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Leif Østergaard

Publications and source records attributed to Leif Østergaard.

At least 19 recordsLinked to original sources
PubMed2006

Modeling dendrite density from magnetic resonance diffusion measurements.

Diffusion-weighted imaging (DWI) provides a noninvasive tool to probe tissue microstructure. We propose a simplified model of neural cytoarchitecture intended to capture the essential features important for water diffusion as measured by NMR. Two components contribute to the NMR signal in this model: (i) the dendrites and axons, which are modeled as long cylinders with two diffusion coefficients, parallel (D(L)) and perpendicular (D(T)) to the cylindrical axis, and (ii) an isotropic monoexponential diffusion component describing water diffusion within and across all other structures, i.e., in extracellular space and glia cells. The model parameters are estimated from 153 diffusion-weighted images acquired from a formalin-fixed baboon brain. A close correspondence between the data and the signal model is found, with the model parameters consistent with literature values. The model provides an estimate of dendrite density from noninvasive MR diffusion measurements, a parameter likely to be of value for understanding normal as well as abnormal brain development and function.

Computer Simulation↗
PubMed2006

Statistical mapping of effects of middle cerebral artery occlusion (MCAO) on blood flow and oxygen consumption in porcine brain.

The volume of cerebral tissue perturbed in experimental models of middle cerebral artery occlusion (MCAO) can be highly variable. Thus, the territories of reduced cerebral blood flow (CBF) or oxygen consumption (CMRO(2)) following MCAO might properly be defined using statistical parametric mapping within a population. In order to establish such a method, we mapped CBF and CMRO(2) in 18 pigs with acute MCAO. Parametric maps were flipped about the axis of symmetry, and CBF and CMRO(2) in the infarcted hemisphere were calculated as percentages of the magnitudes in mirror-image pixels. There were log-linear relationships between the volumes of affected tissue and the percentages of normal CFB or CMRO(2). This graphical analysis showed that the volume of the core deficit was smaller for CBF that for CMRO(2), but expanded more rapidly with decreasing CBF deficit than did the corresponding volumes of reduced CMRO(2). Thus, acute changes in CBF and CMRO(2) following MCAO in the pig can be defined as probabilistic volumes.

Animals↗
PubMed2006

Bayesian estimation of cerebral perfusion using a physiological model of microvasculature.

Perfusion weighted MRI has proven very useful for deriving hemodynamic parameters such as CBF, CBV and MTT. These quantities are important diagnostically, e.g. in acute stroke, where they are used to delineate ischemic regions. Yet the standard method for estimating CBF based on singular value decomposition (SVD) has been demonstrated to underestimate (especially high) flow components and to be sensitive to delays in the arterial input function (AIF). Furthermore, the estimated residue functions often oscillate. This compromises their physiological interpretation/basis and makes estimation of related measures such as flow heterogeneity difficult. In this study, we estimate perfusion parameters based on a vascular model (VM) which represents heterogeneous capillary flow and explicitly leads to monotonically decreasing residue functions. We use a fully Bayesian approach to obtain posterior probability distributions for all parameters. In simulation studies, we show that the VM method has less bias in CBF estimates than the SVD based method for realistic SNRs. This also applies to cases where the AIF is delayed. We employ our method to estimate perfusion maps using data from (i) a healthy volunteer and (ii) from a stroke patient.

Bayes Theorem↗
PubMed2006

Characterizing physiological heterogeneity of infarction risk in acute human ischaemic stroke using MRI.

Viable tissues at risk of infarction in acute stroke patients have been hypothesized to be detectable as volumetric mismatches between lesions on perfusion-weighted (PWI) and diffusion-weighted magnetic resonance imaging (DWI). Because tissue response to ischaemic injury and to therapeutic intervention is tissue- and patient-dependent, changes in infarct progression due to treatment may be better detected with voxel-based methods than with volumetric mismatches. Acute DWI and PWI were combined using a generalized linear model (GLM) to predict infarction risk on a voxel-wise basis for patients treated either with non-thrombolytic (Group 1; n = 11) or with thrombolytic therapy (Group 2; n = 27). Predicted infarction risk for both groups was evaluated in four ipsilateral regions of interest: tissue acutely abnormal on DWI (Core), tissue acutely abnormal on PWI but normal on DWI that either infarcts (Recruited) or does not (Salvaged), and tissue normal on both DWI and PWI that does not infarct (Normal) by follow-up imaging > or = 5 days. The performance of the models was significantly reduced for the thrombolysed group compared with the group receiving standard treatment, suggesting an alteration in natural progression of the ischaemic cascade. Average GLM-predicted infarction risk values in the four regions were different from one another for both groups. GLM-predicted infarction risk in Salvaged tissue was significantly higher (P = 0.02) for thrombolysed patients than for non-thrombolysed patients, suggesting that thrombolysis rescued tissue with higher infarction risk than typically measured in tissue that spontaneously recovered. The observed spatial heterogeneity of GLM-predicted infarction risk values probably reflects the varying degrees of tissue injury and salvageability that exist after stroke. MRI-based algorithms may therefore provide a more sensitive means for monitoring therapeutic effects on a voxel-wise basis.

Acute Disease↗
PubMed2006

The impact of susceptibility gradients on cartesian and spiral EPI for BOLD fMRI.

High sensitivity to magnetic susceptibility changes and accurate localization of functional activations are key requisites for pulse sequences used for BOLD fMRI. This paper seeks to develop a framework for analysing the performance of various k-space sampling techniques in this respect, with special emphasis on spiral EPI (spiral) and cartesian EPI (EPI) and their performance under influence of induced field gradients (SFGs) and stochastic noise. A numerical method for calculating synthetic MR images is developed and used to simulate BOLD fMRI experiments using EPI and spirals. The data is then examined for activation using a pixel-wise t test. Nine subjects are scanned with both techniques while performing a motor task. SPM99 is used for analysing the experimental data. The simulated spirals provide generally higher t scores at low SFGs but lose more strength than EPI at higher SFGs, where EPI activation is offset from the true position. In the primary motor area spirals provide significantly higher t scores (P < 0.0002). In-plane variation of EPI is higher in phase-encoding direction than in frequency-encoding direction (P < 0.003). In the low SFG areas spirals provide stronger activation than EPI and less spatial variability. Thus, spirals are recommended for fMRI in motor area and language areas.

Algorithms↗
PubMed2006

[Thrombolysis of apoplexy patients. A year's experience and results in Aarhus Hospital].

INTRODUCTION: Treatment of acute stroke with thrombolysis within three hours is a challenging aspect of the organization of state-of-the-art stroke care. Indication for thrombolysis is based on studies where CT was used as a diagnostic tool. MR-based techniques are in some aspects superior to CT, though the scan times are longer. In this study, the feasibility and effectiveness of MR-based thrombolysis was examined. MATERIALS AND METHODS: Prospective registration of patient time delays, demographics, initial NIHSS (National Institute of Health Stroke Scale) and MR data for all patients referred to Aarhus Hospital with symptoms of acute stroke was done over a one-year period. For patients receiving thrombolysis, additional MR data, complications, NIHSS at follow-up (2 hours, 24 hours, 7 days and 3 months) and modified Rankin score at 3 months were recorded. Results were compared to the data in the international thrombolysis database (SITS-MOST). RESULTS: During the period, 112 patients were referred and 86 were scanned using MR techniques. 22 patients received thrombolysis (17/5 after MR/CT). 54% of patients had a good outcome at 3 months (mRS = 0-1) compared to 34% in SITS-MOST (n.s). No symptomatic haemorrhages were recorded; mortality was 9% (13% in SITS-MOST). Treatment was not delayed compared to SITS-MOST despite the longer MR scan time. CONCLUSION: Effective organization of treatment with thrombolysis using MR imaging is feasible. The MR techniques were beneficial in decision making and did not cause delay of treatment. Thrombolysis in this setup was as efficient with respect to outcome and complications as was that recorded in the SITS-MOST register.

Adult↗
PubMed2006

Radiation administered as a large single dose or in a fractionated schedule: Role of the tumour vasculature as a target for influencing response.

This study was designed to demonstrate a differential tumour response to radiation given as a large single dose or fractionated, and to investigate the postulated role of the tumour vasculature as a target for this difference. A C3H mammary carcinoma grown in the right rear foot of female CDF1 mice was used when at 200 mm3. Radiation (240 kV x-rays) was given locally to the tumour bearing foot either as 1 x 20 Gy or 10 x 2 Gy (2 fractions/day). Tumour response was assessed by calculating tumour growth time (TGT; time to grow to 3 times treatment volume). Vascular effects were monitored by performing dynamic contrast enhanced-magnetic resonance imaging using a 3-Tesla magnet and the contrast agent gadolinium (Gd)-DTPA. The endpoint was the initial area under the concentration curve (IAUC) following Gd-DTPA. The mean (+/-1 S.E.) TGT for control mice was 4.0 days (+/-0.2). This was significantly (Student's t-test; p < 0.05) increased to 12.9 (+/-0.6) and 19.8 (+/-0.7) days, by 10 x 2 and 1 x 20 Gy, respectively. The mean (+/-1 S.E.) of the median IAUC values for control tumours was 8.4 mMs (+/-0.5). This was non-significantly increased to 9.4 mMs (+/-0.4) 6-hours after 1 x 20 Gy, but then significantly decreased to a nadir of 6.8 mMs (+/-0.5) after 48-hours. IAUC recovered at longer time intervals. With 10 x 2 Gy, IAUC significantly decreased during irradiation, reaching 6.7 (+/-0.3) and 5.6 (+/-0.3) mMs at the mid-point and end of the irradiation period, respectively. IAUC recovered 24-hours after irradiating before significantly decreasing to 4.4 mMs (+/-0.3) at 48-hours. Our results confirm that radiation given in a large single dose is superior to the same dose given in a more conventional fractionated schedule, but vascular-mediated effects did not account for this difference in radiation sensitivity.

Animals↗
PubMed2005

To musicians, the message is in the meter pre-attentive neuronal responses to incongruent rhythm are left-lateralized in musicians.

Musicians exchange non-verbal cues as messages when they play together. This is particularly true in music with a sketchy outline. Jazz musicians receive and interpret the cues when performance parts from a regular pattern of rhythm, suggesting that they enjoy a highly developed sensitivity to subtle deviations of rhythm. We demonstrate that pre-attentive brain responses recorded with magnetoencephalography to rhythmic incongruence are left-lateralized in expert jazz musicians and right-lateralized in musically inept non-musicians. The left-lateralization of the pre-attentive responses suggests functional adaptation of the brain to a task of communication, which is much like that of language.

Acoustic Stimulation↗
PubMed2005

Ischemic injury detected by diffusion imaging 11 minutes after stroke.

A 78-year-old woman suffered a stroke inside a magnetic resonance scanner while being imaged because of a brief transient ischemic attack 2 hours earlier. Diffusion-weighted images obtained 11 minutes after stroke showed tissue injury not found on initial images. The data show early, abrupt diffusion changes in hypoperfused tissue, adding to our understanding of the progression of microstructural abnormalities in the hyperacute phase of stroke.

Aged↗
PubMed2005

Principles of cerebral perfusion imaging by bolus tracking.

The principles of cerebral perfusion imaging by the method of dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) (bolus tracking) are described. The MRI signals underlying DSC-MRI are discussed. Tracer kinetics procedures are defined to calculate images of cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT). Two general categories of numerical procedures are reviewed for deriving CBF from the residue function. Procedures that involve deconvolution, such as Fourier deconvolution or singular value decomposition (SVD), are classified as model-independent methods because they do not require a model of the microvascular hemodynamics. Those methods in principle also yield a measure of the tissue impulse response function and the residue function, from which microvascular hemodynamics can be characterized. The second category of methods is the model-dependent methods, which use models of tracer transport and retention in the microvasculature. These methods do not yield independent measures of the residue function and may introduce bias when the physiology does not follow the model. Statistical methods are sometimes used, which involve treating the residue function as a deconvolution kernel and optimizing (fitting) the kernel from the experimental data using procedures such as maximum likelihood. Finally, other hemodynamic indices that can be measured from DSC-MRI data are described.

Blood Volume↗
PubMed2005

Applying instance-based techniques to prediction of final outcome in acute stroke.

OBJECTIVE: Acute cerebral stroke is a frequent cause of death and the major cause of adult neurological disability in the western world. Thrombolysis is the only established treatment of ischemic stroke; however, its use carries a substantial risk of symptomatic intracerebral hemorrhage. A clinical tool to guide the use of thrombolysis would be very valuable. One of the major goals of such a tool would be the identification of potentially salvageable tissue. This requires an accurate prediction of the extent of infarction if untreated. In this study, we investigate the applicability of highly flexible instance-based (IB) methods for such predictions. METHODS AND MATERIALS: Based on information obtained from magnetic resonance imaging of 14 patients with acute stroke, we explored three different implementations of the IB method: k-NN, Gaussian weighted, and constant radius search classification. Receiver operating characteristics analysis, in particular area under the curve (AUC), was used as performance measure. RESULTS: We found no significant difference (P = 0.48) in performance for the optimal k-NN (k = 164, AUC = 0.814 +/- 0.001) and Gaussian weight (sigma = 0.17, AUC = 0.813 +/- 0.001) implementations, while they were both significantly better (P < 1 x 10(-6) for both) than the constant radius implementation (R = 0.28, AUC = 0.809 +/- 0.001). Qualitative analyses of the distribution of instances in the feature space indicated that non-infarcted instances tends to cluster together while infarcted instances are more dispersed, and that there may not exist a stringent boundary separating infarcted from non-infarcted instances. CONCLUSIONS: This study shows that IB methods can be used, and may be advantageous, for predicting final infarct in patients with acute stroke, but further work must be done to make them clinically applicable.

Adult↗
PubMed2004

Abnormal intravoxel cerebral blood flow heterogeneity in human ischemic stroke determined by dynamic susceptibility contrast magnetic resonance imaging.

BACKGROUND AND PURPOSE: The determination of cerebral blood flow heterogeneity (FH) by dynamic susceptibility contrast (DSC) magnetic resonance imaging has recently been proposed as a tool to predict final infarct size in acute stroke. In this study, we describe the evolution of FH during the first week as well as its correlation to the patients' clinical status. METHODS: Ten patients with ischemic stroke were studied with DSC MRI and diffusion-weighted imaging in hyperacute (<6 hours) phase, at 24 hours, and 1 week after symptom onset. In addition to intravoxel FH, cerebral blood volume (CBV), cerebral blood flow (CBF), and contrast agent mean transit time (MTT) were determined from DSC MRI. All patients were evaluated neurologically with National Institute of Health Stroke Scale concurrently with the imaging sessions. RESULTS: All patients showed infarct growth, judged by diffusion-weighted imaging, during the week with simultaneous decrease in the sizes of FH, CBV, CBF, and MTT abnormalities. The FH abnormality was shown to be larger than CBV and CBF abnormalities at the hyperacute phase and 24 hours, but smaller than MTT abnormality in all 3 imaging sessions. The sizes of hyperacute FH, CBV, CBF, and MTT abnormalities correlated well with infarct size at 24 hours and at 1 week. Additionally, FH was the only perfusion parameter that correlated with the clinical score. CONCLUSIONS: FH predicts infarct size equally well with the other perfusion parameters but is superior in correlation with the clinical score. FH can easily be incorporated to hyperacute stroke imaging without additional efforts.

Aged↗
PubMed2004

Do indomethacin and propofol cause cerebral ischemic damage? Diffusion-weighted magnetic resonance imaging in patients undergoing craniotomy for brain tumors.

BACKGROUND: Diffusion-weighted magnetic resonance imaging was used to determine whether indomethacin and propofol induce cerebral ischemic damage in patients undergoing craniotomy for cerebral tumors. As a secondary aim, the authors investigated whether low jugular bulb oxygen saturation values were associated with brain parenchymal damage as evaluated by diffusion-weighted imaging. METHODS: Nine patients subjected to craniotomy for supratentorial brain tumors in propofol-fentanyl anesthesia were studied. Magnetic resonance imaging including diffusion- and perfusion-weighted and structural sequences were performed (1) on the day before surgery, (2) before and (3) 20 min after administration of indomethacin (bolus of 0.2 mg/kg followed by infusion of 0.2 mg.kg.h) in the propofol-fentanyl-anesthetized patient, and (4) 2 days after surgery. Apparent diffusion coefficient maps were calculated. Jugular bulb oxygen saturation, arteriovenous oxygen difference, mean arterial blood pressure, and arterial oxygen and carbon dioxide tensions were measured simultaneously with the magnetic resonance examinations performed during anesthesia. RESULTS: No ischemic lesions were detected in the diffusion-weighted or apparent diffusion coefficient images. A nonsignificant decrease in jugular bulb oxygen saturation from 51% (range, 40-61%) to 43% (range, 37-63%) and increase in arteriovenous oxygen difference from 4.4 mm (range, 2.7-4.6 mm) to 4.7 mm (range, 2.9-5.2 mm) was observed after indomethacin administration. CONCLUSION: Administration of indomethacin during propofol anesthesia is not associated with evidence of ischemic damage in patients with brain tumors, as evaluated by diffusion-weighted imaging.

Adult↗
PubMed2004

Cerebral perfusion imaging by bolus tracking.

Cerebral perfusion may be visualized by the dynamic imaging of an intravenously injected bolus (a few milliliters) of clinically approved gadolinium-containing contrast media. During its passage through the vasculature of the brain, the contrast agent induces magnetic field disturbances, which can be seen as signal loss on appropriately weighted dynamic MRI. This article deals with the quantitative analysis of such signal changes, first in terms of tracer concentration and then, via the mathematical approach of deconvolution, in terms of tissue microvascular physiology, culminating in quantitative estimates on a pixel-by-pixel basis of physiologic parameters, such as cerebral blood volume, mean transit time, and cerebral blood flow.

Blood Flow Velocity↗
PubMed2003

Tracer arrival timing-insensitive technique for estimating flow in MR perfusion-weighted imaging using singular value decomposition with a block-circulant deconvolution matrix.

Relative cerebral blood flow (CBF) and tissue mean transit time (MTT) estimates from bolus-tracking MR perfusion-weighted imaging (PWI) have been shown to be sensitive to delay and dispersion when using singular value decomposition (SVD) with a single measured arterial input function. This study proposes a technique that is made time-shift insensitive by the use of a block-circulant matrix for deconvolution with (oSVD) and without (cSVD) minimization of oscillation of the derived residue function. The performances of these methods are compared with standard SVD (sSVD) in both numerical simulations and in clinically acquired data. An additional index of disturbed hemodynamics (oDelay) is proposed that represents the tracer arrival time difference between the AIF and tissue signal. Results show that PWI estimates from sSVD are weighted by tracer arrival time differences, while those from oSVD and cSVD are not. oSVD also provides estimates that are less sensitive to blood volume compared to cSVD. Using PWI data that can be routinely collected clinically, oSVD shows promise in providing tracer arrival timing-insensitive flow estimates and hence a more specific indicator of ischemic injury. Shift maps can continue to provide a sensitive reflection of disturbed hemodynamics.

Aged↗
PubMed2003

Effects of tracer arrival time on flow estimates in MR perfusion-weighted imaging.

A common technique for calculating cerebral blood flow (CBF) and mean transit time (MTT) is to track a bolus of contrast agent using perfusion-weighted MRI (PWI) and to deconvolve the change in concentration with an arterial input function (AIF) using singular value decomposition (SVD). This method has been shown to often overestimate the volume of tissue that infarcts and in cases of severe vasculopathy to produce CBF maps that are inconsistent with clinical presentation. This study examines the effects of tracer arrival time differences between tissue and a user-selected global AIF on flow estimates. CBF and MTT were calculated in both numerically simulated and clinically acquired PWI data where the AIF and tissue signals were shifted backward and forward in time with respect to one another. Results show that when the AIF leads the tissue, CBF is underestimated independent of extent of delay, but dependent on MTT. When the AIF lags the tissue, flow may be over- or underestimated depending on MTT and extent of timing differences. These conditions may occur in practice due to the application of a user-selected AIF that is not the "true AIF" and therefore caution must be taken in interpreting CBF and MTT estimates.

Aged↗
PubMed2002

Time evolution of cerebral perfusion and apparent diffusion coefficient measured by magnetic resonance imaging in a porcine stroke model.

PURPOSE: To demonstrate the feasibility of sequential diffusion-weighted (DW) and perfusion-weighted (PW) magnetic resonance imaging (MRI) of a recently developed porcine stroke model and to evaluate the evolution of cerebral perfusion and the apparent diffusion coefficient (ADC) over time. Materials and Methods In five pigs, DW imaging (DWI) and PW imaging (PWI) was carried out for 7 hours after stroke onset, starting 1 hour after middle cerebral artery occlusion (MCAO). RESULTS: The DWI lesion volume increased significantly with time, and final DWI lesion volume correlated well with lesion area on histological sections (r = 0.910). T2 changes could be recognized 3 hours after stroke onset. At 1 hour the ADC ratio (ischemic lesion/contralateral side) was reduced to 0.81 in the caudate-putamen and to 0.87 in the cortex, and the cerebral blood flow ratio was reduced to 0.40 in the caudate-putamen and 0.51 in the cortex. CONCLUSION: The level of flow reduction in the caudate-putamen and the cortex after 1 hour is in good correlation with human thresholds of irreversible and reversible ischemic damage, and accordingly, this model might be a model for mechanisms of infarct evolution and therapeutic intervention.

Analysis of Variance↗