Using the adiabatic approximation, which assumes that the tracer concentration in parenchymal tissue changes slowly relative to that in capillaries, we derived a time-domain, closed-form solution of the tissue homogeneity model. This solution, which is called the adiabatic solution, is similar in form to those of two-compartment models. Owing to its simplicity, the adiabatic solution can be used in CBF experiments in which kinetic data with only limited time resolution or signal-to-noise ratio, or both, are obtained. Using computer simulations, we investigated the accuracy and the precision of the parameters in the adiabatic solution for values that reflect 2H-labeled water (D2O) clearance from the brain (see Part II). It was determined that of the three model parameters, (1) the vascular volume (Vi), (2) the product of extraction fraction and blood flow (EF), and (3) the clearance rate constant (kadb), only the last one could be determined accurately, and therefore CBF must be determined from this parameter only. From the error analysis of the adiabatic solution, it was concluded that for the D2O clearance experiments described in Part II, the coefficient of variation of CBF was approximately 7% in gray matter and 22% in white matter.

No abstract

Abstract-The recent "Advanced Neuroimaging for Acute Stroke Treatment" meeting on September 7 and 8, 2007 in Washington DC, brought together stroke neurologists, neuroradiologists, emergency physicians, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), industry representatives, and members of the US Food and Drug Administration (FDA) to discuss the role of advanced neuroimaging in acute stroke treatment. The goals of the meeting were to assess state-of-the-art practice in terms of acute stroke imaging research and to propose specific recommendations regarding: (1) the standardization of perfusion and penumbral imaging techniques, (2) the validation of the accuracy and clinical utility of imaging markers of the ischemic penumbra, (3) the validation of imaging biomarkers relevant to clinical outcomes, and (4) the creation of a central repository to achieve these goals. The present article summarizes these recommendations and examines practical steps to achieve them. (Stroke. 2008;39:1621-1628.)

Edaravone, a novel free radical scavenger, demonstrates neuroprotective effects by inhibiting vascular endothelial cell injury and ameliorating neuronal damage in ischemic brain models. The present study was undertaken to verify its therapeutic efficacy following acute ischemic stroke. We performed a multicenter, randomized, placebo-controlled, double-blind study on acute ischemic stroke patients commencing within 72 h of onset. Edaravone was infused at a dose of 30 mg, twice a day, for 14 days. At discharge within 3 months or at 3 months after onset, the functional outcome was evaluated using the modified Rankin Scale. Two hundred and fifty-two patients were initially enrolled. Of these, 125 were allocated to the edaravone group and 125 to the placebo group for analysis. Two patients were excluded because of subarachnoid hemorrhage and disseminated intravascular coagulation. A significant improvement in functional outcome was observed in the edaravone group as evaluated by the modified Rankin Scale (p = 0.0382). Edaravone represents a neuroprotective agent which is potentially useful for treating acute ischemic stroke, since it can exert significant effects on functional outcome as compared with placebo.

No abstract

Severely premature infants are often at increased risk of cerebral hemorrhage and/or ischemic injury caused by immature autoregulatory control of blood flow to the brain. If blood flow is too high, the infant is at risk of hemorrhage, whereas too little blood flow can result in ischemic injury. The development of a noninvasive, bedside means of measuring cerebral hemodynamics would greatly facilitate both diagnosis and monitoring of afflicted individuals. It is to this end that we have developed a near infrared spectroscopy (NIRS) system that allows for quantitative, bedside measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). The technique requires an i.v. injection of the near infrared chromophore indocyanine green. Six newborn piglets, median age of 18 h (range 6 -54 h), median weight of 1.75 kg (range 1.5-2.1 kg), were studied. Measurements of CBF, CBV, and MTT were made at normocapnia, hypocapnia, and hypercapnia to test the technique over a range of hemodynamic conditions. The accuracy of our new approach has been determined by direct comparison with measurements made using a previously validated computed tomography technique. Paired t tests showed no significant difference between computed tomography and NIRS measurements of CBF, CBV, and MTT, and mean biases between the two methods were Ϫ2.05 mL·min Ϫ1 ·100 g Ϫ1 , Ϫ0.18 mL·100 g Ϫ1 , and 0.43 s, respectively. The precision of NIRS CBF, CBV, and MTT measurements, as determined by repeatedmeasures ANOVA, was 9.71%, 13.05%, and 7.57%, respectively. Since the first publication by Jobsis in 1977 (1), NIRS has been used in a variety of studies to investigate cerebral hemodynamics (2, 3). The underlying principles behind the use of NIRS to probe biologic media are relatively simple and have been described in detail elsewhere (1, 4 -8). There exist in biologic tissue four endogenous near infrared (NIR) light absorbers-oxy-Hb (HbO 2 ), deoxy-Hb (Hb), cytochrome oxidase (Cyt), and water. Because HbO 2 and Hb are generally present at relatively low concentrations in tissue, NIR light is able to penetrate tissue to a greater extent than other low-energy forms of light, in some cases up to distances of 8 -9 cm (6).As NIR light enters tissue, it is multiply scattered. The result of this scatter is that the total path length traveled by the NIR light is greater than the physical distance between the points of emission and detection. This extra distance can be accounted for using the differential path length factor (DPF), first described by Delpy et al. (9). With accurate knowledge of the DPF, a modified version of the Beer-Lambert law can be used to determine absolute changes in concentrations of NIR absorbers within tissue:where ⌬c is the change in concentration, ⌬A is the change in attenuation, ␣ is the extinction coefficient, L is the physical distance between emission and detection of NIR light, and B is the DPF. Measurement of concentration changes over time can

Dynamic single-section CT scanning to measure CBV and CBF on the basis of a noncarotid input is a highly accessible and cost-effective blood flow measurement technique.

A primary focus of neurointensive care is the prevention of secondary brain injury, mainly caused by ischemia. A noninvasive bedside technique for continuous monitoring of cerebral blood flow (CBF) could improve patient management by detecting ischemia before brain injury occurs. A promising technique for this purpose is diffuse correlation spectroscopy (DCS) since it can continuously monitor relative perfusion changes in deep tissue. In this study, DCS was combined with a time-resolved near-infrared technique (TR-NIR) that can directly measure CBF using indocyanine green as a flow tracer. With this combination, the TR-NIR technique can be used to convert DCS data into absolute CBF measurements. The agreement between the two techniques was assessed by concurrent measurements of CBF changes in piglets. A strong correlation between CBF changes measured by TR-NIR and changes in the scaled diffusion coefficient measured by DCS was observed (R2 = 0.93) with a slope of 1.05 ± 0.06 and an intercept of 6.4 ± 4.3% (mean ± standard error).