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Biomedical subjects

O Haraldseth

Publications and source records attributed to O Haraldseth.

At least 37 records · Page 2Linked to original sources

Differentiating benign and malignant breast lesions with T2*-weighted first pass perfusion imaging.

PURPOSE: Invasive breast carcinomas and fibroadenomas are often difficult to differentiate in dynamic contrast-enhanced T1-weighted MR imaging of the breast, because both tumors can enhance strongly after contrast injection. The purpose of this study was to evaluate whether the addition of T2*-weighted first pass perfusion imaging can increase the differentiation of malignant from benign lesions. MATERIAL AND METHODS: Nine patients with invasive carcinomas and 10 patients with contrast enhancing fibroadenomas were examined by a dynamic contrast-enhanced T1-weighted 3D sequence immediately followed by a single slice T2*-weighted first pass perfusion sequence positioned in the contrast-enhancing lesion. RESULTS: The carcinomas and the fibroadenomas were impossible to differentiate based on the contrast enhancement characteristics in the T1-weighted sequence. The signal loss in the T2*-weighted perfusion sequence was significantly stronger in the carcinomas than in the fibroadenomas (p = 0.0004). CONCLUSION: Addition of a T2*-weighted first pass perfusion sequence with a high temporal resolution can probably increase the differentiation of fibroadenomas from invasive carcinomas in contrast-enhanced MR imaging of the breast.

Adult↗

Neuroprotective effect of the novel glutamate AMPA receptor antagonist YM872 assessed with in vivo MR imaging of rat MCA occlusion.

The neuroprotective effect of post-ischemic treatment with the novel, highly water-soluble, glutamate AMPA receptor antagonist YM872 was evaluated by using MR imaging and histopathology of rats subjected to permanent MCA occlusion. Two treatment groups with continuous i.v. infusion of 20 mg kg-1 h-1 YM872 during either the first 4 h or first 24 h after MCA occlusion, called 4 h YM872 treatment group (n=9) and 24 h YM872 treatment group (n=8) respectively, were compared to a control group (n=8). The main end-point was T2 weighted MR imaging and histopathology 24 h after MCA occlusion. Also the time evolution of the ischemic tissue damage was studied by diffusion weighted MR imaging 412 and 24 h after MCA occlusion. The volume of ischemic tissue damage as assessed by diffusion weighted MR imaging 412 h after MCA occlusion was significantly smaller in both YM872 treatment groups (99+/-52 mm3 and 102+/-44 mm3 compared to 186+/-72 mm3 in the control group, +/-S.D. and p=0.008). The infarct volume as assessed by T2 weighted MR imaging 24 h after MCA occlusion was significantly smaller only in the 24 h YM872 treatment group (262+/-57 mm3 compared to 366+/-49 mm3 in the control group, +/-S.D. and p=0.01) while the infarct volume in the 4 h YM872 treatment group (357+/-88 mm3) was similar to the control group. YM872 treatment significantly reduced the infarct volume 24 h after MCA occlusion when the drug was administered as continuous infusion during the 24-h observation period.

Animals↗

Acute treatment of whiplash neck sprain injuries. A randomized trial of treatment during the first 14 days after a car accident.

STUDY DESIGN: A single-blinded, randomized treatment study with a follow-up period of 6 months. OBJECTIVE: To study the long-term consequences of whiplash neck sprain injuries in patients treated with two different regimes during the first 14 days after the car accident. Patients in the first group were encouraged to act as usual, i.e., continue to engage in their normal, pre-injury activities; that group was compared with another group of patients who were given time off from work and who were immobilized using a soft neck collar. The end point of the comparison was the evaluation of subjective symptoms 6 months after the accident. SUMMARY OF BACKGROUND DATA: Few randomized treatment studies have been performed to evaluate the clinical outcome for patients with neck sprain. METHOD: Patients who participated in the study were recruited from the Emergency Clinic at the University Hospital in Trondheim, Norway. The study group included 201 patients (47% of the study group) with neck sprain that resulted from a car accident. Neck and shoulder movements and subjective symptoms, which were assessed using several different measurements, were assessed during the follow-up period. RESULTS: There was a significant reduction of symptoms from the time of intake to 24 weeks after the treatment period in both groups. There was a significantly better outcome for the act-as-usual group in terms of subjective symptoms, including pain localization, pain during daily activities, neck stiffness, memory, and concentration, and in terms of visual analog scale measurements of neck pain and headache. CONCLUSIONS: The outcome was better for patients who were encouraged to continue engaging in their normal, pre-injury activities as usual than for patients who took sick leave from work and who were immobilized during the first 14 days after the neck sprain injury.

Accidents, Traffic↗

In vivo injection of [1-13C]glucose and [1,2-13C]acetate combined with ex vivo 13C nuclear magnetic resonance spectroscopy: a novel approach to the study of middle cerebral artery occlusion in the rat.

Astrocytes play a pivotal role in cerebral glutamate homeostasis. After 90 minutes of middle cerebral artery occlusion in the rat, the changes induced in neuronal and astrocytic metabolism and in the neuronal-astrocytic interactions were studied by combining in vivo injection of [1-13C]glucose and [1,2-13C]acetate with ex vivo 13C nuclear magnetic resonance spectroscopy and HPLC analysis of amino acids of the lateral caudoputamen and lower parietal cortex, representing the putative ischemic core, and the upper frontoparietal cortex, corresponding to the putative penumbra. In the putative ischemic core, evidence of compromised de novo glutamate synthesis located specifically in the glutamatergic neurons was detected, and a larger proportion of glutamate was derived from astrocytic glutamine. In the same region, pyruvate carboxylase activity, representing the anaplerotic pathway in the brain and exclusively located in astrocytes, was abolished. However, astrocytic glutamate uptake and conversion to glutamine took place, and cycling of intermediates in the astrocytic tricarboxylic acid cycle was elevated. In the putative penumbra, glutamate synthesis was improved compared with the ischemic core, the difference appeared to be brought on by better neuronal de novo glutamate synthesis, combined with normal levels of glutamate formed from astrocytic glutamine. In both ischemic regions, gamma-aminobutyric acid synthesis directly from glucose was reduced to about half, indicating impaired pyruvate dehydrogenase activity; still, gamma-aminobutyric acid reuptake and cycling was increased. The results obtained in the current study demonstrate that by combining in vivo injection of [1-13C]glucose and [1,2-13C]acetate with ex vivo 13C nuclear magnetic resonance spectroscopy, specific metabolic alterations in small regions within the rat brain suffering a focal ischemic lesion can be studied.

Acetates↗

In vitro and ex vivo 13C-NMR spectroscopy studies of pyruvate recycling in brain.

Pyruvate recycling is a well established pathway in the liver, but in the brain, the cellular localization of pyruvate recycling remains controversial and its physiological significance is unknown. In cultured cortical astrocytes, pyruvate formed from [U-13C]glutamate was shown to re-enter the TCA cycle after conversion to acetyl-CoA, as demonstrated by the labelling patterns in aspartate C-2 and C-3, lactate C-2, and glutamate C-4, which provides evidence for pyruvate recycling in astrocytes. This finding is in agreement with previous studies of astrocytic cultures, in which pyruvate recycling has been described from [U-13C]glutamine, in the presence of glutamate, and from [U-13C]aspartate. Pyruvate recycling in brain was studied in fasted rats receiving either an intraperitoneal or a subcutaneous injection of [1,2-13C]acetate followed by decapitation 30 min later. Extracts of cortical tissue were analysed with 13C-NMR spectroscopy and total amounts of amino acids quantified by HPLC. Plasma extracts were analysed with 1H- and 13C-NMR spectroscopy, and showed a significantly larger amount of [1, 2-13C]acetate in the intraperitoneal group compared to the subcutaneous group. Furthermore, a small amount of label was detected in glucose in both groups. In the subcutaneously injected rats, [4-13C]glutamate and [2-13C]GABA were less enriched than plasma glucose, which might have been the precursor. In the intraperitoneally injected rats, however, pyruvate formation from [1, 2-13C]acetate, and re-entry of this pyruvate into the TCA cycle was demonstrated by the presence of greater 13C enrichment in [4-13C]glutamate and [4-13C]glutamine compared to the subcutaneous group, probably resulting from the significantly higher [1, 2-13C]acetate concentration in brain and plasma.

Acetates↗

A study of the contribution of changes in the cerebral blood volume to the haemodynamic response to anoxia in rat brain.

A susceptibility contrast agent which does not pass into the extra-cellular space was used to study the effect of changes in the relative cerebral blood volume (CBV) on the haemodynamic response to anoxia, for both normal and ischaemic brain tissue, in a rat model of acute focal ischaemia. In non-ischaemic tissue a strong CBV component was observed in the haemodynamic response, both during and after anoxia. During anoxia the change in the CBV of the non-ischaemic tissue was estimated to be 40% in the caudate putamen and 70% in the frontal-parietal cortex. For severely ischaemic tissue (ischaemic caudate putamen) there was no change in the CBV during anoxia while in areas of moderate ischaemia (ischaemic frontal parietal cortex) a change of 20% was observed. The effect of the contrast agent on spin-echo images was consistent with a small reduction in the microvascular blood volume of the ischaemic tissue.

Animals↗

A quantitative in-vivo MR imaging study of brain dehydration in diabetic rats and rats treated with peptide hormones.

The main aim of the study was to evaluate the combination of quantitative diffusion, T2 and Magnetisation Transfer Imaging of brain water homeostasis using untreated diabetes as an animal model of brain dehydration. In addition, experimental groups of diabetic rats treated with insulin and insulin-like growth factor (IGF-I) and normal rats treated with IGF-I and growth hormone were studied using the same MR imaging protocol. Untreated diabetes caused weight reduction and an increase in water intake, indicating a general body dehydration linked to chronic blood hyperosmolarity. In the investigated cortical gray matter untreated diabetes caused a significant reduction in the apparent diffusion coefficient of water (ADC) and an increase in T2 relaxtivity (R2) when compared to a control group. No significant changes were observed for the calculated magnetisation transfer parameters Kfor and T1sat. Both ADC and R2 normalized after appropriate insulin treatment whereas only ADC was normalized after IGF-I treatment. IGF-I treatment of normal rats caused significantly higher rate of increase in body weight compared to normal controls. There were, however, no significant changes in ADC, R2 nor the magnetisation transfer parameters measured in the cortical gray matter of the IGF-I treated normal rats. In conclusion, we found that changes in brain water homeostasis during diabetes were detected by quantitative MR imaging, and that the dehydration induced by diabetes was normalized by insulin treatment but not by IGF-I.

Animals↗

Pulmonary embolism: detection with MR perfusion imaging of lung--a feasibility study.

PURPOSE: To evaluate the feasibility of magnetic resonance (MR) perfusion imaging in the human lung to help detect perfusion defects distal to suspected pulmonary embolism. MATERIALS AND METHODS: Seven patients suspected of having pulmonary embolism first underwent ventilation-perfusion lung scintigraphy followed by MR perfusion imaging with rapid acquisition of two sets of dynamic images in the coronal and transaxial planes. A bolus of 0.05 mmol per kilogram of body weight gadopentetate dimeglumine or gadodiamide was administered. Single images obtained in each section that showed peak signal intensity from the first passage of contrast material were evaluated visually. An analysis of change in signal intensity over time was performed both on a pixel-by-pixel basis and in selected regions of interest. RESULTS: In the seven patients, a total of 18 regions of lung tissue with perfusion defects were shown on the ventilation-perfusion scans. In 16 of these regions, MR perfusion images showed a reduced peak signal intensity during first passage of the contrast agent. Perfusion defects could be detected in both the coronal and the transaxial planes on MR perfusion images. CONCLUSION: MR perfusion imaging was feasible for detection of perfusion defects distal to a pulmonary embolism.

Adult↗

A study of the contribution of changes in the cerebral blood volume to the haemodynamic response to anoxia in rat brain.

A susceptibility contrast agent which does not pass into the extra-cellular space was used to study the effect of changes in the relative cerebral blood volume (CBV) on the haemodynamic response to anoxia, for both normal and ischaemic brain tissue, in a rat model of acute focal ischaemia. In non-ischaemic tissue a strong CBV component was observed in the haemodynamic response, both during and after anoxia. During anoxia the change in the CBV of the non-ischaemic tissue was estimated to be 40% in the caudate putamen and 70% in the frontal-parietal cortex. For severely ischaemic tissue (ischaemic caudate putamen) there was no change in the CBV during anoxia while in areas of moderate ischaemia (ischaemic frontal parietal cortex) a change of 20% was observed. The effect of the contrast agent on spin-echo images was consistent with a small reduction in the microvascular blood volume of the ischaemic tissue.

Animals↗

Cerebrovascular changes in rats during ischemia and reperfusion: a comparison of BOLD and first pass bolus tracking techniques.

Both first pass bolus tracking of a susceptibility contrast agent and blood oxygenation level dependent (BOLD) sequences provide information on the tissue perfusion and the cerebral blood volume, but each sequence has its own particular limitations. In this article, both techniques were used to assess the cerebrovascular changes occurring in a rat model of focal cerebral ischemia with reperfusion after 2 h of ischemia. The blood oxygenation level dependent studies were performed before, during, and after 60 s of anoxia to observe the response of the tissue to a respiratory challenge. Both techniques were able to detect ischemia and reperfusion; however, first pass bolus tracking provided better sensitivity and was easier to interpret. Because the blood oxygenation level dependent sequence did not provide any additional information, bolus tracking would appear to be the method of choice for studies of cerebral ischemia with reperfusion.

Animals↗

Comparison of MR perfusion imaging and microsphere measurements of regional cerebral blood flow in a rat model of middle cerebral artery occlusion.

The purpose of this investigation was to correlate magnetic resonance (MR) perfusion measurements with absolute regional cerebral blood flow (rCBF) in a rat model of focal ischemia. The MR perfusion measurements were made using dynamic first-pass bolus tracking of a susceptibility contrast agent, whereas rCBF was measured using radioactive microspheres. Two simple MR perfusion parameters, the maximum change in R2* (m delta R2*) and time delay to m delta R2* (t delta R2*), were derived from the signal intensity versus time curves on a pixel-to-pixel basis, without applying curve-fitting procedures or tracer kinetic theory. In each hemisphere, m delta R2* and t delta R2* were compared with the rCBF measurements in four selected regions of interest. Sixteen MR bolus tracking series were performed in 12 rats with occlusion of the middle cerebral artery. In all of the individual series there was a significant correlation (.0001 < or = p < or = .02) between m delta R2* and the microsphere rCBF measurements, with correlation coefficients ranging from .784 to .983. Pooling the m delta R2* data resulted in a correlation coefficient of .809 (p = .0001). There was a nonlinear correlation between the t delta R2* and rCBF. For both parameters there was considerable variation between different measurements regarding both the slope of the regression line and its intercept with the y-axis. Our results justify the use of m delta R2* as a relative measure of perfusion during acute cerebral ischemia. Because of the interindividual variation, calibration of MR perfusion measurements for the estimation of absolute flow values must be considered unreliable. The t delta R2* may have physiological relevance as a marker of collateral flow.

Animals↗

National health insurance consumption and chronic symptoms following mild neck sprain injuries in car collisions.

OBJECTIVE: To map the extent of sick leave and number of claims made for health insurance among persons who had suffered neck sprain (whiplash) injuries in traffic accidents, and to map subjective feeling of health and quality of life among patients several years after the injury. DESIGN: A retrospective study of neck sprain injuries after car accidents and a comparison to the patients' use of sick leave caused by neck pain prior to the accident. SETTING: The Emergency Clinic at The University Hospital in Trondheim, Norway. SUBJECTS: 426 patients with neck sprain injuries after car accidents during 1985-1990. MAIN OUTCOME MEASURES: Information from Trondheim Social Security office about sick leave, and results from 345 patients who answered a questionnaire with respect to quality of life measures. RESULTS: 27% had been reported sick during the period after the car accident, and 5% had claimed health insurance, 58% reported sustained symptoms linked to the accident. CONCLUSIONS: Many reported sustained symptoms after neck sprain injuries, 16% of them reported being in a bad state of health.

Accidents, Traffic↗

Combined perfusion and diffusion-weighted magnetic resonance imaging in a rat model of reversible middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging and dynamic first-pass bolus tracking of susceptibility contrast agents (perfusion imaging) are two new magnetic resonance imaging techniques that offer the possibility of early diagnosis of stroke. The present study was performed to evaluate the diagnostic information derived from these two methods in a rat model of temporary focal ischemia. METHODS: Fifteen male Wistar rats were assigned to 45 (n = 7) or 120 minutes (n = 8) of middle cerebral artery occlusion followed by reperfusion using the intraluminal filament technique. The diffusion-weighted images were collected, and areas of hyperintensity were compared with histologically assessed areas of ischemic injury. The magnetic resonance perfusion image series were postprocessed to produce topographic maps reflecting the maximum reduction in the signal obtained during the first passage of the contrast agent and the time delay between the arrival of the bolus and the point of maximum contrast-agent effect. RESULTS: Hyperintensity in diffusion-weighted images was demonstrated after 30 minutes of middle cerebral artery occlusion and was mainly expressed in the lateral caudoputamen and parts of the lower frontoparietal cortex. Reperfusion after 45 minutes of occlusion reduced the area of hyperintensity from 24.2% to 9.9% of hemispheric area. In the group with 120 minutes of occlusion, the hyperintense area increased from 24.4% to 29.1%. Relative to the nonischemic hemisphere, the changes in the topographic maps of maximum signal reduction occurred in the lateral caudoputamen and adjacent lower neocortical areas. Increased time delay to maximum effect, however, was seen also in the upper frontoparietal cortex. CONCLUSIONS: Hyperintensity in diffusion-weighted images was reversible after 45 minutes but not after 120 minutes of middle cerebral artery occlusion. Analysis of the signal-reduction and time-delay parametric maps demonstrated regions of different perfusion changes in the ischemic hemisphere.

Animals↗

Perfusion and diffusion-weighted MR imaging for in vivo evaluation of treatment with U74389G in a rat stroke model.

BACKGROUND AND PURPOSE: The present study was performed to examine the potential of diffusion-weighted (DW) imaging and dynamic first-passage bolus tracking of susceptibility contrast agents (perfusion imaging) for early in vivo evaluation of the effects of treatment with the free radical scavenger U74389G in a rat model of temporary focal ischemia. METHODS: After 45 minutes of middle cerebral artery occlusion, the treatment group (n = 9) received an infusion of U74389G, and the control group (n = 9) received the identical volume of the vehicle. Reperfusion was instituted in both groups after 120 minutes of middle cerebral artery occlusion. The DW images were collected during middle cerebral artery occlusion and reperfusion and were compared with histologically assessed areas of tissue injury after 2 hours of reperfusion. The dynamic perfusion series were processed on a pixel-to-pixel basis to produce parametric maps reflecting the maximum reduction in the signal obtained during the first passage of the contrast agent and the time delay between the arrival of the bolus and the point of maximum contrast-agent effect. RESULTS: The area of ischemic injury, as assessed from the DW imaging at 60 minutes of reperfusion, was significantly smaller in the treatment group: 9 +/- 8% of ipsilateral hemisphere compared with 19 +/- 8% in the control group. The histological examination after 2 hours of reperfusion demonstrated an area of ischemic injury of 10 +/- 8% for the treatment group compared to 25 +/- 10% in the control group. In the treatment group, the perfusion imaging showed a reduction in time delay to maximum effect of the contrast agent in the ischemic hemisphere compared with the control group. CONCLUSIONS: The DW imaging during early reperfusion showed a protective effect of postocclusion treatment with the free radical scavenger U74389G. The improvement of time delay to maximum effect of the contrast agent observed in the perfusion imaging of the treatment group may reflect an improvement in the collateral flow to the ischemic tissue.

Animals↗

NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) did not affect recovery of high energy phosphates and pH in early reperfusion in a rat model of transient forebrain ischemia. Or: an in vivo 31P NMR spectroscopy study.

The new non-NMDA (N-methyl-D-aspartate) receptor antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) has previously been shown to exert a neuroprotective effect in animal models of cerebral ischemia when administered in the post-ischemic phase. In this investigation the effect of NBQX on acidosis and energy recovery in early reperfusion after 10 min of transient forebrain ischemia with the 2-vessel occlusion model in the rat was studied with 31P NMR spectroscopy. In the intervention group the animals received a bolus dose of NBQX 30 mg.kg-1 i.v. at the start of reperfusion. 31P NMR spectroscopy was used to measure intracellular pH, ATP and phosphocreatine continuously in-vivo during, and after, the ischemic event. The recovery of high energy phosphates and pH was followed during 30 min of reperfusion. Pre-ischemic levels of phosphocreatine were reached after approximately 9-10 min in both groups. Although a slight improvement could be seen in the intervention group there was no significant difference in the rate of recovery between the two groups. ATP reached 90% of preischemic levels after about 8 min without significant difference between the two groups. With respect to the recovery of intracellular pH, no difference could be shown. Our results do not contradict previously published results, but suggest that the potential protective effect of NBQX is not mediated through improved recovery of energy metabolism in early reperfusion.

Acidosis↗

K-space substitution: a novel dynamic imaging technique.

A rapid dynamic imaging sequence has been developed in which only the 32 phase encoding steps that encode low spatial frequencies are collected for each dynamic image. These are substituted into a previously acquired, 128 x 128 raw data set prior to image reconstruction. In this way the dynamic information is retained while the overall appearance is improved in comparison with images obtained by zero filling to 128 x 128, leading to better qualitative evaluation. The limited k-space sampling means that the technique is most effective for large homogeneous areas of signal change since fine changes in contrast are imperfectly recorded.

Animals↗

Hyperglycemia in global cerebral ischemia and reperfusion: a 31-phosphorous NMR spectroscopy study in rats.

31-phosphorous magnetic resonance spectroscopy was used in a rat model of 10 min severe incomplete forebrain ischemia (two-vessel occlusion with hypotension) to assess the effect of hyperglycemia on intracellular pH and high energy phosphates during ischemia and early reperfusion. One group (n = 8) with preischemic hyperglycemia (serum glucose 20 mmol.l-1) showed an increased intracellular acidosis (pH 6.35) during ischemia compared to 6.55 in the normoglycemic control group (n = 7, P less than 0.001), but the recovery of phosphocreatine and ATP in early reperfusion was the same in the two groups. Another group (n = 7) was normoglycemic during ischemia, but received an i.v. bolus of glucose during the first minute of reperfusion. In this group the recovery of intracellular pH in early reperfusion was slower than in the control group (0.034 +/- 0.006 pH units per minute compared to 0.052 +/- 0.11 in the controls, +/- s.d. and P less than 0.01).

Acidosis↗

The effects of brain temperature on temporary global ischaemia in rat brain. A 31-phosphorous NMR spectroscopy study.

31-Phosphorus magnetic resonance spectroscopy was used in a rat model of 10 min severe incomplete forebrain ischaemia (2-vessel occlusion with hypotension) to assess the effect of mild brain hypo- and hyperthermia (+/- 2 degrees C) on intracellular pH and high energy phosphates. In three experimental groups intracerebral temperature was maintained at levels of 34, 36 and 38 degrees C during ischaemia and early reperfusion. The steady level of intracellular pH during ischaemia was 6.63, 6.58 and 6.53 in the 34, 36, and 38 degrees C groups, respectively. The rate of initial recovery of intracellular pH in reperfusion was 0.046 +/- 0.012 pH units per min (+/- s.d.) in the 36 degrees C group compared to 0.056 +/- 0.010 (+/- s.d., P less than 0.05) in the 34 degrees C group and 0.032 +/- 0.009 (+/- s.d., P less than 0.01) in the 38 degrees C group. The recovery in early reperfusion of phosphocreatine and ATP was slower in the 38 degrees C group compared to the other groups. The findings were consistent with recent studies, suggesting that even mild hypothermia may afford protection to the ischaemic brain, and furthermore indicate that mild hyperthermia as fever or even subfebricity may be deleterious for the outcome in stroke patients.

Adenosine Triphosphate↗