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(Stroke. 1995;26:2053-2060.)
© 1995 American Heart Association, Inc.

Articles

Can Transcranial Doppler Really Detect Reduced Cerebral Perfusion States?

Hiroshi Sugimori, MD; Setsuro Ibayashi, MD; Kenichiro Fujii, MD; Seizo Sadoshima, MD; Yasuo Kuwabara, MD Masatoshi Fujishima, MD

From the Second Department of Internal Medicine and the Department of Radiology (Y.K.), Faculty of Medicine, Kyushu University, Japan.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose This study was designed to determine whether transcranial Doppler ultrasonography (TCD) may detect reduced perfusion states of the brain in patients with hypertension or diabetes mellitus with suspected cerebral atherosclerosis and arteriolosclerosis.

Methods We determined blood flow velocity with TCD in the middle cerebral artery and cerebrovascular vasodilator responses to carbon dioxide in 22 patients with or without carotid artery occlusive disease and minor stroke; we compared the results with the measurements of cerebral blood flow and oxygen metabolism by positron emission tomography (PET).

Results Blood flow velocity measured by TCD correlated with ipsilateral cerebral blood flow measured by PET in frontal, temporal, and striatal regions and throughout the entire hemisphere (P<.05 to P<.005). Relative changes in blood flow velocity and calculated cerebrovascular resistance tested by carbon dioxide inhalation both correlated closely with regional mean transit time (calculated as the ratio of cerebral blood volume divided by cerebral blood flow) in frontal, striatal, temporal, parietal, and occipital regions and also in the entire hemisphere (P<.05 to P<.0001). TCD variables did not correlate with hemispheric measurements of oxygen metabolism by PET.

Conclusions Although TCD is not useful in assessing impairments of cerebral metabolism, it is useful for detecting abnormalities of cerebral hemodynamics among patients with risk factors for cerebrovascular disease.

Key Words: blood flow velocity • positron emission tomography • transcranial Doppler • vasomotor reactivity • risk factors

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Hypertension and diabetes mellitus are important risk factors contributing to the occurrence and severity of stroke.^{1 2 3 4 5} Many studies suggest that patients with these major risk factors have decreased cerebral perfusion even in the absence of neurological symptoms or strokes.^{6 7 8} Thus, a reliable noninvasive technique for evaluating cerebral hemodynamics should be useful for managing such patients.

TCD, introduced by Aaslid et al,⁹ has been used for noninvasive evaluations of cerebral hemodynamics. Dahl et al^{10 11 12} reported that changes in blood flow velocity measured by TCD correlate well with changes in cerebral blood flow measured by single-photon emission computed tomography; direct comparisons of TCD measurements with estimates of cerebral perfusion and metabolism are available only in the works by Kuwert et al¹³ and Sitzer et al.¹⁴ PET enables reliable and simultaneous measurement of oxygen metabolism and cerebral perfusion states. However, PET is expensive and not generally available. We designed the present study to determine whether cerebral hemodynamics measured by TCD correlate with PET measurements among patients with hypertension or diabetes mellitus and whether TCD measurements correlate with PET measurements of oxygen metabolism.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Subjects
In our clinic, most patients with hypertension or diabetes mellitus routinely undergo TCD examinations. We conducted a PET study of 33 consecutive patients with hypertension or diabetes mellitus in our clinic between June 1992 and July 1994. Eleven patients were excluded from the present study because of insufficient permeability of the skull for Doppler signal (10 patients, aged 54 to 79 years) or prior history of extracranial-intracranial bypass surgery (1 patient). The remaining 22 patients were studied with both PET and TCD; 15 were men and 7 were women, with a mean age of 64 years (range, 33 to 78 years). Each patient underwent carotid color duplex examination, brain CT, and MR imaging (patient 14 did not undergo MRI because of pacemaker implantation). Conventional angiography (n=12) or MR arteriography (n=7) was performed among 19 patients suspected of having cerebral atherosclerosis. We excluded patients with cardioembolic stroke diagnosed on the basis of syndromes including (1) sudden onset of clinical symptoms with maximal focal neurological deficits at onset, (2) sharply marginated hypodense areas involving cortex by brain CT with hemorrhagic infarction, (3) evidence of embolism in other parts of the body, and (4) intracardiac thrombi demonstrated by echocardiography. Subjects were classified into four groups according to presence and size of plaques identified in the carotid arterial systems, regardless of plaque in the posterior circulation: group 1, normal findings (n=7); group 2, hemodynamically insignificant stenosis (<70%, n=6); group 3, unilateral hemodynamically significant stenosis (70%, n=4); and group 4, bilateral hemodynamically significant stenosis (n=5). Clinical, radiological, and vascular findings are shown in Tables 1 and 2.

View this table: [in this window] [in a new window]   Table 1. Clinical Profile of 22 Subjects

View this table: [in this window] [in a new window]   Table 2. Radiological and Vascular Profile of 22 Subjects

Regarding vascular risk factors, 14 of 22 patients had hypertension, 3 had diabetes mellitus, and 5 had both. None had severe anemia (hemoglobin, 10.8 to 16.0 g/dL; hematocrit, 35.2 to 48.6%; respectively). Symptomatic but not disabling small strokes were present in 7 patients (patients 8, 9, 11, 14, 15, 18, and 19). Old ischemic lesions, including white matter hyperintensities on T₂-weighted MRI, were detected in 19 patients with no hemorrhagic lesions detected. Mild to moderate vascular dementia diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R¹⁵ ) was present in 4 patients (Mini-Mental State Examination, 8 to 25 points).

Informed consent was obtained from all patients before they entered the study. In patients with small strokes, cerebral hemodynamics were evaluated at least 1 month after the last stroke.

TCD Study
Resting
TCD examinations were performed within 1 month before PET studies using methods previously described.¹⁶ After the patient rested for 5 minutes in a supine position, a map of the circle of Willis and additional major intracranial arteries was generated by transtemporal TCD mapping with 2-MHz Trans-scan (EME Co Ltd). Sample volumes were fixed at 6 mm in diameter. Maps and sonograms were stored for later analysis on hard IBM-PC compatible disks included in the Trans-scan system. MCAs were insonated at a depth of 45 to 60 mm.

Response to Carbon Dioxide
A TCD probe was fixed on the temporal bone above the zygomatic arch with a probe holder (IMP-2, EME). Blood flow signals of the MCA were insonated and monitored. P_ECO₂ was also monitored using Normocap 200 (Datex Co Ltd), and blood pressures were recorded every minute by a measuring device (BP-203I, Nippon Colin Co Ltd). After a stable state was reached, we recorded MCA waveforms of 15 cardiac cycles. Using a face mask, patients inhaled a mixture of 5% CO₂ and 95% air for 2 minutes. Blood pressure, P_ECO₂, and another 15 cardiac cycles of blood flow velocity were then recorded.

Calculation of Variables
We calculated the time-averaged MFV from five to seven consecutive heart beats. VMR was defined as relative changes in MFV divided by the difference in P_ECO₂ (P_ECO₂) before versus after inhalation of CO₂: VMR=(post-CO₂ MFV-resting MFV)x100/resting MFV/P_ECO₂.

Slight but significant increases in blood pressure were observed in some patients after they inhaled CO₂ and air. We determined percentage of change in CVRI as follows: CVRI=MABP/MFV¹⁶ and %CVRI=(resting CVRI–post-CO₂ CVRI)x100/resting CVRI/P_ECO₂. We used these parameters for the MCA on the side presumed to have the more severe impairment of cerebral hemodynamics. Lateralization of the lesions was judged by clinical profile, MRI and MRA, or angiography.

PET Measurements
For PET studies, we used a Headtome–III device (Shimadzu Inc) with spatial resolutions of 8.2 mm. As described previously,¹⁷ rCBF, rOEF, and rCMRO₂ were measured by the ¹⁵O steady-state technique. rCBV was determined by single inhalations of ¹⁵O-labeled carbon monoxide gas. rMTTs were calculated as rCBV/rCBF and were considered reliable indicators of cerebral perfusion pressure. Regions of interest were determined in frontal, temporal, parietal, and occipital regions; striatum; and white matter (Fig 1). All values on the orbitomeatal plane plus 50 mm were averaged and used as values for entire hemispheres. PET studies were conducted blinded, without knowledge of TCD results.

View larger version (23K): [in this window] [in a new window]   Figure 1. Diagrams show regions of interest examined with PET. Regions of interest were set in the frontal, temporal, parietal, and occipital lobes; striatum; and white matter. The values of pixels on the plane of orbitomeatal (OM) line plus 50 mm were averaged and used as entire hemisphere (upper right; shaded area).

Statistics
Differences in TCD and PET variables between groups were assessed by ANOVA followed by Scheffé's F test. Correlations between variables with TCD and PET were assessed by simple regression analysis. Statistical significance was assumed at a value of P<.05.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
TCD Results
Wide ranges of resting MFVs, from 27 to 95 cm/s (mean±SD, 52.2±19.5), were observed in TCD measurements. There were no differences in average MFV among groups (Table 3). No segmental increases in MFV were observed in the MCA, suggesting that MFV values were not influenced by any turbulent flows often caused by proximal or distal focal stenotic lesions nearby.

View this table: [in this window] [in a new window]   Table 3. Results of TCD and PET Measurements

Regarding CO₂ reactivity, impaired VMR (<2%/mm Hg) was found in 3 of 7 patients in group 1, in 2 of 6 patients in group 2, in 2 of 4 patients in group 3, and in 4 of 5 patients in group 4. Mean VMR values or relative changes in CVRI did not differ among groups.

PET Results
PET revealed wide ranges of hemodynamic and metabolic states, but no differences in PET measurements were found among the four groups (Table 3). Positive correlations between rMTT and rOEF were seen in temporal, parietal, and striatal regions and for entire hemisphere (r=.44, r=.60, r=.54, and r=.53, respectively [P<.05 to P<.005]). rMTT negatively correlated with rCMRO₂ in parietal, striatal, and white matter regions (r=.42, r=.52, and r=.70, respectively [P<.05 to P<.0005]).

Comparison of TCD and PET
Since TCD or PET measurements did not differ significantly among groups 1 through 4, analyses were performed by combining all four groups. Relationships between TCD and PET measurements are shown in Table 4. MFV correlated with rCBF by PET for entire hemisphere (P<.05), frontal region (P<.01), and in the territory of the MCA of temporal and striatal regions (P<.05; Fig 2). In temporal and striatal regions and for entire hemisphere, MFV also correlated with rMTT (P<.05). MFV also correlated with rOEF in frontal and striatal regions.

View this table: [in this window] [in a new window]   Table 4. Brain Regions Showing Significant Relationships Between TCD and PET Measurements

View larger version (14K): [in this window] [in a new window]   Figure 2. Plots show relationship between MFV and rCBF. MFV and rCBF were significantly correlated in the frontal, temporal, and striatal regions and in the entire hemisphere.

VMR demonstrated good correlation with rMTT in territorial areas of the anterior, middle, and posterior cerebral arteries (P<.05 to P<.0005; Fig 3). Relative changes in CVRI also correlated well with rMTT in each region of gray matter (P<.02 to P<.0001; Fig 4).

View larger version (17K): [in this window] [in a new window]   Figure 3. Plots show correlation between VMR and rMTT in each region of interest. VMR was significantly correlated with rMTT in the territory of the MCA and in the frontal and occipital regions (P<.05 to P<.0005).

View larger version (18K): [in this window] [in a new window]   Figure 4. Plots show correlation between relative changes in CVRI and rMTT in each region of interest. CVRI changes were significantly correlated with rMTT in the gray matter (P<.02 to P<.0001).

For entire hemisphere, VMR and relative changes in CVRI correlated with rMTT (Fig 5A and 5B). Relationships between VMR and oxygen metabolism for entire hemisphere are shown in Fig 5C and 5E. As VMR decreased, rOEF subsequently increased and rCMRO₂ declined. These trends achieved significance only in frontal region. Relative changes in CVRI did not correlate with rOEF or rCMRO₂ for entire hemisphere (Fig 5D and 5F) or other regions.

View larger version (17K): [in this window] [in a new window]   Figure 5. Top, Plots show relationships between VMR and rMTT (A), rOEF (C), or rCMRO2 (E) in the entire hemisphere; bottom, relationships between relative changes in CVRI and rMTT (B), rOEF (D), and rCMRO2 (F) in the entire hemisphere. As the VMR or CVRI changes decreased, the rOEF increased and the rCMRO2 declined in the entire hemisphere. This trend did not achieve statistical significance (r=.2 and r=.35 in panels C and E and r=.17 and r=.25 in panels D and F, respectively).

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Methodology
We could not evaluate blood flow velocity in 10 of 32 patients because of poor permeation through bone of the Doppler signal. Itoh and his coworkers¹⁸ examined rates of successful detection of MCA blood flow signals by TCD in 597 patients (16 to 89 years old) and found that the rate was 82% in men and 61% in women aged 50 years or older. Our rate of successful TCD evaluation in this study was only 69% (22/32) because stable and sufficient signals are required to measure CO₂ responsiveness.

MFV and rCBF
MFV by TCD slightly but significantly correlated with rCBF measured by PET in some carotid arterial territorial regions and also throughout the entire hemisphere. Bishop et al¹⁹ also demonstrated weak but statistically significant correlations between blood flow velocity by TCD and CBF measured by ¹³³Xe among patients with or without carotid occlusion.

Van der Zwan et al²⁰ demonstrated that territorial distributions of human basal cerebral arteries correlate with vascular diameters. Thus, the diameter of the MCA trunk and the size of the area perfused by the MCA may be assumed to correlate. MFV should have applications for estimating rCBF in a standardized area, since relationships between rCBF and MFV can be expressed as follows: rCBF_STDxPA_MCA=MFVxLA_MCA, where rCBF_STD indicates rCBF in a standardized area; PA_MCA, perfusion area of the MCA; and LA_MCA, luminal area of the MCA trunk. These assumptions, however, can only be reasonably applied to patients without significant stenosis or a collateral circulation, such as in groups 1 or 2.

VMR or CVRI Changes Versus Perfusion State
Patients in our study had differing degrees of cerebral atherosclerosis or arteriolosclerosis. Heistad et al²¹ demonstrated that responsiveness of the cerebral arteries to CO₂ is impaired in monkeys with extracranial atherosclerosis. Clinically, MCA responses to vasodilatory stimuli are reduced among patients with severe carotid occlusive disease.^{22 23 24 25 26 27 28} Some patients with severe carotid atherosclerosis show compromised intracranial hemodynamics as measured by PET.²⁹ Maeda and associates³⁰ reported that CO₂ reactivity was reduced among patients with lacunar infarctions, ie, by intracranial arteriolopathy. Similarly, Meguro et al³¹ showed reductions in CBF and CBF-CBV ratios in patients with severe periventricular hyperintensities by MRI, presumably indicating arteriolopathy.

Regarding relationships between cerebral vasodilatory responses and perfusions, Herold et al³² compared PET parameters with CO₂ reactivity measured by intravenous ¹³³Xe techniques among patients with carotid artery occlusive disease and found significantly linear relationships between CBF-CBV ratio and CO₂ reactivity. Hirano et al³³ also found that vasomotor reactivity to acetazolamide correlated with the CBF-CBV ratios. Our results indicate that decreases in perfusion pressure due to atherosclerosis or arteriolosclerosis are compensated by vasodilatory reserves. Thus, VMR and relative change in CVRI become reduced in states of compromised cerebral hemodynamics.

CO₂ response of the MCA correlated with rMTT in the anterior and posterior cerebral arterial territories; this is probably because the MCA influences maintenance of blood flow to other territories, through bone and degrees of arteriosclerosis (and also vasodilatory response) may not differ significantly within territories of the MCA and anterior and posterior arteries in patients without embolic strokes.

Changes in VMR or CVRI and Metabolism
We failed to show the expected contributions of decreased CO₂ responses to the presence of elevated rOEF and decreased rCMRO₂, as reported previously.^{32 33 34 35} In addition to the small sample size of this study, the following causes would explain the results.

Although 1 patient with extracranial-intracranial bypass surgery was excluded from the present study and all brain lesions present in our patients were in chronic stages, PET revealed heterogeneous relationships between hemodynamics and metabolic states. The "misery perfusion pattern" (a decreased rCBF with an increased rOEF greater than 48%) was seen in only 2 patients (Table 3; patients 16 and 18), and 6 patients demonstrated the "matched hypoperfusion"; rCMRO₂ was 1.8 mL/100 mL per minute or less, and rOEF was below 48% (patients 4, 14, 15, 19, 21, and 22). Metabolic conditions of the brain are altered according to the severity and stages of ischemia.³⁶ For example, in patients with unilateral carotid artery occlusive disease, asymptomatic patients do not show an increase in OEF, suggesting efficient compensatory mechanism of hemodynamics,¹³ whereas symptomatic patients (ie, those with advanced stages of occlusive disease) tend to have exhausted vasodilatory capacity and elevated OEF.³⁶ Thus, it seems likely that the ischemic brain lesions were in different stages, even in the same group.

We included 8 diabetic patients (patients 1, 8, 10, 12, 16, 18, 19, and 22). Diabetes mellitus is known to decrease vasodilatory responses^{37 38} and is involved in progression of arteriolosclerosis and atherosclerosis.³⁹ Grill et al⁴⁰ observed that global cerebral productions of lactate and pyruvate are higher in diabetic than nondiabetic subjects, and they proposed that a larger fraction of glucose is anaerobically metabolized in diabetic patients. Diabetes mellitus, therefore, influences both vasodilatory responses and cerebral metabolism of glucose and oxygen.

The perfusional states and the oxidative metabolic conditions appear not to be correlated in a simple manner among patients with different stages of brain ischemia, particularly among diabetic patients.

Conclusions
TCD is a reliable method to evaluate decreases in the cerebral circulation in patients with hypertension or diabetes mellitus. TCD promises to be useful for the management of such patients when used in combination with noninvasive morphological imaging such as MR arteriography and carotid duplex examinations.

	Selected Abbreviations and Acronyms

 

CVRI = cerebrovascular resistance index MABP = mean arterial blood pressure MCA = middle cerebral artery MFV = mean flow velocity PECO2 = partial pressure of end-tidal CO2 PET = positron emission tomography rCBF = regional cerebral blood flow rCBV = regional cerebral blood volume rCMRO2 = regional metabolic rate for oxygen rMTT = regional mean transit time rOEF = regional oxygen extraction fraction TCD = transcranial Doppler VMR = vasomotor reactivity

	Acknowledgments

 
The authors are grateful to Dr Yuichi Ichiya for performing the PET examinations. We also thank Drs Katsumi Irie and Kentaro Takano for important advice on this study.

	Footnotes

 
Reprint requests to Hiroshi Sugimori, MD, Second Department of Internal Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, Japan.

Received May 15, 1995; revision received July 20, 1995; accepted July 27, 1995.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Kiyohara Y, Ueda K, Hasuo Y, Fujii I, Yanai T, Wada J, Kawano H, Shikata T, Omae T, Fujishima M. Hematocrit as a risk factor of cerebral infarction: long-term prospective population survey in a Japanese rural community. Stroke.. 1986;17:687-692. [Abstract/Free Full Text]
2. Barnett-Connor E, Khaw K-T. Diabetes mellitus: an independent risk factor for stroke? Am J Epidemiol.. 1988;128:116-123. [Abstract/Free Full Text]
3. Ueda K, Omae T, Hasuo Y, Kiyohara Y, Yanai T, Kato I, Wada J, Kawano H, Kajiwara E, Fujishima M. Prevalence and long-term prognosis of mild hypertensives and hypertensives in a Japanese community, Hisayama. J Hypertens.. 1988;6:981-989. [Medline] [Order article via Infotrieve]
4. Collins R, Peto R, MacMahon S, Hebert P, Fiebach NH, Eberlein KA, Godwin J, Qizilbash N, Taylor JO, Hennekens CH. Blood pressure, stroke, and coronary heart disease, II: short-term reduction in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet.. 1990;335:827-838. [Medline] [Order article via Infotrieve]
5. Chobanian AV. Vascular effects of systemic hypertension. Am J Cardiol.. 1992;69:3E-7E. [Medline] [Order article via Infotrieve]
6. Meyer JS, Ishihara N, Deshmukh VD, Naritomi H, Sakai F, Hsu M-C, Pollack P. Improved method for noninvasive measurement of regional cerebral blood flow by ¹³³xenon inhalation, I: description of method and normal values obtained in healthy volunteers. Stroke.. 1978;9:195-210. [Abstract/Free Full Text]
7. Naritomi H, Meyer JS, Sakai F, Yamaguchi F, Shaw T. Effects of advancing age on regional cerebral blood flow: studies in normal subjects and subjects with risk factors for atherothrombotic stroke. Arch Neurol.. 1979;36:410-416. [Abstract]
8. Nobili F, Rodriguez G, Marenco S, De CF, Gambaro M, Castello C, Pontremoli R, Rosadini G. Regional cerebral blood flow in chronic hypertension: a correlative study. Stroke.. 1993;24:1148-1153. [Abstract/Free Full Text]
9. Aaslid R, Markwalder TM, Nornes H. Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg.. 1982;57:769-774. [Medline] [Order article via Infotrieve]
10. Dahl A, Russel D, Nyberg-Hansen R, Rootwelt K. Effect of nitroglycerin on cerebral circulation measured by transcranial Doppler and SPECT. Stroke.. 1989;20:1733-1735. [Abstract/Free Full Text]
11. Dahl A, Lindegaard K-F, Russel D, Nyberg-Hansen R, Rootwelt K, Sorteberg W, Nornes H. A comparison of transcranial Doppler and cerebral blood flow studies to assess cerebral vasoreactivity. Stroke.. 1992;23:15-19. [Abstract/Free Full Text]
12. Dahl A, Russel D, Nyberg-Hansen R, Rootwelt K, Bakke SJ. Cerebral vasoreactivity in unilateral carotid artery disease: a comparison of blood flow velocity and regional cerebral blood flow measurements. Stroke.. 1994;25:621-626. [Abstract]
13. Kuwert T, Hennerici M, Langen KJ, Herzog H, Kops ER, Aulich A, Rautenberg W, Feinendegen LE. Compensatory mechanisms in patients with asymptomatic carotid artery occlusion. Neurol Res.. 1990;12:89-93. [Medline] [Order article via Infotrieve]
14. Sitzer M, Knorr U, Seitz RJ. Cerebral hemodynamics during sensorimotor activation in humans. J Appl Physiol.. 1994;77:2804-2811. [Abstract/Free Full Text]
15. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R). Washington, DC: American Psychiatric Association; 1987:103-122.
16. Sugimori H, Ibayashi S, Irie K, Ooboshi H, Nagao T, Fujii K, Sadoshima S, Fujishima M. Cerebral hemodynamics in hypertensive patients compared with normotensive volunteers: a transcranial Doppler study. Stroke. 1994;25:1384-1389. [Abstract]
17. Fujii K, Sadoshima S, Okada Y, Yao H, Kuwabara Y, Ichiya Y, Fujishima M. Cerebral blood flow and metabolism in normotensive and hypertensive patients with transient neurologic deficits. Stroke.. 1990;21:283-290. [Abstract/Free Full Text]
18. Itoh T, Matsumoto M, Handa N, Maeda H, Hougaku H, Hashimoto H, Etani H, Tsukamoto Y, Kamada T. Rate of successful recording of blood flow signals in the middle cerebral artery using transcranial Doppler sonography. Stroke.. 1993;24:1192-1195. [Abstract/Free Full Text]
19. Bishop CCR, Powel S, Rutt D, Browse NL. Transcranial Doppler measurement of middle cerebral artery blood flow velocity: a validation study. Stroke.. 1986;17:913-915. [Abstract/Free Full Text]
20. van der Zwan A, Hillen B, Tulleken CAF, Dujovny M. A quantitative investigation of the variability of the major cerebral artery territories. Stroke.. 1993;24:1951-1959. [Abstract/Free Full Text]
21. Heistad DD, Marcus ML, Piegors DJ, Armstrong ML. Regulation of cerebral blood flow in atherosclerotic monkeys. Am J Physiol.. 1980;239:H539-H544.
22. Bullock R, Mendelow AD, Bone I, Patterson J, Macleod WN, Allardice G. Cerebral blood flow and CO₂ responsiveness as an indicator of collateral reserve capacity in patients with carotid arterial disease. Br J Surg.. 1985;72:348-351. [Medline] [Order article via Infotrieve]
23. Lindegaard K-F, Bakke SJ, Aaslid R, Nornes H. Doppler diagnosis of intracranial artery occlusive disorders. J Neurol Neurosurg Psychiatry.. 1986;49:510-518. [Abstract]
24. Ringelstein EB, Sievers C, Ecker S, Schneider PA, Otis SM. Noninvasive assessment of CO₂-induced cerebral vasomotor response in normal individuals and patients with internal carotid artery occlusions. Stroke.. 1988;19:963-969. [Abstract/Free Full Text]
25. Chollet F, Celsis P, Clanet M, Guiraud-Chaumeli B, Rascol A, Marc-Vergnes J-P. SPECT study of cerebral blood flow reactivity after acetazolamide in patients with transient ischemic attacks. Stroke.. 1989;20:458-464. [Abstract/Free Full Text]
26. Widder B. The Doppler CO₂ test to exclude patients not in need of extracranial/intracranial bypass surgery. J Neurol Neurosurg Psychiatry.. 1989;52:38-42. [Abstract]
27. Ley-Pozo J, Ringelstein EB. Noninvasive detection of occlusive disease of the carotid siphon and middle cerebral artery. Ann Neurol.. 1990;28:640-647. [Medline] [Order article via Infotrieve]
28. Maeda H, Matsumoto M, Handa N, Hougaku H, Ogawa S, Itoh T, Tsukamoto Y, Kamada T. Reactivity of cerebral blood flow to carbon dioxide in various types of ischemic cerebrovascular disease: evaluation by the transcranial Doppler method. Stroke.. 1993;24:670-675. [Abstract/Free Full Text]
29. Powers WJ, Press GA, Grubb RL Jr, Gado M, Raichle ME. The effects of hemodynamically significant carotid artery disease on the hemodynamic status of the cerebral circulation. Ann Intern Med.. 1987;106:27-35.
30. Maeda H, Matsumoto M, Handa N, Hougaku H, Ogawa S, Itoh T, Tsukamoto Y, Kamada T. Reactivity of cerebral blood flow to carbon dioxide in hypertensive patients: evaluation by the transcranial Doppler method. J Hypertens.. 1994;12:191-197. [Medline] [Order article via Infotrieve]
31. Meguro K, Hatazawa J, Yamaguchi T, Itoh M, Matsuzawa T, Ono S, Miyazawa H, Hishinuma T, Yanai K, Sekita Y, Yamada K. Cerebral circulation and oxygen metabolism associated with subclinical periventricular hyperintensity as shown by magnetic resonance imaging. Ann Neurol.. 1990;28:378-383. [Medline] [Order article via Infotrieve]
32. Herold S, Brown MM, Frackowiak RSJ, Mansfield AO, Thomas DJ, Marshal J. Assessment of cerebral hemodynamic reserve: correlation between PET parameters and CO₂ reactivity measured by intravenous 133xenon injection technique. J Neurol Neurosurg Psychiatry.. 1988;51:1045-1050. [Abstract]
33. Hirano T, Minematsu K, Hasegawa Y, Tanaka Y, Hayashida K, Yamaguchi T. Acetazolamide reactivity on ¹²³I-IMP-single photon emission computed tomography in patients with major cerebral artery occlusive disease: correlation with positron emission tomography parameters. J Cereb Blood Flow Metab.. 1994;14:763-770. [Medline] [Order article via Infotrieve]
34. Fujishima M, Scheinberg P, Busto R, Reinmuth O. The relation between cerebral oxygen consumption and cerebral vascular reactivity to carbon dioxide. Stroke.. 1971;2:251-257. [Abstract/Free Full Text]
35. Kanno I, Uemura K, Higano S, Murakami M, Iida H, Miura S, Shishido F, Inugami A, Sayama I. 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.. 1988;8:227-235. [Medline] [Order article via Infotrieve]
36. Powers WJ. Cerebral hemodynamics in ischemic cerebrovascular disease. Ann Neurol.. 1991;29:231-240. [Medline] [Order article via Infotrieve]
37. Mayhan WG, Simmons LK, Sharpe GM. Mechanism of impaired responses of cerebral arterioles during diabetes mellitus. Am J Physiol.. 1991;29:H319-H326.
38. Johnstone MT, Creager SJ, Scales KM, Cusco JA, Lee BK, Creager MA. Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation. 1993;88:2510-2516. [Abstract/Free Full Text]
39. Robertson WB, Strong JP. Atherosclerosis in persons with hypertension and diabetes mellitus. Lab Invest.. 1968;18:538-551. [Medline] [Order article via Infotrieve]
40. Grill V, Gutniak M, Björkman O, Lindqvist M, Stone-Elander S, Seitz RJ, Blomqvist G, Reichard P, Widén L. Cerebral blood flow and substrate utilization in insulin-treated diabetic subjects. Am J Physiol.. 1990;258:E813-E820.[Abstract/Free Full Text]

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				D. A. Dulli Subcortical Infarctions, Transcranial Doppler, and Cerebral Vasomotor Reactivity Arch Neurol, April 1, 2001; 58(4): 551 - 552. [Full Text] [PDF]

				C. Tantucci, P. Bottini, C. Fiorani, M. L. Dottorini, F. Santeusanio, L. Provinciali, C. A. Sorbini, and G. Casucci Cerebrovascular reactivity and hypercapnic respiratory drive in diabetic autonomic neuropathy J Appl Physiol, March 1, 2001; 90(3): 889 - 896. [Abstract] [Full Text] [PDF]

				H. Markus and M. Cullinane Severely impaired cerebrovascular reactivity predicts stroke and TIA risk in patients with carotid artery stenosis and occlusion Brain, March 1, 2001; 124(3): 457 - 467. [Abstract] [Full Text] [PDF]

				R. A. Rodriguez, G. Cornel, W. M. Splinter, N. A. Weerasena, and C. W. Reid Cerebral vascular effects of aortovenous cannulations for pediatric cardiopulmonary bypass Ann. Thorac. Surg., April 1, 2000; 69(4): 1229 - 1235. [Abstract] [Full Text] [PDF]

				C. P. Derdeyn, R. L. Grubb Jr., and W. J. Powers Cerebral hemodynamic impairment: Methods of measurement and association with stroke risk Neurology, July 1, 1999; 53(2): 251 - 251. [Abstract] [Full Text] [PDF]

				M. Matteis, E. Troisi, B. C. Monaldo, C. Caltagirone, and M. Silvestrini Age and Sex Differences in Cerebral Hemodynamics : A Transcranial Doppler Study Stroke, May 1, 1998; 29(5): 963 - 967. [Abstract] [Full Text] [PDF]

				R. A. Rodriguez, N. Weerasena, G. Cornel, W. M. Splinter, and D. J. Roberts Cerebral effects of aortic clamping during coarctation repair in children: A transcranial Doppler study Eur. J. Cardiothorac. Surg., February 1, 1998; 13(2): 124 - 129. [Abstract] [Full Text] [PDF]

				T. Omae, S. Ibayashi, K. Kusuda, H. Nakamura, H. Yagi, and M. Fujishima Effects of High Atmospheric Pressure and Oxygen on Middle Cerebral Blood Flow Velocity in Humans Measured by Transcranial Doppler Stroke, January 1, 1998; 29(1): 94 - 97. [Abstract] [Full Text] [PDF]

				M. Silvestrini, E. Troisi, M. Matteis, L. M. Cupini, and C. Caltagirone Transcranial Doppler Assessment of Cerebrovascular Reactivity in Symptomatic and Asymptomatic Severe Carotid Stenosis Stroke, November 1, 1996; 27(11): 1970 - 1973. [Abstract] [Full Text]

				J. van der Grond, B.C. Eikelboom, and W.P.Th.M. Mali Flow-Related Anaerobic Metabolic Changes in Patients With Severe Stenosis of the Internal Carotid Artery Stroke, November 1, 1996; 27(11): 2026 - 2032. [Abstract] [Full Text]

				P. Demolis, Y. R. T. Dinh, and J.-F. Giudicelli Relationships Between Cerebral Regional Blood Flow Velocities and Volumetric Blood Flows and Their Respective Reactivities to Acetazolamide Stroke, October 1, 1996; 27(10): 1835 - 1839. [Abstract] [Full Text]

				R. Kodaka, Y. Itagaki, M. Matsumoto, T. Nagai, and S. Okada A Transcranial Doppler Ultrasonography Study of Cerebrovascular CO2 Reactivity in Mitochondrial Encephalomyopathy Stroke, August 1, 1996; 27(8): 1350 - 1353. [Abstract] [Full Text]

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