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  • 1.
    Badoud, Simon
    et al.
    Univ Hosp Geneva, Neurol Unit, Dept Clin Neurosci, Geneva, Switzerland.;Univ Fribourg CH, Neurophysiol Unit, Dept Med, Fribourg, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland..
    Nicastro, Nicolas
    Univ Hosp Geneva, Neurol Unit, Dept Clin Neurosci, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland..
    Garibotto, Valentina
    Univ Geneva, Fac Med, Geneva, Switzerland.;Geneva Univ Hosp, Nucl Med & Mol Imaging Unit, Dept Med Imaging, Geneva, Switzerland..
    Burkhard, Pierre R.
    Univ Hosp Geneva, Neurol Unit, Dept Clin Neurosci, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland.;Ctr Diagnost Radiolog Carouge, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany..
    Distinct spatiotemporal patterns for disease duration and stage in Parkinson's disease2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, no 3, p. 509-516Article in journal (Refereed)
    Abstract [en]

    Purpose To assess correlations between the degree of dopaminergic depletion measured using single-photon emission computed tomography (SPECT) and different clinical parameters of disease progression in Parkinson's disease (PD). Methods This retrospective study included 970 consecutive patients undergoing I-123-ioflupane SPECT scans in our institution between 2003 and 2013, from which we selected a study population of 411 patients according to their clinical diagnosis: 301 patients with PD (69.4 +/- 11.0 years, of age, 163 men) and 110 patients with nondegenerative conditions included as controls (72.7 +/- 8.0 years of age, 55 men). Comprehensive and operator-independent data analysis included spatial normalization into standard space, estimation of the mean uptake values in the striatum (caudate nucleus + putamen) and voxel-wise correlation between SPECT signal intensity and disease stage as well as disease duration in order to investigate the spatiotemporal pattern of the dopaminergic nigrostriatal degeneration. To compensate for potential interactions between disease stage and disease duration, one parameter was used as nonexplanatory coregressor for the other. Results Increasing disease stage was associated with an exponential decrease in I-123-ioflupane uptake (R (2) = 0.1501) particularly in the head of the ipsilateral caudate nucleus (p < 0.0001), whereas increasing disease duration was associated with a linear decrease in I-123-ioflupane uptake (p < 0.0001; R (2) = 0.1532) particularly in the contralateral anterior putamen (p < 0.0001). Conclusion We observed two distinct spatiotemporal patterns of posterior to anterior dopaminergic depletion associated with disease stage and disease duration in patients with PD. The developed operator-independent reference database of 411 I-123-ioflupane SPECT scans can be used for clinical and research applications.

  • 2. Badoud, Simon
    et al.
    Van De Ville, Dimitri
    Nicastro, Nicolas
    Garibotto, Valentina
    Burkhard, Pierre R
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Discriminating among degenerative parkinsonisms using advanced (123)I-ioflupane SPECT analyses2016In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 12, p. 234-240Article in journal (Refereed)
    Abstract [en]

    (123)I-ioflupane single photon emission computed tomography (SPECT) is a sensitive and well established imaging tool in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS), yet a discrimination between PD and APS has been considered inconsistent at least based on visual inspection or simple region of interest analyses. We here reappraise this issue by applying advanced image analysis techniques to separate PD from the various APS. This study included 392 consecutive patients with degenerative parkinsonism undergoing (123)I-ioflupane SPECT at our institution over the last decade: 306 PD, 24 multiple system atrophy (MSA), 32 progressive supranuclear palsy (PSP) and 30 corticobasal degeneration (CBD) patients. Data analysis included voxel-wise univariate statistical parametric mapping and multivariate pattern recognition using linear discriminant classifiers. MSA and PSP showed less ioflupane uptake in the head of caudate nucleus relative to PD and CBD, yet there was no difference between MSA and PSP. CBD had higher uptake in both putamen relative to PD, MSA and PSP. Classification was significant for PD versus APS (AUC 0.69, p < 0.05) and between APS subtypes (MSA vs CBD AUC 0.80, p < 0.05; MSA vs PSP AUC 0.69 p < 0.05; CBD vs PSP AUC 0.69 p < 0.05). Both striatal and extra-striatal regions contain classification information, yet the combination of both regions does not significantly improve classification accuracy. PD, MSA, PSP and CBD have distinct patterns of dopaminergic depletion on (123)I-ioflupane SPECT. The high specificity of 84-90% for PD versus APS indicates that the classifier is particularly useful for confirming APS cases.

  • 3.
    Barnaure, I.
    et al.
    Univ Hosp Geneva, Div Neuroradiol, Geneva, Switzerland.
    Montandon, M-L.
    Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland.
    Rodriguez, C.
    Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland.
    Herrmann, F.
    Univ Hosp Geneva, Dept Internal Med, Geneva, Switzerland; Univ Hosp Geneva, Dept Rehabil, Geneva, Switzerland; Univ Hosp Geneva, Dept Geriatr, Geneva, Switzerland.
    Lövblad, K. O.
    Univ Hosp Geneva, Div Neuroradiol, Geneva, Switzerland.
    Giannakopoulos, P.
    Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany; Univ Geneva, Fac Med, Geneva, Switzerland.
    Clinicoradiologic Correlations of Cerebral Microbleeds in Advanced Age2017In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 38, p. 39-45Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The presence of cerebral microbleeds has been associated with dementia and cognitive decline, although studies report conflicting results. Our aim was to determine the potential role of the presence and location of cerebral microbleeds in early stages of cognitive decline.

    MATERIALS AND METHODS: Baseline 3T MR imaging examinations including SWI sequences of 328 cognitively intact community-dwelling controls and 72 subjects with mild cognitive impairment were analyzed with respect to the presence and distribution of cerebral microbleeds. A neuropsychological follow-up of controls was performed at 18 months post inclusion and identified cases with subtle cognitive deficits were referred to as controls with a deteriorating condition. Group differences in radiologic parameters were studied by using nonparametric tests, 1-way analysis of variance, and Spearman correlation coefficients.

    RESULTS: Cerebral microbleed prevalence was similar in subjects with mild cognitive impairment and controls with stable and cognitively deteriorating conditions (25%-31.9%). In all diagnostic groups, lobar cerebral microbleeds were more common. They occurred in 20.1% of all cases compared with 6.5% of cases with deep cerebral microbleeds. None of the investigated variables (age, sex, microbleed number, location and depth, baseline Mini-Mental State Examination score, and the Fazekas score) were significantly associated with cognitive deterioration with the exception of education of >12 years showing a slight but significant protective effect (OR, 0.44; 95% CI, 0.22-0.92; P = .028). The Mini-Mental State Examination and the Buschke total score were correlated with neither the total number nor lobar-versus-deep location of cerebral microbleeds.

    CONCLUSIONS: Cerebral microbleed presence, location, and severity are not related to the early stages of cognitive decline in advanced age.

  • 4.
    Cunningham, Gregory
    et al.
    Univ Hosp Geneva, Dept Surg, Div Orthoped & Trauma Surg, Geneva, Switzerland..
    Zanchi, Davide
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland..
    Emmert, Kirsten
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Lausanne, Switzerland..
    Kopel, Rotem
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Lausanne, Switzerland..
    Van De Ville, Dimitri
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Lausanne, Switzerland..
    Laedermann, Alexandre
    Univ Hosp Geneva, Dept Surg, Div Orthoped & Trauma Surg, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1227 Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, CH-1227 Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Ctr Diagnost Radiol Carouge, Affidea, Carouge, Switzerland..
    Hoffmeyer, Pierre
    Univ Hosp Geneva, Dept Surg, Div Orthoped & Trauma Surg, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1227 Geneva, Switzerland..
    Neural Correlates of Clinical Scores in Patients with Anterior Shoulder Apprehension2015In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 47, no 12, p. 2612-2620Article in journal (Refereed)
    Abstract [en]

    Introduction Anterior shoulder apprehension is a commonly reported complaint in anterior shoulder instability, which may lead to patient morbidity and impede shoulder function. It is the result of a cognitively complex mechanism, which includes anxiety, salience, fear, and anticipation. Purpose The aim of this prospective case-control study was to correlate five clinically established scores using functional magnetic resonance imaging to assess brain activation patterns in patients with apprehension related to anterior shoulder instability. Methods This study includes 28 consecutive male right-handed patients ( mean +/- SEM, 26.8 +/- 1.2 yr) with positive shoulder apprehension test and 10 healthy matched control participants without apprehension or a history of instability. Task- related and functional connectivity functional magnetic resonance imaging activation patterns occurring during apprehension video cue stimulation were correlated with five clinical tests and scores: Visual Analog Scale ( VAS), Rowe score for instability, Simple Shoulder Test, Subjective Shoulder Value ( SSV), and Western Ontario Shoulder Instability ( WOSI). Results Rowe, pain VAS, and WOSI scores correlated with prefrontal cortex, dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, somatosensory area, and parieto-occipital and temporal areas (default mode network). Rowe score additionally correlated with frontal pole, anterior midcingulate cortex, and visual areas. Moreover, SSV correlated with task-related brain activity in the bilateral precentral gyrus, bilateral postcentral gyrus, and bilateral superior parietal lobe. Conclusions Overall, Rowe score provides the strongest link between shoulder apprehension and brain level alterations as it correlates with the highest number of independent components involving areas responsible for both motor and cognitive functions, whereas pain VAS and WOSI occupy an intermediately strong link recruiting less brain networks. Finally, Simple Shoulder Test and SSV have the weakest link at the brain level.

  • 5. Emmert, Kirsten
    et al.
    Breimhorst, Markus
    Bauermann, Thomas
    Birklein, Frank
    Rebhorn, Cora
    Van De Ville, Dimitri
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Centre de Diagnostic Radiologique de Carouge CDRC, Geneva, Switzerland; Faculty of Medicine of the University of Geneva, Geneva, Switzerland; Department of Neuroradiology, University Hospital Freiburg, Freiburg im Breisgau, Germany.
    Active pain coping is associated with the response in real-time fMRI neurofeedback during pain2017In: Brain Imaging and Behavior, ISSN 1931-7557, E-ISSN 1931-7565, Vol. 11, no 3, p. 712-721Article in journal (Refereed)
    Abstract [en]

    Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback is used as a tool to gain voluntary control of activity in various brain regions. Little emphasis has been put on the influence of cognitive and personality traits on neurofeedback efficacy and baseline activity. Here, we assessed the effect of individual pain coping on rt-fMRI neurofeedback during heat-induced pain. Twenty-eight healthy subjects completed the Coping Strategies Questionnaire (CSQ) prior to scanning. The first part of the fMRI experiment identified target regions using painful heat stimulation. Then, subjects were asked to down-regulate the pain target brain region during four neurofeedback runs with painful heat stimulation. Functional MRI analysis included correlation analysis between fMRI activation and pain ratings as well as CSQ ratings. At the behavioral level, the active pain coping (first principal component of CSQ) was correlated with pain ratings during neurofeedback. Concerning neuroimaging, pain sensitive regions were negatively correlated with pain coping. During neurofeedback, the pain coping was positively correlated with activation in the anterior cingulate cortex, prefrontal cortex, hippocampus and visual cortex. Thermode temperature was negatively correlated with anterior insula and dorsolateral prefrontal cortex activation. In conclusion, self-reported pain coping mechanisms and pain sensitivity are a source of variance during rt-fMRI neurofeedback possibly explaining variations in regulation success. In particular, active coping seems to be associated with successful pain regulation.

  • 6.
    Emmert, Kirsten
    et al.
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Kopel, Rotem
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Koush, Yury
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Maire, Raphael
    Univ Hosp Lausanne, Neurotol & Audiol Unit, Dept ENT Head & Neck Surg, Switzerland.
    Senn, Pascal
    Univ Hosp Geneva, Dept Clin Neurosci, Switzerland.
    Van De Ville, Dimitri
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Continuous vs. intermittent neurofeedback to regulate auditory cortex activity of tinnitus patients using real-time fMRI: A pilot study2017In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 14, p. 97-104Article in journal (Refereed)
    Abstract [en]

    The emerging technique of real-time fMRI neurofeedback trains individuals to regulate their own brain activity via feedback from an fMRI measure of neural activity. Optimum feedback presentation has yet to be determined, particularly when working with clinical populations. To this end, we compared continuous against intermittent feedback in subjects with tinnitus.

    Fourteen participants with tinnitus completed the whole experiment consisting of nine runs (3 runs × 3 days). Prior to the neurofeedback, the target region was localized within the auditory cortex using auditory stimulation (1 kHz tone pulsating at 6 Hz) in an ON-OFF block design. During neurofeedback runs, participants received either continuous (n = 7, age 46.84 ± 12.01, Tinnitus Functional Index (TFI) 49.43 ± 15.70) or intermittent feedback (only after the regulation block) (n = 7, age 47.42 ± 12.39, TFI 49.82 ± 20.28). Participants were asked to decrease auditory cortex activity that was presented to them by a moving bar. In the first and the last session, participants also underwent arterial spin labeling (ASL) and resting-state fMRI imaging. We assessed tinnitus severity using the TFI questionnaire before all sessions, directly after all sessions and six weeks after all sessions. We then compared neuroimaging results from neurofeedback using a general linear model (GLM) and region-of-interest analysis as well as behavior measures employing a repeated-measures ANOVA. In addition, we looked at the seed-based connectivity of the auditory cortex using resting-state data and the cerebral blood flow using ASL data.

    GLM group analysis revealed that a considerable part of the target region within the auditory cortex was significantly deactivated during neurofeedback. When comparing continuous and intermittent feedback groups, the continuous group showed a stronger deactivation of parts of the target region, specifically the secondary auditory cortex. This result was confirmed in the region-of-interest analysis that showed a significant down-regulation effect for the continuous but not the intermittent group. Additionally, continuous feedback led to a slightly stronger effect over time while intermittent feedback showed best results in the first session. Behaviorally, there was no significant effect on the total TFI score, though on a descriptive level TFI scores tended to decrease after all sessions and in the six weeks follow up in the continuous group. Seed-based connectivity with a fixed-effects analysis revealed that functional connectivity increased over sessions in the posterior cingulate cortex, premotor area and part of the insula when looking at all patients while cerebral blood flow did not change significantly over time.

    Overall, these results show that continuous feedback is suitable for long-term neurofeedback experiments while intermittent feedback presentation promises good results for single session experiments when using the auditory cortex as a target region. In particular, the down-regulation effect is more pronounced in the secondary auditory cortex, which might be more susceptible to voluntary modulation in comparison to a primary sensory region.

  • 7.
    Emmert, Kirsten
    et al.
    Univ Geneva, Dept Radiol & Med Informat, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Lausanne, Switzerland..
    Kopel, Rotem
    Univ Geneva, Dept Radiol & Med Informat, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Lausanne, Switzerland..
    Sulzer, James
    Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA..
    Bruehl, Annette B.
    Univ Zurich, Hosp Psychiat, Dept Psychiat Psychotherapy & Psychosomat, Zurich, Switzerland.;Univ Cambridge, Behav & Clin Neurosci Inst, Dept Psychiat, Cambridge, England..
    Berman, Brian D.
    Univ Colorado, Dept Neurol, Aurora, CO USA..
    Linden, David E. J.
    Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales..
    Horovitz, Silvina G.
    NINDS, NIH, Bethesda, MD 20892 USA..
    Breimhorst, Markus
    Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Neurol, D-55122 Mainz, Germany..
    Caria, Andrea
    Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany..
    Frank, Sabine
    Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany..
    Johnston, Stephen
    Long, Zhiying
    Swansea Univ, Dept Psychol, Swansea, W Glam, Wales.;Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China.;Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China..
    Paret, Christian
    Heidelberg Univ Mannheim, Med Fac Mannheim, Cent Inst Mental Hlth Mannheim, Dept Psychosomat Med & Psychotherapy, Mannheim, Germany.;Heidelberg Univ Mannheim, Med Fac Mannheim, Cent Inst Mental Hlth Mannheim, Dept Neuroimaging, Mannheim, Germany..
    Robineau, Fabien
    Univ Geneva, Dept Neurosci, Lab Neurol & Imaging Cognit, CH-1211 Geneva 4, Switzerland..
    Veit, Ralf
    Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany.;Univ Tubingen, Helmholtz Ctr Munich, Inst Diabet Res & Metab Dis, Tubingen, Germany..
    Bartsch, Andreas
    Heidelberg Univ, Dept Neuroradiol, Heidelberg, Germany.;Univ Wurzburg, Dept Neuroradiol, D-97070 Wurzburg, Germany.;Univ Oxford, FMRIB Ctr, Oxford, England.;Bamberg Hosp, Dept Radiol, Bamberg, Germany..
    Beckmann, Christian F.
    Radboud Univ Nijmegen, Ctr Cognit Neuroimaging, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neuroimaging, NL-6525 ED Nijmegen, Netherlands.;Univ Oxford, Oxford Ctr Funct MRI Brain, Nuffield Dept Clin Neurosci, Oxford OX1 2JD, England..
    Van De Ville, Dimitri
    Univ Geneva, Dept Radiol & Med Informat, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Lausanne, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiolog Carouge CDRC, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland..
    Meta-analysis of real-time fMRI neurofeedback studies using individual participant data: How is brain regulation mediated?2016In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 124, no Part A, p. 806-812Article in journal (Refereed)
    Abstract [en]

    An increasing number of studies using real-time fMRI neurofeedback have demonstrated that successful regulation of neural activity is possible in various brain regions. Since these studies focused on the regulated region(s), little is known about the target-independent mechanisms associated with neurofeedback-guided control of brain activation, i.e. the regulating network. While the specificity of the activation during self-regulation is an important factor, no study has effectively determined the network involved in self-regulation in general. In an effort to detect regions that are responsible for the act of brain regulation, we performed a post-hoc analysis of data involving different target regions based on studies from different research groups. We included twelve suitable studies that examined nine different target regions amounting to a total of 175 subjects and 899 neurofeedback runs. Data analysis included a standard first-(single subject, extracting main paradigm) and second-level (single subject, all runs) general linear model (GLM) analysis of all participants taking into account the individual timing. Subsequently, at the third level, a random effects model GLM included all subjects of all studies, resulting in an overall mixed effects model. Since four of the twelve studies had a reduced field of view (FoV), we repeated the same analysis in a subsample of eight studies that had a well-overlapping FoV to obtain a more global picture of self-regulation. The GLM analysis revealed that the anterior insula as well as the basal ganglia, notably the striatum, were consistently active during the regulation of brain activation across the studies. The anterior insula has been implicated in interoceptive awareness of the body and cognitive control. Basal ganglia are involved in procedural learning, visuomotor integration and other higher cognitive processes including motivation. The larger FoV analysis yielded additional activations in the anterior cingulate cortex, the dorsolateral and ventrolateral prefrontal cortex, the temporo-parietal area and the visual association areas including the temporo-occipital junction. In conclusion, we demonstrate that several key regions, such as the anterior insula and the basal ganglia, are consistently activated during self-regulation in real-time fMRI neurofeedback independent of the targeted region-ofinterest. Our results imply that if the real-time fMRI neurofeedback studies target regions of this regulation network, such as the anterior insula, care should be given whether activation changes are related to successful regulation, or related to the regulation process per se. Furthermore, future research is needed to determine how activation within this regulation network is related to neurofeedback success.

  • 8.
    Emmert, Kirsten
    et al.
    Univ Geneva, Fac Med, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Geneva, Switzerland..
    Zoller, Daniela
    Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Geneva, Switzerland.;Univ Geneva, Dept Psychiat, Off Medicopedag, Geneva, Switzerland..
    Preti, Maria Giulia
    Univ Geneva, Fac Med, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Geneva, Switzerland..
    Van De Ville, Dimitri
    Univ Geneva, Fac Med, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Geneva, Switzerland..
    Giannakopoulos, Panteleimon
    Univ Geneva, Dept Psychiat, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland.;Affidea Ctr Diagnost Radiol Carouge CDRC, Carouge, Switzerland..
    Influence of Vascular Variant of the Posterior Cerebral Artery (PCA) on Cerebral Blood Flow, Vascular Response to CO2 and Static Functional Connectivity2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 8, article id e0161121Article in journal (Refereed)
    Abstract [en]

    Introduction The fetal origin of the posterior cerebral artery (fPCA) is a frequent vascular variant in 11-29% of the population. For the fPCA, blood flow in the PCA originates from the anterior instead of the posterior circulation. We tested whether this blood supply variant impacts the cerebral blood flow assessed by arterial spin labeling (ASL), cerebrovascular reserve as well as resting-state static functional connectivity (sFC) in the sense of a systematic confound. Methods The study included 385 healthy, elderly subjects (mean age: 74.18 years [range: 68.9-90.4]; 243 female). Participants were classified into normal vascular supply (n = 296, 76.88%), right fetal origin (n = 23, 5.97%), left fetal origin (n = 16, 4.16%), bilateral fetal origin (n = 4, 1.04%), and intermediate (n = 46, 11.95%, excluded from further analysis) groups. ASL-derived relative cerebral blood flow (relCBF) maps and cerebrovascular reserve (CVR) maps derived from a CO2 challenge with blocks of 7% CO2 were compared. Additionally, sFC between 90 regions of interest (ROIs) was compared between the groups. Results CVR was significantly reduced in subjects with ipsilateral fPCA, most prominently in the temporal lobe. ASL yielded a non-significant trend towards reduced relCBF in bilateral posterior watershed areas. In contrast, conventional atlas-based sFC did not differ between groups. Conclusions In conclusion, fPCA presence may bias the assessment of cerebrovascular reserve by reducing the response to CO2. In contrast, its effect on ASL-assessed baseline perfusion was marginal. Moreover, fPCA presence did not systematically impact resting-state sFC. Taken together, this data implies that perfusion variables should take into account the vascularization patterns.

  • 9.
    Fällmar, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Med Ctr Freiburg, Dept Neuroradiol, Freiburg, Germany.; Univ Geneva, Fac Med, Geneva, Switzerland.; Affidea CDRC Ctr Diagnost Radiol Carouge, Carouge, Switzerland..
    Lilja, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Hermes Med Solut, Stockholm, Sweden.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Tolboom, Nelleke
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.
    Egger, Karl
    Univ Med Ctr Freiburg, Dept Neuroradiol, Freiburg, Germany.
    Kellner, Elias
    Univ Freiburg, Dept Radiol, Med Ctr, Fac Med,Med Phys, Freiburg, Germany.
    Croon, Philip M
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.
    Verfaillie, Sander C J
    Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Med Ctr, Amsterdam, Netherlands.
    van Berckel, Bart N M
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.
    Ossenkoppele, Rik
    Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Med Ctr, Amsterdam, Netherlands.
    Barkhof, Frederik
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.; UCL, Inst Neurol & Healthcare Engn, London, England..
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Arterial spin labeling-based Z-maps have high specificity and positive predictive value for neurodegenerative dementia compared to FDG-PET.2017In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 27, no 10, p. 4237-4246Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Cerebral perfusion analysis based on arterial spin labeling (ASL) MRI has been proposed as an alternative to FDG-PET in patients with neurodegenerative disease. Z-maps show normal distribution values relating an image to a database of controls. They are routinely used for FDG-PET to demonstrate disease-specific patterns of hypometabolism at the individual level. This study aimed to compare the performance of Z-maps based on ASL to FDG-PET.

    METHODS: Data were combined from two separate sites, each cohort consisting of patients with Alzheimer's disease (n = 18 + 7), frontotemporal dementia (n = 12 + 8) and controls (n = 9 + 29). Subjects underwent pseudocontinuous ASL and FDG-PET. Z-maps were created for each subject and modality. Four experienced physicians visually assessed the 166 Z-maps in random order, blinded to modality and diagnosis.

    RESULTS: Discrimination of patients versus controls using ASL-based Z-maps yielded high specificity (84%) and positive predictive value (80%), but significantly lower sensitivity compared to FDG-PET-based Z-maps (53% vs. 96%, p < 0.001). Among true-positive cases, correct diagnoses were made in 76% (ASL) and 84% (FDG-PET) (p = 0.168).

    CONCLUSION: ASL-based Z-maps can be used for visual assessment of neurodegenerative dementia with high specificity and positive predictive value, but with inferior sensitivity compared to FDG-PET.

    KEY POINTS: • ASL-based Z-maps yielded high specificity and positive predictive value in neurodegenerative dementia. • ASL-based Z-maps had significantly lower sensitivity compared to FDG-PET-based Z-maps. • FDG-PET might be reserved for ASL-negative cases where clinical suspicion persists. • Findings were similar at two study sites.

  • 10.
    Georgiopoulos, Charalampos
    et al.
    Department of Radiology and Department ofMedical and Health Sciences, Linköping University; Center for Medical ImageScience and Visualization (CMIV), Linköping University.
    Warntjes, Marcel
    Center for Medical ImageScience and Visualization (CMIV), Linköping University; SyntheticMR AB .
    Dizdar, Nil
    Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University.
    Zachrisson, Helene
    Center for Medical ImageScience and Visualization (CMIV), Linköping University; Department of Clinical Physiology and Departmentof Medical and Health Sciences, Linköping University, Linköping.
    Engström, Maria
    Center for Medical ImageScience and Visualization (CMIV), Linköping University, Linköping; Department of Medical andHealth Sciences, Linköping University, Linköping.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDRC Centre de Diagnostic Radiologiquede Carouge SA, Geneva, Switzerland .
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Olfactory Impairment in Parkinson's Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging.2017In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 7, no 2, p. 301-311Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Olfactory impairment is an early manifestation of Parkinson's disease (PD). Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) are two imaging techniques that allow noninvasive detection of microstructural changes in the cerebral white matter.

    OBJECTIVE: To assess white matter alterations associated with olfactory impairment in PD, using a binary imaging approach with DTI and MT.

    METHODS: 22 PD patients and 13 healthy controls were examined with DTI, MT and an odor discrimination test. DTI data were first analyzed with tract-based spatial statistics (TBSS) in order to detect differences in fractional anisotropy, mean, radial and axial diffusivity between PD patients and controls. Voxelwise randomized permutation was employed for the MT analysis, after spatial and intensity normalization. Additionally, ROI analysis was performed on both the DTI and MT data, focused on the white matter adjacent to olfactory brain regions.

    RESULTS: Whole brain voxelwise analysis revealed decreased axial diffusivity in the left uncinate fasciculus and the white matter adjacent to the left olfactory sulcus of PD patients. ROI analysis demonstrated decreased axial diffusivity in the right orbitofrontal cortex, as well as decreased mean diffusivity and axial diffusivity in the white matter of the left entorhinal cortex of PD patients. There were no significant differences regarding fractional anisotropy, radial diffusivity or MT between patients and controls.

    CONCLUSIONS: ROI analysis of DTI could detect microstructural changes in the white matter adjacent to olfactory areas in PD patients, whereas MT imaging could not.

  • 11. Georgiopoulos, Charalampos
    et al.
    Witt, Suzanne T
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDRC Centre de Diagnostic Radiologique de Carouge SA, Geneva, Switzerland.
    Dizdar, Nil
    Zachrisson, Helene
    Engström, Maria
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Olfactory fMRI: implications of stimulation length and repetition time2018In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 43, no 6, p. 389-398Article in journal (Refereed)
    Abstract [en]

    Studying olfaction with functional Magnetic Resonance imaging (fMRI) poses various methodological challenges. This study aimed to investigate the effects of stimulation length and repetition time (TR) on the activation pattern of four olfactory brain regions: the anterior and the posterior piriform cortex, the orbitofrontal cortex and the insula. 22 healthy participants with normal olfaction were examined with fMRI, with two stimulation lengths (6 seconds and 15 seconds) and two TRs (0.901 seconds and 1.34 seconds). Data were analyzed using General Linear Model (GLM), Tensorial Independent Component Analysis (TICA) and by plotting the event related time course of brain activation in the four olfactory regions of interest. The statistical analysis of the time courses revealed that short TR was associated with more pronounced signal increase and short stimulation was associated with shorter time to peak signal. Additionally, both long stimulation and short TR were associated with oscillatory time courses, whereas both short stimulation and short TR resulted in more typical time courses. GLM analysis showed that the combination of short stimulation and short TR could result in visually larger activation within these olfactory areas. TICA validated that the tested paradigm was spatially and temporally associated with a functionally connected network that included all four olfactory regions. In conclusion, the combination of short stimulation and short TR is associated with higher signal increase and shorter time to peak, making it more amenable to standard GLM-type analyses than long stimulation and long TR, and it should, thus, be preferable for olfactory fMRI.

  • 12.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDRC Ctr Diagnost Radiolog Carouge Clos d, CH-1227 Carouge, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Univ Geneva, Fac Med, Geneva, Switzerland.
    Advance MR imaging in sports-related concussion and mild traumatic brain injury: ready for clinical use? (Commentary on Tremblay et al. 2017)2017In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 46, no 4, p. 1954-1955Article in journal (Other academic)
  • 13.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Univ Geneva, Fac Med, Geneva, Switzerland.
    The Concept of "Number Needed to Image"2017In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 38, no 10, p. E79-E80Article in journal (Other academic)
  • 14.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Carouge, Switzerland; Univ Geneva, Dept Radiol, Geneva, Switzerland .
    Use of MR Imaging-defined Connectome to Predict the Recovery of Patients after Cardiac Arrest.2018In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 287, no 1, p. 256-257Article in journal (Refereed)
  • 15.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Geneva, Switzerland.; Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.; Univ Geneva, Fac Med, Geneva, Switzerland..
    Barkhof, Frederik
    Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med & PET Res, Amsterdam, Netherlands.; UCL, Inst Neurol, London, England.; UCL, Inst Healthcare Engn, London, England..
    Interaction of Vascular Damage and Alzheimer Dementia: Focal Damage and Disconnection2017In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 282, no 2, p. 311-313Article in journal (Refereed)
    Abstract [en]

    Dementia is a major health and socioeconomic problem with ever-increasing prevalence due to the increasing age of the population (1). Alzheimer disease (AD) and vascular dementia are both common disorders in the elderly, and although they are commonly co-occurring, they are generally considered to be separate nosologic entities. Neuroimaging biomarkers have evolved considerably over the past decade and demonstrate new insights into disease mechanisms in dementia. Of particular interest is the evolving view of interaction between pathophysiological mechanisms in AD and vascular dementia, as demonstrated with neuroimaging.

  • 16.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDRC Ctr Diagnost Radiol Carouge, Geneva, Switzerland; Univ Geneva, Med Fac, Geneva, Switzerland.
    Barkhof, Frederik
    Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands; UCL, Inst Neurol, Dept Neuroradiol, London, England.
    Peri-hippocampal developmental venous anomalies and memory loss: more than a normal variant?2018In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 60, no 6, p. 579-582Article in journal (Refereed)
  • 17.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiologique Carouge CDRC, Geneva, Switzerland.;Univ Geneva, Fac Med, Rue Gabrielle Perret Gentil 4, CH-1211 Geneva 14, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany..
    Barkhof, Frederik
    UCL, Neuroradiol Acad Unit, Dept Brain Repair & Rehabil, Inst Neurol, London, England.;UCL, Dept Healthcare Engn, London, England.;Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands..
    Thomas, David
    UCL Institute of Neurology, University College Hospital, London, England.
    Lovblad, Karl-Olof
    Univ Hosp Geneva, Dept Neuroradiol, Geneva, Switzerland..
    Golay, Xavier
    Univ Coll Hosp, UCL Inst Neurol, London, England..
    Zaharchuk, Greg
    Stanford Univ, Dept Radiol, Stanford, CA 94305 USA..
    Response to: Further Implications of Off-Label Use of Acetazolamide in the Management of Moyamoya Disease in Japan Response2017In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 284, no 1, p. 302-303Article in journal (Other academic)
  • 18.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDRC Ctr Diagnost Radiol Carouge, Clos Fonderie 1, CH-1277 Carouge, Switzerland.
    Burke, Michael
    GE Healthcare GmbH, Munich, Germany.
    Mueller, Thomas L
    Pearl Technol AG, Schlieren, Switzerland.
    MR skin signal loss effect/artifact2018In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 60, no 6, p. 661-662Article in journal (Refereed)
  • 19.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDRC Ctr Diagnost Radiol Carouge SA, Clos Fonderie 1, CH-1227 Geneva, Switzerland.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Susceptibility weighted imaging in dementia with Lewy bodies: will it resolve the blind spot of MRI?2016In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 58, no 2, p. 217-218Article in journal (Refereed)
  • 20.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany..
    Montandon, M. -L
    Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland.
    Rodriguez, C.
    Univ Hosp Geneva, Div Inst Measures, Med Direct, Geneva, Switzerland..
    Ackermann, M.
    Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland..
    Herrmann, F. R.
    Univ Geneva, Fac Med, Geneva, Switzerland.;Univ Hosp Geneva, Div Geriatr, Dept Internal Med Rehabil & Geriatr, Geneva, Switzerland..
    Giannakopoulos, P.
    Univ Geneva, Fac Med, Geneva, Switzerland.;Univ Hosp Geneva, Div Inst Measures, Med Direct, Geneva, Switzerland..
    APOE*E4 Is Associated with Gray Matter Loss in the Posterior Cingulate Cortex in Healthy Elderly Controls Subsequently Developing Subtle Cognitive Decline2017In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 38, no 7, p. 1335-1342Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The presence of apolipoprotein E4 (APOE*E4) is the strongest currently known genetic risk factor for Alzheimer disease and is associated with brain gray matter loss, notably in areas involved in Alzheimer disease pathology. Our objective was to assess the effect of APOE*E4 on brain structures in healthy elderly controls who subsequently developed subtle cognitive decline.

    MATERIALS AND METHODS: This prospective study included 382 community-dwelling elderly controls. At baseline, participants underwent MR imaging at 3T, extensive neuropsychological testing, and genotyping. After neuropsychological follow-up at 18 months, participants were classified into cognitively stable controls and cognitively deteriorating controls. Data analysis included whole-brain voxel-based morphometry and ROI analysis of GM.

    RESULTS: APOE*E4-related GM loss at baseline was found only in the cognitively deteriorating controls in the posterior cingulate cortex. There was no APOE*E4-related effect in the hippocampus, mesial temporal lobe, or brain areas not involved in Alzheimer disease pathology. Controls in the cognitively deteriorating group had slightly lower GM concentration in the hippocampus at baseline. Higher GM densities in the hippocampus, middle temporal lobe, and amygdala were associated with a decreased risk for cognitively deteriorating group status at follow-up.

    CONCLUSIONS: APOE*E4-related GM loss in the posterior cingulate cortex (an area involved in Alzheimer disease pathology) was found only in those elderly controls who subsequently developed subtle cognitive decline but not in cognitively stable controls. This finding might explain the partially conflicting results of previous studies that typically did not include detailed neuropsychological assessment and follow-up. Most important, APOE*E4 status had no impact on GM density in areas affected early by neurofibrillary tangle formation such as the hippocampus and mesial temporal lobe.

  • 21.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Carouge, Switzerland.; Med Sch Univ, Geneva, Switzerland.; Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany. .
    Montandon, Marie-Louise
    Med Sch Univ, Geneva, Switzerland.
    Lazeyras, François
    Univ Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland.
    Scheffler, Max
    Univ Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland.
    Meckel, Stephan
    Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.
    Herrmann, Francois R
    Med Sch Univ, Geneva, Switzerland.; Univ Hosp Geneva, Dept Internal Med Rehabil & Geriatr, Div Geriatr, Geneva, Switzerland.
    Giannakopoulos, Panteleimon
    Med Sch Univ, Geneva, Switzerland.; Univ Hosp Geneva, Geneva, Switzerland.
    Kövari, Enikö
    Med Sch Univ, Geneva, Switzerland.
    Radiologic-Histopathologic Correlation of Cerebral Microbleeds Using Pre-Mortem and Post-Mortem MRI2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 12, article id e0167743Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Cerebral microbleeds (CMB), also known as cerebral microhemorrhages, are small areas of susceptibility on brain magnetic resonance imaging (MRI), that are increasingly detected due to the higher availability of high-field MRI systems and dedicated pulse sequences. The prevalence of CMBs increases in cases with cognitive decline. The current investigation assessed the poorly investigated radiologic-histopathologic correlation of CMBs on MRI.

    METHODS: The local ethical committee approved the current investigation. We retrospectively assessed a consecutive series of 1303 autopsy cases hospitalized in Geneva University Hospitals between 2000-2014. Of 112 cases with pre-mortem T2* sequences, we included 25 cases (mean age 77.3 ± 9.6, 9 females) with at least one CMB. We compared pre-mortem CMBs with targeted histopathology and post-mortem MRI.

    RESULTS: 25 cases had 31 CMB lesions detected by pre-mortem MRI. 25 additional CMB were detected on histopathology. 4 CMBs on pre-mortem MRI were false positives, resulting in a total of 52 CMBs. 27 CMBs on pre-mortem MRI were confirmed on histopathology, corresponding to a sensitivity or true positive rate of 51.9% (95% CI 37.6-66.0%). The false negative rate of pre-mortem MRI was 48.1% (95% CI 34.0-62.4%). Post-mortem MRI showed only 3 cases with additional CMBs. Overall, pre-mortem MRI significantly underestimated CMBs (p = 0.0001).

    CONCLUSIONS: Routine clinical brain MRI underestimates the prevalence of CMBs by approximately 50%, and 12% of radiologic pre-mortem MRI CMBs were false positives. Post-mortem MRI confirmed that this discordance is not explained by microbleeds occurring after the pre-mortem MRI.

  • 22.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Clos de la Fonderie 1, CH-1277 Geneva, Switzerland..
    Montandon, Marie-Louise
    Univ Hosp Geneva, Dept Psychiat, Fac Med, Med Direct, Geneva, Switzerland..
    Rodriguez, Cristelle
    Univ Hosp Geneva, Dept Psychiat, Fac Med, Med Direct, Geneva, Switzerland..
    Moser, Dominik
    Univ Hosp Geneva, Dept Psychiat, Fac Med, Med Direct, Geneva, Switzerland..
    Toma, Simona
    Univ Hosp Geneva, Dept Psychiat, Fac Med, Med Direct, Geneva, Switzerland..
    Hofmeister, Jeremy
    Univ Hosp Geneva, Dept Psychiat, Fac Med, Med Direct, Geneva, Switzerland..
    Giannakopoulos, Panteleimon
    Univ Hosp Geneva, Dept Psychiat, Fac Med, Med Direct, Geneva, Switzerland..
    Caffeine impact on working memory-related network activation patterns in early stages of cognitive decline2017In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 59, no 4, p. 387-395Article in journal (Refereed)
    Abstract [en]

    Purpose Recent evidence indicates that caffeine may have a beneficial effect on cognitive decline and dementia. The current investigation assessed the effect of acute caffeine administration on working memory during the earliest stage of cognitive decline in elderly participants. Methods The study includes consecutive 45 elderly controls and 18 individuals with mild cognitive impairment (MCI, 71.6 +/- 4.7 years, 7 females). During neuropsychological follow-up at 18 months, 24 controls remained stable (sCON, 70.0 +/- 4.3 years, 11 women), while the remaining 21 showed subtle cognitive deterioration (dCON, 73.4 +/- 5.9 years, 14 women). All participants underwent an established 2-back working task in a crossover design of 200 mg caffeine versus placebo. Data analysis included task-related general linear model and functional connectivity tensorial independent component analysis. Results Working memory behavioral performances did not differ between sCON and dCON, while MCI was slower and less accurate than both control groups (p < 0.05). The dCON group had a less pronounced effect of acute caffeine administration essentially restricted to the right hemisphere (p < 0.05 corrected) and reduced default mode network (DMN) deactivation compared to sCON (p < 0.01 corrected). Conclusion dCON cases are characterized by decreased sensitivity to caffeine effects on brain activation and DMN deactivation. These complex fMRI patterns possibly reflect the instable status of these cases with intact behavioral performances despite already existing functional alterations in neocortical circuits.

  • 23.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Geneva, Switzerland; Univ Geneva, Fac Med, Geneva, Switzerland; Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany .
    Vernooij, Meike W
    Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands; Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Kuijer, Joost P A
    Vrije Univ Amsterdam, Med Ctr, Amsterdam Neurosci, Dept Radiol & Nucl Med, Amsterdam, Netherlands.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Jäger, Hans Rolf
    UCL, Inst Neurol, Neuroradiol Acad Unit, Dept Brain Repair & Rehabil, London, England.
    Barkhof, Frederik
    Vrije Univ Amsterdam, Med Ctr, Amsterdam Neurosci, Dept Radiol & Nucl Med, Amsterdam, Netherlands; UCL, Inst Neurol, Neuroradiol Acad Unit, Dept Brain Repair & Rehabil, London, England.
    Cerebral Microbleeds: Imaging and Clinical Significance2018In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 287, no 1, p. 11-28Article, review/survey (Refereed)
    Abstract [en]

    Cerebral microbleeds (CMBs), also referred to as microhemorrhages, appear on magnetic resonance (MR) images as hypointense foci notably at T2*-weighted or susceptibility-weighted (SW) imaging. CMBs are detected with increasing frequency because of the more widespread use of high magnetic field strength and of newer dedicated MR imaging techniques such as three-dimensional gradient-echo T2*-weighted and SW imaging. The imaging appearance of CMBs is mainly because of changes in local magnetic susceptibility and reflects the pathologic iron accumulation, most often in perivascular macrophages, because of vasculopathy. CMBs are depicted with a true-positive rate of 48%–89% at 1.5 T or 3.0 T and T2*-weighted or SW imaging across a wide range of diseases. False-positive “mimics” of CMBs occur at a rate of 11%–24% and include microdissections, microaneurysms, and microcalcifications; the latter can be differentiated by using phase images. Compared with postmortem histopathologic analysis, at least half of CMBs are missed with premortem clinical MR imaging. In general, CMB detection rate increases with field strength, with the use of three-dimensional sequences, and with postprocessing methods that use local perturbations of the MR phase to enhance T2* contrast. Because of the more widespread availability of high-field-strength MR imaging systems and growing use of SW imaging, CMBs are increasingly recognized in normal aging, and are even more common in various disorders such as Alzheimer dementia, cerebral amyloid angiopathy, stroke, and trauma. Rare causes include endocarditis, cerebral autosomal dominant arteriopathy with subcortical infarcts, leukoencephalopathy, and radiation therapy. The presence of CMBs in patients with stroke is increasingly recognized as a marker of worse outcome. Finally, guidelines for adjustment of anticoagulant therapy in patients with CMBs are under development.

  • 24.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Zaharchuk, Greg
    Thomas, David L
    Lövblad, Karl-Olof
    Barkhof, Frederik
    Golay, Xavier
    Arterial Spin Labeling Perfusion of the Brain: Emerging Clinical Applications2016In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 281, no 2, p. 337-356Article, review/survey (Refereed)
    Abstract [en]

    Arterial spin labeling (ASL) is a magnetic resonance (MR) imaging technique used to assess cerebral blood flow noninvasively by magnetically labeling inflowing blood. In this article, the main labeling techniques, notably pulsed and pseudocontinuous ASL, as well as emerging clinical applications will be reviewed. In dementia, the pattern of hypoperfusion on ASL images closely matches the established patterns of hypometabolism on fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) images due to the close coupling of perfusion and metabolism in the brain. This suggests that ASL might be considered as an alternative for FDG, reserving PET to be used for the molecular disease-specific amyloid and tau tracers. In stroke, ASL can be used to assess perfusion alterations both in the acute and the chronic phase. In arteriovenous malformations and dural arteriovenous fistulas, ASL is very sensitive to detect even small degrees of shunting. In epilepsy, ASL can be used to assess the epileptogenic focus, both in peri- and interictal period. In neoplasms, ASL is of particular interest in cases in which gadolinium-based perfusion is contraindicated (eg, allergy, renal impairment) and holds promise in differentiating tumor progression from benign causes of enhancement. Finally, various neurologic and psychiatric diseases including mild traumatic brain injury or posttraumatic stress disorder display alterations on ASL images in the absence of visualized structural changes. In the final part, current limitations and future developments of ASL techniques to improve clinical applicability, such as multiple inversion time ASL sequences to assess alterations of transit time, reproducibility and quantification of cerebral blood flow, and to measure cerebrovascular reserve, will be reviewed.

  • 25.
    Kopel, Rotem
    et al.
    Univ Geneva, Fac Med, CH-1211 Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland..
    Emmert, Kirsten
    Univ Geneva, Fac Med, CH-1211 Geneva, Switzerland..
    Scharnowski, Frank
    Univ Zurich, Neurosci Ctr Zurich, Psychiat Univ Hosp, Zurich, Switzerland.;Univ Zurich, Zurich Ctr Integrat Human Physiol, Zurich, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany..
    Van De Ville, Dimitri
    Univ Geneva, Fac Med, CH-1211 Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland..
    Distributed Patterns of Brain Activity Underlying Real-Time fMRI Neurofeedback Training2017In: IEEE Transactions on Biomedical Engineering, ISSN 0018-9294, E-ISSN 1558-2531, Vol. 64, no 6, p. 1228-1237Article in journal (Refereed)
    Abstract [en]

    Neurofeedback (NF) based on real-time functional magnetic resonance imaging (rt-fMRI) is an exciting neuroimaging application. In most rt-fMRI NF studies, the activity level of a single region of interest (ROI) is provided as a feedback signal and the participants are trained to up or down regulate the feedback signal. NF training effects are typically analyzed using a confirmatory univariate approach, i.e., changes in the target ROI are explained by a univariate linear modulation. However, learning to self-regulate the ROI activity through NF is mediated by distributed changes across the brain. Here, we deploy a multivariate decoding model for assessing NF training effects across the whole brain. Specifically, we first explain the NF training effect by a posthoc multivariate model that leads to a pattern of coactivation based on 90 functional atlas regions. We then use cross validation to reveal the set of brain regions with the best fit. This novel approach was applied to the data from a rt-fMRI NF study where the participants learned to down regulate the auditory cortex. We found that the optimal model consisted of 16 brain regions whose coactivation patterns best described the training effect over the NF training days. Cross validation of the multivariate model showed that it generalized across the participants. Interestingly, the participants could be clustered into two groups with distinct patterns of coactivation, potentially reflecting different NF learning strategies. Overall, our findings revealed that multiple brain regions are involved in learning to regulate an activity in a single ROI, and thus leading to a better understanding of the mechanisms underlying NF training.

  • 26.
    Lazarczyk, Maciej J
    et al.
    Univ Geneva, Dept Med Direct, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDR Radiol Diagnost Ctr Carouge, Geneva, Switzerland..
    Savioz, Armand
    Univ Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland..
    Gimelli, Stefania
    Univ Geneva, Univ Hosp Geneva, Dept Med Genet & Labs, Geneva, Switzerland..
    Bena, Frédérique
    Univ Geneva, Univ Hosp Geneva, Dept Med Genet & Labs, Geneva, Switzerland..
    Giannakopoulos, Panteleimon
    Univ Geneva, Fac Med, Dept Psychiat, Geneva, Switzerland..
    Heterozygous Deletion of Chorein Exons 70-73 and GNA14 Exons 3-7 in a Brazilian Patient Presenting With Probable Tau-Negative Early-Onset Alzheimer Disease2017In: Alzheimer Disease and Associated Disorders, ISSN 0893-0341, E-ISSN 1546-4156, Vol. 31, no 1, p. 82-85Article in journal (Refereed)
  • 27. Meskaldji, Djalel-Eddine
    et al.
    Preti, Maria Giulia
    Bolton, Thomas Aw
    Montandon, Marie-Louise
    Rodriguez, Cristelle
    Morgenthaler, Stephan
    Giannakopoulos, Panteleimon
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Van De Ville, Dimitri
    Prediction of long-term memory scores in MCI based on resting-state fMRI2016In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 12, p. 785-795Article in journal (Refereed)
    Abstract [en]

    Resting-state functional MRI (rs-fMRI) opens a window on large-scale organization of brain function. However, establishing relationships between resting-state brain activity and cognitive or clinical scores is still a difficult task, in particular in terms of prediction as would be meaningful for clinical applications such as early diagnosis of Alzheimer's disease. In this work, we employed partial least square regression under cross-validation scheme to predict episodic memory performance from functional connectivity (FC) patterns in a set of fifty-five MCI subjects for whom rs-fMRI acquisition and neuropsychological evaluation was carried out. We show that a newly introduced FC measure capturing the moments of anti-correlation between brain areas, discordance, contains key information to predict long-term memory scores in MCI patients, and performs better than standard measures of correlation to do so. Our results highlighted that stronger discordance within default mode network (DMN) areas, as well as across DMN, attentional and limbic networks, favor episodic memory performance in MCI.

  • 28.
    Pezzoli, S.
    et al.
    Univ Sheffield, Dept Neurosci, Sheffield, S Yorkshire, England.;Kings Coll London, Dept Psychosis Studies, London, England..
    Emsell, L.
    Katholieke Univ Leuven, Dept Imaging & Pathol, Leuven, Belgium.;Natl Univ Ireland Galway, Neuroimaging Cognit & Genom Ctr NICOG, Galway, Ireland.;NCBES Galway Neurosci Ctr, Galway, Ireland.;Katholieke Univ Leuven, Dept Old Age Psychiat, Leuven, Belgium..
    Yip, S.
    Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.;Kings Coll London, Ctr Neuroimaging Sci, London, England..
    Dima, D.
    Kings Coll London, Social Genet & Dev Psychiat Ctr, London, England.;Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA..
    Giannakopoulos, P.
    Univ Geneva, Dept Psychiat, Geneva, Switzerland..
    Zarei, M.
    Univ Geneva, Dept Psychiat, Geneva, Switzerland..
    Tognin, S.
    Kings Coll London, Dept Psychosis Studies, London, England..
    James, A.
    Univ Oxford, Dept Psychiat, Oxford, England..
    Haller, Sven
    Shahid Beheshti Univ, Natl Brain Mapping Ctr, Tehran, Iran.;Affidea CDRC Ctr Diagnost Radiol Carouge, Carouge, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany..
    Frangou, S.
    Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA..
    Goodwin, G.
    Univ Oxford, Dept Psychiat, Oxford, England..
    McDonald, C.
    Natl Univ Ireland Galway, Neuroimaging Cognit & Genom Ctr NICOG, Galway, Ireland.;NCBES Galway Neurosci Ctr, Galway, Ireland..
    Kempton, M.
    Kings Coll London, Dept Psychosis Studies, London, England..
    Meta-analysis of regional white matter volume in bipolar disorder with replication in an independent sample2016In: Bipolar Disorders, ISSN 1398-5647, E-ISSN 1399-5618, Vol. 18, p. 111-112Article in journal (Other academic)
  • 29.
    Zanchi, Davide
    et al.
    Univ Basel, Dept Psychiat UPK, Basel, Switzerland..
    Brody, Arthur
    Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA.;VA Greater Los Angeles Healthcare Syst, Dept Res, Los Angeles, CA USA..
    Borgwardt, Stefan
    Univ Basel, Dept Psychiat UPK, Basel, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany..
    Sex Effects on Smoking Cue Perception in Non-Smokers, Smokers, and Ex-Smokers: A Pilot Study2016In: Frontiers in Psychiatry, ISSN 1664-0640, E-ISSN 1664-0640, Vol. 7, article id 187Article in journal (Refereed)
    Abstract [en]

    Introduction: Recent neuroimaging research suggests sex-related brain differences in smoking addiction, In the present pilot study, we assessed gender-related differences in brain activation in response to cigarette-related video cues, investigating non-smokers, smokers, and ex-smokers. Methods: First, we compared 29 females (28.6 +/- 5.3) vs. 23 males (31.5 +/- 6.4), regardless of current smoking status to assess global gender-related effects. Second, we performed a post hoc analysis of non-smokers (9 females and 7 males). Participants performed a block-design functional magnetic resonance imaging paradigm contrasting smoking with control cue video exposures. Data analyses included task-related general linear model, voxel-based morphometry of gray matter (GM), and tract-based spatial statistics of white matter (WM). Results: First, the global effect regardless of current smoking status revealed higher activation in the bilateral superior frontal gyrus and anterior cingulate cortex (ACC) for females compared to males. Second, the analysis according to current smoking status demonstrated higher activation in female vs. male smokers vs. non-smokers in the superior frontal gyrus, anterior and posterior cingulate cortex, and precuneus, and higher activationi in female vs. male ex-smokers vs. non-smokers in the right precentral gyrus, in the right insula and ACC. No structural differences were found in GM or WM. Conclusion: The current study identifies gender-related brain functional differences in smokers and ex-smokers compared to non-smokers. The current work can be considered as a starting point for future investigations into gender differences in brain responses to cigarette-related cues

  • 30.
    Zanchi, Davide
    et al.
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland..
    Brody, Arthur L.
    Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA.;VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA.;VA Greater Los Angeles Healthcare Syst, Dept Res, Los Angeles, CA USA..
    Montandon, Marie-Louise
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland..
    Kopel, Rotem
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland..
    Emmert, Kirsten
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland..
    Preti, Maria Giulia
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland..
    Van de Ville, Dimitri
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Affidea Ctr Diagnost Radiol Carouge CDRC, Geneva, Switzerland..
    Cigarette smoking leads to persistent and dose-dependent alterations of brain activity and connectivity in anterior insula and anterior cingulate2015In: Addiction Biology, ISSN 1355-6215, E-ISSN 1369-1600, Vol. 20, no 6, p. 1033-1041Article in journal (Refereed)
    Abstract [en]

    Although many smokers try to quit smoking, only about 20-25 percent will achieve abstinence despite 6months or more of gold-standard treatment. This low success rate suggests long-term changes in the brain related to smoking, which remain poorly understood. We compared ex-smokers to both active smokers and non-smokers using functional magnetic resonance imaging (fMRI) to explore persistent modifications in brain activity and network organization. This prospective and consecutive study includes 18 non-smokers (29.5 +/- 6.7years of age, 11 women), 14 smokers (10 cigarettes a day >2years of smoking, 29.3 +/- 6.0years of age, 10 women) and 14 ex-smokers (>1year of quitting 30.5 +/- 5.7years of age, 10 women). Participants underwent a block-design fMRI study contrasting smoking cue with control (neutral cue) videos. Data analyses included task-related general linear model, seed-based functional connectivity, voxel-based morphometry (VBM) of gray matter and tract-based spatial statistics (TBSS) of white matter. Smoking cue videos versus control videos activated the right anterior insula in ex-smokers compared with smokers, an effect correlating with cumulative nicotine intake (pack-years). Moreover, ex-smokers had a persistent decrease in functional connectivity between right anterior insula and anterior cingulate cortex (ACC) compared with control participants, but similar to active smokers. Potentially confounding alterations in gray or white matter were excluded in VBM and TBSS analyses. In summary, ex-smokers with long-term nicotine abstinence have persistent and dose-dependent brain network changes notably in the right anterior insula and its connection to the ACC.

  • 31.
    Zanchi, Davide
    et al.
    Univ Basel, Dept Psychiat UPK, Basel, Switzerland..
    Cunningham, Gregory
    Univ Hosp Geneva, Div Orthopaed & Trauma Surg, Dept Surg, Geneva, Switzerland..
    Ladermann, Alexandre
    Univ Hosp Geneva, Div Orthopaed & Trauma Surg, Dept Surg, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;La Tour Hosp, Div Orthopaed & Trauma Surg, Geneva, Switzerland..
    Ozturk, Mehmet
    Univ Hosp Geneva, Div Orthopaed & Trauma Surg, Dept Surg, Geneva, Switzerland..
    Hoffmeyer, Pierre
    Univ Hosp Geneva, Div Orthopaed & Trauma Surg, Dept Surg, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland.;Affidea Carouge Radiol Diagnost Ctr, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany..
    Brain activity in the right-frontal pole and lateral occipital cortex predicts successful post-operatory outcome after surgery for anterior glenoumeral instability2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 498Article in journal (Refereed)
    Abstract [en]

    Shoulder apprehension is more complex than a pure mechanical problem of the shoulder, creating a scar at the brain level that prevents the performance of specific movements. Surgery corrects for shoulder instability at the physical level, but a re-dislocation within the first year is rather common. Predicting which patient will be likely to have re-dislocation is therefore crucial. We hypothesized that the assessment of neural activity at baseline and follow-up is the key factor to predict the postoperatory outcome. 13 patients with shoulder apprehension (30.03 +/- 7.64 years) underwent clinical and fMRI examination before and one year after surgery for shoulder dislocation contrasting apprehension cue videos and control videos. Data analyses included task-related general linear model (GLM) and correlations imaging results with clinical scores. Clinical examination showed decreased pain and increased shoulder functions for post-op vs. pre-op. Coherently, GLM results show decreased activation of the left pre-motor cortex for post-surgery vs. pre-surgery. Right-frontal pole and right-occipital cortex activity predicts good recovery of shoulder function measured by STT. Our findings demonstrate that beside physical changes, changes at the brain level also occur one year after surgery. In particular, decreased activity in pre-motor and orbito-frontal cortex is key factor for a successful post-operatory outcome.

  • 32. Zanchi, Davide
    et al.
    Cunningham, Gregory
    Lädermann, Alexandre
    Ozturk, Mehmet
    Hoffmeyer, Pierre
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Structural white matter and functional connectivity alterations in patients with shoulder apprehension2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 42327Article in journal (Refereed)
    Abstract [en]

    Previous functional magnetic resonance imaging (fMRI) findings indicate that shoulder apprehension is more complex than a pure mechanical problem of the shoulder, showing a direct modification in functional brain networks associated with motor inhibition and emotional regulation. The current study extends these findings by investigating further structural alterations in patients with shoulder apprehension compared to controls. 14 aged patients with shoulder apprehension (27.3 ± 2.0 years) and 10 matched healthy controls (29.6 ± 1.3 years) underwent clinical and fMRI examination including fMRI and diffusion tensor imaging (DTI). Tract-based spatial statistics procedure was used to analyze white matter (WM) alterations. Functional images were analyzed investigating resting state network connectivity. DTI results were correlated with different shoulder clinical scores and functional connectivity networks. Fractional anisotropy (FA), representing white matter integrity, is increased in the left internal capsule and partially in the thalamus in patients compared to controls. Moreover, FA correlates negatively with simple shoulder test (SST) scores (p < .05) and positively with a functional connectivity network qualitatively replicating previous results (p < .01). This study extends previous findings, showing that in addition to functional changes, structural white matter changes are also present in patients with shoulder apprehension.

  • 33.
    Zanchi, Davide
    et al.
    University of Basel, Department of Psychiatry (UPK), CH-4012 Basel, Switzerland.
    Depoorter, Antoinette
    Division of Neuropaediatrics & Developmental Medicine, University Children's Hospital, Basel, Switzerland.
    Egloff, Laura
    University of Basel, Department of Psychiatry (UPK), CH-4012 Basel, Switzerland.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Centre de Diagnostic Radiologique de Carouge CDRC, Geneva, Switzerland.; Faculty of Medicine of the University of Geneva, Switzerland.; Department of Neuroradiology, University Hospital Freiburg, Germany.
    Mählmann, Laura
    University of Basel, Department of Psychiatry (UPK), CH-4012 Basel, Switzerland.
    Lang, Undine E
    University of Basel, Department of Psychiatry (UPK), CH-4012 Basel, Switzerland.
    Drewe, Jürgen
    Department of Research, St. Claraspital, Switzerland.
    Beglinger, Christoph
    Department of Research, St. Claraspital, Switzerland.
    Schmidt, André
    University of Basel, Department of Psychiatry (UPK), CH-4012 Basel, Switzerland.
    Borgwardt, Stefan
    University of Basel, Department of Psychiatry (UPK), CH-4012 Basel, Switzerland.
    The impact of gut hormones on the neural circuit of appetite and satiety: A systematic review2017In: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 80, p. 457-475, article id S0149-7634(17)30138-0Article in journal (Refereed)
    Abstract [en]

    The brain-gut-axis is an interdependent system affecting neural functions and controlling our eating behaviour. In recent decades, neuroimaging techniques have facilitated its investigation. We systematically looked into functional and neurochemical brain imaging studies investigating how key molecules such as ghrelin, glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), cholecystokinin (CCK), leptin, glucose and insulin influence the function of brain regions regulating appetite and satiety. Of the 349 studies published before July 2016 identified in the database search, 40 were included (27 on healthy and 13 on obese subjects). Our systematic review suggests that the plasma level of ghrelin, the gut hormone promoting appetite, is positively correlated with activation in the pre-frontal cortex (PFC), amygdala and insula and negatively correlated with activation in subcortical areas such as the hypothalamus. In contrast, the plasma levels of glucose, insulin, leptin, PYY, GLP-1 affect the same brain regions conversely. Our study integrates previous investigations of the gut-brain matrix during food-intake and homeostatic regulation and may be of use for future meta-analyses of brain-gut interactions.

  • 34.
    Zanchi, Davide
    et al.
    Univ Basel, Dept Psychiat, Basel, Switzerland.;Univ Psychiat Clin, Dept Neuropsychiat, Basel, Switzerland..
    Giannakopoulos, Panteleimon
    Univ Geneva, Fac Med, Dept Psychiat, Geneva, Switzerland..
    Borgwardt, Stefan
    Univ Basel, Dept Psychiat, Basel, Switzerland..
    Rodriguez, Cristelle
    Univ Geneva, Fac Med, Dept Psychiat, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Carouge Radiol Diagnost Ctr, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Univ Geneva, Fac Med, Dept Neuroradiol, Geneva, Switzerland..
    Hippocampal and Amygdala Gray Matter Loss in Elderly Controls with Subtle Cognitive Decline2017In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 9, article id 50Article in journal (Refereed)
    Abstract [en]

    In contrast to the idea that hippocampal and amygdala volume loss occur in late phases of neurodegeneration, recent contributions point to the relevance of preexisting structural deficits that are associated with aging and are independent of amyloid deposition in preclinical Alzheimer disease cases. The present work explores GM hippocampal and amygdala volumes in elderly controls displaying the first signs of cognitive decline. 455 subjects (263 females), including 374 controls (228 females) and 81 middle cognitive impairment subjects (35 females), underwent two neuropsychological evaluations (baseline and 18 months follow-up) and a MRI-T1 examination (only baseline). Clinical assessment included Mini-Mental State Examination (MMSE), Clinical Dementia Rating scale, Hospitalized Anxiety and Depression scale, the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery and RI-48 Cued Recall Test (RI-48) for episodic memory. Based on their cognitive performance, we defined the controls as stable controls (sCON) and deteriorating controls (dCONs). Analyses included volumetric assessment, shape analyses and linear regressions between GM volume loss and differences in clinical scores between baseline and follow-up. Significant GM volume decrease in hippocampus bilaterally and right amygdala was found in dCON compared to sCON (p < 0.05). Lower right amygdala volumes were measured in mild cognitive impairment (MCI) compared to sCON (p < 0.05). Shape analyses revealed that atrophy was more pronounced at the superior-posterior lateral side of the hippocampus and amygdala. Significant correlations were found between GM volume of left hippocampus and the delta of MMSE and RI-48 scores in dCON and MCI groups separately. Decreased hippocampal and right amygdala volumes precede the first signs of cognitive decline in healthy elderly controls at the pre-MCI state. Left hippocampus volume may also predict short-term changes of overall cognition in these vulnerable cases.

  • 35.
    Zanchi, Davide
    et al.
    Univ Basel Hosp, Dept Psychiat, CH-4012 Basel, Switzerland..
    Meyer-Gerspach, Anne Christin
    Univ Hosp, Dept Biomed, CH-4031 Basel, Switzerland..
    Suenderhauf, Claudia
    Univ Basel Hosp, Dept Psychiat, CH-4012 Basel, Switzerland..
    Janach, Katharina
    Univ Hosp, Dept Biomed, CH-4031 Basel, Switzerland..
    le Roux, Carel W.
    Univ Coll Dublin, Conway Inst, Diabet Complicat Res Ctr, Dublin, Ireland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland.;Affidea CDRC Ctr Diagnost Radiolog Carouge, Carouge, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland..
    Drewe, Jurgen
    St Clara Hosp, Dept Res, Basel, Switzerland..
    Beglinger, Christoph
    St Clara Hosp, Dept Res, Basel, Switzerland..
    Wlnerhanssen, Bettina K.
    Univ Hosp, Dept Biomed, CH-4031 Basel, Switzerland.;St Clara Hosp, Dept Res, Basel, Switzerland..
    Borgwardt, Stefan
    Univ Basel Hosp, Dept Psychiat, CH-4012 Basel, Switzerland..
    Differential effects of L-tryptophan and L-leucine administration on brain resting state functional networks and plasma hormone levels2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 35727Article in journal (Refereed)
    Abstract [en]

    Depending on their protein content, single meals can rapidly influence the uptake of amino acids into the brain and thereby modify brain functions. The current study investigates the effects of two different amino acids on the human gut-brain system, using a multimodal approach, integrating physiological and neuroimaging data. In a randomized, placebo-controlled trial, L-tryptophan, L-leucine, glucose and water were administered directly into the gut of 20 healthy subjects. Functional MRI (fMRI) in a resting state paradigm (RS), combined with the assessment of insulin and glucose blood concentration, was performed before and after treatment. Independent component analysis with dual regression technique was applied to RS-fMRI data. Results were corrected for multiple comparisons. In comparison to glucose and water, L-tryptophan consistently modifies the connectivity of the cingulate cortex in the default mode network, of the insula in the saliency network and of the sensory cortex in the somatosensory network. L-leucine has lesser effects on these functional networks. L-tryptophan and L-leucine also modified plasma insulin concentration. Finally, significant correlations were found between brain modifications after L-tryptophan administration and insulin plasma levels. This study shows that acute L-tryptophan and L-leucine intake directly influence the brain networks underpinning the food-reward system and appetite regulation.

  • 36. Zanchi, Davide
    et al.
    Montandon, Marie-Louise
    Sinanaj, Indrit
    Rodriguez, Cristelle
    Depoorter, Antoinette
    Herrmann, Francois R
    Borgwardt, Stefan
    Giannakopoulos, Panteleimon
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Carouge Radiologic Diagnostic Center, Geneva, Switzerland.
    Decreased Fronto-Parietal and Increased Default Mode Network Activation is Associated with Subtle Cognitive Deficits in Elderly Controls2017In: NeuroSignals (Print), ISSN 1424-862X, E-ISSN 1424-8638, Vol. 25, no 1, p. 127-138Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cognitive functions progressively deteriorate during aging and neurodegenerative diseases. The present study aims at investigating differences in working memory performance as well as functional brain changes during the earliest stages of cognitive decline in health elderly individuals.

    METHODS: 62 elderly individuals (41 females), including 41 controls (35 females) and 21 middle cognitive impairment subjects (6 females), underwent neuropsychological assessment at baseline and an fMRI examination in a N-back paradigm contrasting 2-back vs. 0-back condition. Upon a 18 months follow-up, we identified stable controls (sCON) with preserved cognition and deteriorating controls (dCON) with -1SD decrease of performances in at least two neuropsychological tests. Data analyses included accuracy and reaction time (RT) for the 2-back condition and general linear model (GLM) for the fMRI sequence.

    RESULTS: At the behavioral level, sCON and dCON performed better than MCI in terms of accuracy and reaction time. At the brain level, functional differences in regions of the fronto-parietal network (FPN) and of the Default Mode Network (DFM) were observed. Significantly lower neural activations in the bilateral inferior and middle frontal gyri were found in MCI versus both dCON / sCON and for dCON versus sCON. Significantly increased activations in the anterior cingulate cortex and posterior cingulate cortex and bilateral insula were found in MCI versus both dCON / sCON and in dCON versus sCON.

    CONCLUSION: The present study suggests that brain functional changes in FPN and DMN anticipate differences in cognitive performance in healthy elderly individuals with subsequent subtle cognitive decline.

  • 37.
    Zanchi, Davide
    et al.
    Univ Basel Hosp, Dept Psychiat, Basel, Switzerland.
    Viallon, Magalie
    Univ Jean Monnet St Etienne, Univ Lyon, INSA Lyon, CNRS,UMR 5220,INSERM,U1206,CREATIS, St Etienne, France.; CHU St Etienne, Dept Radiol, St Etienne, France.
    Le Goff, Caroline
    Univ Liege, Dept Clin Chem, Liege, Belgium.
    Millet, Grégoire P
    Univ Lausanne, Inst Sports Sci, Lausanne, Switzerland.
    Giardini, Guido
    Department of Neurology and Stroke Unit, Mountain Medicine and Neurology Center Valle d'Aosta Regional Hospital, Aosta, Italy.
    Croisille, Pierre
    Univ Jean Monnet St Etienne, Univ Lyon, INSA Lyon, CNRS,UMR 5220,INSERM,U1206,CREATIS, St Etienne, France.; CHU St Etienne, Dept Radiol, St Etienne, France.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Geneva, Switzerland.; Univ Geneva, Fac Med, Geneva, Switzerland.; Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.
    Extreme Mountain Ultra-Marathon Leads to Acute but Transient Increase in Cerebral Water Diffusivity and Plasma Biomarkers Levels Changes2017In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 7, article id 664Article in journal (Refereed)
    Abstract [en]

    Background: Pioneer studies demonstrate the impact of extreme sport load on the human brain, leading to threatening conditions for athlete's health such as cerebral edema. The investigation of brain water diffusivity, allowing the measurement of the intercellular water and the assessment of cerebral edema, can give a great contribution to the investigation of the effects of extreme sports on the brain. We therefore assessed the effect of supra-physiological effort (extreme distance and elevation changes) in mountain ultra-marathons (MUMs) athletes combining for the first time brain magnetic resonance imaging (MRI) and blood parameters.

    Methods:This longitudinal study included 19 volunteers (44.2 ± 9.5 years) finishing a MUM (330 km, elevation + 24000 m). Quantitative measurements of brain diffusion-weighted images (DWI) were performed at 3 time-points: Before the race, upon arrival and after 48 h. Multiple blood biomarkers were simultaneously investigated. Data analyses included brain apparent diffusion coefficient (ADC) and physiological data comparisons between three time-points.

    Results:The whole brain ADC significantly increased from baseline to arrival (p = 0.005) and then significantly decreased at recovery (p = 0.005) to lower values than at baseline (p = 0.005). While sodium, potassium, calcium, and chloride as well as hematocrit (HCT) changed over time, the serum osmolality remained constant. Significant correlations were found between whole brain ADC changes and osmolality (p = 0.01), cholesterol (p = 0.009), c-reactive protein (p = 0.04), sodium (p = 0.01), and chloride (p = 0.002) plasma level variations.

    Conclusions:These results suggest the relative increase of the inter-cellular volume upon arrival, and subsequently its reduction to lower values than at baseline, indicating that even after 48 h the brain has not fully recovered to its equilibrium state. Even though serum electrolytes may only indirectly indicate modifications at the brain level due to the blood brain barrier, the results concerning osmolality suggest that body water might directly influence the change in cerebral ADC. These findings establish therefore a direct link between general brain inter-cellular water content and physiological biomarkers modifications produced by extreme sport.

1 - 37 of 37
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