CT attenuation correction (AC) is a major clinical advantage of PET/CT. However, motion can induce artifacts because of misregistration of the CT attenuation map and emission data. The aim of this study was to investigate the effect of misregistration in cerebrovascular disease patients. We collected six patients who showed mismatch between clinical finding and 15O gas PET/CT imaging, and confirmed dislocation less than 2 cm from initial position. Three patients showed decreased cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) on the opposite side or ipsilateral side. The other patients showed an unexpected artifact on oxygen extraction fraction (OEF) map. These data suggest that misregistration can affect patient diagnosis with dependent on the degree of misregistration.
Objectives: The significance of preoperative cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) measurement in patients with carotid artery stenosis was evaluated. Methods: Two-hundred and twenty surgeries [carotid endarterectomy (CEA): 99, carotid artery stenting (CAS): 121] in which preoperative CBF measurement with single photon emission computed tomography was done were studied. CBF was evaluated as type I, II and III, using Kuroda’s CBF classification. The number of type I was 115 (CEA: 35, CAS: 80), that of type II was 83 (CEA: 46, CAS: 37), and that of type III was 22 (CEA: 18, CAS: 4). Results: Postoperative ischemic lesions on diffusion-weighted magnetic resonance imaging was detected in 28 (24.3%) cases in type I, in 21 (25.3%) cases in type II, and in two (9.1%) cases in type III. There were no significant differences among these type groups. These lesions were detected frequently in CAS than in CEA, and a significant difference was recognized in type I between CEA and CAS. Postoperative ischemic neurological symptoms were recognized in 5 (4.3%) cases in type I, in 1 (1.2%) cases in type II, and in 2 (9.1%) cases in type III, and there were no significant differences among these type groups. Symptoms were recognized frequently in CAS than in CEA, but these differences were not significant. Postoperative hyperperfusion syndrome was observed in 0 (0.0%) cases in type I, in 2 (2.4%) cases in type II, and in 4 (18.2%) cases in type III. This syndrome was recognized more frequently in type III than in other types. There was no significant difference in occurrence of hyperperfusion syndrome, when comparing CEA and CAS. Conclusions: Preoperative CVR is related to the occurrence of postoperative hyperperfusion syndrome and can be used to predict hyperperfusion syndrome causing fatal cerebral hemorrhage.
The introduction of magnetic resonance imaging (MRI) in preclinical research requires the development of new MRI machines for both small animals, such as mice and rats, and larger animals, such as pigs and monkeys, and there is a substantial cost associated with the development of such machines. The objective of this study was to develop a mouse brain imaging environment using a mouse head coil and a clinical 3T-MRI machine. First, optimal acquisition parameters were determined by the phantom experiment. Next, T2-weighted images and magnetic resonance angiography (MRA) images were taken of mice in a mouse model of cerebral aneurysm. Sufficiently good quality T2-weighted images of the brain parenchyma over time were obtained, and major cerebral arteries and cerebral aneurysms were depicted with MRA. The imaging environment developed in this study achieved mouse brain imaging of sufficient quality without the need of a small animal MRI machine.
Objective: Oral care and dysphagia rehabilitation are useful in stroke patients. In our hospital, we provide oral care and dysphagia rehabilitation from the acute stage of stroke in the clinical path. We investigated preventive effect of aspiration pneumonia and predictive factors for resumption of oral intake at discharge. Subjects and Methods: We examined factors of age, sex, severity of stroke (NIHSS, mRS), ADL index (FIM), propriety of oral intake, the number of remaining teeth, oral hygiene, tongue activity on admission and at discharge in 324 acute stroke patients between January 1 and December 31 in 2012. Preventive effect of post-stroke pneumonia and predictive factors for resumption of oral intake at discharge were investigated statistically. Results: Male 181 patients, female 143 patients, mean age 70.1±13.6 years-old. 262 patients (80.9%) were with resumption of oral intake at discharge, and 62 patients (19.1%) were with difficulty of oral intake. The incidence of post-stroke pneumonia is 10.2% in all patients, 7.6% in patients with resumption of oral intake, 21.0% in patients with difficulty of oral intake. Logistic regression analysis identified tongue activity on admission predicts the resumption of oral intake (p<0.01). Conclusion: Oral care and dysphagia rehabilitation from the acute stage of stroke reduce the incidence of post-stroke pneumonia. Tongue activity on admission predicts the resumption of oral intake at discharge.
Endothelial damage following plaque rupture triggers platelet thrombosis. Therefore in the acute phase of atherosclerosis, strong dual antiplatelet therapy (DAPT) is effective in suppression of further thrombosis. In addition, novel therapeutic approaches targeting on the damaged endothelium is under development, which include acceleration of re-endothelialization on the ruptured plaque, promotion of endothelial cell division/migration, tightening endothelial cell junction, reinforcing endothelial attachment to the underlying connective tissue, and replacing adhered platelets with endothelial cells. In addition, we developed tissue engineered blood vessel system in a membrane, which can effectively induce meningeal collateral flow and save ischemic lesion in the territory of major artery stenosis. We reported the validity of this method in mouse using MCA permanent occlusion model. In this membrane structure, vessel endothelial cells and supporting cells would develop tissue engineered vessels and create anastomosis with meningeal vessels. Among constituents of neurovascular unit, pericyte might play the most pivotal role in the regenerative therapy after ischemic event. We now propose “proximal integration model” as a mechanism to control capillary flow after neural activation. Since capillary does not have constriction apparatus, precapillary arteriole may regulate capillary flow. Instead of constricting by itself, pericyte may transduce information of neural activation proximally.
The brain consists of neurons as well as glial cells that outnumber neurons. There are at least three different types of glial cells; astroglia, oligodendroglia, and microglia. Our research has focused on the roles and function of astroglia with regard to metabolic compartment for decades. Recently, it has been elucidated that glial cells function coordinately, making metabolic compartment with each other. This short review introduces the importance of communication of glial cell network in the pathophysiology of stroke, leading the development of novel therapeutic strategy of ischemic stroke.
Post-ischemic inflammation is re-appraised as an important player in the progression of ischemic stroke. Activation of inflammatory cells via Toll-like receptor (TLR) is caused by several damage-associated molecular patterns (DAMPs), including high mobility group box-1 and nucleotides. We have recently found that peroxiredoxin (Prx) is one of the strong DAMPs and activates infiltrating macrophages via TLR2 and TLR4 in brain ischemia. We have also found that interleukin-23 (IL-23) from the activated macrophages stimulates γδT cells which release IL-17, thereby causing the delayed expansion of infarct lesions. Further investigation of the innate immune response would lead to development of novel stroke treatment with a broad therapeutic time window.
In central nervous system, a growth factor progranulin (PGRN) is considered to play crucial roles in maintaining physiological functions, and mutations in PGRN gene cause TDP-43-positive frontotemporal lobar degeneration. We demonstrated a dynamic change of PGRN expression in ischemic rats, including increased levels of PGRN expression in microglia within the ischemic core, and those in survived neurons as well as induction of PGRN expression in endothelial cells within the ischemic penumbra. We observed that PGRN could protect against acute focal cerebral ischemia by variety of mechanisms, which we call “brain protection,” including neuroprotection in part by inhibition of cytoplasmic redistribution of TDP-43, suppression of neuroinflammation via anti-inflammatory interleukin-10 in microglia, and attenuation of blood-brain barrier disruption via vascular endothelial growth factor. Finally, we demonstrated the therapeutic potential of PGRN against acute focal cerebral ischemia using a rat autologous thromboembolic model with delayed tissue plasminogen activator treatment. Intravenously administered recombinant PGRN significantly reduced volumes of cerebral infarct and edema, suppressed hemorrhagic transformation, and improved motor outcome. PGRN may be a novel therapeutic target that provides brain protection such as vascular protection, antineuroinflammation, and neuroprotection. We accelerate further research towards the development of PGRN-based treatments against stroke.
The concept of the neurovascular unit (NVU) has been established recently. It is a minimal theoretical unit composed of neurons, astrocytes, endothelial cells, pericytes, and extracellular matrix proteins to exert neurological functions. It has been elucidated that pericytes are absolutely needed for the formation of the tight junction between endothelial cells, i.e. blood-brain barrier (BBB), by directly interacting with endothelial cells. Genetic factors, ageing, and life-style diseases can affect pericyte functions. Dysfunctions of pericytes directly cause the disruption of the BBB and subsequent impairment of neurological functions. In this review, I will mention shortly the development and physiological functions of pericyte and then the roles of pericytes in the maintenance and repair of the BBB and in the repair of infarct lesions after brain infarction. Now pericytes could be thought as a therapeutic target in various disorders of the central nervous system, including cerebrovascular diseases.
It was generally known that there were many pathological mechanisms in stroke. Treatment strategy of cerebral ischemia was recanalization of occluded vessels. Because various pathological changes were included in recanalization therapy, it was expected to treat each problem. In addition, treatment strategy of cerebral ischemia was extremely changed in very short period. First, researchers evaluated the various drugs for protection of neuron itself. After intravenous tissue plasminogen activator therapy was approved, the evaluation of therapeutic time window and hemorrhagic complication were needed. In addition, it was suggested that the protection of whole neurovascular unit was necessary for neuroprotection. We aimed to clarify these clinical questions by single drug called cilostazol from the viewpoint of basic research. Through a series of studies using cilostazol developed as an antiplatelet agent, it was shown that the medicine dose not have only single efficacy but would also have multiple functions.
Oral anticoagulants and antiplatelet drugs are increasingly used for prevention and treatment of thromboembolic events. We retrospectively analyzed consecutive 892 cases of intracerebral hemorrhage (ICH) treated from 01/2009 to 03/2015 at our Stroke Center, specially focused on with or without oral antithrombotic drugs (ATD). A total of 198 patients (22.2%) with oral ATD were identified among them. Compared with cases without ATD, enlargement of ICH under intensive blood pressure management (target systolic blood pressure <140 mmHg) was found in 18.7% with ATD vs 3.2% without ATD. Regarding clinical outcomes, poor outcomes (modified Rankin Scale score [mRS]: 4-6) were found in 70.8% vs 54.3%, respectively. Stricter control of blood pressure (130/80 mmHg) is required for patients of ICH with ATD. In order to prevent inappropriate medication of ATD and to manage with stricter control of blood pressure, supporting system by regional medical network is required.
Background: Few reports have documented the effect of pretreatment of anti-thrombotic agents on hematoma expansion in patients with intracerebral hemorrhage (ICH) under strict blood pressurelowering management in the acute phase. Methods: Patients (n=211) with hematoma in the supratentorial region were enrolled. Continuous intravenous administration of the anti-hypertensive drug nicardipine was commenced within 3 h of ICH onset at 10 hospitals in Japan, and systolic blood pressure was controlled between 120 and 160 mmHg. The correlation between pretreatment of anti-thrombotic agents and hematoma expansion (growth volume and rate 24 h after admission) was analyzed. Results: Subjects (n=211; 81 females, mean age, 65.6±12.0 years) had a median NIHSS score on admission of 13. Twenty-four patients were taking anti-thrombotic agents on admission, 14 aspirin alone, 1 aspirin+dipyridamole, 2 aspirin+cilostazol, 1 aspirin+clopidogrel, 2 ticlopidine alone, 2 cilostazol alone, and 2 warfarin. When divided into 3 groups according to hematoma volume on admission (≤3.0 ml, 3.1-11.9 ml, >11.9 ml), a significant difference (p=0.008) was observed between patients with and without pretreatment of anti-thrombotic agents (mean growth volume 24 h after admission: not taking anti-thrombotic agents, 4.73 ml: taking anti-thrombotic agents, 12.15 ml) only in the 3rd tertile group (volume>11.9 ml). By three months after discharge, four deaths unrelated to anti-thrombotic agents had occurred. Conclusions: Pretreatment of anti-thrombotic agents is likely significantly related to hematoma expansion in ICH patients with higher hematoma volume (>11.9 ml) on admission under strict blood pressure management in the acute phase.
In the prospective, multicenter, observational Bleeding with Antithrombotic Therapy (BAT) Study, dual antithrombotic therapy was independently related to an increased risk of bleeding events in Japanese patients with cerebrovascular or cardiovascular disease. In its sub-study, an increase in blood pressure levels during antithrombotic medication was positively associated with development of intracerebral hemorrhage, suggesting the importance of adequate blood pressure control for avoiding intracerebral hemorrhage. The retrospective observational study performed by the same investigators (the BAT-Retrospective Study) demonstrated that prior medication with antiplatelet agents, warfarin, or both was predictive of hematoma enlargement and early death after intracerebral hemorrhage.
In this paper, we discuss about the feature of cerebral aneurysm in Japan, our method and ourcome of cerebral aneurysmal surgery and MEP monitoring during temporary vessels occlusion (TO). The incidence of subarachnoid hemorrhage in Finland and Japan is the highest in the world and rupture rate of unruptured cerebral aneurysm in Japan is reported to be about three times more than western countries. According to the Japan Standard Stroke Registry Study, the rate of poor outcome (modified Rankin scale 3-6) of almost ISAT criteria patients was 18.3% and 24.2% in surgical clipping (SC) and coil emblolization (CE) group, respectively. These rates were both superior to ISAT data (36.4% by SC and 25.4% by EC). According to the survey in Japan neurosurgical society from 2001 to 2011, the clipping rate for cerebral aneurysm was decreasing in number from 88.2% in 2001 to 71.2% in 2011. The number of clipping cases for ruptured cerebral aneurysm was decreasing, however, clipping for unruptured cerebral aneurysm was increasing. Our method against cerebral ischemia is keeping the systolic blood pressure over 100 mmHg, administration of brain protective drugs and extra-mild hypothermia during aneurysmal surgery. Number of postoperative major complication of unruptured cerebral aneurysm was 4 cases (2.2%), including 2 hemiparesis of symptomatic internal carotid artery aneurysm and 2 visual disturbance of paraclinoid aneurysms. Evaluation of transcranial motor evoked potential during TO revealed that the incidence of positive change due to TO was 10.3% and significant factor was body temperature over 37 degree Celsius.
While several studies have reported an improvement in cognition after carotid endarterectomy (CEA), others have demonstrated cognitive impairment associated with cerebral hyperperfusion. The mechanisms underlying these changes have remained unclear. Benzodiazepine receptor binding potential on 123I iomazenil (IMZ) single photon emission computed tomography (SPECT) images correlates with brain neural density, and a reduction in cortical benzodiazepine receptor binding indicates cortical neural damage or loss. Recent IMZ-SPECT studies also suggest plasticity in the central benzodiazepine receptors and dynamic changes in the regulatory mechanisms of the neurotransmitter system. The purpose of our study was to determine the mechanisms leading to postoperative cognitive improvement and impairment using IMZ-SPECT. Postoperative hyperperfusion was significantly associated with postoperative hemispheric reduction of benzodiazepine receptor binding potential. Postoperative hyperperfusion and postoperative hemispheric reduction of benzodiazepine receptor binding potential were also significantly associated with postoperative cognitive impairment. Postoperative cognitive improvement was significantly associated with postoperative hemispheric increase in IMZ uptake when compared with postoperative increase in cerebral blood flow. In conclusion, cerebral hyperperfusion after CEA results in postoperative cortical neural loss that correlates with postoperative cognitive impairment, and cognitive improvement after CEA is related to the recovery of function of the neurotransmitter system in the cerebral cortex.
Moyamoya disease is a chronic, occlusive cerebrovascular disease of unknown ethology characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. In Japan, patients with moyamoya disease who meet the diagnostic criteria established by the Research Committee on Spontaneous Occlusion of the Circle of Willis (Moyamoya Disease) of the Ministry of Health and Welfare can receive full reimbursement of their medical expenses from the government. As such, the diagnostic criteria are extremely important. In the 2015 revision of the diagnostic criteria, recognition of flow voids of the sylvian valley, which is a characteristic finding in moyamoya disease, was added to the criteria. Microbleeds on T2* weighted imaging and the ivy sign on fluid-attenuated inversion recovery (FLAIR) imaging are well-known characteristic findings. Cortical and subcortical hyposignals on T2* weighted imaging and white matter hyperintensities on FLAIR imaging are valuable in evaluating ischemic findings. For evaluation of cerebral blood flow during the perioperative period in moyamoya disease, arterial spin labeling has contributed to the detection of hyperperfusion syndrome. In future work, we hope to promote imaging analysis to further our understanding of the pathophysiology of moyamoya disease.
Functional neuroimaging and modern multivariate analysis techniques have greatly contributed to research into the pathophysiology, diagnosis, and new treatments of neurodegenerative diseases, such as Parkinson’s disease (PD). The pathogenesis of PD symptoms, especially akinesia and rigidity, is associated with abnormalities of cortico-striato-pallido-thalamocortical circuits. Although a resting tremor is one of the cardinal features of PD, the pathophysiology underlying this symptom is unclear and is thought to differ from those of akinesia and rigidity. The application of network analyses to metabolic positron emission tomography scans of patients with PD has provided valuable information concerning functional neural connectivity and identified patterns of covariance that are specific to the motor manifestations and many nonmotor features of the disease, such as cognitive dysfunction. Functional imaging methods have revealed PD-specific brain activation patterns, including a parkinsonian tremor-related network. Network-based algorithms might aid in the clinical diagnosis of patients with PD from early symptoms and provide objective evidence of treatment responses.