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Biomedical subjects

F Barkhof

Publications and source records attributed to F Barkhof.

At least 163 records · Page 9Linked to original sources
PubMed1998

Cine phase-contrast MR imaging in normal pressure hydrocephalus patients: relation to surgical outcome.

Phase-contrast cine MR flow imaging through the aqueduct was used to establish the diagnosis of normal pressure hydrocephalus (NPH), and to predict outcome after shunting. From 1990-1994 16 patients, who were participants in the Dutch Normal Pressure Hydrocephalus Study [3], were studied. The patients included in this study met clinical and CT-scan criteria as described in this study, underwent cine phase-contrast MR imaging prior to placement of a CSF shunt, and had a follow-up 12 months after the operation. Claustrophobic patients, patients with a pacemaker or extremely agitated patients were excluded. Normal Flux was calculated in each patients, as the average difference in caudal and rostral flux (Fdiff) +2 times standard deviation (0.97 cc/sec) [2]. The clinical outcome was measured with a modified scale of activities of daily living (ADL) as described by Rankin. Of the 16 patients, 8 could not be evaluated due to restlessness during MR measurements, disabling cerebral vascular accidents or death before the end of the follow-up period. Of the remaining 8 patients, 5 had a normal flux, of which only one improved. Two patients had a Fdiff twice the normal range, which improved in both patients. One patient had no measurable flux, consistent with an aqueduct stenosis; he too improved. Overall, there was a concordance of MR findings with final outcome after shunting in 7 out of 8 patients. This pilot study, therefore, support the need to further evaluate flow with MR imaging techniques to select patients with shunt responsive NPH.

Cerebrospinal Fluid Shunts↗
PubMed1998

Within-subject reproducibility of visual activation patterns with functional magnetic resonance imaging using multislice echo planar imaging.

Within-subject reproducibility of visual brain activation using multislice echo planar functional magnetic resonance imaging (fMRI) was tested. Ten healthy subjects underwent fMRI with visual stimulation on three occasions: two studies in one scanning session (without repositioning); and a third study 1 h to 2 weeks later. Following a three-dimensional matching procedure, activation was measured and compared between sessions on a voxel-by-voxel basis. Data were filtered to full-width-at-half-maximum of 4.0 x 4.0 x 5.0 mm and a conservative Bonferroni-corrected significance threshold was applied to correlation maps. For reproducibility, change in centre of mass of the activated volume, a ratio of the number of pixels and a ratio of the number of overlapping pixels was calculated. Further, reproducibility was tested varying significance thresholds and at different filter widths. Average changes in centre of mass of the activated volume were 2.63 and 3.96 mm between Studies 1 and 2 and 1 and 3, respectively. The reproducibility of the number of activated voxels was 90% and 88% (Studies 1 and 2 and 1 and 3). The ratio of overlapping pixels was 74% between Studies 1 and 2 and 64% between Studies 1 and 3. Varying the significance threshold showed that at a certain range, the overlap reached a maximum, and increasing the filter widths increased reproducibility. It is concluded that fMRI with visual stimulation can be used to measure brain activity with reasonably good reproducibility on a routine clinical system equipped with echo planar imaging. Difficulties remain in separating the contribution of motion, repositioning errors, and true physiological changes.

Adolescent↗
PubMed1998

Magnetization transfer contrast (MTC) and long repetition time spin-echo MR imaging in multiple sclerosis.

PURPOSE: To study whether application of magnetization transfer contrast (MTC) improves visibility and detection of multiple sclerosis (MS) lesions on long repetition time (TR) conventional spin-echo (CSE) or fast spin-echo (FSE) magnetic resonance (MR) imaging. MATERIAL AND METHODS: In 20 patients and 5 controls, MR images were obtained using long repetition time CSE and FSE sequences with and without MTC. Signal-to-noise ratios of normal appearing white matter (NAWM) and selected lesions, and contrast-to-noise ratios between lesions and NAWM, were calculated. Lesions were counted and total lesion volume was measured in a blinded fashion for each sequence. RESULTS: In controls, MT effect in white matter (16.3% vs. 12.2%) was higher for CSE than for FSE (p < 0.01). Application of MTC to either CSE or FSE resulted in a significantly lower decrease in signal intensity of NAWM in patients compared to white matter in controls (p < 0.01). Furthermore, in patients signal intensity of lesions was less decreased than signal intensity of NAWM (p < 0.01). Compared to sequences without MTC, contrast-to-noise ratios were significantly higher on both CSE (10.9%) and FSE (6.3%) when MTC was applied (p < 0.01). Despite better visibility, the number of lesions detected on either sequences did not increase when MTC was applied. For CSE with MTC, we found an almost equal number of lesions and for FSE with MTC, we found even less lesions (p < 0.01). Total lesion volume did not change significantly when MTC was applied. CONCLUSION: Although contrast between lesions and NAWM improved when magnetization transfer contrast was applied, this did not increase detection of MS lesions on either CSE or FSE MR imaging.

Adult↗
PubMed1998

Secondary progressive multiple sclerosis: the relationship between short-term MRI activity and clinical features.

We report the findings in 60 patients with secondary progressive multiple sclerosis who had monthly brain MRI studies for 4 months (one baseline and three follow-up scans). The purpose was to define the short-term MRI natural history in a large cohort with secondary progressive disease and to ascertain its relationship with other clinical and MRI features. The patients were participating in either a natural history study or the placebo arm or non-treatment phase of a therapeutic trial. The cohort had clinical features typical of secondary progressive disease: thus, all had moderate or severe locomotor disabilities [Expanded Disability Status Scale (EDSS), score 3.5-8], with a median disease duration of 12 years. There was equal representation of males and females. During the 3 months of follow-up there was a total of 362 new enhancing lesions seen in 42 patients, and there were 24 relapses in 20 patients. There was no correlation between new enhancing lesions and age at study entry, age of disease onset, gender disease duration or EDSS, but there was a strong correlation with the number of enhancing lesions on the baseline scan (r = 0.65, P < 0.0001) and subsequent activity. There was a non-significant trend for higher numbers of new enhancing lesions in those having relapses during the 3 months of scanning (P = 0.14) or in the preceding 6 months (P = 0.06). The 34 patients who did not relapse in either period had significantly fewer new active lesions (P = 0.02) than those who relapsed at some stage during the 9 months. Nevertheless, considerable activity was seen in the non-relapsing cohorts: there was a mean of 3.5 (median 2) new enhancing lesions in those not relapsing during the 3 month study, and 5.5 (median 2) in those not relapsing in the previous 6 months. We conclude that short-term MRI activity is generally high in secondary progressive disease, confirming a useful role for the technique in exploratory trials. Further work should concentrate on elucidating the mechanisms of secondary progression by longer term follow-up studies of larger cohorts using multiple MRI and clinical measurements.

Adult↗
PubMed1998

Brain and spinal cord abnormalities in multiple sclerosis. Correlation between MRI parameters, clinical subtypes and symptoms.

We investigated various magnetic resonance MRI parameters for both brain and spinal cord to see if any improved the clinicoradiological correlation in multiple sclerosis. Ninety-one multiple sclerosis patients (28 relapsing-remitting, 32 secondary progressive and 31 primary progressive) were imaged using conventional T1, proton density- and T2-weighted MRI of the brain and spinal cord. Focal brain and spinal cord lesion load was scored, as were diffuse signal abnormalities, brain ventricular volume and spinal cord cross-sectional area. Clinical measures included the expanded disability status scale (EDSS), the functional systems score and a dedicated urology complaint questionnaire. Secondary progressive patients differed from relapsing-remitting and primary progressive patients by a larger number of hypointense T1 lesions in the brain, ventricular enlargement and spinal cord atrophy. Primary progressive patients more often had diffuse abnormalities in the brain and/or spinal cord than did relapsing-remitting and secondary progressive patients. In the entire study population, EDSS correlated with both brain and spinal cord MRI parameters, which were independent. The urological complaint score correlated only with spinal cord MRI parameters. In relapsing-remitting and secondary progressive multiple sclerosis, the correlation between MRI and clinical parameters was better than in the entire population. In this subgroup EDSS variance could be explained best by T1 brain lesion load, ventricle volume and spinal cord cross-sectional area. In the primary progressive subgroup the clinicoradiological correlation was weak for brain parameters but was present between spinal cord symptoms and spinal cord MRI parameters. In conclusion, the different brain and spinal cord MRI parameters currently available revealed considerable heterogeneity between clinical subtypes of multiple sclerosis. In relapsing-remitting and secondary progressive multiple sclerosis both brain and spinal cord MRI may provide a tool for monitoring patients, while in primary progressive multiple sclerosis the clinicoradiological correlation is weak for brain imaging.

Adult↗
PubMed1998

Exploratory treatment trials in multiple sclerosis using MRI: sample size calculations for relapsing-remitting and secondary progressive subgroups using placebo controlled parallel groups.

OBJECTIVES: Serial brain MRI is widely used in pilot studies of new agents to monitor treatment efficacy in relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS). For pilot trials, sample size calculations for the RR subgroup are based on the data from small numbers of patients and separate calculations for the SP subgroup have not been performed. The present study considers these issues. METHODS: The sample size calculations were based on data from six months of monthly T2 weighted and gadolinium enhanced MRI in 31 RR and 28 SP untreated patients undergoing natural history studies or in the placebo arm of a therapeutic trial. The calculations were for a placebo controlled, parallel groups design lasting six months. The sample sizes were based on bootstrap analysis with an 80% likelihood of showing a given treatment effect. RESULTS: With a single pretreatment scan, demonstration of a 70% reduction in newly active lesions required 2x30 RR and 2x50 SP patients. With an extra run-in scan one month before treatment, the sample sizes were 2x20 for RR and 2x30 for SP patients. CONCLUSIONS: The sample sizes required for RR patients were comparable with previous smaller studies. Larger sample sizes were needed for the SP group, but the extra run in scan resulted in a reduction in both groups. The larger sample sizes in the SPMS group were probably due to the combination of a higher proportion of patients with low MRI activity (< or =2 active MRI lesions in 50% of SP and 32% RR patients), as well as a few patients who displayed extremely high activity, thus increasing interpatient variability. These data should be considered in planning pilot MRI outcome trials.

Adult↗
PubMed1998

White matter changes on CT and MRI: an overview of visual rating scales. European Task Force on Age-Related White Matter Changes.

Since the recognition of white matter changes on CT (leukoaraiosis), rating scales for the location and severity of white matter changes have been developed, mainly for research purposes, to investigate factors such as the relation with cognition, risk factors, and pathology. The main purpose of rating scales is to provide scores that can be used in statistical analyses. The development of the NINDS-AIREN criteria for vascular dementia have introduced a new application for these rating scales in investigating and delineating the amount of white matter changes on CT/MRI sufficient to fulfill the criteria. Furthermore, in Alzheimer's disease, recognition of white matter changes may serve to delineate homogeneous groups and help to identify patients with different symptomatology. We reviewed the existing rating scales for CT and MRI and judged their properties and reliability. The ideal rating scale does not yet exist, but different rating scales may serve different purposes, for which some recommendations are made.

Brain Ischemia↗
PubMed1998

Patterns of brain magnetic resonance abnormalities on T2-weighted spin echo images in clinical subgroups of multiple sclerosis: a large cross-sectional study.

To substantiate differences in magnetic resonance (MR) patterns in clinical subgroups of multiple sclerosis (MS), we analyzed T2-weighted MR images of a large regional population of MS patients (n = 188). The patients had already been classified according to recent consensus definitions regarding the clinical course of MS into relapsing-remitting (RR), secondary progressive (SP) or primary progressive (PP). Significant (p < 0.01; Spearman test) differences were present between RR and SP patients regarding total lesion load, size and location of lesions. RR and PP patients showed similar MR patterns. PP and SP patients differed in total lesion load, small and medium-sized lesions. The degree of atrophy was highest for SP patients. The clinical progression rate [Expanded Disability Status Scale (EDSS)/disease duration] was similar for various subgroups; the MR progression rate (total lesion score/disease duration) was significantly larger for SP than for PP patients. The lesions load disability quotient (total lesion load/EDSS) differed between RR and PP patients and also between SP and PP patients. In SP patients, the total lesion load correlated significantly (Spearman rank correlation coefficient of 0.52) with EDSS. We conclude that PP patients differ in MR abnormalities from SP patients, that PP and RR patients have similar MR abnormalities and that RR and SP patients are at a different end of the same spectrum of the disease. As the dynamics and clinical impact of MS lesions are different in the various clinical subgroups, they should be considered separately in clinical trials.

Adult↗
PubMed1998

Effect of training and different measurement strategies on the reproducibility of brain MRI lesion load measurements in multiple sclerosis.

In this study, we evaluated the intra- and interobserver variabilities in measuring lesion load of brain MRI abnormalities present on proton-density scans from patients with MS, using using both manual outlining or a semiautomated local thresholding technique (LTT). We also evaluated how these variabilities were affected by the use of standard rules for lesion load measurements, training, and different measurement strategies. The intraobserver variabilities obtained after establishing rules for lesion load measurements and training were not significantly different from those obtained before any consensus among the observers, both for manual outlining and for the LTT. On the contrary, the interobserver variabilities obtained with manual outlining or the LTT were significantly reduced when rules for lesion load measurements were used. For manual outlining, the intraobserver variability did not significantly change when the measurements were performed after an experienced radiologist identified lesions or when using adjacent slices and the corresponding T2-weighted images as reference for lesion identification. On the contrary, for the LTT, the intraobserver variability was significantly reduced by the use of the radiologic marking. The interobserver variabilities for both manual outlining and the LTT were reduced compared with the free condition when these measurement strategies were used. Our findings demonstrate that both lesion identification and outlining are important sources of variation for MRI lesion load measurements in MS and that there are simple strategies to reduce such variation that might be useful when planning clinical trials.

Brain↗
PubMed1998

Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis.

Postmortem unfixed whole brains from five multiple sclerosis (MS) patients were examined by MRI using a T2- and T1-weighted spin-echo (SE) sequence and histology to investigate the histopathologic characteristics of hypointense lesions on T1-weighted SE MR images. The degree of hypointensity was scored semiquantitatively by two blinded observers in reference to normal-appearing white matter. Signal intensities of the lesions and the normal-appearing white matter were measured to obtain contrast ratios. Hematoxylin-eosin stain was used to assess degree of matrix destruction (decrease of density of the neuropil) and cellularity of a lesion, Klüver-Barrera stain for degree of demyelination, Bodian stain for axonal density, and immunostaining of glial fibrillary acid protein for reactive astrocytes and fibrillary gliosis. Nineteen lesions were selected for analysis. Nearly all lesions were compatible with the chronic MS plaque: hypocellularity, absence of myelinated axons, in the presence of reactive astrocytes. Contrast ratios of the lesions were highly correlated (R = -0.90; p < 0.01), with degree of hypointensity scored semiquantitatively. Degree of hypointensity on T1-weighted SE images did not correlate with degree of demyelination or number of reactive astrocytes, but was associated with axonal density (R = -0.71; p = 0.001). A trend was found with degree of matrix destruction (R = 0.45; p = 0.052). We conclude that, in our limited sample, hypointense lesions seen on T1-weighted SE MR images are associated histopathologically with severe tissue destruction, including axonal loss. Our results need to be substantiated in a larger study on more varied patient material to evaluate the use of hypointense lesions as a surrogate marker of persistent deficit in MS patients.

Adult↗
PubMed1998

Visual activation patterns in patients with optic neuritis: an fMRI pilot study.

We studied the use of functional MRI (fMRI) with visual stimulation in nine patients with unilateral optic neuritis. Eight healthy subjects served as controls. Patients showed reduced activation upon stimulation of the affected eye, on average 33% (range 0 to 156%) of the average monocular activation in the control group. Decreased activation was also seen for the unaffected eye (61% of control values, range 3 to 133%). We conclude that fMRI with visual stimulation is feasible in patients with optic neuritis and deserves future study.

Adult↗
PubMed1998

Choosing drug therapy for multiple sclerosis. An update.

Multiple sclerosis (MS) is an immunologically mediated disorder in which inflammation and demyelination of the central nervous system white matter are prominent features, resulting in various neurological signs and symptoms. In most patients, the course of the disease is initially characterised by relapses and remissions. In patients with chronic disease there is a tendency towards a gradually progressive disease course. MS relapses can best be treated with a course of high dose intravenous methylprednisolone. In ambulatory patients with relapsing remitting MS, partial prevention of relapses can be achieved by the use of interferon-beta-1a or -1b, whereas there is (as yet less convincing) evidence that glatiramer acetate (copolymer-1) might also be effective. At this time, there is no proof that these drugs are effective in patients with progressive MS, although trial results are expected to be available soon. In patients with rapidly progressive disease, it might be worth considering the effect of methotrexate. Future treatment options include new strategies to interfere with disease-relevant, specific or nonspecific immune mechanisms as well as drugs that might promote remyelination. In spite of the advances that have been made over the past few years, symptomatic treatment, including a multidisciplinary rehabilitation approach, remains the mainstay of treatment of the majority of MS patients.

Anti-Inflammatory Agents↗
PubMed1998

Sagittal MR of multiple sclerosis in the spinal cord: fast versus conventional spin-echo imaging.

PURPOSE: We compared conventional spin-echo (CSE) with fast spin-echo (FSE) dual-echo MR images to determine which of these sequences was better able to depict spinal cord abnormalities in patients with multiple sclerosis (MS). METHODS: CSE and FSE dual-echo MR images were obtained in 37 patients with MS and in six healthy control subjects, all of whom were examined on a 1.0-T MR unit with a phased-array coil and cardiac triggering. Two blinded interpreters graded the MR studies, first separately and then by consensus. Images were scored for presence of artifacts, number of focal lesions, and presence of a diffuse increase in signal intensity. RESULTS: No abnormalities were seen in the volunteers. The CSE sequences were significantly less hindered by MR imaging artifacts than were the FSE sequences. Interobserver agreement was slightly higher for the CSE than the FSE sequences. After reaching a consensus, the observers found that both CSE and FSE techniques enabled detection of approximately the same number of focal lesions; however, in three patients, small single lesions seen on the CSE images were missed on the FSE images. Also, depiction of a diffuse increase in signal intensity was better on the CSE images. As a result, more patients had abnormal findings on the CSE sequences than on the FSE sequences (35 versus 31). CONCLUSION: Cardiac-triggered dual-echo FSE sequences are almost as good as CSE sequences for depicting spinal MS lesions. Therefore, in cases of established spinal MS, FSE techniques may be as effective as CSE techniques. Because sensitivity for subtle abnormalities is lower with FSE imaging, CSE remains the preferred technique for patients with suspected MS of the spinal cord.

Adult↗
PubMed1998

Patterns of lesion development in multiple sclerosis: longitudinal observations with T1-weighted spin-echo and magnetization transfer MR.

PURPOSE: We evaluated the appearance of enhancing multiple sclerosis (MS) lesions on unenhanced T1-weighted MR images and the natural course of enhancing MS lesions on serial unenhanced T1-weighted and magnetization transfer (MT) MR images. METHODS: One hundred twenty-six enhancing lesions were followed up monthly for 6 to 12 months to determine their signal intensity on unenhanced T1-weighted and MT MR images. At the time of initial enhancement, the size of the lesion and the contrast ratio of enhancement were calculated for each enhancing lesion. During follow-up, the contrast ratio on the corresponding unenhanced T1-weighted image was measured, and an MT ratio (MTR) was calculated. RESULTS: Twenty-five enhancing lesions (20%) appeared isointense and 101 lesions (80%) appeared hypointense relative to normal-appearing white matter on unenhanced T1-weighted images. During 6 months of follow-up, four MR patterns of active lesions were detected: initially isointense lesions remained isointense (15%); initially isointense lesions became hypointense (5%, most of which reenhanced); initially hypointense lesions became isointense (44%); and initially hypointense lesions remained hypointense (36%). MTR was significantly lower for hypointense lesions as compared with isointense lesions at the time of initial enhancement. For lesions that changed from hypointense to isointense, MTR increased significantly during 6 months of follow-up. Multiple regression analysis showed that strongly decreased MTR at the time of initial enhancement and enhancement duration of more than one scan were predictive of a hypointense appearance on unenhanced T1-weighted images at 6 months' follow-up. Ring enhancement was found to be the only (weak) predictor of persistently hypointense signal intensity. CONCLUSION: Most enhancing lesions appear slightly to significantly hypointense on unenhanced T1-weighted images. Although most hypointensities are reversible, only those lesions that fail to recover on unenhanced T1-weighted and MT images may have considerable irreversible structural changes.

Adolescent↗
PubMed1998

Unenhanced and enhanced magnetic resonance imaging in the diagnosis of multiple sclerosis.

Initial enthusiasm about the role of magnetic resonance imaging (MRI) in the diagnosis of multiple sclerosis decreased substantially with the notion that (a) lesions of various pathological origins may resemble demyelinating plaques and (b) a dissemination of lesions throughout the brain is not unique for multiple sclerosis but may even be a "normal" finding. Current experience still does not allow the identification of the aetiology of a single hyperintensity but has identified multiple features of multiple sclerosis related signal abnormalities which, in combination, provide rather high diagnostic accuracy. Useful characteristics include the distribution of lesions such as a strictly periventricular, infratentorial or juxtacortical location, and involvement of the corpus callosum. The presence of contrast enhancement in some but not all lesions-that is, evidence of both old and new lesions-provides additional diagnostic support. Improved instrumentation for imaging of the spine further extends the diagnostic options. Intramedullary signal abnormalities are detected with increased sensitivity and may disclose the presence of multiple lesions even in patients with an equivocal or a negative MRI of the brain. The high sensitivity to plaques and the opportunity to simultaneously rule out other gross morphological damage justifies the use of MRI as the primary diagnostic modality in the evaluation of multiple sclerosis.

Brain↗
PubMed1998

Hypointense multiple sclerosis lesions on T1-weighted spin echo magnetic resonance images: their contribution in understanding multiple sclerosis evolution.

The predictive value of T2-weighted imaging in multiple sclerosis is only moderate, due to low specificity of high signal on such images. Among new MR techniques with acclaimed higher pathological specificity, hypointense lesions on moderately T1-weighted spin echo images show improved correlation with disability. The degree of hypointensity of so called black holes correlates with loss of magnetisation transfer, a marker of matrix destruction. Severe tissue loss is also shown histopathologically in a post-mortem MR study of black holes. In this review unresolved issues regarding black holes are discussed including standardisation of sequences, definition of hypointensity, interobserver variation in measuring lesion load with this technique, and significance of acute black holes. The role of black holes in monitoring treatment efficacy is as yet unexplored.

Brain↗
PubMed1997

Visual association encoding activates the medial temporal lobe: a functional magnetic resonance imaging study.

The involvement of structures in the medial temporal lobe during the encoding of visual associations was studied with functional magnetic resonance imaging. In 11 out of 12 normal healthy volunteers this task resulted in activation in posterior portions of the parahippocampal region, close to the collateral sulcus. In seven subjects activation was encountered in the hippocampal formation. The visual association task as adapted for this study may provide a sensitive measure to study anterograde amnesia prevalent in Alzheimer's disease. Therefore, the present paradigm enables the study of individual changes in learning and memory capacities over time.

Adult↗