Correlation between special brain area and blood perfusion in patients with cerebral infarction at convalescent period Feasibility for quantitative determination and estimation of learning and memory function

BACKGROUND： Presently, clinic memory scale is used to evaluate learning memory ability in most studies, and the influence of difference in measurement condition of individuals exists. OBJECTIVE： To study the correlation between regional cerebral blood flow （rCBF） perfusion and learning memory function in special brain regions of patients with cerebral infarction at convalescent period, and to try to find out a method which can quantitatively evaluate learning ability. DESIGN： Case observation, and correlation analysis. SETTINGS： Shandong Institute for Behavioral Medicine; the Affiliated Hospital of Jining Medical College. PARTICIPANTS： Totally 70 patients with cerebral infarction admitted to Department of Neurology, Jining Medical College between January 2004 and December 2005 were involved. The involved patients, 58 male and 12 female, were averaged （52±3） years, and they were all right handed. They all met the diagnosis criteria instituted by the Fourth National Conference on Cerebrovascular Disease, and were confirmed as cerebral infarction by skull CT or MRI. Informed consents of detected items were obtained from all the patients and relatives. METHODS： When the patients were at convalescent period, their learning and memory ability were measured with “ clinic memory scale （set A）”. The 18 patients whose total mark over 100 were regarded as good learning memory function group; The 23 cases whose total mark less than 70 were regarded as poor learning memory function group. RCBF of hippocampus, nucleus amygdalae, temporal cortex and prefrontal lobe of patients between two groups were measured and compared by single photon emission computed tomography （SPECT）. The total scores of the 18 good learning memory patients and 23 poor learning memory patients were taken as dependent variable Y, and their rCBFs of hippocampus, nucleus amygdale, temporal cortex and prefrontal lobe respectively as independent variable X for linear correlation analysis. MAIN OUTCOME MEASURES： Correlation of rCBF in different brain regions and learning memory ability in patients with cerebral infarction. RESULTS： ①The rCBF of hippocampus, nucleus amygdale, temportal cortex and prefrontal cortex of good learning memory function group were significantly higher than those of poor learning memory function group （P 〈 0.05）. ②In the good learning memory function group, rCBF of hippocampus, nucleus amygdale, temportal cortex and prefrontal cortex were significantly positively correlated with memory scale scores （ r = 0.961, 0.926, 0.954, 0.907, P 〈 0.05 ） , and also in the poor learning memory function group （r = 0.979, 0.976, 0.991, 0.953, P 〈 0.05 ） . CONCLUSION： The rCBF of hippocampus, nucleus amygdale, temportal cortex and prefrontal cortex of patients with cerebral infarction are significantly positively correlated with memory scale scores. Predicting learning memory ability of patients by quantitative determination of rCBF provides a quantitative and objective method for evaluating learning memory ability.

STUDY OF REGIONAL STABILITY OF ECD DISTRIBUTION IN NORMAL BRAIN

Objective To evaluate in vivo stability of ethylenedylbis cysteine diethylester (ECD) brain SPECT. Methods Each of 13 normal volunteers (31. 2 ± 11. 8 years) has 12 dynamic SPECK scans ac-quired in 60min 1h after an injection of 99mTc-ECD using a triple headed gamma camera equipped with ultra high resolution fan beam collimators. Average counts per pixel were measured from frontal, temporal, parie-tal, occipital regions, cerebellum, basal ganglia, thalamus and white matter. Regional ECD clearance rates, regional gray-to-white matter (G/W) ratios and the change of the G/W ratio were calculated. Results The average ECD clearance rate was 4. 2% /h, ranged from 3. 03% /h to 5. 41% /h corresponding to white matter and occipital. There was no significant difference between regional ECD clearance rates. Regional G 7W ratio was between 1.27 to 1.75. The G/W ratio of temporal lobe was lower than the occipital ( P <0.05). The change of regional G/W ratio with time is slow. Conclusion Regional ECD distribution is stable in normal brain. ECD clearance from brain is slow and no significant regional difference.

Pre-and postoperative changes of regional cortical cerebral blood flow in patients with cerebral arteriovenous malformation

Objective To investigate pre- and postoperative changes of regional cerebral cortical blood flow in patients with cerebral arteriovenous malformation. Method Twenty-two adult patients with arteriovenous malformation(AVM) were recruited into this study at Beijing Tiantan Hospital from September 2001 to May 2002. Eight patients had giant cerebral AVM and the other 14 had a small one. Cortical cerebral blood flow (CBF) was measured by laser Doppler flowmetry (LDF) before and after AVM resections. After surgery,the probe of LDF was implanted adjacent to the area of AVM and monitored for 24 hours.Results CBF increased significantly after the resection in all patients regardless of AVM size. In patients with small AVM,CBF returned to the baseline level within 4 hours,but in patients with giant AVM,CBF remained high even after 24 hours.Conclusions Monitoring CBF is helpful to understand pre- and postoperative changes of regional cortical CBF in patients with cerebral AVM.

Regional cerebral blood flow in children with autism spectrum disorders： a quantitative 99mTc-ECD brain SPECT study with statistical parametric mapping evaluation

Background Autism spectrum disorders （ASD）, which include autism, asperger syndrome （AS） and pervasive developmental disorder-not otherwise specified （PDD-NOS）, are devastating neurodevelopmental disorders of childhood resulting in deficits in social interaction, repetitive patterns of behaviors, and restricted interests and activities. Single photon emission computed tomography （SPECT） is a common technique used to measure regional cerebral blood flow （rCBF）. Several studies have measured rCBF in children with ASD using SPECT, however, findings are discordant. In addition, the majority of subjects used in these studies were autistic. In this study, we aimed to investigate changes in rCBF in children with ASD using SPECT.Methods A Technetium-99m-ethyl cysteinate dimmer （99mTc-ECD） brain SPECT study was performed on an ASD group consisting of 23 children （3 girls and 20 boys; mean age （7.2±3.0） years） who were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition （DSM-Ⅳ） criteria and an age-matched control group with 8children （1 girl and 7 boys, mean age （5.5±2.4） years）. Image data were evaluated with Statistical Parametric Mapping,5th version （SPM5）. A Student＇s t test for unpaired data was used to compare rCBF and asymmetry in the autism and corresponding control group. The covariance analysis, taking age as covariance, was performed between the ASD and control group.Results There was a significant reduction in rCBF in the bilateral frontal lobe （frontal poles, arcula frontal gyrus） and the bilateral basal ganglia in the autism group, and a reduction in the bilateral frontal, temporal, parietal, legumina nucleus and cerebellum in the AS group compared to the control. In addition, asymmetry of hemispheric hypoperfusion in the ASD group was observed. Inner-group comparison analysis revealed that rCBF decreased significantly in the bilateral frontal lobe （42.7%）, basal nucleus （24.9%） and temporal lobe （22.8%） in the autism group, and in the bilateral cerebellum （22.8%）, basal nucleus （19.3%） and right thalamencephalon （16.6%）in the AS group （P ＜0.05）.Conclusions The decrease in rCBF in ASD is a global event, which involves the bilateral frontal, temporal, limbic system and basal ganglias. Asymmetry of hemispheric hypoperfusion was more obvious in the AS group than the autism group, which indicates a different neurobiological mechanism from that of autism.

Laser Doppler flowmeter study on regional cerebral blood flow in early stage after standard superficial temporal artery-middle cerebral artery bypass surgery for moyamoya disease

Background Standard superficial temporal artery-middle cerebral artery （STA-MCA） bypass surgery is an effective treatment for moyamoya disease, but recent evidence suggests that postoperative cerebral hyperperfusion can occur. In this study, the trendline of changes in regional cerebral blood flow （rCBF） after surgery were continually monitored near the site of anastomosis in order to investigate both the efficacy of the procedure for improving rCBF and the possible risk of hyperperfusion . Methods Standard STA-MCA bypass surgery was performed on 13 patients, rCBF was measured continually using laser Doppler flowmetry （LDF） until the 5th day after the operation with the LDF probe implanted adjacent to the area of the anastomosis. The trendline of rCBF changes postoperatively was recorded for the analysis performed using SPSS 13.0. Results The baseline LDF value of cortical rCBF was （84.68±14.39） perfusion unit （PU）, which was linear relative to absolute perfusion volume before anastomosis and （88.90±11.26） PU immediately after anastomosis （P 〉0.05）. The value changed significantly from before to after anastomosis （P 〈0.05）; it was （417.72±21.35） PU on the 1st day after surgery, and （358.99±18.01） PU, （323.46±17.38） PU, （261.60±16.38） PU and （375.72±18.45） PU on the following 4 days, respectively. The rCBF decreased gradually from the 2nd day until the 4th postoperative day, but still was at a high level （P 〈0.05）. However, on the 5th postoperative day the rCBF increased again to the second highest level, which was significantly different compared with the baseline value （P 〈0.05）, but not significantly different compared with the values on the other 4 days （P〉0.05）. Conclusions STA-MCA anastomosis improves the cerebral blood supply significantly in the early stage after surgery, however, the risk of symptomatic hyperperfusion may exist, which may possibly occur on the 1st day and 5th day after surgery. A LDF is useful for postoperative monitoring for both the efficacy of bypass and possible risk of neurologic deterioration or bleeding from hyperperfusion.

Effects of CO2 pneumoperitoneum on blood flow vol-ume of abdominal organs of rabbits with controlled hem-orrhagic shock and liver impact injuries

Objective: To investigate the effects of CO2 pneumo-peritoneum on blood flow volume of abdominal organs of rabbits with controlled hemorrhagic shock model and liver impact injuries.Methods: After controlled hemorrhagic shock and liver impact injuries, the rabbit model was established. Eighteen rabbits subjected to hemorrhagic shock and liver impact inju-ries were divided into 3 groups randomly according to the volume of lost blood: light hemorrhagic shock (blood loss volume was 10%, 6 ml/kg), moderate hemorrhagic shock (20%, 12 ml/kg) and severe hemorrhagic shock (40%, 22 ml/kg). Intraabdominal pressures of CO2 pneumoperitoneum was 10 mmHg. Color-labeled microspheres were used to mea-sure the blood flow volume of the liver, kidney and stomach before pneumoperitoneum at 30 minutes and 2 hours after pneumoperitoneum and 30 minutes after deflation. And the mortality and hepatic traumatic condition of rabbits were recorded.Results: Of the 18 rabbits, there were 9 with liver impact injuries at Grade Ⅰ, 8 at Grade Ⅱ and Ⅰ at Grade Ⅲ (according to AIS-2005). The mortality rate in light hemorrhagic shock group was 33.33%, and that in moderate or severe hemor-rhagic shock group was 100% within 30 minutes and 2 hours after pneumoperitoneum, respectively. The blood flow vol-ume in the organs detected decreased at 30 minutes under pneumoperitoneum in light and moderate hemorrhagic shock groups. At the same time, the blood flow volume of the liver in moderate hemorrhagic shock group decreased more sig-nificantly than that in light hemorrhagic shock group.Conclusions: The blood flow volume of abdominal organs in rabbits is decreased obviously under CO2 pneumoperitoneum, with fairly high mortality rate. It is be-lieved that CO2 pneumoperitoneum should cautiously be used in abdominal injury accompanied with hemorrhagic shock, especially under non-resuscitation conditions.

Effects of phacoemulsification surgery on ocular hemodynamics

AIM:To evaluate the possible effects of phacoemulsification cataract surgery on ocular hemodynamics.·METHODS:In this prospective study,intraocular pressure(IOP),pulsatile ocular blood flow(POBF),and ocular pulse amplitude(OPA) were measured pre-operatively(baseline) and at 1 week and 3 weeks postoperation in 52 eyes of 26 patients(mean age 63.15±10.25 years) scheduled for unilateral phacoemulsification cataract surgery with intraocular lens implantation.In all of the eyes,a blood flow analyzer(Paradigm DICON;Paradigm Medical Industries Inc.;USA) was used to obtain measurements of IOP,POBF,and OPA.The data obtained from operated eyes were compared statistically to untreated fellow phakic eyes of the patients.·RESULTS:For operated eyes,the mean baseline IOP,POBF,and OPA values were 15.9±4.64mmHg,17.41±4.84μL/s,and 2.91 ±1.12mmHg,respectively.The IOP,POBF,and OPA values were 17.19 ±4.34mmHg,17.56 ±6.46μL/s,and3.12 ±1.1mmHg,respectively,in the nonoperated control eyes.Statistically significant differences from baseline measurements were not observed 1 week and 3 weeks postoperation for the operated or nonoperated eyes.There were also no statistically significant differences in any measurements between the operated and nonoperated eyes in all the examination periods(P 】0.05for all).·CONCLUSION:Uncomplicated phacoemulsification surgery does not affect ocular hemodynamics in normotensive eyes with cataracts.

Apolipoprotein E polymorphisms increase the risk of post-stroke depression

Recent reports have shown that apolipoprotein E （APOE） polymorphisms are involved in neurodegenerative disease. However, it is unclear whether APOE affects post-stroke depression. Accordingly, we hypothesized that APOE polymorphisms modify the risk of post-stroke depression. Here, we performed a hospital-based case-control study （including 76 cerebral infarction cases with post-stroke depression, 88 cerebral infarction cases without post-stroke depression, and 109 controls without any evidence of post-stroke depression or cerebral infarction） to determine possible association between APOE rs429358 and rs7412 polymorphisms and risk of post-stroke depression. Our findings show no difference among the groups with regards genotype distribution of the rs7412 polymorphism. In contrast, APOE genotypes with rs429358-C alleles increased the risk of post-stroke depression. Further, the rs429358 polymorphism was associated with significantly decreased regional cerebral blood flow values in the left temporal lobe of post-stroke depression cases. Additionally, the rs429358 polymorphism was not only associated with depression severity, but with increasing serum levels of total cholesterol. These resuits suggest that the APOE rs429358 polymorphism is associated with increased risk of developing post-stroke depression, and that APOE rs429358-C allele genotypes may be detrimental to recovery of nerve function after stoke. Indeed, these findings provide clinical data for future post-stroke depression gene interventions.

Treatment of Epilepsy with Bipolar Electro-coagulation： An Analysis of Cortical Blood Flow and Histological Change in Temporal Lobe

Background：Bipolar electro-coagulation has a reported efficacy in treating epilepsy involving functional cortex by pure electro-coagulation or combination with resection.However,the mechanisms of bipolar electro-coagulation are not completely known.We studied the acute cortical blood flow and histological changes after bipolar electro-coagulation in 24 patients with intractable temporal lobe epilepsy.Methods：Twenty-four patients were consecutively enrolled,and divided into three groups according to the date of admission.The regional cortical blood flow （rCBF）,electrocorticography,the depth of cortex damage,and acute histological changes （H and E staining,neuronal staining and neurofilament （NF） staining） were analyzed before and after the operation.The t-test analysis was used to compare the rCBF before and after the operation.Results：The rCBF after coagulation was significantly reduced （P 〈 0.05）.The spikes were significantly reduced after electro-coagulation.For the temporal cortex,the depth of cortical damage with output power of 2-9 W after electro-coagulation was 0.34 ± 0.03,0.48 ± 0.06,0.69 ± 0.06,0.84 ± 0.09,0.98 ± 0.08,1.10 ± 0.1 l,1.11 ± 0.09,and 1.22 ± 0.11 mm,respectively.Coagulation with output power of 4-5 W completely damaged the neurons and NF protein in the molecular layer,external granular layer,and external pyramidal layer.Conclusions：The electro-coagulation not only destroyed the neurons and NF protein,but also reduced the rCBF.We concluded that the injuries caused by electro-coagulation would prevent horizontal synchronization and spread of epileptic discharges,and partially destroy the epileptic focus.

Influences of Age and Length of Education on rCBF-SPECT in Healthy Elderly:Diagnostic Implications for Dementia

Background: Few previous studies have described other than age- and gender related changes in regional cerebral blood flow (rCBF) in healthy elderly. What is the influence of other common clinically relevant variables such as ache, education, MMSE, and smoking history? Purpose: To study rCBF in Swedish healthy elderly by single-photon emission computed tomography (SPECT) and evaluate the influence on rCBF of age, gender, education, MMSE, ache, and smoking with a focus on education in relation to the ‘cognitive reserve’. Methods: Healthy subjects (n = 45, 50 -75 y), sampled from a large longitudinal aging study took part in an extensive examination of health and memory, including cognitive testing and socio-economic survey. After injection of 99 mTc-hexamethylpropylene amine oxime (HMPAO) followed by SPECT the rCBF-SPECT images were analyzed using statistical parametric mapping (SPM). Results: Age-related decreases in uptake were seen in interhemispheric and interlobar regions. There was a positive rCBF correlation with education in the inferior frontal lobe and a higher uptake in the left temporal lobe in an age-gender-matched high education subgroup. Conclusion: The localization of the age related findings except for the medial temporal lobe differs markedly from typical dementia related findings. A reduction close to interhemispheric or interlobar space should always be related to chronological age. Education seems to have an influence on basal brain function at a resting-state condition. Knowledge of normal rCBF variations for variables such as age and education should be considered when making clinical diagnosis. The findings could be interpreted as further support for the theory of cognitive reserve.

Solitary pulmonary nodules： comparison of multi-slice computed tomography perfusion study with vascular endothelial growth factor and microvessel density

Background The solitary pulmonary nodule （SPN） is one of the most common findings on chest radiographs. The objectives of clinical practice are to differentiate malignant nodules from benign nodules in the least invasive way and to make a specific diagnosis. This study was aimed to evaluate the correlation between perfusion imaging features and microvessel density （MVD） and vascular endothelial growth factors （VEGF） in SPNs using multi-slice computed tomography （MSCT）; and to provide the theoretical basis for SPN blood flow pattern and blood flow quantitative features. Also, the study called for the discussion of the method＇s clinical application value in the differential diagnosis of benign and malignant SPNs.Methods Sixty-eight patients with SPN underwent multi-location dynamic contrast enhanced （nonionic contrast material was administrated via the antecubital vein at a rate of 4 ml/s） MSCT. Precontrast and postcontrast attenuations on every scan was studied. Perfusion, peak height, and the ratio of the peak height of the SPN to that of the aorta were analyzed. Perfusion was calculated using the maximum gradient of the time-density curves （TDC） and the peak height of the aorta. The quantitative parameters （perfusion, peak height, ratio of peak height of the SPN to that of the aorta） of the blood flow pattern were compared with MVD and the VEGF expression of immunohistochemistry. Results The perfusion peak heights of malignant （（96.15±11.55） HU） and inflammatory （（101.15±8.41） HU） SPNs were significantly higher than those of benign （（47.24±9.15） HU） SPNs （P 〈0.05, P 〈0.05）. Ratios of SPN-to-aorta of malignant and inflammatory SPNs were significantly higher than those of benign SPNs （P 〈0.05, P 〈0.05）. No significant differences were found between the peak height and SPN-to-aorta ratio of malignant SPNs and inflammatory SPNs （P 〉0.05, P 〉0.05）. The precontrast densities of inflammatory SPNs were lower than those of malignant SPNs （P 〈0.05）. Perfusion values of malignant and inflammatory SPNs were significantly higher than those of the benign SPNs （P 〈0.05, P 〈0.05）. The VEGF positive expressions appeared in 32 patients with malignant SPNs and 2 patients with benign SPNs, and the average value of the MVD was higher in patients with malignant SPNs （36.88±6.76） than in patients with either benign （4.51±0.60） or inflammatory （26.11±5.43） SPNs （P 〈0.05, P 〈0.05）. There were statistically significant correlations between the CT perfusion feature and the MVD. The highest correlation was between the peak height of SPN and the MVD （r=0.657, P 〈0.05）.Conclusions Tumor microvessel density and VEGF expression facilitate the exploration of the pathophysiological basis of CT perfusion in SPNs. Multi-slice CT perfusion has shown strong positive correlations with angiogenesis in SPNs.

Inflammatory reaction after focal cerebral ischemia in mouse

Background In response to the inflammatory reaction, circulating leukocytes aggregate and adhere to the endothelial cells and eventually pervade into tissues, resulting in cell damage. This study was to detect the inflammatory reactions in mouse focal cerebral ischemia and their distinct characteristics in the ischemic basal ganglia and surrounding cortex.Methods Mice were subjected to permanent occlusion of the left middle cerebral artery (MCAO) by introducing a suture for 2 to 120 hours. The expression of intercellular adhesion molecule 1 (ICAM-1) and Mac-1 was determined immunohistochemically. The myeloperoxidase (MPO) activity of the ischemic regions was measured.Results Four hours after MCAO, the number of ICAM-1 positive vessels in the ischemic basal ganglia increased (9.2±2.8 per mm 2), peaked at 48 hours (29.6±4.8 per mm 2), and decreased after 72 hours. In the ischemic cortex, the number increased rapidly 4 hours after MCAO (19.4±6.1 per mm 2), peaked at 48 hours (44.4±16.8 per mm 2), and declined after 72 hours. Mac-1 positive cells were seen in the ischemic basal ganglia (3.4±1.2 per mm 2) 12 hours after MCAO, peaked after 48 hours (20.2±6.3 per mm 2), and decreased after 72 hours. In the ischemic cortex, however, the number increased 4 hours after MCAO (4.3±1.7 per mm 2), peaked after 48 hours (20.9±8.4 per mm 2), and remained high at 120 hours. The MPO activity increased in the ischemic basal ganglia 12 hours after MCAO (0.111±0.023 U/g), peaked after 24 hours (0.194±0.059 U/g), and decreased after 72 hours. In the ischemic cortex, the MPO activity increased 12 hours after MCAO (0.110±0.032 U/g), peaked after 24 hours (0.210±0.067 U/g), and remained elevated at 120 hours.Conclusions The increased expression of ICAM-1 in the ischemic brain of mouse in the early phase of MCAO followed by the over-expression of Mac-1 and the increased MPO activity suggests that focal ischemia leads to early onset of inflammation. The inflammatory response is more persistent and intensive in the ischemic cortex than in the ischemic basal ganglia.

Mechanism of action of prostaglandin E_2 in the dog skeletal muscle circulation

Objective To determine whether prostaglandin E2 (PGE2) influences the dog skeletal muscle circulation by a direct action on the vascular smooth muscle or via pre- or post-synaptic modulation of sympathetic neurotransmission.Methods In 18 anaesthetised dogs, a gracilis muscle was vascularly isolated and perfused at constant flow. Sympathetic vasoconstrictor tone on the muscles was reflexly controlled by alterations to the pressure at which the isolated carotid sinuses were perfused. The effects of PGE2 injection into the muscle were compared at low carotid sinus pressure, high carotid sinus pressure, and following denervation of the muscle, with or without noradrenaline infusion.Results At all levels of sympathetic tone, PGE2 produced significantly more vasodilation than the saline vehicle. However, at a carotid sinus pressure of 46.0±2.3 mmHg (1 mmHg=0.133 kPa), PGE2 caused a decrease in femoral arterial perfusion pressure of 52.6±7.1 mmHg, which was significantly greater than the response at a carotid sinus pressure of 208.5±3.7 (33.6±4.2 mmHg decrease) or following denervation (25.6±3.7 mmHg decrease). In a separate group of denervated muscles, PGE2 caused a similar decrease in perfusion pressure in the presence or absence of a noradrenaline infusion.Conclusions PGE2 appears to cause vasodilation through two separate mechanisms: one mechanism involves presynaptic inhibition of sympathetic vasoconstrictor tone, whilst the other is independent of the sympathetic nervous system, and is therefore presumably a direct action on the vascular smooth muscle or endothelium. Under our experimental conditions, both mechanisms contributed equally to the vasodilation.