary depending on the embedding medium used. To investigate this, our study evaluated the impact of 5 widely used media on: (1) image quality, (2) contrast of high spatial resolution gradient-echo (T and T -weighted) MR images, (3) effective transverse relaxation rate (R ), and (4) quantitative susceptibility measurements (QSM) of post-mortem brain specimens.

Methods: Five formaldehyde-fixed brain slices were scanned using 7.0T MRI in: (1) formaldehyde solution (formalin), (2) phosphate-buffered saline (PBS), (3) deuterium oxide (D O), (4) perfluoropolyether (Galden), and (5) agarose gel. SNR and contrast-to-noise ratii (SNR/CNR) were calculated for cortex/white matter (WM) and basal ganglia/WM regions. In addition, median R and QSM values were extracted from caudate nucleus, putamen, globus pallidus, WM, and cortical regions.

Results: PBS, Galden, and agarose returned higher SNR/CNR compared to formalin and D O. Formalin fixation, and its use as embedding medium for scanning, increased tissue R . Imaging with agarose, D O, and Galden returned lower R values than PBS (and formalin). No major QSM offsets were observed, although spatial variance was increased (with respect to R behaviors) for formalin and agarose.

Conclusions: Embedding media affect gradient-echo image quality, R , and QSM in differing ways. In this study, PBS embedding was identified as the most stable experimental setup, although by a small margin. Agarose and Galden were preferred to formalin or D O embedding. Formalin significantly increased R causing noisier data and increased QSM variance.
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http://dx.doi.org/10.1002/mrm.27595DOI Listing
April 2019

In vivo visualization of age-related differences in the locus coeruleus.

Neurobiol Aging 2019 02 20;74:101-111. Epub 2018 Oct 20.

Wellcome Centre for Human Neuroimaging, UCL Institute of Neurology, University College London, London, UK; Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany; Institute of Cognitive Neuroscience, University College London, London, UK.

The locus coeruleus (LC), the major origin of noradrenergic modulation of the central nervous system, may play an important role in neuropsychiatric disorders including Parkinson's disease and Alzheimer's disease. The pattern of age-related change of the LC across the life span is unclear. We obtained normalized, mean LC signal intensity values, that is, contrast ratios (CRs), from magnetization transfer-weighted images to investigate the relationship between LC CR and age in cognitively normal healthy adults (N = 605, age range 18-88 years). Study participants were part of the Cambridge Centre for Ageing and Neuroscience-an open-access, population-based data set. We found a quadratic relationship between LC CR and age, the peak occurring around 60 years, with no differences between males and females. Subregional analyses revealed that age-related decline in LC CR was confined to the rostral portion of the LC. Older adults showed greater variance in overall LC CR than younger adults, and the functional and clinical implications of these observed age-related differences require further investigation. Visualization of the LC in this study may inform how future scanning parameters can be optimized, and provides insight into how LC integrity changes across the life span.
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http://dx.doi.org/10.1016/j.neurobiolaging.2018.10.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338679PMC
February 2019

Prospective motion correction improves high-resolution quantitative susceptibility mapping at 7T.

Magn Reson Med 2019 03 9;81(3):1605-1619. Epub 2018 Oct 9.

Department of Biomedical Magnetic Resonance, Institute for Physics, Otto-von-Guericke-University, Magdeburg, Germany.

Purpose: Recent literature has shown the potential of high-resolution quantitative susceptibility mapping (QSM) with ultra-high field MRI for imaging the anatomy, the vasculature, and investigating their magnetostatic properties. Higher spatial resolutions, however, translate to longer scans resulting, therefore, in higher vulnerability to, and likelihood of, subject movement. We propose a gradient-recalled echo sequence with prospective motion correction (PMC) to address such limitation.

Methods: Data from 4 subjects were acquired at 7T. The effect of small and large motion on QSM with and without PMC was assessed qualitatively and quantitatively. Full brain QSM and QSM-based venograms with up to 0.33 mm isotropic voxel size were reconstructed.

Results: With PMC, motion artifacts in QSM and QSM-based venograms were largely eliminated, enabling-in both large- and small-amplitude motion regimes-accurate depiction of the cortex, vasculature, and other small anatomical structures that are often blurred as a result of head movement or indiscernible at lower image resolutions. Quantitative analyses demonstrated that uncorrected motion could bias regional susceptibility distributions, a trend that was greatly reduced with PMC.

Conclusion: Qualitatively, PMC prevented image degradation because of motion artifacts, providing highly detailed QSM images and venograms. Quantitatively, PMC increased the reproducibility of susceptibility measures.
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http://dx.doi.org/10.1002/mrm.27509DOI Listing
March 2019

Weak-harmonic regularization for quantitative susceptibility mapping.

Magn Reson Med 2019 02 28;81(2):1399-1411. Epub 2018 Sep 28.

Wellcome Centre for Human Neuroimaging, UCL Institute of Neurology, University College London, London, United Kingdom.

Purpose: Background-field removal is a crucial preprocessing step for quantitative susceptibility mapping (QSM). Remnants from this step often contaminate the estimated local field, which in turn leads to erroneous tissue-susceptibility reconstructions. The present work aimed to mitigate this undesirable behavior with the development of a new approach that simultaneously decouples background contributions and local susceptibility sources on QSM inversion.

Methods: Input phase data for QSM can be seen as a composite scalar field of local effects and residual background components. We developed a new weak-harmonic regularizer to constrain the latter and to separate the 2 components. The resulting optimization problem was solved with the alternating directions of multipliers method framework to achieve fast convergence. In addition, for convenience, a new alternating directions of multipliers method-based preconditioned nonlinear projection onto dipole fields solver was developed to enable initializations with wrapped-phase distributions. Weak-harmonic QSM, with and without nonlinear projection onto dipole fields preconditioning, was compared with the original (alternating directions of multipliers method-based) total variation QSM algorithm in phantom and in vivo experiments.

Results: Weak-harmonic QSM returned improved reconstructions regardless of the method used for background-field removal, although the proposed nonlinear projection onto dipole fields method often obtained better results. Streaking and shadowing artifacts were substantially suppressed, and residual background components were effectively removed.

Conclusion: Weak-harmonic QSM with field preconditioning is a robust dipole inversion technique and has the potential to be extended as a single-step formulation for initialization with uncombined multi-echo data.
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http://dx.doi.org/10.1002/mrm.27483DOI Listing
February 2019

Significance of CSF NfL and tau in ALS.

J Neurol 2018 Nov 5;265(11):2633-2645. Epub 2018 Sep 5.

Department of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120, Magdeburg, Germany.

Cerebrospinal fluid (CSF) neurofilament light chain (NfL) has emerged as putative diagnostic biomarker in amyotrophic lateral sclerosis (ALS), but it remains a matter of debate, whether CSF total tau (ttau), tau phosphorylated at threonine 181 (ptau) and the ptau/ttau ratio could serve as diagnostic biomarker in ALS as well. Moreover, the relationship between CSF NfL and tau measures to further axonal and (neuro)degeneration markers still needs to be elucidated. Our analysis included 89 ALS patients [median (range) age 63 (33-83) years, 61% male, disease duration 10 (0.2-190) months] and 33 age- and sex-matched disease controls [60 (32-76), 49%]. NfL was higher and the ptau/ttau ratio was lower in ALS compared to controls [8343 (1795-35,945) pg/ml vs. 1193 (612-2616), H(1) = 70.8, p < 0.001; mean (SD) 0.17 (0.04) vs. 0.2 (0.03), F(1) = 14.3, p < 0.001], as well as in upper motor neuron dominant (UMND, n = 10) compared to classic (n = 46) or lower motor neuron dominant ALS [n = 31; for NfL: 16,076 (7447-35,945) vs. 8205 (2651-35,138) vs. 8057 (1795-34,951)], Z ≥ 2.5, p ≤ 0.01; for the ptau/ttau ratio: [0.13 (0.04) vs. 0.17 (0.04) vs. 0.18 (0.03), p ≤ 0.02]. In ALS, NfL and the ptau/ttau ratio were related to corticospinal tract (CST) fractional anisotropy (FA) and radial diffusivity (ROI-based approach and whole-brain voxelwise analysis). Factor analysis of mixed data revealed a co-variance pattern between NfL (factor load - 0.6), the ptau/ttau ratio (0.7), CST FA (0.8) and UMND ALS phenotype (- 2.8). NfL did not relate to any further neuroaxonal injury marker (brain volumes, precentral gyrus thickness, peripheral motor amplitudes, sonographic cross-sectional nerve area), but a lower ptau/ttau ratio was associated with whole-brain gray matter atrophy and widespread white matter integrity loss. Higher NfL baseline levels were associated with greater UMN disease burden, more rapid disease progression, a twofold to threefold greater hazard of death and shorter survival times. The findings that higher CSF NfL levels and a reduced ptau/ttau ratio are more associated with clinical UMN involvement and with reduced CST FA offer strong converging evidence that both are markers of central motor degeneration. Furthermore, NfL is a marker of poor prognosis, while a low ptau/ttau ratio indicates extramotor pathology in ALS.
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http://dx.doi.org/10.1007/s00415-018-9043-0DOI Listing
November 2018

Establishing intra- and inter-vendor reproducibility of T relaxation time measurements with 3T MRI.

Magn Reson Med 2019 01 29;81(1):454-465. Epub 2018 Aug 29.

Laboratory for Social and Neural Systems Research, University of Zurich, Zürich, Switzerland.

Purpose: Parametric imaging methods (e.g., T relaxation time mapping) have been shown to be more reproducible across time and vendors than weighted (e.g., T -weighted) images. The purpose of this work was to more extensively evaluate the validity of this assertion.

Methods: Seven volunteers underwent twice-repeated acquisitions of variable flip-angle T mapping, including B calibration, on a 3T Philips Achieva and 3T Siemens Trio scanner. Intra-scanner and inter-vendor T variability were calculated. To determine T reproducibility levels in longitudinal settings, or after changing hardware or software, four additional data sets were acquired from two of the participants; one participant was scanned on a different 3T Siemens Trio scanner and another on the same 3T Philips Achieva scanner but after a software upgrade.

Results: Intra-scanner variability of voxel-wise T values was consistent between the two vendors, averaging 0.7/0.7/1.3/1.4% in white matter/cortical gray matter/subcortical gray matter/cerebellum, respectively. We observed, however, a systematic bias between the two vendors of https://doi.org/10.0/7.8/8.6/10.0%, respectively. The T bias across two scanners of the same model was greater than intra-scanner variability, although still only at 1.4/1.0/1.9/2.3%, respectively. A greater bias was identified for data sets acquired before/after software upgrade in white matter/cortical gray matter (3.6/2.7%) whereas variability in subcortical gray matter/cerebellum was comparable (1.7/1.9%).

Conclusion: We established intra- and inter-vendor reproducibility levels for a widely used T mapping protocol. We anticipate that these results will guide the design of multi-center studies, particularly those encompassing multiple vendors. Furthermore, this baseline level of reproducibility should be established or surpassed during the piloting phase of such studies.
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http://dx.doi.org/10.1002/mrm.27421DOI Listing
January 2019

Can neuroimaging predict dementia in Parkinson's disease?

Brain 2018 09;141(9):2545-2560

Wellcome Centre for Human Neuroimaging, UCL, Queen Square, London, UK.

Dementia in Parkinson's disease affects 50% of patients within 10 years of diagnosis but there is wide variation in severity and timing. Thus, robust neuroimaging prediction of cognitive involvement in Parkinson's disease is important: (i) to identify at-risk individuals for clinical trials of potential new treatments; (ii) to provide reliable prognostic information for individuals and populations; and (iii) to shed light on the pathophysiological processes underpinning Parkinson's disease dementia. To date, neuroimaging has not made major contributions to predicting cognitive involvement in Parkinson's disease. This is perhaps unsurprising considering conventional methods rely on macroscopic measures of topographically distributed neurodegeneration, a relatively late event in Parkinson's dementia. However, new technologies are now emerging that could provide important insights through detection of other potentially relevant processes. For example, novel MRI approaches can quantify magnetic susceptibility as a surrogate for tissue iron content, and increasingly powerful mathematical approaches can characterize the topology of brain networks at the systems level. Here, we present an up-to-date overview of the growing role of neuroimaging in predicting dementia in Parkinson's disease. We discuss the most relevant findings to date, and consider the potential of emerging technologies to detect the earliest signs of cognitive involvement in Parkinson's disease.
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http://dx.doi.org/10.1093/brain/awy211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113860PMC
September 2018

A robust multi-scale approach to quantitative susceptibility mapping.

Neuroimage 2018 12 31;183:7-24. Epub 2018 Jul 31.

Wellcome Centre for Human Neuroimaging, UCL Institute of Neurology, University College London, London, United Kingdom.

Quantitative Susceptibility Mapping (QSM), best known as a surrogate for tissue iron content, is becoming a highly relevant MRI contrast for monitoring cellular and vascular status in aging, addiction, traumatic brain injury and, in general, a wide range of neurological disorders. In this study we present a new Bayesian QSM algorithm, named Multi-Scale Dipole Inversion (MSDI), which builds on the nonlinear Morphology-Enabled Dipole Inversion (nMEDI) framework, incorporating three additional features: (i) improved implementation of Laplace's equation to reduce the influence of background fields through variable harmonic filtering and subsequent deconvolution, (ii) improved error control through dynamic phase-reliability compensation across spatial scales, and (iii) scalewise use of the morphological prior. More generally, this new pre-conditioned QSM formalism aims to reduce the impact of dipole-incompatible fields and measurement errors such as flow effects, poor signal-to-noise ratio or other data inconsistencies that can lead to streaking and shadowing artefacts. In terms of performance, MSDI is the first algorithm to rank in the top-10 for all metrics evaluated in the 2016 QSM Reconstruction Challenge. It also demonstrated lower variance than nMEDI and more stable behaviour in scan-rescan reproducibility experiments for different MRI acquisitions at 3 and 7 Tesla. In the present work, we also explored new forms of susceptibility MRI contrast making explicit use of the differential information across spatial scales. Specifically, we show MSDI-derived examples of: (i) enhanced anatomical detail with susceptibility inversions from short-range dipole fields (hereby referred to as High-Pass Susceptibility Mapping or HPSM), (ii) high specificity to venous-blood susceptibilities for highly regularised HPSM (making a case for MSDI-based Venography or VenoMSDI), (iii) improved tissue specificity (and possibly statistical conditioning) for Macroscopic-Vessel Suppressed Susceptibility Mapping (MVSSM), and (iv) high spatial specificity and definition for HPSM-based Susceptibility-Weighted Imaging (HPSM-SWI) and related intensity projections.
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http://dx.doi.org/10.1016/j.neuroimage.2018.07.065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215336PMC
December 2018

Quantitative Susceptibility MRI to Detect Brain Iron in Amyotrophic Lateral Sclerosis.

Radiology 2018 10 24;289(1):195-203. Epub 2018 Jul 24.

From the German Center for Neurodegenerative Diseases, Magdeburg, Germany (J.A., J.M., N.S., H.J.H., P.J.N.); Wellcome Centre for Human Neuroimaging, UCL Institute of Neurology, University College London, 12 Queen Square, London WC1N 3BG, England (J.A.); Department of Neurology, Otto von Guericke University, Magdeburg, Germany (J.M., S.S., S.A., J.K., H.J.H., S.V.); Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany (S.A., K.K., S.P., R.D.); Leibniz Institute for Neurobiology, Magdeburg, Germany (H.J.H.); and Queensland Brain Institute, University of Queensland, Brisbane, Australia (P.J.N.).

Purpose To investigate the whole-brain landscape of iron-related abnormalities in amyotrophic lateral sclerosis (ALS) by using the in vivo MRI technique of quantitative susceptibility mapping (QSM). Materials and Methods For this prospective study, 28 patients with ALS (mean age, 61 years; age range, 43-77 years; 18 men [mean age, 61 years; range, 43-77 years] and 10 women [mean age, 61 years; range, 47-74 years]) recruited between January 17, 2014, and September 4, 2015, and 39 matched control subjects (mean age, 61 years; age range, 39-77 years; 24 men [mean age, 62 years; range, 39-77 years] and 15 women [mean age, 59 years; range, 39-73 years]) were examined by using structural and susceptibility 3.0-T MRI techniques. Group data were cross sectionally compared with family-wise error (FWE) corrections by using voxel-based morphometry (random-field theory), cortical thickness analysis (Monte Carlo simulated), subcortical volumetry (Bonferroni-corrected Wilcoxon rank-sum testing), and QSM analysis (cluster-enhanced whole-brain permutation testing and Bonferroni-corrected rank-sum testing in regions of interest). In patients with ALS, a potential relationship between diffusion and susceptibility measurements in the corticospinal tracts (CSTs) was also examined by using Spearman rank-correlation tests. Results Conventional structural measures failed to identify atrophy in the present cohort (FWE P > .05). However, QSM identified several whole-brain abnormalities (FWE P < .05) in ALS. Regionally, higher susceptibility (expressed as means in parts per million ± standard errors of the mean) was confirmed in the motor cortex (ALS = 0.0188 ± 0.0003, control = 0.0173 ± 0.0003; P < .001), the left substantia nigra (ALS = 0.127 ± 0.004, control = 0.113 ± 0.003; P = .008), the right substantia nigra (ALS = 0.141 ± 0.005, control = 0.120 ± 0.003; P < .001), the globus pallidus (ALS = 0.086 ± 0.003, control = 0.075 ± 0.002; P = .003), and the red nucleus (ALS = 0.115 ± 0.004, control = 0.098 ± 0.003; P < .001). Lower susceptibility was found in CST white matter (ALS = -0.047 ± 0.001, control = -0.043 ± 0.001; P = .01). Nigral and pallidal QSM values were cross correlated in ALS (ρ = 0.42, P < .001), a phenomenon visually traceable in many individual patients. QSM in the CST in ALS also correlated with diffusion-tensor metrics in this tract (ρ = 0.25, P = .007). Conclusion Whole-brain MRI quantitative susceptibility mapping analysis is sensitive to tissue alterations in amyotrophic lateral sclerosis that may be relevant to pathologic changes. © RSNA, 2018.
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http://dx.doi.org/10.1148/radiol.2018180112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166868PMC
October 2018

Prefrontal cortical thickness in motor neuron disease.

Neuroimage Clin 2018 2;18:648-655. Epub 2018 Mar 2.

German Center for Neurodegenerative Diseases (DZNE), Site Magdeburg, Leipziger Straße 44, 39120 Magdeburg, Germany.

Objective: To examine whether the distribution of prefrontal cortical thickness in patients with motor neuron disease is normal or bimodal and how it compares to the normal population.

Methods: 158 patients with motor neuron disease (MND) and 86 healthy controls (HC) were enrolled in a prospective, two-center study with a common structural MRI protocol. Cortical thickness measures were extracted for the prefrontal cortex, premotor cortex, motor cortex, and occipital cortex using FreeSurfer, adjusted for age and sex, and tested for normality of distribution.

Results: Cortical thickness measures of the bilateral prefrontal, premotor, motor, and occipital cortex were normally distributed in patients and healthy controls. MND-related cortical thinning was observed in the right motor cortex ( = 0.002), reflected in a significantly higher proportion of MND cases being worse than -1 standard deviation of the healthy control mean: 29.1% in the right motor cortex ( = 0.002). Cortical thinning of the left motor cortex was a function of clinical phenotype and physical disability. Left prefrontal cortical thickness was reduced in patients with additional cognitive and/or behavioural deficits compared to MND patients without cognitive deficits. Prefrontal, premotor, motor, and occipital cortical thickness was related to patients' general cognitive abilities.

Conclusion: The study shows that prefrontal cortical thickness in MND is normally distributed but shifted towards thinner cortex in MND patients with cognitive and/or behavioural impairment. The distribution of thickness values did not indicate the assumption of a bimodal distribution although patients with comorbid cognitive deficits are more likely to suffer from prefrontal cortical thinning.
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http://dx.doi.org/10.1016/j.nicl.2018.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987868PMC
January 2019

A new discrete dipole kernel for quantitative susceptibility mapping.

Magn Reson Imaging 2018 09 16;51:7-13. Epub 2018 Apr 16.

Department of Electrical Engineering, Pontificia Universidad Catolica de Chile, Avda. Vicuña Mackenna 4686, Macul, Santiago, Chile; Biomedical Imaging Center, Pontificia Universidad Catolica de Chile, Avda. Vicuña Mackenna 4686, Macul, Santiago, Chile. Electronic address:

Purpose: Most approaches for quantitative susceptibility mapping (QSM) are based on a forward model approximation that employs a continuous Fourier transform operator to solve a differential equation system. Such formulation, however, is prone to high-frequency aliasing. The aim of this study was to reduce such errors using an alternative dipole kernel formulation based on the discrete Fourier transform and discrete operators.

Methods: The impact of such an approach on forward model calculation and susceptibility inversion was evaluated in contrast to the continuous formulation both with synthetic phantoms and in vivo MRI data.

Results: The discrete kernel demonstrated systematically better fits to analytic field solutions, and showed less over-oscillations and aliasing artifacts while preserving low- and medium-frequency responses relative to those obtained with the continuous kernel. In the context of QSM estimation, the use of the proposed discrete kernel resulted in error reduction and increased sharpness.

Conclusion: This proof-of-concept study demonstrated that discretizing the dipole kernel is advantageous for QSM. The impact on small or narrow structures such as the venous vasculature might by particularly relevant to high-resolution QSM applications with ultra-high field MRI - a topic for future investigations. The proposed dipole kernel has a straightforward implementation to existing QSM routines.
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http://dx.doi.org/10.1016/j.mri.2018.04.004DOI Listing
September 2018

Fast nonlinear susceptibility inversion with variational regularization.

Magn Reson Med 2018 08 10;80(2):814-821. Epub 2018 Jan 10.

Department of Electrical Engineering, Pontificia Universidad Catolica de Chile, Santiago, Chile.

Purpose: Quantitative susceptibility mapping can be performed through the minimization of a function consisting of data fidelity and regularization terms. For data consistency, a Gaussian-phase noise distribution is often assumed, which breaks down when the signal-to-noise ratio is low. A previously proposed alternative is to use a nonlinear data fidelity term, which reduces streaking artifacts, mitigates noise amplification, and results in more accurate susceptibility estimates. We hereby present a novel algorithm that solves the nonlinear functional while achieving computation speeds comparable to those for a linear formulation.

Methods: We developed a nonlinear quantitative susceptibility mapping algorithm (fast nonlinear susceptibility inversion) based on the variable splitting and alternating direction method of multipliers, in which the problem is split into simpler subproblems with closed-form solutions and a decoupled nonlinear inversion hereby solved with a Newton-Raphson iterative procedure. Fast nonlinear susceptibility inversion performance was assessed using numerical phantom and in vivo experiments, and was compared against the nonlinear morphology-enabled dipole inversion method.

Results: Fast nonlinear susceptibility inversion achieves similar accuracy to nonlinear morphology-enabled dipole inversion but with significantly improved computational efficiency.

Conclusion: The proposed method enables accurate reconstructions in a fraction of the time required by state-of-the-art quantitative susceptibility mapping methods. Magn Reson Med 80:814-821, 2018. © 2018 International Society for Magnetic Resonance in Medicine.
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http://dx.doi.org/10.1002/mrm.27073DOI Listing
August 2018

Magnetic resonance imaging of the human locus coeruleus: A systematic review.

Neurosci Biobehav Rev 2017 Dec 28;83:325-355. Epub 2017 Oct 28.

Division of Psychiatry, University College London, UK.

The locus coeruleus (LC), the major origin of noradrenergic modulation of the central nervous system, innervates extensive areas throughout the brain and is implicated in a variety of autonomic and cognitive functions. Alterations in the LC-noradrenergic system have been associated with healthy ageing and neuropsychiatric disorders including Parkinson's disease, Alzheimer's disease and depression. The last decade has seen advances in imaging the structure and function of the LC, and this paper systematically reviews the methodology and outcomes of sixty-nine structural and functional MRI studies of the LC in humans. Structural MRI studies consistently showed lower LC signal intensity and volume in clinical groups compared to healthy controls. Within functional studies, the LC was activated by a variety of tasks/stimuli and had functional connectivity to a range of brain regions. However, reported functional LC location coordinates were widely distributed compared to previously published neuroanatomical locations. Methodological and demographic factors potentially contributing to these differences are discussed, together with recommendations to optimize the reliability and validity of future LC imaging studies.
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http://dx.doi.org/10.1016/j.neubiorev.2017.10.023DOI Listing
December 2017

Brain-predicted age in Down syndrome is associated with beta amyloid deposition and cognitive decline.

Neurobiol Aging 2017 08 18;56:41-49. Epub 2017 Apr 18.

Cambridge Intellectual and Developmental Disabilities Research Group, Department of Psychiatry, University of Cambridge, Cambridge, UK.

Individuals with Down syndrome (DS) are more likely to experience earlier onset of multiple facets of physiological aging. This includes brain atrophy, beta amyloid deposition, cognitive decline, and Alzheimer's disease-factors indicative of brain aging. Here, we employed a machine learning approach, using structural neuroimaging data to predict age (i.e., brain-predicted age) in people with DS (N = 46) and typically developing controls (N = 30). Chronological age was then subtracted from brain-predicted age to generate a brain-predicted age difference (brain-PAD) score. DS participants also underwent [C]-PiB positron emission tomography (PET) scans to index the levels of cerebral beta amyloid deposition, and cognitive assessment. Mean brain-PAD in DS participants' was +2.49 years, significantly greater than controls (p < 0.001). The variability in brain-PAD was associated with the presence and the magnitude of PiB-binding and levels of cognitive performance. Our study indicates that DS is associated with premature structural brain aging, and that age-related alterations in brain structure are associated with individual differences in the rate of beta amyloid deposition and cognitive impairment.
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http://dx.doi.org/10.1016/j.neurobiolaging.2017.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476346PMC
August 2017