Papers by Olav Haraldseth

Magnetic Resonance in Medicine, 2000
The aim of this study was to investigate whether apparent diffusion coefficients (ADCs) could be ... more The aim of this study was to investigate whether apparent diffusion coefficients (ADCs) could be used as measures of cell density and necrotic fraction of tumors. Tumors of four human melanoma xenograft lines were subjected to diffusion-weighted magnetic resonance imaging (DWI). ADCs were calculated from the images and related to cell density and necrotic fraction, as determined from histological sections. A significant correlation was found between the ADC of the viable tissue and cell density, regardless of whether tumors of different lines or different regions within individual tumors were considered. Necrosis was found in two of the lines. A single region of massive necrosis that could be differentiated from the viable tissue in ADC maps was found in one line, whereas a number of smaller necrotic regions that could not be identified in ADC maps were found in the other line. Tumor ADC was significantly correlated with the necrotic fraction of the former, but not of the latter line. Our results suggest that ADCs can be used as measures of cell density and necrotic fraction of some but not of all tumors, depending on whether the individual necrotic regions are large enough to be differentiated from the viable tissue with the obtained spatial resolution of the DW images. Magn Reson Med 43:828-836, 2000.

Journal of Magnetic Resonance Imaging, 2001
Recent studies have demonstrated the potential of dynamic contrast-enhanced magnetic resonance im... more Recent studies have demonstrated the potential of dynamic contrast-enhanced magnetic resonance imaging (MRI) describing pulmonary perfusion. However, breathing motion, susceptibility artifacts, and a low signal-tonoise ratio (SNR) make automatic pixel-by-pixel analysis difficult. In the present work, we propose a novel method to compensate for breathing motion. In order to test the feasibility of this method, we enrolled 53 patients with pulmonary embolism (N ؍ 24), chronic obstructive pulmonary disease (COPD) (N ؍ 14), and acute pneumonia (N ؍ 15). A crucial part of the method, an automatic diaphragm detection algorithm, was evaluated in all 53 patients by two independent observers. The accuracy of the method to detect the diaphragm showed a success rate of 92%. Furthermore, a Bayesian noise reduction technique was implemented and tested. This technique significantly reduced the noise level without removing important clinical information. In conclusion, the combination of a motion correction method and a Bayesian noise reduction method offered a rapid, semiautomatic pixel-by-pixel analysis of the lungs with great potential for research and clinical use. J. Magn. Reson. Imaging 2001;13:577-587.

Injury, 1997
The present study was undertaken to evaluate if MRI within 2 days of a motor vehicle accident cou... more The present study was undertaken to evaluate if MRI within 2 days of a motor vehicle accident could reveal pathology of importance for understanding long-term disability after whiplash neck-sprain injuries. As part of a prospective study cervical and cerebral MRI was performed on 40 neck sprain patients with whiplash injury after car accidents. The imaging was done within 2 days of the injury to make sure that any neck muscle bleeding, oedema or other soft tissue injuries could be detected. The MRI findings from the patients were both correlated to reported symptoms 6 months after the accident and compared to a control group of 20 volunteers. The MRI of both brain and neck revealed no significant differences between the patients and the control group. When the patients were grouped according to the main MRI findings at intake and compared according to the development of subjective symptoms reported by the patients, the only significant difference was more headaches at 6 months in the groups with disk pathology or spondylosis when compared to the group with no pathology. In conclusion, MRI within 2 days of the whiplash neck-sprain injury could not detect pathology connected to the injury nor predict symptom development and outcome.

IEEE Transactions on Medical Imaging, 1996
Dynamic magnetic resonance (MR) imaging with contrast agents is a very promising technique for st... more Dynamic magnetic resonance (MR) imaging with contrast agents is a very promising technique for studying tissue perfusion in vivo. A temporal series of magnetic resonance images of the same slice are acquired following the injection of a contrast agent into the blood stream. The image intensity depends on the local concentration of the contrast agent, so that tissue perfusion can be studied by the image series. A new method of analyzing such series is described here. Nonparametric linear regression is used for modeling the image intensity along the series on a pixel by pixel basis. After modeling, some relevant quantities describing the time series are obtained and displayed as images. Due to its flexibility, this approach is preferred to parametric modeling when pathology is present since this can induce a wide spread of patterns for the pixel image intensity along time. Results of the application of the method to series of dynamic magnetic resonance images from ischaemic rat brains after the injection of the susceptibility agent Sprodiamide Inj. (Dy-DTPA-BMA) are shown and compared to results from a related known method.

International journal of microcirculation, clinical and experimental / sponsored by the European Society for Microcirculation
The dynamic changes in microcirculation were investigated with laser Doppler flowmetry in two sel... more The dynamic changes in microcirculation were investigated with laser Doppler flowmetry in two selected regions of interest (ROI) of a stroke lesion during ischemia and early reperfusion using a rat model of temporary middle cerebral artery (MCA) occlusion. In each ROI measurements were made either during 30 min or 2 h of MCA occlusion followed by 1 h of reperfusion. On the periphery of the MCA territory, an area of mild ischemia with a mean reduction of flow to 38% (39.9% in the group with 30 min MCA occlusion and 35.9% in the group with 2 h MCA occlusion) of preischemic values was demonstrated. Closer to the center of the MCA territory, more severe ischemia with a mean reduction of flow to 21% (19.9% in the 30-min group and 22.9% in the 2-hour group) was seen. In the two groups with laser Doppler flowmetry in the ROI of mild ischemia, a compensatory increase in flow during the first 3-6 min after MCA occlusion could be seen. All rats displayed a peak hyperperfusion immediately afte...

Recent studies have demonstrated the potential of dynamic contrast-enhanced magnetic resonance im... more Recent studies have demonstrated the potential of dynamic contrast-enhanced magnetic resonance imaging (MRI) describing pulmonary perfusion. However, breathing motion, susceptibility artifacts, and a low signal-tonoise ratio (SNR) make automatic pixel-by-pixel analysis difficult. In the present work, we propose a novel method to compensate for breathing motion. In order to test the feasibility of this method, we enrolled 53 patients with pulmonary embolism (N ؍ 24), chronic obstructive pulmonary disease (COPD) (N ؍ 14), and acute pneumonia (N ؍ 15). A crucial part of the method, an automatic diaphragm detection algorithm, was evaluated in all 53 patients by two independent observers. The accuracy of the method to detect the diaphragm showed a success rate of 92%. Furthermore, a Bayesian noise reduction technique was implemented and tested. This technique significantly reduced the noise level without removing important clinical information. In conclusion, the combination of a motion correction method and a Bayesian noise reduction method offered a rapid, semiautomatic pixel-by-pixel analysis of the lungs with great potential for research and clinical use. J. Magn. Reson. Imaging 2001;13:577-587.
Neuroimage, 2006
Tumour angiogenesis is a tightly regulated process involving cross-talk between tumour cells and ... more Tumour angiogenesis is a tightly regulated process involving cross-talk between tumour cells and the host tissue. The underlying mechanisms that regulate such interactions remain largely unknown. NG2 is a transmembrane proteoglycan whose presence on transformed cells has been demonstrated to increase proliferation in vitro and angiogenesis in vivo. To study the effects of NG2 during tumour growth and progression, we
Acta Neuropsychiatrica, 2006
... Additional Information. How to Cite. Berntsen, EM, Rasmussen, I.-A., Samuelsen, P., Xu, J., H... more ... Additional Information. How to Cite. Berntsen, EM, Rasmussen, I.-A., Samuelsen, P., Xu, J., Haraldseth, O., Lagopoulos, J. and Malhi, GS (2006), Putting the brain in Jeopardy: a novel comprehensive and expressive language task?. ... 19 Morris GL, Mueller WM, Yetkin FZ et al. ...
Brain Research, 1998
The neuroprotective effect of post-ischemic treatment with the novel, highly water-soluble, gluta... more 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

Journal of Neurochemistry, 2001
Adenosine is a neuromodulator, and it has been suggested that cerebral acetate metabolism induces... more Adenosine is a neuromodulator, and it has been suggested that cerebral acetate metabolism induces adenosine formation. In the present study the effects that acetate has on cerebral intermediary metabolism, compared with those of glucose, were studied using the adenosine A 1 receptor agonist 2-chloro-N 6 -cyclopentyladenosine (CCPA) and antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Fasted rats received an intravenous injection of CCPA, DPCPX, or vehicle. Fifteen minutes later either [1,2-13 C]acetate or [1-13 C]glucose was given intraperitoneally; after another 30 min the rats were decapitated. Cortical extracts were analyzed with 13 C NMR spectroscopy and HPLC analysis. DPCPX affected neuronal and astrocytic metabolism. De novo synthesis of GABA from neuronal and astrocytic precursors was significantly reduced. De novo syntheses of glutamate and aspartate were at control levels, but their degradation was significantly elevated. In glutamine the anaplerotic activity and the amount of label in the position representing the second turn in the tricarboxylic acid cycle were significantly increased, suggesting elevated metabolic activity in astrocytes. CCPA did not influence GABA, aspartate, or glutamine synthesis. In glutamate the contribution from the astrocytic anaplerotic pathway was significantly decreased. In the present study the findings in the [1,2-13 C]acetate and [1-13 C]glucose control, CCPA, and DPCPX groups were complementary, and no adenosine A 1 agonist effects arising from cerebral acetate metabolism were detected. Key Words: A 1 receptor agonist-A 1 receptor antagonist-Adenosine-Acetate-Amino acids-Cerebral metabolism-NMR spectroscopy.
Journal of Cerebral Blood Flow and Metabolism, 2001
Astrocytes are intimately involved in both glutamate and γ-aminobutric acid (GABA) synthesis, and... more Astrocytes are intimately involved in both glutamate and γ-aminobutric acid (GABA) synthesis, and ischemia-induced disruption of normal neuroastrocytic interactions may have important implications for neuronal survival. The effects of middle cerebral artery occlusion (MCAO) on neuronal and astrocytic intermediary metabolism were studied in rats 30, 60, 120, and 240 minutes after MCAO using in vivo injection of [1-13C]glucose and [1,2-13C]acetate
Journal of Cerebral Blood Flow and Metabolism, 1998
Astrocytes play a pivotal role in cerebral glutamate homeostasis. After 90 minutes of middle cere... more 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 vivo13C nuclear magnetic resonance spectroscopy and HPLC analysis of amino acids of the lateral
Developmental Neuroscience, 2000
In order to address the question whether lactate in blood can serve as a precursor for cerebral m... more In order to address the question whether lactate in blood can serve as a precursor for cerebral metabolites, fully awake rats were injected intravenously with [U-13C]lactate or [U-13C]glucose followed 15 min later by decapitation. Incorporation of label from [U-13C]glucose was seen mainly in glutamate, GABA, glutamine, aspartate, alanine and lactate. More label was found in glutamate than glutamine, underscoring the
Spectroscopy Letters, 2006
The potential for detecting fluorinated compounds in a 2.35 T nuclear magnetic resonance system w... more The potential for detecting fluorinated compounds in a 2.35 T nuclear magnetic resonance system was assessed to evaluate the possibility for in vivo monitoring of fluorinated drugs applied to the eye. Time‐share proton decoupled F NMR spectroscopy was implemented for signal enhancement in an experimental eye model. Signal‐to‐noise in F NMR spectra of dexamethasone phosphate was enhanced by 56%. However, decoupling
Neuroimage, 2007
Mesial temporal lobe epilepsy is associated with structural and functional abnormalities, such as... more Mesial temporal lobe epilepsy is associated with structural and functional abnormalities, such as hippocampal sclerosis and axonal reorganization. The temporal evolution of these changes remains to be determined, and there is a need for in vivo imaging techniques that can uncover the epileptogenic processes at an early stage. Manganese-enhanced magnetic resonance imaging may be useful in this regard. The aim
Journal of Magnetic Resonance Imaging, 2008
To develop and validate an objective technique for 3D segmentation of manganese-enhanced MR image... more To develop and validate an objective technique for 3D segmentation of manganese-enhanced MR images of the optic nerve/tract (ON) in adult rats to improve contrastto-noise (CNR) calculations and use the technique to ascertain if manganese dipyridoxyl diphosphate (MnDPDP) gives sufficient Mn 2ϩ enhancement compared to MnCl 2 when used for functional imaging of the visual pathway.

Nmr in Biomedicine - NMR BIOMED, 1996
A susceptibility contrast agent which does not pass into the extra-cellular space was used to stu... more 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 frontalparietal 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. ©

The FASEB Journal, 2002
During embryogenesis, the NG2 proteoglycan is expressed on immature capillary vessels, but as the... more During embryogenesis, the NG2 proteoglycan is expressed on immature capillary vessels, but as the vessels mature they lose this expression. NG2 is up-regulated in high-grade gliomas, but it is not clear to what extent it contributes to malignant progression. Using a combination of high spatial and temporal resolution functional magnetic resonance imaging and histopathological analyses, we show here that overexpression of NG2 increases tumor initiation and growth rates, neovascularization, and cellular proliferation, which predisposes to a poorer survival outcome. By confocal microscopy and cDNA gene array expression profiles, we also show that NG2 tumors express lower levels of hypoxia inducible factor-1α, vascular endothelial growth factor, and endogenous angiostatin in vivo compared with wild-type tumors. Moreover, we demonstrate that NG2-positive cells bind, internalize, and coimmunoprecipitate with angiostatin. These results indicate a unique role for NG2 in regulating the transition from small, poorly vascularized tumors to large, highly vascular gliomas in situ by sequestering angiostatin.
Scandinavian Journal of Public Health, 1996

NMR in Biomedicine, 1996
A susceptibility contrast agent which does not pass into the extra-cellular space was used to stu... more 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 frontalparietal 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. ©
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Papers by Olav Haraldseth