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Biomedical subjects

Mark A van Buchem

Publications and source records attributed to Mark A van Buchem.

At least 19 recordsLinked to original sources
PubMed2004

Rheumatoid arthritis: epidural enhancement as an underestimated cause of subaxial cervical spinal stenosis.

PURPOSE: To assess the frequency and site of subaxial spinal canal stenosis due to enhancing tissue in patients with rheumatoid arthritis. MATERIALS AND METHODS: Data from 33 consecutive patients with rheumatoid arthritis were evaluated; these patients had undergone 1.5-T magnetic resonance imaging following gadolinium chelate administration, in combination with a frequency selective fat-suppression technique. Stenosis and enhancement were scored for each of six cervical spinal levels and were compared with results in a control population consisting of 16 patients with degenerative disease. Enhancement was scored as superficial or deep on the anterior and posterior sides from the cervical spinal cord. Differences between patient groups were tested by using the chi(2) test for trend and the Fisher exact test. RESULTS: No significant difference was found in the frequency or severity of subaxial stenosis between rheumatoid arthritis and degenerative disease. Deep epidural enhancement was observed more often with rheumatoid arthritis than with degenerative disease both anterior (25 of 33 patients vs seven of 16 patients, respectively; P <.001) and posterior (24 of 33 patients vs two of 16 patients, respectively; P =.001) to the spinal cord. Enhancing stenosing tissue in rheumatoid arthritis frequently occurred anterior and posterior at the same time and at the same level, with segmental cufflike extension of enhancing tissue around the dural sac. Stenosing tissue enhanced more frequently with rheumatoid arthritis than with degenerative disease (22 of 33 vs four of 16 patients, respectively; P =.008). CONCLUSION: In patients with rheumatoid arthritis, subaxial stenosis is frequently caused by enhancing epidural tissue. This enhancing tissue presumably represents pannus.

Adult↗
PubMed2004

Migraine as a risk factor for subclinical brain lesions.

CONTEXT: Clinical series have suggested an increased prevalence of cerebral infarction and white matter lesions (WMLs) in migraine patients. It is not known whether these lesions are prevalent in the general migraine population. OBJECTIVES: To compare the prevalence of brain infarcts and WMLs in migraine cases and controls from the general population and to identify migraine characteristics associated with these lesions. DESIGN: Cross-sectional, prevalence study of population-based sample of Dutch adults aged 30 to 60 years. PARTICIPANTS: Randomly selected patients with migraine with aura (n = 161), patients with migraine without aura (n = 134), and controls (n = 140), who were frequency matched to cases for age, sex, and place of residence. Nearly 50% of the cases had not been previously diagnosed by a physician. MAIN OUTCOME MEASURES: Brain magnetic resonance images were evaluated for infarcts, by location and vascular supply territory, and for periventricular WMLs (PVWMLs) and deep WMLs (DWMLs). The odds ratios (ORs) and 95% confidence intervals (CIs) of these brain lesions compared with controls were examined by migraine subtype (with or without aura) and monthly attack frequency (<1 attack, > or =1 attack), controlling for cardiovascular risk factors and use of vasoconstrictor migraine agents. All participants underwent a standard neurological examination. RESULTS: No participants reported a history of stroke or transient ischemic attack or had relevant abnormalities at standard neurological examination. We found no significant difference between patients with migraine and controls in overall infarct prevalence (8.1% vs 5.0%). However, in the cerebellar region of the posterior circulation territory, patients with migraine had a higher prevalence of infarct than controls (5.4% vs 0.7%; P =.02; adjusted OR, 7.1; 95% CI, 0.9-55). The adjusted OR for posterior infarct varied by migraine subtype and attack frequency. The adjusted OR was 13.7 (95% CI, 1.7-112) for patients with migraine with aura compared with controls. In patients with migraine with a frequency of attacks of 1 or more per month, the adjusted OR was 9.3 (95% CI, 1.1-76). The highest risk was in patients with migraine with aura with 1 attack or more per month (OR, 15.8; 95% CI, 1.8-140). Among women, the risk for high DWML load (top 20th percentile of the distribution of DWML load vs lower 80th percentile) was increased in patients with migraine compared with controls (OR, 2.1; 95% CI, 1.0-4.1); this risk increased with attack frequency (highest in those with > or =1 attack per month: OR, 2.6; 95% CI, 1.2-5.7) but was similar in patients with migraine with or without aura. In men, controls and patients with migraine did not differ in the prevalence of DWMLs. There was no association between severity of PVWMLs and migraine, irrespective of sex or migraine frequency or subtype. CONCLUSIONS: These population-based findings suggest that some patients with migraine with and without aura are at increased risk for subclinical lesions in certain brain areas.

Brain↗
PubMed2004

Memory complaints in patients with normal cognition are associated with smaller hippocampal volumes.

We aimed to investigate volumetry of the medial temporal lobe in patients with subjective memory complaints without any cognitive impairment. This study included 20 patients with subjective memory complaints and normal cognitive function and 28 controls without memory complaints. Volumes of the hippocampus and parahippocampal gyrus (PHG) were measured using coronal T1-weighted MR images. Cognitive functions were assessed using the Cambridge Cognitive Examination. Depressive symptoms were assessed using the Geriatric Depression Scale. Differences between groups were analysed using t-tests. Patients with subjective memory complaints had a higher education and more depressive symptoms than controls ( p < 0.01). Moreover, they had smaller left hippocampal volumes than controls ( p < 0.01). There were no differences between groups in the volume of the right hippocampus or PHG. There was a moderate association between the volume of left hippocampus and left PHG and memory-score (r = 0.32, p = 0.03; r = 0.34, p = 0.02). We concluded that memory complaints in patients without any cognitive impairment were associated with smaller left hippocampal volumes and more depressive symptoms. These preliminary results suggest that memory complaints may reflect minimal brain deficits associated with impending dementia, depression or a combination of both disorders.

Aged↗
PubMed2004

Basal cerebral blood flow is dependent on the nitric oxide pathway in elderly but not in young healthy men.

OBJECTIVE: Brain perfusion is tightly regulated over a wide range of blood pressures by local regulation of cerebral blood flow (CBF). Ageing is associated with impaired CBF and impaired nitric oxide mediated vasodilator responses. The role of nitric oxide in the regulation of basal CBF in young and older subjects was investigated, using the nitric oxide synthase inhibitor L-NMMA as pharmacological tool. METHODS: We used a gradient echo phase-contrast magnetic resonance imaging technique to investigate the role of nitric oxide in the regulation of cerebral blood flow in young (25+/-7.1 years; n=8) and old (78+/-6.6 years; n=7) volunteers. The study was performed in a double-blinded fashion and consisted of two study days. On one day the effects of the intravenously infused L-NMMA on CBF and blood pressure was measured and on the other day the effects of a matching placebo. RESULTS: Basal CBF was significantly lower in old compared to young subjects (590+/-20 vs 704+/-20 ml/min), while the cerebral vascular resistance (CVR) levels were significantly higher (0.15+/-0.01 (arbitrary units) vs 0.12+/-0.01, respectively). Infusion of L-NMMA significantly increased mean arterial pressure in both groups (2.8+/-1.2 mmHg; p=0.02 in the young and in the old subjects 5.6+/-1.1 mmHg; p<0.001). Infusion of L-NMMA significantly decreased CBF (49+/-12 ml/min; p<0.001) and increased CVR (0.02+/-0.004; p<0.001) in the old subjects but did not significantly influence cerebral circulation in the young subjects. CONCLUSION: We conclude that compared to young subjects, in old people CBF is impaired, and dependent on the intactness of the nitric oxide pathway.

Adult↗
PubMed2004

Head and neck paragangliomas: improved tumor detection using contrast-enhanced 3D time-of-flight MR angiography as compared with fat-suppressed MR imaging techniques.

BACKGROUND AND PURPOSE: MR imaging techniques have proved their efficacy in imaging the head and neck region. In this study, we compared T1-weighted, dual T2-weighted, and fat-suppressed MR imaging and unenhanced and contrast-enhanced 3D time-of-flight MR angiography sequences for detection of head and neck paragangliomas. METHODS: Thirty-one patients with 70 paragangliomas were examined. Four combinations of MR images were reviewed by two neuroradiologists: T1-weighted and dual T2-weighted fast spin-echo images, T1- and T2-weighted fat-suppressed fast spin-echo images, T1-weighted and contrast-enhanced T1-weighted fat-suppressed spin-echo images, and unenhanced and contrast-enhanced 3D time-of-flight MR angiograms. The randomized examinations were independently evaluated for image quality, presence of tumor, tumor size, and intratumoral flow signal intensity. The standard of reference for presence of tumor was digital subtraction angiography. Data were analyzed by using the logistic regression method. RESULTS: Mean sensitivity, specificity, and negative predictive values, respectively, were assessed by the two observers to be as follows: for dual T2-weighted fast spin-echo, 74%/99%/86%; for T2-weighted fat-suppressed fast spin-echo, 70%/100%/85%; for contrast-enhanced T1-weighted fat-suppressed spin-echo, 73%/100%/86%; and for unenhanced and contrast-enhanced 3D time-of-flight MR angiography, 89%/99%/93%. Sensitivity was significantly better for unenhanced and contrast-enhanced 3D time-of-flight MR angiography (P =.000028). More intratumoral flow signal intensity was depicted with unenhanced and contrast-enhanced 3D time-of-flight MR angiography. CONCLUSION: A combination of unenhanced and contrast-enhanced 3D time-of-flight MR angiography is superior for detecting paragangliomas and should be added to a standard imaging protocol, especially for patients with familial paragangliomas because they are more susceptible to multicentric disease.

Adult↗
PubMed2003

Reproducibility of brain ADC histograms.

The aim of this study was to assess the effect of differences in acquisition technique on whole-brain apparent diffusion coefficient (ADC) histogram parameters, as well as to assess scan-rescan reproducibility. Diffusion-weighted imaging (DWI) was performed in 7 healthy subjects with b-values 0-800, 0-1000, and 0-1500 s/mm(2) and fluid-attenuated inversion recovery (FLAIR) DWI with b-values 0-1000 s/mm(2). All sequences were repeated with and without repositioning. The peak location, peak height, and mean ADC of the ADC histograms and mean ADC of a region of interest (ROI) in the white matter were compared using paired-sample t tests. Scan-rescan reproducibility was assessed using paired-sample t tests, and repeatability coefficients were reported. With increasing maximum b-values, ADC histograms shifted to lower values, with an increase in peak height ( p<0.01). With FLAIR DWI, the ADC histogram shifted to lower values with a significantly higher, narrower peak ( p<0.01), although the ROI mean ADC showed no significant differences. For scan-rescan reproducibility, no significant differences were observed. Different DWI pulse sequences give rise to different ADC histograms. With a given pulse sequence, however, ADC histogram analysis is a robust and reproducible technique. Using FLAIR DWI, the partial-voluming effect of cerebrospinal fluid, and thus its confounding effect on histogram analyses, can be reduced.

Adult↗
PubMed2003

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: MR imaging findings at different ages--3rd-6th decades.

PURPOSE: To depict various brain lesions that have been described in patients who have cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with prospective standardized magnetic resonance (MR) imaging in patients of different age groups. MATERIALS AND METHODS: Forty patients with CADASIL in different age groups (20-30 years, n = 5; 31-40 years, n = 4; 41-50 years, n = 16; 51-60 years, n = 15) underwent transverse MR imaging with T1-weighted dual fast spin-echo, fluid-attenuated inversion-recovery, and T2*-weighted gradient-echo sequences. Images were analyzed by one neuroradiologist for the presence of areas of hyperintensity, lacunar infarcts, microbleeds, and subcortical lacunar lesions (SLLs) in different anatomic locations. Descriptive statistics were obtained for the presence of MR imaging abnormalities in various brain areas and for distribution according to age. RESULTS: The mean age of the 40 mutation carriers (21 women, 19 men) was 45 years +/- 10 (SD). In patients with CADASIL who were 20-30 years old, characteristic hyperintense lesions in the anterior temporal lobe (100% [five of five]) and SLLs (20% [one of five]) were the only abnormalities seen on MR images. In patients who were 30-40 years old, lacunar infarcts were found in 75% (three of four) of cases. More areas of hyperintensity were noted, and they frequently involved the external capsule, basal ganglia, and brainstem. In patients 41-50 years old, microbleeds were observed in 19% (three of 16). In patients older than 50 years, areas of hyperintensity (100% [15 of 15]), SLLs (73% [11 of 15]), lacunar infarcts (93% [14 of 15]), and microbleeds (47% [seven of 15]) were frequently observed. CONCLUSION: The four types of brain lesions that are observed in patients with CADASIL were seen in patients of different age groups.

Adult↗
PubMed2003

Operational definitions for the NINDS-AIREN criteria for vascular dementia: an interobserver study.

BACKGROUND AND PURPOSE: Vascular dementia (VaD) is thought to be the most common cause of dementia after Alzheimer's disease. The commonly used International Workshop of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria for VaD necessitate evidence of vascular disease on CT or MRI of the brain. The purposes of our study were to operationalize the radiological part of the NINDS-AIREN criteria and to assess the effect of this operationalization on interobserver agreement. METHODS: Six experienced and 4 inexperienced observers rated a set of 40 MRI studies of patients with clinically suspected VaD twice using the NINDS-AIREN set of radiological criteria. After the first reading session, operational definitions were conceived, which were subsequently used in the second reading session. Interobserver reproducibility was measured by Cohen's kappa. RESULTS: Overall agreement at the first reading session was poor (kappa=0.29) and improved slightly after application of the additional definitions (kappa=0.38). Raters in the experienced group improved their agreement from almost moderate (kappa=0.39) to good (0.62). The inexperienced group started out with poor agreement (kappa=0.17) and did not improve (kappa=0.18). The experienced group improved in both the large- and small-vessel categories, whereas the inexperienced group improved generally in the extensive white matter hyperintensities categories. CONCLUSIONS: Considerable interobserver variability exists for the assessment of the radiological part of the NINDS-AIREN criteria. Use of operational definitions improves agreement but only for already experienced observers.

Brain↗
PubMed2003

Evaluation of diagnostic NOTCH3 immunostaining in CADASIL.

CADASIL is caused by mutations in the NOTCH3 gene. Although increasingly recognized as a disease entity, the diagnostic confirmation can be lengthy or inconclusive. Recently, NOTCH3 immunostaining of skin biopsy specimens has been introduced as a new diagnostic test. The aim of this study was to independently assess the diagnostic value of NOTCH3 immunostaining, and determine whether the degree of immunostaining correlates with other disease parameters. We determined NOTCH3 mutation carrier status in 62 symptomatic and asymptomatic individuals from 15 CADASIL families. Skin biopsy specimens of these individuals, as well as of a disease control group, were immunostained with NOTCH3 antibody and blindly analyzed by two independent observers to determine sensitivity and specificity. A semiquantitative NOTCH3 immunostaining score was correlated with clinical, genetic and MRI parameters. The sensitivity was 90.2% and 85.4%, respectively, for the two observers, the specificity 95.2% and 100%; both lower than previously reported. Certain NOTCH3 mutations may underlie false-negative results. False-positive results were found in a non-mutated control, and also in one disease control. There was no difference in immunostaining between symptomatic and asymptomatic NOTCH3 mutated individuals. Furthermore, the NOTCH3 immunostaining score did not correlate with clinical or MRI parameters. NOTCH3 immunostaining is a supportive, but not definitive, CADASIL diagnostic test, and should be interpreted in the context of clinical and radiological data. Confirmation by DNA analysis is requisite for positive results, and when there exists high clinical suspicion, also for negative results.

Adult↗
PubMed2003

Voxel-based morphometry in hypocretin-deficient narcolepsy.

STUDY OBJECTIVES: Recent studies suggest that narcolepsy is caused by degeneration of hypocretin (orexin) producing neurons. To find evidence for this hypothesis, we aimed to detect structural changes in the hypothalamus and/or hypocretin projection areas of patients with narcolepsy. DESIGN: We used voxel-based morphometry (VBM), an unbiased MRI morphometric method with a high sensitivity for subtle changes in gray and white matter volumes. SETTING: Image acquisition was carried out in the department of Radiology at Leiden University Medical Center; image post-processing was performed in the Wellcome Department of Cognitive Neurology, London. PARTICIPANTS: Fifteen narcoleptic patients were studied, all having cataplexy and typical findings on Multiple Sleep Latency Testing. All patients were HLA-DQB1*0602 positive and hypocretin-1 deficient. The control group consisted of 15 age and sex matched healthy subjects. MEASUREMENTS AND RESULTS: We found no differences in global gray or white matter volumes between patients and controls. Furthermore, regional gray or white matter volumes in the hypothalamus and hypocretin projection areas did not differ between patients and controls. CONCLUSIONS: VBM failed to show structural changes in the brains of patients with narcolepsy. This suggests that narcolepsy either is associated with microscopic changes undetectable by VBM or that functional abnormalities of hypocretin neurons are not associated with structural correlates.

Adult↗
PubMed2003

Incipient CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene. Knowledge of disease expression in young adult NOTCH3 mutation carriers (MCs) is limited. OBJECTIVE: To characterize clinical, neuropsychological, and radiological status in NOTCH3 MCs younger than 35 years. DESIGN: Clinical characterization and blinded survey comparing MCs with non-MCs. SETTING: Referral center. PARTICIPANTS: Individuals younger than 35 years who were at a 50% risk of a NOTCH3 mutation, from our CADASIL database. Thirteen individuals, from 8 families, met the criteria. METHODS: Comprehensive clinical, genetic, neuropsychological, and radiological investigations. Magnetic resonance images were scored according to a standardized white matter hyperintensities rating scale. RESULTS: Six individuals, from 5 families, were MCs. Clinical symptoms consisted of migraine (with aura), stroke, and stroke-like episodes. We did not find evidence for psychiatric disturbances, functional disability, or cognitive dysfunction, compared with non-MCs. Radiologically, a characteristic magnetic resonance imaging lesion pattern emerged for all MCs. This comprised white matter hyperintensities in the anterior temporal lobes, the frontal lobes, and the periventricular frontal caps. CONCLUSIONS: Migraine (with aura) and stroke can present in NOTCH3 MCs younger than 35 years; however, more importantly, physical function and cognition are intact. Possible subtle cognitive dysfunction needs to be assessed in a larger study. White matter hyperintensities on magnetic resonance imaging are characteristic, and are consistently visualized from the age of 21 years and onward. Awareness of the clinical and radiological features of CADASIL in those younger than 35 years should increase early diagnosis and allow for customized counseling of young adults from families with CADASIL.

Adult↗
PubMed2003

Cerebral hemodynamics and white matter hyperintensities in CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small-vessel disease caused by mutations in the NOTCH3 gene on chromosome 19. On magnetic resonance imaging (MRI), subcortical white matter hyperintensities and lacunar infarcts are visualized. It is unknown whether a decrease in cerebral blood flow or cerebrovascular reactivity is primarily responsible for the development of white matter hyperintensities and lacunar infarcts. The authors used phase-contrast MRI in 40 NOTCH3 mutation carriers (mean age 45 +/- 10 years) and 22 nonmutated family members (mean age 39 +/- 12 years), to assess baseline total cerebral blood flow (TCBF) and cerebrovascular reactivity after acetazolamide. Mean baseline TCBF was significantly decreased in NOTCH3 mutation carriers. In young subjects, baseline TCBF was significantly lower than in nonmutation carriers (mean difference 124 mL/min). Furthermore, baseline TCBF did not differ significantly between mutation carriers with minimal and mutation carriers with moderate or severe white matter hyperintensities. No significant difference in mean cerebrovascular reactivity was found between mutation carriers and nonmutation carriers. This study suggests that a decrease in baseline TCBF in NOTCH3 mutation carriers precedes the development of white matter hyperintensities.

Adult↗
PubMed2003

No influence of melatonin on cerebral blood flow in humans.

Melatonin has been attributed a role in a number of physiological processes. Changes in distal skin temperature and blood pressure after intake of melatonin suggest that melatonin induces peripheral vasodilation. The effect on the cerebral blood flow is still unknown. We examined the effect of a single pulse of melatonin on cerebral and peripheral blood flow, using the latter as a positive control. Ten male healthy volunteers (mean age, 22 +/- 3.2 yr) participated in a double-blind, randomized, placebo-controlled, cross-over study. On one occasion 10 microg melatonin were infused i.v., and on the other occasion saline was infused as the matching placebo. Cerebral blood flow was measured using phase contrast magnetic resonance imaging. Peripheral blood flow was determined from changes in the distal to proximal skin temperature gradient and finger pulse volume. Serum melatonin concentration increased from 12 +/- 5 pg/ml at baseline to 487 +/- 377 pg/ml at 5 min and 156 +/- 68 pg/ml at 10 min after melatonin administration. There was no significantly different time course for cerebral blood flow and cerebrovascular resistance. Compared with placebo, melatonin significantly increased peripheral blood flow, as measured by distal to proximal skin temperature gradient and finger pulse volume. These data demonstrate that melatonin does not have an acute regulatory effect on cerebral blood flow in humans.

Adult↗
PubMed2002

Magnetization transfer imaging in normal aging, mild cognitive impairment, and Alzheimer's disease.

The purpose of this study was to assess whether structural brain damage as detected by volumetric magnetization transfer imaging (MTI) is present in mild cognitive impairment (MCI) and Alzheimer's disease (AD) and, if so, whether these abnormalities are global in character or restricted to the temporal lobe. Volumetric MTI analysis of the whole brain and temporal and frontal lobes was performed in 25 patients with probable AD, in 13 patients with MCI, and in 28 controls. Magnetization transfer ratio (MTR) histograms were produced, from which we derived measures for structural brain damage and atrophy. The peak heights of the MTR histograms of MCI and AD patients were lower than those of controls for the whole brain and temporal and frontal lobes, reflecting structural brain damage. AD patients had more atrophy than controls in all regions that were studied. MCI patients differed from controls for temporal lobe atrophy only. Volumetric MTI demonstrates structural changes that are related to cognitive decline in large parts of the brain of AD patients. Moreover, structural changes also were observed in MCI patients, indicating that widespread brain damage can be demonstrated before patients are clinically demented.

Aged↗
PubMed2002

Reproducibility of total cerebral blood flow measurements using phase contrast magnetic resonance imaging.

PURPOSE: To evaluate reproducibility of total cerebral blood flow (CBF) measurements with phase contrast magnetic resonance imaging (pcMRI). MATERIALS AND METHODS: We repeated total CBF measurements in 15 healthy volunteers with and without cardiac triggering, and with and without repositioning. In eight volunteers measurements were performed at two different occasions. In addition, measurement of flow in a phantom was performed to validate MR measurements. RESULTS: A difference of 40.4 ml/minute was found between CBF measurements performed with and without triggering (P < 0.05). For repeated triggered measurements, the coefficient of variation (CV) was 7.1%, and for nontriggered measurements 10.3%. For repeated measurements with repositioning, the CV was 7.1% with and 11.2% without triggering. Repeated measurements at different occasions showed a CV of 8.8%. Comparing measured with real flow in the phantom, the triggered differed 4.9% and the nontriggered 8.3%. CONCLUSION: The findings of this study demonstrate that pcMRI is a reliable method to measure total CBF in terms of both accuracy and reproducibility.

Adult↗
PubMed2002

MR assessment of cerebral vascular response: a comparison of two methods.

PURPOSE: To compare the results and reproducibility of two MR-based methods of measuring the cerebrovascular response (CVR). MATERIALS AND METHODS: In eight volunteers, CVR was assessed with two MR-based methods upon a challenge with acetazolamide. CVR was assessed by measuring changes in total cerebral blood flow (TCBF) using phase contrast (PC) MRI, and by measuring perfusion MRI. To assess reproducibility the measurements were repeated after 1 week. RESULTS: The average CVR with the PC-MRI method was 46% (SD = 16%), and for perfusion MR the measured CVR was 44% (SD = 16%). The coefficient of variation (COV) for PC-MRI was 28%, while perfusion MR had a COV of 26%. The limits of agreement between the two methods were -49% and 45%, demonstrating a lack of agreement between the two methods in terms of CVR estimation. CONCLUSION: CVR estimates based on PC-MRI and perfusion MRI showed reproducibility but a lack of agreement in healthy volunteers. This lack of agreement can be attributed to the different aspects of the CVR reflected by these methods: TCBF reflects changes in CBF, whereas our perfusion MRI method reflects cerebral blood volume (CBV).

Acetazolamide↗