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Abstract

Hypercapnia induces cerebral vasodilation and increases cerebral blood flow (CBF), and hypocapnia induces cerebral vasoconstriction and decreases CBF. The relation between changes in CBF and cerebral blood volume (CBV) during hypercapnia and hypocapnia in humans, however, is not clear. Both CBF and CBV were measured at rest and during hypercapnia and hypocapnia in nine healthy subjects by positron emission tomography. The vascular responses to hypercapnia in terms of CBF and CBV were 6.0 ± 2.6%/mm Hg and 1.8 ± 1.3%/mm Hg, respectively, and those to hypocapnia were −3.5 ± 0.6%/mm Hg and −1.3 ± 1.0%/mm Hg, respectively. The relation between CBF and CBV was CBV = 1.09 CBF^0.29. The increase in CBF was greater than that in CBV during hypercapnia, indicating an increase in vascular blood velocity. The degree of decrease in CBF during hypocapnia was greater than that in CBV, indicating a decrease in vascular blood velocity. The relation between changes in CBF and CBV during hypercapnia was similar to that during neural activation; however, the relation during hypocapnia was different from that during neural deactivation observed in crossed cerebellar diaschisis. This suggests that augmentation of CBF and CBV might be governed by a similar microcirculatory mechanism between neural activation and hypercapnia, but diminution of CBF and CBV might be governed by a different mechanism between neural deactivation and hypocapnia.

Keywords

CBF CBV PET

Hypercapnia induces cerebral vasodilation and increases cerebral blood flow (CBF), and hypocapnia induces cerebral vasoconstriction and decreases CBF (Kety and Schmidt, 1948; Raper et al., 1971; Ito et al., 2000). Because the vascular responsiveness to vasodilator in the brain with insufficient cerebral perfusion pressure is reduced by autoregulatory vasodilation (Kanno et al., 1988), hypercapnia can be used to estimate cerebral perfusion reserve in occlusive cerebrovascular disease (Herold et al., 1988; Levine et al., 1991; Kuwabara et al., 1997).

An increase in CBF with no change in the density of perfused capillaries during hypercapnia has been observed in animals at the microvascular level (Gobel et al., 1989); change in capillary diameter during hypercapnia and hypocapnia has also been observed in animals (Duelli and Kuschinsky, 1993). The increase in cerebral blood volume (CBV), including arterial, capillary, and venous blood volume, during hypercapnia in animals has been shown to be less than the increase in CBF (Grubb et al., 1974; Bereczki et al., 1993; Keyeux et al., 1995; Lee et al., 2001). The degree of decrease in CBV during hypocapnia in animals has also been shown to be less than that in CBF (Grubb et al., 1974). To our knowledge, however, there has been no investigation into the relation between changes in CBF and changes in CBV during hypercapnia and hypocapnia in humans.

Previously, we investigated changes in both regional CBF and CBV in humans during visually evoked neural activation; investigation was by positron emission tomography (PET) with H₂¹⁵O and ¹¹CO (Ito et al., 2001). Our results indicated that when the increase in CBF is great, it is caused primarily by an increase in vascular blood velocity rather than by an increase in CBV. We also investigated changes in both regional CBF and CBV in humans during neural deactivation observed under crossed cerebellar diaschisis; investigation was by PET with H₂¹⁵O and C¹⁵O (Ito et al., 2002). The degree of decrease in CBF and CBV during neural deactivation was almost identical, indicating no change in vascular blood velocity during neural deactivation.

In the present study, changes in CBF and CBV during hypercapnia and hypocapnia were measured in humans by PET with H₂¹⁵O and ¹¹CO, respectively. H₂¹⁵O and ¹¹CO PET studies were performed at rest and during hypercapnia and hypocapnia in each of nine normal subjects, and changes in CBF and CBV were determined.

METHODS

Subjects

The study was approved by the Ethics Committee of the Akita Research Institute of Brain and Blood Vessels. Nine healthy men (20 to 24 years of age) were recruited and gave written informed consent to participate. The subjects were judged healthy on the basis of their medical history, a physical examination, blood screening analysis, and magnetic resonance imaging (MRI) of the brain.

PET procedures

The Headtome-V PET system (Shimadzu Corp., Kyoto, Japan) used for all studies provides 47 slices with center-to-center distances of 3.125 mm (Iida et al., 1996). The intrinsic spatial resolution was 4.0 mm in plane and 4.3 mm full width at half maximum (FWHM) axially. Reconstruction with a Butterworth filter resulted in a final in-plane resolution of approximately 8 mm full width at half maximum (FWHM). Data were acquired in two-dimensional mode.

PET measurements with H₂¹⁵O and ¹¹CO were performed in each subject under three conditions: at rest (baseline), during hypercapnia, and during hypocapnia with the eyes closed. Hypercapnia was induced by inhalation of 7% CO₂ gas starting 1 minute before scanning and continuing until the end of scanning. Hypocapnia was induced by hyperventilation starting 1 minute before scanning and continuing until the end of scanning (Kanno et al., 1988). H₂¹⁵O and ¹¹CO PET studies were performed at rest, during hypercapnia, and during hypocapnia in four subjects; studies were performed at rest, during hypocapnia, and then during hypercapnia in the other five subjects.

H₂¹⁵O PET study

H₂¹⁵O PET studies were performed at rest and during hypercapnia and hypocapnia, after transmission scanning. The interval between studies was at least 15 minutes. The protocol consisted of 180 seconds of static scanning after continuous intravenous infusion of H₂¹⁵O during 2 minutes. The dose of radioactivity was 1.1 to 1.8 GBq at the start of scanning. The arterial input function was obtained by continuous beta probe measurement of radioactivity in arterial whole blood taken from the radial artery. Dispersion and delay in the beta detector system and in the internal arterial line were corrected as reported previously (Iida et al., 1986, 1988). Cerebral blood flow images were calculated by the autoradiographic method (Raichle et al., 1983; Kanno et al., 1987; Iida et al., 1998). Two arterial blood samples were taken—one at the beginning and one at the end of scanning—for measurement of arterial CO₂ gaseous pressure. A head fixation system with individualized molds for each subject was used to minimize head movement during PET.

¹¹CO PET study

¹¹CO PET studies were then performed to measure CBV (Phelps et al., 1979). After 5 minutes of continuous inhalation of ¹¹CO gas (approximately 5 GBq by mouth), static PET scanning was started at 5, 19, and 33 minutes. Each scan was performed at rest and during hypercapnia and hypocapnia, with a scan time of 4 minutes. Three arterial blood samples were taken during each scanning for measurement of whole blood radioactivity concentration and arterial CO₂ gaseous pressure.

Data analyses

All CBF and CBV images were transformed into the standard brain size and shape by linear and nonlinear parameters with the SPM99 system for anatomic standardization (Friston et al., 1990). Thus, the brain images of all subjects had the same anatomic format. Regions of interest were drawn on all standardized images. Elliptical regions of interest were defined for the cerebellar cortex and four cerebral cortices representing the frontal, temporal, parietal, and occipital lobes (16 mm × 32 mm). Average values of four cerebral cortices were calculated.

The vascular response to change in PaCO₂ was calculated as the percentage changes in CBF and CBV per absolute change in PaCO₂ (mm Hg) in response to hypercapnia and hypocapnia (Kanno et al., 1988):

Vascular response to PaCO₂ change in CBF (%/mm Hg) =

100 \times \frac{{CBF}_{a} - {CBF}_{r}}{{CBF}_{r}} \times \frac{1}{| P_{a} {CO}_{2 a} - P_{a} {CO}_{2 r} |}

(1)

Vascular response to PaCO₂ change in CBV (%/mm Hg) =

100 \times \frac{{CBV}_{a} - {CBV}_{r}}{{CBV}_{r}} \times \frac{1}{| P_{a} {CO}_{2 a} - P_{a} {CO}_{2 r} |}

(2)

where the subscripts “r” and “a” denote rest and activation conditions (hypercapnia or hypocapnia), respectively.

The vascular mean transit time (MTT) was calculated as follows (Powers et al., 1984):

MTT = \frac{CBV}{CBF}

(3)

RESULTS

Average PaCO₂, PaO₂, pH, blood pressure, and heart rate during each PET scanning are given in Table 1. PaCO₂ values increased significantly during hypercapnia (P < 0.001) and decreased significantly during hypocapnia (P < 0.001) in both H₂¹⁵O and ¹¹CO PET studies. Arterial hemoglobin concentrations and hematocrit were 14.9 ± 1.3 g/dL and 44.4 ± 3.6%, respectively (mean ± SD). Significant differences between H₂¹⁵O and ¹¹CO PET studies were observed in systolic and diastolic blood pressures obtained during baseline study and heart rate obtained during hypercapnia (P < 0.05). No significant differences between studies were observed in PaCO₂, PaO₂, or pH.

TABLE 1.

P_aco₂, P_ao₂, pH, BP and HR during PET scanning

	P_aco₂ (mm Hg)	P_aO₂ (mm Hg)	pH	BP (systole/diastole) (mm Hg)	HR (beats/min)
H₂¹⁵O PET
Baseline	41.7 ± 1.6	98.7 ± 4.8	7.415 ± 0.018	123 ± 20/66 ± 9	70 ± 10
Hypercapnia	46.9 ± 2.7*	120.4 ± 8.0*	7.375 ± 0.022*	130 ± 17/74 ± 7*	77 ± 10
Hypocapnia	31.0 ± 2.2*	134.3 ± 7.8*	7.513 ± 0.022*	125 ± 24/71 ± 14	73 ± 10
¹¹CO PET
Baseline	40.4 ± 2.3	101.5 ± 5.3	7.414 ± 0.025	133 ± 19†/77 ± 10†	68 ± 13
Hypercapnia	45.8 ± 3.2*	120.9 ± 6.4*	7.371 ± 0.023*	134 ± 17/76 ± 12	70 ± 9†
Hypocapnia	29.9 ± 3.8*	133.2 ± 10.0*	7.518 ± 0.043*	132 ± 13/77 ± 12	74 ± 12

Values are shown as mean ± SD.

Significant differences from baseline values (paired t-test, P < 0.001)

†

Significant differences between H₂¹⁵O and ¹¹CO PET studies (paired t-test, P < 0.05)

BP, blood pressure; HR, heart rate; PET, positron emission tomography.

Baseline CBF, CBV, MTT, and values during hypercapnia and hypocapnia in the cerebral cortex and cerebellum are given in Table 2. Both CBF and CBV increased significantly during hypercapnia (P < 0.001–0.05) and decreased significantly during hypocapnia (P < 0.001–0.05). Mean transit time decreased significantly during hypercapnia (P < 0.001–0.01), and increased significantly during hypocapnia (P < 0.001–0.01). Average CBF and CBV images for baseline, hypercapnia, and hypocapnia conditions are shown in Fig. 1. Both CBF and CBV increased globally during hypercapnia and decreased globally during hypocapnia.

TABLE 2.

CBF, CBV, and MTT during the three study conditions

	Baseline	Hypercapnia	Hypocapnia
Cerebral cortex
CBF (mL/100 mL/min)	52.8 ± 11.8	67.9 ± 11.8*	32.1 ± 2.9*
CBV (mL/100 mL)	3.3 ± 0.3	3.7 ± 0.3*	3.0 ± 0.2*
MTT (sec)	3.9 ± 0.6	3.3 ± 0.5†	5.6 ± 0.4*
Cerebellum
CBF (mL/100 mL/min)	62.0 ± 12.4	99.7 ± 22.2*	36.7 ± 3.4*
CBV (mL/100 mL)	3.5 ± 0.4	4.1 ± 0.5‡	3.2 ± 0.3‡
MTT (sec)	3.5 ± 0.6	2.5 ± 0.6†	5.3 ± 0.7*

Values are shown as mean ± SD.

Significant differences from baseline values (paired t-test):

P < 0.001;

†

P < 0.01;

‡

P < 0.05.

CBF, cerebral blood flow; CBV, cerebral blood volume; MTT, mean transit time.

FIG. 1.

Average cerebral blood flow (CBF) and cerebral blood volume (CBV) images for baseline, hypercapnia, and hypocapnia conditions. All images are transaxial sections parallel to the anterior–posterior commissure (AC-PC) line. The slice positions are −36, 0, and 34 mm from the AC-PC line in the standard brain. Scale maximum and minimum values are 70 and 0 mL·100 mL⁻¹min⁻¹ for CBF, and 8 and 0 mL/100 mL for CBV, respectively.

Changes in both CBF and CBV during hypercapnia and hypocapnia are given in Table 3. Significant differences between changes in CBF and CBV were observed for both hypercapnia and hypocapnia in both the cerebral cortex and cerebellum (P < 0.001–0.01).

TABLE 3.

Percentage changes in both CBF and CBV in response to hypercapnia and hypocapnia for the cerebral cortex and cerebellum

	Hypercapnia	Hypocapnia
Cerebral cortex
CBF	30.5 ± 14.6%	−37.5 ± 9.5%
CBV	9.6 ± 5.7%†	−10.6 ± 5.2%*
Cerebellum
CBF	62.2 ± 29.9%	−39.0 ± 12.0%
CBV	15.7 ± 15.0%†	−8.8 ± 9.7%*

Values are shown as mean ± SD.

Significant differences between percentage changes in CBF and CBV (paired t-test):

P < 0.001;

†

P < 0.01.

CBF, cerebral blood flow; CBV, cerebral blood volume.

Vascular responses in terms of both CBF and CBV in response to changes in PaCO₂ due to hypercapnia and hypocapnia are given in Table 4. Significant differences between vascular responses in terms of CBF and CBV were observed for both hypercapnia and hypocapnia in the cerebral cortex (P < 0.001–0.01) and for hypercapnia in the cerebellum (P < 0.05).

TABLE 4.

Vascular responses in both CBF and CBV in response to changes in P_aco₂ caused by hypercapnia and hypocapnia for the cerebral cortex and cerebellum

	Hypercapnia	Hypocapnia
Cerebral cortex
CBF (%/mm Hg)	6.0 ± 2.6	−3.5 ± 0.6
CBV (%/mm Hg)	1.8 ± 1.3†	−1.3 ± 1.0*
Cerebellum
CBF (%/mm Hg)	12.0 ± 3.8	−3.6 ± 0.6
CBV (%/mm Hg)	4.5 ± 6.3‡	−1.5 ± 3.1

Values are shown as mean ± SD.

Significant differences between vascular responses in CBF and CBV (paired t-test):

P < 0.001;

†

P < 0.01;

‡

P < 0.05.

CBF, cerebral blood flow; CBV, cerebral blood volume.

The relation between CBF and CBV values for baseline, hypercapnia, and hypocapnia conditions in the cerebral cortex is shown for all subjects in Fig. 2. The relation between CBF and CBV was determined by leastsquares analysis as previously reported (Grubb et al., 1974): CBV = 1.09CBF^0.29.

FIG. 2.

The relations between cerebral blood flow and cerebral blood volume values for baseline, hypercapnia, and hypocapnia conditions for all subjects.

DISCUSSION

In our study, the increase in CBF was greater than that in CBV during hypercapnia, resulting in a decrease in MTT. This indicates that the vascular blood velocity increases during hypercapnia if the vascular path length does not change. The degree of decrease in CBF during hypocapnia was also greater than that in CBV, resulting in an increase in MTT. This indicates that the vascular blood velocity decreases during hypocapnia if the vascular path length does not change. The present results are closely aligned with reported findings in animals studied during hypercapnia and hypocapnia (Grubb et al., 1974; Bereczki et al., 1993; Keyeux et al., 1995; Lee et al., 2001). The relation between CBF and CBV values during changes in PaCO₂ in monkeys has been estimated as CBV = 0.80CBF^0.38. (Grubb et al., 1974). The relation between CBF and CBV during changes in PaCO₂ in humans was determined in the present study to be CBV = 1.09CBF^0.29, which corresponded closely with that reported previously. According to Poiseuille's law, the flow of blood through a vessel is proportional to the fourth power of the vessel diameter; blood volume is proportional to the square of the diameter. Thus, CBV = cCBF^0.5 (c: constant) (Ito et al., 2001; Ito et al., 2002), which corresponds to the relation between CBF and CBV we observed.

In animal studies at the microvascular level, an increase in CBF with no change in density of perfused capillaries during hypercapnia has been observed (Gobel et al., 1989); however, change in capillary diameter during hypercapnia and hypocapnia has also been observed (Duelli and Kuschinsky, 1993). The CBV measured by PET is made up of three components: artery, capillary, and vein CBV (Lammertsma and Jones, 1983; Mintun et al., 1984). Although the capillary fraction is only a small percentage of the CBV (Mintun et al., 1984), the present relation between changes in CBF and CBV during changes in PaCO₂ might be similar to that at the microvessel level.

Previously, we investigated changes in both regional CBF and CBV in humans during visually evoked neural activation by PET (Ito et al., 2001). Our results indicated that when the increase in CBF is great, it is caused primarily by an increase in vascular blood velocity rather than by an increase in CBV. The relation between CBF and CBV during neural activation was CBV = 0.88CBF^0.30 (Ito et al., 2001), which corresponds closely with the present results. This suggests that augmentation for CBF and CBV might be governed by a common microcirculatory mechanism during both neural activation and hypercapnia. We also used PET to investigate changes in both regional CBF and CBV in crossed cerebellar diaschisis (Ito et al., 2002), which can be considered neural deactivation (Gold and Lauritzen, 2002). The degree of decrease in CBF and CBV during neural deactivation was almost identical (approximately 20% decrease in both CBF and CBV), indicating no change in vascular blood velocity during neural deactivation (Yamauchi et al., 1992; Ito et al., 2002). However, the degree of decrease in CBF during hypocapnia was greater than that in CBV (approximately 40% decrease in CBF and 10% decrease in CBV), indicating a decrease in vascular blood velocity during hypocapnia. The relation between CBF and CBV during neural deactivation was CBV = 0.29CBF^0.56 (Ito et al., 2002). This suggests that diminution for CBF and CBV might be governed by different microcirculatory mechanisms between neural deactivation and hypocapnia.

In determining CBV, we measured the radioactivity concentration of ¹¹CO-labeled hemoglobin. Therefore, CBV was calculated assuming the small- to large-vessel hematocrit ratio to be 0.85 (Phelps et al., 1979). However, a decrease in hematocrit in cerebral vessels during hypercapnia has been reported (Bereczki et al., 1993; Keyeux et al., 1995), perhaps causing an underestimation of CBV during hypercapnia. Change in CBV during hypercapnia was recently measured by perfluorocarbon with ¹⁹F nuclear magnetic resonance (Lee et al., 2001). Because the MRI technique measures plasma blood volume, a decrease in cerebral hematocrit will cause overestimation of CBV. However, the relation between changes in CBF and CBV during hypercapnia measured by MRI was almost identical to the relation we observed (Lee et al., 2001).

In conclusion, changes in both CBF and CBV during hypercapnia and hypocapnia were measured in humans by PET. The increase in CBF was greater than that in CBV during hypercapnia, indicating an increase in vascular blood velocity. The degree of decrease in CBF during hypocapnia was also greater than that in CBV, indicating a decrease in vascular blood velocity. The relation between changes in CBF and CBV during hypercapnia was similar to that during neural activation; however, the relation during hypocapnia differed from that during neural deactivation observed under crossed cerebellar diaschisis. This suggests that augmentation for CBF and CBV might be governed by a common microcirculatory mechanism during both neural activation and hypercapnia, but diminution for CBF and CBV might be governed by different microcirculatory mechanisms between neural deactivation and hypocapnia.

Footnotes

Acknowledgments:

Assistance of members of the Akita Research Institute of Brain and Blood Vessels in performing the PET experiments is gratefully acknowledged.

References

Bereczki

Wei

Otsuka

Hans

Acuff

Patlak

Fenstermacher

(1993) Hypercapnia slightly raises blood volume and sizably elevates flow velocity in brain microvessels. Am J Physiol 264:H1360–H1369

Duelli

Kuschinsky

(1993) Changes in brain capillary diameter during hypocapnia and hypercapnia. J Cereb Blood Flow Metab 13:1025–1028

Friston

Frith

Liddle

Dolan

Lammertsma

Frackowiak

(1990) The relationship between global and local changes in PET scans. J Cereb Blood Flow Metab 10:458–466

Gobel

Klein

Schrock

Kuschinsky

(1989) Lack of capillary recruitment in the brains of awake rats during hypercapnia. J Cereb Blood Flow Metab 9:491–499

Gold

Lauritzen

(2002) Neuronal deactivation explains decreased cerebellar blood flow in response to focal cerebral ischemia or suppressed neocortical function. Proc Natl Acad Sci U S A 99:7699–7704

Grubb

Jr Raichle

Eichling

Ter-Pogossian

(1974) The effects of changes in P_aCO₂ on cerebral blood volume, blood flow, and vascular mean transit time. Stroke 5:630–639

Herold

Brown

Frackowiak

Mansfield

Thomas

Marshall

(1988) Assessment of cerebral haemodynamic reserve: correlation between PET parameters and CO₂ reactivity measured by the intravenous ¹³³xenon injection technique. J Neurol Neurosurg Psychiatry 51:1045–1050

Iida

Kanno

Miura

Murakami

Takahashi

Uemura

(1986) Error analysis of a quantitative cerebral blood flow measurement using H₂¹⁵O autoradiography and positron emission tomography, with respect to the dispersion of the input function. J Cereb Blood Flow Metab 6:536–545

Iida

Higano

Tomura

Shishido

Kanno

Miura

Murakami

Takahashi

Sasaki

Uemura

(1988) Evaluation of regional differences of tracer appearance time in cerebral tissues using [¹⁵O] water and dynamic positron emission tomography. J Cereb Blood Flow Metab 8:285–288

10.

Iida

Miura

Kanno

Ogawa

Uemura

(1996) A new PET camera for noninvasive quantitation of physiological functional parametric images: Headtome-V-dual. In: Quantification of brain function using PET ( Myers

Cunningham

Bailey

Jones

, eds), San Diego: Academic Press, pp 57–61

11.

Iida

Miura

Shoji

Ogawa

Kado

Narita

Hatazawa

Eberl

Kanno

Uemura

(1998) Non-invasive quantitation of cerebral blood flow using oxygen-15-water and a dual-PET system. J Nucl Med 39:1789–1798

12.

Ito

Yokoyama

Iida

Kinoshita

Hatazawa

Shimosegawa

Okudera

Kanno

(2000) Regional differences in cerebral vascular response to P_aCO₂ changes in humans measured by positron emission tomography. J Cereb Blood Flow Metab 20:1264–1270

13.

Ito

Takahashi

Hatazawa

Kim

Kanno

(2001) Changes in human regional cerebral blood flow and cerebral blood volume during visual stimulation measured by positron emission tomography. J Cereb Blood Flow Metab 21:608–612

14.

Ito

Kanno

Shimosegawa

Tamura

Okane

Hatazawa

(2002) Hemodynamic changes during neural deactivation in human brain: a positron emission tomography study of crossed cerebellar diaschisis. Ann Nucl Med 16:249–254

15.

Kanno

Iida

Miura

Murakami

Takahashi

Sasaki

Inugami

Shishido

Uemura

(1987) A system for cerebral blood flow measurement using an H₂¹⁵O autoradiographic method and positron emission tomography. J Cereb Blood Flow Metab 7:143–153

16.

Kanno

Uemura

Higano

Murakami

Iida

Miura

Shishido

Inugami

Sayama

(1988) Oxygen extraction fraction at maximally vasodilated tissue in the ischemic brain estimated from the regional CO₂ responsiveness measured by positron emission tomography. J Cereb Blood Flow Metab 8:227–235

17.

Kety

Schmidt

(1948) The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J Clin Invest 27:484–492

18.

Keyeux

Ochrymowicz-Bemelmans

Charlier

(1995) Induced response to hypercapnia in the two-compartment total cerebral blood volume: influence on brain vascular reserve and flow efficiency. J Cereb Blood Flow Metab 15:1121–1131

19.

Kuwabara

Ichiya

Sasaki

Yoshida

Masuda

Matsushima

Fukui

(1997) Response to hypercapnia in moyamoya disease. Cerebrovascular response to hypercapnia in pediatric and adult patients with moyamoya disease. Stroke 28:701–707

20.

Lammertsma

Jones

(1983) Correction for the presence of intravascular oxygen-15 in the steady-state technique for measuring regional oxygen extraction ratio in the brain: 1. Description of the method. J Cereb Blood Flow Metab 3:416–424

21.

Lee

Duong

Yang

Iadecola

Kim

(2001) Relative changes of cerebral arterial and venous blood volumes during increased cerebral blood flow: implications for BOLD fMRI. Magn Reson Med 45:791–800

22.

Levine

Dobkin

Rozental

Satter

Nickles

(1991) Blood flow reactivity to hypercapnia in strictly unilateral carotid disease: Preliminary results. J Neurol Neurosurg Psychiatry 54:204–209

23.

Mintun

Raichle

Martin

Herscovitch

(1984) Brain oxygen utilization measured with O-15 radiotracers and positron emission tomography. J Nucl Med 25:177–187

24.

Phelps

Huang

Hoffman

Kuhl

(1979) Validation of tomographic measurement of cerebral blood volume with C-11-labeled carboxyhemoglobin. J Nucl Med 20:328–334

25.

Powers

Grubb

Raichle

(1984) Physiological responses to focal cerebral ischemia in humans. Ann Neurol 16:546–552

26.

Raichle

Martin

Herscovitch

Mintun

Markham

(1983) Brain blood flow measured with intravenous H₂¹⁵O. II. Implementation and validation. J Nucl Med 24:790–798

27.

Raper

Kontos

Patterson

Jr (1971) Response of pial precapillary vessels to changes in arterial carbon dioxide tension. Circ Res 28:518–523

28.

Yamauchi

Fukuyama

Kimura

(1992) Hemodynamic and metabolic changes in crossed cerebellar hypoperfusion. Stroke 23:855–860

Changes in Human Cerebral Blood Flow and Cerebral Blood Volume during Hypercapnia and Hypocapnia Measured by Positron Emission Tomography

Abstract

Keywords

METHODS

Subjects

PET procedures

H215O PET study

11CO PET study

Data analyses

RESULTS

DISCUSSION

Footnotes

Acknowledgments:

References

H₂¹⁵O PET study

¹¹CO PET study