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Biomedical subjects

S Ropele

Publications and source records attributed to S Ropele.

At least 19 recordsLinked to original sources

Risk factors for progression of brain atrophy in aging: six-year follow-up of normal subjects.

OBJECTIVES: To determine the rate of brain atrophy in neurologically asymptomatic elderly and to investigate the impact of baseline variables including conventional cerebrovascular risk factors, APOE epsilon4, and white matter hyperintensity (WMH) on its progression. METHODS: We assessed the brain parenchymal fraction at baseline and subsequent annual brain volume changes over 6 years for 201 participants (F/M = 96/105; 59.8 +/- 5.9 years) in the Austrian Stroke Prevention Study from 1.5-T MRI scans using SIENA (structural image evaluation using normalization of atrophy)/SIENAX (an adaptation of SIENA for cross-sectional measurement)(www.fmrib.ox.ac.uk/fsl). Hypertension, cardiac disease, diabetes mellitus, smoking, and regular alcohol intake were present in 64 (31.8%), 60 (29.9%), 5 (2.5%), 70 (39.3%), and 40 (20.7%) subjects, respectively. Plasma levels of fasting glucose (93.7 +/- 18.6 mg/dL), glycated hemoglobin A (HbA1c; 5.6 +/- 0.7%), total cholesterol (228.3 +/- 40.3 mg/dL), and triglycerides (127.0 +/- 75.2 mg/dL) were determined. WMH was rated as absent (n = 56), punctate (n = 120), early confluent (n = 14), and confluent (n = 11). RESULTS: The baseline brain parenchymal fraction of the entire cohort was 0.80 +/- 0.02 with a mean annual brain volume change of -0.40 +/- 0.29%. Univariate analysis demonstrated a higher rate of brain atrophy in older subjects (p = 0.0001), in those with higher HbA1c (p = 0.0001), higher body mass index (p = 0.02), high alcohol intake (p = 0.04), severe WMH (p = 0.03), and in APOE epsilon4 carriers (p = 0.07). Multivariate analysis suggested that baseline brain parenchymal fraction, HbA1c, and WMH score explain a major proportion of variance in the rates of brain atrophy in the cohort (corrected R2 = 0.27; p = 0.0001). CONCLUSIONS: Neurologically asymptomatic elderly experience continuing brain volume loss, which appears to accelerate with age. Glycated hemoglobin A (HbA1c) was identified as a risk factor for a greater rate of brain atrophy. Clustering of factors associated with the so-called metabolic syndrome in subjects with high HbA1c suggests a link between this syndrome and late-life brain tissue loss.

Age Distribution↗

Discrimination of white matter lesions and multiple sclerosis plaques by short echo quantitative 1H-magnetic resonance spectroscopy.

Multiple sclerosis (MS) plaques and age related white matter lesions (WML) are of similar morphological appearance on T2 weighted MRI. Therefore their differentiation is sometimes crucial. Proton magnetic resonance spectroscopy ((1)H-MRS) adds metabolic information to conventional imaging and may help to distinguish inflammatory MS plaques from vascular related WML. This study was performed to evaluate the metabolite pattern in MS plaques and WML. 15 MS patients, 14 elderly individuals with WML and 16 controls were investigated by conventional MRI and short echo quantitative (1)H-MRS (TE: 30ms, TR: 3000ms). The mean metabolite concentrations in normal control white matter (NCWM), MS plaques and WML were: t-NAA: 8.96 mmol/l (SD: 0.93) vs 6.79 mmol/l (SD: 1.99) vs 7.18 mmol/l (SD: 1.41); Cho:1.66 mmol/l (SD: 0.4) vs 1.49 mmol/l (SD: 0.45) vs 1.46 mmol/l (SD: 0.34); PCr:5.64 mmol/l (SD: 0.83) vs 4.9mmol/l (SD: 1.3) vs 4.95 mmol/l (SD: 0.86); myo-Ins: 4.57 mmol/l (SD:1.05) vs 6.34 mmol/l (SD: 2.03) vs 4.5 mmol/l (SD: 0.96). t-NAA reduction in MS plaques and WML was significant compared with controls (p <or= 0.001). MS plaques showed significantly elevated myo- Ins concentrations compared with controls (p = 0.002) and to WML (p = 0.003). In summary MS plaques and WML show a decrease in their t-NAA concentrations compared with controls. Elevated concentrations of myo-Ins in MS plaques but not in WML makes this metabolite of special interest for their differentiation.

Adult↗

Relapsing acute transverse myelitis: a specific entity.

Acute transverse myelitis (ATM) not related to systemic disease may present in a relapsing manner. Data in the literature about this condition are scarce. We describe three patients suffering from relapsing myelitis in whom no association with systemic disease, i.e. infectious or connective tissue disease was found. Magnetic resonance imaging (MRI) findings were also distinctly different from multiple sclerosis and consistent with a necrotizing type of inflammation. Despite various treatment strategies, all patients became severely disabled. Relapsing ATM not related to systemic disease appears to be a specific entity which accounts for severe disability and currently lacks effective treatment.

Disability Evaluation↗

MRI results from the European Study on Intravenous Immunoglobulin in Secondary Progressive Multiple Sclerosis (ESIMS).

BACKGROUND: Monthly application of high-dose intravenous immunoglobulin (IVIG) to patients with secondary progressive multiple sclerosis (MS) showed no clinical benefit in the European Study on Immunoglobulin in MS (ESIMS). Magnetic resonance imaging (MRI) results may provide insights into the morphologic consequences of such treatment. METHODS: A total of 318 patients (mean age 44 +/- 7 years) were enrolled in 31 European and Canadian centres and treated monthly with 1 g/kg body weight of IVIG or equivalent amounts of albumin 0.1% for 27 months. MRI was performed at baseline and after 12 and 24 months and comprised of conventional dual-echo T2-weighted and T1-weighted scans before and after application of 0.1 mmol/kg Gd-DTPA. RESULTS: Similar to clinical variables, MRI measures at baseline were well comparable between treatment groups except for a somewhat lower mean number of contrast-enhancing lesions and number of active scans in IVIG-treated patients. Over the trial period there was almost no change of the T2-lesion load and the 'black hole' volume in both treatment groups and the cumulative number of contrast-enhancing lesions were similar. There was only a trend for fewer new or enlarged T2-lesions in IVIG patients, which disappeared after correction for the imbalance in the number of contrast-enhancing lesions at baseline. Brain volume in terms of a partial cerebral fraction decreased significantly less with IVIG than placebo treatment (final visit: -0.62 -/+ 0.88% versus -0.88 +/- 0.91%; P=0.009). This difference remained statistically significant with correction for active lesions at baseline (P=0.02) and was seen primarily in male patients and those with an Expanded Disability Status Scale score > or = 6 and no relapses in the two years before the study. CONCLUSION: The absence of significant differences in conventional MRI measures between both treatment groups parallels the negative clinical results of ESIMS. The causes for and possible long-term clinical effects of a lower rate of brain volume loss in IVIG patients should be explored further.

Adult↗

Midbrain ischemia presenting as vertical gaze palsy: value of diffusion-weighted magnetic resonance imaging.

BACKGROUND: Conventional magnetic resonance imaging may fail to identify very small but clinically relevant acute subcortical brain infarcts. Diffusion-weighted magnetic resonance imaging (DWI) is very sensitive and specific for acute cerebral ischemia and should contribute to the early detection of such lesions. METHODS: We analyzed 6 patients who presented with acute vertical gaze palsy and in whom DWI was performed within 1-6 days from symptom onset. RESULTS: DWI accurately identified ischemia in an area supplied by the posterior thalamosubthalamic paramedian artery in all patients. T(2)-weighted and FLAIR imaging failed to identify the clinically relevant lesion in 2 and 3 patients, respectively. CONCLUSION: DWI improves the clinicoanatomical correlation in patients presenting with supranuclear oculomotor disturbances.

Acute Disease↗

Acupuncture using laser needles modulates brain function: first evidence from functional transcranial Doppler sonography and functional magnetic resonance imaging.

Acupuncture using laser needles is a new totally painless stimulation method which has been described for the first time. This paper presents an experimental double-blind study in acupuncture research in healthy volunteers using a new optical stimulation method. We investigated 18 healthy volunteers (mean age +/- SD: 25.4 +/- 4.3 years; range: 21-30 years; 11 female, 7 male) in a randomized controlled cross-over trial using functional multidirectional transcranial ultrasound Doppler sonography (fTCD; n = 17) and performed functional magnetic resonance imaging (fMRI) in one volunteer. Stimulation of vision-related acupoints resulted in an increase of mean blood flow velocity in the posterior cerebral artery measured by fTCD [before stimulation (mean +/- SE): 42.2 +/- 2.5; during stimulation: 44.2 +/- 2.6; after stimulation: 42.3 +/- 2.4 cm/s, n.s.]. Mean blood flow velocity in the middle cerebral artery decreased insignificantly. Significant changes (p < 0.05) of brain activity were demonstrated in the occipital and frontal gyrus by fMRI. Optical stimulation using properly adjusted laser needles has the advantage that the stimulation cannot be felt by the patient (painless and no tactile stimulation) and the operator may also be unaware of whether the stimulation system is active. Therefore true double-blind studies in acupuncture research can be performed.

Acupuncture↗

CT and MRI rating of white matter changes.

The impact of white matter changes (WMC) detectable on CT or MRI on various diseases like ischemic stroke and intracerebral hemorrhage and their association with cognitive impairment was and still is under debate. To assess WMC in a qualitative and/or semiquantitative fashion rating scales have been developed. For MRI most widely used scales are the scales of Manolio, Fazekas, Schmidt, and Scheltens. Most recently a new scale extending earlier suggestions has been introduced by Wahlund et al. applicable for both CT and MRI. This article will review strengths and weaknesses of these rating scales and will discuss further requirements and future perspectives.

Aged↗

Risk factors and progression of small vessel disease-related cerebral abnormalities.

A three year follow-up of 273 participants (mean age 60 years) of the Austrian Stroke Prevention Study provides first information on the rate and clinical predictors of progression of small vessel disease related cerebral abnormalities including white matter changes and lacunes. White matter hyperintensity progression was found in 17.9% of individuals over the 3 year period. New lacunes occurred in 2.2% of subjects. The overall frequency of progression of small vessel disease related brain changes was 19%. Diastolic blood pressure and early confluent or confluent white matter hyperintensities at baseline predicted lesion progression. Genetic association studies in the setting of the Austrian Stroke Prevention Study described that polymorphisms in the renin angiotensin system (RAS) increase the susceptibility for progression of cerebral small vessel disease. Homozygosity for the T allele of the M235T polymorphism of the angiotensinogen gene was associated with a 3.19-fold increased risk for lesion progression independently of arterial hypertension. These data suggest that drugs influencing the RAS system may allow to intervene with an unfavorable course of cerebral small vessel disease.

Aged↗

Can small-vessel disease-related cerebral abnormalities be used as a surrogate marker for vascular dementia trials?

Clinical scales for measuring the effectiveness of disease-modifying therapies in patients with vascular dementia are of limited sensitivity. Moreover, they cannot serve to directly probe the potential of a drug in slowing further progression of vascular damage. Assessment of morphologic abormalities that reflect ischemia-related cerebral tissue changes and have a bearing on cognitive function could serve to address both of these aspects and, if sensitive enough, could constitute an ideal surrogate for measuring progression of the disease. For drug licensing agencies a validated surrogate has to meet several requirements: First, the surrogate must predict the future clinical course. Second, the effect of treatment on the disease must be explained by the effect of the treatment on the surrogate; the treatment needs to affect clinical outcome by working through mechanisms related to the surrogate. Third, evidence must exist that treatments of various classes affect the surrogate in the same and predictable manner. Apart from these requirements, regulatory guidelines may also allow the use of even an unvalidated surrogate if it is considered reasonably likely to predict future clinical outcome or disease activity. Various morphologic measures, particularly those using conventional or more sophisticated MRI techniques have already shown a close correlation to neuropsychologic functions. If these associations can also be confirmed in longitudinal studies and following specific treatments, morphologic markers will play a major role in future clinical trials of vascular dementia.

Aged↗

TACE mRNA expression in peripheral mononudear cells precedes new lesions on MRI in multiple sclerosis.

Tumor necrosis factor-alpha (TNF-alpha) is involved in the pathogenesis of multiple sclerosis (MS). It has to be released from its cell membrane-bound precursor by proteolytic cleavage. This is mainly performed by a member of the ADAM (a disintegrin and metalloproteinase) family of enzymes, TNF-alpha-converting enzyme (TACE, ADAM 17). In a longitudinal study on 11 relapsing-remitting MS patients, we qualitatively determined mRNA expression of TNF-alpha and TACE in peripheral blood mononuclear cells (PBMCs) without ex vivo stimulation. mRNA expression was related to disease activity as assessed by monthly gadolinium (Gd)-enhanced brain magnetic resonance imaging (MRI). Patients found positive for TACE mRNA in PBMCs showed a significantly higher mean number of new Gd-enhancing lesions per scan one month following PBMC sampling.

ADAM Proteins↗

Quantitative magnetization transfer imaging of pre-lesional white-matter changes in multiple sclerosis.

OBJECTIVE: Previous magnetization transfer (MT) studies in multiple sclerosis (MS) suggest a reduction of the MT ratio (MTR) precedes new lesion development. To gain further insight into pre-lesional tissue abnormalities, we investigated the time course of additional quantitative MT parameters. METHODS: Serial magnetic resonance imaging (MRI), including a gadolinium-enhanced T1 scan and MT imaging by means of a FastPACE sequence, was performed on 12 patients (4 males, 8 females) with relapsing-remitting MS. Quantitative MT values including the magnetization exchange rate (kfor) and the native relaxation time (T1free were analysed in the six months prior to the appearance of 44 enhancing lesions and in 88 control regions of persistently normal-appearing white matter (NAWM). RESULTS: Appearance of new active lesions was preceded by a significant decrease of the MTR (F7,166=91.5; p<0.0001) and of kfor (F7,166=105.2; p<0.0001), and by an increase of T1free (F7,166=57.3; p<0.0001). The drop of kfor was the most pronounced pre-lesional change and together with the MTR was statistically significant already four months before the appearance of new lesion. The observed increase of T1free was relatively small. MT variables of reactivated lesions were always different from NAWM but showed no characteristic time course. CONCLUSIONS: Multiparametric MT measurements suggest both a reduction of macromolecular material and a focal increase of free water to occur several months before the appearance of an active lesion. Reduction of the magnetization exchange rate, which may result from primary damage to myelin, appears to be the leading event

Adjuvants, Immunologic↗

T1 maps from shifted spin echoes and stimulated echoes.

A new pulse sequence for fast multislice T1 mapping is presented. This method is based on calculating T1 from spin echo (SE) and stimulated echo (STE) images obtained with different degrees of T1 weighting, and uses the interleaved acquisition scheme of the fast phase acquisition of composite echoes (FastPACE) technique. In contrast to the FastPACE technique, the two echoes are sampled separately. Experimental comparisons confirm that the new sequence layout overcomes most of the FastPACE restrictions, such as its motion sensitivity and the need for a fully complex data set. Moreover, this method offers a higher precision for long T1 values and a further reduction of acquisition time.

Brain↗

Estimation of magnetization transfer rates from PACE experiments with pulsed RF saturation.

A new imaging method has been developed for estimating the magnetization transfer rate (MTR) in a biologic two-pool system such as the brain tissue. The transfer rate is calculated from the ratio of the MTR to T(1sat), where T(1sat) is the apparent longitudinal relaxation time under complete saturation of the macromolecular pool. MTR and T(1sat) maps were obtained with a phase acquisition of composite echo (PACE) technique combined with pulsed radiofrequency (RF) saturation. The influences of RF saturation power and frequency offset on quantitative results were investigated with phantom and in vivo measurements. In white matter of seven healthy volunteers we found a mean transfer rate of 1.5 sec(-1), where the highest transfer rate was found in the genu of the corpus callosum (k(f) = 1. 9 sec(-1)). It could be shown that conditions near to complete saturation can also be reached under common restrictions by the specific absorption rate.

Brain↗

Novel imaging technologies in the assessment of cerebral ageing and vascular dementia.

Introduction of magnetic resonance imaging (MRI) has opened new possibilities for detecting age-related brain tissue changes. The majority of these abnormalities consists of hyperintense foci in the deep and subcortical white matter probably related to microvascular disturbances and of signal hyperintensities around the lateral ventricles. It has also been suggested that these abnormalities may contribute to the development of cognitive impairment. The correlation between age-related signal abnormalities on conventional MRI and neuropsychologic dysfunction is limited, however, and a threshold beyond which such a relation may come into existence has not yet been defined. Poor tissue characterisation by conventional MRI may be one explanation. Therefore, new pulse sequences are expected not only to provide a higher lesion contrast such as the fluid attenuated inversion recovery (FLAIR) technique but also to offer new insights concerning the composition of incidental brain lesions. In this context both magnetisation transfer imaging (MTI) and diffusion weighted imaging (DWI) may serve to gain information about the integrity of cell membranes and organelles and the preservation of axons and fibre tracts. We will review the technical background of these recently developed MR sequences and their first applications to age-associated brain abnormalities.

Aging↗

Apolipoprotein E genotype related differences in brain lesions of multiple sclerosis.

OBJECTIVES: Clinical reports have speculated on a more severe course of multiple sclerosis in patients with the apolipoprotein E (apoE) epsilon4 allele. As this could be reflected by differences in the severity of tissue damage MRI was used to obtain further support for a disease modifying effect of the apoE genotype. METHODS: Brain MR scans of 83 patients (mean age 35.5 (SD 9.5 years) who participated in a cross sectional study on the distribution of genotype patterns in multiple sclerosis. The total lesion load on proton density weighted (T2-LL) and T1 weighted scans (T1-LL) obtained with conventional spin echo sequences at 1.5 T was measured. A "black hole" ratio ((T1-LL/T2-LL)x100) was also calculated. This indicates the proportion of multiple sclerosis lesions with more severe tissue damage and may reflect disease aggressiveness or quality of repair. RESULTS: Patients with the apoE-epsilon3/epsilon4 genotype (n=19) showed a non-significantly greater T2-LL (16.0 (SD 14.0) cm(3)) than patients with the epsilon2/epsilon3 (n=11; 13.3 (9.5) cm(3)) or the epsilon3/epsilon3 genotype (n=49; 9.4 (SD 9.2) cm(3)). Both the T1-LL (2.6 (SD 3.3) v 1.6 (SD 2.4) and 1.2 (SD 3.0) cm(3); p=0.04) and the black hole ratio (14.3 SD 11.9) v 7.4 (SD 9.3) and 8.4 (SD 13.3)%; p=0.02), however, were significantly higher in epsilon3/epsilon4 patients. Similar differences were seen when comparing patients with at least one epsilon4 allele with the remainder of the group. CONCLUSIONS: These data support speculations on a modulation of multiple sclerosis severity by the apoE genotype which can be attributed to more extensive tissue destruction or less efficient repair in carriers of the epsilon4 allele.

Adolescent↗

T1 imaging using phase acquisition of composite echoes.

A new magnetic resonance method for T1 imaging is presented. It is based on the simultaneous acquisition of a spin echo and a phase-shifted, stimulated echo. The phase of this composite echo image is modulated heavily by the spin-lattice relaxation time T1, whereas spin density and T2 do not influence the phase information. This phase information can be assigned easily to corresponding T1 values. Although this method is sensitive to radiofrequency inhomogenities, phantom studies showed that high precision and reasonable accuracy of T1 determination can be achieved. Moreover, this method was found to be very robust, because no fitting is required. T1 imaging of the human brain was performed to confirm the in vivo utility of this method.

Adult↗

Fast multislice T(1) and t(1sat) imaging using a phase acquisition of composite echoes (PACE) technique.

An optimized multislice data acquisition scheme for phase acquisition of composite echoes (PACE) imaging is presented. This new scheme uses a repetition time equal to the mixing time and an appropriate phase cycling scheme, which allows for more efficient exploitation of all composite echoes. These modifications provide true multislice capability in parallel to a reduction of the acquisition time by a factor >2 compared with the original PACE method. Moreover, T(1) values can be obtained directly from phase images without the use of a lookup table. Because of the symmetrical application of the radio frequency pulses, this method is also well suited for T(1sat) imaging. Phantom studies showed a significantly better accuracy of the multislice fast PACE technique compared with a conventional two-point method in multislice acquisition mode, although precision was limited at high T(1) values. T(1) and T(1sat) measurements in brain tissue of eight healthy volunteers confirmed the stability of the fast PACE technique in a clinical setting. Magn Reson Med 42:1089-1097, 1999.

Adult↗

Diffusion-weighted imaging with navigated interleaved echo-planar imaging and a conventional gradient system.

PURPOSE: To demonstrate the technical feasibility and precision of a navigated diffusion-weighted (DW) MR imaging method with interleaved echo-planar imaging and test its diagnostic sensitivity for detection of ischemic stroke. MATERIALS AND METHODS: Apparent diffusion coefficient (ADC) measurements were performed in phantoms, and six healthy adult volunteers were examined to determine intrasubject (precision) and intersubject (reference range) variations in absolute ADC and relative ADC (rADC) measurements. DW imaging maps and lesion rADC values were also obtained in 34 consecutive stroke patients to evaluate the sensitivity and reliability of DW-interleaved echo-planar imaging for detection of ischemic brain damage. RESULTS: Phantom and volunteer ADC values were in excellent agreement with published data. The intrasubject variation of rADC was 6.2%. The ADC precision ranged from 6.5% in the subcortical white matter in the frontal lobe to 12.9% in the head of the caudate nucleus. Interleaved echo-planar imaging enabled rapid acquisition of high-quality images of the entire brain without substantial artifacts. Within the 1st week, the sensitivity of DW-interleaved echo-planar imaging for detection of acute infarction was 90% (18 of 20 true-positive studies) and independent of lesion location. CONCLUSION: DW-interleaved echo-planar imaging with phase navigation and cardiac triggering is robust, reliable, and fast. With high sensitivity for detection of early ischemic infarction, it is useful for examining stroke patients by using MR systems with conventional gradient hardware.

Adult↗