p53 expression in neurofibroma and malignant peripheral nerve sheath tumor. An immunohistochemical study of sporadic and NF1-associated tumors

OBJECTIVES--(1) to evaluate regional cerebral blood flow (rCBF) with single photon emission computed tomography and 99mTc-hexamethylpropyleneamine oxime in patients with the idiopathic adult hydrocephalus syndrome (IAHS); (2) to examine regional cerebral blood flow (rCBF), gait, and psychometric functions before and after CSF removal (CSF tap test); (3) to assess abnormalities in subcortical white matter by MRI. METHODS--Thirty one patients fulfilling the criteria for IAHS (according to history and clinical and neuroradiological examination) were studied. Quantified gait measurements, psychometric testing, and rCBF before and after removal of CSF were obtained. Pressure of CSF and CSF outflow conductance were investigated with a constant pressure infusion method. Brain MRI was used to quantify the severity of white matter lesions and periventricular hyperintensities. In IAHS a widespread rCBF hypoperfusion pattern was depicted, with a caudal frontal and temporal grey matter and subcortical white matter reduction of rCBF as the dominant feature. Removal of CSF was not accompanied by a concomitant increase in rCBF. Significant white matter lesions were detected only in a minority of patients by MRI. An altered CSF hydrodynamic state with a higher CSF pressure and lower conductance was confirmed. IAHS is characterised by an abnormal CSF hydrodynamic state, associated with a widespread rCBF reduction with preference for subcortical white matter and frontal-temporal cortical regions. Furthermore in most patients MRI did not show white matter changes suggestive of a coexistent subcortical arteriosclerotic encephalopathy. At least in the idiopathic group of patients with AHS, measurements of rCBF before and after temporary relief of the CSF hydrodynamic disturbance will not provide additional information that would be helpful in the preoperative evaluation but is suggestive of a preserved autoregulation of rCBF.     

Metabolic rate in the right amygdala predicts negative affect in depressed patients

The role of the amygdala in major depression was investigated. Resting regional cerebral metabolic rate (rCMRglu) was measured with [18F]fluorodeoxyglucose positron emission tomography (PET) in two samples of subjects using two different PET cameras. The samples consisted of 10 and 17 medication-free depressives and 11 and 13 controls, respectively. Using coregistration of PET and magnetic resonance images, regions were individually delineated for the amygdala and thalamus, the latter of which was used as a control region. Within the depressed groups, right amygdalar rCMRglu was positively correlated with negative affect. Thalamic rCMRglu was not related to negative affect, and amygdalar rCMRglu accounted for a significant portion of variance in depressives' negative affect scores over and above the contribution of thalamic rCMRglu.     

Carotid artery stenosis in peripheral vascular disease

We describe the implementation and validation of a combined dynamic-autoradiographic approach for measuring the regional cerebral blood flow (rCBF) with 15O-butanol. From arterial blood data sampled at a rate of 1 s and list mode data of the cerebral radioactivity accumulated over 100 s, the time shift between blood and tissue curves, the dispersion constant DC, the partition coefficient p, and the CBF were estimated by least squares fitting. Using the fit results, a pixel-by-pixel parametrization of rCBF was computed for a single 40-s (autoradiographic) 15O-butanol uptake image. The mean global CBF found in 27 healthy subjects was 49 +/- 8 ml 100 g-1 min-1. Gray and white matter rCBF were 83 +/- 20 and 16 +/- 3 ml 100 g-1 min-1, respectively, with a corresponding partition coefficient p of 0.77 +/- 0.18 and 0.77 +/- 0.29 ml/g in both compartments. The quantitative images resulted in a significantly higher gray matter rCBF than the autoradiographic images.     

Assessment of brain perfusion by 99mTc-HMPAO SPECT in akinetic mutism due to high-dose intravenous methotrexate therapy

Chemotherapy of the central nervous system may cause neurotoxicity in children with acute lymphocytic leukemia. We evaluated regional blood flow in a 6-year-old child presenting with akinetic mutism, using 99mTc-HMPAO single photon emission tomography (SPECT) following high-dose intravenous methotrexate therapy. While findings in X-ray computerized tomography were decreased density in bilateral basal ganglia and thalamic nuclei with diffusely decreased attenuation of the periventricular white matter, a global, frontal dominant profoundly abnormal perfusion pattern involving both gray and white matter was observed in the SPECT study. Treatment of the central nervous system with high dose intravenous chemotherapy may cause profound abnormalities in white and gray matter blood flow and early assessment of the neurotoxicity may be identified by 99mTc-HMPAO SPECT in the pediatric age group.     

Differentiation of gray matter and white matter perfusion in patients with unilateral internal carotid artery occlusion

In this study, we investigated differences between gray matter and white matter perfusion in patients with a unilateral occlusion of the internal carotid artery (ICA) with dynamic susceptibility contrast. Seventeen patients and 17 control subjects were studied, using T2*-weighted gradient echo acquisition. Gray and white matter regions were obtained by segmentation of inversion recovery MRI. Lesions were excluded by segmentation of T2-weighted MRI. In the symptomatic hemisphere, cerebral blood volume was increased in white matter (P < .05) but not in gray matter. No cerebral blood flow changes were found. All timing parameters (mean transit time [MTT], time of appearance, and time to peak) showed a significant delay for both white and gray matter (P < .05), but the MTT increase of white matter was significantly larger than for gray matter (P < .05). These findings indicate that differentiation between gray and white matter is essential to determine the hemodynamic effects of an ICA occlusion.     

Cerebral blood volume maps with dynamic contrast-enhanced T1-weighted FLASH imaging: normal values and preliminary clinical results

PURPOSE: In this article we investigate the application of a method that uses the relaxation effect of bolus-like injected Gd-DTPA to quantify regional cerebral blood volume (rCBV). The aim of the study was to determine if the method provides correct rCBV values in healthy subjects as well as to obtain additional diagnostic information for patients with a glioma or stroke. METHOD: Twenty healthy subjects, 12 patients with brain infarctions, and 18 patients with gliomas were examined. A series of 64 sequential images of one slice was recorded during bolus transit with a FLASH sequence. The measured signal intensity-time curves were converted pixel-wise to concentration-time curves from which the rCBV images were calculated applying the indicator dilution method. RESULTS: An average value for gray and white matter of 4.4 +/- 1.6 vol% was obtained for the group of healthy subjects. The grading of the tumors could be classified according to the differences of their corresponding rCBV values. Fifty percent of the infarct patients had to be excluded from the analysis in the acute phase due to mispositioning of the slice and data degradation by gross motion artifact. Different rCBV values were found for areas that develop later into gliotic scars or cystic necrosis. CONCLUSION: The proposed method is easy to apply in clinical routine MR investigations and provides valuable information for noninvasive, preoperative assessment of tumor grading. It can also provide additional criteria for estimating the histological outcome and with it the degree of ischemia in stroke patients.     

Neural activation of the brain with hemodynamic insufficiency

Little is known about how ischemia affects hemodynamic responses to neural activation in the brain. We compare the effects of a motor activation task and a cerebral vasodilating agent, acetazolamide (ACZ), on regional cerebral blood flow (rCBF) in primary sensorimotor cortex (PSM) in six patients with major cerebral artery steno-occlusive lesions without paresis of the upper extremities. Quantitative rCBF was measured in all patients using H2(15)O autoradiographic method and positron emission tomography. The CBF was determined at rest, during a bimanual motor activation task, and 10 minutes after ACZ administration. With bimanual motor activation, rCBF increased significantly in both PSM compared with at rest (P < 0.01 on lesion side, and P < 0.02 on contralateral side). However, rCBF did not increase after ACZ injection in the PSM on the lesion side, whereas rCBF increased significantly in the contralateral PSM after ACZ injection compared with the level at rest. This result suggests that despite a decreased hemodynamic reserve, there is a nearly normal flow response to neural activation, indicating that the mechanism of vasodilation responsible for perfusion change is different for acetazolamide and neural activation. The relations among neural activation, hemodynamic status, and cerebral metabolism in the ischemic stroke patients are discussed.     

A voxel-based method for the statistical analysis of gray and white matter density applied to schizophrenia

We describe a novel technique for characterizing regional cerebral gray and white matter differences in structural magnetic resonance images by the application of methods derived from functional imaging. The technique involves automatic scalp-editing of images followed by segmentation, smoothing, and spatial normalization to a symmetrical template brain in stereotactic Talairach space. The basic idea is (i) to convert structural magnetic resonance image data into spatially normalized images of gray (or white) matter density, effected by segmenting the images and smoothing, and then (ii) to use Statistical Parametric Mapping to make inferences about the relationship between gray (or white) matter density and symptoms (or other pathophysiological measures) in a regionally specific fashion. Because the whole brain sum of gray (or white) matter indices is treated as a confound, the analysis reduces to a characterization of relative gray (or white) matter density on a voxel by voxel basis. We suggest that this is a powerful approach to voxel-based statistical anatomy. Using the technique, we constructed maps of the regional cerebral gray and white matter density correlates of syndrome scores (distinct psychotic symptoms) in a group of 15 schizophrenic patients. There was a negative correlation between the score for the reality distortion syndrome and regional gray matter density in the left superior temporal lobe (P = 0.01) and regional white matter density in the corpus callosum (P < 0.001). These abnormalities may be associated with functional changes predisposing to auditory hallucinations and delusions. This method permits the detection of structural differences within the entire brain (as opposed to selected regions of interest) and may be of value in the investigation of structural gray and white matter abnormalities in a variety of brain diseases.     

Correlation between regional cerebral blood flow and oxidative metabolism. In vivo studies in man

To test the hypothesis that regional cerebral blood flow (rCBF) is normally regulated by regional metabolic activity, rCBF and the regional cerebral metabolic rate for oxygen (rCMRO2) were compared in selected human subjects. In normal subjects and patients with chronic, stable diseases of brain, rCBF correlated well with rCMRO2. In one individual with mild dementia, rCBF and rCMRO2 were measured before and during exercise of the hand and forearm contralateral to the hemisphere studied. Appropriate parallel changes occurred in both rCBF and rCMRO2 during hand exercise. In patients with acute diseases affecting the hemisphere studied, however, the correlation between rCBF and rCMRO2 was unpredictable.     

Right-sided human prefrontal brain activation during acquisition of conditioned fear.

This H/21?O positron emission tomography (PET) study reports on relative regional cerebral blood flow (rCBF) alterations during fear conditioning in humans. In the PET scanner, subjects viewed a TV screen with either visual white noise or snake videotapes displayed alone, then with electric shocks, followed by final presentations of white noise and snakes. Autonomic nervous system responses confirmed fear conditioning only to snakes. To reveal neural activation during acquisition, while equating sensory stimulation, scans during snakes with shocks and white noise alone were contrasted against white noise with shocks and snakes alone. During acquisition, rCBF increased in the right medial frontal gyrus, supporting a role for the prefrontal cortex in fear conditioning to unmasked evolutionary fearrelevant stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Subcortical hypoperfusion associated with asymptomatic white matter lesions on magnetic resonance imaging

BACKGROUND AND PURPOSE: We examined whether hemodynamic and metabolic abnormalities in the cerebral white matter, basal ganglia, and thalamus are associated with asymptomatic white matter lesions (WML) depicted on MR images. METHODS: A positron emission tomographic study with H2(15)O, C15O, and 15O2 was performed in eight normal control subjects without any WML (mean +/- 1 SD age, 68.5 +/- 10.2 years) and in 15 asymptomatic subjects with WML (71.3 +/- 8.5 years) to measure regional cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and oxygen metabolic rate. RESULTS: In the cerebral white matter in the asymptomatic subjects with WML, significantly lower CBF (20.3 +/- 3.9 mL/100 mL per minute; P < .05) and significantly higher OEF (0.43 +/- 0.08; P < .05) were found compared with those for control subjects (23.5 +/- 2.6 mL/100 mL per minute and 0.37 +/- 0.06, respectively). The severity of WML was not related to the magnitude of hypoperfusion. In the basal ganglia, significantly lower CBF (44.9 +/- 6.9 mL/100 mL per minute; P < .01) and significantly higher OEF (0.54 +/- 0.08; P < .01) were found in the WML group than in control subjects (70.1 +/- 12.0 mL/100 mL/min and 0.39 +/- 0.03, respectively). In the thalamus, there was no significant difference in CBF and OEF between the control and WML groups. CONCLUSIONS: Hypoperfusion of the cerebral white matter and basal ganglia in asymptomatic WML subjects may be induced by the arteriosclerosis of long penetrating medullary arteries and lenticulostriate arteries but may not be directly related to the production of WML. The role of hypoperfusion in the production of WML and acceleration of its development remains to be elucidated.     

Comparison of technetium-99m-ECD to Xenon-133 SPECT in normal controls and in patients with mild to moderate regional cerebral blood flow abnormalities

Technetium-99m-1,1-ethyl cysteinate dimer (ECD) has been proposed as a "chemical microsphere" for SPECT measurement of regional cerebral blood flow (rCBF). However, its distribution has not yet been compared in humans to an established rCBF measure. Therefore, we compared the uptake and distribution of ECD with rCBF measured by 133Xe SPECT in subjects with mild to moderate flow abnormalities and in normal volunteers. Blood and urine chemistries and vital signs were unchanged from pre-ECD values up to seven days postinjection. Profile plots demonstrated pattern agreement between rCBF ratios (133Xe) and ECD count density ratios. A significant correlation of rCBF ratios to ECD count density ratios was observed (r = 0.77), with a slope of 0.64 and intercept of 0.36. To explore whether or not the relationship between rCBF and ECD was dependent on absolute flow, ECD region of interest data were expressed in units of ml/min/100 g by equating global CBF (133Xe) and ECD global count density. A closer correlation (r = 0.88) was found for these data than for the count ratio data. The slope was closer to one (m = 0.83) and the intercept was closer to zero (b = 8.2). Also, a significant correlation was observed between ECD-derived rCBF and 133Xe rCBF in the lesion area (r = 0.92) for patients with well-demarcated rCBF lesions. The slope (0.80) suggested a slight underestimation of lesion flow by ECD. Finally, ECD clearance from cortical gray matter ROIs derived from high-resolution scans from 1 to 4 hr postinjection was slow (2.4%/hr). In summary, ECD is a safe and effective marker of regional cerebral perfusion. The distribution of ECD is linearly related to rCBF measured by 133Xe SPECT, although our data suggest a mild underestimation of flow at the high end of the normal range.     

No evidence for an ischemic penumbra in massive experimental intracerebral hemorrhage

OBJECTIVES: To determine the effect of massive intracerebral hemorrhage (ICH) on regional cerebral blood flow (rCBF) and metabolism, and to test the hypothesis that there is persistent ischemia in the perihematoma region after ICH. BACKGROUND: Cerebral ischemia is postulated to be one of the mechanisms of neural injury after ICH. Presumably the hematoma induces ischemia by mechanical compression of the surrounding microvasculature. METHODS: The authors induced ICH in eight anesthetized mongrel dogs by autologous blood injection (7.5 mL) under arterial pressure in the deep white matter adjacent to the left basal ganglia. They measured serial rCBF using radiolabeled microspheres in regions around and distant to the hematoma, as well as cerebral oxygen extraction, oxygen consumption (CMRO2), glucose utilization, and lactate production by serial sampling of cerebral venous blood from the sagittal sinus. Mean arterial pressure (MAP) and intracranial pressure (ICP) were monitored continuously. All measurements were recorded at 0.5, 1.0, 2.0, 3.5, and 5.0 hours after induction of ICH and compared with prehematoma values. Evans Blue dye was injected at the end of the experiment, and intensity of staining was compared with three control animals. RESULTS: Compared with prehematoma ICP (12.5+/-2.0 mm Hg, mean+/-standard error), significant elevation in ICP was observed after ICH peaking at 5 hours (34.4+/-5.2 mm Hg). Compared with prehematoma MAP (125.8+/-7.0 mm Hg), significant elevation in MAP was observed at 120 minutes after onset of hematoma (139.1+/-4.6 mm Hg), with return to the prehematoma value by 5 hours. There were no significant changes observed in cerebral oxygen extraction (51.4+/-4.3% versus 44.8+/-4.9%) and CMRO2 (1.8+/-0.3 versus 1.64+/-0.2 mL O2/100 g/min) at 5 hours posthematoma (or any other posthematoma measurement) compared with prehematoma values. There were no significant differences observed in rCBF in the perihematoma gray (18.2+/-0.9 mL/100 g/min versus 20.1+/-1.5 mL/100 g/min) or white matter (15.6+/-1.4 mL/100 g/min versus 15.3+/-1.1 mL/100 g/min) at 5 hours posthematoma (or any other posthematoma measurement) compared with prehematoma values. No changes were observed in cerebral glucose utilization, lactate production, and rCBF in other regions after introduction of ICH. Permeability of the blood-brain barrier was more prominent in the ipsilateral hemisphere in animals with ICH compared with control animals. CONCLUSIONS: Despite a prominent increase in ICP and MAP after ICH, the authors found no evidence to support the presence of an ischemic penumbra in the first 5 hours after ICH. Thus, other mechanisms for acute neural injury and late rCBF changes after ICH must be investigated.     

Increased circulating antiganglioside antibodies in primary and secondary progressive multiple sclerosis

We report the case of an infant with Sturge-Weber syndrome whose regional cerebral blood flow (rCBF) showed an increase and a subsequent decrease. As compared with simultaneous CT and MR findings, we speculate that the transient increase in rCBF reflects the neuronal reaction to hypoxia caused by congestion.     

Analysis of Parkinson's disease and related syndromes using 123I-IMP-SPECT with the ARG method

We studied regional cerebral blood flow (rCBF) in 8 patients with non-demented Parkinson's disease (PD). 1 patient with progressive supranuclear palsy (PSP), 1 patient with multiple system atrophy (MSA), and 7 normal control subjects using single photon emission computed tomography (SPECT) with the IMP-ARG method. Regions of interest were studied in the cerebral cortex (upper frontal, lower frontal, temporal, occipital, parietal), thalamus, basal ganglia, and cerebellum. In patients with PD, rCBF was normal in 4/8, and decreased in occipital lobe in 4/8. In patient with PSP, rCBF was decreased in the upper and lower frontal lobes, and in the cerebellum. In patient with MSA, rCBF was diminished in the cerebellum. The results of our study were almost compatible with the conventional rCBF study by positron emission tomography (PET), however, the decrease of rCBF in occipital lobe had rarely been reported, suggesting that might be related to visuospatial dysfunction in Parkinson's disease.     

Lactate and pyruvate changes in the cerebral gray and white matter during posthypoxic seizures in newborn pigs

Cerebral lactate rises after chemically induced seizures, but it is not known if this occurs with posthypoxic seizures. We examined changes in lactate and pyruvate in gray and white matter in the newborn pig brain after a hypoxic insult known to produce seizures and permanent brain damage. Fourteen halothane-anesthetized piglets aged 24-49 h, were instrumented with a two-channel scalp EEG and microdialysis probes positioned in white and gray matter. Forty-five minutes of hypoxia were induced by reducing the fraction of inspired O2 to the maximum concentration at which EEG amplitude was < 7 microV. Postinsult EEG was classified as electroconvulsive activity (ECA) (n = 4) or burst suppression (n = 2), persistently low amplitude (n = 2), or intermittent spikes on normal background activity (n = 6). Six hours after the insult the brains were perfusion fixed for histologic probe localization. Plasma lactate and brain lactate had different time courses with brain having a persistently elevated lactate/pyruvate (L/P) ratio. The highest L/P ratios in gray and white matter were in the two pigs with persistently low amplitude EEG. There was no association between onset of electroconvulsive activity and an increase in lactate or L/P ratio. Posthypoxic energy metabolism is disturbed in both gray and white matter probably because of mitochondrial dysfunction. Seizure activity does not increase cerebral lactate or L/P ratio above the already raised levels found in posthypoxic encephalopathy. These findings cast further doubt on the hypothesis that such seizures are, in themselves, damaging.     

Phosphocreatine and creatine kinase in piglet cerebral gray and white matter in situ

Rates of adenosine triphosphate (ATP) metabolism are higher in cerebral gray matter than in white matter. Like other excitable tissues, brain contains a phosphocreatine (PCr)/creatine kinase (CK)/ATP system including cytosolic (B-CK) and mitochondrial (Mi-CK) isozymes. High B-CK activity is present in white and gray matter while Mi-CK is mostly in gray matter. An in situ localizing 31P-NMR technique, one-dimensional chemical shift imaging (1D-CSI), has been used to study the PCr/CK/ATP system in these regions. In the metabolically mature 4-week-old piglet, the PCr/nucleoside triphosphate (NTP) ratio measured by the 1D-CSI technique is at least 50% higher in white than gray matter. Total creatine (Cr), ATP, and total NTP concentrations are the same in rapidly frozen rat white and gray matter, suggesting that PCr/Cr ratio is much higher in white matter. The PCr increases more in gray than white matter between 4 days and 4 weeks of age in piglet brain. The CK catalyzed reaction rate constant, measured by combining the saturation transfer experiment with the 1D-CSI, is also much higher in white than gray matter at both ages. The postnatal maturational increase in the CK rate constant is greater in gray matter. In summary, these differences in PCr concentration and CK reaction rates and isozymes characterize two physiologically different PCr/CK/ATP systems in gray and white matter.     

Adrenoleukodystrophy: cortical hypoperfusion demonstrated with 99mTc-HMPAO SPECT

Regional cerebral blood flow was investigated in an 8-year-old boy with adrenoleukodystrophy by single photon emission computed tomography. The use of 99mTc-hexamethylpropylene amine oxime revealed markedly reduced blood flow in the occipital, parietal, and temporal cortical gray matter, in addition to the anticipated reduction in white matter. The area with a decreased blood flow was more extensive than that detected by x-ray computed tomography.     

Correlation of MR imaging-determined cerebral blood volume maps with histologic and angiographic determination of vascularity of gliomas

OBJECTIVE: Our purpose was to evaluate the relationships between the ratio of maximum relative cerebral blood volume (rCBV) (rCBV ratio = rCBV[tumor]/rCBV[contralateral white matter]) and histologic and angiographic vascularities of gliomas using the gradient-echo echoplanar MR imaging technique. We also evaluated the usefulness of rCBV maps for grading gliomas. SUBJECTS AND METHODS: We examined 30 patients with histologically verified gliomas. Gliomas were classified as glioblastoma, anaplastic glioma with enhancement, anaplastic glioma without enhancement, and low-grade glioma. The maximum rCBV ratio of each glioma was compared with both histologic and angiographic vascularities, and the relationship between the maximum rCBV ratios and each type of glioma was established. RESULTS: The maximum rCBV ratios of the gliomas significantly correlated with both histologic and angiographic vascularities (p < .001). Mean values and SDs of maximum rCBV ratios of each type of tumor were 7.32+/-4.39 for glioblastomas, 5.84+/-1.82 for anaplastic gliomas with enhancement, 1.53+/-0.75 for anaplastic gliomas without enhancement, and 1.26+/-0.55 for low-grade gliomas. The maximum rCBV ratios of the glioblastomas were significantly higher than those of the anaplastic gliomas without enhancement (p = .002) and the low-grade gliomas (p < .001). The maximum rCBV ratios of the anaplastic gliomas with enhancement were higher than those of the anaplastic gliomas without enhancement and the low-grade gliomas, but the differences were not statistically significant (p = .08 and p = .03, respectively). CONCLUSION: The results of perfusion-sensitive MR imaging with gradient-echo echoplanar technique correlated with both histologic and angiographic vascularities.     

Backbone mutations in transmembrane domains of a ligand-gated ion channel: implications for the mechanism of gating

The relationship between regional parenchymal cerebral blood volume (CBV), regional cerebral blood flow (CBF) and the calculated mean transit time (MTT) was investigated in 14 newborn piglets. The effects of combined hypoxic hypoxia (PaO2 = 32 +/- 5 mm Hg) and hypercapnia (paCO2 = 68 +/- 5 mm Hg) were measured in seven animals. Remaining animals served as the control group. During baseline conditions the highest CBF and CVB values were found in the lower brainstem and cerebellum, whereas white matter exhibited the lowest values (p < 0.05). MTT was prolonged within the cerebral cortex (2.34 +/- 0.42 s-1) compared with the thalamic MTT (1.53 +/- 0.38 s-1) (p < 0.05). Under moderate hypoxia/hypercapnia, a CBF increase to the forebrain (p < 0.05) resulted in an elevated brain oxygen delivery (p < 0.05) and so CMRO2 remained unchanged. Moreover, a moderate increase of CBV and a marked shortening of MTT occurred (p < 0.05). The CBV increase was higher in structures with lowest baseline values, i.e., thalamus (66% increase) and white matter (62% increase) (p < 0.05). MTT was between 22% of baseline in the lower brainstem and 49% in white matter (p < 0.05). We conclude that under normoxic and normocapnic conditions the newborn piglets exhibit a comparatively enlarged intraparenchymal CBV. Moderate hypoxia and hypercapnia induced a marked increase in cerebral blood flow which appears to be caused by an increased perfusion velocity, expressed by a strongly reduced mean transit time and by a concomitant CBV increase.