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Relationship Between Vasodilatation and Cerebral Blood Flow Increase in Impaired Hemodynamics: a PET Study with the Acetazolamide Test in Cerebrovascular Disease

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Relationship Between Vasodilatation and Cerebral Blood Flow Increase in Impaired Hemodynamics: a PET Study with the Acetazolamide Test in Cerebrovascular Disease CLINICAL INVESTIGATIONS Relationship Between Vasodilatation and Cerebral Blood Flow Increase in Impaired Hemodynamics: A PET Study with the Acetazolamide Test in Cerebrovascular Disease Hidehiko Okazawa, MD, PhD1,2; Hiroshi Yamauchi, MD, PhD1; Hiroshi Toyoda, MD, PhD1,2; Kanji Sugimoto, MS1; Yasuhisa Fujibayashi, PhD2; and Yoshiharu Yonekura, MD, PhD2 1PET Unit, Research Institute, Shiga Medical Center, Moriyama, Japan; and 2Biomedical Imaging Research Center, Fukui Medical University, Fukui, Japan Key Words: acetazolamide; cerebrovascular disease; cerebral The changes in cerebral blood flow (CBF) and arterial-to- blood volume; vasodilatory capacity; cerebral perfusion pressure capillary blood volume (V0) induced by acetazolamide (ACZ) are expected to be parallel each other in the normal circula- J Nucl Med 2003; 44:1875–1883 tion; however, it has not been proven that the same changes in those parameters are observed in patients with cerebro- vascular disease. To investigate the relationship between changes in CBF, vasodilatory capacity, and other hemody- namic parameters, the ACZ test was performed after an The ability of autoregulation to maintain the cerebral 15O-gas PET study. Methods: Twenty-two patients with uni- blood flow (CBF), which resides in the cerebral circulation lateral major cerebral arterial occlusive disease underwent despite transient changes in systemic mean arterial blood 15 PET scans using the H2 O bolus method with the ACZ test pressure, has been shown to occur via the mechanism of 15 after the O-gas steady-state method. CBF and V0 for each arteriolar vasodilatation in the cerebral circulation (1). The subject were calculated using the 3-weighted integral vasodilatory change in the cerebral arteries is assumed for method as well as the nonlinear least-squares fitting method. the compensatory hemodynamic stages in occlusive cere- After evaluation of accuracy in V0 values, a new parameter, the CBF/V0 ratio, which is expected to disclose arterial per- brovascular disease (CVD) (2), which is the basis of the fusion pressure, was also compared between the conditions. acetazolamide (ACZ) test for evaluating the residual vaso- Results: The regional CBF (rCBF) and V0 increased signifi- dilatory capacity in those patients. The test assesses the cantly after ACZ administration in the hemisphere contralat- cerebrovascular response to a vasodilatory stimulus by mea- eral to the ischemic side. However, in a subgroup of patients suring changes in CBF or blood velocity (3–5), and it has who showed a significant reduction in the rCBF increase in the ipsilateral hemisphere (group A), the ACZ injection been used for evaluation of the cerebral hemodynamic sta- caused no change or a slight decrease in rCBF even though tus and the risk of cerebral ischemia in patients with cere- the V0 showed a significant increase. Thus, the increases in rCBF bral arterial occlusive diseases. However, it remains un- and V0 did not necessarily parallel each other in the ipsilateral known whether the CBF increase induced by ACZ hemispheres of patients who have impaired cerebral circulation. A administration accurately represents the vasodilatory capac- parameter defined by the rCBF/V0 ratio decreased significantly in ity under the varying hemodynamic conditions observed in the ipsilateral hemisphere of group A after ACZ administration, although the ratio showed no change in the contralateral hemi- stenoocclusive CVD. Although our previous study with sphere or in the other subgroup (group B). Conclusion: The healthy volunteers proved that changes in CBF were accom- change in the rCBF/V0 ratio after ACZ challenge may represent an panied by changes in the vascular distribution volume (V0), alteration in arterial perfusion pressure that is expected to indicate which represents the arterial-to-capillary blood volume a critical hemodynamic status in patients with cerebrovascular (6,7), a vasodilatory stimulus in the affected area of patients disease, especially in patients who have a reduced rCBF response. may induce a different hemodynamic response to the stim- ulus because a severe occlusive change in the major cerebral arteries would affect the regional perfusion pressure. The Received Mar. 10, 2003; revision accepted Aug. 14, 2003. For correspondence or reprints contact: Hidehiko Okazawa, MD, PhD, relationship between arterial vasodilatation and an increase Biomedical Imaging Research Center, Fukui Medical University, 23-3 Shi- of regional CBF (rCBF) seems more complicated in the moaizuki, Matcuoka-cho, Fukui, 910-1193, Japan. E-mail: [email protected] affected part of the brain compared with the normal cerebral VASODILATATION AND CBF INCREASE IN CVD • Okazawa et al. 1875 circulation, suggesting that the measurement of rCBF with severe stenosis in the major cerebral arteries had collateral changes induced by ACZ may not properly evaluate the circulations from the contralateral hemisphere via the anterior or status of hemodynamic impairment. Furthermore, a de- posterior communicating arteries, the ophthalmic artery, or the crease in rCBF after ACZ administration, the so-called steal leptomeningeal arteries in the same side of the occlusion. The phenomenon, may be observed instead of an increase in other 6 patients with severe stenosis did not show visible collateral patients with CVD (8,9). circulation. The study was approved by the Ethical Committee of the Research Institute of Shiga Medical Center, and written in- The phenomenon is presumed to be caused by the redis- formed consent was obtained from each subject before the study. tribution of blood from the impaired regions, where auto- regulatory vasodilatation is already at its maximum in re- PET Procedures sponse to a reduced perfusion pressure, to the relieved areas, All subjects underwent PET scans with a whole-body tomog- where the ability of vasodilatation still exists. This also may raphy scanner (Advance; General Electric Medical Systems), be induced by the redistribution of regional arterial perfu- which permits simultaneous acquisition of 35 image slices with an sion pressure according to the relative differences in the interslice spacing of 4.25 mm (13). Performance tests showed the regional vasodilatory capacity. However, it has not yet been intrinsic resolution of the scanner to be 4.6–5.7 mm and 4.0–5.3 proven that the maximal vasodilatation with the exhaustion mm in the transaxial direction and the axial direction, respectively. of vasodilatory capacity causes the steal phenomenon in- A transmission scan was performed using 68Ge/68Ga for attenua- duced by a vasodilatory stimulus. Additional information tion correction in each subject before tracer administration. All obtained from regional changes in V in the ACZ test would emission scans were acquired in a 2-dimensional mode. The PET 0 data were reconstructed using a Hanning filter with a resolution of reveal the relationship between blood flow and vasodilatory 6.0-mm full width at half maximum in the transaxial direction. capacity as well as provide a new index for the assessment The subjects were positioned on the scanner bed with their of impaired hemodynamic status in patients with severe heads immobilized using a head holder. A small cannula was arterial occlusive disease. Because the cerebral perfusion placed in the left brachial artery for blood sampling. The patients pressure (Cpp) is considered to be correlated with the flow- underwent PET scans using the bolus method with 1,110 MBq ϰ 15 to-volume ratio (Cpp F/V) (2,10,11), the arterial perfusion H2 O and dynamic data acquisition, followed by the steady-state pressure would be related to the CBF/V0 that will reveal a method with 15O-gas inhalation as described (14). An additional 15 change in arterial Cpp. The result that the changes in CBF H2 O bolus PET scan was performed 10 min after ACZ injection. 15 and V0 induced by ACZ were parallel in healthy subjects For the CBF measurement using the bolus method with H2 O was consistent with this assumption under no change in the injection, a 3-min dynamic PET scan was started at the time of tracer administration from the right antecubital vein with frame systemic blood pressure and the stable Cpp (8). To investigate whether changes in rCBF induced by ACZ durations of 5 s ϫ 12, 10 s ϫ 6, and 20 s ϫ 3. The radioactivity accurately reflect the vasodilatory capacity and hemody- in the arterial blood was counted continuously using an automatic namic stages in patients with CVD, PET scans were used for coincidental radioactive counter (Pico-Count; Bioscan Inc.) during 15 the measurement of CBF, V , and other hemodynamic pa- the H2 O scans (15). The arterial blood was drawn using a 0 Bio-minipump (AC-2120; Atto Co.) at a constant rate of 7 mL/min rameters to assess the status of cerebral circulation and the for the first 2 min, followed by manual sampling of 0.5 mL of vasodilatory capacity. Time–activity curves obtained from blood every 20 s during the rest of the scan time (16). Radioac- 15 dynamic data of H2 O PET were analyzed to evaluate tivity counted by the automatic radioactive counter was calibrated whether the impaired cerebral circulation affected the tim- with that of the arterial blood sampled manually. Decay of the ing of tracer arrival, which may cause a difference in the radioactivity from PET and blood data was corrected to the starting tracer kinetics of each hemisphere in patients. To ensure that point of each scan, and dispersion for the external tube in the the V0 values were not affected by the calculation methods, V0 arterial curves was corrected with a double-exponential dispersion was calculated using both a nonlinear least-squares (NLS) function (16,17). 15 fitting and the 3-weighted integral (3-WI) method (9,12). In the steady-state method (18,19), the subjects inhaled C O2 15 (400 MBq/min) and O2 (800 MBq/min) continuously for approx- imately 10 min, followed by static data acquisition for 5 min to MATERIALS AND METHODS obtain images of the CBF, oxygen extraction fraction (OEF), and Subjects cerebral metabolic rate of oxygen (CMRO2).
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