Search PubMed⌕ Search

Biomedical subjects

Leif Ostergaard

Publications and source records attributed to Leif Ostergaard.

11 recordsLinked to original sources
PubMed2006

Infarct prediction and treatment assessment with MRI-based algorithms in experimental stroke models.

There is increasing interest in using algorithms combining multiple magnetic resonance imaging (MRI) modalities to predict tissue infarction in acute human stroke. We developed and tested a voxel-based generalized linear model (GLM) algorithm to predict tissue infarction in an animal stroke model in order to directly compare predicted outcome with the tissue's histologic outcome, and to evaluate the potential for assessing therapeutic efficacy using these multiparametric algorithms. With acute MRI acquired after unilateral embolic stroke in rats (n=8), a GLM was developed and used to predict infarction on a voxel-wise basis for saline (n=6) and recombinant tissue plasminogen activator (rt-PA) treatment (n=7) arms of a trial of delayed thrombolytic therapy in rats. Pretreatment predicted outcome compared with post-treatment histology was highly accurate in saline-treated rats (0.92+/-0.05). Accuracy was significantly reduced (P=0.04) in rt-PA-treated animals (0.86+/-0.08), although no significant difference was detected when comparing histologic lesion volumes. Animals that reperfused had significantly lower (P<0.01) GLM-predicted infarction risk (0.73+/-0.03) than nonreperfused animals (0.81+/-0.05), possibly reflecting less severe initial ischemic injury and therefore tissue likely more amenable to therapy. Our results show that acute MRI-based algorithms can predict tissue infarction with high accuracy in animals not receiving thrombolytic therapy. Furthermore, alterations in disease progression due to treatment were more sensitively monitored with our voxel-based analysis techniques than with volumetric approaches. Our study shows that predictive algorithms are promising metrics for diagnosis, prognosis and therapeutic evaluation after acute stroke that can translate readily from preclinical to clinical settings.

Algorithms↗
PubMed2006

Effect of impermeable boundaries on diffusion-attenuated MR signal.

The nonlinear dependence between the logarithm of the diffusion weighted signal, lnS, and the b-value, b, has often been interpreted as a manifestation of two physically distinct compartments, resulting in a biexponential form of the signal. This model fits to experimental data, however, has failed to yield realistic compartment sizes, severely jeopardizing the use of DWI to infer structural information on a cellular level. It has been hypothesized that the biexponential behavior can be attributed to the effect of confining boundaries that restrict diffusion in individual physical compartments. This interpretation is based on the analysis of diffusion in the presence of impermeable interfaces for short diffusion times such that the layer in which diffusion is affected by the boundary is thin as compared with the dimensions of the whole compartment. This model system is analyzed from the point of view of the cumulant expansion of the diffusion-weighted signal that results in a Taylor expansion of lnS in powers of b. Termination of this expansion to a polynomial form provides an excellent accuracy for small b-factors, but the series diverges for large b. The convergence of the series is studied, yielding a large range of b-values in which the absolute error of terminating the series at the second term remains smaller than 1% relative to the signal magnitude without diffusion weighting. With this accuracy, the signal in the studied model can be described as lnS approximately -A.bD+B.(bD)2, where the parameters A and B can be expressed in terms of correlation functions of molecular velocity. Fitting of these parameters to the exact signal is more stable than for the three parameters of the biexponential function. This description fails for large b, for which the cumulant expansion diverges. The signal at even larger b-values is proportional to 1/b, 1/b3/2, and 1/b2 in one-, two-, and three-dimensional systems, respectively.

Journal Article↗
PubMed2006

Automatic selection of arterial input function using cluster analysis.

Quantification of cerebral blood flow (CBF) using dynamic susceptibility contrast MRI requires determination of the arterial input function (AIF) representing the delivery of intravascular tracer to tissue. This is typically accomplished manually by inspection of concentration time curves (CTCs) in regions containing the ICA, VA, and MCA. This is, however, a time consuming and operator dependent procedure. We suggest a completely automatic procedure for establishing the AIF based on a cluster analysis algorithm. In 20 normal subjects CBF maps calculated in 2 slices by the automatic procedure were compared to maps obtained with AIFs selected individually by 7 experienced operators. The average manual to automatic CBF ratio was 1.03+/-0.15 in the lower slice and 1.05+/-0.12 in the upper slice, demonstrating excellent agreement between the manual and automatic method. The algorithm provides means for objectively assessing AIF candidates in local AIF search algorithms designed to reduce bias due to delay and dispersion. Given the reproducibility and speed (10 s) of the automatic method, we speculate that it will greatly improve the accuracy of perfusion images and facilitate their use in clinical diagnosis and decision-making, particularly in acute stroke but also in cerebrovascular disease in general.

Aged↗
PubMed2005

Motion verb sentences activate left posterior middle temporal cortex despite static context.

The left posterior middle temporal region, anterior to V5/MT, has been shown to be responsive both to images with implied motion, to simulated motion, and to motion verbs. In this study, we investigated whether sentence context alters the response of the left posterior middle temporal region. 'Fictive motion' sentences are sentences in which an inanimate subject noun, semantically incapable of self movement, is coupled with a motion verb, yielding an apparent semantic contradiction (e.g. 'The path comes into the garden.'). However, this context yields no less activation in the left posterior middle temporal region than sentences in which the motion can be applied to the subject noun. We speculate that the left posterior middle temporal region activity in fictive motion sentences reflects the fact that the hearer applies motion to the depicted scenario by scanning it egocentrically.

Acoustic Stimulation↗
PubMed2005

Intravascular contrast agent-enhanced MRI measuring contrast clearance and tumor blood volume and the effects of vascular modifiers in an experimental tumor.

PURPOSE: To examine the feasibility of using the MRI blood pool agent NC100150 for evaluation of tumor blood volume (TBV) estimates by both dynamic contrast-enhanced MRI (DCE-MRI) and susceptibility contrast MRI assays in an experimental tumor. Contrast agent clearance (K(trans); depends on perfusion and permeability) from the DCE-MRI time curves was estimated, and changes in TBV and K(trans) were measured after administration of two drugs that reduce perfusion by different mechanisms. METHODS AND MATERIALS: The DCE-MRI experiments were simulated with expected physiologic values for the C3H mouse mammary carcinoma. The C3H tumor was examined by DCE-MRI and susceptibility contrast MRI with NC100150 (NC100150 Injection, Clariscan; Amersham Health, Oslo, Norway) after treatment with either hydralazine or combretastatin (Oxigene, Boston, MA). RESULTS: Simulations showed that reliable estimates of changes in TBV and K(trans) could be performed with DCE-MRI. Hydralazine was shown to reduce TBV as measured by both assays and to reduce K(trans). Dynamic contrast-enhanced MRI also suggested that TBV and K(trans) were reduced in combretastatin-treated tumors, and the TBV reduction was confirmed by susceptibility contrast MRI. Data suggested the drug to affect mainly the total TBV, whereas microvessels as such seemed less altered. CONCLUSION: The study supports the use of the combined DCE-MRI and susceptibility contrast MRI assay with a blood pool agent in characterizing tumors and their response to treatment.

Animals↗
PubMed2005

Concrete spatial language: see what I mean?

Conveying complex mental scenarios is at the heart of human language. Advances in cognitive linguistics suggest this is mediated by an ability to activate cognitive systems involved in non-linguistic processing of spatial information. In this fMRI-study, we compare sentences with a concrete spatial meaning to sentences with an abstract meaning. Using this contrast, we demonstrate that sentence meaning involving motion in a concrete topographical context, whether linked to animate or inanimate subjects nouns, yield more activation in a bilateral posterior network, including fusiform/parahippocampal, and retrosplenial regions, and the temporal-occipital-parietal junction. These areas have previously been shown to be involved in mental navigation and spatial memory tasks. Sentences with an abstract setting activate an extended largely left-lateralised network in the anterior temporal, and inferior and superior prefrontal cortices, previously found activated by comprehension of complex semantics such as narratives. These findings support a model of language, where the understanding of spatial semantic content emerges from the recruitment of brain regions involved in non-linguistic spatial processing.

Acoustic Stimulation↗
PubMed2005

Technical aspects of perfusion-weighted imaging.

There is increasing interest in using diffusion-weighted (DWI) MR imaging and perfusion-weighted MR imaging (PWI) to assist clinical decision-making in the management of acute stroke patients. Larger PWI than DWI lesions have been speculated to represent potentially salvageable tissue that is at risk of infarction unless nutritive flow is restored and presence of these mismatches have been proposed as inclusion criteria for identifying patients most likely to benefit from therapeutic intervention. Understanding the technical aspects of PWI may improve comprehension of the capabilities and limitations of this technique.

Brain↗
PubMed2005

Cerebral metabolic response to low blood flow: possible role of cytochrome oxidase inhibition.

The reactions of cerebral metabolism to imposed changes of cerebral blood flow (CBF) are poorly understood. A common explanation of the mismatched CBF and oxygen consumption (CMR(O(2))) during neuronal excitation holds that blood flow rises more than oxygen consumption to compensate for an absent oxygen reserve in brain mitochondria. The claim conversely implies that oxygen consumption must decline when blood flow declines. As the prevailing rate of reaction of oxygen with cytochrome c oxidase is linked to the tension of oxygen, the claim fails to explain how oxygen consumption is maintained during moderate reductions of CBF imposed by hyperventilation (hypocapnia) or cyclooxygenase (COX) inhibition. To resolve this contradiction, we extended the previously published oxygen delivery model with a term allowing for the adjustment of the affinity of cytochrome c oxidase to a prevailing oxygen tension. The extended model predicted constant oxygen consumption at moderately reduced blood flow. We determined the change of affinity of cytochrome c oxidase in the extended model by measuring CBF in seven, and CMR(O(2)) in five, young healthy volunteers before and during COX inhibition with indomethacin. The average CBF declined 35%, while neither regional nor average CMR(O(2)) changed significantly. The adjustment of cytochrome c oxidase affinity to the declining oxygen delivery could be ascribed to a hypothetical factor with several properties in common with nitric oxide.

Adult↗
PubMed2004

Quantitative cerebral perfusion using the PRESTO acquisition scheme.

PURPOSE: To evaluate the feasibility of using the rapid principles of echo shifting with a train of observations (PRESTO) sequence for measurements of cerebral hemodynamic parameters based on first pass of a contrast agent. MATERIALS AND METHODS: Simulations were performed to investigate potential resolution loss due to relaxation effects. Experimental evaluation was conducted in healthy monkey brains using PRESTO and echo-planar imaging (EPI). RESULTS: For short echo trains, an insignificant contribution of the longitudinal and transversal relaxation rates to the signal amplitude in white matter and gray matter was found, whereas a contribution as large as 40% was found in large vessels. Simulations of the point spread function demonstrated that PRESTO, despite its shorter readout trains, only has a small advantage in terms of maintenance of image resolution during bolus passage compared to EPI as long as the EPI echo train can be kept similar to the T2* value at the top of the bolus. Experimental studies revealed that the PRESTO and EPI gray matter to white matter ratio were similar with respect to cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). CONCLUSION: The study showed that PRESTO and EPI led to comparable quantitative perfusion parameters.

Animals↗