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 ( V_i), (2) the product of extraction fraction and blood flow ( EF), and (3) the clearance rate constant ( k_adb), 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.

Background and Purpose— We investigated whether computed tomography (CT) perfusion–derived cerebral blood flow (CBF) and cerebral blood volume (CBV) could be used to differentiate between penumbra and infarcted gray matter in a limited, exploratory sample of acute stroke patients. Methods— Thirty patients underwent a noncontrast CT (NCCT), CT angiography (CTA), and CT perfusion (CTP) scan within 7 hours of stroke onset, NCCT and CTA at 24 hours, and NCCT at 5 to 7 days. Twenty-five patients met the criteria for inclusion and were subsequently divided into 2 groups: those with recanalization at 24 hours (n=16) and those without (n=9). Penumbra was operationally defined as tissue with an admission CBF <25 mL · 100 g ⁻¹ · min ⁻¹ that was not infarcted on the 5- to 7-day NCCT. Logistic regression was applied to differentiate between infarct and penumbra data points. Results— For recanalized patients, CBF was significantly lower ( P <0.05) for infarct (13.3±3.75 mL · 100 g ⁻¹ · min ⁻¹ ) than penumbra (25.0±3.82 mL · 100 g ⁻¹ · min ⁻¹ ). CBV in the penumbra (2.15±0.43 mL · 100 g ⁻¹ ) was significantly higher than contralateral (1.78±0.30 mL · 100 g ⁻¹ ) and infarcted tissue (1.12±0.37 mL · 100 g ⁻¹ ). Logistic regression using an interaction term (CBF×CBV) resulted in sensitivity, specificity, and accuracy of 97.0%, 97.2%, and 97.1%, respectively. The interaction term resulted in a significantly better ( P <0.05) fit than CBF or CBV alone, suggesting that the CBV threshold for infarction varies with CBF. For patients without recanalization, CBF and CBV for infarcted regions were 15.1±5.67 mL · 100 g ⁻¹ · min ⁻¹ and 1.17±0.41 mL · 100 g ⁻¹ , respectively. Conclusions— We have shown in a limited sample of patients that CBF and CBV obtained from CTP can be sensitive and specific for infarction and should be investigated further in a prospective trial to assess their utility for differentiating between infarct and penumbra.

Preterm infants are highly susceptible to ischemic brain injury; consequently, continuous bedside monitoring to detect ischemia before irreversible damage occurs would improve patient outcome. In addition to monitoring cerebral blood flow (CBF), assessing the cerebral metabolic rate of oxygen ($CMRO2$) would be beneficial considering that metabolic thresholds can be used to evaluate tissue viability. The purpose of this study was to demonstrate that changes in absolute $CMRO2$ could be measured by combining diffuse correlation spectroscopy (DCS) with time-resolved near-infrared spectroscopy (TR-NIRS). Absolute CBF was determined using bolus-tracking TR-NIRS to calibrate the DCS measurements. Cerebral venous blood oxygenation ($SvO2$) was determined by multiwavelength TR-NIRS measurements, the accuracy of which was assessed by directly measuring the oxygenation of sagittal sinus blood. In eight newborn piglets, $CMRO2$ was manipulated by varying the anesthetics and by injecting sodium cyanide. No significant differences were found between the two sets of $SvO2$ measurements obtained by TR-NIRS or sagittal sinus blood samples and the corresponding $CMRO2$ measurements. Bland–Altman analysis showed a mean $CMRO2$ difference of $0.0268±0.8340mL$$O2/100g/min$ between the two techniques over a range from 0.3 to 4 mL $O2/100g/min$.

Cerebral metabolic rate of oxygen (CMRO2), the rate at which O2 is consumed in the brain by metabolic processes, is one of the most useful measures of normal brain function. The present study investigated the use of near-infrared spectroscopy (NIRS) in the noninvasive measurement of O2 extraction fraction (OEF) and CMRO2 in the newborn piglet. Indomethacin, although used successfully to effect closure of patent ductus arteriosus in the preterm infant, is known to cause transient reductions in cerebral blood flow (CBF) in both infant and adult humans and pigs. As a test of the NIRS method, the present study also examined the effect of indomethacin-induced reductions in CBF on both OEF and CMRO2. CBF, OEF, and CMRO2 were assessed in 20 newborn piglets, 0.2–3.0 d old. Ten piglets received 0.2 mg/kg of indomethacin infused over 30 min; remaining piglets received saline infusion as control. CBF, OEF, and CMRO2 measurements were performed before infusion and at 30-min intervals for a period of 90 min post-infusion. Saline infusion elicited no response in CBF, OEF, or CMRO2. Immediately after indomethacin infusion, CBF decreased 18.1% below (p < 0.05) and OEF increased 26.2% above (p < 0.05) pre-infusion values, whereas CMRO2 showed no significant changes throughout the study. Both CBF and OEF returned to baseline within 60 min after infusion of indomethacin. The proficiency of NIRS in the measurement of OEF and CMRO2 was demonstrated through the observation of transient increases in OEF, which served to maintain CMRO2 during indomethacin-induced reductions in CBF.

A primary focus of neurointensive care is monitoring the injured brain to detect harmful events that can impair cerebral blood flow (CBF), resulting in further injury. Since current noninvasive methods used in the clinic can only assess blood flow indirectly, the goal of this research is to develop an optical technique for measuring absolute CBF. A time-resolved near-infrared (TR-NIR) apparatus is built and CBF is determined by a bolus-tracking method using indocyanine green as an intravascular flow tracer. As a first step in the validation of this technique, CBF is measured in newborn piglets to avoid signal contamination from extracerebral tissue. Measurements are acquired under three conditions: normocapnia, hypercapnia, and following carotid occlusion. For comparison, CBF is concurrently measured by a previously developed continuous-wave NIR method. A strong correlation between CBF measurements from the two techniques is revealed with a slope of $0.79±0.06$, an intercept of $−2.2±2.5ml∕100g∕min$, and an $R2$ of $0.810±0.088$. Results demonstrate that TR-NIR can measure CBF with reasonable accuracy and is sensitive to flow changes. The discrepancy between the two methods at higher CBF could be caused by differences in depth sensitivities between continuous-wave and time-resolved measurements.