Kohei Chida

Postoperative Cortical Neural Loss Associated With Cerebral Hyperperfusion and Cognitive Impairment After Carotid Endarterectomy 123I-iomazenil SPECT Study

Background and Purpose— Although cerebral hyperperfusion after carotid endarterectomy (CEA) often impairs cognitive function, MRI does not always demonstrate structural brain damage associated with postoperative cognitive impairment. The purpose of the present study was to determine whether postoperative cortical neural loss, which can be detected by 123I-iomazenil single-photon emission CT, is associated with cerebral hyperperfusion after CEA and whether it correlates with postoperative cognitive impairment. Methods— In 60 patients undergoing CEA for ipsilateral internal carotid artery stenosis (>70%), cerebral blood flow was measured using N-isopropyl-p-[123I]-iodoamphetamine single-photon emission CT before and immediately after CEA and on the third postoperative day. The distribution of benzodiazepine receptor binding potential in the cerebral cortex was assessed using 123I-iomazenil single-photon emission CT before and 1 month after surgery and was analyzed using 3-dimensional stereotactic surface projection. Neuropsychological testing was also performed preoperatively and at the first postoperative month. Results— Post-CEA hyperperfusion and postoperative cognitive impairment were observed in 9 patients (15%) and 8 patients (13%), respectively. Post-CEA hyperperfusion was significantly associated with postoperative hemispheric reduction of benzodiazepine receptor binding potential (95% CIs, 2.765 to 148.804; P=0.0031). Post-CEA hyperperfusion (95% CIs, 1.183 to 229.447; P=0.0370) and postoperative hemispheric reduction of benzodiazepine receptor binding potential (95% CIs, 1.003 to 77.381; P=0.0496) were also significantly associated with postoperative cognitive impairment. Conclusions— Cerebral hyperperfusion after CEA results in postoperative cortical neural loss that correlates with postoperative cognitive impairment.

Postcarotid endarterectomy improvement in cognition is associated with resolution of crossed cerebellar hypoperfusion and increase in 123I-iomazenil uptake in the cerebral cortex: a SPECT study.

Background: The purpose of the present study was to investigate whether resolution of crossed cerebellar hypoperfusion (CCH) and increase in 123I-iomazenil (IMZ) uptake in the ipsilateral cerebral cortex after carotid endarterectomy (CEA) are associated with postoperative improvement of cognitive function. Methods: Neuropsychological testing was performed preoperatively and after 1 postoperative month in 79 patients undergoing CEA for ipsilateral internal carotid artery stenosis (≧70%). Brain perfusion single photon emission computed tomography (SPECT) using N-isopropyl-p-123I-iodoamphetamine and 123I-IMZ SPECT were also performed before and after surgery. Data were analyzed using a three-dimensional stereotaxic region of interest template. Results: Seven patients (9%) showed improvement in postoperative cognitive function. All the 7 patients exhibited both postoperative increase in blood flow in the ipsilateral cerebral cortex and resolution of CCH. Five patients (6%) had a postoperative hemispheric increase in 123I-IMZ uptake, and cognitive function improved in all of these 5 patients. Analysis by a receiver operating characteristic (ROC) curve was used to estimate the ability to discriminate between patients with and without postoperative cognitive improvement. The area under the ROC curve was significantly greater when analyzing the magnitude of postoperative resolution of CCH (0.991; 95% CI 0.984–1.001) or postoperative hemispheric increase in 123I-IMZ uptake (0.981; 95% CI 0.972–0.999) when compared with the magnitude of postoperative increase in cerebral blood flow (0.929; 95% CI 0.886–0.971) (p < 0.05). Conclusions: Resolution of CCH and increase in 123I-IMZ uptake in the ipsilateral cerebral cortex after CEA is associated with postoperative improvement in cognitive function. These results may indicate that cognitive impairment is related to a state of potentially reversible central benzodiazepine receptor downregulation in the cortex in response to transient ischemic attack or minor stroke.

PREDICTION OF CEREBRAL HYPERPERFUSION AFTER CAROTID ENDARTERECTOMY USING MIDDLE CEREBRAL ARTERY SIGNAL INTENSITY IN PREOPERATIVE SINGLE-SLAB 3-DIMENSIONAL TIME-OF-FLIGHT MAGNETIC RESONANCE ANGIOGRAPHY

OBJECTIVECerebral hyperperfusion after carotid endarterectomy (CEA) occurs in patients with preoperative impairments in cerebral hemodynamics. Signal intensity of the middle cerebral artery (MCA) on single-slab 3-dimensional time-of-flight magnetic resonance angiography (MRA) can assess hemodynamic impairment in the cerebral hemisphere. The purpose of the present study was to determine whether the signal intensity of the MCA on preoperative MRA could identify patients at risk for cerebral hyperperfusion after CEA. METHODSThe signal intensity of the MCA ipsilateral to CEA on preoperative MRA was graded according to the ability to visualize the MCA in 81 patients with ipsilateral internal carotid artery stenosis (≥70%). Cerebral blood flow was also quantified using single-photon emission computed tomography before and immediately after CEA and on the third postoperative day. RESULTSCerebral hyperperfusion immediately after CEA (cerebral blood flow increase ≥100% compared with preoperative values) was observed in 10 patients. Multivariate analysis revealed that only reduced signal intensity of the MCA was significantly associated with the development of postoperative cerebral hyperperfusion (95% confidence interval, 1.015–1.401; P = 0.0319). When the reduced signal intensity of the MCA on MRA was defined as an impairment in cerebral hemodynamics, MRA grading resulted in 100% sensitivity and 63% specificity, with a 28% positive predictive value and a 100% negative predictive value for the development of post-CEA hyperperfusion. Hyperperfusion syndrome developed on the fourth and sixth postoperative days in 2 of the 10 patients who exhibited hyperperfusion immediately after CEA. CONCLUSIONSignal intensity of the MCA, as assessed by this simple MRA method, may identify patients at risk for post-CEA cerebral hyperperfusion.

Brain Temperature Measured Using Proton MR Spectroscopy Detects Cerebral Hemodynamic Impairment in Patients With Unilateral Chronic Major Cerebral Artery Steno-Occlusive Disease Comparison With Positron Emission Tomography

Background and Purpose— Brain temperature is determined by the balance between heat produced by cerebral energy turnover and heat removed by cerebral blood flow. The purpose of the present study was to investigate whether brain temperature measured noninvasively using proton MR spectroscopy can detect cerebral hemodynamic impairment in patients with unilateral chronic internal carotid or middle cerebral artery occlusive disease when compared with positron emission tomography. Methods— Brain temperature, cerebral blood flow, and metabolism were measured using proton MR spectroscopy and 15O-positron emission tomography, respectively, in 21 normal subjects and 37 patients. Positron emission tomography images were coregistered with MR images and resliced automatically using image analysis software. Regions of interest placed in both cerebral hemispheres on MR images were automatically superimposed in these resliced positron emission tomography images. Results— A significant correlation was observed between brain temperature difference (affected hemisphere–contralateral hemisphere) and both cerebral blood volume and oxygen extraction fraction ratio (affected hemisphere/contralateral hemisphere; r=0.607; P=0.0004 and r=0.631; P=0.0002). With abnormally elevated cerebral blood volume or oxygen extraction fraction ratio defined as higher than the mean +2 SDs obtained from normal subjects, brain temperature difference provided 86% or 92% sensitivity and 87% or 84% specificity with 80% or 73% positive and 91% or 95% negative predictive values for detecting abnormally elevated cerebral blood volume or oxygen extraction fraction ratios, respectively. Conclusions— Brain temperature measured using proton MR spectroscopy can detect cerebral hemodynamic impairment in patients with unilateral chronic major cerebral artery steno-occlusive disease.

Intraoperative Microemboli and Low Middle Cerebral Artery Blood Flow Velocity Are Additive in Predicting Development of Cerebral Ischemic Events After Carotid Endarterectomy

Background and Purpose— Microemboli generated during dissection of the carotid arteries in patients undergoing carotid endarterectomy result in postoperative cerebral ischemic events. The purpose of this study was to determine whether these events correlate with middle cerebral artery blood flow velocity. Methods— One hundred sixty-three patients with ipsilateral internal carotid artery stenosis (>70%) underwent carotid endarterectomy under transcranial Doppler monitoring of mean blood flow velocity and microembolic signals in the ipsilateral middle cerebral artery. Results— Logistic regression analysis of several variables demonstrated that only middle cerebral artery mean blood flow velocity during carotid dissection was significantly associated with new postoperative neurological deficits in patients with microembolic signals during carotid dissection (95% CI, 1.069 to 1.528; P=0.0072). The combination of low middle cerebral artery mean blood flow velocity (≤28 cm/s) and microembolic signals ≥10 during carotid dissection resulted in improved specificity and positive predictive value for the development of new postoperative neurological deficits when compared with either criterion used alone. Conclusions— Intraoperative microemboli and low middle cerebral artery mean blood flow velocity are additive in predicting the development of cerebral ischemic events after carotid endarterectomy.

Central benzodiazepine receptor binding potential and CBF images on SPECT correlate with oxygen extraction fraction images on PET in the cerebral cortex with unilateral major cerebral artery occlusive disease.

Oxygen extraction fraction (OEF) is a key predictor of stroke recurrence in patients with symptomatic major cerebral arterial occlusive disease. The purpose of the present study was to compare central benzodiazepine receptor binding potential (BRBP) and cerebral blood flow (CBF) images on SPECT with OEF images on PET in patients with chronic unilateral middle cerebral artery (MCA) or internal carotid artery (ICA) occlusive disease. Methods: OEF, CBF, and BRBP were assessed using 15O PET and N-isopropyl-p-123I-iodoamphetamine and 123I-iomazenil SPECT, respectively, in 20 healthy subjects and in 34 patients with unilateral MCA or ICA occlusive disease. All images were transformed into the standard brain size and shape by linear and nonlinear transformation using statistical parametric mapping for anatomic standardization. A region of interest (ROI) was automatically placed according to the arterial supply using a 3-dimensional stereotactic ROI template, and the ratio of the value in the affected side to that in the contralateral side was calculated in each image. Results: Among patients with occlusive disease, a significant positive correlation was observed between PET OEF and SPECT BRBP/CBF ratios in 3 cerebral cortical regions (r = 0.851, P < 0.0001, for anterior cerebral artery [ACA] ROI; r = 0.807, P < 0.0001, for MCA ROI; and r = 0.774, P < 0.0001, for posterior cerebral artery [PCA] ROI), but there were no correlations between these 2 parameters in the basal ganglia or the cerebellum. When an abnormally elevated PET OEF ratio was defined as a value greater than the mean + 2 SDs obtained in healthy subjects, sensitivity and specificity were, respectively, 100% and 96% for the ACA ROI, 100% and 89% for the MCA ROI, and 100% and 93% for the PCA ROI for the SPECT BRBP/CBF ratio for detecting an abnormally elevated PET OEF ratio. Conclusion: BRBP/CBF images on SPECT correlate with OEF images on PET in a specific clinical setting—that is, in the cerebral cortex of patients with chronic unilateral MCA or ICA occlusive disease.

Simple Assessment of Cerebral Hemodynamics Using Single-Slab 3D Time-of-Flight MR Angiography in Patients with Cervical Internal Carotid Artery Steno-Occlusive Diseases : Comparison with Quantitative Perfusion Single-Photon Emission CT

BACKGROUND AND PURPOSE: Visualization of the peripheral arteries on single-slab 3D time-of-flight (TOF) MR angiography (MRA) can reflect blood flow velocity. The velocity in the middle cerebral artery (MCA) may correlate with cerebrovascular reactivity (CVR) to acetazolamide, which can be used to assess hemodynamic impairment. The goal of this study was to compare the signal intensity of the MCA on MRA versus CVR quantified by perfusion single-photon emission CT (SPECT). MATERIALS AND METHODS: The signal intensity of the MCA on single-slab 3D time-of-flight MRA was graded according to the ability to visualize the MCA in 108 cerebral hemispheres of 87 patients with unilateral or bilateral cervical internal carotid artery (ICA) steno-occlusive diseases. SPECT-CVR was also calculated by measuring cerebral blood flow before and after acetazolamide challenge. Ten healthy subjects were studied to obtain control SPECT-CVR values. All subjects provided written informed consent before the study. RESULTS: CVR was significantly lower in cerebral hemispheres with reduced MCA signal intensity than in those with normal intensity (P < .05). When the reduced signal intensity of the MCA on MRA was defined as abnormal, and when a CVR less than the mean − 2 SD of healthy subjects was defined as reduced, MRA grading resulted in a 86.2% sensitivity and 69.6% specificity, with 51.0% positive-predictive and 93.2% negative-predictive values to detect reduced CVR. CONCLUSIONS: This simple MRA method can assess hemodynamic impairment with a high negative-predictive value.

Significance of postoperative crossed cerebellar hypoperfusion in patients with cerebral hyperperfusion following carotid endarterectomy: SPECT study

PurposeCerebral hyperperfusion after carotid endarterectomy (CEA) results in cerebral hyperperfusion syndrome and cognitive impairment. The goal of the present study was to clarify the clinical significance of postoperative crossed cerebellar hypoperfusion (CCH) in patients with cerebral hyperperfusion after CEA by assessing brain perfusion with single-photon emission computed tomography (SPECT).MethodsBrain perfusion was quantitatively measured using SPECT and the [123I]N-isopropyl-p-iodoamphetamine-autoradiography method before and immediately after CEA and on the third postoperative day in 80 patients with ipsilateral internal carotid artery stenosis (≥70%). Postoperative CCH was determined by differences between asymmetry of perfusion in bilateral cerebellar hemispheres before and after CEA. Neuropsychological testing was also performed preoperatively and at the first postoperative month.ResultsEleven patients developed cerebral hyperperfusion (cerebral blood flow increase of ≥100% compared with preoperative values) on SPECT imaging performed immediately after CEA. In seven of these patients, CCH was observed on the third postoperative day. All three patients with hyperperfusion syndrome exhibited cerebral hyperperfusion and CCH on the third postoperative day and developed postoperative cognitive impairment. Of the eight patients with asymptomatic hyperperfusion, four exhibited CCH despite resolution of cerebral hyperperfusion on the third postoperative day, and three of these patients experienced postoperative cognitive impairment. In contrast, four patients without postoperative CCH did not experience postoperative cognitive impairment.ConclusionsThe presence of postoperative CCH with concomitant cerebral hyperperfusion reflects the development of hyperperfusion syndrome. Further, the presence of postoperative CCH in patients with cerebral hyperperfusion following CEA suggests development of postoperative cognitive impairment, even when asymptomatic.

Accuracy of central benzodiazepine receptor binding potential/cerebral blood flow SPECT imaging for detecting misery perfusion in patients with unilateral major cerebral artery occlusive diseases: comparison with cerebrovascular reactivity to acetazolamide and cerebral blood flow SPECT imaging.

Purpose: The aim of the present study was to determine whether central benzodiazepine receptor binding potential (BRBP)/cerebral blood flow (CBF) or a combination of CBF and cerebrovascular reactivity (CVR) to acetazolamide on single-photon emission computed tomography (SPECT) more accurately detects misery perfusion, indicating elevation of absolute value of oxygen extraction fraction (OEF) on positron emission tomography (PET), in patients with unilateral major cerebral artery occlusive diseases. Methods: In 84 patients, OEF, CBF, CVR to acetazolamide, and BRBP were assessed using 15O-PET and N-isopropyl-p-[123I]-iodoamphetamine and [123I]-iomazenil SPECT, respectively. A region of interest was automatically placed in the middle cerebral artery territory using a 3-dimensional stereotactic region of interest template. Results: Sensitivity, specificity, and positive and negative predictive values for the affected side-to-contralateral side asymmetry on SPECT-BRBP/CBF to detect the abnormally elevated PET-OEF in the affected hemisphere were 100%, 86.4%, 66.7%, and 100%, respectively. Area under the receiver operating characteristic curve in detecting the abnormally elevated PET-OEF in the affected hemisphere did not differ between analysis of the combination of SPECT-CBF and SPECT-CVR in the affected hemisphere (0.89; 95% confidence interval, 0.80–0.94) and that of the affected side-to-contralateral side asymmetry on SPECT-BRBP/CBF (0.93; 95% confidence interval, 0.86–0.97). The combination of the 3 detected abnormally elevated PET-OEF with 97.0% specificity and 90.0% positive predictive value. Conclusions: The accuracy of central BRBP/CBF asymmetry on SPECT is equivalent to that of the combination of CBF and CVR to acetazolamide on SPECT for detecting misery perfusion in patients with unilateral major cerebral artery occlusive disease.

Concentration of Matrix Metalloproteinase-9 in the Jugular Bulb during Carotid Endarterectomy Correlates with Severity of Intraoperative Cerebral Ischemia

Background: Matrix metalloproteinase (MMP)-9 targets major components of the basal lamina of cerebral blood vessels and is a biochemical marker of blood-brain barrier disruption. The goal of this study was to determine whether plasma concentrations of MMP-9 in the jugular bulb during carotid endarterectomy (CEA) correlate with severity of intraoperative cerebral ischemia. Methods:In 41 patients undergoing CEA for ipsilateral internal carotid artery (ICA) stenosis, plasma samples for measurement of MMP-9 concentration were intraoperatively obtained from a venous catheter inserted into the ipsilateral jugular bulb. Transcranial cerebral oxygen saturation using near-infrared spectroscopy was also monitored intraoperatively to assess the severity of the ischemic insult during ICA clamping. Results: The MMP-9 concentrations were significantly higher after ICA declamping than before ICA clamping (p = 0.0023). A strong linear correlation was observed between the severity of the ischemic insult during carotid clamping and the increase in MMP-9 levels after ICA declamping (r = 0.776; p < 0.0001). At the postoperative neurological assessment, 3 patients showed transient minor neurological deficits. The MMP-9 level in the jugular bulb after ICA declamping was increased in patients with postoperative transient neurological deficits relative to those without. Conclusions: The concentration of MMP-9 in the jugular bulb during CEA correlates with the severity of intraoperative cerebral ischemia.