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Claus Kiefer

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7 papers

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YNICL Journal 2024 Journal Article

Cerebral blood flow and white matter alterations in adults with phenylketonuria

Leonie Steiner
Raphaela Muri
Dilmini Wijesinghe
Kay Jann
Stephanie Maissen-Abgottspon
Piotr Radojewski
Katarzyna Pospieszny
Roland Kreis

BACKGROUND: Phenylketonuria (PKU) represents a congenital metabolic defect that disrupts the process of converting phenylalanine (Phe) into tyrosine. Earlier investigations have revealed diminished cognitive performance and changes in brain structure and function (including the presence of white matter lesions) among individuals affected by PKU. However, there exists limited understanding regarding cerebral blood flow (CBF) and its potential associations with cognition, white matter lesions, and metabolic parameters in patients with PKU, which we therefore aimed to investigate in this study. METHOD: H spectroscopy, and white matter lesions were rated by two neuroradiologists on T2 weighted images. White matter integrity was examined with diffusion tensor imaging (DTI). For patients only, concurrent plasma Phe levels were assessed after an overnight fasting period. Furthermore, past Phe levels were collected to estimate historical metabolic control. On the day of the MRI, each participant underwent a cognitive assessment measuring IQ and performance in executive functions, attention, and processing speed. RESULTS: No significant group difference was observed in global CBF between patients and controls (F (1, 87) = 3.81, p = 0.054). Investigating CBF on the level of cerebral arterial territories, reduced CBF was observed in the left middle and posterior cerebral artery (MCA and PCA), with the most prominent reduction of CBF in the anterior subdivision of the MCA (F (1, 87) = 6.15, p = 0.015, surviving FDR correction). White matter lesions in patients were associated with cerebral blood flow reduction in the affected structure. Particularly, patients with lesions in the occipital lobe showed significant CBF reductions in the left PCA (U = 352, p = 0.013, surviving FDR correction). Additionally, axial diffusivity measured with DTI was positively associated with CBF in the ACA and PCA (surviving FDR correction). Cerebral blood flow did not correlate with cognitive performance or metabolic parameters. CONCLUSION: The relationship between cerebral blood flow and white matter indicates a complex interplay between vascular health and white matter alterations in patients with PKU. It highlights the importance of considering a multifactorial model when investigating the impact of PKU on the brain.

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YNICL Journal 2018 Journal Article

Resting-state connectivity and executive functions after pediatric arterial ischemic stroke

Salome Kornfeld
Rui Yuan
Bharat B. Biswal
Sebastian Grunt
Sandeep Kamal
Juan Antonio Delgado Rodríguez
Mária Regényi
Roland Wiest

BACKGROUND: The aim of this study was to compare the relationship between core executive functions and frontoparietal network connections at rest between children who had suffered an arterial ischemic stroke and typically developing peers. METHODS: Children diagnosed with arterial ischemic stroke more than two years previously and typically developing controls were included. Executive function (EF) measures comprised inhibition (Go-NoGo task), fluency (category fluency task), processing speed (processing speed tasks), divided attention, working memory (letter-number sequencing), conceptual reasoning (matrices) and EF in everyday life (questionnaire). High-resolution T1-weighted magnetic resonance (MR) structural images and resting-state functional MR imaging were acquired. Independent component analysis was used to identify the frontoparietal network. Functional connections were obtained through correlation matrices; associations between cognitive measures and functional connections through Pearson's correlations. RESULTS: Twenty participants after stroke (7 females; mean age 16.0 years) and 22 controls (13 females; mean age 14.8 years) were examined. Patients and controls performed within the normal range in all executive tasks. Patients who had had a stroke performed significantly less well in tests of fluency, processing speed and conceptual reasoning than controls. Resting-state functional connectivity between the left and right inferior parietal lobe was significantly reduced in patients after pediatric stroke. Fluency, processing speed and perceptual reasoning correlated positively with the interhemispheric inferior parietal lobe connection in patients and controls. CONCLUSION: Decreased interhemispheric connections after stroke in childhood may indicate a disruption of typical interhemispheric interactions relating to executive functions. The present results emphasize the relationship between functional organization of the brain at rest and cognitive processes.

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YNICL Journal 2016 Journal Article

T2-relaxometry predicts outcome of DBS in idiopathic Parkinson's disease

Tarja Lönnfors-Weitzel
Thilo Weitzel
Johannes Slotboom
Claus Kiefer
Claudio Pollo
Michael Schüpbach
Markus Oertel
Alain Kaelin

INTRODUCTION: Deep brain stimulation (DBS) nowadays is a well-established treatment of motor symptoms in Parkinson's disease. The subthalamic nucleus (STN) is a common target for DBS, because motor improvements have been shown to be superior to best medical therapy, if DBS electrodes have been appropriately positioned. DBS target identification can be assisted by MRI beyond structural imaging by spatially resolved measurement of T2-relaxation times (T2r). AIM: We pose the question, whether T2r of the STN is linked to the severity of the disease and whether outcome of DBS may be correlated to an asymmetric manifestation of the disease. Further, we investigated if abnormal T2r in the STN may be predictive for outcome of DBS. METHODS: Twelve patients underwent preoperative MR imaging including a multi echo relaxometry sequence (3 Tesla, Siemens Medical Systems, Erlangen, Germany) ahead of DBS. T2r were determined for STN, substantia nigra (SN), red nucleus (RN) and centrum semiovale (CSO). Unified Parkinson's disease Rating Scale (UPDRS) scores were tested before and after DBS. Patients' T2r and deduced values representing left-right asymmetry of measurements were correlated with UPDRS scores and measures for outcome of DBS. Furthermore, patients' T2r were compared with T2r measurements in 12 healthy controls (HC). RESULTS: Patients' T2r for SN (mean 45.4 ms ± 4.4 ms) and STN (mean 56.4 ms ± 3.8 ms) were significantly shorter than T2r in HCs for SN (mean 60.7 ± 4.6) and STN (mean 66.1 ms ± 4.0 ms). While no mean T2r asymmetry was found in the SN, patients' mean T2r for STN showed a weakened left-right correlation (Pearson correlation coefficient 0.19 versus 0.72 in HC) indicating asymmetric degeneration. T2r asymmetry was not linked to the more severely affected hemisphere. The respective lower T2r within the left or right target region was significantly correlated to the outcome in terms of UPDRS III improvement in "off" state (Pearson correlation 0.82 corresponding to p ≪ 0.01). Patients with T2r of STN lower than 50 ms showed no response to DBS in the UPDRS. The maximum T2r for SN correlated to the improvement between UPDRS "off" minus and "on" (Dopamine response) but failed to predict DBS outcome. CONCLUSIONS: The lower boundaries of T2r in the STN predict motor outcome in DBS. T2r asymmetry in the STN is not associated with increased clinical symptoms, but with response to therapy. Thus, patients with very low T2r may be inappropriate candidates for DBS.

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YNIMG Journal 2009 Journal Article

Multi-parametric classification of Alzheimer's disease and mild cognitive impairment: The impact of quantitative magnetization transfer MR imaging

Claus Kiefer
Lisa Brockhaus
Katja Cattapan-Ludewig
Pietro Ballinari
Yuliya Burren
Gerhard Schroth
Roland Wiest

Multi-parametric and quantitative magnetic resonance imaging (MRI) techniques have come into the focus of interest, both as a research and diagnostic modality for the evaluation of patients suffering from mild cognitive decline and overt dementia. In this study we address the question, if disease related quantitative magnetization transfer effects (qMT) within the intra- and extracellular matrices of the hippocampus may aid in the differentiation between clinically diagnosed patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI) and healthy controls. We evaluated 22 patients with AD (n =12) and MCI (n =10) and 22 healthy elderly (n =12) and younger (n =10) controls with multi-parametric MRI. Neuropsychological testing was performed in patients and elderly controls (n =34). In order to quantify the qMT effects, the absorption spectrum was sampled at relevant off-resonance frequencies. The qMT-parameters were calculated according to a two-pool spin-bath model including the T1- and T2 relaxation parameters of the free pool, determined in separate experiments. Histograms (fixed bin-size) of the normalized qMT-parameter values (z-scores) within the anterior and posterior hippocampus (hippocampal head and body) were subjected to a fuzzy-c-means classification algorithm with downstreamed PCA projection. The within-cluster sums of point-to-centroid distances were used to examine the effects of qMT- and diffusion anisotropy parameters on the discrimination of healthy volunteers, patients with Alzheimer and MCIs. The qMT-parameters T2r (T2 of the restricted pool) and F (fractional pool size) differentiated between the three groups (control, MCI and AD) in the anterior hippocampus. In our cohort, the MT ratio, as proposed in previous reports, did not differentiate between MCI and AD or healthy controls and MCI, but between healthy controls and AD.

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YNIMG Journal 2006 Journal Article

Examining the gateway to the limbic system with diffusion tensor imaging: The perforant pathway in dementia

Peter Kalus
Johannes Slotboom
Jürgen Gallinat
Richard Mahlberg
Katja Cattapan-Ludewig
Roland Wiest
Thomas Nyffeler
Caroline Buri

Current treatments for Alzheimer's disease (AD) are only able to slow the progression of mental deterioration, making early and reliable diagnosis an essential part of any promising therapeutic strategy. In the initial stages of AD, the first neuropathological alterations occur in the perforant pathway (PP), a large neuronal fiber tract located at the entrance to the limbic system. However, to date, there is no sensitive diagnostic tool for performing in vivo assessments of this structure. In the present bimodal magnetic resonance imaging (MRI) study, we examined 10 elderly controls, 10 subjects suffering from mild cognitive impairment (MCI), and 10 AD patients in order to evaluate the sensitivity of diffusion tensor imaging (DTI), a new MRI technique, for detecting changes in the PP. Furthermore, the diagnostic explanatory power of DTI data of the PP should be compared to high-resolution MRI volumetry and intervoxel coherences (COH) of the hippocampus and the entorhinal cortex, two limbic regions also involved in the pathophysiology of early AD. DTI revealed a marked decrease in COH values in the PP region of MCI (right side: 26%, left side: 29%, as compared to controls) and AD patients (right side: 37%, left side: 43%, as compared to controls). Reductions in COH values of the PP region were significantly correlated with cognitive impairment. DTI data of the PP zone were the only parameter differing significantly between control subjects and MCI patients, while the volumetric measures and the COH values of the hippocampus and the entorhinal cortex did not. DTI of medial temporal brain regions is a promising non-invasive tool for the in vivo diagnosis of the early/preclinical stages of AD.

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YNIMG Journal 2005 Journal Article

New evidence for involvement of the entorhinal region in schizophrenia: a combined MRI volumetric and DTI study

Peter Kalus
Johannes Slotboom
Jürgen Gallinat
Andrea Federspiel
Jan Gralla
Luca Remonda
Werner K. Strik
Gerhard Schroth

Postmortem examinations and magnetic resonance imaging (MRI) studies suggest involvement of the entorhinal cortex (EC) in schizophrenic psychoses. However, the extent and nature of the possible pathogenetical process underlying the observed alterations of this limbic key region for processing of multimodal sensory information remains unclear. Three-dimensional high-resolution MRI volumetry and evaluation of the regional diffusional anisotropy based on diffusion tensor imaging (DTI) were performed on the EC of 15 paranoid schizophrenic patients and 15 closely matched control subjects. In schizophrenic patients, EC volumes showed a slight, but not significant, decrease. However, the anisotropy values, expressed as inter-voxel coherences (COH), were found to be significantly decreased by 17. 9% (right side) and 12. 5% (left side), respectively, in schizophrenics. Reduction of entorhinal diffusional anisotropy can be hypothesized to be functionally related to disturbances in the perforant path, the principal efferent EC fiber tract supplying the limbic system with neuronal input from multimodal association centers. Combinations of different MRI modalities are a promising approach for the detection and characterization of subtle brain tissue alterations.

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YNIMG Journal 2004 Journal Article

Differentiating hippocampal subregions by means of quantitative magnetization transfer and relaxometry: preliminary results

Claus Kiefer
Johannes Slotboom
Caroline Buri
Jan Gralla
Luca Remonda
Thomas Dierks
Werner K. Strik
Gerhard Schroth

The hippocampal formation (HF) of healthy control subjects and schizophrenic patients was examined using an MRI experiment that implements sequences for relaxometry and magnetization transfer (MT) quantification. In addition to the semi-quantitative magnetization transfer ratio (MTR), all of the observable properties of the binary spin bath model were included. The study demonstrates that, in contrast to the MTR, quantitative MT parameters (especially the T2 relaxation time of restricted protons, T2b) are capable to differentiate functionally significant subregions within the HF. The MT methodology appears to be a promising new tool for the differential microstructural evaluation of the HF in neuropsychiatric disorders accompanied by memory disturbances.

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