Clinical Features and Treatment Outcomes in Patients in Their Twenties with Ischemic Moyamoya Disease.

INTRODUCTION: Revascularization surgery is recommended for all pediatric patients with moyamoya disease (MMD) with ischemic symptoms because the brains of such patients are still developing. By contrast, no clear guidelines for selective revascularization surgery in adult patients (30 years or more) with ischemic presentation have been established. Regarding the age of initial onset of ischemic MMD, patients in their 20s are at the bottom of the distribution and this age group may share features with both adult and pediatric patients. The present prospective study aimed to clarify the clinical features and treatment outcomes of patients in their 20s (younger patients) with ischemic MMD compared with patients aged 30-60 years (older patients). METHODS: While patients with misery perfusion in the symptomatic cerebral hemisphere on 15O-positron emission tomography underwent combined surgery including direct and indirect revascularizations in the first study period and indirect revascularization alone in the second study period, patients without misery perfusion in that hemisphere received pharmacotherapy alone through the two study periods. Cerebral angiography via arterial catheterization and neuropsychological testing were performed before and after surgery. RESULTS: During 12 years, 12 younger patients were included and comprised 6% of all adult patients (194 patients). The incidence of misery perfusion in the affected hemisphere was significantly higher in younger (12/12 [100%]) than in older patients (57/182 [31%]) (p < 0.0001). No difference in the incidence of cerebral hyperperfusion syndrome and postoperatively declined cognition was seen between younger (2/5 [40%] and 2/5 [40%], respectively) and older (11/36 [31%] and 15/36 [42%], respectively) cerebral hemispheres undergoing combined revascularization surgery. No difference in the incidence of postoperatively formed collateral flows feeding more than one-third of the middle cerebral artery cortical territory on angiograms and postoperatively improved cognition was seen between younger (9/10 [90%] and 6/10 [60%], respectively) and older (18/22 [83%] and 14/22 [64%], respectively) cerebral hemispheres undergoing indirect revascularization surgery alone. CONCLUSION: Patients in their 20s with ischemic MMD always exhibit misery perfusion in the affected hemisphere, unlike older patients, and sometimes develop cerebral hyperperfusion syndrome after combined revascularization surgery, leading to cognitive decline, similar to older patients. Moreover, indirect revascularization surgery alone forms sufficient collateral circulation and restores cognitive function in patients in their 20s, similar to older patients.

Influence of atherosclerotic burden on adult patients with ischemic moyamoya disease: combined analysis of two prospective cohorts.

OBJECTIVE: This study aimed to determine the influence of atherosclerotic risk factors on initial and further cerebrovascular events in adult patients with moyamoya disease (MMD) by combined analysis of two prospective cohorts in which patients received pharmacotherapy alone and were prospectively followed-up for 5 years. METHODS: In 71 patients, smoking status, home blood pressure, hemoglobin (Hb)A1c and low-density lipoprotein cholesterol (LDL-chol) were checked at inclusion and at further cerebrovascular event or at the end of 5-year follow-up. When a patient had daily smoking, increased HbA1c, increased LDL-chol, increased systolic blood pressure, or increased diastolic blood pressure, the patient was categorized as showing atherosclerotic burden. Angiographic disease progression was determined using changes on magnetic resonance angiography. RESULTS: Eleven patients showed angiographic disease progression and seven of these 11 patients experienced further cerebrovascular events during the follow-up period. The remaining 60 patients did not exhibit either condition. At inclusion, the incidence of atherosclerotic burden was significantly greater in patients without angiographic disease progression (80%) than in those with such progression (45%; p = 0.0249). For patients without angiographic disease progression, values or incidence of almost all variables showed significant interval decreases at the end of 5-year follow-up (p < 0.05). CONCLUSIONS: Adult patients with ischemic MMD who do not exhibit angiographic disease progression appear more strongly affected by atherosclerotic burden at the initial onset of cerebrovascular events than those exhibiting angiographic disease progression. A reduction in atherosclerotic burden by medical treatments for the former patients prevents further cerebrovascular events.

Effect of the addition of 123I-iomazenil single-photon emission computed tomography to brain perfusion single-photon emission computed tomography on the detection accuracy of misery perfusion in adult patients with ischemic moyamoya disease.

OBJECTIVE: The present prospective study aimed to determine whether the addition of 123I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) to brain perfusion SPECT could improve the detection accuracy of misery perfusion on positron emission tomography (PET) in adult patients with ischemic moyamoya disease (MMD). METHODS: Oxygen extraction fraction (OEF) and brain perfusion were assessed using 15O gas PET and N-isopropyl-p-[123I]-iodoamphetamine (IMP) SPECT, respectively, in 137 patients. IMZ SPECT was also performed. Regions of interest (ROIs) were automatically placed in the five middle cerebral artery (MCA) territories ipsilateral to the symptomatic cerebral hemisphere and in the contralateral posterior cerebral artery territory using a three-dimensional stereotaxic ROI template. The radioactive count of the MCA ROI to the contralateral posterior cerebral artery ROI was calculated on IMP SPECT (relative SPECT-IMP uptake) and IMZ SPECT (relative SPECT-IMZ uptake). The relative SPECT-IMZ uptake to the relative SPECT-IMP uptake was also calculated (relative SPECT-IMZ/IMP uptake). Of the five MCA ROIs in the symptomatic cerebral hemisphere in each patient, the ROI with the highest PET-OEF value (one ROI per patient) was selected for analysis. RESULTS: Significant correlations were observed between the PET-OEF and relative SPECT-IMP uptake (correlation coefficient, - 0.683) and relative SPECT-IMZ/IMP uptake (correlation coefficient, 0.875). The area under the receiver operating characteristic curve for detecting misery perfusion (PET-OEF > 51.3%) was significantly greater for the relative SPECT-IMZ/IMP uptake than for the relative SPECT-IMP uptake (difference between areas, 0.080; p = 0.0004). The sensitivity, specificity, and positive- and negative-predictive values for the relative SPECT-IMZ/IMP uptake for detecting misery perfusion were 100%, 92%, 81%, and 100%, respectively. The specificity and positive-predictive value were significantly greater for the relative SPECT-IMZ/IMP uptake than for the relative SPECT-IMP uptake. CONCLUSIONS: The addition of IMZ SPECT to brain perfusion SPECT improves the detection accuracy of misery perfusion on PET in adult patients with ischemic MMD.

Outcomes of Medical Management Alone for Adult Patients with Cerebral Misery Perfusion Due to Ischemic Moyamoya Disease.

OBJECTIVES: Although revascularization surgery is recommended for adult patients with moyamoya disease (MMD) who present with ischemic symptoms due to hemodynamic compromise, the clinical course of such patients who are treated with medical management alone remains unclear. Here, we report outcomes of adult patients with cerebral misery perfusion due to ischemic MMD who received medical management alone. MATERIALS AND METHODS: We prospectively followed up patients who showed misery perfusion in the symptomatic cerebral hemisphere on 15O gas positron emission tomography (PET) and received strict medical management alone after refusing revascularization surgery. RESULTS: Of 57 patients who showed symptomatic misery perfusion on 15O gas PET, three (5%) were included into the present study. Two of these patients suffered further ischemic events at 7 and 8 months after inclusion, after which, their modified Rankin disability scale scores deteriorated. In the remaining patient, fatal intracerebral hemorrhage developed at 10 months after inclusion. CONCLUSIONS: These findings suggest that receiving medical management alone is associated with considerably poor outcomes for adult patients with cerebral misery perfusion due to ischemic MMD.

Recovery of Cortical Neurotransmitter Receptor Function and Its Impact on Cognitive Improvement after Indirect Revascularization Surgery Alone for Adult Patients with Ischemic Moyamoya Disease: 123I-Iomazenil Single-Photon Emission Computed Tomography Study.

OBJECTIVE: Brain 123I-iomazenil single-photon emission computed tomography (SPECT) can assess the distribution of the binding potential of central benzodiazepine receptors in the cerebral cortex. This binding potential may reflect neuronal function in viable tissues. The present prospective study using brain 123I-iomazenil SPECT aimed to determine whether improvements in cognitive function after indirect revascularization surgery alone are associated with postoperative recovery in neurotransmitter receptor function in the affected cerebral hemisphere among adult patients with moyamoya disease accompanied by ischemic presentation due to misery perfusion. METHODS: Twenty-two patients who underwent indirect revascularization surgery alone also underwent brain SPECT scanning at 180 minutes after 123I-iomazenil administration and neuropsychological testing before and at 6 months after surgery. The affected-to-contralateral cerebral hemispheric asymmetry of tracer uptake before and after surgery was then calculated. RESULTS: The asymmetry of tracer uptake was significantly increased after surgery (P < 0.0001). A significant difference between the preoperative and postoperative asymmetry of tracer uptake was seen in patients with improved cognition compared with those with unchanged cognition (P = 0.0001). The area under the receiver operating characteristic curve was 0.99 for the difference between the preoperative and postoperative asymmetry of tracer uptake to assess the ability to discriminate patients with improved cognition from those with unchanged cognition. CONCLUSIONS: Improvements in cognitive function after indirect revascularization surgery alone are associated with postoperative recovery in the binding potential of central benzodiazepine receptors in the affected cerebral hemisphere in adult patients with moyamoya disease accompanied by ischemic presentation due to misery perfusion.

PET With 11C-Methyl-l-Methionine as a Predictor of Consequential Outcomes at the Time of Discontinuing Temozolomide-Adjuvant Chemotherapy in Patients With Residual IDH-Mutant Lower-Grade Glioma.

PURPOSE: The aim of this study was to clarify whether PET with 11C-methyl-l-methionine (11C-met PET) can predict consequential outcomes at the time of discontinuing temozolomide (TMZ)-adjuvant chemotherapy in patients with residual isocitrate dehydrogenase gene (IDH)-mutant lower-grade glioma. PATIENTS AND METHODS: Among 30 patients showing residual lesions of IDH-mutant lower-grade glioma, we compared the tumor-to-normal brain tissue ratio of standardized uptake values (SUVT/N) from 11C-met PET at the time of discontinuing TMZ-adjuvant chemotherapy with putative predictive factors including age, Karnofsky Performance Scale, number of courses of adjuvant therapy, residual tumor size, and promotor methylation status of O6-methylguanine-DNA methyl-transferase gene (MGMT). For each factor, progression-free survival (PFS) was compared between groups divided by cutoff values, determined to predict tumor relapse using receiver operating characteristic curves for each factor. Univariate and multivariate analyses were conducted using log-rank testing and Cox regression analysis, respectively. In addition, PFS was compared between patients grouped by combined findings from multiple predictors identified from univariate and multivariate analyses. RESULTS: Univariate and multivariate analyses identified SUVT/N from 11C-met PET and MGMT methylation status as independent predictors of outcomes after TMZ discontinuation. When comparing 3 groups assigned by the combination of MGMT and SUVT/N findings, PFS differed significantly among groups. CONCLUSIONS: The present study suggested that 11C-met PET at the time of discontinuing TMZ-adjuvant chemotherapy allows prediction of outcomes at least comparable to MGMT methylation status in patients with residual IDH-mutant lower-grade glioma. Further, 11C-met PET allows more precise prediction of outcomes by assessment in combination with MGMT findings.

Angiographic, Cerebral Hemodynamic, and Cognitive Outcomes of Indirect Revascularization Surgery Alone for Adult Patients With Misery Perfusion due to Ischemic Moyamoya Disease.

BACKGROUND: Revascularization surgery for adult patients with ischemic moyamoya disease (MMD) may improve both cognitive function and cerebral perfusion. OBJECTIVE: To determine angiographic, cerebral hemodynamic, and cognitive outcomes of indirect revascularization surgery alone for adult patients with misery perfusion due to ischemic MMD (IDR group) and to test the superiority of indirect revascularization surgery for cognitive improvement by conducting comparisons with historical control patients who had undergone direct revascularization surgery (DR group) through prospective cohort study with historical controls. METHODS: Twenty adult patients with cerebral misery perfusion underwent encephalo-duro-myo-arterio-pericranial-synangiosis alone. Cerebral angiography through arterial catheterization, brain perfusion single-photon emission computed tomography, and neuropsychological testing were performed preoperatively and at 6 months postoperatively. RESULTS: In 17 patients of the IDR group, collateral flows that were newly formed after surgery on angiograms fed more than one-third of the middle cerebral artery (MCA) cortical territory. In the IDR group, perfusion in the MCA territory was significantly increased after surgery (P < .0001), and the difference in MCA perfusion between before and after surgery was significantly greater (P = .0493) compared with the DR group. Improved cognition was significantly more frequent in the IDR group (65%) than in the DR group (31%, P = .0233). CONCLUSION: Indirect revascularization surgery alone forms sufficient collateral circulation, improves cerebral hemodynamics, and recovers cognitive function in adult patients with misery perfusion due to ischemic MMD. The latter 2 beneficial effects may be higher when compared with patients undergoing direct revascularization surgery.

Delayed development of cerebral atrophy after cerebral hyperperfusion following arterial bypass for adult patients with ischemic moyamoya disease: supplementary analysis of a 5-year prospective cohort.

BACKGROUND: Adult patients with moyamoya disease (MMD) occasionally exhibit cerebral hyperperfusion after arterial bypass surgery, leading to persistent cognitive decline. The present supplementary analysis of a prospective 5-year cohort study aimed to determine whether cerebral hyperperfusion after arterial bypass surgery for adult patients with misery perfusion due to ischemic MMD causes cerebral atrophy, and whether the development of cerebral atrophy is related to persistent cognitive decline. METHODS: In total, 31 patients who underwent arterial bypass surgery also underwent fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) and neuropsychological testing before surgery and at the end of a 5-year follow-up. The development of cerebral hyperperfusion and hyperperfusion syndrome after surgery was defined based on brain perfusion single-photon emission computed tomography (SPECT) findings and clinical symptoms. Univariate and multivariate logistic regression analyses of factors related to the development of cerebral atrophy on FLAIR MRI or cognitive decline on neuropsychological testing at the end of the 5-year follow-up were performed. RESULTS: Eleven patients (35%) developed cerebral atrophy in the frontal lobe where the superficial temporal artery was anastomosed. Cerebral hyperperfusion on brain perfusion SPECT (odds ratio [OR], 50.6; p = 0.0008) or cerebral hyperperfusion syndrome (OR, 41.8; p = 0.0026) was independently associated with the development of cerebral atrophy, and cerebral atrophy development was significantly associated with cognitive decline (OR, 47.7; p = 0.0010). CONCLUSIONS: Cerebral hyperperfusion after arterial bypass surgery for adult patients with misery perfusion due to ischemic MMD can cause cerebral atrophy related to persistent cognitive decline.

Five-Year Outcomes of Medical Management Alone for Adult Patients with Ischemic Moyamoya Disease without Cerebral Misery Perfusion.

INTRODUCTION: No clear guidelines for treating adult patients with ischemic moyamoya disease (MMD) without cerebral hemodynamic compromise such as misery perfusion have been established. Our previous prospective cohort study of adult patients with MMD without misery perfusion who were treated with medical management alone, including an antiplatelet drug, showed a recurrent ischemic event rate of 3% per 2 years. The present prospective study aimed to elucidate the 5-year clinical, cerebral perfusion, and cognitive outcomes of medical management alone for Japanese adult patients with ischemic MMD without cerebral misery perfusion by following the same patients for another 3 years. METHODS: In total, 68 patients without recurrent events at a 2-year follow-up were prospectively followed up for another 3 years. Cerebral blood flow (CBF) in the symptomatic cerebral hemisphere was measured using brain perfusion single-photon emission computed tomography at inclusion and at the end of the subsequent 3-year follow-up. Neuropsychological testing was performed at inclusion and at the end of the initial 2- and subsequent 3-year follow-ups. RESULTS: During the subsequent 3-year follow-up, 2 patients (3%) developed further ischemic events. In patients without further ischemic events, CBF was significantly greater at the end of the subsequent 3-year follow-up than at inclusion (p = 0.0037), and all neuropsychological test scores improved or remained unchanged at the end of initial 2- and subsequent 3-year follow-ups compared with that at inclusion. CONCLUSION: In adult patients receiving medical management alone for ischemic MMD without cerebral misery perfusion, the incidence of further ischemic events was 6% per 5 years and did not change between the initial 2 years after the last is-chemic event and the subsequent 3 years. In patients without further ischemic events, CBF and cognitive function had not deteriorated at 5 years after the last ischemic event.

Angiographic disease progression in medically treated adult patients with ischemic moyamoya disease without cerebral misery perfusion: supplementary analysis of a 5-year prospective cohort.

Angiographic disease progression reportedly develops in adult moyamoya disease (MMD). However, more than half of patients analyzed underwent revascularization surgery. The present supplementary analysis of a 5-year prospective cohort with follow-up using magnetic resonance angiography (MRA) and cerebral blood flow (CBF) measurements was to elucidate the incidence and clinical features of angiographic disease progression in adult patients receiving medical management alone for ischemic MMD. Sixty-eight patients without misery perfusion in the symptomatic cerebral hemispheres underwent MRA and CBF measurement using brain perfusion single-photon emission computed tomography at inclusion and at the end of the 5-year follow-up. When neurological symptoms recurred or newly developed during the 5-year follow-up period, additional MRA and CBF measurements were also performed at that time. All four patients with further ischemic events during the 5-year follow-up period exhibited angiographic disease progression on MRA at such events. Of the remaining 64 patients without further events during the 5-year follow-up period, four exhibited angiographic disease progression on MRA at the end of the 5-year follow-up. CBF was significantly lower at the time of further ischemic events or at the end of the 5-year follow-up than at inclusion in eight patients with angiographic disease progression (p = 0.0117). The incidence of angiographic disease progression was 12% for 5 years in medically treated adult patients with ischemic MMD without cerebral misery perfusion. Patients with further ischemic events always exhibited angiographic disease progression. Cerebral perfusion was reduced in patients with angiographic disease progression even when further ischemic events did not occur.

De Novo Cerebral Microbleeds and Cognitive Decline in Cerebral Hyperperfusion After Direct Revascularization for Adult Moyamoya Disease.

OBJECTIVES: Adult patients with moyamoya disease (MMD) occasionally develop cognitive decline due to cerebral hyperperfusion following direct revascularization surgery. However, how the hyperperfusion phenomenon contributes to declines in cognitive function remains unclear. The present supplementary analysis of a prospective study aimed to determine whether cerebral hyperperfusion following direct revascularization surgery for adult MMD with ischemic presentation and misery perfusion leads to development of de novo cerebral microbleeds (CMBs) and whether postoperative cognitive decline is related to these CMBs. MATERIALS AND METHODS: In total, 32 patients who underwent direct revascularization surgery also underwent T2*-weighted magnetic resonance imaging (T2*WI) and neuropsychological testing before and 2 months after surgery. Development of cerebral hyperperfusion and hyperperfusion syndrome following surgery was defined based on brain perfusion single-photon emission computed tomography (SPECT) findings and clinical symptoms. RESULTS: Cerebral hyperperfusion on brain perfusion SPECT (95% confidence interval [CI], 1.1-10.8; p = 0.0175) or cerebral hyperperfusion syndrome (95%CI, 1.3-15.3; p = 0.0029) was significantly associated with postoperatively increased CMBs on T2*WI. Postoperatively increased CMBs were significantly associated with postoperative cognitive decline (95%CI, 1.8-20.4, p = 0.0041). For patients with cerebral hyperperfusion on brain perfusion SPECT, the incidence of postoperative cognitive decline was significantly greater in patients with than in those without postoperatively increased CMBs (p = 0.0294). CONCLUSIONS: Cerebral hyperperfusion following direct revascularization surgery for adult MMD with ischemic presentation and misery perfusion contributes to the development of de novo CMBs and postoperative cognitive decline is related to these CMBs.

Long-Term Cognitive Changes after Revascularization Surgery in Adult Patients with Ischemic Moyamoya Disease.

INTRODUCTION: Revascularization surgery for adult moyamoya disease (MMD) with ischemic presentation changes cognitive function and prevents further cerebral ischemic events. Most studies however repeated neuropsychological evaluation within 1 year after surgery. Our previous prospective cohort study of adult patients with MMD with misery perfusion who underwent direct revascularization surgery showed cognitive improvement and decline in 31% and 44%, respectively, of the patients 2 months after surgery. The present prospective study aimed to elucidate the 5-year cognitive changes after direct revascularization surgery in adult patients with cerebral misery perfusion due to ischemic MMD by following the same patients. METHODS: In total, 31 patients were prospectively followed up for 5 years after direct revascularization surgery. Five types of neuropsychological tests were performed preoperatively, 2 months after surgery, and at the end of the 5-year follow-up. Cerebral blood flow (CBF) in the symptomatic cerebral hemisphere relative to that in the ipsilateral cerebellar hemisphere (hemispheric relative CBF [RCBF]) was measured using brain perfusion single-photon emission computed tomography preoperatively and at the end of the 5-year follow-up. RESULTS: Based on results of pre- and postoperative neuropsychological tests, 11, 10, and 10 patients showed cognitive improvement, no change in cognitive function, and cognitive decline, respectively, at the end of the 5-year follow-up. These ratios were not significantly different compared with those 2 months after surgery (cognitive improvement, no change in cognitive function, and cognitive decline in 10, 8, and 13 patients, respectively). Although hemispheric RCBF was significantly greater at the end of the 5-year follow-up than before surgery in patients with cognitive improvement (80.7 ± 6.1% vs. 92.9 ± 5.5%; p = 0.0033) and in those showing no change in cognitive function (85.6 ± 3.5 vs. 91.5 ± 5.2%; p = 0.0093), this value was significantly lower at the end of the 5-year follow-up than before surgery in patients with cognitive decline (83.8 ± 3.7 vs. 81.0 ± 5.8%; p = 0.0367). CONCLUSION: One-third of adult patients with cerebral misery perfusion due to ischemic MMD who underwent direct revascularization surgery exhibited cognitive improvement, and one-third exhibited decline at the end of the 5-year follow-up. The former and latter patients had increased and decreased CBF, respectively, in the affected cerebral hemisphere at the end of the 5-year follow-up compared with preoperative brain perfusion.

Development of cerebral microbleeds in patients with cerebral hyperperfusion following carotid endarterectomy and its relation to postoperative cognitive decline.

OBJECTIVE: A primary cause of cognitive decline after carotid endarterectomy (CEA) is cerebral injury due to cerebral hyperperfusion. However, the mechanisms of how cerebral hyperperfusion induces cerebral cortex and white matter injury are not known. The presence of cerebral microbleeds (CMBs) on susceptibility-weighted imaging (SWI) is independently associated with a decline in global cognitive function. The purpose of this prospective observational study was to determine whether cerebral hyperperfusion following CEA leads to the development of CMBs and if postoperative cognitive decline is related to these developed CMBs. METHODS: During the 27-month study period, patients who underwent CEA for ipsilateral internal carotid artery stenosis (≥ 70%) also underwent SWI and neuropsychological testing before and 2 months after surgery, as well as quantitative brain perfusion SPECT prior to and immediately after surgery. RESULTS: According to quantitative brain perfusion SPECT and SWI before and after surgery, 12 (16%) and 7 (9%) of 75 patients exhibited postoperative cerebral hyperperfusion and increased CMBs in the cerebral hemisphere ipsilateral to surgery, respectively. Cerebral hyperperfusion was associated with an increase in CMBs after surgery (logistic regression analysis, 95% CI 5.08-31.25, p < 0.0001). According to neuropsychological assessments before and after surgery, 10 patients (13%) showed postoperative cognitive decline. Increased CMBs were associated with cognitive decline after surgery (logistic regression analysis, 95% CI 6.80-66.67, p < 0.0001). Among the patients with cerebral hyperperfusion after surgery, the incidence of postoperative cognitive decline was higher in those with increased CMBs (100%) than in those without (20%; p = 0.0101). CONCLUSIONS: Cerebral hyperperfusion following CEA leads to the development of CMBs, and postoperative cognitive decline is related to these developed CMBs.

Optimal timing for measuring cerebral blood flow after acetazolamide administration to detect preexisting cerebral hemodynamics and metabolism in patients with bilateral major cerebral artery steno-occlusive diseases: 15O positron emission tomography studies.

The present study determined the optimal timing of scanning for measurement of cerebral blood flow (CBF) after acetazolamide (ACZ) administration for detection of preexisting cerebral hemodynamics and metabolism in bilateral major cerebral artery steno-occlusive diseases. Thirty three patients underwent 15O gas positron emission tomography (PET) and each parameter was obtained in the bilateral middle cerebral artery (MCA) territories. CBF was also obtained using H2 15O PET scanning performed at baseline and at 5, 15, and 30 min after ACZ administration. Relative CBF at each time point after ACZ administration to baseline CBF was calculated. For MCA territories with normal cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO2), CBF continued increasing until 15 min after ACZ administration. For MCA territories with abnormally increased CBV, CBF decreased 5 min after ACZ administration. After that, CBF continued increasing until 30 min after ACZ administration. For MCA territories with abnormally decreased CMRO2, CBF did not change 5 min after ACZ administration. Ten min later, CBF increased. The accuracy to detect abnormally increased CBV was significantly greater for relative CBF5 than for relative CBF15. The accuracy to detect abnormally decreased CMRO2 was significantly greater for relative CBF5 or CBF15 than for relative CBF30. For detecting abnormally increased oxygen extraction fraction, the accuracy did not differ among each relative CBF. These findings suggested that CBF measurement at 5 min after ACZ administration is the optimal timing for detection of preexisting cerebral hemodynamics and metabolism in bilateral major cerebral artery steno-occlusive diseases.

A concentration-based microscale method for 18F-nucleophilic substitutions and its testing on the one-pot radiosynthesis of [18F]FET and [18F]fallypride.

When applied to a radiosynthesis, a microscale approach can help to save precursor and improve yields. Thus, a 5-10 µL microscale method based on a concentration procedure was developed and applied to the radiosynthesis of [18F]FET and [18F]fallypride. In spite of using an amount of precursor ca. 100 times smaller, radiochemical yields were comparable or even higher than those reported in literature. Because of the very low reaction volumes, the possible effects of concentrated dose of activity and carrier fluoride were also investigated.

Improvement in gait function after carotid endarterectomy is associated with postoperative recovery in perfusion and neurotransmitter receptor function in the motor-related cerebral cortex: a 123I-iomazenil SPECT study.

OBJECTIVE: Carotid endarterectomy (CEA) often restores cerebral perfusion and neurotransmitter receptor function, which is seen on early and late images, respectively, on brain I-iomazenil single-photon emission computed tomography (SPECT). The reliability of gait-related parameters obtained using a triaxial accelerometer, a portable device for gait assessment, has been confirmed with test-retest measurements. The purpose of the present prospective cohort study was to determine whether improvement in gait function after CEA is associated with postoperative recovery in perfusion and neurotransmitter receptor function in the motor-related cerebral cortex. METHODS: Gait testing using a triaxial accelerometer was performed preoperatively and 6 months postoperatively in 64 patients undergoing CEA for ipsilateral internal carotid artery stenosis (≥70%). I-iomazenil SPECT was also performed with scanning within 30 min (early images) and at 180 min (late images) after tracer administration before and after surgery. SPECT data were analyzed using a three-dimensional stereotactic surface projection, and motor (Brodmann 4) and premotor (Brodmann 6) cortexes in each hemisphere were combined and defined as the motor-related cortex. RESULTS: Based on preoperative and postoperative gait testing, seven patients (11%) showed postoperative improved gait. Logistic regression analysis revealed that postoperative increase in I-iomazenil uptake in the motor-related cortex ipsilateral to surgery on early [95% confidence interval (CI), 4.32-365.21; P = 0.0477) or late (95% CI, 9.45-1572.57; P = 0.0173) images was an independent predictor of postoperative improved gait. CONCLUSIONS: Improvement in gait function after CEA is associated with postoperative recovery in perfusion and neurotransmitter receptor function in the motor-related cerebral cortex.

Decrease in 18F-Florbetapir Accumulation in the Cerebral Hemisphere With Hypoperfusion and Misery Perfusion Due to Chronic Atherosclerotic Occlusion of the Internal Carotid Artery.

A 67-year-old man had a slowly progressing impairment of recent memory. Cerebral angiography showed atherosclerotic occlusion of the right internal carotid artery with insufficient collateral circulation. Positron emission tomography (PET) using O2 gas showed reduced cerebral blood flow, reduced cerebral metabolic rate of oxygen, and elevated oxygen extraction fraction in the precentral region of the right cerebral hemisphere. Use of F-florbetapir PET depicted amyloid ß deposition as decreased tracer uptake in the precentral region in the right cerebral hemisphere when compared with the contralateral hemisphere.

Impacts on Histological Features and 11C-Methyl-L-methionine Uptake After "One-Shot" Administration with Bevacizumab Before Surgery in Newly Diagnosed Glioblastoma.

BACKGROUND: Bevacizumab (BEV), an antiangiogenic agent, induces dramatic normalization of the tumor vasculature in glioblastoma. This study aimed to clarify how one-time administration of BEV changes histological features in glioblastoma and how histological changes affect the uptake of 11C-methyl-L-methionine (11C-met) as an amino-acid tracer. MATERIALS AND METHODS: Subjects were 18 patients with newly diagnosed glioblastoma who were assigned to two groups: BEV group, single intravenous administration of BEV before surgical tumor removal; and control group, surgical tumor removal alone. After surgery, we compared the densities of tumor cells and microvessels, and microvascular structures including vascular pericytes and L-type amino acid transporter-1 (LAT1) between the BEV and control groups. Correlations between 11C-met uptake on positron emission tomography before surgery, microvascular density, and LAT1 expression were assessed in each group. RESULTS: BEV induced significant reductions in microvascular density, while tumor cell density and proliferation were retained in the BEV group. Percentages of vessels with pericytes and vascular endothelium with LAT1 expression were lower in the BEV group than in controls. Uptake of 11C-met correlated significantly with microvascular density in the BEV group but not with LAT1expression. CONCLUSIONS: The present study showed that even one course of BEV administration induced reductions in microvessels, vascular pericytes, and LAT1 expression in glioblastomas. One course of BEV therapy also reduced 11C-met uptake, which might have been largely attributed to reductions in microvessels rather than reductions in LAT1 expression.

Reduced Hypoxic Tissue and Cognitive Improvement after Revascularization Surgery for Chronic Cerebral Ischemia.

BACKGROUND: Hypoxic but viable neural tissue is seen on 1-(2-18F-fluoro-1-[hydroxymethyl]ethoxy) methyl-2-nitroimidazole (18F-FRP170) positron emission tomography (PET) in patients with chronic cerebral ischemia with a combination of misery perfusion and moderately reduced oxygen metabolism. Cognitive function sometimes improves after revascularization surgery in patients with chronic cerebral ischemia. OBJECTIVES: We used brain perfusion single-photon emission computed tomography (SPECT) and 18F-FRP170 PET to determine whether hypoxic tissue was reduced following the restoration of cerebral perfusion after carotid endarterectomy (CEA) in patients with severe stenosis of the cervical internal carotid artery (ICA) and whether the reduction in hypoxic tissue was associated with cognitive improvement. METHOD: Eighteen patients with abnormally reduced cerebral blood flow (CBF) in the affected cerebral hemispheres on preoperative brain perfusion SPECT -underwent CEA. They underwent 18F-FRP170 PET and neuropsychological tests preoperatively and 6 months postoperatively. Brain perfusion SPECT was also performed 6 months postoperatively. Regions of interest were placed in the bilateral middle cerebral artery territories on SPECT and PET images, and the ratio of values in the affected versus contralateral hemispheres was calculated. RESULTS: The CBF ratio (p = 0.0006) and 18F-FRP170 ratio (p = 0.0084) were significantly increased and reduced, respectively, after surgery compared to the corresponding ratios before surgery. The difference in the 18F-FRP170 ratio (postoperative - preoperative value) was negatively correlated with the difference in the CBF ratio (ρ = -0.695; p = 0.0009). The difference in the 18F-FRP170 ratio was significantly lower in patients with postoperative improved cognition compared to that in those without (p = 0.0007). The area under the receiver operating characteristics curve for the difference in the 18F-FRP170 ratio for detecting postoperative improved cognition was significantly greater than that for the difference in the CBF ratio (difference between areas, 0.278; p = 0.0248). CONCLUSIONS: Hypoxic tissue is reduced following the restoration of cerebral perfusion with revascularization surgery in patients with severe atherosclerotic stenosis of the cervical ICA. The reduction in hypoxic tissue is associated with cognitive improvement in such patients.