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Featured researches published by Audun N. Øksendal.


Stroke | 1995

Perfusion and Diffusion-Weighted MR Imaging for In Vivo Evaluation of Treatment With U74389G in a Rat Stroke Model

Tomm B. Müller; Olav Haraldseth; Richard A. Jones; Giovanni Sebastiani; Christian F. Lindboe; Geirmund Unsgård; Audun N. Øksendal

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.


Investigative Radiology | 1993

Sodium-calcium balance and cardiac function with isotonic iodixanol. An experimental study in the isolated rat heart.

Per Jynge; Holten T; Audun N. Øksendal

RATIONALE AND OBJECTIVES.Three formulations of the nonionic dimer iodixanol (150/200/300 mg I/mL), made isotonic by the addition of NaCl (70/53/24 mM), were investigated regarding their potential for depressing cardiac contractility during coronary angiography. To maintain a stable cardiac function, the authors sought the requirements for the addition of a balanced amount of calcium (Ca). METHODS.Iodixanol 150, 200, and 300 mg I/mL were applied as a short-lasting bolus in isolated perfused rat hearts in the absence and presence of added Ca. The contractile function was assessed by measurement of changes in left ventricular developed pressure (LVDP). RESULTS.A transient LVDP depression was markedly alleviated by adding 0.2 to 0.4 mM Ca and almost abolished by 0.4 to 0.9 mM. Ca higher than 0.9 mM led to unstable hearts and too-extensive Ca loading. CONCLUSIONS.Caution should be used when adding Ca to iodixanol, particularly with sodium-calcium (Na–Ca) relationships. Appropriate Ca concentrations are probably 0.6 mM for iodixanol (150 mg I/mL); 0.4 to 0.6 mM for iodixanol (200 mg I/mL; and 0.4 mM for iodixanol (300 mg I/mL).


Acta Radiologica | 1996

Double-Contrast MR Imaging of Reperfused Porcine Myocardial Infarction An Experimental Study Using Gd-DTPA-BMA and Dy-DTPA-BMA

Sven Nilsson; Gerhard Wikström; A. Ericsson; M. Wikström; Audun N. Øksendal; Anders Waldenström; A. Hemmingsson

Purpose: Myocardial infarctions were induced in 12 pigs to investigate whether a double-contrast method, combining a positive and a negative MR contrast agent, could improve the visualization of reperfused myocardial infarctions. Material and Methods: All 12 pigs were subjected to 80 min of occlusion followed by reperfusion. In the double-contrast group (6 pigs), Gd-DTPA-BMA (0.3 mmol/kg b.w.) and Dy-DTPA-BMA (1.0 mmol/kg b.w.) were administered i.v. after 30 min of reperfusion. In the remaining 6 pigs, a single injection of Gd-DTPA-BMA (0.3 mmol/kg b.w.) was given after 30 min of reperfusion. All pigs were sacrificed 10 min postcontrast injection, corresponding to a reperfusion time of 40 min. The hearts were excised and imaged with MR. The concentrations of Gd and Dy were measured in infarcted and nonischaemic myocardium using ICP-AES. Results and Conclusion: Contrast media concentrations were more than 4-fold higher in infarcted compared with nonischaemic myocardium. The infarctions were best shown on T1-weighted images, and there were no differences between the double and single contrast groups. In the T2-weighted images, the infarctions were significantly better visualized in the double-contrast group, due to a Dy-induced signal intensity loss in nonischaemic myocardium.


Investigative Radiology | 1993

Sodium-calcium balance in nonionic contrast media. Effects on the risk of ventricular fibrillation in the isolated rabbit heart

Lars Bååth; Jack Besjakov; Audun N. Øksendal

RATIONALE AND OBJECTIVESDuring coronary arteriography the blood is replaced for a short period of time with a contrast medium (CM) solution. The CM may cause a risk of arrhythmias and ventricular fibrillation (VF). Previous investigations have shown that the addition of small amounts of sodium (10–30 mmol/L) to nonionic CM may decrease the risk of VF from these media. Calcium addition to nonionic CM may reduce a negative inotropic effect. In the current investigation, the changed risk of VF from nonionic CM with 19 to 30 mmol/L NaCl was studied when the media also contained calcium or calcium and magnesium. METHODSAn isolated rabbit heart model was used. The risk of arrhythmias and VF from the nonionic monomer iohexol and the nonionic dimer iodixanol containing 19 to 30 mmol/L NaCl with 0 to 2.5 mmol/L calcium as CaCl2 was studied. In the series with iodixanol, 0 to 0.95 mmol/L MgCl2 also was added to the solutions with sodium and calcium, but the role of magnesium was not especially evaluated in the investigation. RESULTSNonionic CM with small amounts of NaCl (19–30 mmol/L), without calcium or with calcium at the level of 0.05 to 0.3 mmol/L, caused the lowest risk of VF. When relatively higher additions of calcium reached the physiologic concentration of 2.5 mmol/L, the CM caused a greater risk of arrhythmias and VF. CONCLUSIONSWhen calcium is added to a nonionic CM, the concentration of calcium must be balanced against the NaCl concentration to minimize the risk of VF. Excessive calcium concentration will increase the risk of VF.


Journal of Magnetic Resonance Imaging | 1999

Myocardial "low reflow" assessed by Dy-DTPA-BMA-enhanced first-pass MR imaging in a dog model.

C. Arteaga; D. Revel; Shihua Zhao; G. Hadour; R. Forrat; Audun N. Øksendal; Emmanuelle Canet

The aim of this study was to determine whether the use of a magnetic resonance (MR) susceptibility contrast medium, dysprosium diethylenetriamine pentaacetic acid‐bismethylamide (Dy DTPA‐BMA; Sprodiamide), may characterize myocardial perfusion abnormalities in a dog model of 90 minutes of coronary occlusion followed by 24 hours of reperfusion (no‐reflow phenomenon installed). First‐pass MR imaging after an intravenous bolus administration of the contrast agent was performed at the end of reperfusion. Signal intensity analysis on MR imaging, planimetry of pathological data, and blood flow determination were obtained by reference methods for comparison. Dogs were separated into two groups according to the level of collateral blood flow level (group I, <22.5 % of the flow in the non‐ischemic zone; group II, >22.5 % of the flow in the non‐ischemic zone). Signal intensity‐time curves in the ischemic and non‐ischemic left ventricle walls were extracted. Mean collateral blood flow was lower during occlusion in group I (9.8 ± 5.4%, n = 5) than in group II (38 ± 12.5%, n = 7, P < 0.05). Mean infarct size (expressed as a percentage of the area at risk) was significantly larger in group I (low collateral blood flow; 25.3 ± 14.6%) than in group II (high collateral blood flow; 5.8 ± 1.1%, P < 0.05). After rapid injection, a transient decrease of signal intensity induced by Dy DTPA‐BMA was observed in both remote and ischemic myocardium but more markedly in remote normally perfused myocardium. Hence, during the transit of a susceptibility‐type contrast agent, ischemic myocardium after ischemia and reperfusion appeared as a relative high signal intensity area. First‐pass MR imaging with susceptibility contrast agent demonstrated the no‐ or low‐reflow phenomenon. However, the behavior of the myocardial signal intensity–time‐related curves did not allow distinction between the two groups of dogs. J. Magn. Reson. Imaging 9:679–684, 1999.


Academic Radiology | 1998

Use of intravascular contrast agents in MRI.

Atle Bjørnerud; Michael F. Wendland; Lars Johansson; Hakan K. Ahlstrom; Charles B. Higgins; Audun N. Øksendal

MRI contrast agents that distribute to the extracellular fluid (ECF agents) have proved to have a large clinical utility in many diagnostic areas. However, the kinetic properties of these agents (short intravascular half-life and rapid leakage into the interstitium) are less than optimal in many situations. This has led to an increasing focus on contrast agents with sustained intravascular circulation (blood-pool agents), and several such agents are currently in preclinical or clinical development. MRI blood-pool agents are thought to have significant potential in different areas such as MR angiography (MRA) (1,2), characterization of endothelial permeability changes (3,4), and functional assessment of blood volume or blood flow using either the T1or T2*-shortening effect of the agent (5,6). The use of Gd-based ECF agents in MRA, as first suggested by Prince (7), has now become clinical routine in many centers and has been shown to significantly improve the quality of MR angiography compared to nonenhanced MRA. In spite of these encouraging results, the rapid extravasation of ECF agents induces some limitations on its use since image acquisition must be performed during the first pass of the contrast agent through the vascular system. Several techniques have been developed to optimally utilize the early passage of ECF agents through the vascular system. With all these techniques there is, however, a trade-off between achievable T1 reduction of the blood, total volume of contrast injected, speed of injection, and image quality. Furthermore, accurate timing of the image acquisition relative to the contrast arrival in the region of interest is crucial for diagnostic results (8). A Tl-shortening contrast agent that remains in the blood pool significantly longer than the ECF agents would allow high-resolution, high-SNR angiograms to be acquired in a steadystate situation where the duration and timing of the early contrast dynamics is no longer a concern. The major hurdle in blood pool-enhanced MRA is the enhancement of both arteries and veins. Various methods have been suggested to overcome this problem. Wang et al have suggested to use the difference in phase induced by differences in oxygenation level to separate arteries from veins (Wang et al, RSNA 1996), whereas Johansson et al have suggested to use vessel tracking algorithms to eliminate venous structures (Johansson et al, ESMRMB 1996). The latter method will be discussed in more detail here. Ultrasmall iron oxide particles (USPIO) have been evaluated as a Tl-enhancing blood-pool agent in two different animal models. The aim of these studies was to investigate the vascular enhancement pattern obtained after USPIO administration relative to that obtained with a gadolinium-based ECF agent. A second aim was to investigate the possibility of performing selective reconstruction of arterial structures (artery-vein segmentation) through image processing of the data sets.


Journal of Magnetic Resonance Imaging | 1999

Enhanced tumor detection in the presence of liver cirrhosis: experimental study on the diagnostic value of a superparamagnetic iron oxide MR imaging contrast agent (NSR 0430).

Rainald Bachmann; Burkhard Kreft; Frank Dombrowski; Wolfgang Block; Audun N. Øksendal; Hans H. Schild

The purpose of this study was to determine the diagnostic value of the superparamagnetic iron oxide NSR 0430 for the detection of focal liver lesions in the presence of advanced cirrhosis. Cirrhosis and growth of cholangiofibromas were induced in 22 rats by administration of thioacetamide. Sixteen non‐cirrhotic animals served as controls. T1 and T2 relaxation times of liver and tumor tissue of 12 animals were measured spectroscopically. In 10 animals in vivo MRI was performed before and 1 hour after contrast administration, and then the tumor‐to‐liver contrast‐to‐noise ratio (CNR) was calculated. All specimens were evaluated histologically. After contrast administration, T1 and T2 values of liver tissue showed a significant decrease of 18% (P = 0.01) and 31% (P = 0.009), respectively, whereas relaxation times of tumor tissue did not change. On precontrast turbo spin‐echo images, 40 tumors could be identified; after contrast administration, 95 lesions were visible. CNR increased significantly after contrast administration by 297% at a TE of 50 msec and by 254% at a TE of 90 msec. In conclusion, our in vitro and in vivo results demonstrate that administration of NSR 0430 substantially improves liver‐to‐tumor CNR and lesion detection on T2‐weighted magnetic resonance images even in the presence of severe cirrhosis. J. Magn. Reson. Imaging 1999;9:251–256.


Acta Radiologica | 1995

MR imaging of double-contrast enhanced porcine myocardial infarction. Correlation with microdialysis.

Stefan Nilsson; Mats Wikstrom; A. Ericsson; Gerhard Wikström; Anders Waldenström; Audun N. Øksendal; Anders Hemmingsson

MR imaging was performed to investigate whether Gd-DTPA-BMA-induced contrast enhancement of myocardial infarction is counteracted by Dy-DTPA-BMA. Myocardial infarction was induced in 5 pigs. Microdialysate probes were inserted in ischemic and nonischemic myocardium. Gd-DTPA-BMA (0.3 mmol/kg b.w.) and Dy-DTPA-BMA (1.0 mmol/kg b.w.) were administered i.v. 4 hours post occlusion. The microdialysate was collected every 10 min and measured for Gd and Dy using inductively coupled plasma atomic emission spectrometry. The pigs were sacrificed 2 hours after administration of contrast media. The concentration of both contrast agents was 3 times higher in infarcted myocardium than in nonischemic myocardium. The infarctions displayed high signal intensity in spin-echo sequences ex vivo. This lack of detectable susceptibility effects from Dy may be caused by loss of cell membrane integrity in infarcted tissue as shown by our microdialysate and biopsy data.


Acta Radiologica | 1990

Effect of Sodium Addition to Non-Ionic Contrast Media on Cardiac Contractile Force Perfusion of the Isolated Rabbit Heart with Iohexol and Iopentol Containing 0 to 154 Mmol Na+/l added as NaCl

Lars Bååth; Torsten Almén; Audun N. Øksendal

Cardiac contractile force after adding NaCl to the non-ionic contrast media iohexol and iopentol was investigated in the isolated rabbit heart. Iodine concentrations of 150, 300 and 350 mg I/ml were used with sodium concentrations ranging from 0 to 154 mmol/l. From physiologic experiences of nutrient solutions it should follow that a sodium-free solution of a non-ionic contrast medium, which also has the lowest hypertonicity, should cause the smallest decrease in contractile force. However, a small amount of sodium added to the contrast medium solutions, in the range of 19.25 to 38.5 mmol/l, caused the least decrease in contractile force. The decrease in contractile force was significantly more pronounced when no sodium was added or when larger amounts of sodium were added. A small amount of sodium also decreases the risk of ventricular fibrillation. Thus there is a possibility that addition of sodium could reduce the adverse effects of cardioangiography.


NMR in Biomedicine | 1996

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

Richard A. Jones; Olav Haraldseth; António M. Baptista; Tomm B. Müller; Audun N. Øksendal

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 micro‐vascular blood volume of the ischaemic tissue

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Anders Hemmingsson

Uppsala University Hospital

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Mats Wikstrom

Slovak Academy of Sciences

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