Autonomic control of cerebral circulation: exercise

On the basis of measurement techniques that require steady-state hemodynamic conditions when the measurement of cerebral blood flow (CBF) is being obtained, cerebral autoregulation (CA) maintains CBF stable over a wide range of cerebral perfusion pressures. When an acute (or dynamic) change in cerebral perfusion pressure (seconds) is imposed, CBF is not maintained. For example, after thigh cuff occlusion, its release induces an acute drop in arterial blood pressure (ABP). The sharp decrease in CBF indicates that CA was unable to respond to the dynamic (or rapid) changes in cerebral perfusion pressure. Therefore, control mechanisms of arterial pressure with short time constants must contribute importantly to CBF regulation. In order for CA to be effective, the cerebral perfusion pressure must lie within an autoregulatory range of perfusion pressures. The traditional thinking is that changes in sympathetic tone have a limited effect on CBF at rest. However, moderate- to heavy-intensity exercise causes only moderate increases in CBF despite large increases in sympathetic activity and ABP. Animal studies demonstrate that increases in sympathetic nerve activity cause cerebral vasoconstriction and protection against disruption of the blood-brain barrier. These findings suggest that the regulation of CBF during exercise is modulated not only by CA but also by autonomic nervous system and the arterial baroreflex-mediated control of the systemic circulation.     

Cerebral blood flow response and its association with symptoms during orthostatic hypotension

INTRODUCTION: The preservation of cerebral blood flow with orthostatic hypotension (e.g., following prolonged bed rest or microgravity exposure) is vital for the attenuation of symptoms and the maintenance of consciousness. We tested the hypothesis that decreasing mean arterial pressure (MAP) by > 30% is associated with compromised cerebral autoregulation and orthostatic symptoms during a squat-stand test (SST). METHODS: There were 19 subjects who performed an SST. MAP and middle cerebral artery blood flow velocity (CBFV) were recorded continuously. Subjects were divided retrospectively into those who reported: (1) at least one orthostatic symptom (Sx; n=9); or (2) no orthostatic symptoms (NSx; n=10). Cerebral autoregulation was assessed via the calculation of time to nadir and time to recovery for MAP and CBFV and linear regression analysis of the dynamic changes in MAP and CBFV (within 10 s of standing). RESULTS: On standing, MAP decreased by 37 +/- 2% (NSx) and 42 +/- 4% (Sx) (p = 0.100). CBFV fell by 6% more in the Sx group than in the NSx group (NSx, -33 +/- 1% vs. Sx, -39 +/- 3%, p = 0.032). Cerebral autoregulation remained intact in both groups as indicated by: (1) a faster time to nadir for CBFV compared with MAP; (2) a faster time to recovery for CBFV compared with MAP; and 3) a poor correlation between CBFV and MAP responses on standing (NSx R2 = 0.43; Sx R2 = 0.60). CONCLUSION: Lower cerebral blood flow during severe hypotension may account for the reporting of orthostatic symptoms, despite the maintenance of cerebral autoregulation.     

Decreased cerebral perfusion correlates with increased BOLD hyperoxia response in transgenic mouse models of sickle cell disease.

Neurological complications such as stroke are known consequences of sickle cell disease (SCD). In order to improve methods for the evaluation of stroke risk in SCD, MRI was used to evaluate cerebrovascular function in transgenic mouse models of human SCD. It is hypothesized that oxygen-sensitive imaging in the brain will reveal areas of excess deoxygenation that are either at risk of or the result of vaso-occlusion. Arterial spin labeling (ASL) perfusion was performed in order to correlate BOLD results with microvascular cerebral blood flow. Upon comparison with control animals, there was a relative increase in BOLD hyperoxia response of 42-67% (P < 0.001) in the transgenic mice while cerebral blood flow during normoxia was reduced by 30-40% (P < 0.02). Hyperoxia caused cerebral blood flow to decrease in control mice, whereas blood flow increased in the sickle transgenic mice. These results indicate impairment in brain autoregulation in the sickle cell transgenic mice leading to increased cerebral deoxyhemoglobin. Increased deoxyhemoglobin coupled with reduced perfusion may further increase the risk of vaso-occlusion and stroke. This may reflect polymer reduction or reduced cell adhesion during hyperoxia. The MRI protocol is noninvasive and thus directly applicable to a clinical population.     

Effect of hyperoxia, hypercapnia, and hypoxia on cerebral interstitial oxygen tension and cerebral blood flow.

The assessment of cerebral interstitial oxygen tension (piO(2)) can provide valuable information regarding cerebrovascular physiology and brain function. Compartment-specific cerebral piO(2) was measured by (19)F NMR following the infusion of an oxygen-sensitive perfluorocarbon directly into the interstitial and ventricular space of the in vivo rat brain. (19)F T(1) measurements were made and cerebral piO(2) were obtained through in vitro calibrations. The effects of graded hyperoxia, hypercapnia, and hypoxia on piO(2) and cerebral blood flow (CBF) were investigated. Under normoxia (arterial pO(2) approximately 120 mm Hg), piO(2) was approximately 30 mm Hg and jugular venous pO(2) was approximately 50 mm Hg. During hyperoxia (arterial pO(2) = 90-300 mm Hg), piO(2) increased linearly with the arterial pO(2). Following hypercapnia (arterial pCO(2) = 20-60 mm Hg), the piO(2) increased sigmoidally with increasing CBF. With hypoxia (arterial pO(2) = 30-40 mm Hg), CBF increased approximately 56% and piO(2) decreased to approximately 15 mm Hg. The hypoxia-induced CBF increase was effective to some extent in compensating for the reduced piO(2). This methodology may prove useful for investigating cerebral piO(2) under pathologically or functionally altered conditions. Magn Reson Med 45:61-70, 2001.     

Regulation of cerebral blood flow during exercise

Constant cerebral blood flow (CBF) is vital to human survival. Originally thought to receive steady blood flow, the brain has shown to experience increases in blood flow during exercise. Although increases have not consistently been documented, the overwhelming evidence supporting an increase may be a result of an increase in brain metabolism. While an increase in metabolism may be the underlying causative factor for the increase in CBF during exercise, there are many modulating variables. Arterial blood gas tensions, most specifically the partial pressure of carbon dioxide, strongly regulate CBF by affecting cerebral vessel diameter through changes in pH, while carbon dioxide reactivity increases from rest to exercise. Muscle mechanoreceptors may contribute to the initial increase in CBF at the onset of exercise, after which exercise-induced hyperventilation tends to decrease flow by pial vessel vasoconstriction. Although elite athletes may benefit from hyperoxia during intense exercise, cerebral tissue is well protected during exercise, and cerebral oxygenation does not appear to pose a limiting factor to exercise performance. The role of arterial blood pressure is important to the increase in CBF during exercise; however, during times of acute hypotension such as during diastole at high-intensity exercise or post-exercise hypotension, cerebral autoregulation may be impaired. The impairment of an increase in cardiac output during exercise with a large muscle mass similarly impairs the increase in CBF velocity, suggesting that cardiac output may play a key role in the CBF response to exercise. Glucose uptake and CBF do not appear to be related; however, there is growing evidence to suggest that lactate is used as a substrate when glucose levels are low. Traditionally thought to have no influence, neural innervation appears to be a protective mechanism to large increases in cardiac output. Changes in middle cerebral arterial velocity are independent of changes in muscle sympathetic nerve activity, suggesting that sympathetic activity does not alter medium-sized arteries (middle cerebral artery).CBF does not remain steady, as seen by apparent increases during exercise, which is accomplished by a multi-factorial system, operating in a way that does not pose any clear danger to cerebral tissue during exercise under normal circumstances.     

Human cerebral circulation: positron emission tomography studies

We reviewed the literature on human cerebral circulation and oxygen metabolism, as measured by positron emission tomography (PET), with respect to normal values and of regulation of cerebral circulation. A multicenter study in Japan showed that between-center variations in cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) values were not considerably larger than the corresponding within-center variations. Overall mean +/- SD values in cerebral cortical regions of normal human subjects were as follows: CBF = 44.4 +/- 6.5 ml/100 ml/min; CBV = 3.8 +/- 0.7 ml/100 ml; OEF = 0.44 +/- 0.06; CMRO2 = 3.3 +/- 0.5 ml/100 ml/min (11 PET centers, 70 subjects). Intrinsic regulation of cerebral circulation involves several factors. Autoregulation maintains CBF in response to changes in cerebral perfusion pressure; chemical factors such as PaCO2 affect cerebral vascular tone and alter CBF; changes in neural activity cause changes in cerebral energy metabolism and CBF; neurogenic control of CBF occurs by sympathetic innervation. Regional differences in vascular response to changes in PaCO2 have been reported, indicating regional differences in cerebral vascular tone. Relations between CBF and CBV during changes in PaCO2 and during changes in neural activity were in good agreement with Poiseuille's law. The mechanisms of vascular response to neural activation and deactivation were independent on those of responses to PaCO2 changes. CBV in a brain region is the sum of three components: arterial, capillary and venous blood volumes. It has been reported that the arterial blood volume fraction is approximately 30% in humans and that changes in human CBV during changes in PaCO2 are caused by changes in arterial blood volume without changes in venous blood volume. These findings should be considered in future studies of the pathophysiology of cerebrovascular diseases.     

Cardiovascular neuroregulation during acute exposure to 40, 70, and 100% oxygen at sea level

BACKGROUND: Humans encounter increased partial pressures of inspired oxygen in some kinds of diving as well as during use of hyperoxic mixtures to shorten decompression times and hyperbaric oxygen therapy for decompression sickness or other clinical conditions. Although it is known that hyperoxia may affect cardiovascular regulation, such effects are generally obscured by stress and the diving reflex. In this study, we evaluated cardiovascular neuroregulation for various levels of hyperoxia in a laboratory setting. METHODS:There were 10 healthy adults who were exposed to 21, 40, 70, and 100% oxygen administered via mask as a series of stepwise increases. Subjects breathed at a fixed respiratory rate of 15 breaths x min(-1) while their heart rate (HR) and blood pressure (BP) were measured continuously over 5-min intervals. RESULTS: HR decreased with increasing fraction of inspired oxygen (FIO2) (21%: 65 +/- 9, 40%: 63 +/- 9, 70%: 61 +/- 8, 100%: 60 +/- 8 bpm) and the high-frequency power of HR variability (an index of cardiac parasympathetic activity) increased as FIO2 rose (21%: 773 +/- 565, 40%: 880 +/- 590, 70%: 966 +/- 681, 100%: 1114 +/- 715 ms2); both changes were significant at the 70% and 100% oxygen levels. The low-frequency power of systolic BP variability (an index of vasomotor sympathetic activity) did not change. Low- and high-frequency transfer function gains (indices of arterial-cardiac baroreflex function) increased with FIO2. CONCLUSION: Parasympathetic activity and arterial-cardiac baroreflex function increased with hyperoxia in a dose-dependent manner. This increase may help reduce the likelihood of arrhythmias during diving.     

Ventilatory effects of prolonged hyperoxia at pressures of 1.5-3.0 ATA

INTRODUCTION: It was hypothesized that long-duration exposures to toxic levels of hyperoxia would have effects on respiratory control function or activity. METHODS: Ventilatory parameters of human subjects breathing spontaneously at rest were measured before, during, and after hyperoxia in a study of organ systems' tolerance to toxic O2 exposures at 1.5 ATA (17.7 h), 2.0 ATA (9.3 h), 2.5 ATA (5.7 h) and 3.0 ATA (3.5 h). RESULTS: Average neurotoxic changes in ventilatory parameters during and after prolonged hyperoxia were mild. They included: 1) timing component of ventilation decreased progressively with exposure duration at all four O2 pressures, slopes increased with O2 pressure, changes were significantly late in exposure at 1.5 ATA (-11%) and 3.0 ATA (-10%); 2) post-O2 exposure respiratory rates were significantly above controls by 15% to 59%; and 3) ventilation increased significantly by 20% late during the 1.5 ATA O2 exposures. There were severe neurotoxic changes prior to occurrence of an "O2 convulsion" at 3.0 ATA in one subject. Expiratory time increased by 184%; resultant reductions in respiratory rate and ventilation caused respiratory Pco2 increase, accelerating rate of brain O2 poisoning. Significant nontoxic physiological hyperventilation (21% to 45% above control) early in hyperoxia at all exposure pressures persisted throughout hyperoxia, and reversed post-O2 exposure. Hyperventilation increased and end-tidal Pco2 decreased as inspired PO2 increased. Changes reached maximum values at approximately 2.0 ATA. DISCUSSION: Hyperoxia has concurrent toxic and physiological effects on respiratory control; degrees depend on O2 dose (exposure pressure and duration).     

Absolute cerebral blood flow quantification with pulsed arterial spin labeling during hyperoxia corrected with the simultaneous measurement of the longitudinal relaxation time of arterial blood

Quantitative arterial spin labeling (ASL) estimates of cerebral blood flow (CBF) during oxygen inhalation are important in several contexts, including functional experiments calibrated with hyperoxia and studies investigating the effect of hyperoxia on regional CBF. However, ASL measurements of CBF during hyperoxia are confounded by the reduction in the longitudinal relaxation time of arterial blood (T(1a) ) from paramagnetic molecular oxygen dissolved in blood plasma. The aim of this study is to accurately quantify the effect of arbitrary levels of hyperoxia on T(1a) and correct ASL measurements of CBF during hyperoxia on a per-subject basis. To mitigate artifacts, including the inflow of fresh spins, partial voluming, pulsatility, and motion, a pulsed ASL approach was implemented for in vivo measurements of T(1a) in the rat brain at 3 Tesla. After accounting for the effect of deoxyhemoglobin dilution, the relaxivity of oxygen on blood was found to closely match phantom measurements. The results of this study suggest that the measured ASL signal changes are dominated by reductions in T(1a) for brief hyperoxic inhalation epochs, while the physiologic effects of oxygen on the vasculature account for most of the measured reduction in CBF for longer hyperoxic exposures.     

Inspiratory resistance, cerebral blood flow velocity, and symptoms of acute hypotension

INTRODUCTION: Symptoms of orthostatic intolerance, e.g., following prolonged bed rest and microgravity exposure, are associated with reductions in cerebral blood flow. We tested the hypothesis that spontaneously breathing through an impedance threshold device (ITD) would attenuate the fall in cerebral blood flow velocity (CBFV) during a hypotensive orthostatic challenge and reduce the severity of reported symptoms. METHODS: While breathing through either an active ITD (-7 cm H2O inspiratory impedance) or a sham ITD (no impedance), 19 subjects performed a squat stand test (SST). Symptoms upon stand were recorded on a 5-point scale (1 = normal; 5 = faint) of subject-perceived rating (SPR). To address our hypothesis, only data from symptomatic subjects (SPR > 1 during the sham trial) were analyzed (N = 9). Mean arterial blood pressure (MAP) and mean CBFV were measured continuously throughout the SST and analyzed in time and frequency domains. RESULTS: Breathing with the active ITD during the SST reduced the severity of orthostatic symptoms in eight of the nine symptomatic subjects (sham ITD SPR, 1.9 +/- 0.1; active ITD SPR, 1.1 +/- 0.1), but there was no statistically distinguishable difference in the reduction of mean CBFV between the two trials (sham ITD, -39 +/- 3% vs. active ITD, -44 +/- 3%). High frequency oscillations in mean CBFV, however, were greater during the active ITD trial (7.8 +/- 2.6 cm x s(-2)) compared with the sham ITD trial (2.5 +/- 0.9 cm x s(-2)). CONCLUSIONS: Higher oscillations in CBFV while breathing with the active ITD may account for the reduction in symptom severity during orthostatic hypotension despite the same fall in absolute CBFV.     

A CT method to measure hemodynamics in brain tumors: validation and application of cerebral blood flow maps

BACKGROUND AND PURPOSE: CT is an imaging technique that is routinely used for evaluating brain tumors. Nonetheless, imaging often cannot show the distinction between radiation necrosis and neoplastic growth among patients with recurrent symptoms after radiation therapy. In such cases, a diagnostic tool that provides perfusion measurements with high anatomic detail would show the separation between necrotic areas, which are characterized by low perfusion, from neoplastic areas, which are characterized by elevated CBF. We attempted to validate a dynamic contrast-enhanced CT method for the measurement of regional CBF in brain tumors, and to apply this method by creating CBF maps. METHODS: We studied nine New Zealand White rabbits with implanted brain tumors. We obtained dynamic CT measurements of CBF, cerebral blood volume (CBV), and permeability surface (PS) from the tumor, peritumor, and contralateral normal tissue regions. In all nine rabbits (two studies per rabbit), we compared CT-derived CBF values with those simultaneously obtained by the standard of reference ex vivo microsphere technique. Using CT, we examined three rabbits to assess the variability of repeated CBF and CBV measurements; we examined the other six to evaluate regional CBF reactivity to arterial carbon dioxide tensions. Finally, CT CBF maps were obtained from a rabbit with a brain tumor during normocapnia and hypocapnia. RESULTS: We found a significant linear correlation (r = 0.847) between the regional CT-and microsphere-derived CBF values, with a slope not significantly different from unity (0.99+/-0.03, P>.01). The mean difference between regional CBF measurements obtained using both methods did not significantly deviate from zero (P>.10). During normocapnia, tumor had significantly higher CBF, CBV, and PS values (P<.05) than did peritumor and normal tissues. The variability in CT-derived CBF and CBV measurements in the repeated studies was 13% and 7%, respectively. CT revealed no significantly different CBF CO2 reactivity from that determined by the microsphere method (P>.10). The CBF map of tumor regions during normocapnia showed much higher flow than normal regions manifested, and this difference was reduced on the hypocapnia CBF map. CONCLUSION: The dynamic CT method presented herein provides absolute CBF measurements in brain tumors that are accurate and precise. Preliminary CBF maps derived with this method demonstrate their potential for depicting areas of different blood flow within tumors and surrounding tissue, indicating its possible use in the clinical setting.     

Database of normal human cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen measured by positron emission tomography with 15O-labelled carbon dioxide or water, carbon monoxide and oxygen: a multicentre study in Japan

Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO₂) by positron emission tomography (PET) with oxygen-15 labelled carbon dioxide (C¹⁵O₂) or ¹⁵O-labelled water (H₂ ¹⁵O), ¹⁵O-labelled carbon monoxide (C¹⁵O) and ¹⁵O-labelled oxygen (¹⁵O₂) is useful for diagnosis and treatment planning in cases of cerebrovascular disease. The measured values theoretically depend on various factors, which may differ between PET centres. This study explored the applicability of a database of ¹⁵O-PET by examining between-centre and within-centre variation in values. Eleven PET centres participated in this multicentre study; seven used the steady-state inhalation method, one used build-up inhalation and three used bolus administration of C¹⁵O₂ (or H₂ ¹⁵O) and ¹⁵O₂. All used C¹⁵O for measurement of CBV. Subjects comprised 70 healthy volunteers (43 men and 27 women; mean age 51.8±15.1 years). Overall mean±SD values for cerebral cortical regions were: CBF=44.4±6.5 ml 100 ml^–1 min^–1; CBV=3.8±0.7 ml 100 ml^–1; OEF=0.44±0.06; CMRO₂=3.3±0.5 ml 100 ml^–1 min^–1. Significant between-centre variation was observed in CBV, OEF and CMRO₂ by one-way analysis of variance. However, the overall inter-individual variation in CBF, CBV, OEF and CMRO₂ was acceptably small. Building a database of normal cerebral haemodynamics obtained by the¹⁵O-PET methods may be practicable.     

Method for improving the accuracy of quantitative cerebral perfusion imaging

PURPOSE: To improve the accuracy of dynamic susceptibility contrast (DSC) measurements of cerebral blood flow (CBF) and volume (CBV). MATERIALS AND METHODS: In eight volunteers, steady-state CBV (CBV(SS)) was measured using TrueFISP readout of inversion recovery (IR) before and after injection of a bolus of contrast. A standard DSC (STD) perfusion measurement was performed by echo-planar imaging (EPI) during passage of the bolus and subsequently used to calculate the CBF (CBF(DSC)) and CBV (CBV(DSC)). The ratio of CBV(SS) to CBV(DSC) was used to calibrate measurements of CBV and CBF on a subject-by-subject basis. RESULTS: Agreement of values of CBV (1.77 +/- 0.27 mL/100 g in white matter (WM), 3.65 +/- 1.04 mL/100 g in gray matter (GM)), and CBF (23.6 +/- 2.4 mL/(100 g min) in WM, 57.3 +/- 18.2 mL/(100 g min) in GM) with published gold-standard values shows improvement after calibration. An F-test comparison of the coefficients of variation of the CBV and CBF showed a significant reduction, with calibration, of the variability of CBV in WM (P < 0.001) and GM (P < 0.03), and of CBF in WM (P < 0.0001). CONCLUSION: The addition of a CBV(SS) measurement to an STD measurement of cerebral perfusion improves the accuracy of CBV and CBF measurements. The method may prove useful for assessing patients suffering from acute stroke.     

Imaging of cerebral blood flow-to-volume distribution using SPECT

The ratio between cerebral blood flow (CBF) and cerebral blood volume (CBV) has been proposed as an adequate parameter for the evaluation of cerebrovascular disease (CVD), but to date it has not been assessed with SPECT. We have chosen [123I]IMP for CBF and [99mTc] erythrocytes for CBV imaging. The distribution of both nuclides was investigated in succession using corrections for the contamination of the 99mTc tomograms by 123I. The ratio between 123I and 99mTc tomograms yielded the CBF/CBV distribution. Quantitation was obtained by side-to-side comparison of both hemispheres and of segments containing the territories affected by CVD. In 16 patients with CVD, CBF of the affected territories was 85 +/- 19% (s.d.) when related to the nonsymptomatic contralateral side (100%). When the regions of interest defined within one slice encompassed the entire affected hemisphere, the average CBF was 95 +/- 9%, again related to the nonsymptomatic side. The corresponding CBF/CBV data in 15 of these 16 patients were 60 +/- 32% and 81 +/- 16%. In unilateral internal carotid artery stenoses greater than 50% (N = 10), segmental CBF averaged 81.1 +/- 10.1% and CBF/CBV 49.6 +/- 15.5% relative to the contralateral side. The figures for the hemispheres were 92.8 +/- 5.8 and 75.8 +/- 12.6, respectively. These clinical findings mirror the characteristics of CBF autoregulation, namely the vasodilation of small vessels in decreased arterial perfusion pressure. They, therefore, substantiate SPECT imaging of CBF/CBV for the assessment of cerebral perfusion reserve in CVD.     

Murine orthostatic response during prolonged vertical studies: effect on cerebral blood flow measured by arterial spin-labeled MRI.

High-field MRI scanners are, in principle, well suited for mouse studies; however, many high-field magnets employ a vertical design that may influence the physiological state of the rodent. The purpose of this study was to investigate the orthostatic response of cerebral blood flow (CBF) in mice during a prolonged MR experiment in the vertical position. Arterial spin-labeled (ASL) MRI was performed at 4.7-Tesla with a 15-cm gradient insert that allowed horizontal and vertical CBF measurements to be obtained with the same scanner. For mice in the head-up (HU) vertical position, CBF decreased by approximately 40% compared to the horizontal position, although blood pressure did not differ. Furthermore, CBF values for vertically positioned mice treated with phenylephrine remained constant while blood pressure increased. These results support the conclusion that cerebral autoregulation was intact, albeit at a lower level. Since CBF recovers to near horizontal values by volume loading with saline, it appears that a decrease in central venous pressure (CVP) leading to an increase in sympathetic tone may be a contributing mechanism for lowered CBF. This suggests that using an HU vertical position for MRI in mice may have broader implications, especially for studies that rely on CBF (such as BOLD and fMRI).     

Cerebral blood flow changes in the primary motor and premotor cortices during hyperventilation

The aim of this study was to clarify the regional differences in cerebral blood flow (CBF) change during hyperventilation by using H₂ ¹⁵O and positron emission tomography (PET). Eight healthy volunteers (age: 63.0 ± 8.9 yr.) were studied. Regional CBF was measured by the H₂ ¹⁵O autoradiographic method and PET. Statistical parametric maps (SPM) and conventional regions of interest (ROI) analysis were used for estimating regional CBF differences in the normocapnic state with normal breathing and the hypocapnic state induced by hyperventilation. Total CBF decreased during the hypocapnic state. The SPM revealed that primary motor and premotor cortices were significantly activated by hyperventilation. In these areas absolute CBF values were significantly higher than those in the temporal, occipital and parietal lobes in the hypocapnic state, but there were no significant regional differences in the normocapnic state. In the hypocapnic state induced by hyperventilation, the primary motor and premotor CBF shows combined changes with vasoreaction to hypocapnia and increase in activation due to hyperventilation.     

Developmental changes of cerebral blood flow and oxygen metabolism in children.

BACKGROUND AND PURPOSE: Normal values for cerebral blood flow (CBF) and metabolism in adults are well established, but not for children. Our goal, therefore, was to clarify functional developmental changes of the brain in children in relation to CBF and oxygen metabolism. METHODS: We measured regional CBF (rCBF), regional cerebral metabolic rate for oxygen (rCMRO2), and regional oxygen extraction fraction (rOEF), using positron emission tomography (PET). We performed 30 PET studies in 24 children ages 10 days to 16 years (nine boys, 15 girls), using a steady inhalation method with C(15)O2, (15)O2, and 15CO in order to measure rCBF, rCMRO2, and rOEF, respectively. Regions of interest were set in the primary cerebral areas (sensorimotor, visual, temporal, and parietal cortex), cerebral association areas (frontal and visual association), basal ganglia (lenticular and thalamus), and posterior fossa (brain stem and cerebellar cortex). Subjects were grouped by age (< 1, 1 to < 3, 3 to < 8, and > or = 8 years), and the absolute values of the parameters were compared with those obtained from 10 healthy adults. RESULTS: rCBF and rCMRO2 were lower in the neonatal period than in older children and adults, and increased significantly during early childhood. rCBF was higher as compared with adults, peaking around age 7, whereas rCMRO2 was relatively high, with the last area to increase being the frontal association cortex. Both rCBF and rCMRO2 reached adult values during adolescence. No difference in rCBF was observed between the basal ganglia and the primary cerebral cortex; however, it was prominent in the occipital lobe in every age bracket. No significant changes in rOEF were found during childhood. CONCLUSION: The dynamic changes of rCBF and rCMRO2 observed in children probably reflect the physiologic developmental state within anatomic areas of the brain.     

Negative pressure oxygen breathing and head-down tilt increase nitrogen elimination.

Negative pressure breathing (NPB) increases the rate of nitrogen elimination, which is thought to be due to an increase in cardiac output due to augmented venous return to the heart. Hyperoxia, however, decreases the rate of nitrogen elimination. The effect of hyperoxia on the increase in nitrogen elimination during NPB is not known. We hypothesized that NPB as and head down tilt (HDT), which is also thought to increase cardiac output, would counteract the detrimental effects of hyperoxia on nitrogen elimination. Nitrogen elimination was measured in 12 subjects while they lay supine breathing 100% O2 supplied at atmospheric pressure (control), -10 cm H2O (NPOB(-10)), and -15 cm H2O (NPOB(-15)). Nitrogen elimination was also measured in the subjects while they breathed 100% O2 supplied at atmospheric pressure in the supine position with a 6 degrees HDT. Over a two-hour washout period, NPOB significantly increased nitrogen elimination by more than 14%, although there was no significant difference between NPOB(-10) and NPOB(-15). HDT also significantly increased nitrogen elimination by almost 8%. Neither NPOB nor HDT significantly affected cardiac output but calf blood flow was significantly lower during NOPB(-15). Combining NPB or HDT with 100% oxygen breathing appear to be useful means of increasing nitrogen elimination and should be considered in situations where this effect may be beneficial, such as with oxygen prebreathing prior to decompression.     

Quantitative, non-invasive cerebral blood flow measurements with non-diffusible tracers using a heart-rate-dependent recirculation correction--application in carotid surgery

A general method is described for computation of blood flow from time-activity curves using intravenous injection of the non-diffusible radio-tracer technetium pertechnetate. A technique of recirculation correction is adopted which predicts the start and end of recirculation depending on the patient's heart rate. This method allows one to clearly separate the first transit from the following recirculation. A correction for bolus dispersion of the intravenously injected tracer is also used. The evaluation of cerebral dynamic perfusion studies in 126 unselected adult patients resulted in a normal CBF of 44.5 ml/min/100 g +/- 5% and a decreased CBF of less than 40 ml/min/100 g. The presented method was also applied for flow measurement on the neck vessels. A good correlation between values obtained from these regions and the corresponding cerebral hemispheres was found. The method was also tested in 40 patients with angiographically proven neck vessel stenosis and in 15 patients before and after surgery of carotid stenosis. The results prove that the haemodynamic relevance of carotid stenosis on cerebral blood flow can be quantified. The accuracy of the method is estimated better than 5% for cerebral blood flow values and better than 15% for blood flow values gained over the neck vessel regions.     

Optimal scan time of oxygen-15-labeled water injection method for measurement of cerebral blood flow

We investigated the optimal scan time for obtaining the maximal signal-to-noise (S/N) ratio in cerebral blood flow (CBF) measured by PET imaging following 15O-water bolus injection. We performed sequential measurements with dynamic scans of six subjects injected at rest while listening to white noise. Each dynamic data set was edited into images corresponding to different scan times and were calibrated to CBF images by the table look-up method. For each scan time, we evaluated a pixel-by-pixel standard deviation of the CBF for sequential measurements. The S/N-ratio of CBF in the gray matter was 10.2 +/- 1.7 and 13.6 +/- 2.9 at a 40 and 120 sec scan time, respectively. The gain of the 120-sec over 40-sec scan time corresponds to an 80% increase in the number of trials to reach the same S/N-ratio in a stimulation-activation study. The simulation study supported the results, in which the maximal S/N-ratio of the CBF was demonstrated to be 90 and 120 sec at a CBF of 80 and 60 ml/100 ml/min, respectively. It is concluded that the optimal scan time of the 15O-water bolus injection method is in the interval from 90 to 120 sec.