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Biomedical subjects

H B Larsson

Publications and source records attributed to H B Larsson.

At least 55 records · Page 3Linked to original sources

White matter magnetic resonance hyperintensities in dementia of the Alzheimer type: morphological and regional cerebral blood flow correlates.

In a prospective MRI study the presence, appearance, volume, and regional cerebral blood flow (rCBF) correlates of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) were examined in 18 patients with probable Alzheimer's disease and in 10 age matched healthy control subjects, all without major cerbrovascular risk factors. The 133Xe inhalation method and the [99mTc]-d,l-hexamethyl-propylene-amine-oxime (HMPAO) technique with single photon emission computed tomography (SPECT) were used to measure rCBF. Rating scores for PVHs were significantly higher in the Alzheimer's disease group (p < 0.01) and correlated significantly with the volume of ventricles (p < 0.05) and with systolic arterial blood pressure (p < 0.01), but not with rCBF. By contrast, there was no significant difference in the rating scores or volumes of DWMHs between the two groups, although three patients had extensive DWMH lesions in the central white matter. In the group of patients with Alzheimer's disease as a whole, the volume of DWMHs correlated well with rCBF in the hippocampal region ( r = -0.72; p < 0.001), but not with frontal, temporal, parietal, or occipital rCBF. Postmortem histopathology of extensive DWMH lesions in one patient with definite Alzheimer's disease showed a partial loss of myelin and astrocytic gliosis, but no ischaemic changes. It is concluded that DWMH lesions may be associated with reduced rCBF in the hippocampal region. The heterogenous topography of neocortical rCBF deficits in Alzheimer's disease could not be explained by deafferentation from underlying white matter hyperintensities and therefore may reflect variations in the topography of cortical abnormalities.

Aged↗

Age dependent white matter lesions and brain volume changes in healthy volunteers.

The brain of 142 healthy volunteers aged 21 to 80 years were investigated using MR imaging. The number and size of the white matter hyperintensity lesions (WMHL) in the cerebral hemispheres were determined. Furthermore, the volume of the cerebral hemispheres and of the lateral ventricles was measured. An almost linear increase in the number of volunteers with WMHL was seen with aging for males and females. With aging a significant decrease in the volume of the cerebral hemispheres was found for males, and a significant increase in the volume of the lateral ventricles was seen for both males and females. Our results suggest that with aging central atrophy increases more (relatively) than cortical atrophy. No correlation was found between the decreasing volume of the cerebral hemispheres and the increasing number and size of WMHL, nor between the increasing volume of the lateral ventricles and the increasing number and size of WMHL.

Adult↗

The concentration of N-acetyl aspartate, creatine + phosphocreatine, and choline in different parts of the brain in adulthood and senium.

The fully relaxed water signal was used as an internal standard in a STEAM experiment to calculate the concentrations of the metabolites: N-acetyl aspartate (NAA), creatine + phosphocreatine (Cr + PCr), and choline (Cho) containing compounds in four different parts of the brain in two age groups of healthy volunteers (20-30 yr, n = 8) and (60-80 yr, n = 8). Furthermore, T1 and T2 relaxation time of the metabolites and signal ratios: NAA/Cho, NAA/Cr + PCr, and Cho/Cr + PCr at TE = 272 msec were calculated. The experiments were carried out using a Siemens Helicon SP 63/84 wholebody MR-scanner at 1.5 T. In the younger age group, the concentration of NAA was significantly higher in the occipital part than in the other three parts of the brain. No significant regional variation was found for any other metabolite concentration. There was a significantly higher concentration of NAA in the occipital part of the brain in the younger age group compared to the older one. No significant regional or age dependent variation was found concerning the T1 and T2 relaxation times.

Adult↗

In vivo quantification of brain metabolites by 1H-MRS using water as an internal standard.

The reliability of absolute quantification of average metabolite concentrations in the human brain in vivo by 1H-MRS using the fully relaxed water signal as an internal standard was tested in a number of in vitro as well as in vivo measurements. The experiments were carried out on a SIEMENS HELICON SP 63/84 wholebody MR-scanner operating at 1.5 T using a STEAM sequence. In vitro studies indicate a very high correlation between metabolite signals (area under peaks) and concentration, R = 0.99 as well as between metabolite signals and the volume of the selected voxel, R = 1.00. The error in quantification of N-acetyl aspartate (NAA) concentration was about 1-2 mM (6-12%). Also in vivo a good linearity between water signal and selected voxel size was seen. The same was true for the studied metabolites, N-acetyl aspartate (NAA), creatine/phosphocreatine (Cr/PCr), and choline (Cho). Calculated average concentrations of NAA, Cr/PCr, and Cho in the occipital lobe of the brain in five healthy volunteers were (mean +/- 1 SD) 11.6 +/- 1.3 mM, 7.6 +/- 1.4 mM, and 1.7 +/- 0.5 mM. The results indicate that the method presented offers reasonable estimation of metabolite concentrations in the brain in vivo and therefore is useful in clinical research.

Body Water↗

Increased water self-diffusion in chronic plaques and in apparently normal white matter in patients with multiple sclerosis.

A new method for measurement of water self-diffusion compensating for zeroth and first order movements was used to study the apparent diffusion coefficient (ADC) in 15 patients with chronic multiple sclerosis (MS) and in two patients with acute MS. Ten healthy volunteers served as controls. A significantly higher ADC was found within chronic plaques compared to the apparently normal white matter of the chronic patients. The ADC was higher in the acute plaques compared to the chronic plaques. The ADC in apparently normal white matter of the chronic patients were significantly higher than in white matter of healthy volunteers. We hypothesize that an increase of the ADC in plaques may be related to an increase in the extracellular space due to oedema and demyelination. The increased ADC in apparently normal white matter suggests that there may be a change in the composition of the white matter of chronic MS patients, perhaps related to oedema and expanded extracellular space.

Adult↗

Functional MR imaging at 1.5 T. Initial results using photic and motoric stimulation.

A preliminary investigation of the effects of stimulation of the visual and the motor cortex was made on a conventional 1.5 T MR imaging scanner. Both types of activation gave a detectable change in the signal between rest and stimulation using a gradient echo sequence with an echo time of 60 ms. The observed effects were assumed to be caused by variation in the amount of paramagnetic deoxyhemoglobin between stimulation and rest due to local increase of capillary blood flow in the human brain during stimulation.

Brain↗

Measurement of blood-brain barrier permeability using dynamic Gd-DTPA scanning--a comparison of methods.

Two recently published methods of blood-brain barrier permeability measurement using Gd-DTPA scanning are compared by authors representing each group. The physiological models are reconciled. Results from both groups agree. These show that the transfer constant (the permeability surface area product per unit volume of tissue) of the defective blood-brain barrier in multiple sclerosis is in the range 1-12.10(-4) s-1.

Blood-Brain Barrier↗

In vivo evaluation of the reproducibility of T1 and T2 measured in the brain of patients with multiple sclerosis.

The precision (reproducibility) of relaxation times derived from magnetic resonance images of patients with multiple sclerosis (MS) were investigated. Measurements of 10 MS patients were performed at 1.5 T on two occasions within 1 wk. T1 and T2 was measured using a partial saturation inversion recovery sequence (6 points) and a Carr-Purcell-Meiboom-Gill phase alternating-phase shift multiple spin-echo sequence with 32 echoes. Regions of interest (ROI) were placed both in apparently normal white matter and plaques. The precision (+/- 1.96 SD) and the confidence intervals for T1 and T2 for white matter and plaques were calculated. The precision of T1 for white matter and plaques was respectively +/- 94 msec and +/- 208 msec. The precision of T2 for white matter and plaques was respectively +/- 18 msec and +/- 26 msec. For all measurements the coefficient of variation was about 9%. Judging from our own study and others as well, a precision better than 10% for T1 and T2 would seem unrealistic at present.

Adult↗

In vivo magnetic resonance diffusion measurement in the brain of patients with multiple sclerosis.

Measurement of water self-diffusion in the brain in 25 patients with multiple sclerosis was performed by magnetic resonance imaging. Quantitative diffusion measurements were obtained using single spin-echo pulse sequences with pulsed magnetic field gradients of different magnitude. Twenty-two of these patients also underwent measurement of the transverse relaxation time (T2). Only one plaque was evaluated in each patient. Based on prior knowledge, 12 plaques were classified as being 3 mo or less in age, and 7 plaques were classified as being more than 3 mo old. In all 25 plaques, water self-diffusion was found to be higher than in apparently normal white matter. Furthermore, water self-diffusion was found to be higher in acute plaques compared with chronic plaques. Finally, a slight tendency toward a relationship between the diffusion capability and T2 was found. We believe that an increased diffusion capability signifies an increase of the extracellular water space, which probably is related to the degree of demyelination. Thus, measurement of water self-diffusion in multiple sclerosis plaques may contribute to the study of pathogenesis of demyelination.

Adult↗

Gd-DTPA-enhanced lesions in the brain of patients with acute optic neuritis.

The cerebral hemispheres of 19 patients with acute monosymptomatic optic neuritis (AMON) were investigated using magnetic resonance imaging (MRI) and Gadolinium-DTPA (Gd-DTPA). Using T1-weighted and T2-weighted imaging sequences it was disclosed that 14 of 19 patients had lesions and that enhancement was seen in seven patients. It is known that patients with AMON and silent lesions in the CNS have a highly increased risk of developing multiple sclerosis (MS) later on. If it is accepted that a silent lesion in patients with AMON does represent a multiple sclerosis (MS) plaque, and that an enhancing silent lesion represents an acute MS lesion, we may hypothesize that the disease process ultimately leading to MS starts long before the first symptom or sign ever appears. It would seem that at least half of the silent lesions in the cerebral hemispheres of patients with AMON had existed before the onset of the AMON, and that the disease actually started before the onset of the AMON.

Adult↗

Correlation of magnetic resonance imaging and CSF findings in patients with acute monosymptomatic optic neuritis.

Acute monosymptomatic optic neuritis (AMON) may be the first indication of multiple sclerosis (MS), and this sign offers a special opportunity to study the very early clinical stages of MS. This prospective investigation compares results of CSF findings and magnetic resonance imaging (MRI) in a large, homogeneous and well-defined group of patients with AMON. Of 68 consecutively referred patients, 11 had clinically definite MS, another 5 refused a lumbar puncture, and 7 could not participate for various reasons. With the remaining 45 untreated patients, aged 12-52 (mean 31) years, with idiopathic AMON, we have studied interrelationships of CSF findings (leucocyte count, IgG-index and in 29 of the patients oligoclonal bands (OB)) and MRI. Lumbar puncture and MRI were performed within median 24 and 16 days of onset, respectively. In the CSF one or more abnormalities (in 17/45 = 38% pleocytosis, in 16/45 = 36% increased IgG-index, and in 20/29 = 69% OB) was found in a total of 23/29 = 79% of patients. MRI at 1.5 T (double SE and IR sequences) showed multiple cerebral lesions in 65% of patients. A significant relation was observed between results of MRI and leucocyte count (p < 0.05) and between results of MRI and IgG-index (p < 0.05), but not between results of MRI and OB (p > 0.20). Over a median observation period of 27 months, 13 patients developed clinically definite MS. All of these patients had lesions on MRI at onset, illustrating the prognostic importance of MRI findings. Results of CSF had until now no marked predictive value for developing clinically definite MS.

Adolescent↗

Localized in vivo proton spectroscopy in the brain of patients with multiple sclerosis.

Localized proton spectroscopy was performed in 15 patients with acute or chronic multiple sclerosis (MS). Some of the patients were investigated serially, being given a total of 22 spectroscopic investigations. Resonances corresponding to free lipids were observed in six plaques. This was distinctly seen in two plaques at Days 70 and 85 after the occurrence of the plaques. A lesser content of lipids in plaques was observed as early as Day 10 and as late as nearly 1 year after occurrence. The relative concentration of N-acetyl asparate (NAA) was significantly lower in patients than in controls, and the relative concentration of choline (Cho) was significantly higher in patients than in controls. These differences were most pronounced in older plaques. MR spectroscopic demonstration of lipids in a MS plaque probably reflects disintegration of myelin, and a decreased NAA/Cho ratio may be related either to gliosis or to axonal degeneration, which sometimes occurs in longstanding MS.

Acute Disease↗

MRI, VEP, SEP and biothesiometry suggest monosymptomatic acute optic neuritis to be a first manifestation of multiple sclerosis.

A cohort of 50 consecutive patients with acute monosymptomatic optic neuritis (ON) from a defined catchment area joined a prospective study. The aim of this study was to compare the sensitivity of magnetic resonance imaging (MRI), electrophysiological methods (VEP and SEP) and biothesiometry to detect abnormalities in other parts of the CNS than the optic nerves during the acute phase of ON. For each method, a scoring system is proposed. This investigation also hoped to achieve a better understanding of the natural history of ON. MRI proved to be the most sensitive tool (63% abnormal) in confirming a second site of involvement, followed by VEP in the clinically unaffected fellow eye (42%), biothesiometry (32%) and SEP (17%). The combination of all these methods, except for MRI (and VEP in eyes with acute ON), revealed abnormalities in 63% of the patients. When the neurophysiological methods were combined with MRI, 79% of the patients had abnormal findings suggesting additional lesions in the CNS. Hence, MRI and neurophysiological examinations supplement each other and together provide evidence that monosymptomatic ON is usually a first manifestation of MS. The development of definite MS at 1-20 months of follow up in 7 patients (all with abnormal MRI initially) supports this view.

Adolescent↗

Plaques causing hemianopsia or quadrantanopsia in multiple sclerosis identified by MRI and VEP.

Four patients with definite multiple sclerosis (MS) gave evidence of demyelinating plaques that produced a form of visual loss atypical of MS, i.e. homonymous quadrantanopsia (women, 22 and 30 years), and homonymous hemianopsia (men, 30 and 42 years). Cerebral magnetic resonance imaging (MRI) identified areas with increased signal intensity situated corresponding to the observed visual field defects. The results of visual evoked potentials (VEP) were in accordance with what should be expected from anatomical considerations.

Adult↗

Acute optic neuritis with normal visual acuity. Comparison of symptoms and signs with psychophysiological, electrophysiological and magnetic resonance imaging data.

In a prospective study of hitherto 70 patients with acute optic neuritis (ON), 18 patients aged 15-49 years (12 women, 6 men) were diagnosed as having very subtle form of ON (bilateral in 4 patients), characterized by normal visual acuity. However, their symptoms were sudden functional visual disturbances, most frequently blurred vision accompanied by pain in or around the affected eye(s). In 5 patients, the ON was a manifestation of clinically definite multiple sclerosis (MS); the remaining 13 patients had monosymptomatic ON. The duration of visual symptoms ranged from 2 to 28 days (median 7 days) at the time of examination. Although 18 patients had a normal visual acuity, i.e. 6/6 c.c. (Snellen's notation) or better, extensive studies of the visual functions (using sensitive supplementary tests) revealed various abnormalities, primarily various visual field defects, abnormal contrast sensitivity, abnormal VEP and colour vision deficiencies (often of blue-yellow type). Magnetic resonance imaging (MRI) of the brain revealed demyelinating lesions in 10 of the 13 patients with monosymptomatic ON, and in all 5 patients with definite MS. The extended disease spectrum gives reason to hypothesixe that ON may occur more frequently than previously reported, and that the described subtle form of ON could be an unnotified precocious manifestation of the demyelinating disease.

Acute Disease↗

Quantitation of blood-brain barrier defect by magnetic resonance imaging and gadolinium-DTPA in patients with multiple sclerosis and brain tumors.

In this study quantitation of the degree of deficiency of the blood-brain barrier (BBB) in patients with multiple sclerosis or brain tumors, by using MRI, is shown to be possible. As a measure of permeability of the BBB to Gadolinium-DTPA (Gd-DTPA) the flux per unit of distribution volume per unit of brain mass was used. This quantity was found by introducing the longitudinal relaxation rate (R1) as a measure of concentration of Gd-DTPA in the brain tissue in the mathematical model for the transcapillary transport over the BBB. High accordance between the observed data points and the model was found, and the results were comparable to results obtained from similar studies using positron emission tomography. The improved possibility of quantitating the defect of the BBB by MRI may give new information about pathogenesis or etiology, and leads to improved methods in monitoring the efficacy of treatments in intracranial diseases.

Blood-Brain Barrier↗

Assessment of demyelination, edema, and gliosis by in vivo determination of T1 and T2 in the brain of patients with acute attack of multiple sclerosis.

This study intended to investigate the possibility of magnetic resonance (MR) to characterize the acute plaque due to multiple sclerosis (MS). To obtain information, in vivo measurements of relaxation processes were performed in 10 patients with known acute MS plaques, using a whole-body superconductive MR-scanner, operating at 1.5 T. The measurements were repeated several times, from onset of the disease and during remission by use of six-point partial saturation inversion recovery and 32-echo multiple spin-echo sequences, giving T1 and T2, respectively. We also focused on the issue, whether T1 and T2 relaxation processes in fact were monoexponential. The results of the first T1 and T2 measurements of the acute plaques were not clearly different from T1 and T2 of presumably chronic plaques obtained in a group of chronic MS patients previously (H.B.W. Larsson, J. Frederiksen, L. Kjär, O. Hendriksen, and J. Olesen, Magn. Reson. Med. 7, 43 (1988)). In some of the acute plaques a slight initial increase in T1 and T2 was seen, when the measurement was repeated in about 10 days. Thereafter T1 decreased slowly in all but one patient as a function of days. In all cases the T1 relaxation process followed a monoexponential course. The T2 relaxation process was a monoexponential function in the acute plaques, when measured within 20 days from onset of disease. After an average of 78 days, however, the T2 relaxation process clearly became biexponential in all but two patients. Later some of the relaxation curves changed back toward monoexponentiality. Thus, the study shows that it is possible to detect significant changes in MR parameters during the evolution of the disease, and these changes are discussed in relation to knowledge of pathoanatomical events in MS.

Acute Disease↗

Magnetic resonance imaging of the brain in patients with acute monosymptomatic optic neuritis.

Ophthalmologists and neurologists from a catchment area of 1.5 million people were asked to refer all patients with symptoms and signs of optic neuritis (ON) to our neurological department immediately. A total of 68 consecutive patients were extensively screened for known etiologies of ON. Eleven had definite multiple sclerosis (MS); 7 patients could not participate for various reasons. The cerebrum, cerebellum and brainstem of the remaining 50 untreated patients with monosymptomatic ON were MRI scanned at 1.5 T with 2 sequences (slice thickness 4 mm, voxel size 1.2 x 1.2 x 4 mm3): double spin-echo (TR = 1.8 s, TE = 30 and 90 ms, 12 slices axially) and inversion recovery (TR = 2.45 s, TI = 400 ms, TE = 30 ms, 5 slices sagittaly). Magnetic resonance imaging (MRI) was performed within 3-49 (median 16) days from onset of symptoms. MRI demonstrated multiple asymptomatic central nervous system (CNS) lesions in 62% of patients. The appearance, locations and extents of lesions were consistent with demyelination. A scoring system based on number and size of lesions is proposed. Seven of 50 patients developed definite MS during a median follow-up of 11 months; they all had CNS lesions on the first scan. MRI has thus improved the pathophysiological knowledge of idiopathic ON, which from the very onset is a manifestation of MS in at least two thirds of cases. Patients who have early CNS lesions run a much higher risk of later developing clinically definite MS.

Adolescent↗