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Biomedical subjects

O Henriksen

Publications and source records attributed to O Henriksen.

At least 37 records · Page 2Linked to original sources

Twelve-hour brain lithium concentration in lithium maintenance treatment of manic-depressive disorder: daily versus alternate-day dosing schedule.

The 12-h brain lithium concentration was measured by lithium-7 magnetic resonance spectroscopy in ten manic-depressive patients receiving daily or alternate-day lithium carbonate treatment. The median dose of lithium carbonate was 800 mg in the daily treatment group and 1200 mg in the alternate-day group. Median 12-h serum lithium concentration in the two groups was 0.86 mmol l-1 and 0.55 mmol l-1, respectively, while the corresponding concentration in brain was 0.67 mmol l-1 and 0.52 mmol l-1, respectively. The 12-h brain lithium concentration was independent of lithium dosing schedule (multiple linear regression), but correlated significantly with the 12-h serum lithium concentration (P = 0.003; B = 0.53, 95% c.l. 0.24-0.82; beta = 0.83). Thus at identical 12-h serum lithium concentrations the 12-h brain lithium concentration is similar with both treatment regimes. As the risk of manic-depressive relapse during alternate-day lithium treatment is in our experience 3-fold greater than with daily treatment (at similar mean 12-h serum lithium concentration), the findings suggest that the difference in the prophylactic efficacy of the two dosing schedules is unrelated to differences in the 12-h brain lithium concentration.

Adult↗

Quantitative assessment of synovial inflammation by dynamic gadolinium-enhanced magnetic resonance imaging. A study of the effect of intra-articular methylprednisolone on the rate of early synovial enhancement.

The effect of temporary inflammatory suppression on synovial membrane enhancement, as determined by dynamic and static gadolinium-DTPA enhanced magnetic resonance imaging (MRI), was studied. MRI of 18 arthritic knees was performed before and 1, 7, 30 and 180 days after intra-articular methylprednisolone injection until clinical relapse. MRI of another six knees was performed twice within 2-4 days in order to assess interobserver and inter-MRI variation. The rate of early enhancement of the entire synovial membrane of a pre-selected central sagittal slice (REEsyn,tot), determined by dynamic T1-weighted FLASH MRI, decreased in all knees within the first post-treatment week and remained low during remission, although gradually increasing. In cases of clinical relapse, REEsyn,tot increased to pre-treatment levels. The interobserver plus inter-MRI variation was maximally 27%. The predictive values of a REEsyn,tot below/above 1.0%/s were 0.94 and 0.91, respectively, with respect to the absence/presence of clinical synovitis. Evaluation of small synovial areas revealed marked regional heterogeneity. Static spin echo MRI was not informative. The study indicates that the rate of early synovial enhancement reflects synovial inflammatory activity. Subclinical changes may be revealed. Evaluation of large synovial areas increases reproducibility and reduces the effect of regional heterogeneity. Dynamic MRI may prove a clinically useful measure of synovial inflammation.

Anti-Inflammatory Agents↗

Double-blind, placebo-controlled trial of topiramate as add-on therapy in patients with refractory partial seizures.

In a double-blind, randomized, parallel-group trial, we compared topiramate (TPM) with placebo as add-on therapy in patients with refractory partial epilepsy. TPM was titrated either to the target dosage of 800 mg/ day [400 mg twice daily (b.i.d)] or to the maximal tolerated dose if lower. Twenty-eight (28) patients were randomized to each treatment group. In the intent-to-treat analysis, the net median percent reduction relative to placebo in average monthly seizure rate was 54% for patients in the TPM group (p < 0.001). None of the placebo-treated patients and 43% of the patients treated with TPM experienced > or = 50% reduction in seizures (p = 0.001), and 36% of patients assigned to TPM had a 75-100% reduction in seizures (p < 0.01). Secondarily generalized seizures were also significantly reduced in the TPM group (p = 0.044). The most common adverse events (AE) reported in the TPM group were fatigue, impaired concentration, weight loss, dizziness, and paresthesias. AE occurring either during the rapid titration of TPM or at high dosages led 21% of TPM-treated patients to withdraw from the study. Half of these occurred during the titration study period. No serious AE or clinically important changes in clinical laboratory measures were observed. The present study further establishes the favorable profile and good benefit/risk ratio of TPM in resistant partial epilepsy.

Adolescent↗

Double-blind, placebo-controlled trial of topiramate (600 mg daily) for the treatment of refractory partial epilepsy.

PURPOSE: We wished to evaluate adjunctive therapy for partial-onset seizures with topiramate (TPM) for efficacy and safety in a double-blind, placebo-controlled, randomized, parallel-group study. METHODS: Sixty outpatients with epilepsy (47 men and 13 women, mean age 32.9 years) were studied. All had a documented history of partial-onset seizures with or without secondarily generalized seizures. After an 8-week baseline during which patients had at least one seizure per week, 30 patients each were randomized to TPM 300 mg twice daily (b.i.d.) or placebo for 12 weeks. RESULTS: TPM was significantly superior to placebo, as indicated by all efficacy assessments: greater median percent reduction from baseline in the average monthly seizure rate (46 vs. -12%, p = 0.004); greater number of treatment responders (patients with > or = 50% reduction in seizure rate) (47 vs. 10%, p = 0.001), and better investigator (p = 0.002) and patient (p = 0.010) global assessments of treatment. Among TPM-treated patients, the most commonly reported adverse events (AE) were headache, somnolence, fatigue, dizziness, and abnormal thinking. Most AE were mild or moderate in severity. CONCLUSIONS: The results of the present trial indicate that TPM 600 mg/day is effective in the treatment of refractory partial-onset seizures with or without secondarily generalized seizures.

Adolescent↗

Use of brain lactate levels to predict outcome after perinatal asphyxia.

Perinatal asphyxia is an important cause of neurological disability, but early prediction of outcome can be difficult. We performed proton magnetic resonance spectroscopy (MRS) and global cerebral blood flow measurements by xenon-133 clearance in 16 infants with evidence of perinatal asphyxia. Cerebral blood flow was determined daily in the first 3 days after birth in seven cases. Proton MRS was performed in 11 infants within the first week (mean 3.7 days), the rest within the first month (mean 22.2 days), and all had a scan around 3 months of age. Four infants died neonatally, three showed neurological deficits and the rest seemed to be progressing normally at neurodevelopmental follow-up at 1 year of age. A significant correlation was found between initial brain lactate levels and severe outcome (p = 0.0003) just as between cerebral hyperperfusion (mean cerebral blood flow (CBF) 86 ml(100 g)-1 min-1), (p = 0.02) and outcome. The diagnostic and prognostic implications of early MRS and CBF are predictive of poor outcome in severely asphyxiated infants.

Asphyxia Neonatorum↗

MR velocity mapping measurement of renal artery blood flow in patients with impaired kidney function.

Renal blood flow (RBF) was measured in 9 patients with chronic impaired kidney function using MR velocity mapping and compared to PAH clearance and 99mTc-DTPA scintigraphy. An image plane suitable for flow measurement perpendicular to the renal arteries was chosen from 2-dimensional MR angiography. MR velocity mapping was performed in both renal arteries using an ECG-triggered gradient echo pulse sequence previously validated in normal volunteers. Effective renal plasma flow was calculated from the clearance rate of PAH during constant infusion and the split of renal function was evaluated by 99mTc-DTPA scintigraphy. A reduction of RBF was found, and there was a significant correlation between PAH clearance multiplied by 1/(1-hematocrit) and RBF determined by MR velocity mapping. Furthermore, a significant correlation between the distribution of renal function and the percent distribution of RBF was found.

Aged↗

Measurement of blood flow in the superior sagittal sinus in healthy volunteers, and in patients with normal pressure hydrocephalus and idiopathic intracranial hypertension with phase-contrast cine MR imaging.

PURPOSE: To measure blood flow and velocity in the superior sagittal ++sinus. MATERIAL AND METHODS: MR velocity mapping was used to examine 14 healthy volunteers, 15 patients with normal pressure hydrocephalus (NPH), 3 patients with high pressure hydrocephalus (HPH), and 11 patients with idiopathic intracranial hypertension (IIH). RESULTS: Mean blood flow was 443 ml/min in healthy volunteers with a tendency towards reduced blood flow with increasing age. In NPH patients significantly lower superior sagittal sinus blood flow values were found, but this difference was no longer significant when patients and controls were matched for age. In HPH and IIH patients blood flow and velocity were within the normal range. In one patient with thrombosis of the superior sagittal sinus the blood flow was reduced to 40 ml/min. CONCLUSION: MR velocity mapping methods may be of value in the assessment of blood flow in the dural sinuses in various pathologies resulting in dural sinus occlusion, such as dural sinus thrombosis, and for following the progress of these patients while undergoing treatment.

Adult↗

Susceptibility contrast imaging of CO2-induced changes in the blood volume of the human brain.

PURPOSE: To investigate changes in the regional cerebral blood volume (rCBV) in human subjects during rest and hypercapnia by MR imaging, and to compare the results from contrast-enhanced and noncontrast-enhanced susceptibility-weighted imaging. MATERIAL AND METHODS: Five healthy volunteers (aged 24-29 years) were studied during inhalation of atmospheric air and 7% CO2. A bolus injection of Gd-DTPA was given during the acquisition of a series of susceptibility-weighted, fast gradient echo images (TR/TE = 27/22 ms). The images were converted to delta R2* maps, and CBV was calculated pixelwise by fitting a gamma-variate function to the data. The tissue concentration vs time curves were deconvoluted using an input function obtained by arterial sampling. RESULTS: The ratio of gray to white matter CBV (1.9-2.5) as well as the fractional increase in rCBV during hypercapnia (about 30%) was found to be in accordance with results obtained by other methods. Noncontrast functional MR (fMR) imaging showed signal increases in gray matter, but also inconsistent changes in some white matter regions. CONCLUSION: In this experiment, contrast-enhanced imaging seemed to show a somewhat higher sensitivity towards changes in cerebral hemodynamics than noncontrast-enhanced imaging. The results of the deconvolution analysis suggested that perfusion calculation by conventional tracer kinetic methods may be impracticable because of nonlinear effects in contrast-enhanced MR imaging.

Administration, Inhalation↗

Cerebral glucose metabolism is decreased in white matter changes in patients with phenylketonuria.

Cerebral magnetic resonance imaging (MRI) has revealed white matter changes in patients with phenylketonuria (PKU), an inborn error of metabolism with increased plasma phenylalanine level. Because the significance of these lesions is unknown, this study was undertaken to determine whether glucose metabolism was depressed in cerebral white matter MRI changes in patients with PKU. Four patients with PKU and nine healthy volunteers with an average age of 23 y (range 19-26 y) and 23 y (range 20-27 y), respectively, were studied. The IQ of patients with PKU was between 58 and 97. Cerebral MRI and positron emission tomography images with 18F-deoxyglucose were obtained, and arteriovenous differences for oxygen and glucose as well as cerebral blood flow was measured simultaneously to determine global cerebral oxygen and glucose metabolism. Cerebral MRI revealed that all patients with PKU had white matter changes with characteristic localization. In patients with PKU, regional glucose metabolism was 36% lower in the anterior periventricular areas, 0.14 +/- 0.06 compared with 0.22 +/- 0.04 mumol.g-1.min-1 in controls (mean +/- SD, p < 0.05, Mann-Whitney). Further, the ratio between glucose metabolism in the affected white matter and the cortex was 14% lower in the patients, decreasing from 0.57 +/- 0.05 to 0.48 +/- 0.06 (p < 0.05). Global cerebral blood flow, oxygen and glucose consumption were similar in the two groups. In conclusion, regional glucose metabolism is lower in MRI-demonstrated white matter changes. In mildly intellectually impaired patients with PKU, global cerebral glucose and oxygen metabolism remain intact.

Adult↗

Changes in synovial membrane and joint effusion volumes after intraarticular methylprednisolone. Quantitative assessment of inflammatory and destructive changes in arthritis by MRI.

OBJECTIVE: To evaluate synovial membrane volumes, effusion volumes, and cartilage and bone erosion scores determined by magnetic resonance imaging (MRI) as markers of disease activity and severity in arthritis. METHODS: Gadolinium-DTPA enhanced MRI of 18 arthritic knees was performed before and 1, 7, 30 and 180 days after intraarticular methylprednisolone injection until clinical relapse. Intraobserver, interobserver, and inter-MRI variations were determined from 2 successive MRI of another 6 knees. RESULTS: In all knees synovial membrane and effusion volumes decreased within the first posttreatment week (median decrease 49 and 65%, respectively), and remained low during remission. Synovial volumes, but not effusion volumes, increased to pretreatment levels in case of clinical relapse, indicating that synovial volumes were most important to the clinical appearance. The intraobserver + interobserver + inter-MRI variation was maximally 26%. Total volumes and volumes in a selected sagittal slice were highly statistically correlated. The duration of clinical remission in patients with rheumatoid arthritis (RA) was significantly inversely correlated to the pretreatment synovial volume (both total and "one slice" volumes), but not to the effusion volume, MRI or radiography scores of erosions or any clinical/laboratory variables. Cartilage and bone erosions, invisible by radiography, were visualized by MRI. No progressive erosive changes were observed. CONCLUSION: MRI-determined synovial and effusion volumes and MRI scores of cartilage and bone erosions are reproducible and may be sensitive measures of disease activity and severity in RA. The synovial volume may rather than the effusion volume determine clinical appearance. Both are influenced by the present inflammatory activity. The pretreatment synovial volume may have predictive value to treatment outcome in RA.

Adult↗

[Shore-term stimulation with myeloid growth factors expands bone marrow hematopoiesis. A magnetic resonance spectroscopic study].

The present study is intended to investigate the expansion of haematopoiesis by localised volume selective proton magnetic resonance spectroscopy (MRS) during treatment with myeloid growth factors. Six consecutive patients were treated with daily subcutaneous injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF, n = 2) or granulocyte-macrophage colony-stimulating factor (rhGM-CSF, n = 4) for five days before marrow harvest. MRS investigations were performed prior to treatment (day 0), day 5 and day 12. The patients responded with a rise in blood absolute neutrophil count from median 3.3 x 10(9)/l (range 1.3-7.3 x 10(9)/l) before to 15.6 x 10(9)l (range 6.8-22.0 x 10(9)/l) after treatment. Concomitantly an increase in bone marrow cellularity and myeloid:erythroid ratios documented the stimulation of myelopoiesis. During priming, the light-density cell proliferation rate in marrow samples increased from median 21.9 (range 4.5-31) x 10(3) cpm to 54.7 (range 13.9-94) x 10(3) cpm and the total number of myeloid progenitors enumerated as day 7/14 GM-CFUs per volume aspirated marrow increased from median 11/8 x 10(3) (range 4.0-87.5/2.2-103.0) to 64/76. x 10(3) (range 28.4-1180.6/23.2-2850.0). MRS detected a significant increase in bone marrow "relative water content" day 12, one week after myeloid growth factor treatment was stopped, from median 30.5% (range 16-45) to 79% (range 56-93) (p < 0.05). Haematopoiesis was concommittantly detected in new areas of femur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Volumetric analysis of the normal infant brain and in intrauterine growth retardation.

Twenty-eight infants with postmenstrual ages (PMA) in the range of 32-80 weeks were investigated. Twenty were newborn; among these the observed birth weight divided by the expected weight ranged from 0.31 to 1.1. Axial magnetic resonance images were recorded with a triple spin-echo sequence and the volumes were determined by encircling each structure of interest on every slice. Segmentation into grey matter, white matter and CSF was done by semi-automatic discriminant analysis. Growth charts for the cerebrum, cerebellum, corpora striata, thalami, ventricles, and grey and white matter are provided for infants with appropriate birth weight. The striatal (P = 0.02) and thalamic (P < 0.001) percentage of the hemispheric volume decreased with age, whereas the ratio of grey matter to white matter (G/W-ratio) increased (P = 0.01). In the neonatal patients, brain volumes were independently associated with both PMA and the degree of growth retardation. It was calculated that the hemispheric volume was reduced by from 16% to 23% if the total bodyweight was reduced by 40%. The G/W-ratio was found to be independently associated with the PMA (P < 0.05) and the degree of IUGR (P < 0.1) suggesting that fetal growth retardation reduces grey matter volume more than white matter.

Birth Weight↗

A controlled comparison of myelography, computed tomography, and magnetic resonance imaging in clinically suspected lumbar disc herniation.

STUDY DESIGN: A controlled prospective blinded study. OBJECTIVES: To compare the diagnostic power of myelography, computed tomography and magnetic resonance imaging in the diagnosis of low lumbar disc herniation. METHODS: Eighty patients with monoradicular sciatica were examined by myelography, computed tomography, and magnetic resonance imaging, and all underwent subsequent surgery. The images were evaluated twice in a blinded fashion, and the diagnostic power of the modalities was expressed by a decision-analytic regret function. RESULTS: In 57 patients (71%) a disc herniation at the expected level was disclosed at surgery. The largest amount of diagnostic information was gained from computed tomography, followed by magnetic resonance imaging and myelography. Both computed tomography and magnetic resonance imaging were significantly informative, whereas this was not the case for myelography. CONCLUSION: The results indicate that computed tomography or magnetic resonance imaging should be the first choice for imaging in patients with suspected lumbar disc herniation.

Adult↗

Decreased right heart blood volume determined by magnetic resonance imaging: evidence of central underfilling in cirrhosis.

Whether the central blood volume is reduced or expanded in cirrhosis is still under debate. Accordingly, the current study was undertaken to assess the volume of the heart cavities. Ten cirrhotic patients and matched controls had their right and left ventricular end-diastolic volumes (RVDV and LVDV), and end-systolic volumes (RVSV and LVSV) determined by magnetic resonance imaging (MRI). RVDV (122 vs. control 166 mL, P < .02), RVSV (41 vs. 80 mL, P < .02) and right atrial volume (47 vs. 64 mL, P < .05) were significantly reduced in the patients. In contrast, LVDV (134 vs. 129 mL, NS), LVSV (54 vs. 40 mL, NS), and left atrial volume (70 vs. 57 mL, P = .08) were normal or slightly increased. The right ejection fraction (68% vs. 53%, P < .05) was significantly increased, but the left ejection fraction was slightly reduced (61% vs. 69%, NS). The central and arterial blood volume (CBV), assessed as the cardiac output (CO) multiplied by the central circulation time, was significantly decreased (1.47 vs. 1.81 L, P < .05). The noncentral blood volume (4.43 vs. 3.64 L, P < .02), plasma volume (4.05 vs. 3.27 L, P < .02), and CO (7.11 vs. control 5.22 L/min, P < .01) were significantly increased in the patients. CCT (13.1 vs. 20.0 sec, P < .005) and the right ventricular transit time (0.79 vs. 1.35 sec, P < .005) were significantly reduced, but the left ventricular transit time was normal (0.91 vs. 0.88 sec, NS). Systemic vascular resistance was reduced (991 vs. 1,490 dyn.sec/cm5, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Signal changes in gradient echo images of human brain induced by hypo- and hyperoxia.

The effect of hypoxia (inspired oxygen fraction, FiO2 of 10% and 16%) and hyperoxia (FiO2) of 100%) on gradient echo images of the brain using long echo times was investigated in six healthy volunteers (age 24-28 years). Different flip angles were used with an FiO2 of 10% to assess the importance of saturation effects. The total cerebral blood flow was measured by a phase mapping technique during normoxia as well as hypoxia (FiO2 of 10% and 16%) and hyperoxia (FiO2 of 50% and 100%). High relative signal changes were found, independently of the flip angle, with FiO2 of 10%. With a flip angle of 40 degrees the values of delta R2* for cortical grey matter, central grey matter, white matter and the sagittal sinus were 0.79, 0.41, 0.26 and 3.00/s; with a flip angle of 10 degrees the corresponding values were 0.70, 0.37, 0.24 and 3.15/s. The total cerebral blood flow increased by 41% during inhalation of 10% O2 and decreased by 27% during 100% O2; no flow changes were seen during moderate changes in FiO2. It is concluded that flow effects play a minor role for fMRI signal strength in this application since (i) they did not abolish the signal changes caused by changes in blood oxygenation during hyper- and hypoxia, (ii) the observed signal changes were closely related to the changes in arterial oxygen saturation during hypoxia and (iii) the signal changes were little affected by changing the flip angle from 40 degrees to 10 degrees.

Adult↗

In vivo quantitation of metabolite concentrations in the brain by means of proton MRS.

MRS offers unique possibilities for non-invasive studies of biochemistry in the human brain in vivo. A growing body of evidence suggests that proton MRS may contribute to the clinical evaluation of a number of pathologies including ischaemia, tumours, epilepsy, metabolic and neuropaediatric disorders. In most cases results are expressed as ratios between metabolite signals obtained at certain experimental conditions. Presenting the results as metabolite signal ratios may lead to misinterpretation because such alterations can be due to changes in the content of either one of the metabolites or both, or may simply be due to changes in relaxation behaviour. Absolute quantitation of metabolite concentrations is therefore warranted. A number of studies using single volume proton MRS indicate that absolute quantitation of metabolite concentration is possible with respect to N-acetyl aspartate (NAA), total creatine, choline containing compounds, (Cho) and inositols (Ins). Internal standards (unsaturated water signal) as well as external standards have been used for signal calibration. Quality control with respect to signal linearity with concentration or with size of selected volume, selection efficiency, outer volume depression and signal contamination is essential for validation of the measurements. Furthermore, corrections for the influence of relaxation behavior are necessary. The results published so far indicate that the concentrations of NAA, total creatine, Cho and Ins in mmoles (kg wet weight)-1 range between 8.2 and 17.2 (mean 10.2), 5.9 and 11.6 (mean 7.2), 1.1 and 2.0 (mean 1.5) and 3.9 and 8.1 (mean 6.1), respectively. So far only a limited number of clinical studies has been published including studies of acute stroke, multiple sclerosis and Alzheimer's disease. The results are promising and encourage further exploitation of the utility of quantitative proton MRS in clinical practise.

Brain↗

Local vascular CO2 reactivity in the infant brain assessed by functional MRI.

The local cerebral vascular response to hyperventilation was investigated in five distressed, intubated infants by means of a T2 sensitive gradient-echo MRI technique at 1.5 T. In one preterm infant, the MR signal change during hyperventilation was sparse. In four term infants, the mean MR signal of the brain slice investigated decreased by 1.2-2.6% per kPa change in PCO2 as a reflection of decreased cerebral blood flow during hyperventilation. Pixel-wise analysis revealed absence of vascular response in the basal ganglia, the thalamus or in the occipital region. In two adult controls, who hyperventilated voluntarily, the vascular reactivity was homogeneously distributed predominantly over the grey matter. The experiments demonstrate that local impairment of vascular CO2 reactivity in the distressed infant brain can be detected by T2 sensitive gradient-echo MRI, which is also known as functional MRI.

Adult↗

Short echo time proton spectroscopy of the brain in healthy volunteers using an insert gradient head coil.

An insert gradient head coil with built-in X, Y, and Z gradients was used for localized proton spectroscopy in the brain of healthy volunteers, using short echo time stimulated echo acquisition mode (STEAM) sequences. Volume of interest size was 3.4 ml, repetition time was 6.0 s, and echo times were 10 and 20 ms, respectively. Good quality proton spectra with practically no eddy current artefacts were acquired allowing observation of strongly coupled compounds, and compounds with short T2 relaxation times. The gradient head coil thus permits further studies of compounds such as glutamine/glutamate and myo-inositols. These compounds were more prominent within grey matter than within white matter. Rough estimations of metabolite concentrations using water as an internal standard were in good agreement with previous reports.

Aspartic Acid↗