Preserved Acetazolamide Reactivity in Lacunar Patients with Severe White-Matter Lesions: ¹⁵O-Labeled Gas and H₂O Positron Emission Tomography Studies

Abstract

Limited evidence exists on the relationships between severity of white-matter lesions (WMLs) and cerebral hemodynamics in patients without major cerebral artery disease. To examine changes of cerebral blood flow (CBF), oxygen metabolism, and vascular reserve capacity associated with severity of WML in patients with lacunar stroke, we used a positron emission tomography (PET). Eighteen lacunar patients were divided into two groups according to the severity of WMLs, assessed by Fazekas classification; grades 0 to 1 as mild WML group and grades 2 to 3 as severe WML group. Rapid dual autoradiography was performed with 15 O-labeled gas-PET followed by 15 O-labeled water-PET with acetazolamide (ACZ) challenge. Compared with the mild WML group, the severe WML group showed lower CBF (20.6±4.4 versus 29.9±8.2 mL/100 g per minute, P = 0.008), higher oxygen extraction fraction (OEF) (55.2 ± 7.4 versus 46.7 ± 5.3%, P = 0.013), and lower cerebral metabolic rate of oxygen (CMRO 2 ) (1.95±0.41 versus 2.44±0.42 mL/100 g per minute, P = 0.025) in the centrum semiovale. There were no significant differences in the ACZ reactivity between the two groups (48.6±22.6% versus 42.5±17.2%, P = 0.524). Lacunar patients with severe WMLs exhibited reduced CBF and CMRO 2 , and increased OEF in the centrum semiovale. The ACZ reactivity was preserved in both patients with severe and mild WMLs in each site of the brain.

Longitudinal Relationship Between Cerebral Small-Vessel Disease and Cerebral Blood Flow

“…For instance, studies in patients with WMHs that investigated the balance between perfusion and metabolic demand provided conflicting results with some showing impaired and others showing preserved oxidative metabolism in addition to reduced CBF. 10,16,17 Also, we found no association between baseline pCBF and WMH volume although other cross-sectional studies did. 4,6 The finding that WMHs but not the presence of lacunes was associated with changes in pCBF over time could be because WMHs cause more widespread hypometabolism and reduction of CBF, whereas the CBF effect of lacunes is probably more local and depends on the location of the infarct.…”

“…9 However, because these studies are cross-sectional, it could also be hypothesized that WMHs and lacunes lead to downregulation of CBF because of reduced metabolic demand, which is a normal function of blood vessels. 10 We aimed to investigate the bidirectional longitudinal relationship between WMHs and lacunes and CBF during 4 years of follow-up in patients with manifest arterial disease. We hypothesize that low CBF at baseline is associated with progression of WMHs and lacunes and that severity of WMHs and presence of lacunes is associated with decline of CBF.…”

Cerebral blood flow and metabolism associated with cerebral microbleeds in small vessel disease

“…A catheter was placed in the brachial artery for continuous monitoring of the arterial blood radioactivity concentration and arterial input function using a scintillator block detector system (BeCON; Molecular Imaging Labo, Suita, Japan) [18]. Quantitative images of CBF, cerebral blood volume (CBV), and oxygen extraction fraction (OEF) were obtained from a series of PET scans with inhalation of 15 O-labeled carbon monoxide (C 15 O), oxygen ( 15 O 2 ), and carbon dioxide (C 15 O 2 ) gases based on a rapid dual autoradiography protocol by Kudomi et al [19,20], as described previously [16]. The cerebral metabolic rate of oxygen (CMRO 2 ) image was calculated by multiplying the arterial oxygen content by the product images of OEF and CBF.…”

“…All patients underwent MRI performed on a 1.5-T scanner as previously described (Magnetom Vision or Magnetom Sonata; Siemens Medical Systems, Erlangen, Germany) [16]. Briefly, the imaging protocol consisted of a T1-weighted spin-echo, a T2-weighted spin-echo, fluid-attenuated inversion recovery (FLAIR), gradient-echo T2*-weighted MRI (GRE-MRI), and magnetization-prepared rapid gradient-echo (MPRAGE).…”

“…Voxel-based analysis was done for all patients to confirm the absence of Alzheimer's-type changes in the brain (atrophy of hippocampal and parahippocampal gyrus) by using commercial software (voxel-based specific regional analysis system for Alzheimer's disease; Eisai, Tokyo, Japan). WMLs were delineated in the cerebral white matter with hyperintense signals on FLAIR images, and WML volume was measured manually based on FLAIR images using the QSPECT software package (National Cerebral and Cardiovascular Center and QSPECT group, Japan) as described previously [16].…”