Biomedical subjects

F Barkhof

Publications and source records attributed to F Barkhof.

At least 73 records · Page 4Linked to original sources

PubMed2003

Interobserver variability in the radiological assessment of response to chemotherapy in glioma.

OBJECTIVE: To assess the interobserver variability in the radiologic assessment of response to chemotherapy in patients with recurrent glioma. METHODS: Five clinicians with experience in the treatment and follow-up of patients with glioma measured tumor size in 20 pairs of CT and 20 pairs of MRI scans of 35 patients who had been treated with chemotherapy for recurrent glioma. Tumor size was defined as the product of the two largest perpendicular enhancing tumor diameters on the postcontrast images. To assess the interobserver variability in the measurements of tumor size, and in the classification according to the widely used Macdonald response criteria, intraclass correlation coefficients (ICC) and weighted kappa values were calculated. RESULTS: Substantial interobserver agreement was noted in the manual, two-dimensional measurements of tumor size on CT and MRI in patients treated with chemotherapy for recurrent glioma (overall ICC 0.64). Classification of response to chemotherapy according to the Macdonald criteria resulted in moderate interobserver agreement (overall weighted kappa 0.51). In 65% of evaluated CT and in 55% of evaluated MRI studies, no complete consensus was found for the categorical tumor response measurement. CONCLUSION: The radiologic assessment of response to chemotherapy in patients with recurrent glioma is susceptible to considerable interobserver variability. This underlines the difficulties that arise in scoring response to chemotherapy by conventional radiologic techniques.

Adult↗

PubMed2003

The effect of interferon beta-1b on quantities derived from MT MRI in secondary progressive MS.

BACKGROUND: Magnetization transfer (MT) MRI can provide in vivo markers reflecting the severity of irreversible, MS-related brain damage occurring within and outside T2-visible lesions. OBJECTIVE: To assess the effect of interferon (IFN) beta-1b treatment on the accumulation of brain damage in patients with secondary progressive (SP) MS, measured using MT MRI. METHODS: Eighty-two patients with SPMS from five centers participating in a European, multicenter, double-blind, placebo-controlled trial of IFNbeta-1b in SPMS underwent brain T2-weighted and MT MRI at baseline. Evaluable follow-up data were available for 75 patients at 12 months, 54 at 24 months, and 47 at 36 months. MT MRI scans were postprocessed and analyzed to obtain histograms of MT ratio (MTR) values from the whole brain. A region of interest-based analysis of MTR values from the normal-appearing white matter (NAWM) was also performed. RESULTS: In both the treatment arms, there was a decrease of average brain MTR values from baseline to month 24 (mean change -4.9%) and month 36 (mean change -4.3%). These changes were significant for the placebo group at both timepoints and for the IFNbeta-1b group at month 24 only, with no significant treatment effect. A decrease of NAWM MTR was also observed, with no significant difference between the two treatment arms. CONCLUSION: In this cohort of patients with secondary progressive MS, interferon beta-1b did not show an overall effect on the worsening of magnetization transfer MRI measures, when compared with placebo. The data show that change in magnetization transfer ratio is a promising tool for monitoring disease evolution in secondary progressive MS and that the information obtained from magnetization transfer MRI complements that obtained from MRI measures of lesion load and inflammation.

Adult↗

PubMed2003

Multiple sclerosis: Neurofilament light chain antibodies are correlated to cerebral atrophy.

OBJECTIVE: To evaluate markers of axonal damage in CSF and serum of patients with different subtypes of MS in relation to measures of disease progression on MRI. METHODS: In 51 patients with MS (21 relapsing-remitting, 20 secondary progressive, 10 primary progressive), levels of heavy and light neurofilaments (NfH and NfL) and antibodies to neurofilaments (anti-NfL and -NfH) as well as the total immunoglobulin G (IgG) were analyzed. MRI analysis included T2 hyperintense, T1 hypointense, and gadolinium enhancing lesions and markers of cerebral atrophy (ventricular and parenchymal fractions). RESULTS: For the total group, correlations were found between the anti-NfL index and the parenchymal fraction (PF) (r = -0.51, p < 0.001), T2 lesion load (r = 0.41, p < 0.05), ventricular fraction (r = 0.37, p < 0.05), and T1 lesion load (r = 0.37, p < 0.05). For the anti-NfH index, a correlation was found with the PF (r = -0.39, p < 0.05). No correlations were found between the IgG index and MRI measures. CONCLUSIONS: Intrathecal production of anti-NfL antibodies may serve as a marker of tissue damage, particularly axonal loss, in MS.

Adult↗

PubMed2003

A comprehensive study of gray matter loss in patients with Alzheimer's disease using optimized voxel-based morphometry.

Voxel-based morphometry (VBM) has already been applied to MRI scans of patients with Alzheimer's disease (AD). The results of these studies demonstrated atrophy of the hippocampus, temporal pole, and insula, but did not describe any global brain changes or atrophy of deep cerebral structures. We propose an optimized VBM method, which accounts for these shortcomings. Additional processing steps are incorporated in the method, to ensure that the whole spectrum of brain atrophy is visualized. A local group template was created to avoid registration bias, morphological opening was performed to eliminate cerebrospinal fluid voxel misclassifications, and volume preserving modulation was used to correct for local volume changes. Group differences were assessed and thresholded at P < 0.05 (corrected). Our results confirm earlier findings, but additionally we demonstrate global cortical atrophy with sparing of the sensorimotor cortex, occipital poles, and cerebellum. Moreover, we show atrophy of the caudate head nuclei and medial thalami. Our findings are in full agreement with the established neuropathological descriptions, offering a comprehensive view of atrophy patterns in AD.

Aged↗

PubMed2003

Identifying confounds to increase specificity during a "no task condition". Evidence for hippocampal connectivity using fMRI.

Functional MRI can be applied to study connectivity in the brain during a "no task condition." This study focuses on applying a multiple linear regression analysis to identify spurious connectivity caused by confounding factors such as physiologic noise and to separate these from hippocampal connectivity caused by the blood oxygen level dependent (BOLD) signal during a no-task condition. Regressors of interest (hippocampal time courses) as well as regressors of no interest (respiratory signal and cerebrospinal fluid), were included in the analysis, and each yielded a connectivity map. This method was applied at high sampling rate (limited volume, proper physiologic noise sampling), low sampling rate (whole brain scans possible), and at high and low spatial resolution in five healthy control subjects. Regressors of no interest showed specific connectivity patterns, different from hippocampal regressors. The latter showed connectivity between left and right hippocampus. The current study shows successful application of a multiple regression analysis to study connectivity between left and right hippocampus. Both maps of hippocampal connectivity caused by BOLD signal and connectivity caused by spurious signals could be identified.

Adult↗

PubMed2003

Magnetic source imaging contributes to the presurgical identification of sensorimotor cortex in patients with frontal lobe epilepsy.

OBJECTIVE: One of the primary goals of preoperative evaluation of patients considered to be candidates for epilepsy surgery is the delineation of eloquent cortex adjacent to the area of resection. The aim of this study is the functional localization of the sensorimotor cortex in relation to an epileptogenic frontal lobe lesion, thus enabling a more complete resection in these patients while minimizing the risk of postoperative neurological deficits. METHODS: Participating in this study were patients with epilepsy, diagnosed as being related to a left or right frontal lobe lesion. Magnetoencephalographic responses evoked by electrical stimulation of the left and right hand median nerve were localized using single time-point equivalent dipole (ED) modeling, taking into account the realistic shape of the head. Instead of relying on the primary component (N/P 20) of the somatosensory evoked magnetic fields (SEFs) in this study ED fits were obtained for each time-point of the somatosensory evoked responses. On a cortical rendering, the reconstructed dipoles were depicted relative to the anatomy obtained from 3D-magnetic resonance imaging. RESULTS: The results of single time-point ED analysis including all the components of the responses indicated that the sources underlying the SEFs are located at the borders of the central sulcus (CS). The opposite direction of the sources underlying, respectively, the primary and subsequent late component of the SEFs indicated distinct sources located at the opposite banks of the CS. These sources, therefore, might correspond to the sensory hand projection area and the primary motor area of the sensorimotor cortex. It appeared that the location of the EDs obtained for the SEFs of 4 of the 7 patients studied were asymmetric for the left and right hemisphere, probably because of a displacement of the sensorimotor areas relative to the CS. The systematic assessment of the dipole fits compared to brain anatomy confirmed that volume conduction changes due to the lesion were not responsible for these observed deviations, thus leaving as explanation space-occupying and neurophysiological changes due to the lesion.

Adolescent↗

PubMed2003

Diffusion-weighted MRI in severe neonatal hypoxic ischaemia: the white cerebrum.

Presently, prognosis of infants with perinatal hypoxia-ischaemia is estimated using the Sarnat scale, which combines clinical evaluation and electroencephalography, in combination with magnetic resonance imaging (MRI) and or evoked potentials. While the value of conventional MRI is limited during the first week of life, diffusion-weighted MRI demonstrates effects of acute cerebral ischaemia within hours of onset. However, the exact value of diffusion MRI in the prognosis of infants with hypoxia-ischaemia has to be established in larger follow-up studies. In this report we describe 5 term (post-conceptional age 40 1/7 to 41 2/7 week) neonates with severe hypoxia-ischaemia and a characteristic pattern of diffusion changes. T 1 -weighted images showed a hyperintense cortical signal in only one case and extensive hyperintensity in the basal nuclei in all 5 cases. T 2 -weighted images showed nearly complete loss of cortical delineation in three cases. Increased signal on diffusion-weighted images was seen throughout all cortical and subcortical areas while the cerebellum remained normal. This pattern, which we refer to as the "white cerebrum", is most readily apparent on coronal images. The apparent diffusion coefficient (ADC) was calculated and compared to that of four control infants. In the cortex ADC values were lowered (0.70 +/- 0.17 micro m 2/msec [mean +/- standard deviation (SD)]; controls [n = 4]: 1.18 +/- 0.02 micro m 2/msec) as compared to values of ADC in the cerebellum (1.31 +/- 0.06 micro m 2/msec [mean +/- SD]; controls [n = 4]: 1.25 +/- 0.06 micro m 2/msec). All infants died in the perinatal period. In summary, the "white cerebrum" on diffusion-weighted MRI indicates severe neonatal hypoxia-ischaemia and is the counterpart of the white cerebellum on CT.

Diffusion Magnetic Resonance Imaging↗

PubMed2003

Visual rating of age-related white matter changes on magnetic resonance imaging: scale comparison, interrater agreement, and correlations with quantitative measurements.

BACKGROUND AND PURPOSE: To provide further insight into the MRI assessment of age-related white matter changes (ARWMCs) with visual rating scales, 3 raters with different levels of experience tested the interrater agreement and comparability of 3 widely used rating scales in a cross-sectional and follow-up setting. Furthermore, the correlation between visual ratings and quantitative volumetric measurement was assessed. METHODS: Three raters from different sites using 3 established rating scales (Manolio, Fazekas and Schmidt, Scheltens) evaluated 74 baseline and follow-up scans from 5 European centers. One investigator also rated baseline scans in a set of 255 participants of the Austrian Stroke Prevention Study (ASPS) and measured the volume of ARWMCs. RESULTS: The interrater agreement for the baseline investigation was fair to good for all scales (kappa values, 0.59 to 0.78). On the follow-up scans, all 3 raters depicted significant ARWMC progression; however, the direct interrater agreement for this task was poor (kappa, 0.19 to 0.39). Comparison of the interrater reliability between the 3 scales revealed a statistical significant difference between the scale of Manolio and that of Fazekas and Schmidt for the baseline investigation (z value, -2.9676; P=0.003), demonstrating better interrater agreement for the Fazekas and Schmidt scale. The rating results obtained with all 3 scales were highly correlated with each other (Spearman rank correlation, 0.712 to 0.806; P< or =0.01), and there was significant agreement between all 3 visual rating scales and the quantitative volumetric measurement of ARWMC (Kendall W, 0.37, 0.48, and 0.57; P<0.001). CONCLUSIONS: Our data demonstrate that the 3 rating scales studied reflect the actual volume of ARWMCs well. The 2 scales that provide more detailed information on ARWMCs seemed preferential compared with the 1 that yields more global information. The visual assessment of ARWMC progression remains problematic and may require modifications or extensions of existing rating scales.

Adult↗

PubMed2003

Oral interferon beta-1a in relapsing-remitting multiple sclerosis: a double-blind randomized study.

BACKGROUND: Interferon beta (IFNB) is available in parenteral formulations for treatment of multiple sclerosis (MS). The purpose of this study was to evaluate safety, tolerability and effects on MRI lesions of three different doses of oral IFNB-1a compared with placebo over six months in relapsing-remitting (RR) MS patients. METHODS: In this multicenter; double-blind randomized trial, RR-MS patients received 0.06, 0.6 or 6 million international units (MIU) IFNB-1a or placebo every other day for up to six months. Gadolinium DTPA-enhanced brain MRI scans were performed at screening and monthly during treatment. The primary variable was the cumulative number of newly active lesions. Secondary variables included volume of enhancing lesions on T1-weighted images each month and lesion volume on T2-weighted images at months three and six. Safety measures included adverse events, laboratory variables, vital signs, ECG, physical examination, EDSS and number of relapses. Neopterin was measured in 21 patients and neutralizing antibodies in 24 patients. RESULTS: Of 194 screened patients, 173 were randomized (42-44 patients per group) in 15 centers. Median cumulative numbers of newly active lesions over six months were 4.0 in the placebo and 0.6 MIU groups, compared with 7.5 and 9.0 in the 0.06 and 6 MIU groups (no significant differences). Secondary efficacy endpoints showed small and inconsistent differences between groups. Adverse events showed no notable group differences. Approximately two-thirds of patients in each group remained relapse free. No patients showed neutralizing antibodies. Neopterin levels were comparable between groups. CONCLUSION: Oral IFNB-1a showed neither beneficial effects in RRMS nor any systemic biological effects. Treatment was safe and well tolerated.

Adjuvants, Immunologic↗

PubMed2002

Axonal damage in the spinal cord of MS patients occurs largely independent of T2 MRI lesions.

OBJECTIVE: To determine the degree of axonal damage in relationship to signal abnormalities on T2-weighted high-resolution MRI in spinal cord tissue of patients with MS. METHODS: Spinal cord specimens of nine patients with MS and four controls were imaged at high resolution (4.7 T) in an axial plane and scored for lesions with increased signal intensity (SI). Histopathologic sections were cut and immunostained with NE14 (neurofilament marker) and Luxol fast blue (myelin stain). For each area, axonal density and diameter were quantified; axonal irregularity, NE14 axonal staining intensity, and myelin content were semiquantitatively scored. Included were 209 areas from MS cases and 109 areas from control cases distributed over lateral, posterior, and anterior columns. RESULTS: In control cases, no SI changes were found, average density of axons was 26,989/mm(2), average diameter was 1.1 micro m, and all scores for axonal irregularity, NE14 staining intensity, and myelin were normal. In MS cases, areas with increased SI were found, average axonal density was 11,807/mm(2) (p < 0.0001), and average axonal diameter 2.0 micro m (p = 0.001). Areas with high SI on MRI had lowest axonal density (average count: 10,504/mm(2); range: 3,433 to 26,325/mm(2)), largest diameter (average: 2.3 micro m; range: 1.0 to 4.0 micro m), and highest axonal irregularity and NE14 staining intensity compared to normal appearing cord tissue (NACT). However, NACT of MS cases also had lower axonal density (14,158/mm(2)) and higher average axonal diameter (1.6 micro m) than controls. CONCLUSIONS: Marked axonal loss occurs in MS spinal cords, largely independent of the degree of signal abnormality on T2-weighted MRI.

Adult↗

PubMed2002

Seasonal variation in immune measurements and MRI markers of disease activity in MS.

BACKGROUND: The exact mechanisms by which T cells contribute to MS progression are not known. Recently, the results of cross-sectional studies suggested seasonal variation of both interferon (IFN)-gamma production and the number of active MRI lesions in MS. OBJECTIVE: To investigate whether seasonal fluctuations of IFN-gamma and active MRI lesions could be confirmed and whether any correlations could be detected. METHODS: Data were analyzed from a group of 28 MS patients in whom detailed longitudinal monitoring of both immune function and MRI measurements had taken place. RESULTS: Significant seasonal variation was observed in T-cell activation as measured by the ability of T cells to secrete the pro-inflammatory cytokines tumor necrosis factor-alpha and IFN-gamma. Maximum values were found in samples obtained during autumn. Even though clear fluctuations were observed, no significant seasonal variation could be detected in the number of active MRI lesions. Fluctuations of in vitro IFN-gamma secretion correlated weakly with changes in active MRI lesions. CONCLUSIONS: The finding of seasonal variation of immune function in serially MRI-monitored MS patients suggests an environmental role in T-cell activation.

Adult↗

PubMed2002

The FAS-670 polymorphism influences susceptibility to multiple sclerosis.

Several studies have reported a defective Fas function in patients with multiple sclerosis (MS). We were interested whether this could result from a genetically altered Fas regulation. We examined the FAS-670 polymorphism in 382 patients with MS and 206 controls, and found that the carriership of allele FAS-670*G was significantly less frequent in patients than in controls. We found no association between the carriership of FAS-670*G and clinical features. For a subgroup of patients, longitudinal MRI data were available. We observed similar brain and lesion volumes in carriers and noncarriers of FAS-670*G. These data suggest that FAS-670*G decreases the risk of developing MS, but does not affect the course of disease.

Adult↗

PubMed2002

Chemokine receptor expression on T cells is related to new lesion development in multiple sclerosis.

The expression of chemokine receptors CCR5 and CXCR3 on CD4 and CD8 positive T cells in blood, measured by flow cytometry, was studied in 124 patients with different clinical subtypes of multiple sclerosis (MS) and 22 healthy controls. In a subgroup of patients (n=69) from whom MRI was available, chemokine receptor expression was correlated to the annualised changes in T1 and T2 lesion load. It was found that CCR5 and CXCR3 on both cell types might have impact on annualised increase in T2 lesion load, but not on T1 lesion load. Our results suggest that chemokines may play a more important role in the development of new lesions in MS than in the long-term outcome of those lesions.

Adult↗

PubMed2002

Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer's disease.

BACKGROUND: Rivastigmine enhances cholinergic activity and has been shown in clinical trials to decrease the rate of deterioration in Alzheimer's disease. It remains unclear where in the brain it exerts its effect. Functional magnetic resonance imaging (fMRI) can be used to measure changes in brain function and relate these to cognition. OBJECTIVES: To use fMRI to study brain activation with rivastigmine treatment. METHODS: The effect on brain activation of a single dose of rivastigmine was tested in seven patients with mild Alzheimer's disease using fMRI during face encoding, and in five patients during a parametric working memory task. RESULTS: During face encoding, rivastigmine increased bilateral activation in the fusiform gyrus. Brain activation was also enhanced in the prefrontal cortex in a simple working memory task. When working memory load was further increased, not only was increased activation seen, but in certain areas there was also decreased activation. CONCLUSIONS: These findings link the previously observed increase in cognitive performance in Alzheimer's disease after treatment with a cholinesterase inhibitor to altered brain activation. Although the results cannot be generalised to the Alzheimer's disease population at large, they provide evidence that in mild Alzheimer's disease, rivastigmine enhances brain activation in the fusiform and frontal cortices. This is compatible with the concept of cholinergic circuitry.

Aged↗

PubMed2002

CT and MRI rating of white matter lesions.

Rating scales play an important role in the evaluation of computed tomography (CT) or magnetic resonance-detected white matter lesions (WML). Unfortunately, this type of visual semiquantitative assessment is not yet an optimal tool because commonly agreed concepts regarding its use are lacking. To generate a discussion platform for further improvement of CT and MRI rating, we will provide some basic definitions, summarize the advantages and disadvantages of scoring schemes and review current efforts towards the improvement of this tool. Future research will have to concentrate on deepening our understanding of the histopathologic substrates of WML and on strategies to document their progression.

Aged↗

PubMed2002

The role of MRI as a surrogate outcome measure in multiple sclerosis.

The need for more specific and more sensitive outcome measures for use in testing new therapies in multiple sderosis (MS) is generally accepted. This need has been accentuated by the realization that the ability to conduct large placebo-controlled trials will be limited in the future. From the first use of magnetic resonance imaging (MRI) to study MS, the ability of this imaging technique to identify areas of the central nervous system damage by the disease process in MS has been impressive. Thus, the possibility that MRI could serve as a surrogate outcome measure in clinical trials in MS has been attractive. The use of MRI as a surrogate outcome measure has been examined by an international group of investigators with expertise in clinical aspects of MS, the use of MRI in MS, and in experimental therapeutics. The group agreed that MRI does not represent a validated surrogate in any clinical form of MS. It was also agreed, however, that MRI does provide a reflection of the underlying pathology in the disease, but no single MRI measurement in isolation was seen as sufficient to monitor disease. The use for multiple imaging techniques, especially new, emerging techniques that may better reflect the underlying pathology, was seen as particularly important in monitoring studies of patients with either secondary or primary progressive MS. The choice of MRI techniques used to monitor new therapies needs to be consistent with the proposed mechanisms of the new therapy and phase of the disease. It was also noted, however, that additional validation is required for nonconventional imaging techniques. Finally, the participants noted that clinical trials using MRI as a primary outcome measure may fail to fully identify the effects of the therapy on dinical measures and that the risk and cost-benefit ratio of the treatment might be unresolved. Thus, before MRI is used as a primary outcome measure, new approaches to trial design must be given careful consideration.

Central Nervous System↗

PubMed2002

Incidence of enhancement of the trigeminal nerve on MRI in patients with multiple sclerosis.

The purpose of this study is to review the incidence of contrast enhancement of the trigeminal nerve on magnetic resonance imaging (MRI) in a large cohort of patients with multiple sclerosis (MS). MRI scans of 851 MS patients participating in a phase III clinical trial were reviewed for the presence of gadolinium enhancement on postcontrast T1-weighted images. If enhancement was present, it was documented whether this involved only the proximal or also the distal part of the fifth nerve, and whether the abnormality was unilateral or bilateral. In 24 (2.8%) patients, enhancement of the trigeminal nerve was observed, and was bilateral in 16 (66.7%) of those. In 19 (79.2%) patients with abnormal nerves, enhancement extended to the distal part of the trigeminal nerve (into Meckel's cave). The results of this study indicate a high, probably clinically silent, incidence of trigeminal nerve demyelination in MS and frequent involvement of the peripheral type of myelin in MS.

Adolescent↗

PubMed2002

Two-year follow-up study of primary and transitional progressive multiple sclerosis.

This study documents changes in clinical and magnetic resonance imaging (MRI) characteristics in a large cohort of patients with primary and transitional progressive multiple sclerosis (PP and TPMS) over 2 years. Patients with PPMS and TPMS were recruited from six European centres and underwent clinical and MRI examination at three time points: baseline, year one and year two. Of the 190 patients recruited clinical data were available on 125 patients (66%, five centres) and MRI data were available on 113 patients (59%, four centres) at 2 years. Significant increases were seen in T2 load and T1 hypointensity, while brain and cord volume decreased. In PPMS significantly higher lesion loads were found in those who presented with non-cord syndromes when compared to cord presentation and there was a trend to greater brain atrophy in those who deteriorated clinically over the course of the study compared to those who remained stable. Significant cord atrophy was only seen in those with a cord presentation. Measurable changes in MRI parameters can be detected in PPMS patients over a relatively short period of time. MRI quantification is likely to be useful in elucidating disease mechanisms in PPMS and in the execution of clinical trials.

Adult↗