Kim Mouridsen

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. Magn Reson Med, 2006.

Comparison of 10 Perfusion MRI Parameters in 97 Sub-6-Hour Stroke Patients Using Voxel-Based Receiver Operating Characteristics Analysis

Background and Purpose— Perfusion-weighted imaging can predict infarct growth in acute stroke and potentially be used to select patients with tissue at risk for reperfusion therapies. However, the lack of consensus and evidence on how to best create PWI maps that reflect tissue at risk challenges comparisons of results and acute decision-making in trials. Deconvolution using an arterial input function has been hypothesized to generate maps of a more quantitative nature and with better prognostic value than simpler summary measures such as time-to-peak or the first moment of the concentration time curve. We sought to compare 10 different perfusion parameters by their ability to predict tissue infarction in acute ischemic stroke. Methods— In a retrospective analysis of 97 patients with acute stroke studied within 6 hours from symptom onset, we used receiver operating characteristics in a voxel-based analysis to compare 10 perfusion parameters: time-to-peak, first moment, cerebral blood volume and flow, and 6 variants of time to peak of the residue function and mean transit time maps. Subanalysis assessed the effect of reperfusion on outcome prediction. Results— The most predictive maps were the summary measures first moment and time-to-peak. First moment was significantly more predictive than time to peak of the residue function and local arterial input function-based methods (P<0.05), but not significantly better than conventional mean transit time maps. Conclusion— Results indicated that if a single map type was to be used to predict infarction, first moment maps performed at least as well as deconvolved measures. Deconvolution decouples delay from tissue perfusion; we speculate this negatively impacts infarct prediction.

Seeing without Seeing? Degraded Conscious Vision in a Blindsight Patient

Blindsight patients, whose primary visual cortex is lesioned, exhibit preserved ability to discriminate visual stimuli presented in their “blind” field, yet report no visual awareness hereof. Blindsight is generally studied in experimental investigations of single patients, as very few patients have been given this “diagnosis”. In our single case study of patient GR, we ask whether blindsight is best described as unconscious vision, or rather as conscious, yet severely degraded vision. In experiment 1 and 2, we successfully replicate the typical findings of previous studies on blindsight. The third experiment, however, suggests that GRs ability to discriminate amongst visual stimuli does not reflect unconscious vision, but rather degraded, yet conscious vision. As our finding results from using a method for obtaining subjective reports that has not previously used in blindsight studies (but validated in studies of healthy subjects and other patients with brain injury), our results call for a reconsideration of blindsight, and, arguably also of many previous studies of unconscious perception in healthy subjects.

MRI Detection of Early Blood-Brain Barrier Disruption Parenchymal Enhancement Predicts Focal Hemorrhagic Transformation After Thrombolysis

Background and Purpose— Blood-brain barrier disruption may be a predictor of hemorrhagic transformation (HT) in ischemic stroke. We hypothesize that parenchymal enhancement (PE) on postcontrast T1-weighted MRI predicts and localizes subsequent HT. Methods— In a prospective study, 33 tPA-treated stroke patients were imaged by perfusion-weighted imaging, T1 and FLAIR before thrombolytic therapy and after 2 and 24 hours. Results— Postcontrast T1 PE was found in 5 of 32 patients (16%) 2 hours post-thrombolysis. All 5 patients subsequently showed HT compared to 11 of 26 patients without PE (P=0.043, specificity 100%, sensitivity 31%), with exact anatomic colocation of PE and HT. Enhancement of cerebrospinal fluid on FLAIR was found in 4 other patients, 1 of which developed HT. Local reperfusion was found in 4 of 5 patients with PE, whereas reperfusion was found in all cases of cerebrospinal fluid hyperintensity. Conclusions— PE detected 2 hours after thrombolytic therapy predicts HT with high specificity. Contrast-enhanced MRI may provide a tool for studying HT and targeting future therapies to reduce risk of hemorrhagic complications.

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.

The capillary dysfunction hypothesis of Alzheimer's disease

It is widely accepted that hypoperfusion and changes in capillary morphology are involved in the etiopathogenesis of Alzheimers disease (AD). This is difficult to reconcile with the hyperperfusion observed in young high-risk subjects. Differences in the way cerebral blood flow (CBF) is coupled with the local metabolic needs during different phases of the disease can explain this apparent paradox. This review describes this coupling in terms of a model of cerebral oxygen availability that takes into consideration the heterogeneity of capillary blood flow patterns. The model predicts that moderate increases in heterogeneity requires elevated CBF in order to maintain adequate oxygenation. However, with progressive increases in heterogeneity, the resulting low tissue oxygen tension will require a suppression of CBF in order to maintain tissue metabolism. The observed biphasic nature of CBF responses in preclinical AD and AD is therefore consistent with progressive disturbances of capillary flow patterns. Salient features of the model are discussed in the context of AD pathology along with potential sources of increased capillary flow heterogeneity.

It don't mean a thing... Keeping the rhythm during polyrhythmic tension, activates language areas (BA47).

Music is experienced and understood on the basis of foreground/background relationships created between actual music and the underlying meter. In contemporary styles of music so-called polyrhythmic, structures hence create tension between a counter pulse and the main pulse. This exerts a marked influence on the listener, particularly when the experience of the original meter is maintained during the counter pulse. We here demonstrate that Brodmann area 47, an area associated with higher processing of language, is activated bilaterally when musicians tap the main pulse in a polymetric context where the music emphasizes a counter meter. This suggests that the processing of metric elements of music relies on brain areas also involved in language comprehension. We propose that BA47 is involved in general neuronal processing of temporal coherence subserving both language and music.

Low Cerebral Oxygen Consumption and Blood Flow in Patients With Cirrhosis and an Acute Episode of Hepatic Encephalopathy

BACKGROUND & AIMS It is unclear whether patients with hepatic encephalopathy (HE) have disturbed brain oxygen metabolism and blood flow. METHODS We measured cerebral oxygen metabolism rate (CMRO(2)) by using (15)O-oxygen positron emission tomography (PET); and cerebral blood flow (CBF) by using (15)O-water PET in 6 patients with liver cirrhosis and an acute episode of overt HE, 6 cirrhotic patients without HE, and 7 healthy subjects. RESULTS Neither whole-brain CMRO(2) nor CBF differed significantly between cirrhotic patients without HE and healthy subjects, but were both significantly reduced in cirrhotic patients with HE (P < .01). CMRO(2) was 0.96 +/- 0.07 mumol oxygen/mL brain tissue/min (mean +/- SEM) in cirrhotic patients with HE, 1.34 +/- 0.08 in cirrhotic patients without HE, and 1.35 +/- 0.05 in healthy subjects; and CBF was 0.29 +/- 0.01 mL blood/mL brain tissue/min in patients with HE, 0.47 +/- 0.02 in patients without HE, and 0.49 +/- 0.03 in healthy subjects. CMRO(2) and CBF were correlated, and both variables correlated negatively with arterial ammonia concentration. Analysis of regional values, using individual magnetic resonance co-registrations, showed that the reductions in CMRO(2) and CBF in patients with HE were essentially generalized throughout the brain. CONCLUSIONS The observations imply that reduced cerebral oxygen consumption and blood flow in cirrhotic patients with an acute episode of overt HE are associated with HE and not cirrhosis as such, and that the primary event in the pathogenesis of HE could be inhibition of cerebral energy metabolism by increased blood ammonia.

The role of the cerebral capillaries in acute ischemic stroke: the extended penumbra model

The pathophysiology of cerebral ischemia is traditionally understood in relation to reductions in cerebral blood flow (CBF). However, a recent reanalysis of the flow-diffusion equation shows that increased capillary transit time heterogeneity (CTTH) can reduce the oxygen extraction efficacy in brain tissue for a given CBF. Changes in capillary morphology are typical of conditions predisposing to stroke and of experimental ischemia. Changes in capillary flow patterns have been observed by direct microscopy in animal models of ischemia and by indirect methods in humans stroke, but their metabolic significance remain unclear. We modeled the effects of progressive increases in CTTH on the way in which brain tissue can secure sufficient oxygen to meet its metabolic needs. Our analysis predicts that as CTTH increases, CBF responses to functional activation and to vasodilators must be suppressed to maintain sufficient tissue oxygenation. Reductions in CBF, increases in CTTH, and combinations thereof can seemingly trigger a critical lack of oxygen in brain tissue, and the restoration of capillary perfusion patterns therefore appears to be crucial for the restoration of the tissue oxygenation after ischemic episodes. In this review, we discuss the possible implications of these findings for the prevention, diagnosis, and treatment of acute stroke.

Dopaminergic stimulation enhances confidence and accuracy in seeing rapidly presented words

Liberal acceptance, overconfidence, and increased activity of the neurotransmitter dopamine have been proposed to account for abnormal sensory experiences, for instance, hallucinations in schizophrenia. In normal subjects, increased sensory experience in Yoga Nidra meditation is linked to striatal dopamine release. We therefore hypothesize that the neurotransmitter dopamine may function as a regulator of subjective confidence of visual perception in the normal brain. Although much is known about the effect of stimulation by neurotransmitters on cognitive functions, their effect on subjective confidence of perception has never been recorded experimentally before. In a controlled study of 24 normal, healthy female university students with the dopamine agonist pergolide given orally, we show that dopaminergic activation increases confidence in seeing rapidly presented words. It also improves performance in a forced-choice word recognition task. These results demonstrate neurotransmitter regulation of subjective conscious experience of perception and provide evidence for a crucial role of dopamine.