Concordance between (99m)Tc-ECD SPECT and 18F-FDG PET interpretations in patients with cognitive disorders diagnosed according to NIA-AA criteria.

PubMed

Ito, Kimiteru; Shimano, Yasumasa; Imabayashi, Etsuko; Nakata, Yasuhiro; Omachi, Yoshie; Sato, Noriko; Arima, Kunimasa; Matsuda, Hiroshi

2014-10-01

The purpose of this study was to clarify the concordance of diagnostic abilities and interobserver agreement between 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and brain perfusion single photon-emission computed tomography (SPECT) in patients with Alzheimer's disease (AD) who were diagnosed according to the research criteria of the National Institute of Aging-Alzheimer's Association Workshop. Fifty-five patients with "AD and mild cognitive impairment (MCI)" (n = 40) and "non-AD" (n = 15) were evaluated with 18F-FDG PET and (99m)Tc-ethyl cysteinate dimer (ECD) SPECT during an 8-week period. Three radiologists independently graded the regional uptake in the frontal, temporal, parietal, and occipital lobes as well as the precuneus/posterior cingulate cortex in both images. Kappa values were used to determine the interobserver reliability regarding regional uptake. The regions with better interobserver reliability between 18F-FDG PET and (99m)Tc-ECD SPECT were the frontal, parietal, and temporal lobes. The (99m)Tc-ECD SPECT agreement in the occipital lobes was not significant. The frontal, temporal, and parietal lobes showed good correlations between 18F-FDG PET and (99m)Tc-ECD SPECT in the degree of uptake, but the occipital lobe and precuneus/posterior cingulate cortex did not show good correlations. The diagnostic accuracy rates of "AD and MCI" ranged from 60% to 70% in both of the techniques. The degree of uptake on 18F-FDG PET and (99m)Tc-ECD SPECT showed significant correlations in the frontal, temporal, and parietal lobes. The diagnostic abilities of 18F-FDG PET and (99m)Tc-ECD SPECT for "AD and MCI," when diagnosed according to the National Institute of Aging-Alzheimer's Association Workshop criteria, were nearly identical. Copyright © 2014 John Wiley & Sons, Ltd.

Sleep Deprivation Reveals Altered Brain Perfusion Patterns in Somnambulism.

PubMed

Dang-Vu, Thien Thanh; Zadra, Antonio; Labelle, Marc-Antoine; Petit, Dominique; Soucy, Jean-Paul; Montplaisir, Jacques

2015-01-01

Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with 99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation. Ten adult sleepwalkers and twelve controls with normal sleep were scanned using 99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers. During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls. Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness.

Voxel-based statistical analysis of cerebral blood flow using Tc-99m ECD brain SPECT in patients with traumatic brain injury: group and individual analyses.

PubMed

Shin, Yong Beom; Kim, Seong-Jang; Kim, In-Ju; Kim, Yong-Ki; Kim, Dong-Soo; Park, Jae Heung; Yeom, Seok-Ran

2006-06-01

Statistical parametric mapping (SPM) was applied to brain perfusion single photon emission computed tomography (SPECT) images in patients with traumatic brain injury (TBI) to investigate regional cerebral abnormalities compared to age-matched normal controls. Thirteen patients with TBI underwent brain perfusion SPECT were included in this study (10 males, three females, mean age 39.8 +/- 18.2, range 21 - 74). SPM2 software implemented in MATLAB 5.3 was used for spatial pre-processing and analysis and to determine the quantitative differences between TBI patients and age-matched normal controls. Three large voxel clusters of significantly decreased cerebral blood perfusion were found in patients with TBI. The largest clusters were area including medial frontal gyrus (voxel number 3642, peak Z-value = 4.31, 4.27, p = 0.000) in both hemispheres. The second largest clusters were areas including cingulated gyrus and anterior cingulate gyrus of left hemisphere (voxel number 381, peak Z-value = 3.67, 3.62, p = 0.000). Other clusters were parahippocampal gyrus (voxel number 173, peak Z-value = 3.40, p = 0.000) and hippocampus (voxel number 173, peak Z-value = 3.23, p = 0.001) in the left hemisphere. The false discovery rate (FDR) was less than 0.04. From this study, group and individual analyses of SPM2 could clearly identify the perfusion abnormalities of brain SPECT in patients with TBI. Group analysis of SPM2 showed hypoperfusion pattern in the areas including medial frontal gyrus of both hemispheres, cingulate gyrus, anterior cingulate gyrus, parahippocampal gyrus and hippocampus in the left hemisphere compared to age-matched normal controls. Also, left parahippocampal gyrus and left hippocampus were additional hypoperfusion areas. However, these findings deserve further investigation on a larger number of patients to be performed to allow a better validation of objective SPM analysis in patients with TBI.

Differences in Cerebral Perfusion Deficits in Mild Traumatic Brain Injury and Depression Using Single-Photon Emission Computed Tomography

PubMed Central

Romero, Kristoffer; Black, Sandra E.; Feinstein, Anthony

2014-01-01

Background: Numerous studies have shown decreased perfusion in the prefrontal cortex following mild traumatic brain injury (mTBI). However, similar hypoperfusion can also be observed in depression. Given the high prevalence of depressive symptoms following mTBI, it is unclear to what extent depression influences hypoperfusion in TBI. Methods: Mild TBI patients without depressive symptoms (mTBI-noD, n = 39), TBI patients with depressive symptoms (mTBI-D, n = 13), and 15 patients with major depressive disorder (MDD), but no TBI were given 99m T-ECD single-photon emission computed tomography (SPECT) scans within 2 weeks of injury. All subjects completed tests of information processing speed, complex attention, and executive functioning, and a self-report questionnaire measuring symptoms of psychological distress. Between-group comparisons of quantified SPECT perfusion were undertaken using univariate and multivariate (partial least squares) analyses. Results: mTBI-D and mTBI-noD groups did not differ in terms of cerebral perfusion. However, patients with MDD showed hypoperfusion compared to both TBI groups in several frontal (orbitofrontal, middle frontal, and superior frontal cortex), superior temporal, and posterior cingulate regions. The mTBI-D group showed poorer performance on a measure of complex attention and working memory compared to both the mTBI-noD and MDD groups. Conclusion: These results suggest that depressive symptoms do not affect SPECT perfusion in the sub-acute phase following a mild TBI. Conversely, MDD is associated with hypoperfusion primarily in frontal regions. PMID:25191305

Sleep Deprivation Reveals Altered Brain Perfusion Patterns in Somnambulism

PubMed Central

Dang-Vu, Thien Thanh; Zadra, Antonio; Labelle, Marc-Antoine; Petit, Dominique; Soucy, Jean-Paul; Montplaisir, Jacques

2015-01-01

Background Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with 99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation. Methods Ten adult sleepwalkers and twelve controls with normal sleep were scanned using 99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers. Results During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls. Conclusions Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness. PMID:26241047

The mechanism of ipsilateral ataxia in lacunar hemiparesis: SPECT perfusion imaging.

PubMed

Yamamoto, Ryoo; Johkura, Ken; Nakae, Yoshiharu; Tanaka, Fumiaki

2015-01-01

Although ataxic hemiparesis is a common lacunar syndrome, the precise mechanism underlying hemiataxia is not clear. We attempted to identify ataxia-related, cerebral blood flow changes in patients presenting with ataxic hemiparesis after acute capsular infarct. We used 99mTc-ECD brain perfusion single-photon emission computed tomography to evaluate regional cerebral blood flow in 12 patients with ataxic hemiparesis caused by capsular infarct, and we compared the regional blood flow of these patients with that of 11 patients with pure motor hemiparesis caused by similar lesions. The ipsilateral red nucleus blood flow was significantly decreased in the ataxic hemiparesis patients, whereas the ipsilateral red nucleus blood flow was increased in the pure motor hemiparesis patients. Crossed cerebellar diaschisis (decreased contralateral cerebellar blood flow) was seen in ataxic hemiparesis patients; similarly, it was seen in pure motor hemiparesis patients. Our findings suggest that ataxia in hemiparetic patients with capsular infarct can be caused by ipsilateral red nucleus dysfunction secondary to cortico-rubral pathway disruption at the internal capsule.

Preimplantation Kidney Biopsies of Extended Criteria Donors Have a Heavier Inflammatory Burden Than Kidneys From Standard Criteria Donors

PubMed Central

Mazeti-Felicio, Camila M.; Caldas, Heloisa C.; Fernandes-Charpiot, Ida M.M.; Dezotti, Camila Z.; Baptista, Maria A.S.F.; Abbud-Filho, Mario

2017-01-01

Background Donors after brain death develop a systemic proinflammatory state that may predispose the kidneys to injury after transplantation. Because it is not known whether this inflammatory environment similarly affects the kidneys from expanded criteria donor (ECD) and standard criteria donors (SCD), we sought to evaluate differences in the gene expression of inflammatory cytokines in preimplantation biopsies (PIBx) from ECD and SCD kidneys. Methods Cytokines gene expression was measured in 80 PIBx (SCD, 52; ECD, 28) and associated with donor variables. Results Normal histology and chronic histological lesions were not different between both types of kidneys. ECD kidneys showed significant increase in the transcripts of MCP-1, RANTES, TGF-β1, and IL-10 when compared with SCD. Kidneys presenting normal histology had similar inflammatory profile except by a higher expression of RANTES observed in ECD (P = 0.04). Interstitial fibrosis and tubular atrophy (interstitial fibrosis and tubular atrophy ≥ 1) were associated with higher expression of TGF-β1, RANTES, and IL-10 in ECD compared with SCD kidneys. Cold ischemia time of 24 hours or longer was significantly associated with upregulation of FOXP3, MCP-1, RANTES, and IL10, whereas longer duration of donor hospitalization significantly increased gene expression of all markers. High FOXP3 expression was also associated with lower level of serum creatinine at 1 year. Donor age was not associated with any of the transcripts studied. Conclusions PIBx of ECD exhibit a higher gene expression of inflammatory cytokines when compared with SCD kidneys. This molecular profile may be a specific ECD kidney response to brain death and may help to predict the posttransplant outcomes of ECD recipients. PMID:28706983

Renal Resistance Trend During Hypothermic Machine Perfusion Is More Predictive of Postoperative Outcome Than Biopsy Score: Preliminary Experience in 35 Consecutive Kidney Transplantations.

PubMed

Bissolati, Massimiliano; Gazzetta, Paolo Giovanni; Caldara, Rossana; Guarneri, Giovanni; Adamenko, Olga; Giannone, Fabio; Mazza, Michele; Maggi, Giulia; Tomanin, Deborah; Rosati, Riccardo; Secchi, Antonio; Socci, Carlo

2018-03-30

Hypothermic machine perfusion (HPM) grants a better postoperative outcome in transplantation of organs procured from extended criteria donors (ECDs) and donors after cardiac death (DCD). So far, the only available parameter for outcome prediction concerning those organs is pretransplant biopsy score. The aim of this study is to evaluate whether renal resistance (RR) trend during HPM may be used as a predictive marker for post-transplantation outcome. From December 2015 to present, HMP has been systematically applied to all organs from ECDs and DCD. All grafts underwent pretransplantation biopsy evaluation using Karpinski's histological score. Only organs that reached RR value ≤1.0 within 3 hours of perfusion were transplanted. Single kidney transplantation (SKT) or double kidney transplantation (DKT) were performed according to biopsy score results. Sixty-five HMPs were performed (58 from ECDs and 7 from DCD/ECMO donors). Fifteen kidneys were insufficiently reconditioned (RR > 1) and were therefore discarded. Forty-nine kidneys were transplanted, divided between 21 SKT and 14 DKT. Overall primary nonfunction (PNF) and delayed graft function (DGF) rate were 2.9 and 17.1%, respectively. DGF were more common in kidneys from DCD (67 vs. 7%; P = 0.004). Biopsy score did not correlate with PNF/DGF rate (P = 0.870) and postoperative creatinine trend (P = 0.796). Recipients of kidneys that reached RR ≤ 1.0 within 1 hour of HMP had a lower PNF/DGF rate (11 vs. 44%; P = 0.033) and faster serum creatinine decrease (POD10 creatinine: 1.79 mg/dL vs. 4.33 mg/dL; P = 0.019). RR trend is more predictive of post-transplantation outcome than biopsy score. Hence, RR trend should be taken into account in the pretransplantation evaluation of the organs. © 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Coexistence of intracranial Langerhans cell histiocytosis and Erdheim-Chester disease in a pediatric patient: a case report.

PubMed

Kim, Seokhwi; Lee, Minju; Shin, Hyung Jin; Lee, Joohee; Suh, Yeon-Lim

2016-05-01

The co-occurrence of Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) is extremely rare and almost all cases were reported in adults. We describe a case of intracranial LCH and ECD that was confirmed by histopathological and molecular studies. A three-year-old boy presented with headache and right exophthalmos and brain magnetic resonance images (MRI) revealed multiple intracranial tumors. Whole body MRI showed osteolytic lesions typical of LCH in flat bones and osteosclerotic changes typical of ECD in long bones. Histologically, the biopsy samples from the posterior fossa and occipital skull mass revealed areas of both LCH and ECD. Immunohistochemically, the LCH contained CD1a-positive Langerhans cells and the ECD had CD1a-negative, CD68-positive foamy histiocytes. BRAF (V600E) mutations were detected in both the LCH and ECD areas. The coexistence of LCH and ECD in the same biopsy and the BRAF (V600E) mutation status in both histologic types support the recent re-classification of the histiocytic disorder into LCH, ECD, and "mixed histiocytosis", which reflects tumorigenesis for all three from a common progenitor cell.

Sequestration of latent TGF-β binding protein 1 into CADASIL-related Notch3-ECD deposits.

PubMed

Kast, Jessica; Hanecker, Patrizia; Beaufort, Nathalie; Giese, Armin; Joutel, Anne; Dichgans, Martin; Opherk, Christian; Haffner, Christof

2014-08-13

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) represents the most common hereditary form of cerebral small vessel disease characterized by early-onset stroke and premature dementia. It is caused by mutations in the transmembrane receptor Notch3, which promote the aggregation and accumulation of the Notch3 extracellular domain (Notch3-ECD) within blood vessel walls. This process is believed to mediate the abnormal recruitment and dysregulation of additional factors including extracellular matrix (ECM) proteins resulting in brain vessel dysfunction. Based on recent evidence indicating a role for the transforming growth factor-β (TGF-β) pathway in sporadic and familial small vessel disease we studied fibronectin, fibrillin-1 and latent TGF-β binding protein 1 (LTBP-1), three ECM constituents involved in the regulation of TGF-β bioavailability, in post-mortem brain tissue from CADASIL patients and control subjects. Fibronectin and fibrillin-1 were found to be enriched in CADASIL vessels without co-localizing with Notch3-ECD deposits, likely as a result of fibrotic processes secondary to aggregate formation. In contrast, LTBP-1 showed both an accumulation and a striking co-localization with Notch3-ECD deposits suggesting specific recruitment into aggregates. We also detected increased levels of the TGF-β prodomain (also known as latency-associated peptide, LAP) indicating dysregulation of the TGF-β pathway in CADASIL development. In vitro analyses revealed a direct interaction between LTBP-1 and Notch3-ECD and demonstrated a specific co-aggregation of LTBP-1 with mutant Notch3. We propose LTBP-1 as a novel component of Notch3-ECD deposits and suggest its involvement in pathological processes triggered by Notch3-ECD aggregation.

Dynamic change in cerebral microcirculation and focal cerebral metabolism in experimental subarachnoid hemorrhage in rabbits.

PubMed

Song, Jin-Ning; Chen, Hu; Zhang, Ming; Zhao, Yong-Lin; Ma, Xu-Dong

2013-03-01

Regional cerebral blood flow (rCBF) in the cerebral metabolism and energy metabolism measurements can be used to assess blood flow of brain cells and to detect cell activity. Changes of rCBF in the cerebral microcirculation and energy metabolism were determined in an experimental model of subarachnoid hemorrhage (SAH) model in 56 large-eared Japanese rabbits about 12 to 16-month old. Laser Doppler flowmetry was used to detect the blood supply to brain cells. Internal carotid artery and vein blood samples were used for duplicate blood gas analysis to assess the energy metabolism of brain cells. Cerebral blood flow (CBF) was detected by single photon emission computed tomography (SPECT) perfusion imaging using Tc-99m ethyl cysteinate dimer (Tc-99m ECD) as an imaging reagent. The percentage of injected dose per gram of brain tissue was calculated and analyzed. There were positive correlations between the percentage of radionuclide injected per gram of brain tissue and rCBF supply and cerebral metabolic rate for oxygen (P < 0.05). However, there was a negative correlation between radioactivity counts per unit volume detected on the SPECT rheoencephalogram and lactic acid concentration in the homolateral internal carotid artery and vein. In summary, this study found abnormal CBF in metabolism and utilization of brain cells after SAH, and also found that deterioration of energy metabolism of brain cells played a significant role in the development of SAH. There are matched reductions in CBF and metabolism. Thus, SPECT imaging could be used as a noninvasive method to detect CBF.

Old wine in new bottles: validating the clinical utility of SPECT in predicting cognitive performance in mild traumatic brain injury.

PubMed

Romero, Kristoffer; Lobaugh, Nancy J; Black, Sandra E; Ehrlich, Lisa; Feinstein, Anthony

2015-01-30

The neural underpinnings of cognitive dysfunction in mild traumatic brain injury (TBI) are not fully understood. Consequently, patient prognosis using existing clinical imaging is somewhat imprecise. Single photon emission computed tomography (SPECT) is a frequently employed investigation in this population, notwithstanding uncertainty over the clinical utility of the data obtained. In this study, subjects with mild TBI underwent (99m)Tc-ECD SPECT scanning, and were administered a brief battery of cognitive tests and self-report symptom scales of concussion and emotional distress. Testing took place 2 weeks (n=84) and 1 year (n=49) post-injury. Multivariate analysis (i.e., partial least squares analysis) revealed that frontal perfusion in right superior frontal and middle frontal gyri predicted poorer performance on the Stroop test, an index of executive function, both at initial and follow-up testing. Conversely, SPECT scans categorized as normal or abnormal by radiologists did not differentiate cognitively impaired from intact subjects. These results demonstrate the clinical utility of SPECT in mild TBI, but only when data are subjected to blood flow quantification analysis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A SPECT study of language and brain reorganization three years after pediatric brain injury.

PubMed

Chiu Wong, Stephanie B; Chapman, Sandra B; Cook, Lois G; Anand, Raksha; Gamino, Jacquelyn F; Devous, Michael D

2006-01-01

Using single photon emission computed tomography (SPECT), we investigated brain plasticity in children 3 years after sustaining a severe traumatic brain injury (TBI). First, we assessed brain perfusion patterns (i.e., the extent of brain blood flow to regions of the brain) at rest in eight children who suffered severe TBI as compared to perfusion patterns in eight normally developing children. Second, we examined differences in perfusion between children with severe TBI who showed good versus poor recovery in complex discourse skills. Specifically, the children were asked to produce and abstract core meaning for two stories in the form of a lesson. Inconsistent with our predictions, children with severe TBI showed areas of increased perfusion as compared to normally developing controls. Adult studies have shown the reverse pattern with TBI associated with reduced perfusion. With regard to the second aim and consistent with previously identified brain-discourse relations, we found a strong positive association between perfusion in right frontal regions and discourse abstraction abilities, with higher perfusion linked to better discourse outcomes and lower perfusion linked to poorer discourse outcomes. Furthermore, brain-discourse patterns of increased perfusion in left frontal regions were associated with lower discourse abstraction ability. The results are discussed in terms of how brain changes may represent adaptive and maladaptive plasticity. The findings offer direction for future studies of brain plasticity in response to neurocognitive treatments.

Particle swarm optimization and its application in MEG source localization using single time sliced data

NASA Astrophysics Data System (ADS)

Lin, Juan; Liu, Chenglian; Guo, Yongning

2014-10-01

The estimation of neural active sources from the magnetoencephalography (MEG) data is a very critical issue for both clinical neurology and brain functions research. A widely accepted source-modeling technique for MEG involves calculating a set of equivalent current dipoles (ECDs). Depth in the brain is one of difficulties in MEG source localization. Particle swarm optimization(PSO) is widely used to solve various optimization problems. In this paper we discuss its ability and robustness to find the global optimum in different depths of the brain when using single equivalent current dipole (sECD) model and single time sliced data. The results show that PSO is an effective global optimization to MEG source localization when given one dipole in different depths.

Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome.

PubMed

Abu-Judeh, H H; Levine, S; Kumar, M; el-Zeftawy, H; Naddaf, S; Lou, J Q; Abdel-Dayem, H M

1998-11-01

Chronic fatigue syndrome is a clinically defined condition of uncertain aetiology. We compared 99Tcm-HMPAO single photon emission tomography (SPET) brain perfusion with dual-head 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Eighteen patients (14 females, 4 males), who fulfilled the diagnostic criteria of the Centers for Disease Control for chronic fatigue syndrome, were investigated. Thirteen patients had abnormal SPET brain perfusion scans and five had normal scans. Fifteen patients had normal glucose brain metabolism scans and three had abnormal scans. We conclude that, in chronic fatigue syndrome patients, there is discordance between SPET brain perfusion and 18F-FDG brain uptake. It is possible to have brain perfusion abnormalities without corresponding changes in glucose uptake.

A potential protective effect in multilingual patients with semantic dementia: two case reports of patients speaking Taiwanese and Japanese.

PubMed

Liu, Yi-Chien; Yip, Ping-Keung; Fan, Yu-Ming; Meguro, Kenichi

2012-03-01

Several reports have suggested that multilingualism has a protective effect against semantic dementia. Here, we provide further evidence for this effect. The patient was a 75-year-old right-handed Taiwanese woman who had retired after working as a tailor. She was able to speak Taiwanese, Japanese and Mandarin Chinese fluently until 5 years ago. She gradually developed symptoms of profound anomia and difficulty with word-finding. Her mother tongue was Taiwanese and she had learned Japanese as her first symbolized language. She had used Mandarin Chinese for most of her life, but depended on Japanese to read and write (such as reading a newspaper and keeping accounts). However, she could now speak only very simple Taiwanese and Japanese, and could recognize only simple Japanese characters. SECOND: The patient was a 62-year-old right-handed man who had worked as an ironworker. He could speak Taiwanese and Mandarin Chinese fluently until 5 years ago. His mother tongue was Taiwanese. After 5 years of language deterioration, he was unable to communicate with his family members or recognize any characters, including numbers. SPECT RESULTS: Brain perfusion ECD SPECT (Tc-99m-ethyl cysteinate dimer single-photon emission computed tomography) showed less perfusion in the multilingual patient (Case #1) than in the bilingual patient (Case #2). Neuropsychological tests also demonstrated a slower rate of degeneration in the multilingual patient. We speculate that reading and writing in Japanese had a greater impact on the semantic system in Case #1. Thus, this patient showed relatively less degeneration or functional inactivity, as shown by perfusion in the frontal lobe, and this might be due to the persistent activation involved in multilingualism.

Mild Thyrotoxicosis Leads to Brain Perfusion Changes: An Arterial Spin Labelling Study.

PubMed

Göbel, A; Heldmann, M; Sartorius, A; Göttlich, M; Dirk, A-L; Brabant, G; Münte, T F

2017-01-01

Hypo- and hyperthyroidism have effects on brain structure and function, as well as cognitive processes, including memory. However, little is known about the influence of thyroid hormones on brain perfusion and the relationship of such perfusion changes with cognition. The present study aimed to demonstrate the effect of short-term experimental hyperthyroidism on brain perfusion in healthy volunteers and to assess whether perfusion changes, if present, are related to cognitive performance. It is known that an interaction exists between brain perfusion and cerebral oxygen consumption rate and it is considered that neural activation increases cerebral regional perfusion rate in brain areas associated with memory. Measuring cerebral blood flow may therefore represent a proxy for neural activity. Therefore, arterial spin labelling (ASL) measurements were conducted and later analysed to evaluate brain perfusion in 29 healthy men before and after ingesting thyroid hormones for 8 weeks. Psychological tests concerning memory were performed at the same time-points and the results were correlated with the imaging results. In the hyperthyroid condition, perfusion was increased in the posterior cerebellum in regions connected with cerebral networks associated with cognitive control and the visual cortex compared to the euthyroid condition. In addition, these perfusion changes were positively correlated with changes of performance in the German version of the Auditory Verbal Learning Task [AVLT, Verbaler Lern-und-Merkfähigkeits-Test (VLMT)]. Cerebellar perfusion and function therefore appears to be modulated by thyroid hormones, likely because the cerebellum hosts a high number of thyroid hormone receptors. © 2016 British Society for Neuroendocrinology.

Perfusion CT of the Brain and Liver and of Lung Tumors: Use of Monte Carlo Simulation for Patient Dose Estimation for Examinations With a Cone-Beam 320-MDCT Scanner.

PubMed

Cros, Maria; Geleijns, Jacob; Joemai, Raoul M S; Salvadó, Marçal

2016-01-01

The purpose of this study was to estimate the patient dose from perfusion CT examinations of the brain, lung tumors, and the liver on a cone-beam 320-MDCT scanner using a Monte Carlo simulation and the recommendations of the International Commission on Radiological Protection (ICRP). A Monte Carlo simulation based on the Electron Gamma Shower Version 4 package code was used to calculate organ doses and the effective dose in the reference computational phantoms for an adult man and adult woman as published by the ICRP. Three perfusion CT acquisition protocols--brain, lung tumor, and liver perfusion--were evaluated. Additionally, dose assessments were performed for the skin and for the eye lens. Conversion factors were obtained to estimate effective doses and organ doses from the volume CT dose index and dose-length product. The sex-averaged effective doses were approximately 4 mSv for perfusion CT of the brain and were between 23 and 26 mSv for the perfusion CT body protocols. The eye lens dose from the brain perfusion CT examination was approximately 153 mGy. The sex-averaged peak entrance skin dose (ESD) was 255 mGy for the brain perfusion CT studies, 157 mGy for the lung tumor perfusion CT studies, and 172 mGy for the liver perfusion CT studies. The perfusion CT protocols for imaging the brain, lung tumors, and the liver performed on a 320-MDCT scanner yielded patient doses that are safely below the threshold doses for deterministic effects. The eye lens dose, peak ESD, and effective doses can be estimated for other clinical perfusion CT examinations from the conversion factors that were derived in this study.

Retrograde Cerebral Perfusion Results in Better Perfusion to the Striatum Than the Cerebral Cortex During Deep Hypothermic Circulatory Arrest: A Microdialysis Study.

PubMed

Liang, Meng-Ya; Chen, Guang-Xian; Tang, Zhi-Xian; Rong, Jian; Yao, Jian-ping; Wu, Zhong-Kai

2016-03-01

It remains controversial whether contemporary cerebral perfusion techniques, utilized during deep hypothermic circulatory arrest (DHCA), establish adequate perfusion to deep structures in the brain. This study aimed to investigate whether selective antegrade cerebral perfusion (SACP) or retrograde cerebral perfusion (RCP) can provide perfusion equally to various anatomical positions in the brain using metabolic evidence obtained from microdialysis. Eighteen piglets were randomly assigned to 40 min of circulatory arrest (CA) at 18°C without cerebral perfusion (DHCA group, n = 6) or with SACP (SACP group, n = 6) or RCP (RCP group, n = 6). Microdialysis parameters (glucose, lactate, pyruvate, and glutamate) were measured every 30 min in cortex and striatum. After 3 h of reperfusion, brain tissue was harvested for Western blot measurement of α-spectrin. After 40 min of CA, the DHCA group showed marked elevations of lactate and glycerol and a reduction in glucose in the microdialysis perfusate (all P < 0.05). The changes in glucose, lactate, and glycerol in the perfusate and α-spectrin expression in brain tissue were similar between cortex and striatum in the SACP group (all P > 0.05). In the RCP group, the cortex exhibited lower glucose, higher lactate, and higher glycerol in the perfusate and higher α-spectrin expression in brain tissue compared with the striatum (all P < 0.05). Glutamate showed no difference between cortex and striatum in all groups (all P > 0.05). In summary, SACP provided uniform and continuous cerebral perfusion to most anatomical sites in the brain, whereas RCP resulted in less sufficient perfusion to the cortex but better perfusion to the striatum. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

A semi-automated volumetric software for segmentation and perfusion parameter quantification of brain tumors using 320-row multidetector computed tomography: a validation study.

PubMed

Chae, Soo Young; Suh, Sangil; Ryoo, Inseon; Park, Arim; Noh, Kyoung Jin; Shim, Hackjoon; Seol, Hae Young

2017-05-01

We developed a semi-automated volumetric software, NPerfusion, to segment brain tumors and quantify perfusion parameters on whole-brain CT perfusion (WBCTP) images. The purpose of this study was to assess the feasibility of the software and to validate its performance compared with manual segmentation. Twenty-nine patients with pathologically proven brain tumors who underwent preoperative WBCTP between August 2012 and February 2015 were included. Three perfusion parameters, arterial flow (AF), equivalent blood volume (EBV), and Patlak flow (PF, which is a measure of permeability of capillaries), of brain tumors were generated by a commercial software and then quantified volumetrically by NPerfusion, which also semi-automatically segmented tumor boundaries. The quantification was validated by comparison with that of manual segmentation in terms of the concordance correlation coefficient and Bland-Altman analysis. With NPerfusion, we successfully performed segmentation and quantified whole volumetric perfusion parameters of all 29 brain tumors that showed consistent perfusion trends with previous studies. The validation of the perfusion parameter quantification exhibited almost perfect agreement with manual segmentation, with Lin concordance correlation coefficients (ρ c ) for AF, EBV, and PF of 0.9988, 0.9994, and 0.9976, respectively. On Bland-Altman analysis, most differences between this software and manual segmentation on the commercial software were within the limit of agreement. NPerfusion successfully performs segmentation of brain tumors and calculates perfusion parameters of brain tumors. We validated this semi-automated segmentation software by comparing it with manual segmentation. NPerfusion can be used to calculate volumetric perfusion parameters of brain tumors from WBCTP.

High-sensitivity brain SPECT system using cadmium telluride (CdTe) semiconductor detector and 4-pixel matched collimator.

PubMed

Suzuki, Atsuro; Takeuchi, Wataru; Ishitsu, Takafumi; Tsuchiya, Katsutoshi; Morimoto, Yuichi; Ueno, Yuichiro; Kobashi, Keiji; Kubo, Naoki; Shiga, Tohru; Tamaki, Nagara

2013-11-07

For high-sensitivity brain imaging, we have developed a two-head single-photon emission computed tomography (SPECT) system using a CdTe semiconductor detector and 4-pixel matched collimator (4-PMC). The term, '4-PMC' indicates that the collimator hole size is matched to a 2 × 2 array of detector pixels. By contrast, a 1-pixel matched collimator (1-PMC) is defined as a collimator whose hole size is matched to one detector pixel. The performance of the higher-sensitivity 4-PMC was experimentally compared with that of the 1-PMC. The sensitivities of the 1-PMC and 4-PMC were 70 cps/MBq/head and 220 cps/MBq/head, respectively. The SPECT system using the 4-PMC provides superior image resolution in cold and hot rods phantom with the same activity and scan time to that of the 1-PMC. In addition, with half the usual scan time the 4-PMC provides comparable image quality to that of the 1-PMC. Furthermore, (99m)Tc-ECD brain perfusion images of healthy volunteers obtained using the 4-PMC demonstrated acceptable image quality for clinical diagnosis. In conclusion, our CdTe SPECT system equipped with the higher-sensitivity 4-PMC can provide better spatial resolution than the 1-PMC either in half the imaging time with the same administered activity, or alternatively, in the same imaging time with half the activity.

Reproducibility Between Brain Uptake Ratio Using Anatomic Standardization and Patlak-Plot Methods.

PubMed

Shibutani, Takayuki; Onoguchi, Masahisa; Noguchi, Atsushi; Yamada, Tomoki; Tsuchihashi, Hiroko; Nakajima, Tadashi; Kinuya, Seigo

2015-12-01

The Patlak-plot and conventional methods of determining brain uptake ratio (BUR) have some problems with reproducibility. We formulated a method of determining BUR using anatomic standardization (BUR-AS) in a statistical parametric mapping algorithm to improve reproducibility. The objective of this study was to demonstrate the inter- and intraoperator reproducibility of mean cerebral blood flow as determined using BUR-AS in comparison to the conventional-BUR (BUR-C) and Patlak-plot methods. The images of 30 patients who underwent brain perfusion SPECT were retrospectively used in this study. The images were reconstructed using ordered-subset expectation maximization and processed using an automatic quantitative analysis for cerebral blood flow of ECD tool. The mean SPECT count was calculated from axial basal ganglia slices of the normal side (slices 31-40) drawn using a 3-dimensional stereotactic region-of-interest template after anatomic standardization. The mean cerebral blood flow was calculated from the mean SPECT count. Reproducibility was evaluated using coefficient of variation and Bland-Altman plotting. For both inter- and intraoperator reproducibility, the BUR-AS method had the lowest coefficient of variation and smallest error range about the Bland-Altman plot. Mean CBF obtained using the BUR-AS method had the highest reproducibility. Compared with the Patlak-plot and BUR-C methods, the BUR-AS method provides greater inter- and intraoperator reproducibility of cerebral blood flow measurement. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Whole brain CT perfusion deficits using 320-detector-row CT scanner in TIA patients are associated with ABCD2 score.

PubMed

Mehta, Bijal K; Mustafa, Ghulam; McMurtray, Aaron; Masud, Mohammed W; Gunukula, Sameer K; Kamal, Haris; Kandel, Amit; Beltagy, Abdelrahman; Li, Ping

2014-01-01

Transient ischemic attacks (TIA) are cerebral ischemic events without infarction. The uses of CT perfusion (CTP) techniques such as cerebral blood volume (CBV), time to peak (TTP), mean transit time (MTT) and cerebral blood flow (CBF) provide real time data about ischemia. It has been shown that CTP changes occur in less sensitive CTP scanners in patients with TIA. Larger detector row CTP (whole brain perfusion studies) may show that CTP abnormalities are more prevalent than previously noted. It is also unclear if these changes are associated with TIA severity. To demonstrate that TIA patients are associated with perfusion deficits using whole brain 320-detector-row CT perfusion, and to determine an association between ABCD2 score and perfusion deficit using whole brain perfusion. We retrospectively reviewed all TIA patients for CTP deficits from 2008-2010. Perfusion imaging was reviewed at admission; and it was determined if a perfusion deficit was present along with vascular territory involved. Of 364 TIA patients, 62 patients had CTP deficits. The largest group of patients had MCA territory involved with 48 of 62 patients (77.42%). The most common perfusion abnormality was increased TTP with 46 patients (74.19%). The ABCD2 score was reviewed in association with perfusion deficit. Increased age >60, severe hypertension (>180/100 mmHg), patients with speech abnormalities, and duration of symptoms >10 min were associated with a perfusion deficit but history of diabetes or minimal/moderate hypertension (140/90-179/99 mmHg) was not. There was no association between motor deficit and perfusion abnormality. Perfusion deficits are found in TIA patients using whole brain CTP and associated with components of the ABCD2 score.

Physiological and psychological individual differences influence resting brain function measured by ASL perfusion.

PubMed

Kano, M; Coen, S J; Farmer, A D; Aziz, Q; Williams, S C R; Alsop, D C; Fukudo, S; O'Gorman, R L

2014-09-01

Effects of physiological and/or psychological inter-individual differences on the resting brain state have not been fully established. The present study investigated the effects of individual differences in basal autonomic tone and positive and negative personality dimensions on resting brain activity. Whole-brain resting cerebral perfusion images were acquired from 32 healthy subjects (16 males) using arterial spin labeling perfusion MRI. Neuroticism and extraversion were assessed with the Eysenck Personality Questionnaire-Revised. Resting autonomic activity was assessed using a validated measure of baseline cardiac vagal tone (CVT) in each individual. Potential associations between the perfusion data and individual CVT (27 subjects) and personality score (28 subjects) were tested at the level of voxel clusters by fitting a multiple regression model at each intracerebral voxel. Greater baseline perfusion in the dorsal anterior cingulate cortex (ACC) and cerebellum was associated with lower CVT. At a corrected significance threshold of p < 0.01, strong positive correlations were observed between extraversion and resting brain perfusion in the right caudate, brain stem, and cingulate gyrus. Significant negative correlations between neuroticism and regional cerebral perfusion were identified in the left amygdala, bilateral insula, ACC, and orbitofrontal cortex. These results suggest that individual autonomic tone and psychological variability influence resting brain activity in brain regions, previously shown to be associated with autonomic arousal (dorsal ACC) and personality traits (amygdala, caudate, etc.) during active task processing. The resting brain state may therefore need to be taken into account when interpreting the neurobiology of individual differences in structural and functional brain activity.

DRAG REDUCING POLYMER ENCHANCES MICROVASCULAR PERFUSION IN THE TRAUMATIZED BRAIN WITH INTRACRANIAL HYPERTENSION

PubMed Central

Bragin, Denis E.; Thomson, Susan; Bragina, Olga; Statom, Gloria; Kameneva, Marina V.; Nemoto, Edwin M.

2016-01-01

SUMMARY Current treatments for traumatic brain injury (TBI) have not focused on improving microvascular perfusion. Drag-reducing polymers (DRP), linear, long-chain, blood soluble non-toxic macromolecules, may offer a new approach to improving cerebral perfusion by primary alteration of the fluid dynamic properties of blood. Nanomolar concentrations of DRP have been shown to improve hemodynamics in animal models of ischemic myocardium and limb, but have not yet been studied in the brain. Recently, we demonstrated that that DRP improved microvascular perfusion and tissue oxygenation in a normal rat brain. We hypothesized that DRP could restore microvascular perfusion in hypertensive brain after TBI. Using the in-vivo 2-photon laser scanning microscopy we examined the effect of DRP on microvascular blood flow and tissue oxygenation in hypertensive rat brains with and without TBI. DRP enhanced and restored capillary flow, decreased microvascular shunt flow and, as a result, reduced tissue hypoxia in both un-traumatized and traumatized rat brains at high ICP. Our study suggests that DRP could be an effective treatment for improving microvascular flow in brain ischemia caused by high ICP after TBI. PMID:27165871

Brain perfusion imaging using a Reconstruction-of-Difference (RoD) approach for cone-beam computed tomography

NASA Astrophysics Data System (ADS)

Mow, M.; Zbijewski, W.; Sisniega, A.; Xu, J.; Dang, H.; Stayman, J. W.; Wang, X.; Foos, D. H.; Koliatsos, V.; Aygun, N.; Siewerdsen, J. H.

2017-03-01

Purpose: To improve the timely detection and treatment of intracranial hemorrhage or ischemic stroke, recent efforts include the development of cone-beam CT (CBCT) systems for perfusion imaging and new approaches to estimate perfusion parameters despite slow rotation speeds compared to multi-detector CT (MDCT) systems. This work describes development of a brain perfusion CBCT method using a reconstruction of difference (RoD) approach to enable perfusion imaging on a newly developed CBCT head scanner prototype. Methods: A new reconstruction approach using RoD with a penalized-likelihood framework was developed to image the temporal dynamics of vascular enhancement. A digital perfusion simulation was developed to give a realistic representation of brain anatomy, artifacts, noise, scanner characteristics, and hemo-dynamic properties. This simulation includes a digital brain phantom, time-attenuation curves and noise parameters, a novel forward projection method for improved computational efficiency, and perfusion parameter calculation. Results: Our results show the feasibility of estimating perfusion parameters from a set of images reconstructed from slow scans, sparse data sets, and arc length scans as short as 60 degrees. The RoD framework significantly reduces noise and time-varying artifacts from inconsistent projections. Proper regularization and the use of overlapping reconstructed arcs can potentially further decrease bias and increase temporal resolution, respectively. Conclusions: A digital brain perfusion simulation with RoD imaging approach has been developed and supports the feasibility of using a CBCT head scanner for perfusion imaging. Future work will include testing with data acquired using a 3D-printed perfusion phantom currently and translation to preclinical and clinical studies.

Optimized retrograde cerebral perfusion reduces ischemic energy depletion.

PubMed

Oda, Teiji; Kimura, Tetsuhiro; Ogata, Yoshitaka; Fujise, Yutaka

2004-01-01

It has been reported that retrograde cerebral perfusion (RCP) provides minimal capillary flow; however, the extent to which RCP can provide aerobic metabolic support is unknown. We evaluated whether perfusate composition optimization for RCP would preserve brain energy metabolism during hypothermic circulatory arrest (HCA) at 20 degrees C in rats. Three types of perfusates were prepared: hemoglobin-free saline, rat red blood cells, and artificial blood substitute (liposome-encapsulated hemoglobin); perfusates were made hypertonic, cooled to 20 degrees C, and oxygenated and CO(2) was administered (pH-stat management). Circulatory arrest was induced in 24 pH-stat-ventilated Wistar rats that had been surface cooled to 20 degrees C; 18 were assigned to the RCP group in which one of the three ( n = 6 each) perfusates was administered via the maxillary vein, and 6 received no perfusion. In two similarly surface-cooled rats (controls), brains were excised when the temperature reached 20 degrees C. After 20 min of RCP or HCA, brains were excised and immediately frozen; brain high-energy phosphates, adenosine, and water content were measured. The liposome-encapsulated hemoglobin perfusate preserved levels of brain tissue adenosine triphosphates and energy charge, but not significantly better than rat red blood cells. Both maintained significantly higher levels than perfusion with oxygenated saline or hypothermic circulatory arrest alone ( P = 0.0419-0.0001), under which regimes high-energy phosphates and energy charge declined to similar low values. RCP with hypertonic solution prevented brain edema. RCP with optimized composition perfusate (pH-stat, hypertonic rat red blood cells or liposome-encapsulated hemoglobin) reduced ischemic energy depletion during 20 min of HCA at 20 degrees C in rats.

Selective Heart, Brain and Body Perfusion in Open Aortic Arch Replacement.

PubMed

Maier, Sven; Kari, Fabian; Rylski, Bartosz; Siepe, Matthias; Benk, Christoph; Beyersdorf, Friedhelm

2016-09-01

Open aortic arch replacement is a complex and challenging procedure, especially in post dissection aneurysms and in redo procedures after previous surgery of the ascending aorta or aortic root. We report our experience with the simultaneous selective perfusion of heart, brain, and remaining body to ensure optimal perfusion and to minimize perfusion-related risks during these procedures. We used a specially configured heart-lung machine with a centrifugal pump as arterial pump and an additional roller pump for the selective cerebral perfusion. Initial arterial cannulation is achieved via femoral artery or right axillary artery. After lower body circulatory arrest and selective antegrade cerebral perfusion for the distal arch anastomosis, we started selective lower body perfusion simultaneously to the selective antegrade cerebral perfusion and heart perfusion. Eighteen patients were successfully treated with this perfusion strategy from October 2012 to November 2015. No complications related to the heart-lung machine and the cannulation occurred during the procedures. Mean cardiopulmonary bypass time was 239 ± 33 minutes, the simultaneous selective perfusion of brain, heart, and remaining body lasted 55 ± 23 minutes. One patient suffered temporary neurological deficit that resolved completely during intensive care unit stay. No patient experienced a permanent neurological deficit or end-organ dysfunction. These high-risk procedures require a concept with a special setup of the heart-lung machine. Our perfusion strategy for aortic arch replacement ensures a selective perfusion of heart, brain, and lower body during this complex procedure and we observed excellent outcomes in this small series. This perfusion strategy is also applicable for redo procedures.

Riluzole in the prelimbic medial prefrontal cortex attenuates veratrine-induced anxiety-like behaviors in mice.

PubMed

Ohashi, Masanori; Saitoh, Akiyoshi; Yamada, Misa; Oka, Jun-Ichiro; Yamada, Mitsuhiko

2015-01-01

We previously demonstrated in mice that the activation of prelimbic medial prefrontal cortex (PL) with the sodium channel activator veratrine induces anxiety-like behaviors via NMDA receptor-mediated glutamatergic neurotransmission. Riluzole directly affects the glutamatergic system and has recently been suggested to have an anxiolytic-like effect in both experimental animals and patients with anxiety disorders. We investigated the effects of co-perfusion of riluzole on veratrine-induced anxiety-like behaviors in mice. Extracellular glutamate levels were measured in 7-week-old male C57BL6 mice by using an in vivo microdialysis-HPLC/ECD system, and behaviors were assessed simultaneously in an open field (OF) test. Basal levels of glutamate were measured by collecting samples every 10 min for 60 min. The medium containing drugs was perfused for 30 min, and the OF test was performed during the last 10 min of drug perfusion. After the drug treatments, the drug-containing medium was switched to perfusion of control medium lacking drugs, and then samples were collected for another 90 min. Riluzole co-perfusion attenuated veratrine-induced increase in extracellular glutamate levels in the PL and completely diminished veratrine-induced anxiety-like behaviors. Interestingly, riluzole perfusion alone in the PL did not affect the basal levels of glutamate and anxiety-like behaviors. Our results suggest that compounds like riluzole that inhibit glutamatergic function in the PL are possible candidates for novel anxiolytics.

A pattern of cerebral perfusion anomalies between Major Depressive Disorder and Hashimoto Thyroiditis

PubMed Central

2011-01-01

Background This study aims to evaluate relationship between three different clinical conditions: Major Depressive Disorders (MDD), Hashimoto Thyroiditis (HT) and reduction in regional Cerebral Blood Flow (rCBF) in order to explore the possibility that patients with HT and MDD have specific pattern(s) of cerebral perfusion. Methods Design: Analysis of data derived from two separate data banks. Sample: 54 subjects, 32 with HT (29 women, mean age 38.8 ± 13.9); 22 without HT (19 women, mean age 36.5 ± 12.25). Assessment: Psychiatric diagnosis was carried out by Simplified Composite International Diagnostic Interview (CIDIS) using DSM-IV categories; cerebral perfusion was measured by 99 mTc-ECD SPECT. Statistical analysis was done through logistic regression. Results MDD appears to be associated with left frontal hypoperfusion, left temporal hypoperfusion, diffuse hypoperfusion and parietal perfusion asymmetry. A statistically significant association between parietal perfusion asymmetry and MDD was found only in the HT group. Conclusion In HT, MDD is characterized by a parietal flow asymmetry. However, the specificity of rCBF in MDD with HT should be confirmed in a control sample with consideration for other health conditions. Moreover, this should be investigated with a longitudinally designed study in order to determine a possible pathogenic cause. Future studies with a much larger sample size should clarify whether a particular perfusion pattern is associated with a specific course or symptom cluster of MDD. PMID:21910915

Detecting stripe artifacts in ultrasound images.

PubMed

Maciak, Adam; Kier, Christian; Seidel, Günter; Meyer-Wiethe, Karsten; Hofmann, Ulrich G

2009-10-01

Brain perfusion diseases such as acute ischemic stroke are detectable through computed tomography (CT)-/magnetic resonance imaging (MRI)-based methods. An alternative approach makes use of ultrasound imaging. In this low-cost bedside method, noise and artifacts degrade the imaging process. Especially stripe artifacts show a similar signal behavior compared to acute stroke or brain perfusion diseases. This document describes how stripe artifacts can be detected and eliminated in ultrasound images obtained through harmonic imaging (HI). On the basis of this new method, both proper identification of areas with critically reduced brain tissue perfusion and classification between brain perfusion defects and ultrasound stripe artifacts are made possible.

Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents

PubMed Central

Sinha, Rajita; Arora, Jagriti; Giannini, Cosimo; Kubat, Jessica; Malik, Saima; Van Name, Michelle A.; Santoro, Nicola; Savoye, Mary; Duran, Elvira J.; Pierpont, Bridget; Cline, Gary; Constable, R. Todd; Sherwin, Robert S.

2016-01-01

Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain. PMID:27207544

Dual role of cerebral blood flow in regional brain temperature control in the healthy newborn infant.

PubMed

Iwata, Sachiko; Tachtsidis, Ilias; Takashima, Sachio; Matsuishi, Toyojiro; Robertson, Nicola J; Iwata, Osuke

2014-10-01

Small shifts in brain temperature after hypoxia-ischaemia affect cell viability. The main determinants of brain temperature are cerebral metabolism, which contributes to local heat production, and brain perfusion, which removes heat. However, few studies have addressed the effect of cerebral metabolism and perfusion on regional brain temperature in human neonates because of the lack of non-invasive cot-side monitors. This study aimed (i) to determine non-invasive monitoring tools of cerebral metabolism and perfusion by combining near-infrared spectroscopy and echocardiography, and (ii) to investigate the dependence of brain temperature on cerebral metabolism and perfusion in unsedated newborn infants. Thirty-two healthy newborn infants were recruited. They were studied with cerebral near-infrared spectroscopy, echocardiography, and a zero-heat flux tissue thermometer. A surrogate of cerebral blood flow (CBF) was measured using superior vena cava flow adjusted for cerebral volume (rSVC flow). The tissue oxygenation index, fractional oxygen extraction (FOE), and the cerebral metabolic rate of oxygen relative to rSVC flow (CMRO₂ index) were also estimated. A greater rSVC flow was positively associated with higher brain temperatures, particularly for superficial structures. The CMRO₂ index and rSVC flow were positively coupled. However, brain temperature was independent of FOE and the CMRO₂ index. A cooler ambient temperature was associated with a greater temperature gradient between the scalp surface and the body core. Cerebral oxygen metabolism and perfusion were monitored in newborn infants without using tracers. In these healthy newborn infants, cerebral perfusion and ambient temperature were significant independent variables of brain temperature. CBF has primarily been associated with heat removal from the brain. However, our results suggest that CBF is likely to deliver heat specifically to the superficial brain. Further studies are required to assess the effect of cerebral metabolism and perfusion on regional brain temperature in low-cardiac output conditions, fever, and with therapeutic hypothermia. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cerebrovascular Pressure Reactivity in Children With Traumatic Brain Injury.

PubMed

Lewis, Philip M; Czosnyka, Marek; Carter, Bradley G; Rosenfeld, Jeffrey V; Paul, Eldho; Singhal, Nitesh; Butt, Warwick

2015-10-01

Traumatic brain injury is a significant cause of morbidity and mortality in children. Cerebral autoregulation disturbance after traumatic brain injury is associated with worse outcome. Pressure reactivity is a fundamental component of cerebral autoregulation that can be estimated using the pressure-reactivity index, a correlation between slow arterial blood pressure, and intracranial pressure fluctuations. Pressure-reactivity index has shown prognostic value in adult traumatic brain injury, with one study confirming this in children. Pressure-reactivity index can identify a cerebral perfusion pressure range within which pressure reactivity is optimal. An increasing difference between optimal cerebral perfusion pressure and cerebral perfusion pressure is associated with worse outcome in adult traumatic brain injury; however, this has not been investigated in children. Our objective was to study pressure-reactivity index and optimal cerebral perfusion pressure in pediatric traumatic brain injury, including associations with outcome, age, and cerebral perfusion pressure. Prospective observational study. ICU, Royal Children's Hospital, Melbourne, Australia. Patients with traumatic brain injury who are 6 months to 16 years old, are admitted to the ICU, and require arterial blood pressure and intracranial pressure monitoring. None. Arterial blood pressure, intracranial pressure, and end-tidal CO2 were recorded electronically until ICU discharge or monitoring cessation. Pressure-reactivity index and optimal cerebral perfusion pressure were computed according to previously published methods. Clinical data were collected from electronic medical records. Outcome was assessed 6 months post discharge using the modified Glasgow Outcome Score. Thirty-six patients were monitored, with 30 available for follow-up. Pressure-reactivity index correlated with modified Glasgow Outcome Score (Spearman ρ = 0.42; p = 0.023) and was higher in patients with unfavorable outcome (0.23 vs -0.09; p = 0.0009). A plot of pressure-reactivity index averaged within 5 mm Hg cerebral perfusion pressure bins showed a U-shape, reaffirming the concept of cerebral perfusion pressure optimization in children. Optimal cerebral perfusion pressure increased with age (ρ = 0.40; p = 0.02). Both the duration and magnitude of negative deviations in the difference between cerebral perfusion pressure and optimal cerebral perfusion pressure were associated with unfavorable outcome. In pediatric patients with traumatic brain injury, pressure-reactivity index has prognostic value and can identify cerebral perfusion pressure targets that may differ from treatment protocols. Our results suggest but do not confirm that cerebral perfusion pressure targeting using pressure-reactivity index as a guide may positively impact on outcome. This question should be addressed by a prospective clinical study.

Modulatory effects of ketamine, risperidone and lamotrigine on resting brain perfusion in healthy human subjects.

PubMed

Shcherbinin, Sergey; Doyle, Orla; Zelaya, Fernando O; de Simoni, Sara; Mehta, Mitul A; Schwarz, Adam J

2015-11-01

Resting brain perfusion, measured using the MRI-based arterial spin labelling (ASL) technique, is sensitive to detect central effects of single, clinically effective, doses of pharmacological compounds. However, pharmacological interaction experiments, such as the modulation of one drug response in the presence of another, have not been widely investigated using a task-free ASL approach. We assessed the effects of three psychoactive compounds (ketamine, risperidone and lamotrigine), and their interaction, on resting brain perfusion in healthy human volunteers. A multivariate Gaussian process classification (GPC) and more conventional univariate analyses were applied. The four pre-infusion conditions for each subject comprised risperidone, lamotrigine and two placebo sessions. The two placebo conditions enabled us to evaluate the classification performance in a test-retest setting, in addition to its performance in distinguishing the active oral drugs from placebo (direct effect on brain perfusion). The post ketamine- or saline-infusion scans allowed the effect of ketamine, and its interaction with risperidone and lamotrigine, on brain perfusion to be characterised. The pseudo-continuous ASL measurements of perfusion were sensitive to the effects of ketamine infusion and risperidone. The GPC captured consistent changes in perfusion across the group and contextualised the univariate changes with a larger pattern of regions contributing to accurate discrimination of ketamine from placebo. The findings argue against perfusion changes confounding in the previously described evoked BOLD response to ketamine and emphasise the blockade of the NMDA receptor over neuronal glutamate release in determining the perfusion changes induced by ketamine.

Impact of CyberKnife Radiosurgery on Overall Survival and Various Parameters of Patients with 1-3 versus ≥ 4 Brain Metastases.

PubMed

Murovic, Judith; Ding, Victoria; Han, Summer S; Adler, John R; Chang, Steven D

2017-10-24

Introduction This study's objective is to compare the overall survivals (OSs) and various parameters of patients with 1-3 versus ≥ 4 brain metastases post-CyberKnife radiosurgery (CKRS) (Accuray, Sunnyvale, California) alone. Methods Charts of 150 patients, from 2009-2014, treated with only CKRS for brain metastases were reviewed retrospectively for overall survival (OS) and patient, tumor, and imaging characteristics. Parameters included demographics, Eastern Cooperative Oncology Group (ECOG) performance scores, number and control of extracranial disease (ECD) sites, cause of death (COD), histology, tumor volume (TV), and post-CKRS whole brain radiotherapy (WBRT). The imaging characteristics assessed were time of complete response (CR), partial response (PR), stable imaging or local failure (LF), and distal brain failure (DBF). Patients and their data were divided into those with 1-3 (group 1) versus ≥ 4 brain metastases (group 2). For each CR and LF patient, absolute neutrophil count (ANC), absolute lymphocyte count (ALC)), and ANC/ALC ratio (NLR) were obtained, when available, at the time of CKRS. Results Both group 1 and group 2 had a median OS of 13 months. The patient median age for the 115 group 1 patients versus the 35 group 2 patients was 62 versus 56 years. Group 1 had slightly more males and group 2, females. The predominant ECOG score for each group was 1 and the number of ECD sites was one and two, respectively. Uncontrolled ECD occurred in the majority of both group 1 and group 2 patients. The main COD was ECD in both groups. The prevalent tumor histology for groups 1 and 2 was non-small cell lung carcinoma. Median TVs were 1.08 cc versus 1.42 cc for groups 1 and 2, respectively. The majority of patients in both groups did not undergo post-CKRS WBRT. Imaging outcomes were LC (CR, PR, or stable imaging) in 93 (80.9%) and 26 (74.3%) group 1 and 2 patients, of whom 32 (27.8%) and six (17.1%) had CR; 38 (33.0%) and 18 (51.4%), PR and 23 (20.0%) and two (5.7%), stable imaging; LF was the outcome in 22 (19.1%) and nine (25.7%) patients, and DBF occurred in 62 (53.9%) and 21 (60.0%), respectively. Uni- and multivariable analyses showed the independent parameters of a lower ECOG score, a greater number of ECD sites and uncontrolled ECD were significantly associated with greater mortality risk with and without accounting for other covariates. At CKRS, 19 group 1 and 2 CR patients had a mean ANC of 5.88 K/µL and a mean ALC of 1.31 K/µL and 13 (68%) of 19 had NLRs ≤ five, while 11 with LFs had a mean ANC of 5.22 K/µL and a mean ALC of 0.93 K/µL and seven (64%) had NLRs > five. An NLR ≤ five and high ALC was associated with a CR and an NLR > five and a low ALC with an LF. Conclusions Median OS post-CKRS was 13 months for both patients with 1-3 brain metastases and with ≥ 4. This is the only study in the literature to evaluate OS in patients with 1-3 and ≥ 4 brain metastases who were treated with CKRS alone. For groups 1 and 2 patients combined, 119 (79.3%) had LC and 38 (25.3%) had CR. The ANC, ALC, and NLR values are likely predictive of CR and LF outcomes.

Electroencephalography in ellipsoidal geometry with fourth-order harmonics.

PubMed

Alcocer-Sosa, M; Gutierrez, D

2016-08-01

We present a solution to the electroencephalographs (EEG) forward problem of computing the scalp electric potentials for the case when the head's geometry is modeled using a four-shell ellipsoidal geometry and the brain sources with an equivalent current dipole (ECD). The proposed solution includes terms up to the fourth-order ellipsoidal harmonics and we compare this new approximation against those that only considered up to second- and third-order harmonics. Our comparisons use as reference a solution in which a tessellated volume approximates the head and the forward problem is solved through the boundary element method (BEM). We also assess the solution to the inverse problem of estimating the magnitude of an ECD through different harmonic approximations. Our results show that the fourth-order solution provides a better estimate of the ECD in comparison to lesser order ones.

Measurement of cerebral perfusion after zolpidem administration in the baboon model.

PubMed

Clauss, R P; Dormehl, I C; Oliver, D W; Nel, W H; Kilian, E; Louw, W K

2001-01-01

A recent report showed that zolpidem (CAS 82626-48-0) can lead to the arousal of a semi-comatosed patient. Zolpidem is clinically used for the treatment of insomnia. It belongs to the imidazopyridine chemical class and is a non benzodiazepine drug. It illicits its pharmacological action via the GABA receptor system through stimulation of particularly the omega 1 receptors. In this study, the effect of zolpidem on brain perfusion was examined by 99mTc hexamethyl-propylene amine oxime (HMPAO) split dose brain SPECT on four normal baboons and in one baboon with abnormal neurological behaviour. The global and regional brain perfusion was not significantly affected in the normal brains. In some regions of the abnormal baboon brain, however, there was a disproportionate increase in perfusion after zolpidem.

A reappraisal of retrograde cerebral perfusion.

PubMed

Ueda, Yuichi

2013-05-01

Brain protection during aortic arch surgery by perfusing cold oxygenated blood into the superior vena cava was first reported by Lemole et al. In 1990 Ueda and associates first described the routine use of continuous retrograde cerebral perfusion (RCP) in thoracic aortic surgery for the purpose of cerebral protection during the interval of obligatory interruption of anterograde cerebral flow. The beneficial effects of RCP may be its ability to sustain brain hypothermia during hypothermic circulatory arrest (HCA) and removal of embolic material from the arterial circulation of the brain. RCP can offer effective brain protection during HCA for about 40 to 60 minutes. Animal experiments revealed that RCP provided inadequate cerebral perfusion and that neurological recovery was improved with selective antegrade cerebral perfusion (ACP), however, both RCP and ACP provide comparable clinical outcomes regarding both the mortality and stroke rates by risk-adjusted and case-matched comparative study. RCP still remains a valuable adjunct for brain protection during aortic arch repair in particular pathologies and patients.

A reappraisal of retrograde cerebral perfusion

PubMed Central

2013-01-01

Brain protection during aortic arch surgery by perfusing cold oxygenated blood into the superior vena cava was first reported by Lemole et al. In 1990 Ueda and associates first described the routine use of continuous retrograde cerebral perfusion (RCP) in thoracic aortic surgery for the purpose of cerebral protection during the interval of obligatory interruption of anterograde cerebral flow. The beneficial effects of RCP may be its ability to sustain brain hypothermia during hypothermic circulatory arrest (HCA) and removal of embolic material from the arterial circulation of the brain. RCP can offer effective brain protection during HCA for about 40 to 60 minutes. Animal experiments revealed that RCP provided inadequate cerebral perfusion and that neurological recovery was improved with selective antegrade cerebral perfusion (ACP), however, both RCP and ACP provide comparable clinical outcomes regarding both the mortality and stroke rates by risk-adjusted and case-matched comparative study. RCP still remains a valuable adjunct for brain protection during aortic arch repair in particular pathologies and patients. PMID:23977600

Designing Real-time Decision Support for Trauma Resuscitations

PubMed Central

Yadav, Kabir; Chamberlain, James M.; Lewis, Vicki R.; Abts, Natalie; Chawla, Shawn; Hernandez, Angie; Johnson, Justin; Tuveson, Genevieve; Burd, Randall S.

2016-01-01

Background Use of electronic clinical decision support (eCDS) has been recommended to improve implementation of clinical decision rules. Many eCDS tools, however, are designed and implemented without taking into account the context in which clinical work is performed. Implementation of the pediatric traumatic brain injury (TBI) clinical decision rule at one Level I pediatric emergency department includes an electronic questionnaire triggered when ordering a head computed tomography using computerized physician order entry (CPOE). Providers use this CPOE tool in less than 20% of trauma resuscitation cases. A human factors engineering approach could identify the implementation barriers that are limiting the use of this tool. Objectives The objective was to design a pediatric TBI eCDS tool for trauma resuscitation using a human factors approach. The hypothesis was that clinical experts will rate a usability-enhanced eCDS tool better than the existing CPOE tool for user interface design and suitability for clinical use. Methods This mixed-methods study followed usability evaluation principles. Pediatric emergency physicians were surveyed to identify barriers to using the existing eCDS tool. Using standard trauma resuscitation protocols, a hierarchical task analysis of pediatric TBI evaluation was developed. Five clinical experts, all board-certified pediatric emergency medicine faculty members, then iteratively modified the hierarchical task analysis until reaching consensus. The software team developed a prototype eCDS display using the hierarchical task analysis. Three human factors engineers provided feedback on the prototype through a heuristic evaluation, and the software team refined the eCDS tool using a rapid prototyping process. The eCDS tool then underwent iterative usability evaluations by the five clinical experts using video review of 50 trauma resuscitation cases. A final eCDS tool was created based on their feedback, with content analysis of the evaluations performed to ensure all concerns were identified and addressed. Results Among 26 EPs (76% response rate), the main barriers to using the existing tool were that the information displayed is redundant and does not fit clinical workflow. After the prototype eCDS tool was developed based on the trauma resuscitation hierarchical task analysis, the human factors engineers rated it to be better than the CPOE tool for nine of 10 standard user interface design heuristics on a three-point scale. The eCDS tool was also rated better for clinical use on the same scale, in 84% of 50 expert–video pairs, and was rated equivalent in the remainder. Clinical experts also rated barriers to use of the eCDS tool as being low. Conclusions An eCDS tool for diagnostic imaging designed using human factors engineering methods has improved perceived usability among pediatric emergency physicians. PMID:26300010

Brain Perfusion and Arterial Blood Flow Velocity During Prolonged Body Tilting.

PubMed

Montero, David; Rauber, Sven

2016-08-01

It remains unknown whether brain perfusion is preserved and mirrored by middle cerebral blood flow velocity (MCA BFV) during prolonged changes in body posture. Herein, we examined the impact of sustained (180 min) 30° head-up (HUT) and head-down (HDT) tilt on brain perfusion, as determined by MCA BFV and blood flow in the extracranial arteries. In 10 healthy male subjects, arterial diameters, BFVs, and blood flows were determined in the left internal carotid (ICA) and vertebral (VA) arteries using duplex Doppler ultrasound in supine rest, and 5, 20, 60, 120, and 180 min following 30° HUT and HDT. MCA BFV was recorded throughout with transcranial Doppler ultrasound. ICA as well as VA diameters and blood flows were unaltered during HUT. Likewise, brain blood flow and MCA BFV were preserved with HUT. In the HDT protocol, ICA and VA diameters were gradually increased, although ICA, VA, and brain blood flows were preserved. MCA BFV was progressively reduced during HDT. In addition, MCA BFV was positively associated with ICA BFV (β = 0.9) and negatively associated with ICA diameter (β = -125.5). MCA BFV was positively associated with brain blood flow during HUT (β = 0.2) but not HDT. Brain perfusion is preserved whereas MCA BFV is progressively decreased and associated with extracranial arterial BFV during sustained 30° HDT. Therefore, MCA BFV may not be a surrogate of brain perfusion in conditions including prolonged HDT. Montero D, Rauber S. Brain perfusion and arterial blood flow velocity during prolonged body tilting. Aerosp Med Hum Perform. 2016; 87(8):682-687.

Cerebral, facial, and orbital involvement in Erdheim-Chester disease: CT and MR imaging findings.

PubMed

Drier, Aurélie; Haroche, Julien; Savatovsky, Julien; Godenèche, Gaelle; Dormont, Didier; Chiras, Jacques; Amoura, Zahir; Bonneville, Fabrice

2010-05-01

To retrospectively review the brain magnetic resonance (MR) imaging and computed tomographic (CT) findings in patients with Erdheim-Chester disease (ECD). The ethics committee required neither institutional review board approval nor informed patient consent for retrospective analyses of the patients' medical records and imaging data. The patients' medical files were retrospectively reviewed in accordance with human subject research protocols. Three neuroradiologists in consensus analyzed the signal intensity, location, size, number, and gadolinium uptake of lesions detected on brain MR images obtained in 33 patients with biopsy-proved ECD. Thirty patients had intracranial, facial bone, and/or orbital involvement, and three had normal neurologic imaging findings. The hypothalamic-pituitary axis was involved in 16 (53%) of the 30 patients, with six (20%) cases of micronodular or nodular masses of the infundibular stalk. Meningeal lesions were observed in seven (23%) patients. Three (10%) patients had bilateral symmetric T2 high signal intensity in the dentate nucleus areas, and five (17%) had multiple intraaxial enhancing masses. Striking intracranial periarterial infiltration was observed in three (10%) patients. Another patient (3%) had a lesion in the lumen of the superior sagittal sinus. Nine (30%) patients had orbital involvement. Twenty-four (80%) patients had osteosclerosis of the facial and/or skull bones. At least two anatomic sites were involved in two-thirds (n = 20) of the patients. Osteosclerosis of the facial bones associated with orbital masses and either meningeal or infundibular stalk masses was seen in eight (27%) patients. Lesions of the brain, meninges, facial bones, and orbits are frequently observed and should be systematically sought on the brain MR and CT images obtained in patients with ECD, even if these patients are asymptomatic. Careful attention should be directed to the periarterial environment.

Bacterial lipopolysaccharide-induced systemic inflammation alters perfusion of white matter-rich regions without altering flow in brain-irrigating arteries: Relationship to blood-brain barrier breakdown?

PubMed

Dhaya, Ibtihel; Griton, Marion; Raffard, Gérard; Amri, Mohamed; Hiba, Bassem; Konsman, Jan Pieter

2018-01-15

To better understand brain dysfunction during sepsis, cerebral arterial blood flow was assessed with Phase Contrast Magnetic Resonance Imaging, perfusion with Arterial Spin Labeling and structure with diffusion-weighted Magnetic Resonance Imaging in rats after intraperitoneal administration of bacterial lipopolysaccharides. Although cerebral arterial flow was not altered, perfusion of the corpus callosum region and diffusion parallel to its fibers were higher after lipopolysaccharide administration as compared to saline injection. In parallel, lipopolysaccharide induced perivascular immunoglobulin-immunoreactivity in white matter. These findings indicate that systemic inflammation can result in increased perfusion, blood-brain barrier breakdown and altered water diffusion in white matter. Copyright © 2017 Elsevier B.V. All rights reserved.

Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report.

PubMed

Crippa, José Alexandre S; Derenusson, Guilherme Nogueira; Ferrari, Thiago Borduqui; Wichert-Ana, Lauro; Duran, Fábio L S; Martin-Santos, Rocio; Simões, Marcus Vinícius; Bhattacharyya, Sagnik; Fusar-Poli, Paolo; Atakan, Zerrin; Santos Filho, Alaor; Freitas-Ferrari, Maria Cecília; McGuire, Philip K; Zuardi, Antonio Waldo; Busatto, Geraldo F; Hallak, Jaime Eduardo Cecílio

2011-01-01

Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging. Regional cerebral blood flow (rCBF) at rest was measured twice using (99m)Tc-ECD SPECT in 10 treatment-naïve patients with SAD. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping. Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001), reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (p < 0.001, uncorrected), and increased ECD uptake in the right posterior cingulate gyrus (p < 0.001, uncorrected). These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.

Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents.

PubMed

Jastreboff, Ania M; Sinha, Rajita; Arora, Jagriti; Giannini, Cosimo; Kubat, Jessica; Malik, Saima; Van Name, Michelle A; Santoro, Nicola; Savoye, Mary; Duran, Elvira J; Pierpont, Bridget; Cline, Gary; Constable, R Todd; Sherwin, Robert S; Caprio, Sonia

2016-07-01

Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

The archetypal R90C CADASIL-NOTCH3 mutation retains NOTCH3 function in vivo.

PubMed

Monet, Marie; Domenga, Valérie; Lemaire, Barbara; Souilhol, Céline; Langa, Francina; Babinet, Charles; Gridley, Thomas; Tournier-Lasserve, Elisabeth; Cohen-Tannoudji, Michel; Joutel, Anne

2007-04-15

Cerebral Autosomal Dominant Arteriopathy with Subcortical infarcts and Leukoencephalopathy (CADASIL) is the most prominent known cause of inherited stroke and vascular dementia in human adult. The disease gene, NOTCH3, encodes a transmembrane receptor primarily expressed in arterial smooth muscle cells (SMC). Pathogenic mutations lead to an odd number of cysteine residues within the NOTCH3 extracellular domain (NOTCH3(ECD)), and are associated with progressive accumulation of NOTCH3(ECD) at the SMC plasma membrane. The murine homolog, Notch3, is dispensable for viability but required post-natally for the elaboration and maintenance of arteries. How CADASIL-associated mutations impact NOTCH3 function remains a fundamental, yet unresolved issue. Particularly, whether NOTCH3(ECD) accumulation may titrate the ligand and inhibit the normal pathway is unknown. Herein, using genetic analyses in the mouse, we assessed the functional significance of an archetypal CADASIL-associated mutation (R90C), in vivo, in brain arteries. We show that transgenic mouse lines expressing either the wild-type human NOTCH3 or the mutant R90C human NOTCH3, at comparable and physiological levels, can rescue the arterial defects of Notch3-/- mice to similar degrees. In vivo assessment of NOTCH3/RBP-Jk activity provides evidence that the mutant NOTCH3 protein exhibits normal level of activity in brain arteries. Remarkably, the mutant NOTCH3 protein remains functional and does not exhibit dominant negative interfering activity, even when NOTCH3(ECD) accumulates. Collectively, these data suggest a model that invokes novel pathogenic roles for the mutant NOTCH3 protein rather than compromised NOTCH3 function as the primary determinant of the CADASIL arteriopathy.

Neurovascular regulation in the ischemic brain.

PubMed

Jackman, Katherine; Iadecola, Costantino

2015-01-10

The brain has high energetic requirements and is therefore highly dependent on adequate cerebral blood supply. To compensate for dangerous fluctuations in cerebral perfusion, the circulation of the brain has evolved intrinsic safeguarding measures. The vascular network of the brain incorporates a high degree of redundancy, allowing the redirection and redistribution of blood flow in the event of vascular occlusion. Furthermore, active responses such as cerebral autoregulation, which acts to maintain constant cerebral blood flow in response to changing blood pressure, and functional hyperemia, which couples blood supply with synaptic activity, allow the brain to maintain adequate cerebral perfusion in the face of varying supply or demand. In the presence of stroke risk factors, such as hypertension and diabetes, these protective processes are impaired and the susceptibility of the brain to ischemic injury is increased. One potential mechanism for the increased injury is that collateral flow arising from the normally perfused brain and supplying blood flow to the ischemic region is suppressed, resulting in more severe ischemia. Approaches to support collateral flow may ameliorate the outcome of focal cerebral ischemia by rescuing cerebral perfusion in potentially viable regions of the ischemic territory.

The Effect of the Presence of EEG Leads on Image Quality in Cerebral Perfusion SPECT and FDG PET/CT.

PubMed

Zhang, Lulu; Yen, Stephanie P; Seltzer, Marc A; Thomas, George P; Willis, Kristen; Siegel, Alan

2018-06-08

Rationale: Cerebral perfusion SPECT and 18 F-FDG PET/CT are commonly performed diagnostic procedures for patients suffering from epilepsy. Individuals receiving these tests are often in-patients undergoing examinations with EEG leads. We have routinely removed these leads before these tests due to concerns that they would lead to imaging artifacts. The leads would then be replaced at the conclusion of the scan. The goal of our study was to determine if the EEG leads actually do cause artifacts that could lead to erroneous scan interpretation or make the scan uninterpretable. Methods: PET/CT with 18 F-FDG and SPECT with technetium-99m ECD were performed on a two dimensional brain phantom. The phantom was scanned with standard leads, CT/MR compatible leads and with no leads. The scans were interpreted by three experienced nuclear medicine physicians who were asked to rank the images by quality and then to determine if they could differentiate each of the scans from a scan in which it was indicated that no leads were present. Results: No differences could be detected between SPECT or PET scans performed without leads or with either set of leads. The standard EEG leads did create an artifact in the CT portion of the PET/CT while the CT/MR compatible leads did not. Conclusion: This phantom study suggest that EEG leads, standard or CT/MR compatible do not need to be removed for SPECT or for PET. Further study evaluating the effect on patients scan would be of value to support this conclusion. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Expanded criteria donor and donation after circulatory death renal allografts in the West of Scotland: Their place in the kidney allocation process.

PubMed

Hesse, Kerrick; Aitken, Emma; Clancy, Marc; Vesey, Alex

2016-06-01

Due to the rising disparity between demand and availability, organs from expanded criteria donors (ECD) and donors after determination of circulatory death (DCD) are increasingly used. The purpose of this study was to report outcomes in recipients of ECD and DCD renal allografts from a single centre. A retrospective analysis from a single centre for all renal transplants performed between 2001 and 2010 inclusive was undertaken. SCD (standard criteria donor) and ECD organs were compared, as were DCD and DBD (donation after determination of brain stem death) organs. Baseline data and predefined standard transplant outcomes were collected and compared using appropriate statistical tests. P < 0.05 was defined as significant. 729 renal transplants were performed. Comparing ECD to SCD organs, there was a significant difference in graft survival between groups (logrank for trend, p = 0.032) with ECD organs doing worse than SCD organs. Short-term outcomes showed a similar disparity with a higher 1-year post-transplant creatinine and delayed graft function (DGF) rate in ECD grafts. Nevertheless, outcomes were still clinically acceptable. When comparing DCD to DBD organs, no such differences were apparent, with DCD organs appearing to perform at least as well as DBD organs. In our cohort, unlike some previous studies, DGF rates were similar in both DCD and DBD groups. Although ECD organs perform less well than SCD organs, outcomes are still acceptable and our results support their continuing use. When considering DCD organs, our data support the view that they should no longer be necessarily regarded as marginal grafts. Our low DGF rates are perhaps explained by local factors contributing to a short CIT. Copyright © 2014 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Postmortem changes in the neuroanatomical characteristics of the primate brain: the hippocampal formation

PubMed Central

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L.; Amaral, David G.

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused, or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger, as compared to perfusion-fixed tissue. Non-phosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well-stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences. PMID:18972553

Postmortem changes in the neuroanatomical characteristics of the primate brain: hippocampal formation.

PubMed

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L; Amaral, David G

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger as compared to perfusion-fixed tissue. Nonphosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells, and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences.

Brain perfusion correlates of visuoperceptual deficits in Mild Cognitive Impairment and mild Alzheimer’s disease

PubMed Central

Alegret, Montserrat; Vinyes-Junqué, Georgina; Boada, Mercè; Martínez-Lage, Pablo; Cuberas, Gemma; Espinosa, Ana; Roca, Isabel; Hernández, Isabel; Valero, Sergi; Rosende-Roca, Maitée; Mauleón, Ana; Becker, James T.; Tárraga, Lluís

2012-01-01

Background Visuoperceptual processing is impaired early in the clinical course of Alzheimer’s disease (AD). The 15-Objects Test (15-OT) detects such subtle performance deficits in Mild Cognitive Impairment (MCI) and mild AD. Reduced brain perfusion in the temporal, parietal and prefrontal regions have been found in early AD and MCI patients. Objectives To confirm the role of the 15-OT in the diagnosis of MCI and AD, and to investigate the brain perfusion correlates of visuoperceptual dysfunction (15-OT) in subjects with MCI, AD and normal aging. Methods Forty-two AD, 42 MCI and 42 healthy elderly control (EC) subjects underwent a brain Single Photon Emission Tomography (SPECT) and separately completed the 15-OT. An analysis of variance compared 15-OT scores between groups. SPM5 was used to analyse the SPECT data. Results 15-OT performace was impaired in the MCI and AD patients. In terms of the SPECT scans, AD patients showed reduced perfusion in temporal-parietal regions, while the MCI subjects had decreased perfusion in the middle and posterior cingulate. When MCI and AD groups were compared, a significant brain perfusion reduction was found in temporo-parietal regions. In the whole sample, 15-OT performance was significantly correlated with the clinical dementia rating scores, and with the perfusion in the bilateral posterior cingulate and the right temporal pole, with no significant correlation in each separate group. Conclusion Our findings suggest that the 15-OT performance provides a useful gradation of impairment from normal aging to AD, and it seems to be related to perfusion in the bilateral posterior cingulate and the right temporal pole. PMID:20555146

Towards mapping the brain connectome in depression: functional connectivity by perfusion SPECT.

PubMed

Gardner, Ann; Åstrand, Disa; Öberg, Johanna; Jacobsson, Hans; Jonsson, Cathrine; Larsson, Stig; Pagani, Marco

2014-08-30

Several studies have demonstrated altered brain functional connectivity in the resting state in depression. However, no study has investigated interregional networking in patients with persistent depressive disorder (PDD). The aim of this study was to assess differences in brain perfusion distribution and connectivity between large groups of patients and healthy controls. Participants comprised 91 patients with PDD and 65 age- and sex-matched healthy controls. Resting state perfusion was investigated by single photon emission computed tomography, and group differences were assessed by Statistical Parametric Mapping. Brain connectivity was explored through a voxel-wise interregional correlation analysis using as covariate of interest the normalized values of clusters of voxels in which perfusion differences were found in group analysis. Significantly increased regional brain perfusion distribution covering a large part of the cerebellum was observed in patients as compared with controls. Patients showed a significant negative functional connectivity between the cerebellar cluster and caudate, bilaterally. This study demonstrated inverse relative perfusion between the cerebellum and the caudate in PDD. Functional uncoupling may be associated with a dysregulation between the role of the cerebellum in action control and of the caudate in action selection, initiation and decision making in the patients. The potential impact of the resting state condition and the possibility of mitochondrial impairment are discussed. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Brain perfusion alterations in tick-borne encephalitis-preliminary report.

PubMed

Tyrakowska-Dadełło, Zuzanna; Tarasów, Eugeniusz; Janusek, Dariusz; Moniuszko-Malinowska, Anna; Zajkowska, Joanna; Pancewicz, Sławomir

2018-03-01

Magnetic resonance imaging (MRI) changes in tick-borne encephalitis (TBE) are non-specific and the pathophysiological mechanisms leading to their formation remain unclear. This study investigated brain perfusion in TBE patients using dynamic susceptibility-weighted contrast-enhanced magnetic resonance perfusion imaging (DSC-MRI perfusion). MRI scans were performed for 12 patients in the acute phase, 3-5days after the diagnosis of TBE. Conventional MRI and DSC-MRI perfusion studies were performed. Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP) parametric maps were created. The bilateral frontal, parietal, and temporal subcortical regions and thalamus were selected as regions of interest. Perfusion parameters of TBE patients were compared to those of a control group. There was a slight increase in CBF and CBV, with significant prolongation of TTP in subcortical areas in the study subjects, while MTT values were comparable to those of the control group. A significant increase in thalamic CBF (p<0.001) and increased CBV (p<0.05) were observed. Increased TTP and a slight reduction in MTT were also observed within this area. The DSC-MRI perfusion study showed that TBE patients had brain perfusion disturbances, expressed mainly in the thalami. These results suggest that DSC-MRI perfusion may provide important information regarding the areas affected in TBE patients. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Regional cerebral blood flow changes in Parkinson's disease: correlation with disease duration].

PubMed

Kapitán, M; Ferrando, R; Diéguez, E; de Medina, O; Aljanati, R; Ventura, R; Amorin, I; Salinas, D; Langhain, M; Gioia, A; Cardoso, A; Lago, G; Buzó, R

2009-01-01

Changes in regional cerebral blood flow (rCBF) have been reported in idiopathic Parkinson's disease (PD). Nonetheless, their typical pattern still remains controversial regarding some features, such as basal ganglia involvement and the main cortical regions affected. Functional neuroimaging makes it possible to identify the brain dysfunctions of the neural circuits underlying the disease. Voxel-based analysis methods make it possible to increase the reliability of the results. To assess the rCBF changes in patients with PD and their relation with disease duration. Thirty PD adult patients without dementia underwent evaluation with (99m)Tc-ECD SPECT. SPM5 was used for statistical comparison with 25 normal controls of similar ages. The disease course duration in years was added as a covariate. Additionally, patients with a 6-year evolution or less and those with more than 6 years were compared separately with normal controls. Significant hypoperfusion was detected in bilateral premotor and posterior parietal cortex and increase of perfusion was present in the cerebellum. These changes correlated with the years of evolution of the illness. Patients with longer evolution also presented thalamic, subthalamic and basal ganglia hypoperfusion. We describe rCBF changes in PD in neural circuits related with control of movements. These changes are more manifest in patients with a longer duration of the disease.

Imaging Human Brain Perfusion with Inhaled Hyperpolarized 129Xe MR Imaging.

PubMed

Rao, Madhwesha R; Stewart, Neil J; Griffiths, Paul D; Norquay, Graham; Wild, Jim M

2018-02-01

Purpose To evaluate the feasibility of directly imaging perfusion of human brain tissue by using magnetic resonance (MR) imaging with inhaled hyperpolarized xenon 129 ( 129 Xe). Materials and Methods In vivo imaging with 129 Xe was performed in three healthy participants. The combination of a high-yield spin-exchange optical pumping 129 Xe polarizer, custom-built radiofrequency coils, and an optimized gradient-echo MR imaging protocol was used to achieve signal sensitivity sufficient to directly image hyperpolarized 129 Xe dissolved in the human brain. Conventional T1-weighted proton (hydrogen 1 [ 1 H]) images and perfusion images by using arterial spin labeling were obtained for comparison. Results Images of 129 Xe uptake were obtained with a signal-to-noise ratio of 31 ± 9 and demonstrated structural similarities to the gray matter distribution on conventional T1-weighted 1 H images and to perfusion images from arterial spin labeling. Conclusion Hyperpolarized 129 Xe MR imaging is an injection-free means of imaging the perfusion of cerebral tissue. The proposed method images the uptake of inhaled xenon gas to the extravascular brain tissue compartment across the intact blood-brain barrier. This level of sensitivity is not readily available with contemporary MR imaging methods. © RSNA, 2017.

Effects of positive end-expiratory pressure on brain tissue oxygen pressure of severe traumatic brain injury patients with acute respiratory distress syndrome: A pilot study.

PubMed

Nemer, Sérgio Nogueira; Caldeira, Jefferson B; Santos, Ricardo G; Guimarães, Bruno L; Garcia, João Márcio; Prado, Darwin; Silva, Ricardo T; Azeredo, Leandro M; Faria, Eduardo R; Souza, Paulo Cesar P

2015-12-01

To verify whether high positive end-expiratory pressure levels can increase brain tissue oxygen pressure, and also their effects on pulse oxygen saturation, intracranial pressure, and cerebral perfusion pressure. Twenty traumatic brain injury patients with acute respiratory distress syndrome were submitted to positive end-expiratory pressure levels of 5, 10, and 15 cm H2O progressively. The 3 positive end-expiratory pressure levels were used during 20 minutes for each one, whereas brain tissue oxygen pressure, oxygen saturation, intracranial pressure, and cerebral perfusion pressure were recorded. Brain tissue oxygen pressure and oxygen saturation increased significantly with increasing positive end-expiratory pressure from 5 to 10 and from 10 to 15 cm H2O (P=.0001 and P=.0001 respectively). Intracranial pressure and cerebral perfusion pressure did not differ significantly with increasing positive end-expiratory pressure from 5 to 10 and from 10 to 15 cm H2O (P=.16 and P=.79 respectively). High positive end-expiratory pressure levels increased brain tissue oxygen pressure and oxygen saturation, without increase in intracranial pressure or decrease in cerebral perfusion pressure. High positive end-expiratory pressure levels can be used in severe traumatic brain injury patients with acute respiratory distress syndrome as a safe alternative to improve brain oxygenation. Copyright © 2015 Elsevier Inc. All rights reserved.

Combination of blood flow asymmetry in the cerebral and cerebellar hemispheres on brain perfusion SPECT predicts 5-year outcome in patients with symptomatic unilateral major cerebral artery occlusion.

PubMed

Nomura, Jun-ichi; Ogasawara, Kuniaki; Saito, Hideo; Terasaki, Kazunori; Matsumoto, Yoshiyasu; Takahashi, Yoshihiro; Ogasawara, Yasushi; Saura, Hiroaki; Yoshida, Koji; Sato, Yuiko; Kubo, Yoshitaka; Ogawa, Akira

2014-03-01

Misery perfusion increases the risk of stroke recurrence in patients with symptomatic major cerebral artery occlusion. The ratio of brain perfusion contralateral-to-affected asymmetry in the cerebellar hemisphere to brain perfusion affected-to-contralateral asymmetry in the cerebral hemisphere (CblPR/CbrPR) indicates affected-to-contralateral asymmetry of oxygen extraction fraction (OEF) in the cerebral hemisphere. The purpose of the present study was to determine whether the CblPR/CbrPR on brain perfusion single-photon emission computed tomography (SPECT) predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the middle cerebral artery (MCA) or internal carotid artery (ICA). Brain perfusion was assessed using N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) SPECT in 70 patients. A region of interest (ROI) was manually placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres, and the CblPR/CbrPR was calculated. All patients were prospectively followed for 5 years. The primary end points were stroke recurrence or death. A total of 17 patients exhibited the primary end points, 11 of whom experienced subsequent ipsilateral strokes. Multivariate analysis revealed that only high CblPR/CbrPR was significantly associated with the development of the primary end point or subsequent ipsilateral strokes (95% confidential limits [CIs], 1.130-3.145; P  =  0.0114 or 95% CIs, 2.558-5.140; P  =  0.0045, respectively). The CblPR/CbrPR provided 65% (11/17) or 91% (10/11) sensitivity and 88% (47/53) or 88% (52/59) specificity in predicting the primary end point or subsequent ipsilateral strokes, respectively. The CblPR/CbrPR on brain perfusion SPECT predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the MCA or ICA.

A methodology for generating normal and pathological brain perfusion SPECT images for evaluation of MRI/SPECT fusion methods: application in epilepsy

NASA Astrophysics Data System (ADS)

Grova, C.; Jannin, P.; Biraben, A.; Buvat, I.; Benali, H.; Bernard, A. M.; Scarabin, J. M.; Gibaud, B.

2003-12-01

Quantitative evaluation of brain MRI/SPECT fusion methods for normal and in particular pathological datasets is difficult, due to the frequent lack of relevant ground truth. We propose a methodology to generate MRI and SPECT datasets dedicated to the evaluation of MRI/SPECT fusion methods and illustrate the method when dealing with ictal SPECT. The method consists in generating normal or pathological SPECT data perfectly aligned with a high-resolution 3D T1-weighted MRI using realistic Monte Carlo simulations that closely reproduce the response of a SPECT imaging system. Anatomical input data for the SPECT simulations are obtained from this 3D T1-weighted MRI, while functional input data result from an inter-individual analysis of anatomically standardized SPECT data. The method makes it possible to control the 'brain perfusion' function by proposing a theoretical model of brain perfusion from measurements performed on real SPECT images. Our method provides an absolute gold standard for assessing MRI/SPECT registration method accuracy since, by construction, the SPECT data are perfectly registered with the MRI data. The proposed methodology has been applied to create a theoretical model of normal brain perfusion and ictal brain perfusion characteristic of mesial temporal lobe epilepsy. To approach realistic and unbiased perfusion models, real SPECT data were corrected for uniform attenuation, scatter and partial volume effect. An anatomic standardization was used to account for anatomic variability between subjects. Realistic simulations of normal and ictal SPECT deduced from these perfusion models are presented. The comparison of real and simulated SPECT images showed relative differences in regional activity concentration of less than 20% in most anatomical structures, for both normal and ictal data, suggesting realistic models of perfusion distributions for evaluation purposes. Inter-hemispheric asymmetry coefficients measured on simulated data were found within the range of asymmetry coefficients measured on corresponding real data. The features of the proposed approach are compared with those of other methods previously described to obtain datasets appropriate for the assessment of fusion methods.

[Disturbances of cerebral perfusion in patients with bacterial meningoencephalitis].

PubMed

Garlicki, Aleksander; Podsiadło-Kleinrok, Beata; Bociaga-Jasik, Monika; Kleinrok, Krzysztof; Tomik, Barbara

2003-01-01

The investigations were done in acute and reconvalescent phase in 34 patients with bacterial meningoencephalitis. Neurologic condition, degree of the brain injury on the basis of Glasgow Coma Scale (GCS), protein level and pleocytosis in cerebrospinal fluid (CSF), and regional cerebral blood flow on dynamic computed tomography (CT) were assessed. The brain blood flow was measured in the white matter of the frontal and occipital horns of lateral ventricles, symmetrically in both hemispheres. Statistically significant reduction of the brain perfusion in acute phase of illness was improved. In reconvalescent phase normalisation of the brain blood supply was observed. 56% of patients had changes of consciousness. There was no significant correlation between these symptoms and parameters describing blood supply. The rest of patients had neurologic abnormalities: seizure, pyramidal syndrome, injury of the central nerves due to the reduction of blood flow in selected regions of the brain. Patients who aggregated low GCS score had high inflow of the blood. In patients who were in better condition, inflow was smaller. High pleocytosis in CSF was associated with small blood inflow and perfusion in investigated regions of the brain. Whereas high protein concentration correlated with higher inflow and increase in regional perfusion. We consider, that the brain blood supply correlate with intensification of inflammatory response in CSF.

Neurovascular Regulation in the Ischemic Brain

PubMed Central

Jackman, Katherine

2015-01-01

Abstract Significance: The brain has high energetic requirements and is therefore highly dependent on adequate cerebral blood supply. To compensate for dangerous fluctuations in cerebral perfusion, the circulation of the brain has evolved intrinsic safeguarding measures. Recent Advances and Critical Issues: The vascular network of the brain incorporates a high degree of redundancy, allowing the redirection and redistribution of blood flow in the event of vascular occlusion. Furthermore, active responses such as cerebral autoregulation, which acts to maintain constant cerebral blood flow in response to changing blood pressure, and functional hyperemia, which couples blood supply with synaptic activity, allow the brain to maintain adequate cerebral perfusion in the face of varying supply or demand. In the presence of stroke risk factors, such as hypertension and diabetes, these protective processes are impaired and the susceptibility of the brain to ischemic injury is increased. One potential mechanism for the increased injury is that collateral flow arising from the normally perfused brain and supplying blood flow to the ischemic region is suppressed, resulting in more severe ischemia. Future Directions: Approaches to support collateral flow may ameliorate the outcome of focal cerebral ischemia by rescuing cerebral perfusion in potentially viable regions of the ischemic territory. Antioxid. Redox Signal. 22, 149–160. PMID:24328757

Brain Perfusion In Asphyxiated Newborns Treated with Therapeutic Hypothermia

PubMed Central

Wintermark, Pia; Hansen, Anne; Gregas, Matthew C.; Soul, Janet; Labrecque, Michelle; Robertson, Richard L.; Warfield, Simon K.

2012-01-01

Background and Purpose Induced hypothermia is thought to work partly by mitigating reperfusion injury in asphyxiated term newborns. The purpose of this study is to assess brain perfusion in the first week of life in these newborns. Patients and Methods In this prospective cohort study, magnetic resonance imaging (MRI) and perfusion imaging by arterial spin labeling (ASL-PI) was used to assess brain perfusion in these newborns. We measured regional cerebral blood flow values on 1–2 MRIs obtained during the first week of life and compared them to values obtained in control term newborns. The same or later MRI scans were obtained to define the extent of brain injury. Results Eighteen asphyxiated and four control term newborns were enrolled; eleven asphyxiated newborns were treated with hypothermia. Those developing brain injury despite being treated with induced hypothermia usually displayed hypoperfusion on day of life (DOL) 1, and then hyperperfusion on DOL 2–3 in brain areas subsequently exhibiting injury. Asphyxiated newborns not treated with hypothermia who developed brain injury also displayed hyperperfusion on DOL 1–6 in brain areas displaying injury. Conclusions Our data show that ASL-PI may be useful for identifying asphyxiated newborns at risk of developing brain injury, whether or not hypothermia is administered. Since hypothermia for 72 hours may not prevent brain injury when hyperperfusion is found early in the course of neonatal hypoxic-ischemic encephalopathy, such newborns may be candidates for adjustments in their hypothermia therapy or for adjunctive neuroprotective therapies. PMID:21979494

Scaling of cerebral blood perfusion in primates and marsupials.

PubMed

Seymour, Roger S; Angove, Sophie E; Snelling, Edward P; Cassey, Phillip

2015-08-01

The evolution of primates involved increasing body size, brain size and presumably cognitive ability. Cognition is related to neural activity, metabolic rate and rate of blood flow to the cerebral cortex. These parameters are difficult to quantify in living animals. This study shows that it is possible to determine the rate of cortical brain perfusion from the size of the internal carotid artery foramina in skulls of certain mammals, including haplorrhine primates and diprotodont marsupials. We quantify combined blood flow rate in both internal carotid arteries as a proxy of brain metabolism in 34 species of haplorrhine primates (0.116-145 kg body mass) and compare it to the same analysis for 19 species of diprotodont marsupials (0.014-46 kg). Brain volume is related to body mass by essentially the same exponent of 0.70 in both groups. Flow rate increases with haplorrhine brain volume to the 0.95 power, which is significantly higher than the exponent (0.75) expected for most organs according to 'Kleiber's Law'. By comparison, the exponent is 0.73 in marsupials. Thus, the brain perfusion rate increases with body size and brain size much faster in primates than in marsupials. The trajectory of cerebral perfusion in primates is set by the phylogenetically older groups (New and Old World monkeys, lesser apes) and the phylogenetically younger groups (great apes, including humans) fall near the line, with the highest perfusion. This may be associated with disproportionate increases in cortical surface area and mental capacity in the highly social, larger primates. © 2015. Published by The Company of Biologists Ltd.

Brain perfusion correlates of cognitive and nigrostriatal functions in de novo Parkinson's disease.

PubMed

Nobili, Flavio; Arnaldi, Dario; Campus, Claudio; Ferrara, Michela; De Carli, Fabrizio; Brugnolo, Andrea; Dessi, Barbara; Girtler, Nicola; Morbelli, Silvia; Abruzzese, Giovanni; Sambuceti, Gianmario; Rodriguez, Guido

2011-12-01

Subtle cognitive impairment is recognized in the first stages of Parkinson's disease (PD), including executive, memory and visuospatial dysfunction, but its pathophysiological basis is still debated. Twenty-six consecutive, drug-naïve, de novo PD patients underwent an extended neuropsychological battery, dopamine transporter (DAT) and brain perfusion single photon emission computed tomography (SPECT). We previously reported that nigrocaudate impairment correlates with executive functions, and nigroputaminal impairment with visuospatial abilities. Here perfusion SPECT was first compared between the PD group and age-matched controls (CTR). Then, perfusion SPECT was correlated with both DAT SPECT and four neuropsychological factors by means of voxel-based analysis (SPM8) with a height threshold of p < 0.005 at peak level and p < 0.05 false discovery rate-corrected at cluster level. Both perfusion and DAT SPECT images were flipped in order to have the more affected hemisphere (MAH), defined clinically, on the same side. Significant hypoperfusion was found in an occipital area of the MAH in PD patients as compared to CTR. Executive functions directly correlated with brain perfusion in bilateral posterior cingulate cortex and precuneus in the less affected hemisphere (LAH), while verbal memory directly correlated with perfusion in the precuneus, inferior parietal lobule and superior temporal gyrus in the LAH. Furthermore, positive correlation was highlighted between nigrocaudate and nigroputaminal impairment and brain perfusion in the precuneus, posterior cingulate and parahippocampal gyri of the LAH. These data support the evidence showing an early involvement of the cholinergic system in the early cognitive dysfunction and point to a more relevant role of parietal lobes and posterior cingulate in executive functions in PD.

Optimization of flow-sensitive alternating inversion recovery (FAIR) for perfusion functional MRI of rodent brain.

PubMed

Nasrallah, Fatima A; Lee, Eugene L Q; Chuang, Kai-Hsiang

2012-11-01

Arterial spin labeling (ASL) MRI provides a noninvasive method to image perfusion, and has been applied to map neural activation in the brain. Although pulsed labeling methods have been widely used in humans, continuous ASL with a dedicated neck labeling coil is still the preferred method in rodent brain functional MRI (fMRI) to maximize the sensitivity and allow multislice acquisition. However, the additional hardware is not readily available and hence its application is limited. In this study, flow-sensitive alternating inversion recovery (FAIR) pulsed ASL was optimized for fMRI of rat brain. A practical challenge of FAIR is the suboptimal global inversion by the transmit coil of limited dimensions, which results in low effective labeling. By using a large volume transmit coil and proper positioning to optimize the body coverage, the perfusion signal was increased by 38.3% compared with positioning the brain at the isocenter. An additional 53.3% gain in signal was achieved using optimized repetition and inversion times compared with a long TR. Under electrical stimulation to the forepaws, a perfusion activation signal change of 63.7 ± 6.3% can be reliably detected in the primary somatosensory cortices using single slice or multislice echo planar imaging at 9.4 T. This demonstrates the potential of using pulsed ASL for multislice perfusion fMRI in functional and pharmacological applications in rat brain. Copyright © 2012 John Wiley & Sons, Ltd.

Arterial Spin Labeling: a one-stop-shop for measurement of brain perfusion in the clinical settings.

PubMed

Golay, Xavier; Petersen, Esben T; Zimine, Ivan; Lim, Tchoyoson C C

2007-01-01

Arterial Spin Labeling (ASL) has opened a unique window into the human brain function and perfusion physiology. Altogether fast and of intrinsic high spatial resolution, ASL is a technique very appealing not only for the diagnosis of vascular diseases, but also in basic neuroscience for the follow-up of small perfusion changes occurring during brain activation. However, due to limited signal-to-noise ratio and complex flow kinetics, ASL is one of the more challenging disciplines within magnetic resonance imaging. In this paper, the theoretical background and main implementations of ASL are revisited. In particular, the different uses of ASL, the pitfalls and possibilities are described and illustrated using clinical cases.

Comparing CT perfusion with oxygen partial pressure in a rabbit VX2 soft-tissue tumor model.

PubMed

Sun, Chang-Jin; Li, Chao; Lv, Hai-Bo; Zhao, Cong; Yu, Jin-Ming; Wang, Guang-Hui; Luo, Yun-Xiu; Li, Yan; Xiao, Mingyong; Yin, Jun; Lang, Jin-Yi

2014-01-01

The aim of this study was to evaluate the oxygen partial pressure of the rabbit model of the VX2 tumor using a 64-slice perfusion CT and to compare the results with that obtained using the oxygen microelectrode method. Perfusion CT was performed for 45 successfully constructed rabbit models of a VX2 brain tumor. The perfusion values of the brain tumor region of interest, the blood volume (BV), the time to peak (TTP) and the peak enhancement intensity (PEI) were measured. The results were compared with the partial pressure of oxygen (PO2) of that region of interest obtained using the oxygen microelectrode method. The perfusion values of the brain tumor region of interest in 45 successfully constructed rabbit models of a VX2 brain tumor ranged from 1.3-127.0 (average, 21.1 ± 26.7 ml/min/ml); BV ranged from 1.2-53.5 ml/100g (average, 22.2 ± 13.7 ml/100g); PEI ranged from 8.7-124.6 HU (average, 43.5 ± 28.7 HU); and TTP ranged from 8.2-62.3 s (average, 38.8 ± 14.8 s). The PO2 in the corresponding region ranged from 0.14-47 mmHg (average, 16 ± 14.8 mmHg). The perfusion CT positively correlated with the tumor PO2, which can be used for evaluating the tumor hypoxia in clinical practice.

[Clinical application of retrograde cerebral perfusion for brain protection during the surgery of ascending aortic aneurysm: 50 cases report].

PubMed

Dong, Pei-qing; Guan, Yu-long; He, Mei-ling; Yang, Jing; Wan, Cai-hong; Du, Shun-ping

2003-02-01

To assess retrospectively the effects of different protective methods on brain in ascending aortic aneurysm surgery. In 65 patients, aneurysm was dissected to the aortic arch or right arch. To protect brain, deep hypothermic circulatory arrest (DHCA) combined with retrograde cerebral perfusion (RCP) through the superior vena cava (n = 50) and simple DHCA (n = 15) were used during the procedure. Blood samples for lactic acid level from the jugular vein were compared in both groups at different phase, and perfusion blood distribution and oxygen content difference between the perfused and returned blood were measured in some RCP patients. The DHCA time was 35.9 +/- 18.8 min (10.0 - 63.0 min) and DHCA + RCP time was 45.5 +/- 17.2 min (16.0 - 81.0 min). The resuscitation time was 7.1 +/- 1.6 h (4.4 - 9.4 h) in DHCA patients and 5.4 +/- 2.2 h (2.0 - 9.0 h) in RCP patients. Operation death was 3/15 in the DHCA group and 1/50 in the RCP patients. Central nervous complication existed in 3/12 of DHCA patients and 1/49 of RCP patients (P < 0.01). The overall survival rate was 96% (RCP) vs 67% (DHCA), central nervous system dysfunction was 20% in DHCA vs 2% in RCP (P < 0.01). The blood lactic acid level increased significantly after reperfusion in DHCA than in RCP. The blood distribution measurement approximated to 20% of the perfused blood returned from arch vessels. Oxygen content between perfused and returned blood showed that oxygen uptake was adequate in the RCP group. The application of RCP could prolong the safety duration of circulation arrest. Cerebral perfusion may reep the brain cool and flush out particulate and air embolism. Open anastomosis of the aortic arch to the prosthesis can be safely performed. RCP is acceptable for brain protection in clinical practice.

Near-infrared spectroscopy versus magnetic resonance imaging to study brain perfusion in newborns with hypoxic-ischemic encephalopathy treated with hypothermia.

PubMed

Wintermark, P; Hansen, A; Warfield, S K; Dukhovny, D; Soul, J S

2014-01-15

The measurement of brain perfusion may provide valuable information for assessment and treatment of newborns with hypoxic-ischemic encephalopathy (HIE). While arterial spin labeled perfusion (ASL) magnetic resonance imaging (MRI) provides noninvasive and direct measurements of regional cerebral blood flow (CBF) values, it is logistically challenging to obtain. Near-infrared spectroscopy (NIRS) might be an alternative, as it permits noninvasive and continuous monitoring of cerebral hemodynamics and oxygenation at the bedside. The purpose of this study is to determine the correlation between measurements of brain perfusion by NIRS and by MRI in term newborns with HIE treated with hypothermia. In this prospective cohort study, ASL-MRI and NIRS performed during hypothermia were used to assess brain perfusion in these newborns. Regional cerebral blood flow (CBF) values, measured from 1-2 MRI scans for each patient, were compared to mixed venous saturation values (SctO2) recorded by NIRS just before and after each MRI. Analysis included groupings into moderate versus severe HIE based on their initial background pattern of amplitude-integrated electroencephalogram. Twelve concomitant recordings were obtained of seven neonates. Strong correlation was found between SctO2 and CBF in asphyxiated newborns with severe HIE (r=0.88; p value=0.0085). Moreover, newborns with severe HIE had lower CBF (likely lower oxygen supply) and extracted less oxygen (likely lower oxygen demand or utilization) when comparing SctO2 and CBF to those with moderate HIE. NIRS is an effective bedside tool to monitor and understand brain perfusion changes in term asphyxiated newborns, which in conjunction with precise measurements of CBF obtained by MRI at particular times, may help tailor neuroprotective strategies in term newborns with HIE. Copyright © 2013 Elsevier Inc. All rights reserved.

Near-Infrared Spectroscopy versus Magnetic Resonance Imaging To Study Brain Perfusion in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia

PubMed Central

Wintermark, P.; Hansen, A.; Warfield, SK.; Dukhovny, D.; Soul, JS.

2014-01-01

Background The measurement of brain perfusion may provide valuable information for assessment and treatment of newborns with hypoxic-ischemic encephalopathy (HIE). While arterial spin labeled perfusion (ASL) magnetic resonance imaging (MRI) provides noninvasive and direct measurements of regional cerebral blood flow (CBF) values, it is logistically challenging to obtain. Near-infrared spectroscopy (NIRS) might be an alternative, as it permits noninvasive and continuous monitoring of cerebral hemodynamics and oxygenation at the bedside. Objective The purpose of this study is to determine the correlation between measurements of brain perfusion by NIRS and by MRI in term newborns with HIE treated with hypothermia. Design/Methods In this prospective cohort study, ASL-MRI and NIRS performed during hypothermia were used to assess brain perfusion in these newborns. Regional cerebral blood flow values (CBF), measured from 1–2 MRI scans for each patient, were compared to mixed venous saturation values (SctO2) recorded by NIRS just before and after each MRI. Analysis included groupings into moderate versus severe HIE based on their initial background pattern of amplitude-integrated electroencephalogram. Results Twelve concomitant recordings were obtained of seven neonates. Strong correlation was found between SctO2 and CBF in asphyxiated newborns with severe HIE (r = 0.88; p value = 0.0085). Moreover, newborns with severe HIE had lower CBF (likely lower oxygen supply) and extracted less oxygen (likely lower oxygen demand or utilization) when comparing SctO2 and CBF to those with moderate HIE. Conclusions NIRS is an effective bedside tool to monitor and understand brain perfusion changes in term asphyxiated newborns, which in conjunction with precise measurements of CBF obtained by MRI at particular times, may help tailor neuroprotective strategies in term newborns with HIE. PMID:23631990

Hypertonic Lactate to Improve Cerebral Perfusion and Glucose Availability After Acute Brain Injury.

PubMed

Carteron, Laurent; Solari, Daria; Patet, Camille; Quintard, Hervé; Miroz, John-Paul; Bloch, Jocelyne; Daniel, Roy T; Hirt, Lorenz; Eckert, Philippe; Magistretti, Pierre J; Oddo, Mauro

2018-06-19

Lactate promotes cerebral blood flow and is an efficient substrate for the brain, particularly at times of glucose shortage. Hypertonic lactate is neuroprotective after experimental brain injury; however, human data are limited. Prospective study (clinicaltrials.gov NCT01573507). Academic ICU. Twenty-three brain-injured subjects (13 traumatic brain injury/10 subarachnoid hemorrhage; median age, 59 yr [41-65 yr]; median Glasgow Coma Scale, 6 [3-7]). Three-hour IV infusion of hypertonic lactate (sodium lactate, 1,000 mmol/L; concentration, 30 µmol/kg/min) administered 39 hours (26-49 hr) from injury. We examined the effect of hypertonic lactate on cerebral perfusion (using transcranial Doppler) and brain energy metabolism (using cerebral microdialysis). The majority of subjects (13/23 = 57%) had reduced brain glucose availability (baseline pretreatment cerebral microdialysis glucose, < 1 mmol/L) despite normal baseline intracranial pressure (10 [7-15] mm Hg). Hypertonic lactate was associated with increased cerebral microdialysis lactate (+55% [31-80%]) that was paralleled by an increase in middle cerebral artery mean cerebral blood flow velocities (+36% [21-66%]) and a decrease in pulsatility index (-21% [13-26%]; all p < 0.001). Cerebral microdialysis glucose increased above normal range during hypertonic lactate (+42% [30-78%]; p < 0.05); reduced brain glucose availability correlated with a greater improvement of cerebral microdialysis glucose (Spearman r = -0.53; p = 0.009). No significant changes in cerebral perfusion pressure, mean arterial pressure, systemic carbon dioxide, and blood glucose were observed during hypertonic lactate (all p > 0.1). This is the first clinical demonstration that hypertonic lactate resuscitation improves both cerebral perfusion and brain glucose availability after brain injury. These cerebral vascular and metabolic effects appeared related to brain lactate supplementation rather than to systemic effects.

Brain protection in aortic arch aneurysm: antegrade or retrograde?

PubMed

Harky, Amer; Fok, Matthew; Bashir, Mohamad; Estrera, Anthony L

2018-01-03

During open aortic arch repair, there is an interruption of cerebral perfusion and to prevent neurological sequelae, the hypothermic circulatory arrest has been established to provide sufficient brain protection coupled with adjuncts including retrograde and antegrade cerebral perfusion. To date, brain protection during open aortic arch repair is a contested topic as to which provides superior brain protection with little evidence existing to suggest supremacy of one modality over the other. This article reviews current literature reflecting on key and emerging studies in brain protection and their associated outcomes in patients undergoing open aortic arch surgery.

Perfusion Neuroimaging Abnormalities Alone Distinguish National Football League Players from a Healthy Population.

PubMed

Amen, Daniel G; Willeumier, Kristen; Omalu, Bennet; Newberg, Andrew; Raghavendra, Cauligi; Raji, Cyrus A

2016-04-25

National Football League (NFL) players are exposed to multiple head collisions during their careers. Increasing awareness of the adverse long-term effects of repetitive head trauma has raised substantial concern among players, medical professionals, and the general public. To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls. A cohort of retired and current NFL players (n = 161) were recruited in a longitudinal study starting in 2009 with ongoing interval follow up. A healthy control group (n = 124) was separately recruited for comparison. Assessments included medical examinations, neuropsychological tests, and perfusion neuroimaging with single photon emission computed tomography (SPECT). Perfusion estimates of each scan were quantified using a standard atlas. We hypothesized that hypoperfusion particularly in the orbital frontal, anterior cingulate, anterior temporal, hippocampal, amygdala, insular, caudate, superior/mid occipital, and cerebellar sub-regions alone would reliably separate controls from NFL players. Cerebral perfusion differences were calculated using a one-way ANOVA and diagnostic separation was determined with discriminant and automatic linear regression predictive models. NFL players showed lower cerebral perfusion on average (p < 0.01) in 36 brain regions. The discriminant analysis subsequently distinguished NFL players from controls with 90% sensitivity, 86% specificity, and 94% accuracy (95% CI 95-99). Automatic linear modeling achieved similar results. Inclusion of age and clinical co-morbidities did not improve diagnostic classification. Specific brain regions commonly damaged in traumatic brain injury show abnormally low perfusion on SPECT in professional NFL players. These same regions alone can distinguish this group from healthy subjects with high diagnostic accuracy. This study carries implications for the neurological safety of NFL players.

Perfusion Neuroimaging Abnormalities Alone Distinguish National Football League Players from a Healthy Population

PubMed Central

Amen, Daniel G.; Willeumier, Kristen; Omalu, Bennet; Newberg, Andrew; Raghavendra, Cauligi; Raji, Cyrus A.

2016-01-01

Background: National Football League (NFL) players are exposed to multiple head collisions during their careers. Increasing awareness of the adverse long-term effects of repetitive head trauma has raised substantial concern among players, medical professionals, and the general public. Objective: To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls. Method: A cohort of retired and current NFL players (n = 161) were recruited in a longitudinal study starting in 2009 with ongoing interval follow up. A healthy control group (n = 124) was separately recruited for comparison. Assessments included medical examinations, neuropsychological tests, and perfusion neuroimaging with single photon emission computed tomography (SPECT). Perfusion estimates of each scan were quantified using a standard atlas. We hypothesized that hypoperfusion particularly in the orbital frontal, anterior cingulate, anterior temporal, hippocampal, amygdala, insular, caudate, superior/mid occipital, and cerebellar sub-regions alone would reliably separate controls from NFL players. Cerebral perfusion differences were calculated using a one-way ANOVA and diagnostic separation was determined with discriminant and automatic linear regression predictive models. Results: NFL players showed lower cerebral perfusion on average (p < 0.01) in 36 brain regions. The discriminant analysis subsequently distinguished NFL players from controls with 90% sensitivity, 86% specificity, and 94% accuracy (95% CI 95-99). Automatic linear modeling achieved similar results. Inclusion of age and clinical co-morbidities did not improve diagnostic classification. Conclusion: Specific brain regions commonly damaged in traumatic brain injury show abnormally low perfusion on SPECT in professional NFL players. These same regions alone can distinguish this group from healthy subjects with high diagnostic accuracy. This study carries implications for the neurological safety of NFL players. PMID:27128374

Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura.

PubMed

Hougaard, Anders; Amin, Faisal M; Christensen, Casper E; Younis, Samaira; Wolfram, Frauke; Cramer, Stig P; Larsson, Henrik B W; Ashina, Messoud

2017-06-01

See Moskowitz (doi:10.1093/brain/awx099) for a scientific commentary on this article.The migraine aura is characterized by transient focal cortical disturbances causing dramatic neurological symptoms that are usually followed by migraine headache. It is currently not understood how the aura symptoms are related to the headache phase of migraine. Animal studies suggest that cortical spreading depression, the likely mechanism of migraine aura, causes disruption of the blood-brain barrier and noxious stimulation of trigeminal afferents leading to activation of brainstem nuclei and triggering of migraine headache. We used the sensitive and validated technique of dynamic contrast-enhanced high-field magnetic resonance imaging to simultaneously investigate blood-brain barrier permeability and tissue perfusion in the brainstem (at the level of the lower pons), visual cortex, and brain areas of the anterior, middle and posterior circulation during spontaneous attacks of migraine with aura. Patients reported to our institution to undergo magnetic resonance imaging during the headache phase after presenting with typical visual aura. Nineteen patients were scanned during attacks and on an attack-free day. The mean time from attack onset to scanning was 7.6 h. We found increased brainstem perfusion bilaterally during migraine with aura attacks. Perfusion also increased in the visual cortex and posterior white matter following migraine aura. We found no increase in blood-brain barrier permeability in any of the investigated regions. There was no correlation between blood-brain barrier permeability, brain perfusion, and time from symptom onset to examination or pain intensity. Our findings demonstrate hyperperfusion in brainstem during the headache phase of migraine with aura, while the blood-brain barrier remains intact during attacks of migraine with aura. These data thus contradict the preclinical hypothesis of cortical spreading depression-induced blood-brain barrier disruption as a possible mechanism linking aura and headache.awx089media15422686892001. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Increased pressure during retrograde cerebral perfusion provides better preservation of the Na+, K+-ATPase activity.

PubMed

Yang, Luojia; Li, Zhijun; Yang, Yanmin; Zhu, Raymound; Summers, Randy; Deslauriers, Roxanne; Ye, Jian

2006-11-01

This study was carried out to determine if increased perfusion pressure during retrograde cerebral perfusion (RCP) provides better preservation of the brain Na+, K+-ATPase activity. Twenty pigs were subjected to anesthesia alone (control group, n=5), hypothermic circulatory arrest (HCA) (HCA group, n = 5), HCA+RCP at perfusion pressures of 24-29 mmHg (Low-pressure group, n=5), or HCA+RCP at perfusion pressures of 34-40 mmHg (High-pressure group, n = 5). The brain was harvested for the measurement of tissue Na+, K+-ATPase activity. Relative to the control pigs (67.2 +/- 2.1%), significant impairment of Na+, K+-ATPase activity was observed in all three experimental groups (29.8 +/- 7.4% in HCA group, 33.5 +/- 2.9% in the Low-pressure group, and 52.0 +/- 1.8% in the High-pressure group, p < 0.01). The best preservation of the enzyme, particularly in the cortex and cerebellum regions, was observed in the High-pressure group (p < 0.01). In conclusion, HCA causes severe impairment of Na+, K+-ATPase activity, and increasing perfusion pressures from 24-29 to 34-40 mmHg during RCP significantly improves preservation of Na+, K+-ATPase activity, and the improvement of the protection varies in different regions of the brain.

Two dose investigation of the 5-HT-agonist psilocybin on relative and global cerebral blood flow.

PubMed

Lewis, Candace R; Preller, Katrin H; Kraehenmann, Rainer; Michels, Lars; Staempfli, Philipp; Vollenweider, Franz X

2017-10-01

Psilocybin, the active compound in psychedelic mushrooms, is an agonist of various serotonin receptors. Seminal psilocybin positron emission tomography (PET) research suggested regional increases in glucose metabolism in frontal cortex (hyperfrontality). However, a recent arterial spin labeling (ASL) study suggests psilocybin may lead to hypo-perfusion in various brain regions. In this placebo-controlled, double-blind study we used pseudo-continuous ASL (pCASL) to measure perfusion changes, with and without adjustment for global brain perfusion, after two doses of oral psilocybin (low dose: 0.160 mg/kg; high dose: 0.215 mg/kg) in two groups of healthy controls (n = 29 in both groups, total N = 58) during rest. We controlled for sex and age and used family-wise error corrected p values in all neuroimaging analyses. Both dose groups reported profound subjective drug effects as measured by the Altered States of Consciousness Rating Scale (5D-ASC) with the high dose inducing significantly larger effects in four out of the 11 scales. After adjusting for global brain perfusion, psilocybin increased relative perfusion in distinct right hemispheric frontal and temporal regions and bilaterally in the anterior insula and decreased perfusion in left hemispheric parietal and temporal cortices and left subcortical regions. Whereas, psilocybin significantly reduced absolute perfusion in frontal, temporal, parietal, and occipital lobes, and bilateral amygdalae, anterior cingulate, insula, striatal regions, and hippocampi. Our analyses demonstrate consistency with both the hyperfrontal hypothesis of psilocybin and the more recent study demonstrating decreased perfusion, depending on analysis method. Importantly, our data illustrate that relative changes in perfusion should be understood and interpreted in relation to absolute signal variations. Copyright © 2017 Elsevier Inc. All rights reserved.

Maximum-likelihood estimation of channel-dependent trial-to-trial variability of auditory evoked brain responses in MEG

PubMed Central

2014-01-01

Background We propose a mathematical model for multichannel assessment of the trial-to-trial variability of auditory evoked brain responses in magnetoencephalography (MEG). Methods Following the work of de Munck et al., our approach is based on the maximum likelihood estimation and involves an approximation of the spatio-temporal covariance of the contaminating background noise by means of the Kronecker product of its spatial and temporal covariance matrices. Extending the work of de Munck et al., where the trial-to-trial variability of the responses was considered identical to all channels, we evaluate it for each individual channel. Results Simulations with two equivalent current dipoles (ECDs) with different trial-to-trial variability, one seeded in each of the auditory cortices, were used to study the applicability of the proposed methodology on the sensor level and revealed spatial selectivity of the trial-to-trial estimates. In addition, we simulated a scenario with neighboring ECDs, to show limitations of the method. We also present an illustrative example of the application of this methodology to real MEG data taken from an auditory experimental paradigm, where we found hemispheric lateralization of the habituation effect to multiple stimulus presentation. Conclusions The proposed algorithm is capable of reconstructing lateralization effects of the trial-to-trial variability of evoked responses, i.e. when an ECD of only one hemisphere habituates, whereas the activity of the other hemisphere is not subject to habituation. Hence, it may be a useful tool in paradigms that assume lateralization effects, like, e.g., those involving language processing. PMID:24939398

Enhanced task-related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation.

PubMed

Bowtell, Joanna L; Aboo-Bakkar, Zainie; Conway, Myra E; Adlam, Anna-Lynne R; Fulford, Jonathan

2017-07-01

Blueberries are rich in flavonoids, which possess antioxidant and anti-inflammatory properties. High flavonoid intakes attenuate age-related cognitive decline, but data from human intervention studies are sparse. We investigated whether 12 weeks of blueberry concentrate supplementation improved brain perfusion, task-related activation, and cognitive function in healthy older adults. Participants were randomised to consume either 30 mL blueberry concentrate providing 387 mg anthocyanidins (5 female, 7 male; age 67.5 ± 3.0 y; body mass index, 25.9 ± 3.3 kg·m -2 ) or isoenergetic placebo (8 female, 6 male; age 69.0 ± 3.3 y; body mass index, 27.1 ± 4.0 kg·m -2 ). Pre- and postsupplementation, participants undertook a battery of cognitive function tests and a numerical Stroop test within a 1.5T magnetic resonance imaging scanner while functional magnetic resonance images were continuously acquired. Quantitative resting brain perfusion was determined using an arterial spin labelling technique, and blood biomarkers of inflammation and oxidative stress were measured. Significant increases in brain activity were observed in response to blueberry supplementation relative to the placebo group within Brodmann areas 4/6/10/21/40/44/45, precuneus, anterior cingulate, and insula/thalamus (p < 0.001) as well as significant improvements in grey matter perfusion in the parietal (5.0 ± 1.8 vs -2.9 ± 2.4%, p = 0.013) and occipital (8.0 ± 2.6 vs -0.7 ± 3.2%, p = 0.031) lobes. There was also evidence suggesting improvement in working memory (2-back test) after blueberry versus placebo supplementation (p = 0.05). Supplementation with an anthocyanin-rich blueberry concentrate improved brain perfusion and activation in brain areas associated with cognitive function in healthy older adults.

Macro- and microelements in the rat liver, kidneys, and brain tissues; sex differences and effect of blood removal by perfusion in vivo.

PubMed

Orct, Tatjana; Jurasović, Jasna; Micek, Vedran; Karaica, Dean; Sabolić, Ivan

2017-03-01

Concentrations of macro- and microelements in animal organs indicate the animal health status and represent reference data for animal experiments. Their levels in blood and tissues could be different between sexes, and could be different with and without blood in tissues. To test these hypotheses, in adult female and male rats the concentrations of various elements were measured in whole blood, blood plasma, and tissues from blood-containing (nonperfused) and blood-free liver, kidneys, and brain (perfused in vivo with an elements-free buffer). In these samples, 6 macroelements (Na, Mg, P, S, K, Ca) and 14 microelements (Fe, Mn, Co, Cu, Zn, Se, I, As, Cd, Hg, Pb, Li, B, Sr) were determined by inductively coupled plasma mass spectrometry following nitric acid digestion. In blood and plasma, female- or male-dominant sex differences were observed for 6 and 5 elements, respectively. In nonperfused organs, sex differences were observed for 3 (liver, brain) or 9 (kidneys) elements, whereas in perfused organs, similar differences were detected for 9 elements in the liver, 5 in the kidneys, and none in the brain. In females, perfused organs had significantly lower concentrations of 4, 5, and 2, and higher concentrations of 10, 4, and 7 elements, respectively, in the liver, kidneys, and brain. In males, perfusion caused lower concentrations of 4, 7, and 2, and higher concentrations of 1, 1, and 7 elements, respectively, in the liver, kidneys, and brain. Therefore, the residual blood in organs can significantly influence tissue concentrations of various elements and their sex-dependency. Copyright © 2017 Elsevier GmbH. All rights reserved.

SPECT brain perfusion findings in mild or moderate traumatic brain injury.

PubMed

Abu-Judeh, H H; Parker, R; Aleksic, S; Singh, M L; Naddaf, S; Atay, S; Kumar, M; Omar, W; El-Zeftawy, H; Luo, J Q; Abdel-Dayem, H M

2000-01-01

The purpose of this manuscript is to present the findings in the largest series of SPECT brain perfusion imaging reported to date for mild or moderate traumatic brain injury. This is a retrospective evaluation of 228 SPECT brain perfusion-imaging studies of patients who suffered mild or moderate traumatic brain injury with or without loss of consciousness (LOC). All patients had no past medical history of previous brain trauma, neurological, or psychiatric diseases, HIV, alcohol or drug abuse. The patient population included 135 males and 93 females. The ages ranged from 11-88 years (mean 40.8). The most common complaints were characteristic of the postconcussion syndrome: headaches 139/228 (61%); dizziness 61/228 (27%); and memory problems 63/228 (28%). LOC status was reported to be positive in 121/228 (53%), negative in 41/228 (18%), and unknown for 63/228 (28%). Normal studies accounted for 52/228 (23%). For abnormal studies (176/228 or 77%) the findings were as follows: basal ganglia hypoperfusion 338 lesions (55.2%); frontal lobe hypoperfusion 146 (23.8%); temporal lobes hypoperfusion 80 (13%); parietal lobes hypoperfusion 20 (3.7%); insular and or occipital lobes hypoperfusion 28 (4.6%). Patients' symptoms correlated with the SPECT brain perfusion findings. The SPECT BPI studies in 122/228 (54%) were done early within 3 months of the date of the accident, and for the remainder, 106/228 (46%) over 3 months and less than 3 years from the date of the injury. In early imaging, 382 lesions were detected; in 92 patients (average 4.2 lesions per study) imaging after 3 months detected 230 lesions: in 84 patients (average 2.7 lesions per study). Basal ganglia hypoperfusion is the most common abnormality following mild or moderate traumatic brain injury (p = 0.006), and is more common in patients complaining of memory problem (p = 0.0005) and dizziness (p = 0.003). Early imaging can detect more lesions than delayed imaging (p = 0.0011). SPECT brain perfusion abnormalities can occur in the absence of LOC.

Fossil skulls reveal that blood flow rate to the brain increased faster than brain volume during human evolution

NASA Astrophysics Data System (ADS)

Seymour, Roger S.; Bosiocic, Vanya; Snelling, Edward P.

2016-08-01

The evolution of human cognition has been inferred from anthropological discoveries and estimates of brain size from fossil skulls. A more direct measure of cognition would be cerebral metabolic rate, which is proportional to cerebral blood flow rate (perfusion). The hominin cerebrum is supplied almost exclusively by the internal carotid arteries. The sizes of the foramina that transmitted these vessels in life can be measured in hominin fossil skulls and used to calculate cerebral perfusion rate. Perfusion in 11 species of hominin ancestors, from Australopithecus to archaic Homo sapiens, increases disproportionately when scaled against brain volume (the allometric exponent is 1.41). The high exponent indicates an increase in the metabolic intensity of cerebral tissue in later Homo species, rather than remaining constant (1.0) as expected by a linear increase in neuron number, or decreasing according to Kleiber's Law (0.75). During 3 Myr of hominin evolution, cerebral tissue perfusion increased 1.7-fold, which, when multiplied by a 3.5-fold increase in brain size, indicates a 6.0-fold increase in total cerebral blood flow rate. This is probably associated with increased interneuron connectivity, synaptic activity and cognitive function, which all ultimately depend on cerebral metabolic rate.

CT Perfusion in Acute Stroke: "Black Holes" on Time-to-Peak Image Maps Indicate Unsalvageable Brain.

PubMed

Meagher, Ruairi; Shankar, Jai Jai Shiva

2016-11-01

CT perfusion is becoming important in acute stroke imaging to determine optimal patient-management strategies. The purpose of this study was to examine the predictive value of time-to-peak image maps and, specifically, a phenomenon coined a "black hole" for assessing infarcted brain tissue at the time of scan. Acute stroke patients were screened for the presence of black holes and their follow-up imaging (noncontrast CT or MR) was reviewed to assess for infarcted brain tissue. Of the 23 patients with signs of acute ischemia on CT perfusion, all had black holes. The black holes corresponded with areas of infarcted brain on follow-up imaging (specificity 100%). Black holes demonstrated significantly lower cerebral blood volumes (P < .001) and cerebral blood flow (P < .001) compared to immediately adjacent tissue. Black holes on time-to-peak image maps represent areas of unsalvageable brain. Copyright © 2016 by the American Society of Neuroimaging.

Theanine, gamma-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats.

PubMed

Yamada, T; Terashima, T; Kawano, S; Furuno, R; Okubo, T; Juneja, L R; Yokogoshi, H

2009-01-01

Theanine (gamma-glutamylethylamide) is one of the major amino acid components in green tea and can pass through the blood-brain barrier. Recent studies suggest that theanine affects the mammalian central nervous system; however, the detailed mechanism remains unclear. In this study, we demonstrated the effect of theanine on neurotransmission in the brain striatum by in vivo brain microdialysis. Theanine injection into the rat brain striatum did not increase the concentration of excitatory neurotransmitters in the perfusate. On the other hand, theanine injection increased the concentration of glycine in the perfusate. Because it has been reported that theanine promotes dopamine release in the rat striatum, we investigated the glycine and dopamine concentrations in the perfusate. Co-injection of glycine receptor antagonist, strychnine, reduced theanine-induced changes in dopamine. Moreover, AMPA receptor antagonist, which regulates glycine and GABA release from glia cells, inhibited these effects of theanine and this result was in agreement with the known inhibitory effect of theanine at AMPA receptors.

Lesional perfusion abnormalities in Leigh disease demonstrated by arterial spin labeling correlate with disease activity.

PubMed

Whitehead, Matthew T; Lee, Bonmyong; Gropman, Andrea

2016-08-01

Leigh disease is a metabolic disorder of the mitochondrial respiratory chain culminating in symmetrical necrotizing lesions in the deep gray nuclei or brainstem. Apart from classic gliotic/necrotic lesions, small-vessel proliferation is also characteristic on histopathology. We have observed lesional hyperperfusion on arterial spin-labeling (ASL) sequence in children with Leigh disease. In this cross-sectional analysis, we evaluated lesional ASL perfusion characteristics in children with Leigh syndrome. We searched the imaging database from an academic children's hospital for "arterial spin labeling, perfusion, necrosis, lactate, and Leigh" to build a cohort of children for retrospective analysis. We reviewed each child's medical record to confirm a diagnosis of Leigh disease, excluding exams with artifact, technical limitations, and without ASL images. We evaluated the degree and extent of cerebral blood flow and relationship to brain lesions. Images were compared to normal exams from an aged-matche cohort. The database search yielded 45 exams; 30 were excluded. We evaluated 15 exams from 8 children with Leigh disease and 15 age-matched normal exams. In general, Leigh brain perfusion ranged from hyperintense (n=10) to hypointense (n=5). Necrotic lesions appeared hypointense/hypoperfused. Active lesions with associated restricted diffusion demonstrated hyperperfusion. ASL perfusion patterns differed significantly from those on age-matched normal studies (P=<.0001). Disease activity positively correlated with cerebral deep gray nuclei hyperperfusion (P=0.0037) and lesion grade (P=0.0256). Children with Leigh disease have abnormal perfusion of brain lesions. Hyperperfusion can be found in active brain lesions, possibly associated with small-vessel proliferation characteristic of the disease.

A comparative analysis of the dependences of the hemodynamic parameters on changes in ROI's position in perfusion CT scans

NASA Astrophysics Data System (ADS)

Choi, Yong-Seok; Cho, Jae-Hwan; Namgung, Jang-Sun; Kim, Hyo-Jin; Yoon, Dae-Young; Lee, Han-Joo

2013-05-01

This study performed a comparative analysis of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and mean time-to-peak (TTP) obtained by changing the region of interest's (ROI) anatomical positions, during CT brain perfusion. We acquired axial source images of perfusion CT from 20 patients undergoing CT perfusion exams due to brain trauma. Subsequently, the CBV, CBF, MTT, and TTP values were calculated through data-processing of the perfusion CT images. The color scales for the CBV, CBF, MTT, and TTP maps were obtained using the image data. Anterior cerebral artery (ACA) was taken as the standard ROI for the calculations of the perfusion values. Differences in the hemodynamic average values were compared in a quantitative analysis by placing ROI and the dividing axial images into proximal, middle, and distal segments anatomically. By performing the qualitative analysis using a blind test, we observed changes in the sensory characteristics by using the color scales of the CBV, CBF, and MTT maps in the proximal, middle, and distal segments. According to the qualitative analysis, no differences were found in CBV, CBF, MTT, and TTP values of the proximal, middle, and distal segments and no changes were detected in the color scales of the the CBV, CBF, MTT, and TTP maps in the proximal, middle, and distal segments. We anticipate that the results of the study will useful in assessing brain trauma patients using by perfusion imaging.

Framework for cognitive analysis of dynamic perfusion computed tomography with visualization of large volumetric data

NASA Astrophysics Data System (ADS)

Hachaj, Tomasz; Ogiela, Marek R.

2012-10-01

The proposed framework for cognitive analysis of perfusion computed tomography images is a fusion of image processing, pattern recognition, and image analysis procedures. The output data of the algorithm consists of: regions of perfusion abnormalities, anatomy atlas description of brain tissues, measures of perfusion parameters, and prognosis for infracted tissues. That information is superimposed onto volumetric computed tomography data and displayed to radiologists. Our rendering algorithm enables rendering large volumes on off-the-shelf hardware. This portability of rendering solution is very important because our framework can be run without using expensive dedicated hardware. The other important factors are theoretically unlimited size of rendered volume and possibility of trading of image quality for rendering speed. Such rendered, high quality visualizations may be further used for intelligent brain perfusion abnormality identification, and computer aided-diagnosis of selected types of pathologies.

Dynamic perfusion CT in brain tumors.

PubMed

Yeung, Timothy Pok Chi; Bauman, Glenn; Yartsev, Slav; Fainardi, Enrico; Macdonald, David; Lee, Ting-Yim

2015-12-01

Dynamic perfusion CT (PCT) is an imaging technique for assessing the vascular supply and hemodynamics of brain tumors by measuring blood flow, blood volume, and permeability-surface area product. These PCT parameters provide information complementary to histopathologic assessments and have been used for grading brain tumors, distinguishing high-grade gliomas from other brain lesions, differentiating true progression from post-treatment effects, and predicting prognosis after treatments. In this review, the basic principles of PCT are described, and applications of PCT of brain tumors are discussed. The advantages and current challenges, along with possible solutions, of PCT are presented. Copyright © 2015. Published by Elsevier Ireland Ltd.

Sub-band denoising and spline curve fitting method for hemodynamic measurement in perfusion MRI

NASA Astrophysics Data System (ADS)

Lin, Hong-Dun; Huang, Hsiao-Ling; Hsu, Yuan-Yu; Chen, Chi-Chen; Chen, Ing-Yi; Wu, Liang-Chi; Liu, Ren-Shyan; Lin, Kang-Ping

2003-05-01

In clinical research, non-invasive MR perfusion imaging is capable of investigating brain perfusion phenomenon via various hemodynamic measurements, such as cerebral blood volume (CBV), cerebral blood flow (CBF), and mean trasnit time (MTT). These hemodynamic parameters are useful in diagnosing brain disorders such as stroke, infarction and periinfarct ischemia by further semi-quantitative analysis. However, the accuracy of quantitative analysis is usually affected by poor signal-to-noise ratio image quality. In this paper, we propose a hemodynamic measurement method based upon sub-band denoising and spline curve fitting processes to improve image quality for better hemodynamic quantitative analysis results. Ten sets of perfusion MRI data and corresponding PET images were used to validate the performance. For quantitative comparison, we evaluate gray/white matter CBF ratio. As a result, the hemodynamic semi-quantitative analysis result of mean gray to white matter CBF ratio is 2.10 +/- 0.34. The evaluated ratio of brain tissues in perfusion MRI is comparable to PET technique is less than 1-% difference in average. Furthermore, the method features excellent noise reduction and boundary preserving in image processing, and short hemodynamic measurement time.

Perfusion MRI: The Five Most Frequently Asked Clinical Questions

PubMed Central

Essig, Marco; Nguyen, Thanh Binh; Shiroishi, Mark S.; Saake, Marc; Provenzale, James M.; Enterline, David S.; Anzalone, Nicoletta; Dörfler, Arnd; Rovira, Àlex; Wintermark, Max; Law, Meng

2013-01-01

OBJECTIVE This article addresses questions that radiologists frequently ask when planning, performing, processing, and interpreting MRI perfusion studies in CNS imaging. CONCLUSION Perfusion MRI is a promising tool in assessing stroke, brain tumors, and neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols. PMID:23971482

TH-CD-206-01: Expectation-Maximization Algorithm-Based Tissue Mixture Quantification for Perfusion MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, H; Xing, L; Liang, Z

Purpose: To investigate the feasibility of estimating the tissue mixture perfusions and quantifying cerebral blood flow change in arterial spin labeled (ASL) perfusion MR images. Methods: The proposed perfusion MR image analysis framework consists of 5 steps: (1) Inhomogeneity correction was performed on the T1- and T2-weighted images, which are available for each studied perfusion MR dataset. (2) We used the publicly available FSL toolbox to strip off the non-brain structures from the T1- and T2-weighted MR images. (3) We applied a multi-spectral tissue-mixture segmentation algorithm on both T1- and T2-structural MR images to roughly estimate the fraction of eachmore » tissue type - white matter, grey matter and cerebral spinal fluid inside each image voxel. (4) The distributions of the three tissue types or tissue mixture across the structural image array are down-sampled and mapped onto the ASL voxel array via a co-registration operation. (5) The presented 4-dimensional expectation-maximization (4D-EM) algorithm takes the down-sampled three tissue type distributions on perfusion image data to generate the perfusion mean, variance and percentage images for each tissue type of interest. Results: Experimental results on three volunteer datasets demonstrated that the multi-spectral tissue-mixture segmentation algorithm was effective to initialize tissue mixtures from T1- and T2-weighted MR images. Compared with the conventional ASL image processing toolbox, the proposed 4D-EM algorithm not only generated comparable perfusion mean images, but also produced perfusion variance and percentage images, which the ASL toolbox cannot obtain. It is observed that the perfusion contribution percentages may not be the same as the corresponding tissue mixture volume fractions estimated in the structural images. Conclusion: A specific application to brain ASL images showed that the presented perfusion image analysis method is promising for detecting subtle changes in tissue perfusions, which is valuable for the early diagnosis of certain brain diseases, e.g. multiple sclerosis.« less

Diffusion and perfusion weighted magnetic resonance imaging for tumor volume definition in radiotherapy of brain tumors.

PubMed

Guo, Lu; Wang, Gang; Feng, Yuanming; Yu, Tonggang; Guo, Yu; Bai, Xu; Ye, Zhaoxiang

2016-09-21

Accurate target volume delineation is crucial for the radiotherapy of tumors. Diffusion and perfusion magnetic resonance imaging (MRI) can provide functional information about brain tumors, and they are able to detect tumor volume and physiological changes beyond the lesions shown on conventional MRI. This review examines recent studies that utilized diffusion and perfusion MRI for tumor volume definition in radiotherapy of brain tumors, and it presents the opportunities and challenges in the integration of multimodal functional MRI into clinical practice. The results indicate that specialized and robust post-processing algorithms and tools are needed for the precise alignment of targets on the images, and comprehensive validations with more clinical data are important for the improvement of the correlation between histopathologic results and MRI parameter images.

Localized Drug Application and Sub-Second Voltammetric Dopamine Release Measurements in a Brain Slice Perfusion Device

PubMed Central

2015-01-01

The use of fast scan cyclic voltammetry (FSCV) to measure the release and uptake of dopamine (DA) as well as other biogenic molecules in viable brain tissue slices has gained popularity over the last 2 decades. Brain slices have the advantage of maintaining the functional three-dimensional architecture of the neuronal network while also allowing researchers to obtain multiple sets of measurements from a single animal. In this work, we describe a simple, easy-to-fabricate perfusion device designed to focally deliver pharmacological agents to brain slices. The device incorporates a microfluidic channel that runs under the perfusion bath and a microcapillary that supplies fluid from this channel up to the slice. We measured electrically evoked DA release in brain slices before and after the administration of two dopaminergic stimulants, cocaine and GBR-12909. Measurements were collected at two locations, one directly over and the other 500 μm away from the capillary opening. Using this approach, the controlled delivery of drugs to a confined region of the brain slice and the application of this chamber to FSCV measurements, were demonstrated. Moreover, the consumption of drugs was reduced to tens of microliters, which is thousands of times less than traditional perfusion methods. We expect that this simply fabricated device will be useful in providing spatially resolved delivery of drugs with minimum consumption for voltammetric and electrophysiological studies of a variety of biological tissues both in vitro and ex vivo. PMID:24734992

Accelerated White Matter Aging in Schizophrenia: Role of White Matter Blood Perfusion

PubMed Central

Chiappelli, Joshua; McMahon, Robert; Muellerklein, Florian; Wijtenburg, S. Andrea; White, Michael G.; Rowland, Laura M.; Hong, L. Elliot

2014-01-01

Elevated rate of age-related decline in white matter integrity, indexed by fractional anisotropy (FA) from diffusion tensor imaging, was reported in patients with schizophrenia. Its etiology is unknown. We hypothesized that a decline of blood perfusion to the white matter may underlie the accelerated age-related reduction in FA in schizophrenia. Resting white matter perfusion and FA were collected using pseudo-continuous arterial spin labeling and high-angular-resolution diffusion tensor imaging, respectively, in 50 schizophrenia patients and 70 controls (age=18-63 years). Main outcome measures were the diagnosis-by-age interaction on whole-brain white matter perfusion, and FA. Significant age-related decline in brain white matter perfusion and FA were present in both groups. Age-by-diagnosis interaction was significant for FA (p<0.001) but not white matter perfusion. Age-by-diagnosis interaction for FA values remained significant even after accounting for age-related decline in perfusion. Therefore, we replicated the finding of an increased rate of age-related white matter FA decline in schizophrenia, and observed a significant age-related decline in white matter blood perfusion, although the latter did not contribute to the accelerated age-related decline in FA. The results suggest that factors other than reduced perfusion account for the accelerated age-related decline in white matter integrity in schizophrenia. PMID:24680326

A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression.

PubMed

Mir, Riyaz A; Bele, Aditya; Mirza, Sameer; Srivastava, Shashank; Olou, Appolinaire A; Ammons, Shalis A; Kim, Jun Hyun; Gurumurthy, Channabasavaiah B; Qiu, Fang; Band, Hamid; Band, Vimla

2015-12-28

Ecdysoneless (ECD) is an evolutionarily conserved protein whose germ line deletion is embryonic lethal. Deletion of Ecd in cells causes cell cycle arrest, which is rescued by exogenous ECD, demonstrating a requirement of ECD for normal mammalian cell cycle progression. However, the exact mechanism by which ECD regulates cell cycle is unknown. Here, we demonstrate that ECD protein levels and subcellular localization are invariant during cell cycle progression, suggesting a potential role of posttranslational modifications or protein-protein interactions. Since phosphorylated ECD was recently shown to interact with the PIH1D1 adaptor component of the R2TP cochaperone complex, we examined the requirement of ECD phosphorylation in cell cycle progression. Notably, phosphorylation-deficient ECD mutants that failed to bind to PIH1D1 in vitro fully retained the ability to interact with the R2TP complex and yet exhibited a reduced ability to rescue Ecd-deficient cells from cell cycle arrest. Biochemical analyses demonstrated an additional phosphorylation-independent interaction of ECD with the RUVBL1 component of the R2TP complex, and this interaction is essential for ECD's cell cycle progression function. These studies demonstrate that interaction of ECD with RUVBL1, and its CK2-mediated phosphorylation, independent of its interaction with PIH1D1, are important for its cell cycle regulatory function. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression

PubMed Central

Mir, Riyaz A.; Bele, Aditya; Mirza, Sameer; Srivastava, Shashank; Olou, Appolinaire A.; Ammons, Shalis A.; Kim, Jun Hyun; Gurumurthy, Channabasavaiah B.; Qiu, Fang; Band, Hamid

2015-01-01

Ecdysoneless (ECD) is an evolutionarily conserved protein whose germ line deletion is embryonic lethal. Deletion of Ecd in cells causes cell cycle arrest, which is rescued by exogenous ECD, demonstrating a requirement of ECD for normal mammalian cell cycle progression. However, the exact mechanism by which ECD regulates cell cycle is unknown. Here, we demonstrate that ECD protein levels and subcellular localization are invariant during cell cycle progression, suggesting a potential role of posttranslational modifications or protein-protein interactions. Since phosphorylated ECD was recently shown to interact with the PIH1D1 adaptor component of the R2TP cochaperone complex, we examined the requirement of ECD phosphorylation in cell cycle progression. Notably, phosphorylation-deficient ECD mutants that failed to bind to PIH1D1 in vitro fully retained the ability to interact with the R2TP complex and yet exhibited a reduced ability to rescue Ecd-deficient cells from cell cycle arrest. Biochemical analyses demonstrated an additional phosphorylation-independent interaction of ECD with the RUVBL1 component of the R2TP complex, and this interaction is essential for ECD's cell cycle progression function. These studies demonstrate that interaction of ECD with RUVBL1, and its CK2-mediated phosphorylation, independent of its interaction with PIH1D1, are important for its cell cycle regulatory function. PMID:26711270

Ultrasonic contrast agents in transcranial perfusion sonography (TPS) for follow-up of patients with high grade gliomas.

PubMed

Ickenstein, G W; Valaikiene, J; Koch, H; Hau, P; Erban, P; Schlachetzki, F

2008-04-01

The aim of this study was to evaluate brain perfusion differences in patients with high grade gliomas after partial tumor resection and irradiation/chemotherapy between tumor and non-tumor hemisphere by transcranial perfusion sonography (TPS) employing a contrast burst imaging (CBI) technique. Six patients with glioblastoma (WHO Grade IV) in the temporoparietal region within the defined axial diencephalic scanning plane were examined by TPS during follow-up. All subjects had an adequate acoustic temporal bone window. Transtemporal insonation on brain tumor and non-tumor hemisphere was performed with a bolus-injection of sulphur hexafluoride-based contrast agent (10 mg i.v., 5mg/ml--SonoVue, Bracco, Altana, Switzerland). Recorded images were analysed off-line by Quanticon Software (3D-Echotech, Munich, Germany) and time intensity curve parameters [area under the curve (AUC, dB s), peak intensity (PI, dB), time to peak (TTP, s)] in five regions of interest (ROI) [thalamus anterior, thalamus posterior, nucleus lentiformis, white matter, whole hemisphere] were evaluated. Statistical analyses were performed. Perfusion differences between brain tumor and non-tumor hemispheres were detected with contrast burst imaging (CBI) technique with a significantly greater mean AUC (5343.69 dB s vs. 4625.04 dB s, p<0.028) and a significantly prolonged TTP (32.72 s vs. 28.91 s, p<0.046) in the tumor hemisphere. Within our study population, TTP and AUC seem to be the most robust parameters for the evaluation of cerebral perfusion differences assessed by transcranial perfusion sonography with CBI technique. We hypothesize that these results correlate with microvascular changes due to treatment regimens, such as microvessel necrosis after irradiation and chemotherapy. Above that, TPS may be of value for the long-term follow-up of brain tumor therapy concept.

Neuroimaging evidence of brain abnormalities in mastocytosis.

PubMed

Boddaert, N; Salvador, A; Chandesris, M O; Lemaître, H; Grévent, D; Gauthier, C; Naggara, O; Georgin-Lavialle, S; Moura, D S; Munsch, F; Jaafari, N; Zilbovicius, M; Lortholary, O; Gaillard, R; Hermine, O

2017-08-08

Mastocytosis is a rare disease in which chronic symptoms are related to mast cell accumulation and activation. Patients can display depression-anxiety-like symptoms and cognitive impairment. The pathophysiology of these symptoms may be associated with tissular mast cell infiltration, mast cell mediator release or both. The objective of this study is to perform morphological or functional brain analyses in mastocytosis to identify brain changes associated with this mast cell disorder. We performed a prospective and monocentric comparative study to evaluate the link between subjective psycho-cognitive complaints, psychiatric evaluation and objective medical data using magnetic resonance imaging with morphological and perfusion sequences (arterial spin-labeled perfusion) in 39 patients with mastocytosis compared with 33 healthy controls. In the test cohort of 39 mastocytosis patients with psycho-cognitive complaints, we found that 49% of them had morphological brain abnormalities, mainly abnormal punctuated white matter abnormalities (WMA). WMA were equally frequent in cutaneous mastocytosis patients and indolent forms of systemic mastocytosis patients (42% and 41% of patients with WMA, respectively). Patients with WMA showed increased perfusion in the putamen compared with patients without WMA and with healthy controls. Putamen perfusion was also negatively correlated with depression subscores. This study demonstrates, for we believe the first time, a high prevalence of morphological and functional abnormalities in the brains of mastocytosis patients with neuropsychiatric complaints. Further studies are required to determine the mechanism underpinning this association and to ascertain its specificity.

Perfusion MRI: The Five Most Frequently Asked Technical Questions

PubMed Central

Essig, Marco; Shiroishi, Mark S.; Nguyen, Thanh Binh; Saake, Marc; Provenzale, James M.; Enterline, David; Anzalone, Nicoletta; Dörfler, Arnd; Rovira, Àlex; Wintermark, Max; Law, Meng

2013-01-01

OBJECTIVE This and its companion article address the 10 most frequently asked questions that radiologists face when planning, performing, processing, and interpreting different MR perfusion studies in CNS imaging. CONCLUSION Perfusion MRI is a promising tool in assessing stroke, brain tumors, and patients with neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols. PMID:23255738

Resting functional imaging tools (MRS, SPECT, PET and PCT).

PubMed

Van Der Naalt, J

2015-01-01

Functional imaging includes imaging techniques that provide information about the metabolic and hemodynamic status of the brain. Most commonly applied functional imaging techniques in patients with traumatic brain injury (TBI) include magnetic resonance spectroscopy (MRS), single photon emission computed tomography (SPECT), positron emission tomography (PET) and perfusion CT (PCT). These imaging modalities are used to determine the extent of injury, to provide information for the prediction of outcome, and to assess evidence of cerebral ischemia. In TBI, secondary brain damage mainly comprises ischemia and is present in more than 80% of fatal cases with traumatic brain injury (Graham et al., 1989; Bouma et al., 1991; Coles et al., 2004). In particular, while SPECT measures cerebral perfusion and MRS determines metabolism, PET is able to assess both perfusion and cerebral metabolism. This chapter will describe the application of these techniques in traumatic brain injury separately for the major groups of severity comprising the mild and moderate to severe group. The application in TBI and potential difficulties of each technique is described. The use of imaging techniques in children will be separately outlined. © 2015 Elsevier B.V. All rights reserved.

Optical monitoring of cerebral microcirculation in neurointensive care.

PubMed

Rejmstad, Peter; Haj-Hosseini, Neda; Åneman, Oscar; Wårdell, Karin

2017-12-08

Continuous optical monitoring of local cerebral microcirculation could benefit neurointensive care patients treated for subarachnoid hemorrhage (SAH). The aim of the study was to evaluate laser Doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) for long-term monitoring of brain microcirculation and oxygen saturation (SO 2 ) in the neurointensive care unit (NICU). A fiber optic probe was designed for intraparenchymal use and connected to LDF and DRS for assessment of the local blood flow (perfusion and tissue reflectance (TLI)) and SO 2 in the brain. The optically monitored parameters were compared with conventional NICU monitors and Xe-CT. The LDF signals were low with median and 25 to 75% interquartiles of perfusion = 70 (59 to 83) a.u. and TLI = 2.0 (1.0 to 2.4) a.u. and showed correlation with the NICU monitors in terms of heart rate. Median and interquartiles of SO 2 were 17.4 (15.7 to 19.8) %. The lack of correlation between local perfusion and cerebral perfusion pressure indicated intact cerebral autoregulation. The systems were capable of monitoring both local perfusion and SO 2 with stable signals in the NICU over 4 days. Further clinical studies are required to evaluate the optical systems' potential for assessing the onset of secondary brain injury.

Mammalian ECD Protein Is a Novel Negative Regulator of the PERK Arm of the Unfolded Protein Response

PubMed Central

Olou, Appolinaire A.; Sarkar, Aniruddha; Bele, Aditya; Gurumurthy, C. B.; Mir, Riyaz A.; Ammons, Shalis A.; Mirza, Sameer; Saleem, Irfana; Urano, Fumihiko; Band, Hamid

2017-01-01

ABSTRACT Mammalian Ecdysoneless (ECD) is a highly conserved ortholog of the Drosophila Ecd gene product whose mutations impair the synthesis of Ecdysone and produce cell-autonomous survival defects, but the mechanisms by which ECD functions are largely unknown. Here we present evidence that ECD regulates the endoplasmic reticulum (ER) stress response. ER stress induction led to a reduced ECD protein level, but this effect was not seen in PKR-like ER kinase knockout (PERK-KO) or phosphodeficient eukaryotic translation initiation factor 2α (eIF2α) mouse embryonic fibroblasts (MEFs); moreover, ECD mRNA levels were increased, suggesting impaired ECD translation as the mechanism for reduced protein levels. ECD colocalizes and coimmunoprecipitates with PERK and GRP78. ECD depletion increased the levels of both phospho-PERK (p-PERK) and p-eIF2α, and these effects were enhanced upon ER stress induction. Reciprocally, overexpression of ECD led to marked decreases in p-PERK, p-eIF2α, and ATF4 levels but robust increases in GRP78 protein levels. However, GRP78 mRNA levels were unchanged, suggesting a posttranscriptional event. Knockdown of GRP78 reversed the attenuating effect of ECD overexpression on PERK signaling. Significantly, overexpression of ECD provided a survival advantage to cells upon ER stress induction. Taken together, our data demonstrate that ECD promotes survival upon ER stress by increasing GRP78 protein levels to enhance the adaptive folding protein in the ER to attenuate PERK signaling. PMID:28652267

Direct visualization of minimal cerebral capillary flow during retrograde cerebral perfusion: an intravital fluorescence microscopy study in pigs.

PubMed

Duebener, Lennart F; Hagino, Ikuo; Schmitt, Katharina; Sakamoto, Takahiko; Stamm, Christof; Zurakowski, David; Schäfers, Hans-Joachim; Jonas, Richard A

2003-04-01

Retrograde cerebral perfusion (RCP) is used in some centers during aortic arch surgery for brain protection during hypothermic circulatory arrest. It is still unclear however whether RCP provides adequate microcirculatory blood flow at a capillary level. We used intravital microscopy to directly visualize the cerebral capillary blood flow in a piglet model of RCP. Twelve pigs (weight 9.7 +/- 0.9 kg) were divided into two groups (n = 6 each): deep hypothermic circulatory arrest (DHCA) and RCP. After the creation of a window over the parietal cerebral cortex, pigs underwent 10 minutes of normothermic bypass and 40 minutes of cooling to 15 degrees C on cardiopulmonary bypass ([CPB] pH-stat, hemocrit 30%, pump flow 100 mL x kg(-1) x min(-1)). This was followed by 45 minutes of DHCA and rewarming on CPB to 37 degrees C. In the RCP group the brain was retrogradely perfused (pump flow 30 mL x kg(-1) x min(-1)) during DHCA through the superior vena cava after inferior vena cava occlusion. Plasma was labeled with fluorescein-isothiocyanate-dextran for assessing microvascular diameter and functional capillary density (FCD), defined as total length of erythrocyte-perfused capillaries per observation area. Cerebral tissue oxygenation was determined by nicotinamide adenine dinucleotide hydrogen (NADH) autofluorescence, which increases during tissue ischemia. During normothermic and hypothermic antegrade cerebral perfusion the FCD did not significantly change from base line (97% +/- 14% and 96% +/- 12%, respectively). During retrograde cerebral perfusion the FCD decreased highly significantly to 2% +/- 2% of base line values (p < 0.001). Thus there was no evidence of significant capillary blood flow during retrograde cerebral perfusion. The microvascular diameter of cerebral arterioles that were slowly perfused significantly decreased to 27% +/- 6% of base line levels during RCP. NADH fluorescence progressively and significantly increased during RCP, indicating poorer tissue oxygenation. At the end of retrograde cerebral perfusion there was macroscopic evidence of significant brain edema. RCP does not provide adequate cerebral capillary blood flow and does not prevent cerebral ischemia. Prolonged RCP induces brain edema. However, there might be a role for a short period of RCP to remove air and debris from the cerebral circulation after DHCA because retrograde flow could be detected in cerebral arterioles.

Validity of endothelial cell analysis methods and recommendations for calibration in Topcon SP-2000P specular microscopy.

PubMed

van Schaick, Willem; van Dooren, Bart T H; Mulder, Paul G H; Völker-Dieben, Hennie J M

2005-07-01

To report on the calibration of the Topcon SP-2000P specular microscope and the Endothelial Cell Analysis Module of the IMAGEnet 2000 software, and to establish the validity of the different endothelial cell density (ECD) assessment methods available in these instruments. Using an external microgrid, we calibrated the magnification of the SP-2000P and the IMAGEnet software. In both eyes of 36 volunteers, we validated 4 ECD assessment methods by comparing these methods to the gold standard manual ECD, manual counting of cells on a video print. These methods were: the estimated ECD, estimation of ECD with a reference grid on the camera screen; the SP-2000P ECD, pointing out whole contiguous cells on the camera screen; the uncorrected IMAGEnet ECD, using automatically drawn cell borders, and the corrected IMAGEnet ECD, with manual correction of incorrectly drawn cell borders in the automated analysis. Validity of each method was evaluated by calculating both the mean difference with the manual ECD and the limits of agreement as described by Bland and Altman. Preset factory values of magnification were incorrect, resulting in errors in ECD of up to 9%. All assessments except 1 of the estimated ECDs differed significantly from manual ECDs, with most differences being similar (< or =6.5%), except for uncorrected IMAGEnet ECD (30.2%). Corrected IMAGEnet ECD showed the narrowest limits of agreement (-4.9 to +19.3%). We advise checking the calibration of magnification in any specular microscope or endothelial analysis software as it may be erroneous. Corrected IMAGEnet ECD is the most valid of the investigated methods in the Topcon SP-2000P/IMAGEnet 2000 combination.

The cell cycle regulator ecdysoneless cooperates with H-Ras to promote oncogenic transformation of human mammary epithelial cells.

PubMed

Bele, Aditya; Mirza, Sameer; Zhang, Ying; Ahmad Mir, Riyaz; Lin, Simon; Kim, Jun Hyun; Gurumurthy, Channabasavaiah Basavaraju; West, William; Qiu, Fang; Band, Hamid; Band, Vimla

2015-01-01

The mammalian ortholog of Drosophila ecdysoneless (Ecd) gene product regulates Rb-E2F interaction and is required for cell cycle progression. Ecd is overexpressed in breast cancer and its overexpression predicts shorter survival in patients with ErbB2-positive tumors. Here, we demonstrate Ecd knock down (KD) in human mammary epithelial cells (hMECs) induces growth arrest, similar to the impact of Ecd Knock out (KO) in mouse embryonic fibroblasts. Furthermore, whole-genome mRNA expression analysis of control vs. Ecd KD in hMECs demonstrated that several of the top 40 genes that were down-regulated were E2F target genes. To address the role of Ecd in mammary oncogenesis, we overexpressed Ecd and/or mutant H-Ras in hTERT-immortalized hMECs. Cell cycle analyses revealed hMECs overexpressing Ecd+Ras showed incomplete arrest in G1 phase upon growth factor deprivation, and more rapid cell cycle progression in growth factor-containing medium. Analyses of cell migration, invasion, acinar structures in 3-D Matrigel and anchorage-independent growth demonstrated that Ecd+Ras-overexpressing cells exhibit substantially more dramatic transformed phenotype as compared to cells expressing vector, Ras or Ecd. Under conditions of nutrient deprivation, Ecd+Ras-overexpressing hMECs exhibited better survival, with substantial upregulation of the autophagy marker LC3 both at the mRNA and protein levels. Significantly, while hMECs expressing Ecd or mutant Ras alone did not form tumors in NOD/SCID mice, Ecd+Ras-overexpressing hMECs formed tumors, clearly demonstrating oncogenic cooperation between Ecd and mutant Ras. Collectively, we demonstrate an important co-oncogenic role of Ecd in the progression of mammary oncogenesis through promoting cell survival.

The cell cycle regulator ecdysoneless cooperates with H-Ras to promote oncogenic transformation of human mammary epithelial cells

PubMed Central

Bele, Aditya; Mirza, Sameer; Zhang, Ying; Ahmad Mir, Riyaz; Lin, Simon; Kim, Jun Hyun; Gurumurthy, Channabasavaiah Basavaraju; West, William; Qiu, Fang; Band, Hamid; Band, Vimla

2015-01-01

The mammalian ortholog of Drosophila ecdysoneless (Ecd) gene product regulates Rb-E2F interaction and is required for cell cycle progression. Ecd is overexpressed in breast cancer and its overexpression predicts shorter survival in patients with ErbB2-positive tumors. Here, we demonstrate Ecd knock down (KD) in human mammary epithelial cells (hMECs) induces growth arrest, similar to the impact of Ecd Knock out (KO) in mouse embryonic fibroblasts. Furthermore, whole-genome mRNA expression analysis of control vs. Ecd KD in hMECs demonstrated that several of the top 40 genes that were down-regulated were E2F target genes. To address the role of Ecd in mammary oncogenesis, we overexpressed Ecd and/or mutant H-Ras in hTERT-immortalized hMECs. Cell cycle analyses revealed hMECs overexpressing Ecd+Ras showed incomplete arrest in G1 phase upon growth factor deprivation, and more rapid cell cycle progression in growth factor-containing medium. Analyses of cell migration, invasion, acinar structures in 3-D Matrigel and anchorage-independent growth demonstrated that Ecd+Ras-overexpressing cells exhibit substantially more dramatic transformed phenotype as compared to cells expressing vector, Ras or Ecd. Under conditions of nutrient deprivation, Ecd+Ras-overexpressing hMECs exhibited better survival, with substantial upregulation of the autophagy marker LC3 both at the mRNA and protein levels. Significantly, while hMECs expressing Ecd or mutant Ras alone did not form tumors in NOD/SCID mice, Ecd+Ras-overexpressing hMECs formed tumors, clearly demonstrating oncogenic cooperation between Ecd and mutant Ras. Collectively, we demonstrate an important co-oncogenic role of Ecd in the progression of mammary oncogenesis through promoting cell survival. PMID:25616580

Voxel-by-voxel analysis of brain SPECT perfusion in Fibromyalgia

NASA Astrophysics Data System (ADS)

Guedj, Eric; Taïeb, David; Cammilleri, Serge; Lussato, David; de Laforte, Catherine; Niboyet, Jean; Mundler, Olivier

2007-02-01

We evaluated brain perfusion SPECT at rest, without noxious stiumuli, in a homogeneous group of hyperalgesic FM patients. We performed a voxel-based analysis in comparison to a control group, matched for age and gender. Under such conditions, we made the assumption that significant cerebral perfusion abnormalities could be demonstrated, evidencing altered cerebral processing associated with spontaneous pain in FM patients. The secondary objective was to study the reversibility and the prognostic value of such possible perfusion abnormalities under specific treatment. Eighteen hyperalgesic FM women (mean age 48 yr; range 25-63 yr; ACR criteria) and 10 healthy women matched for age were enrolled in the study. A voxel-by-voxel group analysis was performed using SPM2 ( p<0.05, corrected for multiple comparisons). All brain SPECT were performed before any change was made in therapy in the pain care unit. A second SPECT was performed a month later after specific treatment by Ketamine. Compared to control subjects, we observed individual brain SPECT abnormalities in FM patients, confirmed by SPM2 analysis with hyperperfusion of the somatosensory cortex and hypoperfusion of the frontal, cingulate, medial temporal and cerebellar cortices. We also found that a medial frontal and anterior cingulate hypoperfusions were highly predictive (PPV=83%; NPV=91%) of non-response on Ketamine, and that only responders showed significant modification of brain perfusion, after treatment. In the present study performed without noxious stimuli in hyperalgesic FM patients, we found significant hyperperfusion in regions of the brain known to be involved in sensory dimension of pain processing and significant hypoperfusion in areas assumed to be associated with the affective dimension. As current pharmacological and non-pharmacological therapies act differently on both components of pain, we hypothesize that SPECT could be a valuable and readily available tool to guide individual therapeutic strategy and provide objective follow-up of pain-processing recovery under treatment.

Evaluation of brain perfusion in specific Brodmann areas in Frontotemporal dementia and Alzheimer disease using automated 3-D voxel based analysis

NASA Astrophysics Data System (ADS)

Valotassiou, V.; Papatriantafyllou, J.; Sifakis, N.; Karageorgiou, C.; Tsougos, I.; Tzavara, C.; Zerva, C.; Georgoulias, P.

2009-05-01

Introduction. Brain perfusion studies with single-photon emission computed tomography (SPECT) have been applied in demented patients to provide better discrimination between frontotemporal dementia (FTD) and Alzheimer's disease (AD). Aim. To assess the perfusion of specific Brodmann (Br) areas of the brain cortex in FTD and AD patients, using NeuroGam processing program to provide 3D voxel-by-voxel cerebral SPECT analysis. Material and methods. We studied 34 consecutive patients. We used the established criteria for the diagnosis of dementia and the specific established criteria for the diagnosis of FTD and AD. All the patients had a neuropsychological evaluation with a battery of tests including the mini-mental state examination (MMSE).Twenty-six patients (16 males, 10 females, mean age 68.76±6.51 years, education 11.81±4.25 years, MMSE 16.69±9.89) received the diagnosis of FTD and 8 patients (all females, mean age 71.25±10.48 years, education 10±4.6 years, MMSE 12.5±3.89) the diagnosis of AD. All the patients underwent a brain SPECT. We applied the NeuroGam Software for the evaluation of brain perfusion in specific Br areas in the left (L) and right (R) hemispheres. Results. Statistically significant hypoperfusion in FTD compared to AD patients, was found in the following Br areas: 11L (p<0.0001), 11R, 20L, 20R, 32L, 38L, 38R, 44L (p<0.001), 32R, 36L, 36R, 45L, 45R, 47R (p<0.01), 9L, 21L, 39R, 44R, 46R, 47L (p<0.05). On the contrary, AD patients presented significant (p<0.05) hypoperfusion in 7R and 39R Br areas. Conclusion. NeuroGam processing program of brain perfusion SPECT could result in enhanced accuracy for the differential diagnosis between AD and FTD patients.

Assessment of cerebral perfusion in post-traumatic brain injury patients with the use of ICG-bolus tracking method.

PubMed

Weigl, W; Milej, D; Gerega, A; Toczylowska, B; Kacprzak, M; Sawosz, P; Botwicz, M; Maniewski, R; Mayzner-Zawadzka, E; Liebert, A

2014-01-15

The aim of this study was to verify the usefulness of the time-resolved optical method utilizing diffusely reflected photons and fluorescence signals combined with intravenous injection of indocyanine green (ICG) in the assessment of brain perfusion in post-traumatic brain injury patients. The distributions of times of flight (DTOFs) of diffusely reflected photons were acquired together with the distributions of times of arrival (DTAs) of fluorescence photons. The data analysis methodology was based on the observation of delays between the signals of statistical moments (number of photons, mean time of flight and variance) of DTOFs and DTAs related to the inflow of ICG to the extra- and intracerebral tissue compartments. Eleven patients with brain hematoma, 15 patients with brain edema and a group of 9 healthy subjects were included in this study. Statistically significant differences between parameters obtained in healthy subjects and patients with brain hematoma and brain edema were observed. The best optical parameter to differentiate patients and control group was variance of the DTOFs or DTAs. Results of the study suggest that time-resolved optical monitoring of inflow of the ICG seems to be a promising tool for detecting cerebral perfusion insufficiencies in critically ill patients. © 2013 Elsevier Inc. All rights reserved.

Crossed cerebellar diaschisis in patients with acute middle cerebral artery infarction: Occurrence and perfusion characteristics

PubMed Central

Sommer, Wieland H; Bollwein, Christine; Thierfelder, Kolja M; Baumann, Alena; Janssen, Hendrik; Ertl-Wagner, Birgit; Reiser, Maximilian F; Plate, Annika; Straube, Andreas

2015-01-01

We aimed to investigate the overall prevalence and possible factors influencing the occurrence of crossed cerebellar diaschisis after acute middle cerebral artery infarction using whole-brain CT perfusion. A total of 156 patients with unilateral hypoperfusion of the middle cerebral artery territory formed the study cohort; 352 patients without hypoperfusion served as controls. We performed blinded reading of different perfusion maps for the presence of crossed cerebellar diaschisis and determined the relative supratentorial and cerebellar perfusion reduction. Moreover, imaging patterns (location and volume of hypoperfusion) and clinical factors (age, sex, time from symptom onset) resulting in crossed cerebellar diaschisis were analysed. Crossed cerebellar diaschisis was detected in 35.3% of the patients with middle cerebral artery infarction. Crossed cerebellar diaschisis was significantly associated with hypoperfusion involving the left hemisphere, the frontal lobe and the thalamus. The degree of the relative supratentorial perfusion reduction was significantly more pronounced in crossed cerebellar diaschisis-positive patients but did not correlate with the relative cerebellar perfusion reduction. Our data suggest that (i) crossed cerebellar diaschisis is a common feature after middle cerebral artery infarction which can robustly be detected using whole-brain CT perfusion, (ii) its occurrence is influenced by location and degree of the supratentorial perfusion reduction rather than infarct volume (iii) other clinical factors (age, sex and time from symptom onset) did not affect the occurrence of crossed cerebellar diaschisis. PMID:26661242

Mammalian ECD Protein Is a Novel Negative Regulator of the PERK Arm of the Unfolded Protein Response.

PubMed

Olou, Appolinaire A; Sarkar, Aniruddha; Bele, Aditya; Gurumurthy, C B; Mir, Riyaz A; Ammons, Shalis A; Mirza, Sameer; Saleem, Irfana; Urano, Fumihiko; Band, Hamid; Band, Vimla

2017-09-15

Mammalian Ecdysoneless (ECD) is a highly conserved ortholog of the Drosophila Ecd gene product whose mutations impair the synthesis of Ecdysone and produce cell-autonomous survival defects, but the mechanisms by which ECD functions are largely unknown. Here we present evidence that ECD regulates the endoplasmic reticulum (ER) stress response. ER stress induction led to a reduced ECD protein level, but this effect was not seen in PKR-like ER kinase knockout (PERK-KO) or phosphodeficient eukaryotic translation initiation factor 2α (eIF2α) mouse embryonic fibroblasts (MEFs); moreover, ECD mRNA levels were increased, suggesting impaired ECD translation as the mechanism for reduced protein levels. ECD colocalizes and coimmunoprecipitates with PERK and GRP78. ECD depletion increased the levels of both phospho-PERK (p-PERK) and p-eIF2α, and these effects were enhanced upon ER stress induction. Reciprocally, overexpression of ECD led to marked decreases in p-PERK, p-eIF2α, and ATF4 levels but robust increases in GRP78 protein levels. However, GRP78 mRNA levels were unchanged, suggesting a posttranscriptional event. Knockdown of GRP78 reversed the attenuating effect of ECD overexpression on PERK signaling. Significantly, overexpression of ECD provided a survival advantage to cells upon ER stress induction. Taken together, our data demonstrate that ECD promotes survival upon ER stress by increasing GRP78 protein levels to enhance the adaptive folding protein in the ER to attenuate PERK signaling. Copyright © 2017 Olou et al.

Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage.

PubMed

Malinova, Vesna; Dolatowski, Karoline; Schramm, Peter; Moerer, Onnen; Rohde, Veit; Mielke, Dorothee

2016-07-01

OBJECT This prospective study investigated the role of whole-brain CT perfusion (CTP) studies in the identification of patients at risk for delayed ischemic neurological deficits (DIND) and of tissue at risk for delayed cerebral infarction (DCI). METHODS Forty-three patients with aneurysmal subarachnoid hemorrhage (aSAH) were included in this study. A CTP study was routinely performed in the early phase (Day 3). The CTP study was repeated in cases of transcranial Doppler sonography (TCD)-measured blood flow velocity (BFV) increase of > 50 cm/sec within 24 hours and/or on Day 7 in patients who were intubated/sedated. RESULTS Early CTP studies revealed perfusion deficits in 14 patients, of whom 10 patients (72%) developed DIND, and 6 of these 10 patients (60%) had DCI. Three of the 14 patients (21%) with early perfusion deficits developed DCI without having had DIND, and the remaining patient (7%) had neither DIND nor DCI. There was a statistically significant correlation between early perfusion deficits and occurrence of DIND and DCI (p < 0.0001). A repeated CTP was performed in 8 patients with a TCD-measured BFV increase > 50 cm/sec within 24 hours, revealing a perfusion deficit in 3 of them (38%). Two of the 3 patients (67%) developed DCI without preceding DIND and 1 patient (33%) had DIND without DCI. In 4 of the 7 patients (57%) who were sedated and/or comatose, additional CTP studies on Day 7 showed perfusion deficits. All 4 patients developed DCI. CONCLUSIONS Whole-brain CTP on Day 3 after aSAH allows early and reliable identification of patients at risk for DIND and tissue at risk for DCI. Additional CTP investigations, guided by TCD-measured BFV increase or persisting coma, do not contribute to information gain.

Automated three-dimensional quantification of myocardial perfusion and brain SPECT.

PubMed

Slomka, P J; Radau, P; Hurwitz, G A; Dey, D

2001-01-01

To allow automated and objective reading of nuclear medicine tomography, we have developed a set of tools for clinical analysis of myocardial perfusion tomography (PERFIT) and Brain SPECT/PET (BRASS). We exploit algorithms for image registration and use three-dimensional (3D) "normal models" for individual patient comparisons to composite datasets on a "voxel-by-voxel basis" in order to automatically determine the statistically significant abnormalities. A multistage, 3D iterative inter-subject registration of patient images to normal templates is applied, including automated masking of the external activity before final fit. In separate projects, the software has been applied to the analysis of myocardial perfusion SPECT, as well as brain SPECT and PET data. Automatic reading was consistent with visual analysis; it can be applied to the whole spectrum of clinical images, and aid physicians in the daily interpretation of tomographic nuclear medicine images.

SPET brain perfusion imaging in mild traumatic brain injury without loss of consciousness and normal computed tomography.

PubMed

Abu-Judeh, H H; Parker, R; Singh, M; el-Zeftawy, H; Atay, S; Kumar, M; Naddaf, S; Aleksic, S; Abdel-Dayem, H M

1999-06-01

We present SPET brain perfusion findings in 32 patients who suffered mild traumatic brain injury without loss of consciousness and normal computed tomography. None of the patients had previous traumatic brain injury, CVA, HIV, psychiatric disorders or a history of alcohol or drug abuse. Their ages ranged from 11 to 61 years (mean = 42). The study was performed in 20 patients (62%) within 3 months of the date of injury and in 12 (38%) patients more than 3 months post-injury. Nineteen patients (60%) were involved in a motor vehicle accident, 10 patients (31%) sustained a fall and three patients (9%) received a blow to the head. The most common complaints were headaches in 26 patients (81%), memory deficits in 15 (47%), dizziness in 13 (41%) and sleep disorders in eight (25%). The studies were acquired approximately 2 h after an intravenous injection of 740 MBq (20.0 mCi) of 99Tcm-HMPAO. All images were acquired on a triple-headed gamma camera. The data were displayed on a 10-grade colour scale, with 2-pixel thickness (7.4 mm), and were reviewed blind to the patient's history of symptoms. The cerebellum was used as the reference site (100% maximum value). Any decrease in cerebral perfusion in the cortex or basal ganglia less than 70%, or less than 50% in the medial temporal lobe, compared to the cerebellar reference was considered abnormal. The results show that 13 (41%) had normal studies and 19 (59%) were abnormal (13 studies performed within 3 months of the date of injury and six studies performed more than 3 months post-injury). Analysis of the abnormal studies revealed that 17 showed 48 focal lesions and two showed diffuse supratentorial hypoperfusion (one from each of the early and delayed imaging groups). The 12 abnormal studies performed early had 37 focal lesions and averaged 3.1 lesions per patient, whereas there was a reduction to--an average of 2.2 lesions per patient in the five studies (total 11 lesions) performed more than 3 months post-injury. In the 17 abnormal studies with focal lesions, the following regions were involved in descending frequency: frontal lobes 58%, basal ganglia and thalami 47%, temporal lobes 26% and parietal lobes 16%. We conclude that: (1) SPET brain perfusion imaging is valuable and sensitive for the evaluation of cerebral perfusion changes following mild traumatic brain injury; (2) these changes can occur without loss of consciousness; (3) SPET brain perfusion imaging is more sensitive than computed tomography in detecting brain lesions; and (4) the changes may explain a neurological component of the patient's symptoms in the absence of morphological abnormalities using other imaging modalities.

Radio-frequency lesioning in brain tissue with coagulation-dependent thermal conductivity: modelling, simulation and analysis of parameter influence and interaction.

PubMed

Johansson, Johannes D; Eriksson, Ola; Wren, Joakim; Loyd, Dan; Wårdell, Karin

2006-09-01

Radio-frequency brain lesioning is a method for reducing e.g. symptoms of movement disorders. A small electrode is used to thermally coagulate malfunctioning tissue. Influence on lesion size from thermal and electric conductivity of the tissue, microvascular perfusion and preset electrode temperature was investigated using a finite-element model. Perfusion was modelled as an increased thermal conductivity in non-coagulated tissue. The parameters were analysed using a 2(4)-factorial design (n=16) and quadratic regression analysis (n=47). Increased thermal conductivity of the tissue increased lesion volume, while increased perfusion decreased it since coagulation creates a thermally insulating layer due to the cessation of blood perfusion. These effects were strengthened with increased preset temperature. The electric conductivity had negligible effect. Simulations were found realistic compared to in vivo experimental lesions.

Bacterial expression and purification of a heterodimeric adrenomedullin receptor extracellular domain complex using DsbC-assisted disulfide shuffling.

PubMed

Hill, Heather E; Pioszak, Augen A

2013-03-01

Adrenomedullin (AM) is a peptide hormone that is a potent vasodilator and is essential for vascular development. The AM receptor is a heterodimeric cell surface receptor composed of the calcitonin receptor-like receptor (CLR), a class B G protein-coupled receptor, in association with either of two receptor activity modifying protein (RAMP) coreceptors, RAMP2 or -3. The extracellular domains (ECDs) of CLR and the RAMPs form the primary AM binding site. Here, we present novel methodology for expression and purification of a heterodimeric AM receptor ECD complex as an MBP-CLR ECD fusion protein in association with the RAMP2 ECD. Co-expression of the RAMP2 ECD with the disulfide bond isomerase DsbC in the oxidizing cytoplasm of E. coli trxB gor enabled proper disulfide formation in vivo. The isolated RAMP2 ECD was purified to homogeneity. Co-expression of a soluble MBP-CLR ECD fusion protein with DsbC in E. coli trxB gor yielded a heterogeneous mixture of species with misfolded ECD. Incubation of affinity-purified MBP-CLR ECD in vitro with purified RAMP2 ECD, DsbC, and glutathione redox buffer promoted proper folding of the CLR ECD and formation of a stable MBP-CLR ECD:RAMP2 ECD complex that was purified by size-exclusion chromatography and which exhibited specific AM binding. Approximately 40mg of highly purified complex was obtained starting with 6L bacterial cultures for each protein. The methodology reported here will facilitate structure/function studies of the AM receptor. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of video game playing on cerebral blood flow in young adults: a SPECT study.

PubMed

Chou, Yuan-Hwa; Yang, Bang-Hung; Hsu, Ju-Wei; Wang, Shyh-Jen; Lin, Chun-Lung; Huang, Kai-Lin; Chien Chang, Alice; Lee, Shin-Min

2013-04-30

To study the impact of video game playing on the human brain, the effects of two video games playing on cerebral blood flow (CBF) in young adults were determined. Thirty healthy subjects comprising 18 males and 12 females who were familiar with video game playing were recruited. Each subject underwent three sessions of single photon emission computed tomography (SPECT) with a bolus injection of 20 mCi (99m)Tc ECD IV to measure their CBF. The first measurement was performed as baseline, the second and third measurements were performed after playing two different video games for 30 min, respectively. Statistic parametric mapping (SPM2) with Matlab 6.5 implemented on a personal computer was used for image analysis. CBF was significantly decreased in the prefrontal cortex and significantly increased in the temporal and occipital cortices after both video games playing. Furthermore, decreased CBF in the anterior cingulate cortex (ACC) which was significantly correlated with the number of killed characters was found after the violent game playing. The major finding of hypo-perfusion in prefrontal regions after video game playing is consistent with a previous study showing reduced or abnormal prefrontal cortex functions after video game playing. The second finding of decreased CBF in the ACC after playing the violent video game provides support for a previous hypothesis that the ACC might play a role in regulating violent behavior. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Abnormal regional cerebral blood flow in childhood autism.

PubMed

Ohnishi, T; Matsuda, H; Hashimoto, T; Kunihiro, T; Nishikawa, M; Uema, T; Sasaki, M

2000-09-01

Neuroimaging studies of autism have shown abnormalities in the limbic system and cerebellar circuits and additional sites. These findings are not, however, specific or consistent enough to build up a coherent theory of the origin and nature of the brain abnormality in autistic patients. Twenty-three children with infantile autism and 26 non-autistic controls matched for IQ and age were examined using brain-perfusion single photon emission computed tomography with technetium-99m ethyl cysteinate dimer. In autistic subjects, we assessed the relationship between regional cerebral blood flow (rCBF) and symptom profiles. Images were anatomically normalized, and voxel-by-voxel analyses were performed. Decreases in rCBF in autistic patients compared with the control group were identified in the bilateral insula, superior temporal gyri and left prefrontal cortices. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in the limbic system and the medial prefrontal cortex. The results confirmed the associations of (i) impairments in communication and social interaction that are thought to be related to deficits in the theory of mind (ToM) with altered perfusion in the medial prefrontal cortex and anterior cingulate gyrus, and (ii) the obsessive desire for sameness with altered perfusion in the right medial temporal lobe. The perfusion abnormalities seem to be related to the cognitive dysfunction observed in autism, such as deficits in ToM, abnormal responses to sensory stimuli, and the obsessive desire for sameness. The perfusion patterns suggest possible locations of abnormalities of brain function underlying abnormal behaviour patterns in autistic individuals.

Brain Perfusion Is Increased at Term in the White Matter of Very Preterm Newborns and Newborns with Congenital Heart Disease: Does this Reflect Activated Angiogenesis?

PubMed

Wintermark, Pia; Lechpammer, Mirna; Kosaras, Bela; Jensen, Frances E; Warfield, Simon K

2015-10-01

This study aims to evaluate brain perfusion at term in very preterm newborns and newborns with congenital heart disease before their corrective surgery, and to search for histopathological indicators of whether the brain perfusion abnormalities of these newborns may be related to an activated angiogenesis. Using magnetic resonance imaging and arterial spin labeling, regional cerebral blood flow was measured at a term-equivalent age for three very preterm newborns (born at < 32 weeks), one newborn with congenital heart disease before his corrective surgery and three healthy newborns. In addition, a histopathological analysis was performed on a newborn with congenital heart disease. The very preterm newborns and the newborn with congenital heart disease included in this study all displayed an increased signal in their white matter on T2-weighted imaging. The cerebral blood flow of these newborns was increased in their white matter, compared with the healthy term newborns. The vascular endothelial growth factor was overexpressed in the injured white matter of the newborn with congenital heart disease. Brain perfusion may be increased at term in the white matter, in very preterm newborns, and newborns with congenital heart disease, and it correlates with white matter abnormalities on conventional imaging. Georg Thieme Verlag KG Stuttgart · New York.

Perfusion in Rat Brain at 7 T with Arterial Spin Labeling Using FAIR-TrueFISP and QUIPSS

PubMed Central

Esparza-Coss, Emilio; Wosik, Jarek; Narayana, Ponnada A.

2010-01-01

Measurement of perfusion in longitudinal studies allows for the assessment of tissue integrity and the detection of subtle pathologies. In this work, the feasibility of measuring brain perfusion in rats with high spatial resolution using arterial spin labeling (ASL) is reported. A flow sensitive alternating recovery (FAIR) sequence, coupled with a balanced gradient fast imaging with steady state precession (TrueFISP) readout section was used to minimize ghosting and geometric distortions, while achieving high SNR. The quantitative imaging of perfusion using a single subtraction (QUIPSS) method was implemented to address the effects of variable transit delays between the labeling of spins and their arrival at the imaging slice. Studies in six rats at 7 T showed good perfusion contrast with minimal geometric distortion. The measured blood flow values of 152.5 ± 6.3 ml/100g/min in gray matter and 72.3 ± 14.0 ml/100g/min in white matter are in good agreement with previously reported values based on autoradiography, considered to be the gold standard. PMID:20299174

Microvascular perfusion during focal vasogenic brain edema: a scanning laser fluorescence microscopy study.

PubMed

Lindsberg, P J; Sirén, A L; Hallenbeck, J M

1997-01-01

Controversy exists about the effect of tissue edema on cerebral microcirculation. High spatial resolution is required for observation of extravasation and microcirculation during focal vasogenic edema formation. To study the relationship between tissue edema and perfusion, we developed a technique for simultaneous visualization of extravasation and microvessel perfusion in rats. Focal intracortical microvascular injury was generated with a 1-sec Nd-YAG laser pulse. Evans blue albumin (EBA) was infused 30 min before decapitation to study extravasation and FITC-dextran was injected 30 sec prior to decapitation to examine microvessel perfusion. Computerized scanning laser-excited fluorescence microscopy followed by high resolution image analysis permitted quantitative assessment of both parameters on single fresh-frozen brain sections. Studied at 30 min (3.66 +/- 0.15 mm), 2 hr (4.14 +/- 0.08 mm, P < .05), and 8 hr (4.69 +/- 0.18 mm, P < .01) after injury, the diameter of the circular, sharply demarcated zone of EBA-extravasation increased progressively. At 30 min, microvessels at a zone surrounding the area of EBA-extravasation contained 69 +/- 14% (P < .05) more fluorescent FITC-filling than in the control hemisphere, but the density of perfused microvessels was unchanged. At 2 hr, secondary tissue changes had already occurred in a zone surrounding the initial laser lesion. While severe reduction in the density (-76 +/- 13%, P < .05) of perfused microvessels was observed within 400 to 240 microm inside the border of EBA extravasation, perfusion indexes were normal despite the presence of extravasated plasma constituents within 0-80 microm from the border. In a narrow zone (80 microm) outside the border of extravasation, individual microvessels contained 34 +/- 9% (P < .01) less FITC-fluorescence than those in a homologous area of the uninjured contralateral hemisphere. This report demonstrates the feasibility of simultaneous measurement and high-resolution mapping of indices of microvascular perfusion (density, filling) and extravasated plasma constituents in damaged and intact brain areas. In this model, the presence of extravasated plasma constituents the size of proteins did not immediately influence indices of cortical microcirculation. However, microvascular perfusion may be perturbed surrounding such an area of advancing vasogenic edema formation.

Crossed cerebellar diaschisis in patients with acute middle cerebral artery infarction: Occurrence and perfusion characteristics.

PubMed

Sommer, Wieland H; Bollwein, Christine; Thierfelder, Kolja M; Baumann, Alena; Janssen, Hendrik; Ertl-Wagner, Birgit; Reiser, Maximilian F; Plate, Annika; Straube, Andreas; von Baumgarten, Louisa

2016-04-01

We aimed to investigate the overall prevalence and possible factors influencing the occurrence of crossed cerebellar diaschisis after acute middle cerebral artery infarction using whole-brain CT perfusion. A total of 156 patients with unilateral hypoperfusion of the middle cerebral artery territory formed the study cohort; 352 patients without hypoperfusion served as controls. We performed blinded reading of different perfusion maps for the presence of crossed cerebellar diaschisis and determined the relative supratentorial and cerebellar perfusion reduction. Moreover, imaging patterns (location and volume of hypoperfusion) and clinical factors (age, sex, time from symptom onset) resulting in crossed cerebellar diaschisis were analysed. Crossed cerebellar diaschisis was detected in 35.3% of the patients with middle cerebral artery infarction. Crossed cerebellar diaschisis was significantly associated with hypoperfusion involving the left hemisphere, the frontal lobe and the thalamus. The degree of the relative supratentorial perfusion reduction was significantly more pronounced in crossed cerebellar diaschisis-positive patients but did not correlate with the relative cerebellar perfusion reduction. Our data suggest that (i) crossed cerebellar diaschisis is a common feature after middle cerebral artery infarction which can robustly be detected using whole-brain CT perfusion, (ii) its occurrence is influenced by location and degree of the supratentorial perfusion reduction rather than infarct volume (iii) other clinical factors (age, sex and time from symptom onset) did not affect the occurrence of crossed cerebellar diaschisis. © The Author(s) 2015.

Cerebral blood flow and autoregulation: current measurement techniques and prospects for noninvasive optical methods

PubMed Central

Fantini, Sergio; Sassaroli, Angelo; Tgavalekos, Kristen T.; Kornbluth, Joshua

2016-01-01

Abstract. Cerebral blood flow (CBF) and cerebral autoregulation (CA) are critically important to maintain proper brain perfusion and supply the brain with the necessary oxygen and energy substrates. Adequate brain perfusion is required to support normal brain function, to achieve successful aging, and to navigate acute and chronic medical conditions. We review the general principles of CBF measurements and the current techniques to measure CBF based on direct intravascular measurements, nuclear medicine, X-ray imaging, magnetic resonance imaging, ultrasound techniques, thermal diffusion, and optical methods. We also review techniques for arterial blood pressure measurements as well as theoretical and experimental methods for the assessment of CA, including recent approaches based on optical techniques. The assessment of cerebral perfusion in the clinical practice is also presented. The comprehensive description of principles, methods, and clinical requirements of CBF and CA measurements highlights the potentially important role that noninvasive optical methods can play in the assessment of neurovascular health. In fact, optical techniques have the ability to provide a noninvasive, quantitative, and continuous monitor of CBF and autoregulation. PMID:27403447

Adult dual kidney transplantations obtained from marginal donors: two case reports.

PubMed

Kim, Y H; Jung, J H; Song, K B; Chung, Y S; Park, J B; Cho, Y M; Jang, H J; Kim, S-C; Han, D J

2012-01-01

Organ shortage has led us to use grafts from expanded criteria donors (ECD). Dual kidney transplantation (DKT) using organs from an ECD, which are not acceptable for single kidney transplantation (KT), may overcome the insufficient functioning nephron mass. We performed DKTs in two recipients, the first DKT to be reported from Korea. In case 1, the donor was a 36-year-old man with hypertension. The cause of his brain death was intracranial hemorrhage. He had no known underlying renal disease; his serum creatinine level was 4.2 mg/dL. Despite the relatively young age of the donor, a biopsy revealed mild interstitial fibrosis and tubular atrophy with moderate arteriolar narrowing. The recipient's postoperative course was uneventful over the 69-month follow-up; her last serum creatinine was 1.3 mg/dL. In case 2, the 80-year-old male donor with a history of hypertension had a normal creatinine. The donor biopsy revealed mild glomerular sclerosis, tubular atrophy, and interstitial fibrosis with moderate arteriolar narrowing. The recipient had undergone a previous KT 14 years previously on the right side of the abdomen, but had resumed dialysis 2 years previously due to chronic allograft nephropathy. There was no delayed graft function. At month 4 posttransplantation, lymphoceles were treated by fenestration. At 6-month follow-up, her creatinine was 1.0 mg/dL. In our experience with these two cases, DKT with ECD kidney grafts seemed to be a successful strategy to avoid poor graft outcomes and overcome the donor organ shortage. Further studies including histological criteria for DKT, should be performed to determine the safest means to utilize ECD grafts. Copyright © 2012. Published by Elsevier Inc.

Structure-function analysis of the extracellular domains of the Duffy antigen/receptor for chemokines: characterization of antibody and chemokine binding sites.

PubMed

Tournamille, Christophe; Filipe, Anne; Wasniowska, Kazimiera; Gane, Pierre; Lisowska, Elwira; Cartron, Jean-Pierre; Colin, Yves; Le Van Kim, Caroline

2003-09-01

The Duffy antigen/receptor for chemokines (DARC), a seven-transmembrane glycoprotein carrying the Duffy (Fy) blood group, acts as a widely expressed promiscuous chemokine receptor. In a structure-function study, we analysed the binding of chemokines and anti-Fy monoclonal antibodies (mAbs) to K562 cells expressing 39 mutant forms of DARC with alanine substitutions spread out on the four extracellular domains (ECDs). Using synthetic peptides, we defined previously the Fy6 epitope (22-FEDVW-26), and we characterized the Fya epitope as the linear sequence 41-YGANLE-46. In agreement with these results, mutations of F22-E23, V25 and Y41, G42, N44, L45 on ECD1 abolished the binding of anti-Fy6 and anti-Fya mAbs to K562 cells respectively, Anti-Fy3 binding was abolished by D58-D59 (ECD1), R124 (ECD2), D263 and D283 (ECD4) substitutions. Mutations of C51 (ECD1), C129 (ECD2), C195 (ECD3) and C276 (ECD4 severely reduced anti-Fy3 and CXC-chemokine ligand 8 (CXCL-8) binding. CXCL-8 binding was also abrogated by mutations of F22-E23, P50 (ECD1) and D263, R267, D283 (ECD4). These results defined the Fya epitope and suggested that (1) two disulphide bridges are involved in the creation of an active chemokine binding pocket; (2) a limited number of amino acids in ECDs 1-4 participate in CXCL-8 binding; and (3) Fy3 is a conformation-dependent epitope involving all ECDs. We also showed that N-glycosylation of DARC occurred on N16SS and did not influence antibody and chemokine binding.

Brain Delivery of Drug and MRI Contrast Agent: Detection and Quantitative Determination of Brain Deposition of CPT-Glu Using LC-MS/MS and Gd-DTPA Using Magnetic Resonance Imaging.

PubMed

Tabanor, Kayann; Lee, Phil; Kiptoo, Paul; Choi, In-Young; Sherry, Erica B; Eagle, Cheyenne Sun; Williams, Todd D; Siahaan, Teruna J

2016-02-01

Successful treatment and diagnosis of neurological diseases depend on reliable delivery of molecules across the blood-brain barrier (BBB), which restricts penetration of pharmaceutical drugs and diagnostic agents into the brain. Thus, developing new noninvasive strategies to improve drug delivery across the BBB is critically needed. This study was aimed at evaluating the activity of HAV6 peptide (Ac-SHAVSS-NH2) in improving brain delivery of camptothecin-glutamate (CPT-Glu) conjugate and gadolinium-diethylenetriaminepentaacetate (Gd-DTPA) contrast agent in Sprague-Dawley rats. Brain delivery of both CPT-Glu and Gd-DTPA was evaluated in an in situ rat brain perfusion model in the presence and absence of HAV6 peptide (1.0 mM). Gd-DTPA (0.6 mmol/kg) was intravenously (iv) administered with and without HAV6 peptide (0.019 mmol/kg) in rats. The detection and quantification of CPT-Glu and Gd-DTPA in the brain were carried out by LC-MS/MS and quantitative magnetic resonance imaging (MRI), respectively. Rats perfused with CPT-Glu in combination with HAV6 had significantly higher deposition of drug in the brain compared to CPT-Glu alone. MRI results also showed that administration of Gd-DTPA in the presence of HAV6 peptide led to significant accumulation of Gd-DTPA in various regions of the brain in both the in situ rat brain perfusion and in vivo studies. All observations taken together indicate that HAV6 peptide can disrupt the BBB and enhance delivery of small molecules into the brain.

Brain Delivery of Drug and MRI Contrast Agent: Detection and Quantitative Determination of Brain Deposition of CPT-Glu Using LC-MS/MS and Gd-DTPA Using Magnetic Resonance Imaging

PubMed Central

Tabanor, Kayann; Lee, Phil; Kiptoo, Paul; Choi, In-Young; Sherry, Erica B.; Eagle, Cheyenne Sun; Williams, Todd D.; Siahaan, Teruna J.

2015-01-01

Successful treatment and diagnosis of neurological diseases depend on reliable delivery of molecules across the blood-brain barrier (BBB), which restricts penetration of pharmaceutical drugs and diagnostic agents into the brain. Thus, developing new non-invasive strategies to improve drug delivery across the BBB is critically needed. This study was aimed at evaluating the activity of HAV6 peptide (Ac-SHAVSS-NH2) in improving brain delivery of camptothecin-glutamate (CPT-Glu) conjugate and gadolinium-diethylenetriaminepentaacetate (Gd-DTPA) contrast agent in Sprague-Dawley rats. Brain delivery of both CPT-Glu and Gd-DTPA was evaluated in an in situ rat brain perfusion model in the presence and absence of HAV6 peptide (1.0 mM). Gd-DTPA (0.6 mmol/kg) was intravenously (i.v.) administered with and without HAV6 peptide (0.019 mmol/kg) in rats. The detection and quantification of CPT-Glu and Gd-DTPA in the brain were carried out by LC-MS/MS and quantitative magnetic resonance imaging (MRI), respectively. Rats perfused with CPT-Glu in combination with HAV6 had significantly higher deposition of drug in the brain compared to CPT-Glu alone. MRI results also showed that administration of Gd-DTPA in the presence of HAV6 peptide led to significant accumulation of Gd-DTPA in various regions of the brain in both the in situ rat brain perfusion and in vivo studies. All observations taken together indicate that HAV6 peptide can disrupt the BBB and enhance delivery of small molecules into the brain. PMID:26705088

Brain perfusion alterations in depressed patients with Parkinson's disease.

PubMed

Kim, Young-Do; Jeong, Hyeonseok S; Song, In-Uk; Chung, Yong-An; Namgung, Eun; Kim, Yong-Duk

2016-12-01

Although Parkinson's disease (PD) is frequently accompanied by depression, brain perfusion deficits in PD with depression remain unclear. This study aimed to assess alterations in regional cerebral blood flow (rCBF) in depressed PD patients using 99m Tc hexamethyl-propylene-amine-oxime single-photon emission computed tomography (SPECT). Among 78 patients with PD, 35 patients were classified into the depressed PD group, while the rest (43 patients) was assigned to the nondepressed PD group based on the scores of the Geriatric Depressive Scale (GDS). All participants underwent brain SPECT imaging. The voxel-wise whole-brain analysis and region-of-interest (ROI) analysis of the limbic areas were conducted to compare rCBF between the depressed and nondepressed PD groups. The depressed PD patients demonstrated higher GDS scores than nondepressed patients, whereas between-group differences in the PD severity and cognitive function were not significant. Perfusion in the left cuneus was increased, while that in the right superior temporal gyrus and right medial orbitofrontal cortex was reduced in the depressed PD patients as compared with nondepressed PD patients. In addition, the ROI analysis demonstrated rCBF decreases in the amygdala, anterior cingulate cortex, hippocampus, and parahippocampal gyrus in the depressed PD group. A positive correlation was found between the GDS scores and rCBF in the left cuneus cluster in the depressed PD patients. This study identified the regional pattern of brain perfusion that distinguished depressed from nondepressed PD patients. Hyperperfusion in the occipital areas and hypoperfusion in the fronto-temporo-limbic regions may be potential imaging biomarkers for depression in PD.

Brain SPECT can differentiate between essential tremor and early-stage tremor-dominant Parkinson's disease.

PubMed

Song, In-Uk; Park, Jeong-Wook; Chung, Sung-Woo; Chung, Yong-An

2014-09-01

There are no confirmatory or diagnostic tests or tools to differentiate between essential tremor (ET) and tremor in idiopathic Parkinson's disease (PD). Although a number of imaging studies have indicated that there are differences between ET and PD, the functional imaging study findings are controversial. Therefore, we analyzed regional cerebral blood flow (CBF) by perfusion brain single-photon emission computed tomography (SPECT) to identify differences between ET and tremor-dominant Parkinson's disease (TPD). We recruited 33 patients with TPD, 16 patients with ET, and 33 healthy controls. We compared the severity of tremor symptoms by comparing the Fahn-Tolosa-Marin rating scale (FTM) score and the tremor score from Unified Parkinson's Disease Rating Scale (UPDRS) between TPD and ET patients. Subjects were evaluated by neuropsychological assessments, MRI and perfusion SPECT of the brain. Total FTM score was significantly higher in ET patients than TPD patients. However, there was no significant difference in FTM Part A scores between the two patient groups, while the scores for FTM Part B and C were significantly higher in ET patients than TPD patients. Brain SPECT analysis of the TPD group demonstrated significant hypoperfusion of both the lentiform nucleus and thalamus compared to the ET group. Brain perfusion SPECT may be a useful clinical method to differentiate between TPD and ET even during early-phase PD, because the lentiform nucleus and thalamus show differences in regional perfusion between these two groups during this time period. Additionally, we found evidence of cerebellar dysfunction in both TPT and ET. Copyright © 2014 Elsevier Ltd. All rights reserved.

Direct Determination of ECD in ECD Kit: A Solid Sample Quantitation Method for Active Pharmaceutical Ingredient in Drug Product

PubMed Central

Chao, Ming-Yu; Liu, Kung-Tien; Hsia, Yi-Chih; Liao, Mei-Hsiu; Shen, Lie-Hang

2011-01-01

Technetium-99m ethyl cysteinate dimer (Tc-99m-ECD) is an essential imaging agent used in evaluating the regional cerebral blood flow in patients with cerebrovascular diseases. Determination of active pharmaceutical ingredient, that is, L-Cysteine, N, N′-1,2-ethanediylbis-, diethyl ester, dihydrochloride (ECD) in ECD Kit is a relevant requirement for the pharmaceutical quality control in processes of mass fabrication. We here presented a direct solid sample determination method of ECD in ECD Kit without sample dissolution to avoid the rapid degradation of ECD. An elemental analyzer equipped with a nondispersive infrared detector and a calibration curve of coal standard was used for the quantitation of sulfur in ECD Kit. No significant matrix effect was found. The peak area of coal standard against the amount of sulfur was linear over the range of 0.03–0.10 mg, with a correlation coefficient (r) of 0.9993. Method validation parameters were achieved to demonstrate the potential of this method. PMID:21687539

Brain calcium - Role in temperature regulation.

NASA Technical Reports Server (NTRS)

Hanegan, J. L.; Williams, B. A.

1973-01-01

Perfusion of the preoptic-anterior hypothalamus with excess calcium ion in ground squirrels produces a drop in core temperature. The magnitude of the drop is directly dependent on ambient temperature. Respiration, heart rate, and oxygen consumption are also reduced during perfusion of calcium ion. It is concluded that the depression of body temperature during calcium ion perfusion is due to generalized depression of the neurons of the preoptic-anterior hypothalamus.

National Survey of Environmental Cleaning and Disinfection in Hospitals in Thailand.

PubMed

Apisarnthanarak, Anucha; Weber, David J; Ratz, David; Saint, Sanjay; Khawcharoenporn, Thana; Greene, M Todd

2017-10-01

More than 90% of Thai hospitals surveyed reported implementing environmental cleaning and disinfection (ECD) protocols. Hospital epidemiologist presence was associated with the existence of an ECD checklist (P=.01) and of ECD auditing (P=.001), while good and excellent hospital administrative support were associated with better adherence to ECD protocols (P<.001) and ECD checklists (P=.005). Infect Control Hosp Epidemiol 2017;38:1250-1253.

Sodium-dependent transport of sugars and iodide from the cerebral venticles of the rabbit.

PubMed

Bradbury, M W; Brondsted, H E

1973-10-01

1. The objective was to discover whether the extraction of sugars and iodide from the perfused cerebral ventricles is Na(+)-dependent.2. In the ventriculo-aqueductal and ventriculo-cisternal perfusion systems in the rabbit the extraction of (14)C-labelled D-hexoses (glucose, 3-O-methyl-glucose, alpha-methyl-glucoside and galactose), (131)I(-) and (24)Na was inhibited when 82% of the Na(+) in the perfusion fluid was replaced by choline. The extraction returned to control levels when the Na(+) concentration in the perfusion fluid was returned to normal.3. Ouabain, 5 x 10(-5)M in the perfusion fluid inhibited the extraction of the above (14)C sugars and (131)I(-), but hardly affected that of [(3)H]2-deoxy-D-glucose. It enhanced the extraction of (24)Na. C.s.f. production was usually totally inhibited.4. The extraction of [(14)C]urea remained unchanged during perfusion with low Na(+) fluid or ouabain.5. Recovery from brain of [(14)C]3-O-methyl-glucose, [(3)H]2-deoxy-glucose and (131)I(-) was low while recovery of [(14)C]alpha-methyl-glucoside and (24)Na was high. On an equal weight basis recovery of [(14)C]3-O-methyl-glucose was about twelve times higher from the choroid plexus than from the brain.6. Part of the movement of (14)C sugars may be explained on basis of a Na(+)-gradient hypothesis with involvement of the Na(+) pump at the blood-c.s.f. or blood-brain barriers.7. The rate of c.s.f. production from the first three ventricles comprised about 40% of the rate from all four ventricles. The extraction of sugars, urea and cations was similar in both perfusion systems while the extraction of (131)I(-) was higher in the ventriculo-cisternal system than in the ventriculo-aqueductal system.

Cerebral Perfusion and Gray Matter Changes Associated With Chemotherapy-Induced Peripheral Neuropathy.

PubMed

Nudelman, Kelly N H; McDonald, Brenna C; Wang, Yang; Smith, Dori J; West, John D; O'Neill, Darren P; Zanville, Noah R; Champion, Victoria L; Schneider, Bryan P; Saykin, Andrew J

2016-03-01

To investigate the longitudinal relationship between chemotherapy-induced peripheral neuropathy (CIPN) symptoms (sx) and brain perfusion changes in patients with breast cancer. Interaction of CIPN-sx perfusion effects with known chemotherapy-associated gray matter density decrease was also assessed to elucidate the relationship between CIPN and previously reported cancer treatment-related brain structural changes. Patients with breast cancer treated with (n = 24) or without (n = 23) chemotherapy underwent clinical examination and brain magnetic resonance imaging at the following three time points: before treatment (baseline), 1 month after treatment completion, and 1 year after the 1-month assessment. CIPN-sx were evaluated with the self-reported Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity four-item sensory-specific scale. Perfusion and gray matter density were assessed using voxel-based pulsed arterial spin labeling and morphometric analyses and tested for association with CIPN-sx in the patients who received chemotherapy. Patients who received chemotherapy reported significantly increased CIPN-sx from baseline to 1 month, with partial recovery by 1 year (P < .001). CIPN-sx increase from baseline to 1 month was significantly greater for patients who received chemotherapy compared with those who did not (P = .001). At 1 month, neuroimaging showed that for the group that received chemotherapy, CIPN-sx were positively associated with cerebral perfusion in the right superior frontal gyrus and cingulate gyrus, regions associated with pain processing (P < .001). Longitudinal magnetic resonance imaging analysis in the group receiving chemotherapy indicated that CIPN-sx and associated perfusion changes from baseline to 1 month were also positively correlated with gray matter density change (P < .005). Peripheral neuropathy symptoms after systemic chemotherapy for breast cancer are associated with changes in cerebral perfusion and gray matter. The specific mechanisms warrant further investigation given the potential diagnostic and therapeutic implications. © 2015 by American Society of Clinical Oncology.

Cerebral Perfusion and Gray Matter Changes Associated With Chemotherapy-Induced Peripheral Neuropathy

PubMed Central

Nudelman, Kelly N.H.; McDonald, Brenna C.; Wang, Yang; Smith, Dori J.; West, John D.; O'Neill, Darren P.; Zanville, Noah R.; Champion, Victoria L.; Schneider, Bryan P.

2016-01-01

Purpose To investigate the longitudinal relationship between chemotherapy-induced peripheral neuropathy (CIPN) symptoms (sx) and brain perfusion changes in patients with breast cancer. Interaction of CIPN-sx perfusion effects with known chemotherapy-associated gray matter density decrease was also assessed to elucidate the relationship between CIPN and previously reported cancer treatment–related brain structural changes. Methods Patients with breast cancer treated with (n = 24) or without (n = 23) chemotherapy underwent clinical examination and brain magnetic resonance imaging at the following three time points: before treatment (baseline), 1 month after treatment completion, and 1 year after the 1-month assessment. CIPN-sx were evaluated with the self-reported Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity four-item sensory-specific scale. Perfusion and gray matter density were assessed using voxel-based pulsed arterial spin labeling and morphometric analyses and tested for association with CIPN-sx in the patients who received chemotherapy. Results Patients who received chemotherapy reported significantly increased CIPN-sx from baseline to 1 month, with partial recovery by 1 year (P < .001). CIPN-sx increase from baseline to 1 month was significantly greater for patients who received chemotherapy compared with those who did not (P = .001). At 1 month, neuroimaging showed that for the group that received chemotherapy, CIPN-sx were positively associated with cerebral perfusion in the right superior frontal gyrus and cingulate gyrus, regions associated with pain processing (P < .001). Longitudinal magnetic resonance imaging analysis in the group receiving chemotherapy indicated that CIPN-sx and associated perfusion changes from baseline to 1 month were also positively correlated with gray matter density change (P < .005). Conclusion Peripheral neuropathy symptoms after systemic chemotherapy for breast cancer are associated with changes in cerebral perfusion and gray matter. The specific mechanisms warrant further investigation given the potential diagnostic and therapeutic implications. PMID:26527786

Cerebral blood flow and oxygenation in infants after birth asphyxia. Clinically useful information?

PubMed

Greisen, Gorm

2014-10-01

The term 'luxury perfusion' was coined nearly 50 years ago after observation of bright-red blood in the cerebral veins of adults with various brain pathologies. The bright-red blood represents decreased oxygen extraction and hence the perfusion is 'luxurious' compared to oxygen needs. Gradual loss of cellular energy charge during the hours following severe birth asphyxia was observed twenty years later by sequential cranial magnetic resonance spectroscopy. This led to the concept of delayed energy failure that is linked to mitochondrial dysfunction and apoptotic cell death. Abnormally increased perfusion and lack of normal cerebral blood flow regulation are also typically present, but whether the perfusion abnormalities at this secondary stage are detrimental, beneficial, or a mere epiphenomenon remains elusive. In contrast, incomplete reoxygenation of the brain during and following resuscitation is likely to compromise outcome. The clinical value of cerebral oximetry in this context can only be examined in a randomised clinical trial. Copyright © 2014 Elsevier Ltd. All rights reserved.

Flat-detector computed tomography PBV map in the evaluation of presurgical embolization for hypervascular brain tumors.

PubMed

Wen, Li-Li; Zhang, Xin; Zhang, Qing-Rong; Wu, Qi; Chen, Shu-Juan; Deng, Jin-Long; Huang, Kaiyi; Wang, Han-Dong

2017-11-01

Preoperative embolization of hypervascular brain tumors is frequently used to minimize intraoperative bleeding. To explore the efficacy of embolization using flat-detector CT (FDCT) parenchymal blood volume (PBV) maps before and after the intervention. Twenty-five patients with hypervascular brain tumors prospectively received pre- and postprocedural FDCT PBV scans using a biplane system under a protocol approved by the institutional research ethics committee. Semiquantitative analysis, based on region of interest measurements of the pre- and post-embolization PBV maps, operating time, and blood loss, was performed to assess the feasibility of PBV maps in detecting the perfusion deficit and to evaluate the efficacy of embolization. Preoperative embolization was successful in 18 patients. The relative PBV decreased significantly from 3.98±1.41 before embolization to 2.10±2.00 after embolization. Seventeen patients underwent surgical removal of tumors 24 hours after embolization. The post-embolic tumor perfusion index correlated significantly with blood loss (ρ=0.55) and operating time (ρ=0.60). FDCT PBV mapping is a useful method for evaluating the perfusion of hypervascular brain tumors and the efficacy of embolization. It can be used as a supplement to CT perfusion, MRI, and DSA in the evaluation of tumor embolization. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro

PubMed Central

Killian, Nathaniel J.; Vernekar, Varadraj N.; Potter, Steve M.; Vukasinovic, Jelena

2016-01-01

Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 μm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations. PMID:27065793

Uptake and metabolism of sulphated steroids by the blood-brain barrier in the adult male rat.

PubMed

Qaiser, M Zeeshan; Dolman, Diana E M; Begley, David J; Abbott, N Joan; Cazacu-Davidescu, Mihaela; Corol, Delia I; Fry, Jonathan P

2017-09-01

Little is known about the origin of the neuroactive steroids dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulphate (PregS) in the brain or of their subsequent metabolism. Using rat brain perfusion in situ, we have found 3 H-PregS to enter more rapidly than 3 H-DHEAS and both to undergo extensive (> 50%) desulphation within 0.5 min of uptake. Enzyme activity for the steroid sulphatase catalysing this deconjugation was enriched in the capillary fraction of the blood-brain barrier and its mRNA expressed in cultures of rat brain endothelial cells and astrocytes. Although permeability measurements suggested a net efflux, addition of the efflux inhibitors GF120918 and/or MK571 to the perfusate reduced rather than enhanced the uptake of 3 H-DHEAS and 3 H-PregS; a further reduction was seen upon the addition of unlabelled steroid sulphate, suggesting a saturable uptake transporter. Analysis of brain fractions after 0.5 min perfusion with the 3 H-steroid sulphates showed no further metabolism of PregS beyond the liberation of free steroid pregnenolone. By contrast, DHEAS underwent 17-hydroxylation to form androstenediol in both the steroid sulphate and the free steroid fractions, with some additional formation of androstenedione in the latter. Our results indicate a gain of free steroid from circulating steroid sulphates as hormone precursors at the blood-brain barrier, with implications for ageing, neurogenesis, neuronal survival, learning and memory. © 2017 International Society for Neurochemistry.

Endothelial cell density to predict endothelial graft failure after penetrating keratoplasty.

PubMed

Lass, Jonathan H; Sugar, Alan; Benetz, Beth Ann; Beck, Roy W; Dontchev, Mariya; Gal, Robin L; Kollman, Craig; Gross, Robert; Heck, Ellen; Holland, Edward J; Mannis, Mark J; Raber, Irving; Stark, Walter; Stulting, R Doyle

2010-01-01

To determine whether preoperative and/or postoperative central endothelial cell density (ECD) and its rate of decline postoperatively are predictive of graft failure caused by endothelial decompensation following penetrating keratoplasty to treat a moderate-risk condition, principally, Fuchs dystrophy or pseudophakic corneal edema. In a subset of Cornea Donor Study participants, a central reading center determined preoperative and postoperative ECD from available specular images for 17 grafts that failed because of endothelial decompensation and 483 grafts that did not fail. Preoperative ECD was not predictive of graft failure caused by endothelial decompensation (P = .91). However, the 6-month ECD was predictive of subsequent failure (P < .001). Among those that had not failed within the first 6 months, the 5-year cumulative incidence (+/-95% confidence interval) of failure was 13% (+/-12%) for the 33 participants with a 6-month ECD of less than 1700 cells/mm(2) vs 2% (+/-3%) for the 137 participants with a 6-month ECD of 2500 cells/mm(2) or higher. After 5 years' follow-up, 40 of 277 participants (14%) with a clear graft had an ECD below 500 cells/mm(2). Preoperative ECD is unrelated to graft failure from endothelial decompensation, whereas there is a strong correlation of ECD at 6 months with graft failure from endothelial decompensation. A graft can remain clear after 5 years even when the ECD is below 500 cells/mm(2).

Effect of Diabetes Mellitus and Metformin on Central Corneal Endothelial Cell Density in Eye Bank Eyes.

PubMed

Chocron, Isaac M; Rai, Dinesh K; Kwon, Ji-Won; Bernstein, Nicole; Hu, Jimmy; Heo, Moonseong; Lee, Jimmy K; Gore, Patrick K; McCartney, Mitchell D; Chuck, Roy S

2018-05-04

To determine whether metformin use and diabetes mellitus (DM) affect central corneal endothelial cell density (ECD) by examining an eye bank corneal donor database. The Lions Eye Institute corneal donor database, which consists of 38,318 corneal samples, was examined. Associations of ECD with metformin use and DM were tested by mixed effects linear models that account for correlations of outcomes between eyes within subjects adjusting for age, intraocular lens status, and glaucoma. Subjects (N = 17,056) with observed ECD counts for both eyes are included for analysis. Average donor age was 56.3 (SD = 15.0). ECD was not associated with metformin use (mean ± SE = 2592 ± 11.9 (N = 1014) versus nonuse [2592 ± 3.0 (N = 16,042), P = 0.302]; further analysis showed that ECD was not significantly associated with metformin use in patients with diabetes. However, metformin use was significantly associated with lower ECD among patients with glaucoma: [2658 ± 50.7 (N = 27) for use versus 2789 ± 19.0 (N = 164) for nonuse, P = 0.018]. The presence of DM was significantly associated with lower ECD 2581 ± 5.6 (N = 4766) for DM versus 2595 ± 3.4 (N = 12,290) for non-DM, P = 0.031). Lower ECD was associated with DM. Lower ECD was not associated with metformin use except in a subgroup of patients with glaucoma, in which subgroup analysis showed lower ECD. The differences in ECD observed were small and unlikely to affect the suitability for transplantation of donor corneas.

A Convenient Method for Extraction and Analysis with High-Pressure Liquid Chromatography of Catecholamine Neurotransmitters and Their Metabolites.

PubMed

Xie, Li; Chen, Liqin; Gu, Pan; Wei, Lanlan; Kang, Xuejun

2018-03-01

The extraction and analysis of catecholamine neurotransmitters in biological fluids is of great importance in assessing nervous system function and related diseases, but their precise measurement is still a challenge. Many protocols have been described for neurotransmitter measurement by a variety of instruments, including high-pressure liquid chromatography (HPLC). However, there are shortcomings, such as complicated operation or hard-to-detect multiple targets, which cannot be avoided, and presently, the dominant analysis technique is still HPLC coupled with sensitive electrochemical or fluorimetric detection, due to its high sensitivity and good selectivity. Here, a detailed protocol is described for the pretreatment and detection of catecholamines with high pressure liquid chromatography with electrochemical detection (HPLC-ECD) in real urine samples of infants, using electrospun composite nanofibers composed of polymeric crown ether with polystyrene as adsorbent, also known as the packed-fiber solid phase extraction (PFSPE) method. We show how urine samples can be easily precleaned by a nanofiber-packed solid phase column, and how the analytes in the sample can be rapidly enriched, desorbed, and detected on an ECD system. PFSPE greatly simplifies the pretreatment procedures for biological samples, allowing for decreased time, expense, and reduction of the loss of targets. Overall, this work illustrates a simple and convenient protocol for solid-phase extraction coupled to an HPLC-ECD system for simultaneous determination of three monoamine neurotransmitters (norepinephrine (NE), epinephrine (E), dopamine (DA)) and two of their metabolites (3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxy-phenylacetic acid (DOPAC)) in infants' urine. The established protocol was applied to assess the differences of urinary catecholamines and their metabolites between high-risk infants with perinatal brain damage and healthy controls. Comparative analysis revealed a significant difference in urinary MHPG between the two groups, indicating that the catecholamine metabolites may be an important candidate marker for early diagnosis of cases at risk for brain damage in infants.

Implementing the Early Childhood Development Teacher Training Framework in Uganda: Gains and Challenges

ERIC Educational Resources Information Center

Ejuu, Godfrey

2012-01-01

Training of quality early childhood development (ECD) teachers is paramount in ensuring quality ECD service provision. This exploratory study focuses on the gains and challenges met in the implementation of the Uganda ECD teacher training framework. Data were obtained using questionnaires and interviews from principals and tutors of ECD teacher…

Technician Consistency in Specular Microscopy Measurements: A "Real-World" Retrospective Analysis of a United States Eye Bank.

PubMed

Rand, Gabriel M; Kwon, Ji Won; Gore, Patrick K; McCartney, Mitchell D; Chuck, Roy S

2017-10-01

To quantify consistency of endothelial cell density (ECD) measurements among technicians in a single US eye bank operating under typical operating conditions. In this retrospective analysis of 51 microscopy technicians using a semiautomated counting method on 35,067 eyes from July 2007 to May 2015, technician- and date-related marginal ECD effects were calculated using linear regression models. ECD variance was correlated with the number of specular microscopy technicians. Technician mean ECDs ranged from 2386 ± 431 to 3005 ± 560 cells/mm. Nine technicians had statistically and clinically significant marginal effects. Annual mean ECDs adjusted for changes in technicians ranged from 2422 ± 433 to 2644 ± 430 cells/mm. The period of 2007 to 2009 had statistically and clinically significant marginal effects. There was a nonstatistically significant association between the number of technicians and ECD standard deviation. There was significant ECD variability associated with specular microscopy technicians and with the date of measurement. We recommend that eye banks collect data related to laboratory factors that have been shown to influence ECD variability.

Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Qiang; The First Affiliated Hospital of Xiamen University, Xiamen; Jiang, Yuan

2011-06-17

Highlights: {yields} Soluble FGFR4 extracellular domain (FGFR4-ECD) was effectively expressed. {yields} FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling. {yields} FGFR4-ECD reduced palmitic acid-induced steatosis of HepG2 cells. {yields} FGFR4-ECD reduced tetracycline-induced fatty liver in mice. {yields} FGFR4-ECD partially restored tetracycline-repressed PPAR{alpha} expression. -- Abstract: Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane tyrosine kinase receptor that plays a crucial role in the regulation of hepatic bile acid and lipid metabolism. FGFR4 underlies high-fat diet-induced hepatic steatosis, suggesting that inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD). To determine whethermore » neutralization of FGFR4 ligands by soluble FGFR4 extracellular domain (FGFR4-ECD) can inhibit the activation of FGFR4, we constructed FGFR4-ECD expression vector and showed that FGFR4-ECD was effectively expressed in cells and secreted into culture medium. FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling and reduced steatosis of HepG2 induced by palmitic acid in vitro. Furthermore, in a tetracycline-induced fatty liver model, expression of FGFR4-ECD in mouse liver reduced the accumulation of hepatic lipids and partially restored the expression of peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}), which promotes the mitochondrial fatty acid beta-oxidation but is repressed by tetracycline. Taken together, these results demonstrate that FGFR4-ECD can block FGFR4 signaling and prevent hepatic steatosis, highlighting the potential value of inhibition of FGFR4 signaling as a method for therapeutic intervention against NAFLD.« less

Memantine transport across the mouse blood-brain barrier is mediated by a cationic influx H+ antiporter.

PubMed

Mehta, Dharmini C; Short, Jennifer L; Nicolazzo, Joseph A

2013-12-02

Memantine (MEM) is prescribed in mono and combination therapies for treating the symptoms of moderate to severe Alzheimer's disease (AD). Despite MEM being widely prescribed with other AD and non-AD medicines, very little is known about its mechanism of transport across the blood-brain barrier (BBB), and whether the nature of this transport lends MEM to a potential for drug-drug interactions at the BBB. Therefore, the purpose of this study was to characterize the mechanisms facilitating MEM brain uptake in Swiss Outbred mice using an in situ transcardiac perfusion technique, and identify the putative transporter involved in MEM disposition into the brain. Following transcardiac perfusion of MEM with increasing concentrations, the brain uptake of MEM was observed to be saturable. Furthermore, MEM brain uptake was reduced (up to 55%) by various cationic transporter inhibitors (amantadine, quinine, tetraethylammonium, choline and carnitine) and was dependent on extracellular pH, while being independent of membrane depolarization and the presence of Na(+) in the perfusate. In addition, MEM brain uptake was observed to be sensitive to changes in intracellular pH, hence, likely to be driven by H(+)/MEM antiport mechanisms. Taken together, these findings implicate the involvement of an organic cation transporter regulated by proton antiport mechanisms in the transport of MEM across the mouse BBB, possibly the organic cation/carnitine transporter, OCTN1. These studies also clearly demonstrate the brain uptake of MEM is significantly reduced by other cationic compounds, highlighting the need to consider the possibility of drug interactions with MEM at the BBB, potentially leading to reduced brain uptake and, therefore, altered efficacy of MEM when used in patients on multidrug regimens.

Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients.

PubMed

Zhao, Xiangshan; Mirza, Sameer; Alshareeda, Alaa; Zhang, Ying; Gurumurthy, Channabasavaiah Basavaraju; Bele, Aditya; Kim, Jun Hyun; Mohibi, Shakur; Goswami, Monica; Lele, Subodh M; West, William; Qiu, Fang; Ellis, Ian O; Rakha, Emad A; Green, Andrew R; Band, Hamid; Band, Vimla

2012-07-01

Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P=0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P=0.013), mitotic index (P=0.032), and Nottingham Prognostic Index score (P=0.014). Ecd expression was positively associated with HER2/neu (P=0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P=0.008) and disease-free survival (DFS) (P=0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients.

β-Ecdysone Augments Peak Bone Mass in Mice of Both Sexes.

PubMed

Dai, Weiwei; Zhang, HongLiang; Zhong, Zhendong A; Jiang, Li; Chen, Haiyan; Lay, Yu-An Evan; Kot, Alexander; Ritchie, Robert O; Lane, Nancy E; Yao, Wei

2015-08-01

One of the strongest predictors for osteoporosis is peak bone mass. Interventions to augment peak bone mass have yet to be developed. β-Ecdysone (βEcd), a natural steroid-like compound produced by arthropods to initiate metamorphosis, is believed to have androgenic effects and so may be used to augment bone mass. The purpose of this study was to use both male and female (1) gonadal-sufficient; and (2) -insufficient mice to investigate sex differences in terms of bone development and structure after βEcd administration. Two-month-old male and female Swiss-Webster mice were randomized to receive either vehicle or βEcd (0.5 mg/kg) for 3 weeks. In a separate experiment to evaluate the effects of βEcd on sex hormone-deficient mice, gonadectomy was performed in male (orchiectomy [ORX]) and female mice (ovariectomy [OVX]). Sham-operated and the ORX/OVX mice were then treated for 3 weeks with βEcd. Primary endpoints for the study were trabecular bone structure and bone strength. In male mice, the trabecular bone volume was 0.18±0.02 in the placebo-treated (PL) and 0.23±0.02 in the βEcd-treated group (p<0.05 versus PL); and 0.09±0.01 in the ORX group (p<0.05 versus PL) and 0.12±0.01 in the ORX+βEcd group. Vertebral bone strength (maximum load) was 43±2 in PL and 51±1 in the βEcd-treated group (p<0.05 versus PL); and 30±4 in the ORX group (p<0.05 versus PL) and 37±3 in the ORX+βEcd group. In female mice, trabecular bone volume was 0.23±0.02 in PL and 0.26±0.02 in the βEcd-treated group (p<0.05 versus PL); and 0.15±0.01 in the OVX group (p<0.05 versus PL) and 0.14±0.01 in the OVX+βEcd group. Maximum load of the vertebrae was 45±2 in PL and 48±4 in the βEcd-treated group; and 39±4 in the OVX group (p<0.05 versus PL) and 44±4 in the OVX+βEcd group. These findings suggest the potential use of βEcd in the augmentation of bone mass in growing male and female mice. It may also partially prevent the detrimental effects of gonadectomy on trabecular bone. Our results support the potential use of βEcd or nature products that are rich in βEcd to augment peak bone mass. βEcd may differ from the other anabolic hormone treatments that may have severe side effects such as serious cardiac complications. However, its effects on humans remain to be determined.

Preparation of silica nanoparticles loaded with nootropics and their in vivo permeation through blood-brain barrier.

PubMed

Jampilek, Josef; Zaruba, Kamil; Oravec, Michal; Kunes, Martin; Babula, Petr; Ulbrich, Pavel; Brezaniova, Ingrid; Opatrilova, Radka; Triska, Jan; Suchy, Pavel

2015-01-01

The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an in vivo model of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain.

Preparation of Silica Nanoparticles Loaded with Nootropics and Their In Vivo Permeation through Blood-Brain Barrier

PubMed Central

Zaruba, Kamil; Kunes, Martin; Ulbrich, Pavel; Brezaniova, Ingrid; Triska, Jan; Suchy, Pavel

2015-01-01

The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an in vivo model of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain. PMID:26075264

Report of a nationwide survey on actual administered radioactivities of radiopharmaceuticals for diagnostic reference levels in Japan.

PubMed

Watanabe, Hiroshi; Ishii, Kazunari; Hosono, Makoto; Imabayashi, Etsuko; Abe, Koichiro; Inubushi, Masayuki; Ohno, Kazuko; Magata, Yasuhiro; Ono, Kinya; Kikuchi, Kei; Wagatsuma, Kei; Takase, Tadashi; Saito, Kyoko; Takahashi, Yasuyuki

2016-07-01

The optimization of medical exposure is one of the major issues regarding radiation protection in the world, and The International Committee of Radiological Protection and the International Atomic Energy Agency recommend establishing diagnostic reference levels (DRLs) as tools for dose optimization. Therefore, the development of DRLs based on the latest survey has been required for nuclear medicine-related societies and organizations. This prompted us to conduct a nationwide survey on the actual administered radioactivity to adults for the purpose of developing DRLs in nuclear medicine. A nationwide survey was conducted from November 25, 2014 to January 16, 2015. The questionnaire was sent to all of the 1249 nuclear medicine facilities in Japan, and the responses were collected on a website using an answered form. Responses were obtained from 516 facilities, for a response rate of 41 %. 75th percentile of (99m)Tc-MDP and (99m)Tc-HMDP: bone scintigraphy, (99m)Tc-HM-PAO, (99m)Tc-ECD and (123)I-IMP: cerebral blood flow scintigraphy, (99m)Tc-Tetrofosmin, (99m)Tc-MIBI and (201)Tl-Cl; myocardial perfusion scintigraphy and (18)F-FDG: oncology PET (in-house-produced or delivery) in representative diagnostic nuclear medicine scans were 932, 937, 763, 775, 200, 831, 818, 180, 235 and 252, respectively. More than 90 % of the facilities were within the range of 50 % from the median of these survey results in representative diagnostic nuclear medicine facilities in Japan. Responses of the administered radioactivities recommended by the package insert, texts and guidelines such as 740 MBq ((99m)Tc-MDP and (99m)Tc-HMDP: bone scintigraphy), 740 MBq ((99m)Tc-ECD and (99m)Tc-HM-PAO: cerebral blood flow scintigraphy) and 740 MBq ((99m)Tc-Tetrofosmin and (99m)Tc-MIBI: myocardial perfusion scintigraphy), etc. were numerous. The administered activity of many radiopharmaceuticals of bone scintigraphy ((99m)Tc-MDP and (99m)Tc-HMDP), cerebral blood flow scintigraphy ((99m)Tc-HM-PAO) and myocardial perfusion scintigraphy ((99m)Tc-Tetrofosmin and (99m)Tc-MIBI), etc. were within the range of the EU DRLs and almost none of the administered radioactivity in Japan exceeded the upper limit of SNMMI standard administered radioactivity. This survey indicated that the administered radioactivity in diagnostic nuclear medicine in Japan had been in the convergence zone and nuclear medicine facilities in Japan show a strong tendency to adhere to the texts and guidelines. Furthermore, the administered radioactivities in Japan were within the range of variation of the EU and the SNMMI administered radioactivities.

Effects of Mild Blast Traumatic Brain Injury on Cerebral Vascular, Histopathological, and Behavioral Outcomes in Rats

PubMed Central

Zeng, Yaping; Deyo, Donald; Parsley, Margaret A.; Hawkins, Bridget E.; Prough, Donald S.; DeWitt, Douglas S.

2018-01-01

Abstract To determine the effects of mild blast-induced traumatic brain injury (bTBI), several groups of rats were subjected to blast injury or sham injury in a compressed air-driven shock tube. The effects of bTBI on relative cerebral perfusion (laser Doppler flowmetry [LDF]), and mean arterial blood pressure (MAP) cerebral vascular resistance were measured for 2 h post-bTBI. Dilator responses to reduced intravascular pressure were measured in isolated middle cerebral arterial (MCA) segments, ex vivo, 30 and 60 min post-bTBI. Neuronal injury was assessed (Fluoro-Jade C [FJC]) 24 and 48 h post-bTBI. Neurological outcomes (beam balance and walking tests) and working memory (Morris water maze [MWM]) were assessed 2 weeks post-bTBI. Because impact TBI (i.e., non-blast TBI) is often associated with reduced cerebral perfusion and impaired cerebrovascular function in part because of the generation of reactive oxygen and nitrogen species such as peroxynitrite (ONOO−), the effects of the administration of the ONOO− scavenger, penicillamine methyl ester (PenME), on cerebral perfusion and cerebral vascular resistance were measured for 2 h post-bTBI. Mild bTBI resulted in reduced relative cerebral perfusion and MCA dilator responses to reduced intravascular pressure, increases in cerebral vascular resistance and in the numbers of FJC-positive cells in the brain, and significantly impaired working memory. PenME administration resulted in significant reductions in cerebral vascular resistance and a trend toward increased cerebral perfusion, suggesting that ONOO− may contribute to blast-induced cerebral vascular dysfunction. PMID:29160141

[Initial diagnosis of Parkinson's disease - neuroradiological diagnosis].

PubMed

Orimo, Satoshi

2013-01-01

Brain MRI is essential for differentiating Parkinson's disease (PD) from other parkinsonian syndromes. The purpose of performing brain MRI is not to make a diagnosis of PD but is to exclude other parkinsonian syndromes. Recently, several new MRI techniques such as voxel based morphometry, relaxometry, magnetization transfer, spectroscopy, tractography, and functional MRI have been introduced in the diagnosis of PD. Neuromelanin imaging is one of the new techniques and can be useful to make an initial diagnosis of PD. MIBG myocardial scintigraphy is a sensitive imaging tool to differentiate PD from other parkinsonian syndromes and is one of the good tools to make an initial diagnosis of PD. Brain perfusion imaging is sometimes useful to make an initial diagnosis of PD, because reduced brain perfusion area can be detected before brain MRI detects morphological changes of the brain. Dopamine transporter imaging, not available in Japan, is a sensitive tool to detect very early parkinsonism and is useful to make an initial diagnosis of PD. However, it is difficult to differentiate PD from other parkinsonian syndromes.

Thyroxine transfer from cerebrospinal fluid into choroid plexus and brain is affected by brefeldin A, low sodium, BCH, and phloretin, in ventriculo-cisternal perfused rabbits.

PubMed

Zibara, Kazem; El-Zein, Ali; Joumaa, Wissam; El-Sayyad, Mohammad; Mondello, Stefania; Kassem, Nouhad

2015-01-01

Thyroxine (T4) hormone is synthesized by the thyroid gland and then released into the systemic circulation where it binds to a number of proteins. Dysfunction in T4 transport mechanisms has been demonstrated in multiple central nervous system (CNS) diseases including Alzheimer's disease. In the presence of different compounds that inhibit potential T4 transport mechanisms, this study investigated the transfer of T4 from cerebrospinal fluid (CSF) into Choroid Plexus (CP) and other brain tissues. The compounds used were brefeldin A, low sodium artificial CSF (aCSF), BCH, phloretin, and taurocholate (TA). Radiolabeled T4 ((125)I-T4) was perfused continuously into the CSF and was assessed in several brain compartments with reference molecule (14)C-mannitol and blue dextran, using the in vivo ventriculo-cisternal perfusion (V-C) technique in the rabbit. The aCSF containing the drug of interest was infused after 1 h of perfusion. Drugs were applied independently to the aCSF after 1 h of control perfusion. Of interest, in presence of low sodium or BCH, the percentage recovery of (125)I-T4, was increased compared to controls, with concomitant increase in T4 clearance. Conversely, brefeldin A, phloretin, and TA did not exert any significant effect on the recovery and clearance of (125)I-T4 assessed in aCSF. On the other hand, the uptake of (125)I-T4 into CP was raised by 18 fold compared to controls in the presence of brefeldin A. In addition, low sodium, BCH, or phloretin alone, enhanced the uptake of (125)I-T4 by almost 3-fold, whereas TA did not show any significant effect. Finally, the uptake and distribution of (125)I-T4 into other brain regions including ependymal region (ER) and caudate putamen (CAP) were significantly higher than in controls. Our study suggests the involvement of different mechanisms for the transfer of (125)I-T4 from CSF into CP and other brain regions. This transfer may implicate sodium-dependent mechanisms, amino acid "L" system, or organic anion transporting polypeptide (OATP).

Improved Diagnostic Accuracy of SPECT Through Statistical Analysis and the Detection of Hot Spots at the Primary Sensorimotor Area for the Diagnosis of Alzheimer Disease in a Community-Based Study: "The Osaki-Tajiri Project".

PubMed

Kaneta, Tomohiro; Nakatsuka, Masahiro; Nakamura, Kei; Seki, Takashi; Yamaguchi, Satoshi; Tsuboi, Masahiro; Meguro, Kenichi

2016-01-01

SPECT is an important diagnostic tool for dementia. Recently, statistical analysis of SPECT has been commonly used for dementia research. In this study, we evaluated the accuracy of visual SPECT evaluation and/or statistical analysis for the diagnosis (Dx) of Alzheimer disease (AD) and other forms of dementia in our community-based study "The Osaki-Tajiri Project." Eighty-nine consecutive outpatients with dementia were enrolled and underwent brain perfusion SPECT with 99mTc-ECD. Diagnostic accuracy of SPECT was tested using 3 methods: visual inspection (SPECT Dx), automated diagnostic tool using statistical analysis with easy Z-score imaging system (eZIS Dx), and visual inspection plus eZIS (integrated Dx). Integrated Dx showed the highest sensitivity, specificity, and accuracy, whereas eZIS was the second most accurate method. We also observed that a higher than expected rate of SPECT images indicated false-negative cases of AD. Among these, 50% showed hypofrontality and were diagnosed as frontotemporal lobar degeneration. These cases typically showed regional "hot spots" in the primary sensorimotor cortex (ie, a sensorimotor hot spot sign), which we determined were associated with AD rather than frontotemporal lobar degeneration. We concluded that the diagnostic abilities were improved by the integrated use of visual assessment and statistical analysis. In addition, the detection of a sensorimotor hot spot sign was useful to detect AD when hypofrontality is present and improved the ability to properly diagnose AD.

Cerebral blood perfusion after treatment with zolpidem and flumazenil in the baboon.

PubMed

Clauss, Ralf P; Dormehl, Irene C; Kilian, Elmaré; Louw, Werner K A; Nel, Wally H; Oliver, Douglas W

2002-01-01

Previous studies have shown that zolpidem (CAS 82626-48-0) can lead to improved perfusion in damaged brain tissue. Zolpidem belongs to the imidazopyridine chemical class and it illicits its pharmacological action via the gamma-aminobutyric acid (GABA) receptor system through stimulation of particularly the omega 1 receptors and to a lesser extent omega 2 receptors. Previously it was reported that no cerebral blood flow effects were observed in normal baboons after treatment with zolpidem, whereas an asymmetric regional increase in cerebral blood flow was observed in a neurologically abnormal baboon. In this study, the effect of a combination of the benzodiazepine receptor antagonist flumazenil (CAS 78755-81-4) and zolpidem on brain perfusion was examined by the 99mTc-hexamethyl-propylene amine oxime (99mTc-HMPAO) split dose brain single photon emission computed tomography (SPECT). Four normal baboons and the neurologically abnormal baboon from the previous zolpidem study were examined. In the current study the asymmetric changes observed after zolpidem--only treatment in the abnormal baboon was attenuated by flumazenil intervention. A decreased brain blood flow was observed after combination treatment of zolpidem and flumazenil in the normal baboons. The involvement of the omega receptors is suggested by these results. Up- or down-regulation of omega receptors may also contribute to the observed responses in the abnormal baboon and a brain injured patient.

Stimulation effect of electric current density (ECD) on microbial community of a three dimensional particle electrode coupled with biological aerated filter reactor (TDE-BAF).

PubMed

Feng, Yan; Li, Xing; Song, Ting; Yu, Yanzhen; Qi, Jingyao

2017-11-01

Improving the stimulation effect of electric current density (ECD) on microbial community is critical in designing and operating TDE-BAF. This study investigated the effect of ECD at 0.00, 4.08, 6.12, 12.20, 14.25, 16.30 and 20.20A·m -2 on the removal performance, diversity and structure of microbial community in TDE-BAF. Results indicated that the ECD of 14.25A·m -2 exhibited the highest COD, TOC and NH 4 + -N average removal rates with 93.33%, 91.26% and 93.87%, respectively; Under high ECD, especially exceeding 14.25A·m -2 , the inhibition of growth and activity because of plasmatorrhexis was in agreement with the sharp biomass decline; there was no significant relation between community richness and diversity and removal efficiency below optimum ECD, while above optimal ECD, it was just the opposite; Microbial communities mainly including Hydrogenophaga, Saprospiraceae_uncultured, Delftia, Enterobacter, Pseudomonas, Pseudoxanthomonas, and Nitrosospira and physicochemical properties well explained the excellent removal performance at the optimum ECD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differential Activation of Pontomedullary Nuclei by Acid Perfusion of Different Regions of the Esophagus

PubMed Central

Lang, Ivan M.; Medda, Bidyut K.; Shaker, Reza

2010-01-01

The objective of this study was to determine the brain stem nuclei and physiological responses activated by esophageal acidification. The effects of perfusion of the cervical (ESOc), or thoracic (ESOt) esophagus with PBS or HCl on c-fos immunoreactivity of the brain stem or on physiological variables, and the effects of vagotomy were examined in anesthetized cats. We found that acidification of the ESOc increased the number of c-fos positive neurons in the area postrema (AP), vestibular nucleus (VN), parabrachial nucleus (PBN), nucleus ambiguus (NA), dorsal motor nucleus (DMN), and all subnuclei of the nucleus tractus solitarius (NTS), but one. Acidification of the ESOt activated neurons in the central (CE), caudal (CD), dorsomedial (DM), dorsolateral (DL), ventromedial (VM) subnuclei of NTS, and the DMN. Vagotomy blocked all c-fos responses to acid perfusion of the whole esophagus (ESOw). Perfusion of the ESOc or ESOt with PBS activated secondary peristalsis (2P), but had no effect on blood pressure, heart rate, or respiratory rate. Perfusion of the ESOc, but not ESOt, with HCL activated pharyngeal swallowing (PS), profuse salivation, or physiological correlates of emesis. Vagotomy blocked all physiological effects of ESOw perfusion. We conclude that acidification of the ESOc and ESOt activate different sets of pontomedullary nuclei and different physiological responses. The NTSce, NTScom, NTSdm, and DMN are associated with activation of 2P, the NTSim and NTSis, are associated with activation of PS, and the AP, VN, and PBN are associated with activation of emesis and perhaps nausea. All responses to esophageal fluid perfusion or acidification are mediated by the vagus nerves. PMID:20655885

Intraoperative Magnetic Resonance Imaging of Cerebral Oxygen Metabolism During Resection of Brain Lesions.

PubMed

Stadlbauer, Andreas; Merkel, Andreas; Zimmermann, Max; Sommer, Björn; Buchfelder, Michael; Meyer-Bäse, Anke; Rössler, Karl

2017-04-01

Tissue oxygen tension is an important parameter for brain tissue viability and its noninvasive intraoperative monitoring in the whole brain is of highly clinical relevance. The purpose of this study was the introduction of a multiparametric quantitative blood oxygenation dependent magnetic resonance imaging (MRI) approach for intraoperative examination of oxygen metabolism during the resection of brain lesions. Sixteen patients suffering from brain lesions were examined intraoperatively twice (before craniotomy and after gross-total resection) via the quantitative blood oxygenation dependent technique and a 1.5-Tesla MRI scanner, which is installed in an operating room. The MRI protocol included T2*- and T2 mapping and dynamic susceptibility weighted perfusion. Data analysis was performed with a custom-made, in-house MatLab software for calculation of maps of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) as well as of cerebral blood volume and cerebral blood flow. Perilesional edema showed a significant increase in both perfusion (cerebral blood volume +21%, cerebral blood flow +13%) and oxygen metabolism (OEF +32%, CMRO 2  +16%) after resection of the lesions. In perilesional nonedematous tissue only, however, oxygen metabolism (OEF +19%, CMRO 2  +11%) was significantly increased, but not perfusion. No changes were found in normal brain. Fortunately, no neurovascular adverse events were observed. This approach for intraoperative examination of oxygen metabolism in the whole brain is a new application of intraoperative MRI additionally to resection control (residual tumor detection) and updating of neuronavigation (brain shift detection). It may help to detect neurovascular adverse events early during surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Fast analytical spectral filtering methods for magnetic resonance perfusion quantification.

PubMed

Reddy, Kasireddy V; Mitra, Abhishek; Yalavarthy, Phaneendra K

2016-08-01

The deconvolution in the perfusion weighted imaging (PWI) plays an important role in quantifying the MR perfusion parameters. The PWI application to stroke and brain tumor studies has become a standard clinical practice. The standard approach for this deconvolution is oscillatory-limited singular value decomposition (oSVD) and frequency domain deconvolution (FDD). The FDD is widely recognized as the fastest approach currently available for deconvolution of MR perfusion data. In this work, two fast deconvolution methods (namely analytical fourier filtering and analytical showalter spectral filtering) are proposed. Through systematic evaluation, the proposed methods are shown to be computationally efficient and quantitatively accurate compared to FDD and oSVD.

Hyperpolarized xenon magnetic resonance of the lung and the brain

NASA Astrophysics Data System (ADS)

Venkatesh, Arvind Krishnamachari

2001-04-01

Hyperpolarized noble gas Magnetic Resonance Imaging (MRI) is a new diagnostic modality that has been used successfully for lung imaging. Xenon is soluble in blood and inhaled xenon is transported to the brain via circulating blood. Xenon also accumulates in the lipid rich white matter of the brain. Hyperpolarized xenon can hence be used as a tissue- sensitive probe of brain function. The goals of this study were to identify the NMR resonances of xenon in the rat brain and evaluate the role of hyperpolarized xenon for brain MRI. We have developed systems to produce sufficient volumes of hyperpolarized xenon for in vivo brain experiments. The specialized instrumentation developed include an apparatus for optical pump-cell manufacture and high purity gas manifolds for filling cells. A hyperpolarized gas delivery system was designed to ventilate small animals with hyperpolarized xenon for transport to the brain. The T1 of xenon dissolved in blood indicates that the lifetime of xenon in the blood is sufficient for significant magnetization to be transferred to distal tissues. A variety of carrier agents for intravenous delivery of hyperpolarized xenon were tested for transport to distal tissues. Using our new gas delivery system, high SNR 129Xe images of rat lungs were obtained. Spectroscopy with hyperpolarized xenon indicated that xenon was transported from the lungs to the blood and tissues with intact magnetization. After preliminary studies that indicated the feasibility for in vivo rat brain studies, experiments were performed with adult rats and young rats with different stages of white matter development. Both in vivo and in vitro experiments showed the prominence of one peak from xenon in the rat brain, which was assigned to brain lipids. Cerebral brain perfusion was calculated from the wash-out of the hyperpolarized xenon signal in the brain. An increase in brain perfusion during maturation was observed. These experiments showed that hyperpolarized xenon MRI can be used to develop unique approaches to studying white matter and gray matter in the brain. Some of the possible applications of hyperpolarized xenon MRI in the brain are clinical diagnosis of white matter diseases, functional MRI (fMRI) and measurement of cerebral blood perfusion.

Damage control of civilian penetrating brain injuries in environments of low neuro-monitoring resources.

PubMed

Charry, José D; Rubiano, Andrés M; Puyana, Juan C; Carney, Nancy; David Adelson, P

2016-01-01

Gunshot wounds to the head are more common in military settings. Recently, a damage control (DC) approach for the management of these lesions has been used in combat areas. The aim of this study was to evaluate the results of civilian patients with penetrating gunshot wounds to the head, managed with a strategy of early cranial decompression (ECD) as a DC procedure in a university hospital with few resources for intensive care unit (ICU) neuro-monitoring in Colombia. Fifty-four patients were operated according to the DC strategy (<12 h after injury), over a 4-year period. Variables were analysed and results were evaluated according to the Glasgow Outcome Scale (GOS) at 12 months post injury; a dichotomous variable was established as 'favourable' (GOS 4-5) or 'unfavourable' (GOS 1-3). A univariate analysis was performed using a χ(2) test. Forty (74.1%) of the patients survived and 36 (90%) of them had favourable GOS. Factors associated with adverse outcomes were: Injury Severity Score (ISS) greater than 25, bi-hemispheric involvement, intra-cerebral haematoma on the first CT, closed basal cisterns and non-reactive pupils in the emergency room. DC for neurotrauma with ECD is an option to improve survival and favourable neurological outcomes 12 months after injury in patients with penetrating traumatic brain injury treated in a university hospital with few resources for ICU neuro-monitoring.

[ARTCEREB irrigation and perfusion solution for cerebrospinal surgery: pharmacological assessment using human astrocytes exposed to test solutions].

PubMed

Nishimura, Masuhiro; Doi, Kazuhisa; Enomoto, Riyo; Lee, Eibai; Naito, Shinsaku; Yamauchi, Aiko

2009-09-01

ARTCEREB irrigation and perfusion solution (Artcereb) is a preparation intended for the irrigation and perfusion of the cerebral ventricles, and it is therefore important to evaluate the effects of Artcereb on brain cells. In vitro assessment of the effects of Artcereb in cell cultures of human fetal astrocytes was conducted in comparison with normal saline and lactated Ringer's solution. The effects of exposure to Artcereb were evaluated based on microscopic images of the mitochondria stained with rhodamine 123. The effects of exposure to Artcereb on cell function were also evaluated by quantitative analysis of mitochondrial activity based on rhodamine 123 and (3)H-thymidine incorporation. Morphological changes in nuclear structure were also evaluated. The results of the present study showed that cell function in cell cultures of human astrocytes was relatively unaffected by exposure to Artcereb as compared with normal saline or lactated Ringer's solution, suggesting that Artcereb has less effect on brain cells than normal saline or lactated Ringer's solution when used for the irrigation or perfusion of the cerebral ventricles.

Prospective comparative study of brain protection in total aortic arch replacement: deep hypothermic circulatory arrest with retrograde cerebral perfusion or selective antegrade cerebral perfusion.

PubMed

Okita, Y; Minatoya, K; Tagusari, O; Ando, M; Nagatsuka, K; Kitamura, S

2001-07-01

The purpose of this study was to compare the results of total aortic arch replacement using two different methods of brain protection, particularly with respect to neurologic outcome. From June 1997, 60 consecutive patients who underwent total arch replacement through a midsternotomy were alternately allocated to one of two methods of brain protection: deep hypothermic circulatory arrest with retrograde cerebral perfusion (RCP: 30 patients) or with selective antegrade cerebral perfusion (SCP: 30 patients). Preoperative and postoperative (3 weeks) brain CT scan, neurological examination, and cognitive function tests were performed. Serum 100b protein was assayed before and after the cardiopulmonary bypass, as well as 24 hours and 48 hours after the operation. Hospital mortality occurred in 2 patients in the RCP group (6.6%) and 2 in the SCP group (6.6%). New strokes occurred in 1 (3.3%) of the RCP group and in 2 (6.6%) of the SCP group (p = 0.6). The incidence of transient brain dysfunction was significantly higher in the RCP group than in the SCP group (10, 33.3% vs 4, 13.3%, p = 0.05). Except in patients with strokes, S-100b values showed no significant differences in the two groups (RCP: SCP, prebypass 0.01+/-0.04: 0.05+/-0.16, postbypass 2.17+/-0.94: 1.97+/-1.00, 24 hours 0.61+/-0.36: 0.60+/-0.37, 48 hours 0.36+/-0.45: 0.46+/-0.40 microg/L, p = 0.7). There were no intergroup differences in the scores of memory decline (RCP 0.74+/-0.99; SCP 0.55+/-1.19, p = 0.6), orientation (RCP 1.11+/-1.29; SCP 0.50+/-0.76, p = 0.08), or intellectual function (RCP 1.21+/-1.27; SCP 1.05+/-1.15, p = 0.7). Both methods of brain protection for patients undergoing total arch replacement resulted in acceptable levels of mortality and morbidity. However, the prevalence of transient brain dysfunction was significantly higher in patients with the RCP.

Dissociative part-dependent resting-state activity in dissociative identity disorder: a controlled FMRI perfusion study.

PubMed

Schlumpf, Yolanda R; Reinders, Antje A T S; Nijenhuis, Ellert R S; Luechinger, Roger; van Osch, Matthias J P; Jäncke, Lutz

2014-01-01

In accordance with the Theory of Structural Dissociation of the Personality (TSDP), studies of dissociative identity disorder (DID) have documented that two prototypical dissociative subsystems of the personality, the "Emotional Part" (EP) and the "Apparently Normal Part" (ANP), have different biopsychosocial reactions to supraliminal and subliminal trauma-related cues and that these reactions cannot be mimicked by fantasy prone healthy controls nor by actors. Arterial spin labeling perfusion MRI was used to test the hypotheses that ANP and EP in DID have different perfusion patterns in response to rest instructions, and that perfusion is different in actors who were instructed to simulate ANP and EP. In a follow-up study, regional cerebral blood flow of DID patients was compared with the activation pattern of healthy non-simulating controls. Compared to EP, ANP showed elevated perfusion in bilateral thalamus. Compared to ANP, EP had increased perfusion in the dorsomedial prefrontal cortex, primary somatosensory cortex, and motor-related areas. Perfusion patterns for simulated ANP and EP were different. Fitting their reported role-play strategies, the actors activated brain structures involved in visual mental imagery and empathizing feelings. The follow-up study demonstrated elevated perfusion in the left temporal lobe in DID patients, whereas non-simulating healthy controls had increased activity in areas which mediate the mental construction of past and future episodic events. DID involves dissociative part-dependent resting-state differences. Compared to ANP, EP activated brain structures involved in self-referencing and sensorimotor actions more. Actors had different perfusion patterns compared to genuine ANP and EP. Comparisons of neural activity for individuals with DID and non-DID simulating controls suggest that the resting-state features of ANP and EP in DID are not due to imagination. The findings are consistent with TSDP and inconsistent with the idea that DID is caused by suggestion, fantasy proneness, and role-playing.

Dissociative Part-Dependent Resting-State Activity in Dissociative Identity Disorder: A Controlled fMRI Perfusion Study

PubMed Central

Schlumpf, Yolanda R.; Reinders, Antje A. T. S.; Nijenhuis, Ellert R. S.; Luechinger, Roger; van Osch, Matthias J. P.; Jäncke, Lutz

2014-01-01

Background In accordance with the Theory of Structural Dissociation of the Personality (TSDP), studies of dissociative identity disorder (DID) have documented that two prototypical dissociative subsystems of the personality, the “Emotional Part” (EP) and the “Apparently Normal Part” (ANP), have different biopsychosocial reactions to supraliminal and subliminal trauma-related cues and that these reactions cannot be mimicked by fantasy prone healthy controls nor by actors. Methods Arterial spin labeling perfusion MRI was used to test the hypotheses that ANP and EP in DID have different perfusion patterns in response to rest instructions, and that perfusion is different in actors who were instructed to simulate ANP and EP. In a follow-up study, regional cerebral blood flow of DID patients was compared with the activation pattern of healthy non-simulating controls. Results Compared to EP, ANP showed elevated perfusion in bilateral thalamus. Compared to ANP, EP had increased perfusion in the dorsomedial prefrontal cortex, primary somatosensory cortex, and motor-related areas. Perfusion patterns for simulated ANP and EP were different. Fitting their reported role-play strategies, the actors activated brain structures involved in visual mental imagery and empathizing feelings. The follow-up study demonstrated elevated perfusion in the left temporal lobe in DID patients, whereas non-simulating healthy controls had increased activity in areas which mediate the mental construction of past and future episodic events. Conclusion DID involves dissociative part-dependent resting-state differences. Compared to ANP, EP activated brain structures involved in self-referencing and sensorimotor actions more. Actors had different perfusion patterns compared to genuine ANP and EP. Comparisons of neural activity for individuals with DID and non-DID simulating controls suggest that the resting-state features of ANP and EP in DID are not due to imagination. The findings are consistent with TSDP and inconsistent with the idea that DID is caused by suggestion, fantasy proneness, and role-playing. PMID:24922512

Partial volume correction of brain perfusion estimates using the inherent signal data of time-resolved arterial spin labeling.

PubMed

Ahlgren, André; Wirestam, Ronnie; Petersen, Esben Thade; Ståhlberg, Freddy; Knutsson, Linda

2014-09-01

Quantitative perfusion MRI based on arterial spin labeling (ASL) is hampered by partial volume effects (PVEs), arising due to voxel signal cross-contamination between different compartments. To address this issue, several partial volume correction (PVC) methods have been presented. Most previous methods rely on segmentation of a high-resolution T1 -weighted morphological image volume that is coregistered to the low-resolution ASL data, making the result sensitive to errors in the segmentation and coregistration. In this work, we present a methodology for partial volume estimation and correction, using only low-resolution ASL data acquired with the QUASAR sequence. The methodology consists of a T1 -based segmentation method, with no spatial priors, and a modified PVC method based on linear regression. The presented approach thus avoids prior assumptions about the spatial distribution of brain compartments, while also avoiding coregistration between different image volumes. Simulations based on a digital phantom as well as in vivo measurements in 10 volunteers were used to assess the performance of the proposed segmentation approach. The simulation results indicated that QUASAR data can be used for robust partial volume estimation, and this was confirmed by the in vivo experiments. The proposed PVC method yielded probable perfusion maps, comparable to a reference method based on segmentation of a high-resolution morphological scan. Corrected gray matter (GM) perfusion was 47% higher than uncorrected values, suggesting a significant amount of PVEs in the data. Whereas the reference method failed to completely eliminate the dependence of perfusion estimates on the volume fraction, the novel approach produced GM perfusion values independent of GM volume fraction. The intra-subject coefficient of variation of corrected perfusion values was lowest for the proposed PVC method. As shown in this work, low-resolution partial volume estimation in connection with ASL perfusion estimation is feasible, and provides a promising tool for decoupling perfusion and tissue volume. Copyright © 2014 John Wiley & Sons, Ltd.

Experience with the first 50 ex vivo lung perfusions in clinical transplantation.

PubMed

Cypel, Marcelo; Yeung, Jonathan C; Machuca, Tiago; Chen, Manyin; Singer, Lianne G; Yasufuku, Kazuhiro; de Perrot, Marc; Pierre, Andrew; Waddell, Thomas K; Keshavjee, Shaf

2012-11-01

Normothermic ex vivo lung perfusion is a novel method to evaluate and improve the function of injured donor lungs. We reviewed our experience with 50 consecutive transplants after ex vivo lung perfusion. A retrospective study using prospectively collected data was performed. High-risk brain death donor lungs (defined as Pao(2)/Fio(2) <300 mm Hg or lungs with radiographic or clinical findings of pulmonary edema) and lungs from cardiac death donors were subjected to 4 to 6 hours of ex vivo lung perfusion. Lungs that achieved stable airway and vascular pressures and Pao(2)/Fio(2) greater than 400 mm Hg during ex vivo lung perfusion were transplanted. The primary end point was the incidence of primary graft dysfunction grade 3 at 72 hours after transplantation. End points were compared with lung transplants not treated with ex vivo lung perfusion (controls). A total of 317 lung transplants were performed during the study period (39 months). Fifty-eight ex vivo lung perfusion procedures were performed, resulting in 50 transplants (86% use). Of these, 22 were from cardiac death donors and 28 were from brain death donors. The mean donor Pao(2)/Fio(2) was 334 mm Hg in the ex vivo lung perfusion group and 452 mm Hg in the control group (P = .0001). The incidence of primary graft dysfunction grade 3 at 72 hours was 2% in the ex vivo lung perfusion group and 8.5% in the control group (P = .14). One patient (2%) in the ex vivo lung perfusion group and 7 patients (2.7%) in the control group required extracorporeal lung support for primary graft dysfunction (P = 1.00). The median time to extubation, intensive care unit stay, and hospital length of stay were 2, 4, and 20 days, respectively, in the ex vivo lung perfusion group and 2, 4, and 23 days, respectively, in the control group (P > .05). Thirty-day mortality (4% in the ex vivo lung perfusion group and 3.5% in the control group, P = 1.00) and 1-year survival (87% in the ex vivo lung perfusion group and 86% in the control group, P = 1.00) were similar in both groups. Transplantation of high-risk donor lungs after 4 to 6 hours of ex vivo lung perfusion is safe, and outcomes are similar to those of conventional transplants. Ex vivo lung perfusion improved our center use of donor lungs, accounting for 20% of our current lung transplant activity. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Conformational Sampling and Binding Site Assessment of Suppression of Tumorigenicity 2 Ectodomain

PubMed Central

Yang, Chao-Yie; Delproposto, James; Chinnaswamy, Krishnapriya; Brown, William Clay; Wang, Shuying; Stuckey, Jeanne A.; Wang, Xinquan

2016-01-01

Suppression of Tumorigenicity 2 (ST2), a member of the interleukin-1 receptor (IL-1R) family, activates type 2 immune responses to pathogens and tissue damage via binding to IL-33. Dysregulated responses contribute to asthma, graft-versus-host and autoinflammatory diseases and disorders. To study ST2 structure for inhibitor development, we performed the principal component (PC) analysis on the crystal structures of IL1-1R1, IL1-1R2, ST2 and the refined ST2 ectodomain (ST2ECD) models, constructed from previously reported small-angle X-ray scattering data. The analysis facilitates mapping of the ST2ECD conformations to PC subspace for characterizing structural changes. Extensive coverage of ST2ECD conformations was then obtained using the accelerated molecular dynamics simulations started with the IL-33 bound ST2ECD structure as instructed by their projected locations on the PC subspace. Cluster analysis of all conformations further determined representative conformations of ST2ECD ensemble in solution. Alignment of the representative conformations with the ST2/IL-33 structure showed that the D3 domain of ST2ECD (containing D1-D3 domains) in most conformations exhibits no clashes with IL-33 in the crystal structure. Our experimental binding data informed that the D1-D2 domain of ST2ECD contributes predominantly to the interaction between ST2ECD and IL-33 underscoring the importance of the D1-D2 domain in binding. Computational binding site assessment revealed one third of the total detected binding sites in the representative conformations may be suitable for binding to potent small molecules. Locations of these sites include the D1-D2 domain ST2ECD and modulation sites conformed to ST2ECD conformations. Our study provides structural models and analyses of ST2ECD that could be useful for inhibitor discovery. PMID:26735493

The diagnostic accuracy of multiparametric MRI to determine pediatric brain tumor grades and types.

PubMed

Koob, Mériam; Girard, Nadine; Ghattas, Badih; Fellah, Slim; Confort-Gouny, Sylviane; Figarella-Branger, Dominique; Scavarda, Didier

2016-04-01

Childhood brain tumors show great histological variability. The goal of this retrospective study was to assess the diagnostic accuracy of multimodal MR imaging (diffusion, perfusion, MR spectroscopy) in the distinction of pediatric brain tumor grades and types. Seventy-six patients (range 1 month to 18 years) with brain tumors underwent multimodal MR imaging. Tumors were categorized by grade (I-IV) and by histological type (A-H). Multivariate statistical analysis was performed to evaluate the diagnostic accuracy of single and combined MR modalities, and of single imaging parameters to distinguish the different groups. The highest diagnostic accuracy for tumor grading was obtained with diffusion-perfusion (73.24%) and for tumor typing with diffusion-perfusion-MR spectroscopy (55.76%). The best diagnostic accuracy was obtained for tumor grading in I and IV and for tumor typing in embryonal tumor and pilocytic astrocytoma. Poor accuracy was seen in other grades and types. ADC and rADC were the best parameters for tumor grading and typing followed by choline level with an intermediate echo time, CBV for grading and Tmax for typing. Multiparametric MR imaging can be accurate in determining tumor grades (primarily grades I and IV) and types (mainly pilocytic astrocytomas and embryonal tumors) in children.

Deleting the Redundant TSH Receptor C-Peptide Region Permits Generation of the Conformationally Intact Extracellular Domain by Insect Cells.

PubMed

Chen, Chun-Rong; Salazar, Larry M; McLachlan, Sandra M; Rapoport, Basil

2015-07-01

The TSH receptor (TSHR) extracellular domain (ECD) comprises a N-terminal leucine-rich repeat domain and an hinge region (HR), the latter contributing to ligand binding and critical for receptor activation. The crystal structure of the leucine-rich repeat domain component has been solved, but previous attempts to generate conformationally intact complete ECD or the isolated HR component for structural analysis have failed. The TSHR HR contains a C-peptide segment that is removed during spontaneous TSHR intramolecular cleavage into disulfide linked A- and B-subunits. We hypothesized that deletion of the redundant C-peptide would overcome the obstacle to generating conformationally intact TSHR ECD protein. Indeed, lacking the C-peptide region, the TSHR ECD (termed ECD-D1) and the isolated HR (termed HR-D1) were secreted into medium of insect cells infected with baculoviruses coding for these modified proteins. The identities of TSHR ECD-D1 and HR-D1 were confirmed by ELISA and immunoblotting using TSHR-specific monoclonal antibodies. The TSHR-ECD-D1 in conditioned medium was folded correctly, as demonstrated by its ability to inhibit radiolabeled TSH binding to the TSH holoreceptor. The TSHR ECD-D1 purification was accomplished in a single step using a TSHR monoclonal antibody affinity column, whereas the HR-D1 required a multistep protocol with a low yield. In conclusion, we report a novel approach to generate the TSHR ECD, as well as the isolated HR in insect cells, the former in sufficient amounts for structural studies. However, such studies will require previous complexing of the ECD with a ligand such as TSH or a thyroid-stimulating antibody.

Dual kidney transplantation: a case-control comparison with single kidney transplantation from standard and expanded criteria donors.

PubMed

Moore, Phillip S; Farney, Alan C; Sundberg, Aimee K; Rohr, Michael S; Hartmann, Erica L; Iskandar, Samy S; Gautreaux, Michael D; Rogers, Jeffrey; Doares, William; Anderson, Teresa K; Adams, Patricia L; Stratta, Robert J

2007-06-27

The purpose of this study was to perform a case-matched cohort analysis of dual kidney transplantation (DKT) from expanded criteria donors (ECDs) compared to single kidney transplantation (SKT) from concurrent ECDs and standard criteria donors (SCDs, defined as non-ECD). Deceased donor (DD) kidney transplants (KTs) performed at a single center between October 2001 and February 2006 were reviewed retrospectively. If the calculated DD creatinine clearance (CrCl) was <65 mL/min, then the kidneys were transplanted dually into a single patient. In the case of DKT and SKT from ECDs, low risk patients were chosen and informed consent was obtained. Patients in each group were matched for age, gender, race, transplant number, and time of transplant. Of 294 adult DD KTs performed, 16 (5%) were DKTs, which were matched with 16 concurrent SCD and 16 ECD SKT patients. Mean donor age in years (65 DKT vs. 33 SCD vs. 61 ECD; P<0.0001) and mean donor CrCl in ml/min (54 DKT vs. 91 SCD vs. 76 ECD; P=0.002) were different between groups. Patient survival was 100% in the DKT and SCD SKT groups and 94% in the ECD SKT group (mean follow up 23-28 months); graft survival rates in the DKT, SCD, and ECD groups were 81%, 81%, and 94%, respectively (P=NS). Graft function, rejection, and morbidity were similar between groups. DKT using kidneys from marginal ECDs is a viable option to counteract the growing shortage of available organs. Excellent short-term results and renal function can be achieved with older, low nephron mass donors provided that both kidneys are transplanted into a single recipient.

Outcomes of dual adult kidney transplants in the United States: an analysis of the OPTN/UNOS database.

PubMed

Gill, Jagbir; Cho, Yong W; Danovitch, Gabriel M; Wilkinson, Alan; Lipshutz, Gerald; Pham, Phuong-Thu; Gill, John S; Shah, Tariq; Bunnapradist, Suphamai

2008-01-15

The organ shortage has resulted in increased use of kidneys from expanded criteria donors (ECD). For ECD kidneys unsuitable for single use, dual kidney transplants (DKT) may be possible. There are limited data comparing outcomes of DKT to single kidney ECD transplants, making it unclear where DKT fits in the current allocation scheme. Our purpose was to compare outcomes of DKT and ECD transplants in the United States. From 2000 to 2005, a total of 625 DKT, 7686 single kidney ECD, and 6,044 SCD transplants from donors aged>or=50 years were identified from the Organ Procurement and Transplantation Network/United Network for Organ Sharing data. Allograft survival was the primary outcome. DKT comprised 4% of kidney transplants from donors aged>or=50 years. Compared to the ECD donor group, the DKT donor group was older (mean age 64.6+/-7.7 years vs. 59.9+/-6.2 years) and consisted of more African Americans (13.1% vs. 9.9%), and more diabetic donors (16.3% vs. 10.4%; P<0.001). Mean cold ischemic time was longer in DKT (22.2+/-9.7 hr), but rates of delayed graft function were lower (29.3%) compared to ECD transplants (33.6%, P=0.03). Three-year overall graft survival was 79.8% for DKT and 78.3% for ECD transplants. DKT were infrequent and had outcomes comparable to ECD transplants, despite the use of organs from higher risk donors. With a more upfront approach to DKT by offering this option to patients at the time of wait-listing as part of an ECD algorithm, we may be able to further optimize outcomes of DKT and minimize discard of potential organs.

Neural Signatures of Phonetic Learning in Adulthood: A Magnetoencephalography Study

PubMed Central

Zhang, Yang; Kuhl, Patricia K.; Imada, Toshiaki; Iverson, Paul; Pruitt, John; Stevens, Erica B.; Kawakatsu, Masaki; Tohkura, Yoh'ichi; Nemoto, Iku

2010-01-01

The present study used magnetoencephalography (MEG) to examine perceptual learning of American English /r/ and /l/ categories by Japanese adults who had limited English exposure. A training software program was developed based on the principles of infant phonetic learning, featuring systematic acoustic exaggeration, multi-talker variability, visible articulation, and adaptive listening. The program was designed to help Japanese listeners utilize an acoustic dimension relevant for phonemic categorization of /r-l/ in English. Although training did not produce native-like phonetic boundary along the /r-l/ synthetic continuum in the second language learners, success was seen in highly significant identification improvement over twelve training sessions and transfer of learning to novel stimuli. Consistent with behavioral results, pre-post MEG measures showed not only enhanced neural sensitivity to the /r-l/ distinction in the left-hemisphere mismatch field (MMF) response but also bilateral decreases in equivalent current dipole (ECD) cluster and duration measures for stimulus coding in the inferior parietal region. The learning-induced increases in neural sensitivity and efficiency were also found in distributed source analysis using Minimum Current Estimates (MCE). Furthermore, the pre-post changes exhibited significant brain-behavior correlations between speech discrimination scores and MMF amplitudes as well as between the behavioral scores and ECD measures of neural efficiency. Together, the data provide corroborating evidence that substantial neural plasticity for second-language learning in adulthood can be induced with adaptive and enriched linguistic exposure. Like the MMF, the ECD cluster and duration measures are sensitive neural markers of phonetic learning. PMID:19457395

In vitro and in vivo physiology of low nanomolar concentrations of Zn2+ in artificial cerebrospinal fluid.

PubMed

Tamano, Haruna; Nishio, Ryusuke; Shakushi, Yukina; Sasaki, Miku; Koike, Yuta; Osawa, Misa; Takeda, Atsushi

2017-02-17

Artificial cerebrospinal fluid (ACSF), i.e., brain extracellular medium, which includes Ca 2+ and Mg 2+ , but not other divalent cations such as Zn 2+ , has been used for in vitro and in vivo experiments. The present study deals with the physiological significance of extracellular Zn 2+ in ACSF. Spontaneous presynaptic activity is suppressed in the stratum lucidum of brain slices from young rats bathed in ACSF containing 10 nM ZnCl 2 , indicating that extracellular Zn 2+ modifies hippocampal presynaptic activity. To examine the in vivo action of 10 nM ZnCl 2 on long-term potentiation (LTP), the recording region was perfused using a recording electrode attached to a microdialysis probe. The magnitude of LTP was not modified in young rats by perfusion with ACSF containing 10 nM ZnCl 2 , compared to perfusion with ACSF without Zn 2+ , but attenuated by perfusion with ACSF containing 100 nM ZnCl 2 . Interestingly, the magnitude of LTP was not modified in aged rats even by perfusion with ACSF containing 100 nM ZnCl 2 , but enhanced by perfusion with ACSF containing 10 mM CaEDTA, an extracellular Zn 2+ chelator. The present study indicates that the basal levels of extracellular Zn 2+ , which are in the range of low nanomolar concentrations, are critical for synaptic activity and perhaps increased age-dependently.

In vitro and in vivo physiology of low nanomolar concentrations of Zn2+ in artificial cerebrospinal fluid

PubMed Central

Tamano, Haruna; Nishio, Ryusuke; Shakushi, Yukina; Sasaki, Miku; koike, Yuta; Osawa, Misa; Takeda, Atsushi

2017-01-01

Artificial cerebrospinal fluid (ACSF), i.e., brain extracellular medium, which includes Ca2+ and Mg2+, but not other divalent cations such as Zn2+, has been used for in vitro and in vivo experiments. The present study deals with the physiological significance of extracellular Zn2+ in ACSF. Spontaneous presynaptic activity is suppressed in the stratum lucidum of brain slices from young rats bathed in ACSF containing 10 nM ZnCl2, indicating that extracellular Zn2+ modifies hippocampal presynaptic activity. To examine the in vivo action of 10 nM ZnCl2 on long-term potentiation (LTP), the recording region was perfused using a recording electrode attached to a microdialysis probe. The magnitude of LTP was not modified in young rats by perfusion with ACSF containing 10 nM ZnCl2, compared to perfusion with ACSF without Zn2+, but attenuated by perfusion with ACSF containing 100 nM ZnCl2. Interestingly, the magnitude of LTP was not modified in aged rats even by perfusion with ACSF containing 100 nM ZnCl2, but enhanced by perfusion with ACSF containing 10 mM CaEDTA, an extracellular Zn2+ chelator. The present study indicates that the basal levels of extracellular Zn2+, which are in the range of low nanomolar concentrations, are critical for synaptic activity and perhaps increased age-dependently. PMID:28211543

Elevated Amygdala Perfusion Mediates Developmental Sex Differences in Trait Anxiety

PubMed Central

Kaczkurkin, Antonia N.; Moore, Tyler M.; Ruparel, Kosha; Ciric, Rastko; Calkins, Monica E.; Shinohara, Russell T.; Elliott, Mark A.; Hopson, Ryan; Roalf, David R.; Vandekar, Simon N.; Gennatas, Efstathios D.; Wolf, Daniel H.; Scott, J. Cobb; Pine, Daniel S.; Leibenluft, Ellen; Detre, John A.; Foa, Edna B.; Gur, Raquel E.; Gur, Ruben C.; Satterthwaite, Theodore D.

2016-01-01

Background Adolescence is a critical period for emotional maturation and is a time when clinically significant symptoms of anxiety and depression increase, particularly in females. However, few studies relate developmental differences in symptoms of anxiety and depression to brain development. Cerebral blood flow (CBF) is one brain phenotype that is known to have marked developmental sex differences. Methods We investigated whether developmental sex differences in CBF mediated sex differences in anxiety and depression symptoms by capitalizing upon a large sample of 875 youths who completed cross-sectional imaging as part of the Philadelphia Neurodevelopmental Cohort. Perfusion was quantified on a voxelwise basis using arterial spin labeled MRI at 3T. Perfusion images were related to trait and state anxiety using a general additive model with penalized splines, while controlling for gray matter density on a voxelwise basis. Clusters found to be related to anxiety were evaluated for interactions with age, sex, and puberty. Results Trait anxiety was associated with elevated perfusion in a network of regions including the amygdala, anterior insula, and fusiform cortex, even after accounting for pre-scanner state anxiety. Notably, these relationships strengthened with age and the transition through puberty. Moreover, higher trait anxiety in post-pubertal females was mediated by elevated perfusion of the left amygdala. Conclusions Taken together, these results demonstrate that differences in the evolution of cerebral perfusion during the adolescent period may be a critical element of the affective neurobiology underlying sex differences in anxiety and mood symptoms. PMID:27395327

Goal-directed-perfusion in neonatal aortic arch surgery.

PubMed

Cesnjevar, Robert Anton; Purbojo, Ariawan; Muench, Frank; Juengert, Joerg; Rueffer, André

2016-07-01

Reduction of mortality and morbidity in congenital cardiac surgery has always been and remains a major target for the complete team involved. As operative techniques are more and more standardized and refined, surgical risk and associated complication rates have constantly been reduced to an acceptable level but are both still present. Aortic arch surgery in neonates seems to be of particular interest, because perfusion techniques differ widely among institutions and an ideal form of a so called "total body perfusion (TBP)" is somewhat difficult to achieve. Thus concepts of deep hypothermic circulatory arrest (DHCA), regional cerebral perfusion (RCP/with cardioplegic cardiac arrest or on the perfused beating heart) and TBP exist in parallel and all carry an individual risk for organ damage related to perfusion management, chosen core temperature and time on bypass. Patient safety relies more and more on adequate end organ perfusion on cardiopulmonary bypass, especially sensitive organs like the brain, heart, kidney, liver and the gut, whereby on adequate tissue protection, temperature management and oxygen delivery should be visualized and monitored.

Measurement of cerebral perfusion volume and 99mTc-HMPAO uptake using SPECT in controls and patients with Alzheimer's disease.

PubMed

Fleming, J S; Kemp, P M; Bolt, L; Goatman, K A

2002-11-01

Methods for quantifying the changes in brain function observed in single photon emission computed tomography (SPECT) using hexamethylenepropylene amine oxime (HMPAO) for patients with Alzheimer's disease have the potential of improving the diagnostic accuracy of the procedure and its ability to monitor response to treatment. The absolute percentage uptake of HMPAO and the cerebral perfusion volume (CPV) of the brain were assessed using SPECT in 26 patients with mild to moderate Alzheimer's disease (AD) and 24 control subjects. A subset of 15 control subjects, which was age-matched to the AD patients, was selected to allow fair statistical comparison of parameters between groups. The percentage of brain volume with reduced perfusion (R) and a volume loss index (VLI), given by /CPV, were also calculated. Eight of the control subjects were studied on a second occasion after a mean period of 6 months. There was no significant difference in percentage uptake between controls and AD patients, the mean value being 5.8%. Cerebral perfusion volume in controls was found to depend on sex (mean value in males and females being 1327 ml and 1222 ml, respectively) and on age. The volume loss index corrected for age and sex provided good discrimination between controls and AD subjects giving a sensitivity and specificity of 81% and 96%, respectively. The repeatability coefficient, the 95% confidence limit for the difference between repeat measurements, on controls was 67 ml (5%). The measurement of cerebral perfusion volume and related indices may be of value in identifying patients with early Alzheimer's disease and in following their response to treatment.

Technetium-99m HMPAO brain SPECT in autistic children and their families.

PubMed

Degirmenci, Berna; Miral, Süha; Kaya, Gamze Capa; Iyilikçi, Leyla; Arslan, Gulhan; Baykara, Ayşen; Evren, Ismail; Durak, Hatice

2008-04-15

The purpose of the study was to investigate perfusion patterns in autistic children (AC) and their families. Ten AC (9 boys, 1 girl; mean age: 6.9+/-1.7 years) with autistic disorder defined by DSM-III-R criteria, five age-matched children (3 boys, 2 girls) as a control group, and the immediate family members of eight AC (8 mothers, 8 fathers, 7 siblings; mean ages: 39+/-4 years, 36+/-5 years and 13+/-5 years, respectively) were included in the study. Age- and sex-matched control groups for both the parents and the siblings were also included in the study. Brain perfusion images were obtained 1 h after the intravenous injection of an adjusted dose of Tc-99m HMPAO to children and the adults. Visual and semiquantitative evaluations were performed. Hypoperfusion was seen in the right posterior parietal cortex in three AC, in bilateral parietal cortex in one AC, bilateral frontal cortex in two AC, left parietal and temporal cortex in one AC, and right parietal and temporal cortex in one AC. Asymmetric perfusion was observed in the caudate nucleus in four AC. In semiquantitative analyses, statistically significant hypoperfusion was found in the right inferior and superior frontal, left superior frontal, right parietal, right mesial temporal and right caudate nucleus. In parents of AC, significant hypoperfusion was noted in the right parietal and bilateral inferior frontal cortex. In siblings of AC, perfusion in the right frontal cortex, right nucleus caudate and left parietal cortex was significantly decreased. This preliminary study suggests the existence of regional brain perfusion alterations in frontal, temporal, and parietal cortex and in caudate nucleus in AC and in their first-degree family members.

Effects of acupuncture on tissue oxygenation of the rat brain.

PubMed

Chen, G S; Erdmann, W

1978-04-01

Acupuncture has been claimed to be effective in restoring consciousness in some comatose patients. Possible mechanisms to explain alleged acupuncture-induced arousal may include vasodilatory effects caused by smypathetic stimulation which leads to an augmentation of cerebral microcirculation and thereby improves oxygen supply to the brain tissue. Experiments were performed in ten albino rats (Wistar) employing PO2 microelectrodes which were inserted into the cortex through small burholes. Brain tissue PO2 was continuously recorded before, during, and after acupuncture. Stimulation of certain acupuncture points (Go-26) resulted in immediate increase of PO2 in the frontal cortex of the rat brain. This effect was reproducible and was comparable to that obtained with increase of inspiratory CO2 known to induce arterial vasodilatation and thus capillary perfusion pressure. The effect was more significant as compared to tissue PO2 increases obtained after increase in inspiratory oxygen concentration from 21% to 100%. It appears that acupuncture causes increased brain tissue perfusion which may be, at least in part, responsible for arousal of unconscious patients.

The Impact of Phosphorylation on Electron Capture Dissociation of Proteins: A Top-Down Perspective

NASA Astrophysics Data System (ADS)

Chen, Bifan; Guo, Xiao; Tucholski, Trisha; Lin, Ziqing; McIlwain, Sean; Ge, Ying

2017-09-01

Electron capture dissociation (ECD) is well suited for the characterization of phosphoproteins, with which labile phosphate groups are generally preserved during the fragmentation process. However, the impact of phosphorylation on ECD fragmentation of intact proteins remains unclear. Here, we have performed a systematic investigation of the phosphorylation effect on ECD of intact proteins by comparing the ECD cleavages of mono-phosphorylated α-casein, multi-phosphorylated β-casein, and immunoaffinity-purified phosphorylated cardiac troponin I with those of their unphosphorylated counterparts, respectively. In contrast to phosphopeptides, phosphorylation has significantly reduced deleterious effects on the fragmentation of intact proteins during ECD. On a global scale, the fragmentation patterns are highly comparable between unphosphorylated and phosphorylated precursors under the same ECD conditions, despite a slight decrease in the number of fragment ions observed for the phosphorylated forms. On a local scale, single phosphorylation of intact proteins imposes minimal effects on fragmentation near the phosphorylation sites, but multiple phosphorylations in close proximity result in a significant reduction of ECD bond cleavages. [Figure not available: see fulltext.

Advanced Pediatric Brain Imaging Research and Training Program

DTIC Science & Technology

2013-10-01

diffusion tensor imaging and perfusion ( arterial spin labeling) MRI data and to relate measures of global and regional brain microstructural organization...AD_________________ Award Number: W81XWH-11-2-0198 TITLE: Advanced Pediatric Brain Imaging...September 2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Advanced Pediatric Brain Imaging Research and Training Program 5b. GRANT NUMBER W81XWH

Indian-Ink Perfusion Based Method for Reconstructing Continuous Vascular Networks in Whole Mouse Brain

PubMed Central

Xue, Songchao; Gong, Hui; Jiang, Tao; Luo, Weihua; Meng, Yuanzheng; Liu, Qian; Chen, Shangbin; Li, Anan

2014-01-01

The topology of the cerebral vasculature, which is the energy transport corridor of the brain, can be used to study cerebral circulatory pathways. Limited by the restrictions of the vascular markers and imaging methods, studies on cerebral vascular structure now mainly focus on either observation of the macro vessels in a whole brain or imaging of the micro vessels in a small region. Simultaneous vascular studies of arteries, veins and capillaries have not been achieved in the whole brain of mammals. Here, we have combined the improved gelatin-Indian ink vessel perfusion process with Micro-Optical Sectioning Tomography for imaging the vessel network of an entire mouse brain. With 17 days of work, an integral dataset for the entire cerebral vessels was acquired. The voxel resolution is 0.35×0.4×2.0 µm3 for the whole brain. Besides the observations of fine and complex vascular networks in the reconstructed slices and entire brain views, a representative continuous vascular tracking has been demonstrated in the deep thalamus. This study provided an effective method for studying the entire macro and micro vascular networks of mouse brain simultaneously. PMID:24498247

OCT imaging of acute vascular changes following mild traumatic brain injury in mice (Conference Presentation)

NASA Astrophysics Data System (ADS)

Chico-Calero, Isabel; Shishkov, Milen; Welt, Jonathan; Blatter, Cedric; Vakoc, Benjamin J.

2016-03-01

While most people recover completely from mild traumatic brain injuries (mTBIs) and concussions, a subset develop lasting neurological disorders. Understanding the complex pathophysiology of these injuries is critical to developing improved prognostic and therapeutic approaches. Multiple studies have shown that the structure and perfusion of brain vessels are altered after mTBI. It is possible that these vascular injuries contribute to or trigger neurodegeneration. Intravital microscopy and mouse models of TBI offer a powerful platform to study the vascular component of mTBI. Because optical coherence tomography based angiography is based on perfusion contrast and is not significantly degraded by vessel leakage or blood brain barrier disruption, it is uniquely suited to studies of brain perfusion in the setting of trauma. However, existing TBI imaging models require surgical exposure of the brain at the time of injury which conflates TBI-related vascular changes with those caused by surgery. In this work, we describe a modified cranial window preparation based on a flexible, transparent polyurethane membrane. Impact injuries were delivered directly through this membrane, and imaging was performed immediately after injury without the need for additional surgical procedures. Using this model, we demonstrate that mTBI induces a transient cessation of flow in the capillaries and smaller vessels near the injury point. Reperfusion is observed in all animals within 3 hours of injury. This work describes new insight into the transient vascular changes induced by mTBI, and demonstrates more broadly the utility of the OCT/polyurethane window model platform in preclinical studies of mTBI.

Brain Perfusion and Diffusion Abnormalities in Children Treated for Posterior Fossa Brain Tumors.

PubMed

Li, Matthew D; Forkert, Nils D; Kundu, Palak; Ambler, Cheryl; Lober, Robert M; Burns, Terry C; Barnes, Patrick D; Gibbs, Iris C; Grant, Gerald A; Fisher, Paul G; Cheshier, Samuel H; Campen, Cynthia J; Monje, Michelle; Yeom, Kristen W

2017-06-01

To compare cerebral perfusion and diffusion in survivors of childhood posterior fossa brain tumor with neurologically normal controls and correlate differences with cognitive dysfunction. We analyzed retrospectively arterial spin-labeled cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) in 21 patients with medulloblastoma (MB), 18 patients with pilocytic astrocytoma (PA), and 64 neurologically normal children. We generated ANCOVA models to evaluate treatment effects on the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, and cerebral white matter at time points an average of 5.7 years after original diagnosis. A retrospective review of patient charts identified 12 patients with neurocognitive data and in whom the relationship between IQ and magnetic resonance imaging variables was assessed for each brain structure. Patients with MB (all treated with surgery, chemotherapy, and radiation) had significantly lower global CBF relative to controls (10%-23% lower, varying by anatomic region, all adjusted P?

Correlation-based perfusion mapping using time-resolved MR angiography: A feasibility study for patients with suspicions of steno-occlusive craniocervical arteries.

PubMed

Nam, Yoonho; Jang, Jinhee; Park, Sonya Youngju; Choi, Hyun Seok; Jung, So-Lyung; Ahn, Kook-Jin; Kim, Bum-Soo

2018-05-22

To explore the feasibility of using correlation-based time-delay (CTD) maps produced from time-resolved MR angiography (TRMRA) to diagnose perfusion abnormalities in patients suspected to have steno-occlusive lesions in the craniocervical arteries. Twenty-seven patients who were suspected to have steno-occlusive lesions in the craniocervical arteries underwent both TRMRA and brain single-photon emission computed tomography (SPECT). TRMRA was performed on the supra-aortic area after intravenous injection of a 0.03 mmol/kg gadolinium-based contrast agent. Time-to-peak (TTP) maps and CTD maps of the brain were automatically generated from TRMRA data, and their quality was assessed. Detection of perfusion abnormalities was compared between CTD maps and the time-series maximal intensity projection (MIP) images from TRMRA and TTP maps. Correlation coefficients between quantitative changes in SPECT and parametric maps for the abnormal perfusion areas were calculated. The CTD maps were of significantly superior quality than TTP maps (p < 0.01). For perfusion abnormality detection, CTD maps (kappa 0.84, 95% confidence interval [CI] 0.67-1.00) showed better agreement with SPECT than TTP maps (0.66, 0.46-0.85). For perfusion deficit detection, CTD maps showed higher accuracy (85.2%, 95% CI 66.3-95.8) than MIP images (66.7%, 46-83.5), with marginal significance (p = 0.07). In abnormal perfusion areas, correlation coefficients between SPECT and CTD (r = 0.74, 95% CI 0.34-0.91) were higher than those between SPECT and TTP (r = 0.66, 0.20-0.88). CTD maps generated from TRMRA were of high quality and offered good diagnostic performance for detecting perfusion abnormalities associated with steno-occlusive arterial lesions in the craniocervical area. • Generation of perfusion parametric maps from time-resolved MR angiography is clinically useful. • Correlation-based delay maps can be used to detect perfusion abnormalities associated with steno-occlusive craniocervical arteries. • Estimation of correlation-based delay is robust for low signal-to-noise 4D MR data.

CAD system for automatic analysis of CT perfusion maps

NASA Astrophysics Data System (ADS)

Hachaj, T.; Ogiela, M. R.

2011-03-01

In this article, authors present novel algorithms developed for the computer-assisted diagnosis (CAD) system for analysis of dynamic brain perfusion, computer tomography (CT) maps, cerebral blood flow (CBF), and cerebral blood volume (CBV). Those methods perform both quantitative analysis [detection and measurement and description with brain anatomy atlas (AA) of potential asymmetries/lesions] and qualitative analysis (semantic interpretation of visualized symptoms). The semantic interpretation (decision about type of lesion: ischemic/hemorrhagic, is the brain tissue at risk of infraction or not) of visualized symptoms is done by, so-called, cognitive inference processes allowing for reasoning on character of pathological regions based on specialist image knowledge. The whole system is implemented in.NET platform (C# programming language) and can be used on any standard PC computer with.NET framework installed.

Structural Determinants Underlying Constitutive Dimerization of Unoccupied Human Follitropin Receptors

PubMed Central

Guan, Rongbin; Wu, Xueqing; Feng, Xiuyan; Zhang, Meilin; Hébert, Terence E.; Segaloff, Deborah L.

2009-01-01

The human follitropin receptor (hFSHR) is a G protein-coupled receptor (GPCR) central to reproductive physiology that is composed of an extracellular domain (ECD) fused to a serpentine region. Using bioluminescence resonance energy transfer (BRET) in living cells, we show that hFSHR dimers form constitutively during their biosynthesis. Mutations in TM1 and TM4 had no effect on hFSHR dimerization, alone or when combined with mutation of Tyr110 in the ECD, a residue predicted to mediate dimerization of the soluble hormone-binding portion of the ECD complexed with FSH (Q. Fan and W. Hendrickson, Nature 433:269–277, 2005). Expressed individually, the serpentine region and a membrane-anchored form of the hFSHR ECD each exhibited homodimerization, suggesting that both domains contribute to dimerization of the full-length receptor. However, even in the context of only the membrane-anchored ECD, mutation of Tyr110 to alanine did not inhibit dimerization. The full-length hFSHR and the membrane-anchored ECD were then each engineered to introduce a consensus site for N-linked glycosylation at residue 110. Despite experimental validation of the presence of carbohydrate on residue 110, we failed to observe disruption of dimerization of either the full-length hFSHR or membrane-anchored ECD containing the inserted glycan wedge. Taken altogether, our data suggest that both the serpentine region and the ECD contribute to hFSHR dimerization and that the dimerization interface of the unoccupied hFSHR does not involve Tyr110 of the ECD. PMID:19800402

Is ultrasound perfusion imaging capable of detecting mismatch? A proof-of-concept study in acute stroke patients.

PubMed

Reitmeir, Raluca; Eyding, Jens; Oertel, Markus F; Wiest, Roland; Gralla, Jan; Fischer, Urs; Giquel, Pierre-Yves; Weber, Stefan; Raabe, Andreas; Mattle, Heinrich P; Z'Graggen, Werner J; Beck, Jürgen

2017-04-01

In this study, we compared contrast-enhanced ultrasound perfusion imaging with magnetic resonance perfusion-weighted imaging or perfusion computed tomography for detecting normo-, hypo-, and nonperfused brain areas in acute middle cerebral artery stroke. We performed high mechanical index contrast-enhanced ultrasound perfusion imaging in 30 patients. Time-to-peak intensity of 10 ischemic regions of interests was compared to four standardized nonischemic regions of interests of the same patient. A time-to-peak >3 s (ultrasound perfusion imaging) or >4 s (perfusion computed tomography and magnetic resonance perfusion) defined hypoperfusion. In 16 patients, 98 of 160 ultrasound perfusion imaging regions of interests of the ischemic hemisphere were classified as normal, and 52 as hypoperfused or nonperfused. Ten regions of interests were excluded due to artifacts. There was a significant correlation of the ultrasound perfusion imaging and magnetic resonance perfusion or perfusion computed tomography (Pearson's chi-squared test 79.119, p < 0.001) (OR 0.1065, 95% CI 0.06-0.18). No perfusion in ultrasound perfusion imaging (18 regions of interests) correlated highly with diffusion restriction on magnetic resonance imaging (Pearson's chi-squared test 42.307, p < 0.001). Analysis of receiver operating characteristics proved a high sensitivity of ultrasound perfusion imaging in the diagnosis of hypoperfused area under the curve, (AUC = 0.917; p < 0.001) and nonperfused (AUC = 0.830; p < 0.001) tissue in comparison with perfusion computed tomography and magnetic resonance perfusion. We present a proof of concept in determining normo-, hypo-, and nonperfused tissue in acute stroke by advanced contrast-enhanced ultrasound perfusion imaging.

Generation of global political priority for early childhood development: the challenges of framing and governance.

PubMed

Shawar, Yusra Ribhi; Shiffman, Jeremy

2017-01-07

Despite progress, early childhood development (ECD) remains a neglected issue, particularly in resource-poor countries. We analyse the challenges and opportunities that ECD proponents face in advancing global priority for the issue. We triangulated among several data sources, including 19 semi-structured interviews with individuals involved in global ECD leadership, practice, and advocacy, as well as peer-reviewed research, organisation reports, and grey literature. We undertook a thematic analysis of the collected data, drawing on social science scholarship on collective action and a policy framework that elucidates why some global initiatives are more successful in generating political priority than others. The analysis indicates that the ECD community faces two primary challenges in advancing global political priority. The first pertains to framing: generation of internal consensus on the definition of the problem and solutions, agreement that could facilitate the discovery of a public positioning of the issue that could generate political support. The second concerns governance: building of effective institutions to achieve collective goals. However, there are multiple opportunities to advance political priority for ECD, including an increasingly favourable political environment, advances in ECD metrics, and the existence of compelling arguments for investment in ECD. To advance global priority for ECD, proponents will need to surmount the framing and governance challenges and leverage these opportunities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sleep Loss and the Inflammatory Response in Mice Under Chronic Environmental Circadian Disruption

PubMed Central

Castanon-Cervantes, Oscar; Natarajan, Divya; Delisser, Patrick; Davidson, Alec J.; Paul, Ketema N.

2013-01-01

Shift work and trans-time zone travel lead to insufficient sleep and numerous pathologies. Here, we examined sleep/wake dynamics during chronic exposure to environmental circadian disruption (ECD), and if chronic partial sleep loss associated with ECD influences the induction of shift-related inflammatory disorder. Sleep and wakefulness were telemetrically recorded across three months of ECD, in which the dark-phase of a light-dark cycle was advanced weekly by 6 h. A three month regimen of ECD caused a temporary reorganization of sleep (NREM and REM) and wake processes across each week, resulting in an approximately 10% net loss of sleep each week relative to baseline levels. A separate group of mice were subjected to ECD or a regimen of imposed wakefulness (IW) aimed to mimic sleep amounts under ECD for one month. Fos-immunoreactivity (IR) was quantified in sleep-wake regulatory areas: the nucleus accumbens (NAc), basal forebrain (BF), and medial preoptic area (MnPO). To assess the inflammatory response, trunk blood was treated with lipopolysaccharide (LPS) and subsequent release of IL-6 was measured. Fos-IR was greatest in the NAc, BF, and MnPO of mice subjected to IW. The inflammatory response to LPS was elevated in mice subjected to ECD, but not mice subjected to IW. Thus, the net sleep loss that occurs under ECD is not associated with a pathological immune response. PMID:23696854

Histological features of localized scleroderma 'en coup de sabre': a study of 16 cases.

PubMed

Taniguchi, T; Asano, Y; Tamaki, Z; Akamata, K; Aozasa, N; Noda, S; Takahashi, T; Ichimura, Y; Toyama, T; Sugita, M; Sumida, H; Kuwano, Y; Miyazaki, M; Yanaba, K; Sato, S

2014-12-01

Early lesions of localized scleroderma are histologically characterized by perivascular lymphocytic infiltrate in the reticular dermis and swollen endothelial cells. However, there have been few information regarding histological features other than these findings in localized scleroderma. Since en coup de sabre (ECDS) is a certain subset of localized scleroderma with a relatively uniform clinical manifestation, we focused on this disease subset and evaluated its histopathological features. A total of 16 patients with ECDS were retrospectively evaluated on the basis of clinical and histological findings. Regardless of clinical manifestations, vacuolar degeneration was found in all of the ECDS patients. Importantly, keratinocyte necroses were restricted to early and active ECDS lesions. In early ECDS patients (disease duration of <3 years), moderate to severe perivascular and/or periappendageal lymphocytic infiltrate and vacuolar changes in follicular epithelium were more prominent, whereas epidermal atrophy was less frequently observed, than in late ECDS patients (disease duration of ≥6 years). Vacuolar degeneration at the dermoepidermal junction is a common histological feature in ECDS and perivascular and/or periappendageal lymphocytic infiltrate and vacuolar degeneration of follicular epithelium are characteristic especially in early ECDS, further supporting a canonical idea that the elimination of mutated epidermal cells by immune surveillance contributes to tissue damage and resultant fibrosis in localized scleroderma. © 2013 European Academy of Dermatology and Venereology.

Impact of a child stimulation intervention on early child development in rural Peru: a cluster randomised trial using a reciprocal control design

PubMed Central

Hartinger, Stella Maria; Lanata, Claudio Franco; Hattendorf, Jan; Wolf, Jennyfer; Gil, Ana Isabel; Obando, Mariela Ortiz; Noblega, Magaly; Verastegui, Hector; Mäusezahl, Daniel

2017-01-01

Objective Stimulation in early childhood can alleviate adverse effects of poverty. In a community-randomised trial, we implemented 2 home-based interventions, each serving as an attention control for the other. One group received an integrated household intervention package (IHIP), whereas the other group received an early child development (ECD) intervention. The primary objective of the study was to evaluate the effect of IHIP on diarrhoea and respiratory infections, the details of which are described elsewhere. Here, we present the impact of the ECD intervention on early childhood development indicators. Methods In this non-blinded community-randomised trial, an ECD intervention, adapted from the Peruvian government's National Wawa Wasi ECD programme, was implemented in 25 rural Peruvian Andean communities. We enrolled 534 children aged 6–35 months, from 50 communities randomised 1:1 into ECD and IHIP communities. In ECD communities, trained fieldworkers instructed mothers every 3 weeks over the 12 months study, to stimulate and interact with their children and to use standard programme toys. IHIP communities received an improved stove and hygiene promotion. Using a nationally validated ECD evaluation instrument, all children were assessed at baseline and 12 months later for overall performance on age-specific developmental milestones which fall into 7 developmental domains. Findings At baseline, ECD-group and IHIP-group children performed similarly in all domains. After 12 months, data from 258 ECD-group and 251 IHIP-group children could be analysed. The proportion of children scoring above the mean in their specific age group was significantly higher in the ECD group in all domains (range: 12–23%-points higher than IHIP group). We observed the biggest difference in fine motor skills (62% vs 39% scores above the mean, OR: 2.6, 95% CI 1.7 to 3.9). Conclusions The home-based ECD intervention effectively improved child development overall across domains and separately by investigated domain. Home-based strategies could be a promising component of poverty alleviation programmes seeking to improve developmental outcomes among rural Peruvian children. Trial registration number ISRCTN28191222; results. PMID:27612978

Objective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance.

PubMed

Carvajal-Hausdorf, Daniel E; Schalper, Kurt A; Bai, Yalai; Black, Jonathan; Santin, Alessandro D; Rimm, David L

2017-04-01

HER2 overexpression/amplification is identified in up to 40% of uterine serous carcinomas (USC) and 10% of ovarian serous carcinomas (OSC). However, clinical trials using various HER2-targeted agents failed to show significant responses. FDA-approved HER2 assays target only the protein's intracellular domain (ICD) and not the extracellular domain (ECD). Previous quantitative studies in breast cancer by our group have shown that ICD of HER2 is expressed in some cases that do not express the HER2 ECD. We measured HER2 ICD and ECD in USC and OSC samples, and determined their relationship with clinico-pathologic characteristics and survival. We measured HER2 ICD and ECD levels in 2 cohorts of USC and OSC comprising 102 and 175 patients, respectively. HER2 antibodies targeting ICD (CB11) and ECD (SP3) were validated and standardized using the AQUA® method of quantitative immunofluorescence (QIF) and a previously reported HER2 standardization tissue microarray (TMA). Objective, population-based cut-points were used to stratify patients according to HER2 ICD/ECD status. In USC, 8% of patients with high HER2 ICD had low ECD levels (6/75 patients). In OSC, 42% of patients with high HER2 ICD had low ECD levels (29/69 patients). HER2 ICD/ECD status in USC and OSC was not significantly associated with major clinico-pathological features or survival. Using objective, domain-specific HER2 measurement, 8% of USC and 42% of OSC patients with high HER2 ICD levels do not show uniform overexpression of the ECD. This may be related to the presence of p95 HER2, an oncogenic fragment generated by full protein cleavage or alternative initiation of translation. These observations raise the possibility that USC/OSCs expressing low ECD despite being HER2-positive by ICD measurement, may benefit from therapies directed against the intracellular domain (e.g. lapatinib or afatinib) alone or in combination with extracellular domain-directed drugs (e.g. trastuzumab, pertuzumab, T-DM1). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Decision Making by Young Transplant Surgeons Regarding Expanded-Criteria Donors With Acute Kidney Injury or Allocation Failure.

PubMed

Jung, D; Park, S; Kim, S H; Eom, M; Kim, J S; Yang, J W; Han, B G; Choi, S O

2016-04-01

The utilization of expanded-criteria donors (ECDs) has increased to overcome donor shortages. Unfortunately, the discard rate has also increased, especially in ECDs with acute kidney injury (AKI). We evaluated the outcomes of kidney transplantation in ECDs and standard-criteria donors (SCDs) with and without AKI. We reviewed the medical records of patients who underwent kidney transplantation. We used the AKI definition published by the Kidney Disease: Improving Global Outcomes group and reviewed the demographic characteristics of donors and recipients. We analyzed transplantation outcomes. Twenty-seven patients underwent kidney transplantation from ECDs with AKI (n = 6) or without AKI (n = 5) and SCDs with AKI (n = 6) or without AKI (n = 10). Initial creatinine and estimated glomerular filtration rate (eGFR) were not significantly different between the groups. The incidence of delayed graft function was highest in ECDs with AKI (n = 3; 36.4%), but this was not a significantly difference. There was no difference in the last creatinine and eGFR in ECDs with AKI (1.32 mg/dL, 58.7 mL/min/1.73 m(2)), ECDs without AKI (1.67 mg/dL, 44.2 mL/min/1.73 m(2)), SCDs with AKI (0.94 mg/dL, 81.5 mL/min/1.73 m(2)) and SCDs without AKI (0.97 mg/dL, 81.8 mL/min/1.73 m(2)). As the donor pool is extended to ECDs, young transplant surgeons may increasingly face decisions regarding ECDs with AKI or allocation failure. There is no consensus regarding discard criteria. However, if the donor showed initially normal creatinine levels or if dual-kidney transplantation can be performed, young transplant surgeons should not hesitate to use ECDs with AKI or allocation failure. Copyright © 2016 Elsevier Inc. All rights reserved.

Cerebral Perfusion Enhancing Interventions: A New Strategy for the Prevention of Alzheimer Dementia.

PubMed

de la Torre, Jack C

2016-09-01

Cardiovascular and cerebrovascular diseases are major risk factors in the development of cognitive impairment and Alzheimer's disease (AD). These cardio-cerebral disorders promote a variety of vascular risk factors which in the presence of advancing age are prone to markedly reduce cerebral perfusion and create a neuronal energy crisis. Long-term hypoperfusion of the brain evolves mainly from cardiac structural pathology and brain vascular insufficiency. Brain hypoperfusion in the elderly is strongly associated with the development of mild cognitive impairment (MCI) and both conditions are presumed to be precursors of Alzheimer dementia. A therapeutic target to prevent or treat MCI and consequently reduce the incidence of AD aims to elevate cerebral perfusion using novel pharmacological agents. As reviewed here, the experimental pharmaca include the use of Rho kinase inhibitors, neurometabolic energy boosters, sirtuins and vascular growth factors. In addition, a compelling new technique in laser medicine called photobiomodulation is reviewed. Photobiomodulation is based on the use of low level laser therapy to stimulate mitochondrial energy production non-invasively in nerve cells. The use of novel pharmaca and photobiomodulation may become important tools in the treatment or prevention of cognitive decline that can lead to dementia. © 2016 International Society of Neuropathology.

Temperatures Achieved in Human and Canine Neocortex During Intraoperative Passive or Active Focal Cooling

PubMed Central

Han, Rowland H.; Yarbrough, Chester K.; Patterson, Edward E.; Yang, Xiao-Feng; Miller, John W.; Rothman, Steven M.; D'Ambrosio, Raimondo

2015-01-01

Focal cortical cooling inhibits seizures and prevents acquired epileptogenesis in rodents. To investigate the potential clinical utility of this treatment modality, we examined the thermal characteristics of canine and human brain undergoing active and passive surface cooling in intraoperative settings. Four patients with intractable epilepsy were treated in a standard manner. Before the resection of a neocortical epileptogenic focus, multiple intraoperative studies of active (custom-made cooled irrigation-perfused grid) and passive (stainless steel probe) cooling were performed. We also actively cooled the neocortices of two dogs with perfused grids implanted for 2 hours. Focal surface cooling of the human brain causes predictable depth-dependent cooling of the underlying brain tissue. Cooling of 0.6–2°C was achieved both actively and passively to a depth of 10–15 mm from the cortical surface. The perfused grid permitted comparable and persistent cooling of canine neocortex when the craniotomy was closed. Thus, the human cortex can easily be cooled with the use of simple devices such as a cooling grid or a small passive probe. These techniques provide pilot data for the design of a permanently implantable device to control intractable epilepsy. PMID:25902001

Measurement of brain perfusion in newborns: Pulsed arterial spin labeling (PASL) versus pseudo-continuous arterial spin labeling (pCASL)

PubMed Central

Boudes, Elodie; Gilbert, Guillaume; Leppert, Ilana Ruth; Tan, Xianming; Pike, G. Bruce; Saint-Martin, Christine; Wintermark, Pia

2014-01-01

Background Arterial spin labeling (ASL) perfusion-weighted imaging (PWI) by magnetic resonance imaging (MRI) has been shown to be useful for identifying asphyxiated newborns at risk of developing brain injury, whether or not therapeutic hypothermia was administered. However, this technique has been only rarely used in newborns until now, because of the challenges to obtain sufficient signal-to-noise ratio (SNR) and spatial resolution in newborns. Objective To compare two methods of ASL-PWI (i.e., single inversion-time pulsed arterial spin labeling [single TI PASL], and pseudo-continuous arterial spin labeling [pCASL]) to assess brain perfusion in asphyxiated newborns treated with therapeutic hypothermia and in healthy newborns. Design/methods We conducted a prospective cohort study of term asphyxiated newborns meeting the criteria for therapeutic hypothermia; four additional healthy term newborns were also included as controls. Each of the enrolled newborns was scanned at least once during the first month of life. Each MRI scan included conventional anatomical imaging, as well as PASL and pCASL PWI-MRI. Control and labeled images were registered separately to reduce the effect of motion artifacts. For each scan, the axial slice at the level of the basal ganglia was used for comparisons. Each scan was scored for its image quality. Quantification of whole-slice cerebral blood flow (CBF) was done afterwards using previously described formulas. Results A total number of 61 concomitant PASL and pCASL scans were obtained in nineteen asphyxiated newborns treated with therapeutic hypothermia and four healthy newborns. After discarding the scans with very poor image quality, 75% (46/61) remained for comparison between the two ASL methods. pCASL images presented a significantly superior image quality score compared to PASL images (p < 0.0001). Strong correlation was found between the CBF measured by PASL and pCASL (r = 0.61, p < 0.0001). Conclusion This study demonstrates that both ASL methods are feasible to assess brain perfusion in healthy and sick newborns. However, pCASL might be a better choice over PASL in newborns, as pCASL perfusion maps had a superior image quality that allowed a more detailed identification of the different brain structures. PMID:25379424

Microchip Capillary Electrophoresis with Electrochemical Detection for Monitoring Environmental Pollutants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Gang; Lin, Yuehe; Wang, Joseph

2006-01-15

This invited paper reviews recent advances and the key strategies in microchip capillary electrophoresis (CE) with electrochemical detection (ECD) for separating and detecting a variety of environmental pollutants. The subjects covered include the fabrication of microfluidic chips, sample pretreatments, ECD, typical applications of microchip CE with ECD in environmental analysis, and future prospects. It is expected that microchip CE-ECD will become a powerful tool in the environmental field and will lead to the creation of truly portable devices.

Study of Small Ligands Which Bind Specifically to Breast Cancer Cells

DTIC Science & Technology

1997-09-01

Sepharose conjugated to three different lectins: ConA, wheat germ and lentil,. Each lectin bound many proteins in both the ECD-AP sup and the control 3T3 sup...control Lanes 13-14: Wheat germ ECD-AP Lanes 15-16: Wheat germ 3T3 control Odd lanes were eluted with a low sugar concentration; even lanes were...ECD-AP post incubation with lentil-Sepharose Lane 6: Protein remaining in pp ECD-AP post incubation with wheat germ -Sepharose Lane 8: Protein

Three-dimensional MRI perfusion maps: a step beyond volumetric analysis in mental disorders

PubMed Central

Fabene, Paolo F; Farace, Paolo; Brambilla, Paolo; Andreone, Nicola; Cerini, Roberto; Pelizza, Luisa; Versace, Amelia; Rambaldelli, Gianluca; Birbaumer, Niels; Tansella, Michele; Sbarbati, Andrea

2007-01-01

A new type of magnetic resonance imaging analysis, based on fusion of three-dimensional reconstructions of time-to-peak parametric maps and high-resolution T1-weighted images, is proposed in order to evaluate the perfusion of selected volumes of interest. Because in recent years a wealth of data have suggested the crucial involvement of vascular alterations in mental diseases, we tested our new method on a restricted sample of schizophrenic patients and matched healthy controls. The perfusion of the whole brain was compared with that of the caudate nucleus by means of intrasubject analysis. As expected, owing to the encephalic vascular pattern, a significantly lower time-to-peak was observed in the caudate nucleus than in the whole brain in all healthy controls, indicating that the suggested method has enough sensitivity to detect subtle perfusion changes even in small volumes of interest. Interestingly, a less uniform pattern was observed in the schizophrenic patients. The latter finding needs to be replicated in an adequate number of subjects. In summary, the three-dimensional analysis method we propose has been shown to be a feasible tool for revealing subtle vascular changes both in normal subjects and in pathological conditions. PMID:17229290

Potential of Contrast-Enhanced Ultrasound as a Bedside Monitoring Technique in Cerebral Perfusion: a Systematic Review.

PubMed

Vinke, Elisabeth J; Kortenbout, Anna J; Eyding, Jens; Slump, Cornelis H; van der Hoeven, Johannes G; de Korte, Chris L; Hoedemaekers, Cornelia W E

2017-12-01

Contrast-enhanced ultrasound (CEUS) has been suggested as a new method to measure cerebral perfusion in patients with acute brain injury. In this systematic review, the tolerability, repeatability, reproducibility and accuracy of different CEUS techniques for the quantification of cerebral perfusion were assessed. We selected studies published between January 1994 and March 2017 using CEUS to measure cerebral perfusion. We included 43 studies (bolus kinetics n = 31, refill kinetics n = 6, depletion kinetics n = 6) with a total of 861 patients. Tolerability was reported in 28 studies describing 12 patients with mild and transient side effects. Repeatability was assessed in 3 studies, reproducibility in 2 studies and accuracy in 19 studies. Repeatability was high for experienced sonographers and significantly lower for less experienced sonographers. Reproducibility of CEUS was not clear. The sensitivity and specificity of CEUS for the detection of cerebral ischemia ranged from 75% to 96% and from 60% to 100%. Limited data on repeatability, reproducibility and accuracy may suggest that this technique could be feasible for use in acute brain injury patients. Copyright © 2017 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Elevated Amygdala Perfusion Mediates Developmental Sex Differences in Trait Anxiety.

PubMed

Kaczkurkin, Antonia N; Moore, Tyler M; Ruparel, Kosha; Ciric, Rastko; Calkins, Monica E; Shinohara, Russell T; Elliott, Mark A; Hopson, Ryan; Roalf, David R; Vandekar, Simon N; Gennatas, Efstathios D; Wolf, Daniel H; Scott, J Cobb; Pine, Daniel S; Leibenluft, Ellen; Detre, John A; Foa, Edna B; Gur, Raquel E; Gur, Ruben C; Satterthwaite, Theodore D

2016-11-15

Adolescence is a critical period for emotional maturation and is a time when clinically significant symptoms of anxiety and depression increase, particularly in females. However, few studies relate developmental differences in symptoms of anxiety and depression to brain development. Cerebral blood flow is one brain phenotype that is known to have marked developmental sex differences. We investigated whether developmental sex differences in cerebral blood flow mediated sex differences in anxiety and depression symptoms by capitalizing on a large sample of 875 youths who completed cross-sectional imaging as part of the Philadelphia Neurodevelopmental Cohort. Perfusion was quantified on a voxelwise basis using arterial spin-labeled magnetic resonance imaging at 3T. Perfusion images were related to trait and state anxiety using general additive models with penalized splines, while controlling for gray matter density on a voxelwise basis. Clusters found to be related to anxiety were evaluated for interactions with age, sex, and puberty. Trait anxiety was associated with elevated perfusion in a network of regions including the amygdala, anterior insula, and fusiform cortex, even after accounting for prescan state anxiety. Notably, these relationships strengthened with age and the transition through puberty. Moreover, higher trait anxiety in postpubertal females was mediated by elevated perfusion of the left amygdala. Taken together, these results demonstrate that differences in the evolution of cerebral perfusion during adolescence may be a critical element of the affective neurobiological characteristics underlying sex differences in anxiety and mood symptoms. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Aromatic Cluster Sensor of Protein Folding: Near-UV Electronic Circular Dichroism Bands Assigned to Fold Compactness.

PubMed

Farkas, Viktor; Jákli, Imre; Tóth, Gábor K; Perczel, András

2016-09-19

Both far- and near-UV electronic circular dichroism (ECD) spectra have bands sensitive to thermal unfolding of Trp and Tyr residues containing proteins. Beside spectral changes at 222 nm reporting secondary structural variations (far-UV range), L b bands (near-UV range) are applicable as 3D-fold sensors of protein's core structure. In this study we show that both L b (Tyr) and L b (Trp) ECD bands could be used as sensors of fold compactness. ECD is a relative method and thus requires NMR referencing and cross-validation, also provided here. The ensemble of 204 ECD spectra of Trp-cage miniproteins is analysed as a training set for "calibrating" Trp↔Tyr folded systems of known NMR structure. While in the far-UV ECD spectra changes are linear as a function of the temperature, near-UV ECD data indicate a non-linear and thus, cooperative unfolding mechanism of these proteins. Ensemble of ECD spectra deconvoluted gives both conformational weights and insight to a protein folding↔unfolding mechanism. We found that the L b 293 band is reporting on the 3D-structure compactness. In addition, the pure near-UV ECD spectrum of the unfolded state is described here for the first time. Thus, ECD folding information now validated can be applied with confidence in a large thermal window (5≤T≤85 °C) compared to NMR for studying the unfolding of Trp↔Tyr residue pairs. In conclusion, folding propensities of important proteins (RNA polymerase II, ubiquitin protein ligase, tryptase-inhibitor etc.) can now be analysed with higher confidence. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Two-dimensional on-line detection of brominated and iodinated volatile organic compounds by ECD and ICP-MS after GC separation.

PubMed

Schwarz, A; Heumann, K G

2002-09-01

Inductively coupled plasma-mass spectrometry (ICP-MS) was coupled to a gas chromatographic (GC) system with electron capture detector (ECD), which enables relatively easy characterization and quantification of brominated and iodinated (halogenated) volatile organic compounds (HVOCs) in aquatic and air samples. The GC-ECD system is connected in series with an ICP-MS by a directly heated transfer line and an outlet port-hole for elimination of the ECD make-up gas during ignition of the plasma. The hyphenated GC-ECD/ICP-MS system provides high selectivity and sensitivity for monitoring individual HVOCs under fast chromatographic conditions. The ECD is most sensitive for the detection of chlorinated and brominated but the ICP-MS for iodinated compounds. The greatest advantage of the use of an ICP-MS is its element-specific detection, which allows clear identification of compounds in most cases. The absolute detection limits for ICP-MS are 0.5 pg for iodinated, 10 pg for brominated, and 50 pg for chlorinated HVOCs with the additional advantage that calibration is almost independent on different compounds of the same halogen. In contrast to that detection limits for ECD vary for the different halogenated compounds and lie in the range of 0.03-11 pg. The two-dimensional GC-ECD/ICP-MS instrumentation is compared with electron impact mass spectrometry (EI-MS) and microwave induced plasma atomic emission detection (MIP-AED). Even if EI-MS has additional power in identifying unknown peaks by its scan mode, the detection limits are much higher compared with GC-ECD/ICP-MS, whereas the selective ion monitoring mode (SIM) reaches similar detection limits. The MIP-AED detection limits are at the same level as EI-MS in the scan mode.

Her2/neu extracellular domain shedding in uterine serous carcinoma: implications for immunotherapy with trastuzumab.

PubMed

Todeschini, P; Cocco, E; Bellone, S; Varughese, J; Lin, K; Carrara, L; Guzzo, F; Buza, N; Hui, P; Silasi, D-A; Ratner, E; Azodi, M; Schwartz, P E; Rutherford, T J; Pecorelli, S; Santin, A D

2011-10-11

We evaluated shedding of epidermal growth factor type II receptor (Her2/neu) extracellular domain (ECD) in primary uterine serous carcinoma (USC) cell lines and in the serum of USC patients and its biological effects in experiments of trastuzumab-induced cytotoxicity in vitro. Her2/neu expression was evaluated by immunohistochemistry (IHC), real-time PCR and flow cytometry, while c-erbB2 gene amplification was assessed using fluorescent in situ hybridisation (FISH). Her2/neu ECD levels in the supernatants of USC cell lines and in the serum of 38 USC patients and 19 controls were tested using ELISA. The biologic effect of Her2/neu ECD on trastuzumab-induced antibody-dependent cell-mediated cytotoxicity (ADCC) was evaluated in 5-h chromium-release assays. Five out of ten USC cell lines overexpressed Her2/neu by IHC and showed amplification of the c-erbB2 gene. High levels of Her2/neu ECD were found in supernatants of all FISH-positive tumours. In contrast, FISH-negative USC was negative for Her2/neu ECD shedding. Serum Her2/neu ECD levels in patients harbouring 3+Her2/neu tumours were higher than those found in healthy women (P=0.02) or USC patients with 2+ or 1+/negative Her2/neu expression (P=0.02). In cytotoxicity experiments, trastuzumab-mediated ADCC was significantly decreased by the addition of Her2/neu ECD-containing supernatants (P=0.01). FISH-positive c-erbB2 USC cell lines shed high levels of Her2/neu ECD. High levels of Her2/neu ECD in USC patients may reduce trastuzumab-mediated ADCC in vitro and potentially neutralise its therapeutic effect in vivo.

Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice.

PubMed

Carneiro, Lionel; Geller, Sarah; Fioramonti, Xavier; Hébert, Audrey; Repond, Cendrine; Leloup, Corinne; Pellerin, Luc

2016-01-15

Monocarboxylates have been implicated in the control of energy homeostasis. Among them, the putative role of ketone bodies produced notably during high-fat diet (HFD) has not been thoroughly explored. In this study, we aimed to determine the impact of a specific rise in cerebral ketone bodies on food intake and energy homeostasis regulation. A carotid infusion of ketone bodies was performed on mice to stimulate sensitive brain areas for 6 or 12 h. At each time point, food intake and different markers of energy homeostasis were analyzed to reveal the consequences of cerebral increase in ketone body level detection. First, an increase in food intake appeared over a 12-h period of brain ketone body perfusion. This stimulated food intake was associated with an increased expression of the hypothalamic neuropeptides NPY and AgRP as well as phosphorylated AMPK and is due to ketone bodies sensed by the brain, as blood ketone body levels did not change at that time. In parallel, gluconeogenesis and insulin sensitivity were transiently altered. Indeed, a dysregulation of glucose production and insulin secretion was observed after 6 h of ketone body perfusion, which reversed to normal at 12 h of perfusion. Altogether, these results suggest that an increase in brain ketone body concentration leads to hyperphagia and a transient perturbation of peripheral metabolic homeostasis. Copyright © 2016 the American Physiological Society.

A thermocouple thermode for small animals

NASA Technical Reports Server (NTRS)

Williams, B. A.

1972-01-01

Thermode composed of two thin-walled stainless steel hypodermic needles and cooper-constantan thermocouple or small thermistor to indicate temperature at point of perfusion is used to measure brain temperature in animals. Because of relatively small size of thermode, structural damage to brain is minimized.

Prevention of glucocorticoid induced bone changes with beta-ecdysone

PubMed Central

Dai, Weiwei; Jiang, Li; Lay, Yu-An Evan; Chen, Haiyan; Jin, Guoqin; Zhang, Hongliang; Kot, Alex; Ritchie, Robert O.; Lane, Nancy E.; Yao, Wei

2015-01-01

Beta-ecdysone (βEcd) is a phytoecdysteroid found in the dry roots and seeds of the asteraceae and achyranthes plants, and is reported to increase osteogenesis in vitro. Since glucocorticoid (GCs) excess is associated with a decrease in bone formation, the purpose of this study was to determine if treatment with βEcd could prevent GC-induced osteoporosis. Two-month-old male Swiss-Webster mice (n=8-10/group) were randomized to either placebo or slow release prednisolone pellets (3.3mg/kg/d) and treated with vehicle control or βEcd (0.5mg/kg/d) for 21 days. GC treatment inhibited age-dependent trabecular gain and cortical bone expansion and this was accompanied by a 30-50% lower bone formation rate (BFR) at both the endosteal and periosteal surfaces. Mice treated with only βEcd significantly increased bone formation on endosteal and periosteal bone surfaces, and increased cortical bone mass were their controls to compare to GC alone. Concurrent treatment of βEcd and GC completely prevented the GC-induced reduction in BFR, trabecular bone volume and partially prevented cortical bone loss. In vitro studies determined that βEcd prevented the GC increase in autophagy of the bone marrow stromal cells as well as in whole bone. In summary, βEcd prevented GC induced changes in bone formation, bone cell viability and bone mass. Additional studies are warranted of βEcd for the treatment of GC induced bone loss. PMID:25585248

Prevention of glucocorticoid induced bone changes with beta-ecdysone.

PubMed

Dai, Weiwei; Jiang, Li; Lay, Yu-An Evan; Chen, Haiyan; Jin, Guoqin; Zhang, Hongliang; Kot, Alexander; Ritchie, Robert O; Lane, Nancy E; Yao, Wei

2015-05-01

Beta-ecdysone (βEcd) is a phytoecdysteroid found in the dry roots and seeds of the asteraceae and achyranthes plants, and is reported to increase osteogenesis in vitro. Since glucocorticoid (GC) excess is associated with a decrease in bone formation, the purpose of this study was to determine if treatment with βEcd could prevent GC-induced osteoporosis. Two-month-old male Swiss-Webster mice (n=8-10/group) were randomized to either placebo or slow release prednisolone pellets (3.3mg/kg/day) and treated with vehicle control or βEcd (0.5mg/kg/day) for 21days. GC treatment inhibited age-dependent trabecular gain and cortical bone expansion and this was accompanied by a 30-50% lower bone formation rate (BFR) at both the endosteal and periosteal surfaces. Mice treated with only βEcd significantly increased bone formation on the endosteal and periosteal bone surfaces, and increased cortical bone mass were their controls to compare to GC alone. Concurrent treatment of βEcd and GC completely prevented the GC-induced reduction in BFR, trabecular bone volume and partially prevented cortical bone loss. In vitro studies determined that βEcd prevented the GC increase in autophagy of the bone marrow stromal cells as well as in whole bone. In summary, βEcd prevented GC induced changes in bone formation, bone cell viability and bone mass. Additional studies are warranted of βEcd for the treatment of GC induced bone loss. Copyright © 2015 Elsevier Inc. All rights reserved.

Functional Roles of the Interaction of APP and Lipoprotein Receptors

PubMed Central

Pohlkamp, Theresa; Wasser, Catherine R.; Herz, Joachim

2017-01-01

The biological fates of the key initiator of Alzheimer’s disease (AD), the amyloid precursor protein (APP), and a family of lipoprotein receptors, the low-density lipoprotein (LDL) receptor-related proteins (LRPs) and their molecular roles in the neurodegenerative disease process are inseparably interwoven. Not only does APP bind tightly to the extracellular domains (ECDs) of several members of the LRP group, their intracellular portions are also connected through scaffolds like the one established by FE65 proteins and through interactions with adaptor proteins such as X11/Mint and Dab1. Moreover, the ECDs of APP and LRPs share common ligands, most notably Reelin, a regulator of neuronal migration during embryonic development and modulator of synaptic transmission in the adult brain, and Agrin, another signaling protein which is essential for the formation and maintenance of the neuromuscular junction (NMJ) and which likely also has critical, though at this time less well defined, roles for the regulation of central synapses. Furthermore, the major independent risk factors for AD, Apolipoprotein (Apo) E and ApoJ/Clusterin, are lipoprotein ligands for LRPs. Receptors and ligands mutually influence their intracellular trafficking and thereby the functions and abilities of neurons and the blood-brain-barrier to turn over and remove the pathological product of APP, the amyloid-β peptide. This article will review and summarize the molecular mechanisms that are shared by APP and LRPs and discuss their relative contributions to AD. PMID:28298885

Potential of optical microangiography to monitor cerebral blood perfusion and vascular plasticity following traumatic brain injury in mice in vivo

NASA Astrophysics Data System (ADS)

Jia, Yali; Alkayed, Nabil; Wang, Ruikang K.

2009-07-01

Optical microanglography (OMAG) is a recently developed imaging modality capable of volumetric imaging of dynamic blood perfusion, down to capillary level resolution, with an imaging depth up to 2.00 mm beneath the tissue surface. We report the use of OMAG to monitor the cerebral blood flow (CBF) over the cortex of mouse brain upon traumatic brain injury (TBI), with the cranium left intact, for a period of two weeks on the same animal. We show the ability of OMAG to repeatedly image 3-D cerebral vasculatures during pre- and post-traumatic phases, and to visualize the changes of regulated CBF and the vascular plasticity after TBI. The results indicate the potential of OMAG to explore the mechanism involved in the rehabilitation of TBI.

Kainic acid-induced albumin leak across the blood-brain barrier facilitates epileptiform hyperexcitability in limbic regions.

PubMed

Noé, Francesco M; Bellistri, Elisa; Colciaghi, Francesca; Cipelletti, Barbara; Battaglia, Giorgio; de Curtis, Marco; Librizzi, Laura

2016-06-01

Systemic administration of kainic acid (KA) is a widely used procedure utilized to develop a model of temporal lobe epilepsy (TLE). Despite its ability to induce status epilepticus (SE) in vivo, KA applied to in vitro preparations induces only interictal-like activity and/or isolated ictal discharges. The possibility that extravasation of the serum protein albumin from the vascular compartment enhances KA-induced brain excitability is investigated here. Epileptiform activity was induced by arterial perfusion of 6 μm KA in the in vitro isolated guinea pig brain preparation. Simultaneous field potential recordings were carried out bilaterally from limbic (CA1, dentate gyrus [DG], and entorhinal cortex) and extralimbic regions (piriform cortex and neocortex). Blood-brain barrier (BBB) breakdown associated with KA-induced epileptiform activity was assessed by parenchymal leakage of intravascular fluorescein-isothiocyanate albumin. Seizure-induced brain inflammation was evaluated by western blot analysis of interleukin (IL)-1β expression in brain tissue. KA infusion caused synchronized activity at 15-30 Hz in limbic (but not extralimbic) cortical areas, associated with a brief, single seizure-like event. A second bolus of KA, 60 min after the induction of the first ictal event, did not further enhance excitability. Perfusion of serum albumin between the two administrations of KA enhanced epileptiform discharges and allowed a recurrent ictal event during the second KA infusion. Our data show that arterial KA administration selectively alters the synchronization of limbic networks. However, KA is not sufficient to generate recurrent seizures unless serum albumin is co-perfused during KA administration. These findings suggest a role of serum albumin in facilitating acute seizure generation. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Neuropsychological functions and rCBF SPECT in Parkinson's disease patients considered candidates for deep brain stimulation.

PubMed

Paschali, Anna; Messinis, Lambros; Lyros, Epameinondas; Constantoyannis, Costas; Kefalopoulou, Zinovia; Lakiotis, Velissarios; Papathanasopoulos, Panagiotis; Vassilakos, Paulos

2009-11-01

In the present study, we examined relationships between neuropsychological functions and brain single photon emission computed tomography (SPECT) regional cerebral blood flow (rCBF) observed at presurgical evaluation for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease (PD) patients. Twenty advanced non-demented PD patients, candidates for DBS surgery, underwent perfusion brain SPECT study and neuropsychological assessment prior to surgery (range: 30-50 days). Patients were further assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H&Y) scale. During all assessments patients were "on" standard medication. NeuroGam software, which permits voxel by voxel analysis, was used to compare the brain perfusion of PD patients with a normal database adjusted for sex and age. Neuropsychological scores were compared to age, education and sex-adjusted normative databases. Our results indicated that the distribution of rCBF showed significant differences when compared to an age- and sex-adjusted normative database. We found impaired blood flow in 17 (85%) of our patients in the left prefrontal lobe, in 14 (70%) in the right prefrontal lobe and in 11 (55%) in the left frontal and right parietal lobes. Neuropsychological testing revealed that 18 (90%) of our patients had significant impairments in measures of executive functions (set-shifting) and 15 (75%) in response inhibition. Furthermore, we found significant correlations between measures of visual attention, executive functions and the right frontal lobe region. The presence of widespread blood flow reduction was observed mainly in the frontal lobes of dementia-free patients with advanced PD. Furthermore, performance on specific cognitive measures was highly related to perfusion brain SPECT findings.

A mutation in the extracellular domain of the α7 nAChR reduces calcium permeability.

PubMed

Colón-Sáez, José O; Yakel, Jerrel L

2014-08-01

The α7 neuronal nicotinic acetylcholine receptor (nAChR) displays the highest calcium permeability among the different subtypes of nAChRs expressed in the mammalian brain and can impact cellular events including neurotransmitter release, second messenger cascades, cell survival, and apoptosis. The selectivity for cations in nAChRs is thought to be achieved in part by anionic residues which are located on either side of the channel mouth and increase relative cationic concentration. Mutagenesis studies have improved our understanding of the role of the second transmembrane domain and the intracellular loop of the channel in ion selectivity. However, little is known about the influence that the extracellular domain (ECD) plays in ion permeation. In the α7 nAChR, it has been found that the ECD contains a ring of ten aspartates (two per subunit) that is believed to face the lumen of the pore and could attract cations for permeation. Using mutagenesis and a combination of electrophysiology and imaging techniques, we tested the possible involvement of these aspartate residues in the calcium permeability of the rat α7 nAChR. We found that one of these residues (the aspartate at position 44) appears to be essential since mutating it to alanine resulted in a decrease in amplitude for both whole cell and single-channel responses and in the complete disappearance of detectable calcium changes in most cells, which indicates that the ECD of the α7 nAChR plays a key role in calcium permeation.

A mutation in the extracellular domain of the α7 nAChR reduces calcium permeability

PubMed Central

Colón-Sáez, José O.

2013-01-01

The α7 neuronal nicotinic acetylcholine receptor (nAChR) displays the highest calcium permeability among the different subtypes of nAChRs expressed in the mammalian brain and can impact cellular events including neurotransmitter release, second messenger cascades, cell survival, and apoptosis. The selectivity for cations in nAChRs is thought to be achieved in part by anionic residues which are located on either side of the channel mouth and increase relative cationic concentration. Mutagenesis studies have improved our understanding of the role of the second transmembrane domain and the intracellular loop of the channel in ion selectivity. However, little is known about the influence that the extracellular domain (ECD) plays in ion permeation. In the α7 nAChR, it has been found that the ECD contains a ring of ten aspartates (two per subunit) that is believed to face the lumen of the pore and could attract cations for permeation. Using mutagenesis and a combination of electrophysiology and imaging techniques, we tested the possible involvement of these aspartate residues in the calcium permeability of the rat α7 nAChR. We found that one of these residues (the aspartate at position 44) appears to be essential since mutating it to alanine resulted in a decrease in amplitude for both whole cell and single-channel responses and in the complete disappearance of detectable calcium changes in most cells, which indicates that the ECD of the α7 nAChR plays a key role in calcium permeation. PMID:24177919

Neuropharmacological and neurochemical properties of N-(2-cyanoethyl)-2-phenylethylamine, a prodrug of 2-phenylethylamine.

PubMed Central

Baker, G. B.; Coutts, R. T.; Rao, T. S.

1987-01-01

1 N-(2-cyanoethyl)-2-phenylethylamine (CEPEA) was examined as a possible prodrug of 2-phenylethylamine (PEA). 2 Pharmacokinetics of PEA and CEPEA were investigated in rat brain, blood and liver by gas chromatography with electron-capture detection (GC-ECD). Interactions of PEA and CEPEA with putative neurotransmitter amines were investigated by use of high performance liquid chromatography with electrochemical detection (h.p.l.c.-e.c.). 3 Administration of PEA caused transient increases in PEA concentrations which decreased rapidly in brain and blood and at a slower rate in liver. Administration of CEPEA caused sustained elevations of PEA concentrations and elimination of PEA was markedly decreased in these tissues relative to the situation after administration of PEA itself. 4 Administration of CEPEA caused more prolonged decreases in brain noradrenaline, dopamine and 5-hydroxytryptamine concentrations than those observed after PEA administration, although values increased to control levels eventually. PMID:2890391

78 FR 37150 - Airworthiness Directives; Eurocopter Deutschland GmbH (ECD) Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-20

... Deutschland GmbH (ECD) Helicopters AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of...): Eurocopter Deutschland GmbH (ECD): Docket No. FAA-2013-0519; Directorate Identifier 2010-SW-068-AD. (a... European Aviation Safety Agency AD No. 2010-0128, dated June 25, 2010. (h) Subject Joint Aircraft Service...

78 FR 52412 - Airworthiness Directives; Eurocopter Deutschland GmbH (ECD) Helicopters

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2013-08-23

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Erdheim-Chester Disease Involving the Central Nervous System with the Unique Appearance of a Coated Vertebral Artery.

PubMed

Suzuki, Hime; Wanibuchi, Masahiko; Komatsu, Katsuya; Akiyama, Yukinori; Mikami, Takeshi; Sugita, Shintaro; Hasegawa, Tadashi; Kaya, Mitsunori; Takada, Kohichi; Mikuni, Nobuhiro

2016-10-01

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. It is characterized by multiple xanthogranulomatous masses throughout the body, predominantly in the tibia. One of the characteristic radiological findings of the lesions associated with ECD is a "coated artery," which is often observed in the aorta. Although approximately one-fourth of ECD cases involve the central nervous system (CNS), an intracranial-coated artery has only been reported in four cases. We report a case of ECD that involves the CNS and has the unique appearance of a coated vertebral artery (VA). These tumors entirely encase the bilateral VAs without stenosis and are attached to the dura. Cranial magnetic resonance imaging also showed multiple extra-axial tumors in the cavernous sinus, the frontal convexity, and the orbital cavity. Further investigation revealed additional extracranial lesions around the cervical carotid artery, at the bilateral tibia, and at the elbow joint. A biopsy of the cervical and tibial lesions confirmed ECD. Steroid therapy resulted in a month-long improvement of preoperative symptoms. However, the patient's condition gradually progressed and he died of pneumonia 1 year after ECD diagnosis. The encasement of the intracranial artery by the tumor without stenosis and the dural attachment suggest ECD, which requires whole body investigation.

Erdheim-Chester Disease Involving the Central Nervous System with the Unique Appearance of a Coated Vertebral Artery

PubMed Central

Suzuki, Hime; Wanibuchi, Masahiko; Komatsu, Katsuya; Akiyama, Yukinori; Mikami, Takeshi; Sugita, Shintaro; Hasegawa, Tadashi; Kaya, Mitsunori; Takada, Kohichi; Mikuni, Nobuhiro

2016-01-01

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. It is characterized by multiple xanthogranulomatous masses throughout the body, predominantly in the tibia. One of the characteristic radiological findings of the lesions associated with ECD is a “coated artery,” which is often observed in the aorta. Although approximately one-fourth of ECD cases involve the central nervous system (CNS), an intracranial-coated artery has only been reported in four cases. We report a case of ECD that involves the CNS and has the unique appearance of a coated vertebral artery (VA). These tumors entirely encase the bilateral VAs without stenosis and are attached to the dura. Cranial magnetic resonance imaging also showed multiple extra-axial tumors in the cavernous sinus, the frontal convexity, and the orbital cavity. Further investigation revealed additional extracranial lesions around the cervical carotid artery, at the bilateral tibia, and at the elbow joint. A biopsy of the cervical and tibial lesions confirmed ECD. Steroid therapy resulted in a month-long improvement of preoperative symptoms. However, the patient’s condition gradually progressed and he died of pneumonia 1 year after ECD diagnosis. The encasement of the intracranial artery by the tumor without stenosis and the dural attachment suggest ECD, which requires whole body investigation. PMID:28664013

Impact of a child stimulation intervention on early child development in rural Peru: a cluster randomised trial using a reciprocal control design.

PubMed

Hartinger, Stella Maria; Lanata, Claudio Franco; Hattendorf, Jan; Wolf, Jennyfer; Gil, Ana Isabel; Obando, Mariela Ortiz; Noblega, Magaly; Verastegui, Hector; Mäusezahl, Daniel

2017-03-01

Stimulation in early childhood can alleviate adverse effects of poverty. In a community-randomised trial, we implemented 2 home-based interventions, each serving as an attention control for the other. One group received an integrated household intervention package (IHIP), whereas the other group received an early child development (ECD) intervention. The primary objective of the study was to evaluate the effect of IHIP on diarrhoea and respiratory infections, the details of which are described elsewhere. Here, we present the impact of the ECD intervention on early childhood development indicators. In this non-blinded community-randomised trial, an ECD intervention, adapted from the Peruvian government's National Wawa Wasi ECD programme, was implemented in 25 rural Peruvian Andean communities. We enrolled 534 children aged 6-35 months, from 50 communities randomised 1:1 into ECD and IHIP communities. In ECD communities, trained fieldworkers instructed mothers every 3 weeks over the 12 months study, to stimulate and interact with their children and to use standard programme toys. IHIP communities received an improved stove and hygiene promotion. Using a nationally validated ECD evaluation instrument, all children were assessed at baseline and 12 months later for overall performance on age-specific developmental milestones which fall into 7 developmental domains. At baseline, ECD-group and IHIP-group children performed similarly in all domains. After 12 months, data from 258 ECD-group and 251 IHIP-group children could be analysed. The proportion of children scoring above the mean in their specific age group was significantly higher in the ECD group in all domains (range: 12-23%-points higher than IHIP group). We observed the biggest difference in fine motor skills (62% vs 39% scores above the mean, OR: 2.6, 95% CI 1.7 to 3.9). The home-based ECD intervention effectively improved child development overall across domains and separately by investigated domain. Home-based strategies could be a promising component of poverty alleviation programmes seeking to improve developmental outcomes among rural Peruvian children. ISRCTN28191222; results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Determination of the rCBF in the Amygdala and Rhinal Cortex Using a FAIR-TrueFISP Sequence

PubMed Central

Martirosian, Petros; Klose, Uwe; Nägele, Thomas; Schick, Fritz; Ernemann, Ulrike

2011-01-01

Objective Brain perfusion can be assessed non-invasively by modern arterial spin labeling MRI. The FAIR (flow-sensitive alternating inversion recovery)-TrueFISP (true fast imaging in steady precession) technique was applied for regional assessment of cerebral blood flow in brain areas close to the skull base, since this approach provides low sensitivity to magnetic susceptibility effects. The investigation of the rhinal cortex and the amygdala is a potentially important feature for the diagnosis and research on dementia in its early stages. Materials and Methods Twenty-three subjects with no structural or psychological impairment were investigated. FAIR-True-FISP quantitative perfusion data were evaluated in the amygdala on both sides and in the pons. A preparation of the radiofrequency FOCI (frequency offset corrected inversion) pulse was used for slice selective inversion. After a time delay of 1.2 sec, data acquisition began. Imaging slice thickness was 5 mm and inversion slab thickness for slice selective inversion was 12.5 mm. Image matrix size for perfusion images was 64 × 64 with a field of view of 256 × 256 mm, resulting in a spatial resolution of 4 × 4 × 5 mm. Repetition time was 4.8 ms; echo time was 2.4 ms. Acquisition time for the 50 sets of FAIR images was 6:56 min. Data were compared with perfusion data from the literature. Results Perfusion values in the right amygdala, left amygdala and pons were 65.2 (± 18.2) mL/100 g/minute, 64.6 (± 21.0) mL/100 g/minute, and 74.4 (± 19.3) mL/100 g/minute, respectively. These values were higher than formerly published data using continuous arterial spin labeling but similar to 15O-PET (oxygen-15 positron emission tomography) data. Conclusion The FAIR-TrueFISP approach is feasible for the quantitative assessment of perfusion in the amygdala. Data are comparable with formerly published data from the literature. The applied technique provided excellent image quality, even for brain regions located at the skull base in the vicinity of marked susceptibility steps. PMID:21927556

Effect of dexamethasone on gliosis, ischemia, and dopamine extraction during microdialysis sampling in brain tissue.

PubMed

Jaquins-Gerstl, Andrea; Shu, Zhan; Zhang, Jing; Liu, Yansheng; Weber, Stephen G; Michael, Adrian C

2011-10-15

Microdialysis sampling of the brain is an analytical technique with numerous applications in neuroscience and the neurointensive care of brain-injured human patients. Even so, implanting microdialysis probes into brain tissue causes a penetration injury that triggers gliosis (the activation and proliferation of glial cells) and ischemia (the interruption of blood flow). Thus, the probe samples injured tissue. Mitigating the effects of the penetration injury might refine the technique. The synthetic glucocorticoid dexamethasone is a potent anti-inflammatory and immunosuppressant substance. We performed microdialysis in the rat brain for 5 days, with and without dexamethasone in the perfusion fluid (10 μM for the first 24 h and 2 μM thereafter). On the first and fourth day of the perfusion, we performed dopamine no-net-flux measurements. On the fifth day, we sectioned and stained the brain tissue and examined it by fluorescence microscopy. Although dexamethasone profoundly inhibited gliosis and ischemia around the probe tracks it had only modest effects on dopamine no-net-flux results. These findings show that dexamethasone is highly effective at suppressing gliosis and ischemia but is limited in its neuroprotective activity. © 2011 American Chemical Society

Conjunctival microcirculatory blood flow is altered but not abolished in brain dead patients: a prospective observational study.

PubMed

Tamosuitis, Tomas; Pranskunas, Andrius; Balciuniene, Neringa; Pilvinis, Vidas; Boerma, E Christiaan

2016-07-11

The conjunctival microcirculation has potential as a window to cerebral perfusion due to related blood supply, close anatomical proximity and easy accessibility for microcirculatory imaging technique, such as sidestream dark field (SDF) imaging. Our study aims to evaluate conjunctival and sublingual microcirculation in brain dead patients and to compare it with healthy volunteers in two diametrically opposed conditions: full stop versus normal arterial blood supply to the brain. In a prospective observational study we analyzed conjunctival and sublingual microcirculation using SDF imaging in brain dead patients after reaching systemic hemodynamic targets to optimize perfusion of donor organs, and in healthy volunteers. All brain death diagnoses were confirmed by cerebral angiography. Microcirculatory images were obtained and analyzed using standardized published recommendations. Study registered at ClinicalTrials.gov, number NCT02483273. Eleven brain dead patients and eleven apparently healthy controls were enrolled in the study. Microvascular flow index (MFI) of small vessels was significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (2.7 [2.4-2.9] vs. 3.0 [2.9-3.0], p = 0.01) and in sublingual mucosa (2.8 [2.6-2.9] vs. 3.0 [2.9-3.0], p = 0.02). Total vessel density (TVD) and perfused vessel density (PVD) of small vessels were significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (10.2 [6.6-14.8] vs. 18.0 [18.0-25.4] mm/mm(2), p = 0.001 and 5.0 [3.5-7.3] vs. 10.9 [10.9-13.5] 1/mm, p = 0.001), but not in sublingual mucosa. In comparison to healthy controls brain dead patients had a significant reduction in conjunctival microvascular blood flow and density. However, the presence of conjunctival flow in case general cerebral flow is completely absent makes it impossible to use the conjunctival microcirculation as a substitute for brain flow, and further research should focus on the link between the ocular microcirculation, intracranial pressure and alternative ocular circulation.

Comparison of manual & automated analysis methods for corneal endothelial cell density measurements by specular microscopy.

PubMed

Huang, Jianyan; Maram, Jyotsna; Tepelus, Tudor C; Modak, Cristina; Marion, Ken; Sadda, SriniVas R; Chopra, Vikas; Lee, Olivia L

2017-08-07

To determine the reliability of corneal endothelial cell density (ECD) obtained by automated specular microscopy versus that of validated manual methods and factors that predict such reliability. Sharp central images from 94 control and 106 glaucomatous eyes were captured with Konan specular microscope NSP-9900. All images were analyzed by trained graders using Konan CellChek Software, employing the fully- and semi-automated methods as well as Center Method. Images with low cell count (input cells number <100) and/or guttata were compared with the Center and Flex-Center Methods. ECDs were compared and absolute error was used to assess variation. The effect on ECD of age, cell count, cell size, and cell size variation was evaluated. No significant difference was observed between the Center and Flex-Center Methods in corneas with guttata (p=0.48) or low ECD (p=0.11). No difference (p=0.32) was observed in ECD of normal controls <40 yrs old between the fully-automated method and manual Center Method. However, in older controls and glaucomatous eyes, ECD was overestimated by the fully-automated method (p=0.034) and semi-automated method (p=0.025) as compared to manual method. Our findings show that automated analysis significantly overestimates ECD in the eyes with high polymegathism and/or large cell size, compared to the manual method. Therefore, we discourage reliance upon the fully-automated method alone to perform specular microscopy analysis, particularly if an accurate ECD value is imperative. Copyright © 2017. Published by Elsevier España, S.L.U.

Differentiating radiation necrosis from tumor progression in brain metastases treated with stereotactic radiotherapy: utility of intravoxel incoherent motion perfusion MRI and correlation with histopathology.

PubMed

Detsky, Jay S; Keith, Julia; Conklin, John; Symons, Sean; Myrehaug, Sten; Sahgal, Arjun; Heyn, Chinthaka C; Soliman, Hany

2017-09-01

Radiation necrosis is a serious potential adverse event of stereotactic radiosurgery that cannot be reliably differentiated from recurrent tumor using conventional imaging techniques. Intravoxel incoherent motion (IVIM) is a magnetic resonance imaging (MRI) based method that uses a diffusion-weighted sequence to estimate quantitative perfusion and diffusion parameters. This study evaluated the IVIM-derived apparent diffusion coefficient (ADC) and perfusion fraction (f), and compared the results to the gold standard histopathological-defined outcomes of radiation necrosis or recurrent tumor. Nine patients with ten lesions were included in this study; all lesions exhibited radiographic progression after stereotactic radiosurgery for brain metastases that subsequently underwent surgical resection due to uncertainty regarding the presence of radiation necrosis versus recurrent tumor. Pre-surgical IVIM was performed to obtain f and ADC values and the results were compared to histopathology. Five lesions exhibited pathological radiation necrosis and five had predominantly recurrent tumor. The IVIM perfusion fraction reliably differentiated tumor recurrence from radiation necrosis (f mean  = 10.1 ± 0.7 vs. 8.3 ± 1.2, p = 0.02; cutoff value of 9.0 yielding a sensitivity/specificity of 100%/80%) while the ADC did not distinguish between the two (ADC mean  = 1.1 ± 0.2 vs. 1.2 ± 0.4, p = 0.6). IVIM shows promise in differentiating recurrent tumor from radiation necrosis for brain metastases treated with radiosurgery, but needs to be validated in a larger cohort.

Head-to-Head Visual Comparison between Brain Perfusion SPECT and Arterial Spin-Labeling MRI with Different Postlabeling Delays in Alzheimer Disease.

PubMed

Kaneta, T; Katsuse, O; Hirano, T; Ogawa, M; Yoshida, K; Odawara, T; Hirayasu, Y; Inoue, T

2017-08-01

Arterial spin-labeling MR imaging has been recently developed as a noninvasive technique with magnetically labeled arterial blood water as an endogenous contrast medium for the evaluation of CBF. Our aim was to compare arterial spin-labeling MR imaging and SPECT in the visual assessment of CBF in patients with Alzheimer disease. In 33 patients with Alzheimer disease or mild cognitive impairment due to Alzheimer disease, CBF images were obtained by using both arterial spin-labeling-MR imaging with a postlabeling delay of 1.5 seconds and 2.5 seconds (PLD 1.5 and PLD 2.5 , respectively) and brain perfusion SPECT. Twenty-two brain regions were visually assessed, and the diagnostic confidence of Alzheimer disease was recorded. Among all arterial spin-labeling images, 84.9% of PLD 1.5 and 9% of PLD 2.5 images showed the typical pattern of advanced Alzheimer disease (ie, decreased CBF in the bilateral parietal, temporal, and frontal lobes). PLD 1.5 , PLD 2.5 , and SPECT imaging resulted in obviously different visual assessments. PLD 1.5 showed a broad decrease in CBF, which could have been due to an early perfusion. In contrast, PLD 2.5 did not appear to be influenced by an early perfusion but showed fewer pathologic findings than SPECT. The distinctions observed by us should be carefully considered in the visual assessments of Alzheimer disease. Further studies are required to define the patterns of change in arterial spin-labeling-MR imaging associated with Alzheimer disease. © 2017 by American Journal of Neuroradiology.

Beyond the basics: brain injuries.

PubMed

Duncan, Tim; Krost, William S; Mistovich, Joseph J; Limmer, Daniel

2007-07-01

Increased intracranial pressure can be a catastrophic event that may lead to death or permanent disability. Without prompt recognition and reversal of hypoxia, hypotension, hypercarbia, acidosis and increased intracranial pressure, the cerebral blood flow and resultant cerebral perfusion can be inadequate, leading to an exacerbation of secondary brain injury.

Evaluation of Brain Nuclear Medicine Imaging Tracers in a Murine Model of Sepsis-Associated Encephalopathy.

PubMed

Szöllősi, Dávid; Hegedűs, Nikolett; Veres, Dániel S; Futó, Ildikó; Horváth, Ildikó; Kovács, Noémi; Martinecz, Bernadett; Dénes, Ádám; Seifert, Daniel; Bergmann, Ralf; Lebeda, Ondřej; Varga, Zoltán; Kaleta, Zoltán; Szigeti, Krisztián; Máthé, Domokos

2018-05-07

The purpose of this study was to evaluate a set of widely used nuclear medicine imaging agents as possible methods to study the early effects of systemic inflammation on the living brain in a mouse model of sepsis-associated encephalopathy (SAE). The lipopolysaccharide (LPS)-induced murine systemic inflammation model was selected as a model of SAE. C57BL/6 mice were used. A multimodal imaging protocol was carried out on each animal 4 h following the intravenous administration of LPS using the following tracers: [ 99m Tc][2,2-dimethyl-3-[(3E)-3-oxidoiminobutan-2-yl]azanidylpropyl]-[(3E)-3-hydroxyiminobutan-2-yl]azanide ([ 99m Tc]HMPAO) and ethyl-7-[ 125 I]iodo-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate ([ 125 I]iomazenil) to measure brain perfusion and neuronal damage, respectively; 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) to measure cerebral glucose uptake. We assessed microglia activity on another group of mice using 2-[6-chloro-2-(4-[ 125 I]iodophenyl)-imidazo[1,2-a]pyridin-3-yl]-N-ethyl-N-methyl-acetamide ([ 125 I]CLINME). Radiotracer uptakes were measured in different brain regions and correlated. Microglia activity was also assessed using immunohistochemistry. Brain glutathione levels were measured to investigate oxidative stress. Significantly reduced perfusion values and significantly enhanced [ 18 F]FDG and [ 125 I]CLINME uptake was measured in the LPS-treated group. Following perfusion compensation, enhanced [ 125 I]iomazenil uptake was measured in the LPS-treated group's hippocampus and cerebellum. In this group, both [ 18 F]FDG and [ 125 I]iomazenil uptake showed highly negative correlation to perfusion measured with ([ 99m Tc]HMPAO uptake in all brain regions. No significant differences were detected in brain glutathione levels between the groups. The CD45 and P2Y12 double-labeling immunohistochemistry showed widespread microglia activation in the LPS-treated group. Our results suggest that [ 125 I]CLINME and [ 99m Tc]HMPAO SPECT can be used to detect microglia activation and brain hypoperfusion, respectively, in the early phase (4 h post injection) of systemic inflammation. We suspect that the enhancement of [ 18 F]FDG and [ 125 I]iomazenil uptake in the LPS-treated group does not necessarily reflect neural hypermetabolism and the lack of neuronal damage. They are most likely caused by processes emerging during neuroinflammation, e.g., microglia activation and/or immune cell infiltration.

Intravascular perfusion of carbon black ink allows reliable visualization of cerebral vessels.

PubMed

Hasan, Mohammad R; Herz, Josephine; Hermann, Dirk M; Doeppner, Thorsten R

2013-01-04

The anatomical structure of cerebral vessels is a key determinant for brain hemodynamics as well as the severity of injury following ischemic insults. The cerebral vasculature dynamically responds to various pathophysiological states and it exhibits considerable differences between strains and under conditions of genetic manipulations. Essentially, a reliable technique for intracranial vessel staining is essential in order to study the pathogenesis of ischemic stroke. Until recently, a set of different techniques has been employed to visualize the cerebral vasculature including injection of low viscosity resin, araldite F, gelatin mixed with various dyes (i.e. carmine red, India ink) or latex with or without carbon black. Perfusion of white latex compound through the ascending aorta has been first reported by Coyle and Jokelainen. Maeda et al. have modified the protocol by adding carbon black ink to the latex compound for improved contrast visualization of the vessels after saline perfusion of the brain. However, inefficient perfusion and inadequate filling of the vessels are frequently experienced due to high viscosity of the latex compound. Therefore, we have described a simple and cost-effective technique using a mixture of two commercially available carbon black inks (CB1 and CB2) to visualize the cerebral vasculature in a reproducible manner. We have shown that perfusion with CB1+CB2 in mice results in staining of significantly smaller cerebral vessels at a higher density in comparison to latex perfusion. Here, we describe our protocol to identify the anastomotic points between the anterior (ACA) and middle cerebral arteries (MCA) to study vessel variations in mice with different genetic backgrounds. Finally, we demonstrate the feasibility of our technique in a transient focal cerebral ischemia model in mice by combining CB1+CB2-mediated vessel staining with TTC staining in various degrees of ischemic injuries.

Rescuing Perishable Neuroanatomical Information from a Threatened Biodiversity Hotspot: Remote Field Methods for Brain Tissue Preservation Validated by Cytoarchitectonic Analysis, Immunohistochemistry, and X-Ray Microcomputed Tomography.

PubMed

Hughes, Daniel F; Walker, Ellen M; Gignac, Paul M; Martinez, Anais; Negishi, Kenichiro; Lieb, Carl S; Greenbaum, Eli; Khan, Arshad M

2016-01-01

Biodiversity hotspots, which harbor more endemic species than elsewhere on Earth, are increasingly threatened. There is a need to accelerate collection efforts in these regions before threatened or endangered species become extinct. The diverse geographical, ecological, genetic, morphological, and behavioral data generated from the on-site collection of an individual specimen are useful for many scientific purposes. However, traditional methods for specimen preparation in the field do not permit researchers to retrieve neuroanatomical data, disregarding potentially useful data for increasing our understanding of brain diversity. These data have helped clarify brain evolution, deciphered relationships between structure and function, and revealed constraints and selective pressures that provide context about the evolution of complex behavior. Here, we report our field-testing of two commonly used laboratory-based techniques for brain preservation while on a collecting expedition in the Congo Basin and Albertine Rift, two poorly known regions associated with the Eastern Afromontane biodiversity hotspot. First, we found that transcardial perfusion fixation and long-term brain storage, conducted in remote field conditions with no access to cold storage laboratory equipment, had no observable impact on cytoarchitectural features of lizard brain tissue when compared to lizard brain tissue processed under laboratory conditions. Second, field-perfused brain tissue subjected to prolonged post-fixation remained readily compatible with subsequent immunohistochemical detection of neural antigens, with immunostaining that was comparable to that of laboratory-perfused brain tissue. Third, immersion-fixation of lizard brains, prepared under identical environmental conditions, was readily compatible with subsequent iodine-enhanced X-ray microcomputed tomography, which facilitated the non-destructive imaging of the intact brain within its skull. In summary, we have validated multiple approaches to preserving intact lizard brains in remote field conditions with limited access to supplies and a high degree of environmental exposure. This protocol should serve as a malleable framework for researchers attempting to rescue perishable and irreplaceable morphological and molecular data from regions of disappearing biodiversity. Our approach can be harnessed to extend the numbers of species being actively studied by the neuroscience community, by reducing some of the difficulty associated with acquiring brains of animal species that are not readily available in captivity.

Rescuing Perishable Neuroanatomical Information from a Threatened Biodiversity Hotspot: Remote Field Methods for Brain Tissue Preservation Validated by Cytoarchitectonic Analysis, Immunohistochemistry, and X-Ray Microcomputed Tomography

PubMed Central

Hughes, Daniel F.; Walker, Ellen M.; Gignac, Paul M.; Martinez, Anais; Negishi, Kenichiro; Lieb, Carl S.; Greenbaum, Eli

2016-01-01

Biodiversity hotspots, which harbor more endemic species than elsewhere on Earth, are increasingly threatened. There is a need to accelerate collection efforts in these regions before threatened or endangered species become extinct. The diverse geographical, ecological, genetic, morphological, and behavioral data generated from the on-site collection of an individual specimen are useful for many scientific purposes. However, traditional methods for specimen preparation in the field do not permit researchers to retrieve neuroanatomical data, disregarding potentially useful data for increasing our understanding of brain diversity. These data have helped clarify brain evolution, deciphered relationships between structure and function, and revealed constraints and selective pressures that provide context about the evolution of complex behavior. Here, we report our field-testing of two commonly used laboratory-based techniques for brain preservation while on a collecting expedition in the Congo Basin and Albertine Rift, two poorly known regions associated with the Eastern Afromontane biodiversity hotspot. First, we found that transcardial perfusion fixation and long-term brain storage, conducted in remote field conditions with no access to cold storage laboratory equipment, had no observable impact on cytoarchitectural features of lizard brain tissue when compared to lizard brain tissue processed under laboratory conditions. Second, field-perfused brain tissue subjected to prolonged post-fixation remained readily compatible with subsequent immunohistochemical detection of neural antigens, with immunostaining that was comparable to that of laboratory-perfused brain tissue. Third, immersion-fixation of lizard brains, prepared under identical environmental conditions, was readily compatible with subsequent iodine-enhanced X-ray microcomputed tomography, which facilitated the non-destructive imaging of the intact brain within its skull. In summary, we have validated multiple approaches to preserving intact lizard brains in remote field conditions with limited access to supplies and a high degree of environmental exposure. This protocol should serve as a malleable framework for researchers attempting to rescue perishable and irreplaceable morphological and molecular data from regions of disappearing biodiversity. Our approach can be harnessed to extend the numbers of species being actively studied by the neuroscience community, by reducing some of the difficulty associated with acquiring brains of animal species that are not readily available in captivity. PMID:27196138

Voxel-level comparison of arterial spin-labeled perfusion magnetic resonance imaging in adolescents with internet gaming addiction

PubMed Central

2013-01-01

Background Although recent studies have clearly demonstrated functional and structural abnormalities in adolescents with internet gaming addiction (IGA), less is known about how IGA affects perfusion in the human brain. We used pseudocontinuous arterial spin-labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) to measure the effects of IGA on resting brain functions by comparing resting cerebral blood flow in adolescents with IGA and normal subjects. Methods Fifteen adolescents with IGA and 18 matched normal adolescents underwent structural and perfusion fMRI in the resting state. Direct subtraction, voxel-wise general linear modeling was performed to compare resting cerebral blood flow (CBF) between the 2 groups. Correlations were calculated between the mean CBF value in all clusters that survived AlphaSim correction and the Chen Internet Addiction Scale (CIAS) scores, Barratt Impulsiveness Scale-11 (BIS-11) scores, or hours of Internet use per week (hours) in the 15 subjects with IGA. Results Compared with control subjects, adolescents with IGA showed significantly higher global CBF in the left inferior temporal lobe/fusiform gyrus, left parahippocampal gyrus/amygdala, right medial frontal lobe/anterior cingulate cortex, left insula, right insula, right middle temporal gyrus, right precentral gyrus, left supplementary motor area, left cingulate gyrus, and right inferior parietal lobe. Lower CBF was found in the left middle temporal gyrus, left middle occipital gyrus, and right cingulate gyrus. There were no significant correlations between mean CBF values in all clusters that survived AlphaSim correction and CIAS or BIS-11 scores or hours of Internet use per week. Conclusions In this study, we used ASL perfusion fMRI and noninvasively quantified resting CBF to demonstrate that IGA alters the CBF distribution in the adolescent brain. The results support the hypothesis that IGA is a behavioral addiction that may share similar neurobiological abnormalities with other addictive disorders. PMID:23937918

Epidemiology of Kidney Discard from Expanded Criteria Donors Undergoing Donation after Circulatory Death.

PubMed

Singh, Sunita K; Kim, S Joseph

2016-02-05

The broader use of combined expanded criteria donor and donation after circulatory death (ECD/DCD) kidneys may help expand the deceased donor pool. The purpose of our study was to evaluate discard rates of kidneys from ECD/DCD donors and factors associated with discard. ECD/DCD donors and kidneys were evaluated from January 1, 2000 to March 31, 2011 using data from the Scientific Registry of Transplant Recipients. The kidney donor risk index was calculated for all ECD/DCD kidneys. Multivariable logistic regression models were used to determine risk factors for discarding both donor kidneys. The Kaplan-Meier product limit method and the log-rank statistic were used to assess the cumulative probability of graft failure for transplants from ECD/DCD donors where the mate kidney was discarded versus both kidneys were used. There were 896 ECD/DCD donors comprising 1792 kidneys. Both kidneys were discarded in 44.5% of donors, whereas 51.0% of all available kidneys were discarded. The kidney donor risk index scores were higher among donors of discarded versus transplanted kidneys (median, 1.82; interquartile range, 1.60, 2.07 versus median, 1.67; interquartile range, 1.49, 1.87, respectively; P<0.001); however, the distributions showed considerable overlap. The adjusted odds ratios for discard were higher among donors who were older, diabetic, AB blood type, and hepatitis C positive. The cumulative probabilities of total graft failure at 1, 3, and 5 years were 17.3%, 36.5%, and 55.4% versus 13.8%, 24.7%, and 40.5% among kidneys from donors where only one versus both kidneys were transplanted, respectively (log rank P=0.04). Our study shows a significantly higher discard rate for ECD/DCD kidneys versus prior reports. Some discarded ECD/DCD kidneys may be acceptable for transplantation. Additional studies are needed to evaluate the factors that influence decision making around the use of ECD/DCD kidneys. Copyright © 2016 by the American Society of Nephrology.

Modeling the Sustainability of a Ceramic Water Filter Intervention

PubMed Central

Mellor, Jonathan; Abebe, Lydia; Ehdaie, Beeta; Dillingham, Rebecca; Smith, James

2014-01-01

Ceramic water filters (CWFs) are a point-of-use water treatment technology that has shown promise in preventing early childhood diarrhea (ECD) in resource-limited settings. Despite this promise, some researchers have questioned their ability to reduce ECD incidences over the long term since most effectiveness trials conducted to date are less than one year in duration limiting their ability to assess long-term sustainability factors. Most trials also suffer from lack of blinding making them potentially biased. This study uses an agent-based model (ABM) to explore factors related to the long-term sustainability of CWFs in preventing ECD and was based on a three year longitudinal field study. Factors such as filter user compliance, microbial removal effectiveness, filter cleaning and compliance declines were explored. Modeled results indicate that broadly defined human behaviors like compliance and declining microbial effectiveness due to improper maintenance are primary drivers of the outcome metrics of household drinking water quality and ECD rates. The model predicts that a ceramic filter intervention can reduce ECD incidence amongst under two year old children by 41.3%. However, after three years, the average filter is almost entirely ineffective at reducing ECD incidence due to declining filter microbial removal effectiveness resulting from improper maintenance. The model predicts very low ECD rates are possible if compliance rates are 80-90%, filter log reduction efficiency is 3 or greater and there are minimal long-term compliance declines. Cleaning filters at least once every 4 months makes it more likely to achieve very low ECD rates as does the availability of replacement filters for purchase. These results help to understand the heterogeneity seen in previous intervention-control trials and reemphasize the need for researchers to accurately measure confounding variables and ensure that field trials are at least 2-3 years in duration. In summary, the CWF can be a highly effective tool in the fight against ECD, but every effort should be made by implementing agencies to ensure consistent use and maintenance. PMID:24355289

Preoperative serum HER2 extracellular domain levels in primary invasive breast cancer.

PubMed

Lee, Sae Byul; Lee, Jong Won; Yu, Jong Han; Ko, Beom Seok; Kim, Hee Jeong; Son, Byung Ho; Gong, Gyungyub; Lee, Hee Jin; Kim, Sung-Bae; Jung, Kyung Hae; Ahn, Jin-Hee; Lee, Woochang; Sung, Joohon; Ahn, Sei-Hyun

2014-12-10

Despite the preclinical outcomes and biologic significance of the presence of the human epidermal growth factor receptor-2 (HER2) extracellular domain (ECD), there is little evidence supporting the measurement of ECD levels in any clinical setting. The aim of this study was to determine the prevalence of elevated serum HER2 ECD levels, the association between these levels and tissue HER2 overexpression, and the potential clinical prognostic value of HER2 ECD in primary invasive breast cancer. Serum HER2 ECD levels were examined preoperatively in 2,862 consecutive stage I-III primary breast cancer patients between 2007 and 2009. Serum HER2 ECD levels were measured by chemiluminescence immunoassay (ADVIA Centaur), and the tissue HER2 status was assessed by immunohistochemistry and fluorescence in situ hybridization. The cutoff value for the serum level of HER2 ECD was set at 15.2 ng/ml. Among the 2,862 patients, 126 (4.4%) had elevated serum HER2 ECD levels, and HER2 was overexpressed in the tumor tissue of 692 patients (24.2%), with a concordance of 78.7%. Multivariate analysis revealed that elevated serum HER2 ECD was a significant independent prognostic factor for worse distant-metastasis-free survival [DMFS; hazard ratio (HR) = 2.50, 95% confidence interval (CI) = 1.5-4.3, P = 0.001] and breast-cancer-specific survival (BCSS; HR = 2.0, 95% CI = 1.1-3.8, P = 0.036), which were much stronger in patients with tissue HER2-positive tumors (DMFS: HR = 3.8, 95% CI = 2.0-7.0, P < 0.001; BCSS: HR = 2.6, 95% CI = 1.2-5.3, P = 0.012). Given the prevalence of HER2 expression, its measurement as an independent prognostic factor can be clinically useful, particularly in patients with tissue HER2-positive tumors.

Epidemiology of Kidney Discard from Expanded Criteria Donors Undergoing Donation after Circulatory Death

PubMed Central

Singh, Sunita K.

2016-01-01

Background and objectives The broader use of combined expanded criteria donor and donation after circulatory death (ECD/DCD) kidneys may help expand the deceased donor pool. The purpose of our study was to evaluate discard rates of kidneys from ECD/DCD donors and factors associated with discard. Design, setting, participants, & measurements ECD/DCD donors and kidneys were evaluated from January 1, 2000 to March 31, 2011 using data from the Scientific Registry of Transplant Recipients. The kidney donor risk index was calculated for all ECD/DCD kidneys. Multivariable logistic regression models were used to determine risk factors for discarding both donor kidneys. The Kaplan–Meier product limit method and the log-rank statistic were used to assess the cumulative probability of graft failure for transplants from ECD/DCD donors where the mate kidney was discarded versus both kidneys were used. Results There were 896 ECD/DCD donors comprising 1792 kidneys. Both kidneys were discarded in 44.5% of donors, whereas 51.0% of all available kidneys were discarded. The kidney donor risk index scores were higher among donors of discarded versus transplanted kidneys (median, 1.82; interquartile range, 1.60, 2.07 versus median, 1.67; interquartile range, 1.49, 1.87, respectively; P<0.001); however, the distributions showed considerable overlap. The adjusted odds ratios for discard were higher among donors who were older, diabetic, AB blood type, and hepatitis C positive. The cumulative probabilities of total graft failure at 1, 3, and 5 years were 17.3%, 36.5%, and 55.4% versus 13.8%, 24.7%, and 40.5% among kidneys from donors where only one versus both kidneys were transplanted, respectively (log rank P=0.04). Conclusions Our study shows a significantly higher discard rate for ECD/DCD kidneys versus prior reports. Some discarded ECD/DCD kidneys may be acceptable for transplantation. Additional studies are needed to evaluate the factors that influence decision making around the use of ECD/DCD kidneys. PMID:26668028

Relation between brain temperature and white matter damage in subacute carbon monoxide poisoning

PubMed Central

Fujiwara, Shunrou; Yoshioka, Yoshichika; Matsuda, Tsuyoshi; Nishimoto, Hideaki; Ogawa, Akira; Ogasawara, Kuniaki; Beppu, Takaaki

2016-01-01

In the previous studies, carbon monoxide (CO) poisoning showed an imbalance between cerebral perfusion and metabolism in the acute phase and the brain temperature (BT) in these patients remained abnormally high from the acute to the subacute phase. As observed in chronic ischemic patients, BT can continuously remain high depending on impairments of cerebral blood flow and metabolism; this is because heat removal and production system in the brain may mainly be maintained by the balance of these two factors; thus, cerebral white matter damage (WMD) affecting normal metabolism may affect the BT in patients with CO poisoning. Here, we investigated whether the BT correlates with the degree of WMD in patients with subacute CO-poisoning. In 16 patients with subacute CO-poisoning, the BT and degree of WMD were quantitatively measured by using magnetic resonance spectroscopy and the fractional anisotropy (FA) value from diffusion tensor imaging dataset. Consequently, the BT significantly correlated with the degree of WMD. In particular, BT observed in patients with delayed neuropsychiatric sequelae, a crucial symptom with sudden-onset in the chronic phase after CO exposure, might indicate cerebral hypo-metabolism and abnormal hemodynamics like “matched perfusion,” in which the reduced perfusion matches the reduced metabolism. PMID:27819312

A computational model of oxygen transport in the cerebrocapillary levels for normal and pathologic brain function.

PubMed

Safaeian, Navid; David, Tim

2013-10-01

The oxygen exchange and correlation between the cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMRO2) in the cortical capillary levels for normal and pathologic brain functions remain the subject of debate. A 3D realistic mesoscale model of the cortical capillary network (non-tree like) is constructed using a random Voronoi tessellation in which each edge represents a capillary segment. The hemodynamics and oxygen transport are numerically simulated in the model, which involves rheological laws in the capillaries, oxygen diffusion, and non-linear binding of oxygen to hemoglobin, respectively. The findings show that the cerebral hypoxia due to a significant decreased perfusion (as can occur in stroke) can be avoided by a moderate reduction in oxygen demand. Oxygen extraction fraction (OEF) can be an important indicator for the brain oxygen metabolism under normal perfusion and misery-perfusion syndrome (leading to ischemia). The results demonstrated that a disproportionately large increase in blood supply is required for a small increase in the oxygen demand, which, in turn, is strongly dependent on the resting OEF. The predicted flow-metabolism coupling in the model supports the experimental studies of spatiotemporal stimulations in humans by positron emission tomography and functional magnetic resonance imaging.

Intracranial pressure and cerebral perfusion pressure in patients developing brain death.

PubMed

Salih, Farid; Holtkamp, Martin; Brandt, Stephan A; Hoffmann, Olaf; Masuhr, Florian; Schreiber, Stephan; Weissinger, Florian; Vajkoczy, Peter; Wolf, Stefan

2016-08-01

We investigated whether a critical rise of intracranial pressure (ICP) leading to a loss of cerebral perfusion pressure (CPP) could serve as a surrogate marker of brain death (BD). We retrospectively analyzed ICP and CPP of patients in whom BD was diagnosed (n = 32, 16-79 years). Intracranial pressure and CPP were recorded using parenchymal (n = 27) and ventricular probes (n = 5). Data were analyzed from admission until BD was diagnosed. Intracranial pressure was severely elevated (mean ± SD, 95.5 ± 9.8 mm Hg) in all patients when BD was diagnosed. In 28 patients, CPP was negative at the time of diagnosis (-8.2 ± 6.5 mm Hg). In 4 patients (12.5%), CPP was reduced but not negative. In these patients, minimal CPP was 4 to 18 mm Hg. In 1 patient, loss of CPP occurred 4 hours before apnea completed the BD syndrome. Brain death was universally preceded by a severe reduction of CPP, supporting loss of cerebral perfusion as a critical step in BD development. Our data show that a negative CPP is neither sufficient nor a prerequisite to diagnose BD. In BD cases with positive CPP, we speculate that arterial blood pressure dropped below a critical closing pressure, thereby causing cessation of cerebral blood flow. Copyright © 2016 Elsevier Inc. All rights reserved.

SPECT assessment of brain activation induced by caffeine: no effect on areas involved in dependence

PubMed Central

Nehlig, Astrid; Armspach, Jean-Paul; Namer, Izzie J.

2010-01-01

Caffeine is not considered addictive, and in animals it does not trigger metabolic increases or dopamine release in brain areas involved in reinforcement and reward. Our objective was to measure caffeine effects on cerebral perfusion in humans using single photon emission computed tomography, with a specific focus on areas of reinforcement and reward. Two groups of nonsmoking subjects were studied, one with a low (8 subjects) and one with a high (6 subjects) daily coffee consumption. The subjects ingested 3 mg/kg caffeine or placebo in a raspberry-tasting drink, and scans were performed 45 min after ingestion. A control group of 12 healthy volunteers receiving no drink was also studied. Caffeine consumption led to a generalized, statistically nonsignificant perfusion decrease of 6% to 8%, comparable in low and high consumers. Compared with controls, low consumers displayed neuronal activation bilaterally in inferior frontal gyrusanterior insular cortex and uncus, left internal parietal cortex, right lingual gyrus, and cerebellum. In high consumers, brain activation occurred bilaterally only in hypothalamus. Thus, on a background of widespread low-amplitude perfusion decrease, caffeine activates a few regions mainly involved in the control of vigilance, anxiety, and cardiovascular regulation, but does not affect areas involved in reinforcing and reward. PMID:20623930

A computational model of oxygen transport in the cerebrocapillary levels for normal and pathologic brain function

PubMed Central

Safaeian, Navid; David, Tim

2013-01-01

The oxygen exchange and correlation between the cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMRO2) in the cortical capillary levels for normal and pathologic brain functions remain the subject of debate. A 3D realistic mesoscale model of the cortical capillary network (non-tree like) is constructed using a random Voronoi tessellation in which each edge represents a capillary segment. The hemodynamics and oxygen transport are numerically simulated in the model, which involves rheological laws in the capillaries, oxygen diffusion, and non-linear binding of oxygen to hemoglobin, respectively. The findings show that the cerebral hypoxia due to a significant decreased perfusion (as can occur in stroke) can be avoided by a moderate reduction in oxygen demand. Oxygen extraction fraction (OEF) can be an important indicator for the brain oxygen metabolism under normal perfusion and misery-perfusion syndrome (leading to ischemia). The results demonstrated that a disproportionately large increase in blood supply is required for a small increase in the oxygen demand, which, in turn, is strongly dependent on the resting OEF. The predicted flow-metabolism coupling in the model supports the experimental studies of spatiotemporal stimulations in humans by positron emission tomography and functional magnetic resonance imaging. PMID:23921901

SPECT assessment of brain activation induced by caffeine: no effect on areas involved in dependence.

PubMed

Nehlig, Astrid; Armspach, Jean-Paul; Namer, Izzie J

2010-01-01

Caffeine is not considered addictive, and in animals it does not trigger metabolic increases or dopamine release in brain areas involved in reinforcement and reward. Our objective was to measure caffeine effects on cerebral perfusion in humans using single photon emission computed tomography with a specific focus on areas of reinforcement and reward. Two groups of nonsmoking subjects were studied, one with a low (8 subjects) and one with a high (6 subjects) daily coffee consumption. The subjects ingested 3 mg/kg caffeine or placebo in a raspberry-tasting drink, and scans were performed 45 min after ingestion. A control group of 12 healthy volunteers receiving no drink was also studied. Caffeine consumption led to a generalized, statistically nonsignificant perfusion decrease of 6% to 8%, comparable in low and high consumers. Compared with controls, low consumers displayed neuronal activation bilaterally in inferior frontal gyrus-anterior insular cortex and uncus, left internal parietal cortex, right lingual gyrus, and cerebellum. In high consumers, brain activation occurred bilaterally only in hypothalamus. Thus, on a background of widespread low-amplitude perfusion decrease, caffeine activates a few regions mainly involved in the control of vigilance, anxiety, and cardiovascular regulation, but does not affect areas involved in reinforcing and reward.

SPECT study of low intensity He-Ne laser intravascular irradiation therapy for brain infarction

NASA Astrophysics Data System (ADS)

Xiao, Xue-Chang; Dong, Jia-Zheng; Chu, Xiao-Fan; Jia, Shao-Wei; Liu, Timon C.; Jiao, Jian-Ling; Zheng, Xi-Yuan; Zhou, Ci-Xiong

2003-12-01

We used single photon emission computed tomography (SPECT) in brain perfusion imaging to study the changes of regional cerebral blood flow (rCBF) and cerebral function in brain infarction patients treated with intravascular laser irradiation of blood (ILIB). 17 of 35 patients with brain infarction were admitted to be treated by ILIB on the base of standard drug therapy, and SPECT brain perfusion imaging was performed before and after ILIB therapy with self-comparison. The results were analyzed in quantity with brain blood flow function change rate (BFCR%) model. Effect of ILIB during the therapy process in the other 18 patients were also observed. In the 18 patients, SPECT indicated an improvement of rCBF (both in focus and in total brain) and cerebral function after a 30 min-ILIB therapy. And the 17 patients showed an enhancement of total brain rCBF and cerebral function after ILIB therapy in comparison with that before, especially for the focus side of the brain. The enhancement for focus itself was extremely obvious with a higher significant difference (P<0.0001). The mirror regions had no significant change (P>0.05). BFCR% of foci was prominently higher than that of mirror regions (P<0.0001). In conclusion, the ILIB therapy can improve rCBF and cerebral function and activate brain cells of patients with brain infarction. The results denote new evidence of ILIB therapy for those patients with cerebral ischemia.

Mechanistic Study on Electron Capture Dissociation of the Oligosaccharide-Mg2+ Complex

NASA Astrophysics Data System (ADS)

Huang, Yiqun; Pu, Yi; Yu, Xiang; Costello, Catherine E.; Lin, Cheng

2014-08-01

Electron capture dissociation (ECD) has shown great potential in structural characterization of glycans. However, our current understanding of the glycan ECD process is inadequate for accurate interpretation of the complex glycan ECD spectra. Here, we present the first comprehensive theoretical investigation on the ECD fragmentation behavior of metal-adducted glycans, using the cellobiose-Mg2+ complex as the model system. Molecular dynamics simulation was carried out to determine the typical glycan-Mg2+ binding patterns and the lowest-energy conformer identified was used as the initial geometry for density functional theory-based theoretical modeling. It was found that the electron is preferentially captured by Mg2+ and the resultant Mg+• can abstract a hydroxyl group from the glycan moiety to form a carbon radical. Subsequent radical migration and α-cleavage(s) result in the formation of a variety of product ions. The proposed hydroxyl abstraction mechanism correlates well with the major features in the ECD spectrum of the Mg2+-adducted cellohexaose. The mechanism presented here also predicts the presence of secondary, radical-induced fragmentation pathways. These secondary fragment ions could be misinterpreted, leading to erroneous structural determination. The present study highlights an urgent need for continuing investigation of the glycan ECD mechanism, which is imperative for successful development of bioinformatics tools that can take advantage of the rich structural information provided by ECD of metal-adducted glycans.

Using ultrasonography to monitor liver blood flow for liver transplant from donors supported on extracorporeal membrane oxygenation.

PubMed

Zhu, Xian-Sheng; Wang, Sha-Sha; Cheng, Qi; Ye, Chuang-Wen; Huo, Feng; Li, Peng

2016-02-01

Extracorporeal membrane oxygenation (ECMO) has been used to support brain-dead donors for liver procurement. This study investigated the potential role of ultrasonographic monitoring of hepatic perfusion as an aid to improve the viability of liver transplants obtained from brain-dead donors who are supported on ECMO. A total of 40 brain-dead patients maintained on ECMO served as the study population. Hepatic blood flow was monitored using ultrasonography, and perioperative optimal perfusion was maintained by calibrating ECMO. Liver function tests were performed to assess the viability of the graft. The hepatic arterial blood flow was well maintained with no significant changes observed before and after ECMO (206 ± 32 versus 241 ± 45 mL/minute; P = 0.06). Similarly, the portal venous blood flow was also maintained throughout (451 ± 65 versus 482 ± 77 mL/minute; P = 0.09). No significant change in levels of total bilirubin, alanine transaminase, and lactic acid were reported during ECMO (P = 0.17, P = 0.08, and P = 0.09, respectively). Before the liver is procured, ultrasonographic monitoring of hepatic blood flow could be a valuable aid to improve the viability of a liver transplant by allowing for real-time calibration of ECMO perfusion in brain-dead liver donors. In our study, ultrasonographic monitoring helped prevent warm ischemic injury to the liver graft by avoiding both overperfusion and underperfusion of the liver. © 2015 American Association for the Study of Liver Diseases.

Evaluation of brain perfusion in Alzheimer disease with perfusion computed tomography and comparison to elderly patient without dementia.

PubMed

Yildirim, Tülin; Karakurum Göksel, Başak; Demir, Şenay; Tokmak, Naime; Tan, Meliha

2016-04-19

The aim of this study was to evaluate perfusion computed tomography (PCT) findings in patients with Alzheimer disease and to compare them with those of patients without dementia. PCT was performed in 35 patients: 20 with Alzheimer disease (mean age, 69.7 ± 5.5 years) and 15 control subjects (mean age, 67.5 ± 3.5 years). Control subjects were elderly individuals with no cognitive problems who were admitted with headaches. All PCT examinations were performed on a 4-slice CT unit. The PCT analysis software program was used to calculate regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), regional time-to-peak (rTTP) values in the bilateral frontal, temporal, and occipital cortices, and bilateral lentiform nucleus. rCBF values in the bilateral frontal and temporal cortices and bilateral lentiform nucleus were significantly lower in the patients with Alzheimer disease than in the control subjects. There were no significant differences in rCBV values between Alzheimer disease and the control group. rTTP values in all cortical areas and bilateral lentiform nucleus were significantly higher in the patients with Alzheimer disease than in the control subjects. PCT is a rapid and reliable imaging modality for evaluating brain perfusion in Alzheimer disease.

Differential Requirement of the Extracellular Domain in Activation of Class B G Protein-coupled Receptors.

PubMed

Zhao, Li-Hua; Yin, Yanting; Yang, Dehua; Liu, Bo; Hou, Li; Wang, Xiaoxi; Pal, Kuntal; Jiang, Yi; Feng, Yang; Cai, Xiaoqing; Dai, Antao; Liu, Mingyao; Wang, Ming-Wei; Melcher, Karsten; Xu, H Eric

2016-07-15

G protein-coupled receptors (GPCRs) from the secretin-like (class B) family are key players in hormonal homeostasis and are important drug targets for the treatment of metabolic disorders and neuronal diseases. They consist of a large N-terminal extracellular domain (ECD) and a transmembrane domain (TMD) with the GPCR signature of seven transmembrane helices. Class B GPCRs are activated by peptide hormones with their C termini bound to the receptor ECD and their N termini bound to the TMD. It is thought that the ECD functions as an affinity trap to bind and localize the hormone to the receptor. This in turn would allow the hormone N terminus to insert into the TMD and induce conformational changes of the TMD to activate downstream signaling. In contrast to this prevailing model, we demonstrate that human class B GPCRs vary widely in their requirement of the ECD for activation. In one group, represented by corticotrophin-releasing factor receptor 1 (CRF1R), parathyroid hormone receptor (PTH1R), and pituitary adenylate cyclase activating polypeptide type 1 receptor (PAC1R), the ECD requirement for high affinity hormone binding can be bypassed by induced proximity and mass action effects, whereas in the other group, represented by glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), the ECD is required for signaling even when the hormone is covalently linked to the TMD. Furthermore, the activation of GLP-1R by small molecules that interact with the intracellular side of the receptor is dependent on the presence of its ECD, suggesting a direct role of the ECD in GLP-1R activation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The clinical spectrum of Erdheim-Chester disease: an observational cohort study

PubMed Central

O’Brien, Kevin J.; Xi, Liqiang; Malayeri, Ashkan A.; Gardner, Pamela J.; Alvarado Enriquez, Jhonell R.; Shah, Nikeith; Gochuico, Bernadette R.; Raffeld, Mark; Gahl, William A.

2017-01-01

Erdheim-Chester disease (ECD) is a rare, potentially fatal multiorgan myeloid neoplasm occurring mainly in adults. The diagnosis is established by clinical, radiologic, and histologic findings; ECD tumors contain foamy macrophages that are CD68+, CD163+, CD1a−, and frequently S100−. The purpose of this report is to describe the clinical and molecular variability of ECD. Between 2011 and 2015, 60 consecutive ECD patients (45 males, 15 females) were prospectively evaluated at the National Institutes of Health Clinical Center. Comprehensive imaging and laboratory studies were performed, and tissues were examined for BRAF V600E and MAPK pathway mutations. Mean age at first manifestations of ECD was 46 years; a diagnosis was established, on average, 4.2 years after initial presentation. Bone was the most common tissue affected, with osteosclerosis in 95% of patients. Other manifestations observed in one-third to two-thirds of patients included cardiac mass and periaortic involvement, diabetes insipidus, retro-orbital infiltration, retroperitoneal, lung, central nervous system, skin, and xanthelasma, affecting patients in variable ways. Methods of detection included imaging studies of various modalities. Mutation in BRAF V600E was detected in 51% of 57 biopsy specimens. One patient had an ARAF D228V mutation, and 1 patient had an activating ALK fusion. Treatments included interferon α, imatinib, anakinra, cladribine, vemurafenib, and dabrafenib with trametinib; 11 patients received no therapy. The diagnosis of ECD is elusive because of the rarity and varied presentations of the disorder. Identification of BRAF and other MAPK pathway mutations in biopsy specimens improves ECD diagnosis, allows for development of targeted treatments, and demonstrates that ECD is a neoplastic disorder. This study was registered at www.clinicaltrials.gov as #NCT01417520. PMID:28553668

Reversibly bound chloride in the atrial natriuretic peptide receptor hormone-binding domain: possible allosteric regulation and a conserved structural motif for the chloride-binding site.

PubMed

Ogawa, Haruo; Qiu, Yue; Philo, John S; Arakawa, Tsutomu; Ogata, Craig M; Misono, Kunio S

2010-03-01

The binding of atrial natriuretic peptide (ANP) to its receptor requires chloride, and it is chloride concentration dependent. The extracellular domain (ECD) of the ANP receptor (ANPR) contains a chloride near the ANP-binding site, suggesting a possible regulatory role. The bound chloride, however, is completely buried in the polypeptide fold, and its functional role has remained unclear. Here, we have confirmed that chloride is necessary for ANP binding to the recombinant ECD or the full-length ANPR expressed in CHO cells. ECD without chloride (ECD(-)) did not bind ANP. Its binding activity was fully restored by bromide or chloride addition. A new X-ray structure of the bromide-bound ECD is essentially identical to that of the chloride-bound ECD. Furthermore, bromide atoms are localized at the same positions as chloride atoms both in the apo and in the ANP-bound structures, indicating exchangeable and reversible halide binding. Far-UV CD and thermal unfolding data show that ECD(-) largely retains the native structure. Sedimentation equilibrium in the absence of chloride shows that ECD(-) forms a strongly associated dimer, possibly preventing the structural rearrangement of the two monomers that is necessary for ANP binding. The primary and tertiary structures of the chloride-binding site in ANPR are highly conserved among receptor-guanylate cyclases and metabotropic glutamate receptors. The chloride-dependent ANP binding, reversible chloride binding, and the highly conserved chloride-binding site motif suggest a regulatory role for the receptor bound chloride. Chloride-dependent regulation of ANPR may operate in the kidney, modulating ANP-induced natriuresis.

Reversibly Bound Chloride in the Atrial Natriuretic Peptide Receptor Hormone Binding Domain: Possible Allosteric Regulation and a Conserved Structural Motif for the Chloride-binding Site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogawa, H.; Qiu, Y; Philo, J

2010-01-01

The binding of atrial natriuretic peptide (ANP) to its receptor requires chloride, and it is chloride concentration dependent. The extracellular domain (ECD) of the ANP receptor (ANPR) contains a chloride near the ANP-binding site, suggesting a possible regulatory role. The bound chloride, however, is completely buried in the polypeptide fold, and its functional role has remained unclear. Here, we have confirmed that chloride is necessary for ANP binding to the recombinant ECD or the full-length ANPR expressed in CHO cells. ECD without chloride (ECD(-)) did not bind ANP. Its binding activity was fully restored by bromide or chloride addition. Amore » new X-ray structure of the bromide-bound ECD is essentially identical to that of the chloride-bound ECD. Furthermore, bromide atoms are localized at the same positions as chloride atoms both in the apo and in the ANP-bound structures, indicating exchangeable and reversible halide binding. Far-UV CD and thermal unfolding data show that ECD(-) largely retains the native structure. Sedimentation equilibrium in the absence of chloride shows that ECD(-) forms a strongly associated dimer, possibly preventing the structural rearrangement of the two monomers that is necessary for ANP binding. The primary and tertiary structures of the chloride-binding site in ANPR are highly conserved among receptor-guanylate cyclases and metabotropic glutamate receptors. The chloride-dependent ANP binding, reversible chloride binding, and the highly conserved chloride-binding site motif suggest a regulatory role for the receptor bound chloride. Chloride-dependent regulation of ANPR may operate in the kidney, modulating ANP-induced natriuresis.« less

Reversibly bound chloride in the atrial natriuretic peptide receptor hormone-binding domain: Possible allosteric regulation and a conserved structural motif for the chloride-binding site

PubMed Central

Ogawa, Haruo; Qiu, Yue; Philo, John S; Arakawa, Tsutomu; Ogata, Craig M; Misono, Kunio S

2010-01-01

The binding of atrial natriuretic peptide (ANP) to its receptor requires chloride, and it is chloride concentration dependent. The extracellular domain (ECD) of the ANP receptor (ANPR) contains a chloride near the ANP-binding site, suggesting a possible regulatory role. The bound chloride, however, is completely buried in the polypeptide fold, and its functional role has remained unclear. Here, we have confirmed that chloride is necessary for ANP binding to the recombinant ECD or the full-length ANPR expressed in CHO cells. ECD without chloride (ECD(−)) did not bind ANP. Its binding activity was fully restored by bromide or chloride addition. A new X-ray structure of the bromide-bound ECD is essentially identical to that of the chloride-bound ECD. Furthermore, bromide atoms are localized at the same positions as chloride atoms both in the apo and in the ANP-bound structures, indicating exchangeable and reversible halide binding. Far-UV CD and thermal unfolding data show that ECD(−) largely retains the native structure. Sedimentation equilibrium in the absence of chloride shows that ECD(−) forms a strongly associated dimer, possibly preventing the structural rearrangement of the two monomers that is necessary for ANP binding. The primary and tertiary structures of the chloride-binding site in ANPR are highly conserved among receptor-guanylate cyclases and metabotropic glutamate receptors. The chloride-dependent ANP binding, reversible chloride binding, and the highly conserved chloride-binding site motif suggest a regulatory role for the receptor bound chloride. Chloride-dependent regulation of ANPR may operate in the kidney, modulating ANP-induced natriuresis. PMID:20066666

The effect of an Ahmed glaucoma valve implant on corneal endothelial cell density in children with glaucoma secondary to uveitis.

PubMed

Kalinina Ayuso, Viera; Scheerlinck, Laura M; de Boer, Joke H

2013-03-01

To assess the effect of Ahmed glaucoma valve implants on corneal endothelial cell density (ECD) in children with uveitic glaucoma. Cross-sectional study. setting: Institutional. patientpopulation: Eighty eyes from 42 patients diagnosed with uveitis before the age of 16. Twenty-eight eyes had an Ahmed glaucoma valve implant because of secondary glaucoma. Fifty-two eyes without an implant served as controls. intervention orobservationprocedure(s): Corneal ECD was examined cross-sectionally using a noncontact specular microscope. Univariate and multivariate generalized estimating equations analyses with correction for paired eyes were performed. mainoutcomemeasure(s): Correlation of ECD with the presence of an Ahmed glaucoma valve implant and with the time following implantation. ECD was significantly lower in the Ahmed glaucoma valve group than in controls (2359 and 3088 cells/mm(2), respectively; P < .001) following an average of 3.5 years after Ahmed glaucoma valve implantation. Presence of an Ahmed glaucoma valve implant, previous intraocular surgery, age, duration of uveitis, and history of corneal touch by the implant tube were all significantly associated with decreased ECD. Following a multivariate analysis, presence of an Ahmed glaucoma valve implant (B = -340; adjusted P < .011) and older age (B = -58; adjusted P = .005) remained independently associated with decreased ECD. Within the implant group, the age-adjusted time interval following Ahmed glaucoma valve implantation was highly correlated with decreased ECD (B = -558, P < .001). Ahmed glaucoma valve implants in children with uveitic glaucoma are independently associated with decreased ECD, and this effect is associated with the time interval following Ahmed glaucoma valve implantation. Copyright © 2013 Elsevier Inc. All rights reserved.

Analyses of Factors Affecting Endothelial Cell Density in an Eye Bank Corneal Donor Database.

PubMed

Kwon, Ji Won; Cho, Kyong Jin; Kim, Hong Kyu; Lee, Jimmy K; Gore, Patrick K; McCartney, Mitchell D; Chuck, Roy S

2016-09-01

To analyze the factors affecting central corneal endothelial cell density (ECD) in an eye bank corneal donor database. The Lion's Eye Institute corneal donor database consisting of 18,665 donors (34,234 corneas) aged 20 years or older was analyzed. In particular, differences in the ECD based on age, sex, race, prior ocular surgery, a history of systemic diseases, and smoking were investigated. Furthermore, risk factors for donor cell count inadequacy (defined here as ECD less than 2000/mm) were identified. ECD decreased with age. Regarding race, the average ECD of African American donors was higher than those of white or Hispanic donors. A history of diabetes mellitus (DM) and ocular surgery were associated with a lower ECD. Donor medical history of hypertension, glaucoma, depression, dementia, Parkinson disease, hyper- or hypothyroidism, or smoking did not seem to affect the ECD. The risk factors for donor cell count inadequacy, based on binary logistic regression analyses were advanced age [65-74 years yielded an odds ratio of 17.8; confidence interval (CI), 10.6-29.8; P < 0.001; and 75-99 years yielded an odds ratio of 24.6 (CI, 14.5-41.61; P < 0.001) when compared with 20-34 years], cataract surgery (odds ratio, 4.3; CI, 4.0-4.8; P < 0.001), and DM (odds ratio, 1.2; CI, 1.1-1.3; P = 0.001). Age, race, ocular surgery (cataract and refractive), and DM seem to significantly affect donor corneal ECD. Of these variables, age, a history of cataract surgery, and DM were found to be the greatest risk factors for inadequate donor cell density (less than 2000/mm).

Research priority setting for integrated early child development and violence prevention (ECD+) in low and middle income countries: An expert opinion exercise.

PubMed

Tomlinson, Mark; Jordans, Mark; MacMillan, Harriet; Betancourt, Theresa; Hunt, Xanthe; Mikton, Christopher

2017-10-01

Child development in low and middle income countries (LMIC) is compromised by multiple risk factors. Reducing children's exposure to harmful events is essential for early childhood development (ECD). In particular, preventing violence against children - a highly prevalent risk factor that negatively affects optimal child development - should be an intervention priority. We used the Child Health and Nutrition Initiative (CHNRI) method for the setting of research priorities in integrated Early Childhood Development and violence prevention programs (ECD+). An expert group was identified and invited to systematically list and score research questions. A total of 186 stakeholders were asked to contribute five research questions each, and contributions were received from 81 respondents. These were subsequently evaluated using a set of five criteria: answerability; effectiveness; feasibility and/or affordability; applicability and impact; and equity. Of the 400 questions generated, a composite group of 50 were scored by 55 respondents. The highest scoring research questions related to the training of Community Health Workers (CHW's) to deliver ECD+ interventions effectively and whether ECD+ interventions could be integrated within existing delivery platforms such as HIV, nutrition or mental health platforms. The priority research questions can direct new research initiatives, mainly in focusing on the effectiveness of an ECD+ approach, as well as on service delivery questions. To the best of our knowledge, this is the first systematic exercise of its kind in the field of ECD+. The findings from this research priority setting exercise can help guide donors and other development actors towards funding priorities for important future research related to ECD and violence prevention. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The levels of bone alkaline phosphatase (BALP) and soluble epidermal growth factor receptor-2 (ECD/HER-2) in pediatric patients with osteosarcoma during clinical treatment.

PubMed

Rychłowska-Pruszyńska, Magdalena; Gajewska, Joanna; Ambroszkiewicz, Jadwiga; Karwacki, Marek; Szamotulska, Katarzyna

2018-01-01

Aim: The aim of this study was to assess the usefulness of bone-specific alkaline phosphatase (BALP) and the extracelluar domain of human epidermal growth factor receptor 2 (ECD/HER-2) measurements in pediatric patients with osteosarcoma as prospective prognostic and predictive markers for monitoring the treatment and early detection of disease recurrence. Material and methods: We studied 22 patients (5 girls, 17 boys) aged 7-20 years with osteosarcoma (OS) treated at the Institute of Mother and Child in Warsaw. All the patients were evaluated for the serum levels of BALP and ECD/HER-2 before treatment, during pre- and postoperative chemotherapy and after the completion of treatment. Healthy children (n=22) were the reference group. The levels of BALP and ECD/HER-2 were measured using immunoenzymatic methods. Results: The values of BALP and ECD/HER-2 proteins were higher (p<0.01; p<0.05, respectively) in patients with osteosarcoma at the time of diagnosis compared with the control group. The values of both markers significantly decreased during chemotherapy in most patients with remission. In contrast to ECD/HER-2, the value of BALP after therapy was higher in patients with progression than with remission (p<0.001). Conclusions: Our results demonstrate the different pattern of BALP and ECD/HER-2 proteins during clinical treatment in patients with osteosarcoma. Higher values of BALP may characterize the progression of the disease and unfavourable prognosis. Further longitudinal studies are necessary to confirm the prognostic values of BALP and ECD/HER-2 proteins in this group of patients.

Electron capture dissociation in a branched radio-frequency ion trap.

PubMed

Baba, Takashi; Campbell, J Larry; Le Blanc, J C Yves; Hager, James W; Thomson, Bruce A

2015-01-06

We have developed a high-throughput electron capture dissociation (ECD) device coupled to a quadrupole time-of-flight mass spectrometer using novel branched radio frequency ion trap architecture. With this device, a low-energy electron beam can be injected orthogonally into the analytical ion beam with independent control of both the ion and electron beams. While ions and electrons can interact in a "flow-through" mode, we observed a large enhancement in ECD efficiency by introducing a short ion trapping period at the region of ion and electron beam intersection. This simultaneous trapping mode still provides up to five ECD spectra per second while operating in an information-dependent acquisition workflow. Coupled to liquid chromatography (LC), this LC-ECD workflow provides good sequence coverage for both trypsin and Lys C digests of bovine serum albumin, providing ECD spectra for doubly charged precursor ions with very good efficiency.

[Successful repair of total anomalous pulmonary venous connection and incomplete endocardial cushion defect associated with left isomerism].

PubMed

Mizuno, A; Nakamura, Y; Takayasu, H; Saitoh, H

1993-05-01

Successful repair of a 8-month-old girl with polysplenia was reported. The cardiovascular anomalies were TAPVC (II b), incomplete ECD, interruption of inferior vena cava with hemiazygos continuation, bilateral superior vena cava, and left superior vena cava draining into the coronary sinus. Cardiopulmonary bypass was established with ascending aortic perfusion and caval cannulation. A left superior vena cava was directly cannulated after establishing partial bypass. In this case the left pulmonary vein drained into the right atrium near the orifice of the coronary sinus, so the atrial septal flap was made and sutured between the orifice of the left pulmonary vein and the coronary sinus in order to avoid late pulmonary vein obstruction. Then, atrium was separated by an intraatrial baffle which was sutured to the atrial septal flap. Recently, it becomes possible to surgical repair of polysplenia syndrome according to the advancements of the diagnostic methods, cardiopulmonary bypass, and the technique of the open heart surgery.

High quality high spatial resolution functional classification in low dose dynamic CT perfusion using singular value decomposition (SVD) and k-means clustering

NASA Astrophysics Data System (ADS)

Pisana, Francesco; Henzler, Thomas; Schönberg, Stefan; Klotz, Ernst; Schmidt, Bernhard; Kachelrieß, Marc

2017-03-01

Dynamic CT perfusion acquisitions are intrinsically high-dose examinations, due to repeated scanning. To keep radiation dose under control, relatively noisy images are acquired. Noise is then further enhanced during the extraction of functional parameters from the post-processing of the time attenuation curves of the voxels (TACs) and normally some smoothing filter needs to be employed to better visualize any perfusion abnormality, but sacrificing spatial resolution. In this study we propose a new method to detect perfusion abnormalities keeping both high spatial resolution and high CNR. To do this we first perform the singular value decomposition (SVD) of the original noisy spatial temporal data matrix to extract basis functions of the TACs. Then we iteratively cluster the voxels based on a smoothed version of the three most significant singular vectors. Finally, we create high spatial resolution 3D volumes where to each voxel is assigned a distance from the centroid of each cluster, showing how functionally similar each voxel is compared to the others. The method was tested on three noisy clinical datasets: one brain perfusion case with an occlusion in the left internal carotid, one healthy brain perfusion case, and one liver case with an enhancing lesion. Our method successfully detected all perfusion abnormalities with higher spatial precision when compared to the functional maps obtained with a commercially available software. We conclude this method might be employed to have a rapid qualitative indication of functional abnormalities in low dose dynamic CT perfusion datasets. The method seems to be very robust with respect to both spatial and temporal noise and does not require any special a priori assumption. While being more robust respect to noise and with higher spatial resolution and CNR when compared to the functional maps, our method is not quantitative and a potential usage in clinical routine could be as a second reader to assist in the maps evaluation, or to guide a dataset smoothing before the modeling part.

The iodide space in rabbit brain

PubMed Central

Ahmed, Nawal; Van Harreveld, A.

1969-01-01

1. The iodide space in rabbit brain varies greatly depending on the conditions under which it is determined. 2. When 131I- only is used the iodide space 4 hr after administration of the marker is of the order of 2%. The iodide content of the cerebrospinal fluid (c.s.f.) is about 1% of that of the serum. 3. Depression of the active iodide transport by perchlorate increases the space to 8·2% and the iodide content of the c.s.f. to 26% of that of the serum. 4. The active iodide transport can also be depressed by saturation with unlabelled iodide. Up to a serum iodide concentration of 5 mM the space determined after 5 hr remained constant at 2·7%. The iodide space grew when the serum iodide content was enhanced from 5 to 20 mM, to become constant at a value of 10·6% on further increase of the serum iodide (up to 50 mM). The iodide content of the c.s.f. increased in a similar manner as the space with the iodide concentration of the serum to about 1/3 of the serum concentration. The iodide space of the muscle was independent of the plasma iodide content. 5. From 4 to 8 hr after administration of 131I- alone or with unlabelled iodide (to a serum concentration of 15 mM) the iodide space remained relatively constant. 6. When 131I- was administered in the fluid with which the ventricles were perfused an iodide space of about 7% was attained after about 5 hr. 7. In experiments in which 131I- was administered intravenously and the sink action of the c.s.f. was eliminated by perfusion of the ventricles with a perfusate containing as much 131I- as the plasma, the iodide space was 10·2%. When in addition active iodide transport was depressed by perchlorate the space increased to 16·8%. 8. Intravenous administration of labelled and unlabelled iodide (to a serum concentration of 20-40 mM) and ventricle perfusion with the same concentration of 131I- and unlabelled iodide as in the plasma yielded an iodide space of 20·8%. In similar experiments the iodide concentration of the perfusate was so adjusted that after 5 hr perfusion its iodide content hardly changed during the passage through the ventricles. Under these conditions the iodide concentration of the extracellular and perfusion fluids can be considered to be near equal. The iodide space computed on the basis of the iodide content of the outflowing fluid was 22·5%. 9. The large iodide space could be equated with the extracellular space if the iodide remained extracellular. This seems to be the case in the muscle where the iodide space is similar to the inulin space. 10. The large effects on the iodide space of perchlorate and saturation with unlabelled iodide in experiments in which the marker was administered intravenously and in the perfusate (7 and 8) suggests the presence of an active iodide transport from the brain extracellular fluid into the blood over the blood—brain barrier. PMID:4310942

Cerebral perfusion alterations in epileptic patients during peri-ictal and post-ictal phase: PASL vs DSC-MRI.

PubMed

Pizzini, Francesca B; Farace, Paolo; Manganotti, Paolo; Zoccatelli, Giada; Bongiovanni, Luigi G; Golay, Xavier; Beltramello, Alberto; Osculati, Antonio; Bertini, Giuseppe; Fabene, Paolo F

2013-07-01

Non-invasive pulsed arterial spin labeling (PASL) MRI is a method to study brain perfusion that does not require the administration of a contrast agent, which makes it a valuable diagnostic tool as it reduces cost and side effects. The purpose of the present study was to establish the viability of PASL as an alternative to dynamic susceptibility contrast (DSC-MRI) and other perfusion imaging methods in characterizing changes in perfusion patterns caused by seizures in epileptic patients. We evaluated 19 patients with PASL. Of these, the 9 affected by high-frequency seizures were observed during the peri-ictal period (within 5hours since the last seizure), while the 10 patients affected by low-frequency seizures were observed in the post-ictal period. For comparison, 17/19 patients were also evaluated with DSC-MRI and CBF/CBV. PASL imaging showed focal vascular changes, which allowed the classification of patients in three categories: 8 patients characterized by increased perfusion, 4 patients with normal perfusion and 7 patients with decreased perfusion. PASL perfusion imaging findings were comparable to those obtained by DSC-MRI. Since PASL is a) sensitive to vascular alterations induced by epileptic seizures, b) comparable to DSC-MRI for detecting perfusion asymmetries, c) potentially capable of detecting time-related perfusion changes, it can be recommended for repeated evaluations, to identify the epileptic focus, and in follow-up and/or therapy-response assessment. Copyright © 2013 Elsevier Inc. All rights reserved.

Measurement of pediatric regional cerebral blood flow from 6 months to 15 years of age in a clinical population.

PubMed

Carsin-Vu, Aline; Corouge, Isabelle; Commowick, Olivier; Bouzillé, Guillaume; Barillot, Christian; Ferré, Jean-Christophe; Proisy, Maia

2018-04-01

To investigate changes in cerebral blood flow (CBF) in gray matter (GM) between 6 months and 15 years of age and to provide CBF values for the brain, GM, white matter (WM), hemispheres and lobes. Between 2013 and 2016, we retrospectively included all clinical MRI examinations with arterial spin labeling (ASL). We excluded subjects with a condition potentially affecting brain perfusion. For each subject, mean values of CBF in the brain, GM, WM, hemispheres and lobes were calculated. GM CBF was fitted using linear, quadratic and cubic polynomial regression against age. Regression models were compared with Akaike's information criterion (AIC), and Likelihood Ratio tests. 84 children were included (44 females/40 males). Mean CBF values were 64.2 ± 13.8 mL/100 g/min in GM, and 29.3 ± 10.0 mL/100 g/min in WM. The best-fit model of brain perfusion was the cubic polynomial function (AIC = 672.7, versus respectively AIC = 673.9 and AIC = 674.1 with the linear negative function and the quadratic polynomial function). A statistically significant difference between the tested models demonstrating the superiority of the quadratic (p = 0.18) or cubic polynomial model (p = 0.06), over the negative linear regression model was not found. No effect of general anesthesia (p = 0.34) or of gender (p = 0.16) was found. we provided values for ASL CBF in the brain, GM, WM, hemispheres, and lobes over a wide pediatric age range, approximately showing inverted U-shaped changes in GM perfusion over the course of childhood. Copyright © 2018 Elsevier B.V. All rights reserved.

Using the ECD Framework to Support Evidentiary Reasoning in the Context of a Simulation Study for Detecting Learner Differences in Epistemic Games

ERIC Educational Resources Information Center

Sweet, Shauna J.; Rupp, Andre A.

2012-01-01

The "evidence-centered design" (ECD) framework is a powerful tool that supports careful and critical thinking about the identification and accumulation of evidence in assessment contexts. In this paper, we demonstrate how the ECD framework provides critical support for designing simulation studies to investigate statistical methods…

Hand-Schüller-Christian Disease and Erdheim-Chester Disease: Coexistence and Discrepancy

PubMed Central

Yin, Jun; Zhang, Feng; Zhang, Huizhen; Shen, Li; Li, Qing; Hu, Shundong; Tian, Qinghua; Bao, Yuqian

2013-01-01

Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) share similar clinical features and mechanisms. In very rare circumstances, the two diseases coexist in the same patient. Here we report such a patient, who was first diagnosed with Hand-Schüller-Christian disease (HSC), a type of LCH. Several years later, the patient presented with severe exophthalmos and osteosclerosis on radiograph. New biopsy revealed ECD. We also analyze 54 cases of LCH and 6 cases of ECD diagnosed in our hospital, as well as their progression during a follow-up period of 8 years. In five cases of HSC (9.3% of LCH), a triad of central diabetes insipidus, hyperprolactinemia, and pituitary stalk thickening on magnetic resonance imaging (MRI) preceded the typical bone lesions by 4–9 years. In addition, LCH was featured as elevated plasma alkaline phosphatase (ALP), which was normal in ECD. Combined with a literature review, several features are summarized to differentiate ECD from HSC. In patients with diabetes insipidus, concomitant hyperprolactinemia and pituitary stalk thickening on MRI indicate a possible HSC. Additionally, if osteosclerosis is observed in a patient with LCH, the coexistence of ECD should be considered. PMID:23299772

Gravity-induced hyperventilation is caused by a reduced brain perfusion.

PubMed

Arieli, R; Farhi, L E

1987-08-01

The suggestion that hyperventilation caused by increased gravity is mediated by a decrease in brain perfusion has led us to propose a mathematical model based on: (1) the CO2 balance equation for the respiratory center (RC), and (2) the relationship between RC blood flow (QRC), foot-to-head acceleration (Gz) and PRCCO2, namely, QRC = [1 - a(Gz - 1)](b X PRCCO2 + c), where the coefficients a, b and c can be calculated from data in the literature. QRC is significantly affected by + GZ only at high PaCO2. The model can be used to calculate oxygen pressure in the RC; the numbers so obtained are in good agreement with measurements of jugular vein PO2 obtained by others.

A Significant Proportion of Pediatric Morphea En Coup De Sabre and Parry-Romberg Syndrome Patients Have Neuroimaging Findings

PubMed Central

Chiu, Yvonne E.; Vora, Sheetal; Kwon, Eun-Kyung M.; Maheshwari, Mohit

2012-01-01

Background/Objectives En coup de sabre (ECDS) and Parry-Romberg syndrome (PRS) are variants of linear morphea on the head and neck that can be associated with neurologic manifestations. Intracranial abnormalities on computed tomography (CT) and magnetic resonance imaging (MRI) can be present in a significant proportion of patients. Methods We describe 32 pediatric patients from our institution with ECDS or PRS, in whom neuroimaging was performed in 21 cases. We also review 51 additional patients from the literature. Results Nineteen percent of the children at our institution had intracranial abnormalities on MRI, half of whom were asymptomatic. Hyperintensities on T2-weighted sequences were the most common finding, present in all patients who had intracranial abnormalities on MRI. Seizures and headaches were the most common neurologic symptom, affecting 13% and 9% of our population, respectively. The presence of neurologic symptoms was not correlated with neuroimaging abnormalities as 2 asymptomatic patients had marked MRI findings, while the MRI was abnormal in only 2/9 symptomatic patients. Similarly, the severity of the superficial disease did not predict neurologic involvement; a patient with subtle skin involvement had striking MRI findings and seizures while another patient with a bony defect had no brain parenchymal involvement. Conclusions Neurologic symptoms and neuroimaging abnormalities are found in a surprisingly substantial percentage of children with ECDS and PRS. Early recognition of neurologic involvement is necessary as it affects treatment choices. As clinical predictors of intracranial abnormalities are poor, strong consideration should be given to obtaining an MRI prior to treatment initiation to assist in management decisions and establish a baseline examination. PMID:23106674

Automated Voxel-Based Analysis of Volumetric Dynamic Contrast-Enhanced CT Data Improves Measurement of Serial Changes in Tumor Vascular Biomarkers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coolens, Catherine, E-mail: catherine.coolens@rmp.uhn.on.ca; Department of Radiation Oncology, University of Toronto, Toronto, Ontario; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario

2015-01-01

Objectives: Development of perfusion imaging as a biomarker requires more robust methodologies for quantification of tumor physiology that allow assessment of volumetric tumor heterogeneity over time. This study proposes a parametric method for automatically analyzing perfused tissue from volumetric dynamic contrast-enhanced (DCE) computed tomography (CT) scans and assesses whether this 4-dimensional (4D) DCE approach is more robust and accurate than conventional, region-of-interest (ROI)-based CT methods in quantifying tumor perfusion with preliminary evaluation in metastatic brain cancer. Methods and Materials: Functional parameter reproducibility and analysis of sensitivity to imaging resolution and arterial input function were evaluated in image sets acquired from amore » 320-slice CT with a controlled flow phantom and patients with brain metastases, whose treatments were planned for stereotactic radiation surgery and who consented to a research ethics board-approved prospective imaging biomarker study. A voxel-based temporal dynamic analysis (TDA) methodology was used at baseline, at day 7, and at day 20 after treatment. The ability to detect changes in kinetic parameter maps in clinical data sets was investigated for both 4D TDA and conventional 2D ROI-based analysis methods. Results: A total of 7 brain metastases in 3 patients were evaluated over the 3 time points. The 4D TDA method showed improved spatial efficacy and accuracy of perfusion parameters compared to ROI-based DCE analysis (P<.005), with a reproducibility error of less than 2% when tested with DCE phantom data. Clinically, changes in transfer constant from the blood plasma into the extracellular extravascular space (K{sub trans}) were seen when using TDA, with substantially smaller errors than the 2D method on both day 7 post radiation surgery (±13%; P<.05) and by day 20 (±12%; P<.04). Standard methods showed a decrease in K{sub trans} but with large uncertainty (111.6 ± 150.5) %. Conclusions: Parametric voxel-based analysis of 4D DCE CT data resulted in greater accuracy and reliability in measuring changes in perfusion CT-based kinetic metrics, which have the potential to be used as biomarkers in patients with metastatic brain cancer.« less

Evaluating the potential of (188)Re-ECD/lipiodol as a therapeutic radiopharmaceutical by intratumoral injection for hepatoma treatment.

PubMed

Luo, Tsai-Yueh; Shih, Ying-Hsia; Chen, Chiung-Yu; Tang, I-Chung; Wu, Yu-Long; Kung, Hong-Chang; Lin, Wuu-Jyh; Lin, Xi-Zhang

2009-10-01

Intratumoral injection of a radiopharmaceutical is a potential modality to treat liver tumors. Rhenium-188 ((188)Re) was used to chelate with ethyl cysteinate dimer (ECD) in lipiodol solution to form (188)Re-ECD/lipiodol, which was then evaluated for its therapeutic potential in a rodent hepatoma model. Male Sprague-Dawley rats were implanted with N1-S1 hepatoma cells orthotopically and randomly divided into two groups. Group 1 (n = 29) and group 2 (n = 10) received (188)Re-ECD/lipiodol (30.4 +/- 21.8 MBq/0.1 mL) and 0.1 mL of normal saline by intratumoral injection, respectively. Three rats in group 1 were imaged by micro-single-photon emission computed tomography/computed tomography scan to evaluate the biodistribution pattern. All rats were monitored for change of tumor size and survival rate after 2 months. The in vitro stability test showed that (188)Re-ECD was well-retained in the lipiodol phase for 48 hours. The biodistribution image revealed that radioactivity was retained well in hepatomas 24 hours postinjection. Long-term studies demonstrated that rats treated with (188)Re-ECD/Lipiodol had smaller tumor volumes and a better survival rate, compared to the control group. At the end of observation, the survival rates in groups 1 and 2 were 62% and 20%, respectively (p < 0.05). (188)Re-ECD/lipiodol via direct intratumoral injection shows potential for treating hepatoma and warrants further clinical trials.

Towards robust deconvolution of low-dose perfusion CT: sparse perfusion deconvolution using online dictionary learning.

PubMed

Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C

2013-05-01

Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. Copyright © 2013 Elsevier B.V. All rights reserved.

Towards robust deconvolution of low-dose perfusion CT: Sparse perfusion deconvolution using online dictionary learning

PubMed Central

Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C.

2014-01-01

Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. PMID:23542422

Rheological effects of drag-reducing polymers improve cerebral blood flow and oxygenation after traumatic brain injury in rats.

PubMed

Bragin, Denis E; Kameneva, Marina V; Bragina, Olga A; Thomson, Susan; Statom, Gloria L; Lara, Devon A; Yang, Yirong; Nemoto, Edwin M

2017-03-01

Cerebral ischemia has been clearly demonstrated after traumatic brain injury (TBI); however, neuroprotective therapies have not focused on improvement of the cerebral microcirculation. Blood soluble drag-reducing polymers (DRP), prepared from high molecular weight polyethylene oxide, target impaired microvascular perfusion by altering the rheological properties of blood and, until our recent reports, has not been applied to the brain. We hypothesized that DRP improve cerebral microcirculation and oxygenation after TBI. DRP were studied in healthy and traumatized rat brains and compared to saline controls. Using in-vivo two-photon laser scanning microscopy over the parietal cortex, we showed that after TBI, nanomolar concentrations of intravascular DRP significantly enhanced microvascular perfusion and tissue oxygenation in peri-contusional areas, preserved blood-brain barrier integrity and protected neurons. The mechanisms of DRP effects were attributable to reduction of the near-vessel wall cell-free layer which increased near-wall blood flow velocity, microcirculatory volume flow, and number of erythrocytes entering capillaries, thereby reducing capillary stasis and tissue hypoxia as reflected by a reduction in NADH. Our results indicate that early reduction in CBF after TBI is mainly due to ischemia; however, metabolic depression of contused tissue could be also involved.

Mannitol-facilitated perfusion staining with 2, 3, 5-triphenyltetrazolium chloride (TTC) for detection of experimental cerebral infarction and biochemical analysis

PubMed Central

Sun, Yu-Yo; Yang, Dianer; Kuan, Chia-Yi

2011-01-01

A simple method to quantify cerebral infarction has great value for mechanistic and therapeutic studies in experimental stroke research. Immersion staining of unfixed brain slices with 2,3,5-triphenyltetrazolium chloride (TTC) is a popular method to determine cerebral infarction in preclinical studies. However, it is often difficult to apply immersion TTC-labeling to severely injured or soft newborn brains in rodents. Here we report an in-vivo TTC perfusion-labeling method based on osmotic opening of blood-brain-barrier with mannitol-pretreatment. This new method delineates cortical infarction correlated with the boundary of morphological cell injury, differentiates the induction or subcellular redistribution of apoptosis-related factors between viable and damaged areas, and easily determines the size of cerebral infarction in both adult and newborn mice. Using this method, we confirmed that administration of lipopolysaccharide 72 h before hypoxia-ischemia increases the damage in neonatal mouse brains, in contrast to its effect of protective preconditioning in adults. These results demonstrate a fast and inexpensive method that simplifies the task of quantifying cerebral infarction in small or severely injured brains and assists biochemical analysis of experimental cerebral ischemia. PMID:21982741

Oxygen-charged HTK-F6H8 emulsion reduces ischemia-reperfusion injury in kidneys from brain-dead pigs.

PubMed

Asif, Sana; Sedigh, Amir; Nordström, Johan; Brandhorst, Heide; Jorns, Carl; Lorant, Tomas; Larsson, Erik; Magnusson, Peetra U; Nowak, Greg; Theisinger, Sonja; Hoeger, Simone; Wennberg, Lars; Korsgren, Olle; Brandhorst, Daniel

2012-12-01

Prolonged cold ischemia is frequently associated with a greater risk of delayed graft function and enhanced graft failure. We hypothesized that media, combining a high oxygen-dissolving capacity with specific qualities of organ preservation solutions, would be more efficient in reducing immediate ischemia-reperfusion injury from organs stored long term compared with standard preservation media. Kidneys retrieved from brain-dead pigs were flushed using either cold histidine-tryptophan-ketoglutarate (HTK) or oxygen-precharged emulsion composed of 75% HTK and 25% perfluorohexyloctane. After 18 h of cold ischemia the kidneys were transplanted into allogeneic recipients and assessed for adenosine triphosphate content, morphology, and expression of genes related to hypoxia, environmental stress, inflammation, and apoptosis. Compared with HTK-flushed kidneys, organs preserved using oxygen-precharged HTK-perfluorohexyloctane emulsion had increased elevated adenosine triphosphate content and a significantly lower gene expression of hypoxia inducible factor-1α, vascular endothelial growth factor, interleukin-1α, tumor necrosis factor-α, interferon-α, JNK-1, p38, cytochrome-c, Bax, caspase-8, and caspase-3 at all time points assessed. In contrast, the mRNA expression of Bcl-2 was significantly increased. The present study has demonstrated that in brain-dead pigs the perfusion of kidneys with oxygen-precharged HTK-perfluorohexyloctane emulsion results in significantly reduced inflammation, hypoxic injury, and apoptosis and cellular integrity and energy content are well maintained. Histologic examination revealed less tubular, vascular, and glomerular changes in the emulsion-perfused tissue compared with the HTK-perfused counterparts. The concept of perfusing organs with oxygen-precharged emulsion based on organ preservation media represents an efficient alternative for improved organ preservation. Copyright © 2012 Elsevier Inc. All rights reserved.

Endothelial Mineralocorticoid Receptor Mediates Parenchymal Arteriole and Posterior Cerebral Artery Remodeling During Angiotensin II-Induced Hypertension.

PubMed

Diaz-Otero, Janice M; Fisher, Courtney; Downs, Kelsey; Moss, M Elizabeth; Jaffe, Iris Z; Jackson, William F; Dorrance, Anne M

2017-12-01

The brain is highly susceptible to injury caused by hypertension because the increased blood pressure causes artery remodeling that can limit cerebral perfusion. Mineralocorticoid receptor (MR) antagonism prevents hypertensive cerebral artery remodeling, but the vascular cell types involved have not been defined. In the periphery, the endothelial MR mediates hypertension-induced vascular injury, but cerebral and peripheral arteries are anatomically distinct; thus, these findings cannot be extrapolated to the brain. The parenchymal arterioles determine cerebrovascular resistance. Determining the effects of hypertension and MR signaling on these arterioles could lead to a better understanding of cerebral small vessel disease. We hypothesized that endothelial MR signaling mediates inward cerebral artery remodeling and reduced cerebral perfusion during angiotensin II (AngII) hypertension. The biomechanics of the parenchymal arterioles and posterior cerebral arteries were studied in male C57Bl/6 and endothelial cell-specific MR knockout mice and their appropriate controls using pressure myography. AngII increased plasma aldosterone and decreased cerebral perfusion in C57Bl/6 and MR-intact littermates. Endothelial cell MR deletion improved cerebral perfusion in AngII-treated mice. AngII hypertension resulted in inward hypotrophic remodeling; this was prevented by MR antagonism and endothelial MR deletion. Our studies suggest that endothelial cell MR mediates hypertensive remodeling in the cerebral microcirculation and large pial arteries. AngII-induced inward remodeling of cerebral arteries and arterioles was associated with a reduction in cerebral perfusion that could worsen the outcome of stroke or contribute to vascular dementia. © 2017 American Heart Association, Inc.

Effects of acupuncture on tissue-oxygenation of the rat brain.

PubMed

Chen, G S; Erdmann, W

1977-01-01

Acupuncture has been claimed to be effective in restoring consciousness in some comatose patients. Possible mechanisms to explain alleged acupuncture-induced arousal may include vasodilatory effects caused by sympathetic stimulation which leads to an augmentation of cerebral microcirculation and thereby improves oxygen supply to the brain tissue. Experiments were performed in ten albino rats (Wistar) employing PO2 microelectrodes which were inserted into the cortex of the animals through small burholes. Brain tissue PO2 was continuously recorded before, during, and after acupuncture. Stimulation of certain acupuncture loci (Go-26) resulted in immediate increase of PO2 in the frontal cortex of the rat brain. This effect was reproducible. The effect was comparable to that obtained with increase of inspiratory CO2 known to induce arterial vasodilatation and thus capillary perfusion pressure. The effect was more significant as compared to tissue PO2 increases obtained after increase of inspiratory oxygen concentration from 21% to 100%. It appears that acupuncture causes an increase of brain tissue perfusion which may be, at least in part, responsible for arousal of unconscious patients. Dilatation of cerebral vascular vessels and improvement of autoregulation in the brain by acupuncture stimulation may also explain the effectiveness of acupuncture in the treatment of migraine headache.

Implementation of Early Childhood Development Education Service Standard Guidelines on Physical Facilities in Public and Private Early Childhood Education Centres Kakamega County, Kenya

ERIC Educational Resources Information Center

Sitati, Emmily M.; Ndirangu, Mwangi; Kennedy, Bota; Rapongo, George S.

2016-01-01

In 2006, the Kenyan Ministry of Education (MoE) developed an early childhood development education (ECDE) service standard guidelines to guide the ECDE stakeholders in provision of early childhood education (ECE) programmes. The study sought to investigate the implementation of the ECDE service standard guidelines on provision of physical…

The effect of donor diabetes history on graft failure and endothelial cell density 10 years after penetrating keratoplasty.

PubMed

Lass, Jonathan H; Riddlesworth, Tonya D; Gal, Robin L; Kollman, Craig; Benetz, Beth A; Price, Francis W; Sugar, Alan; Terry, Mark A; Soper, Mark; Beck, Roy W

2015-03-01

To examine the long-term effect of donor diabetes history on graft failure and endothelial cell density (ECD) after penetrating keratoplasty (PK) in the Cornea Donor Study. Multicenter, prospective, double-masked, controlled clinical trial. One thousand ninety subjects undergoing PK for a moderate risk condition, principally Fuchs' dystrophy or pseudophakic or aphakic corneal edema, were enrolled by 105 surgeons from 80 clinical sites in the United States. Corneas from donors 12 to 75 years of age were assigned by 43 eye banks to participants without respect to recipient factors. Donor and recipient diabetes status was determined from existing medical records. Images of the central endothelium were obtained before surgery (baseline) and at intervals for 10 years after surgery and were analyzed by a central image analysis reading center to determine ECD. Time to graft failure (regraft or cloudy cornea for 3 consecutive months) and ECD. There was no statistically significant association of donor diabetes history with 10-year graft failure, baseline ECD, 10-year ECD, or ECD values longitudinally over time in unadjusted analyses, nor after adjusting for donor age and other significant covariates. The 10-year graft failure rate was 23% in the 199 patients receiving a cornea from a donor with diabetes versus 26% in the 891 patients receiving a cornea from a donor without diabetes (95% confidence interval for the difference, -10% to 6%; unadjusted P=0.60). Baseline ECD (P=0.71), 10-year ECD (P>0.99), and changes in ECD over 10 years (P=0.86) were similar comparing donor groups with and without diabetes. The study results do not suggest an association between donor diabetes and PK outcome. However, the assessment of donor diabetes was imprecise and based on historical data only. The increasing frequency of diabetes in the aging population in the United States affects the donor pool. Thus, the impact of donor diabetes on long-term endothelial health after PK or endothelial keratoplasty, or both, warrants further study with more precise measures of diabetes and its complications. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Modeling the sustainability of a ceramic water filter intervention.

PubMed

Mellor, Jonathan; Abebe, Lydia; Ehdaie, Beeta; Dillingham, Rebecca; Smith, James

2014-02-01

Ceramic water filters (CWFs) are a point-of-use water treatment technology that has shown promise in preventing early childhood diarrhea (ECD) in resource-limited settings. Despite this promise, some researchers have questioned their ability to reduce ECD incidences over the long term since most effectiveness trials conducted to date are less than one year in duration limiting their ability to assess long-term sustainability factors. Most trials also suffer from lack of blinding making them potentially biased. This study uses an agent-based model (ABM) to explore factors related to the long-term sustainability of CWFs in preventing ECD and was based on a three year longitudinal field study. Factors such as filter user compliance, microbial removal effectiveness, filter cleaning and compliance declines were explored. Modeled results indicate that broadly defined human behaviors like compliance and declining microbial effectiveness due to improper maintenance are primary drivers of the outcome metrics of household drinking water quality and ECD rates. The model predicts that a ceramic filter intervention can reduce ECD incidence amongst under two year old children by 41.3%. However, after three years, the average filter is almost entirely ineffective at reducing ECD incidence due to declining filter microbial removal effectiveness resulting from improper maintenance. The model predicts very low ECD rates are possible if compliance rates are 80-90%, filter log reduction efficiency is 3 or greater and there are minimal long-term compliance declines. Cleaning filters at least once every 4 months makes it more likely to achieve very low ECD rates as does the availability of replacement filters for purchase. These results help to understand the heterogeneity seen in previous intervention-control trials and reemphasize the need for researchers to accurately measure confounding variables and ensure that field trials are at least 2-3 years in duration. In summary, the CWF can be a highly effective tool in the fight against ECD, but every effort should be made by implementing agencies to ensure consistent use and maintenance. Copyright © 2013 Elsevier Ltd. All rights reserved.

Impact of early graft function on 10-year graft survival in recipients of kidneys from standard- or expanded-criteria donors.

PubMed

Smail, Nassima; Tchervenkov, Jean; Paraskevas, Steven; Baran, Dana; Mucsi, Istvan; Hassanain, Mazen; Chaudhury, Prosanto; Cantarovich, Marcelo

2013-07-27

The use of kidneys from expanded-criteria donors (ECD) is regarded with caution. We compared 279 kidney transplant recipients (KTxR) from standard-criteria donors (SCD) and 237 from ECD, transplanted between January 1990 and December 2006. We evaluated the impact of immediate graft function (IGF), slow graft function (SGF), and delayed graft function (DGF) and the drop in estimated glomerular filtration rate (ΔeGFR) ≤ 30% or > 30% during the first year after transplantation on long-term patient and death-censored graft survival (DCGS). Ten-year patient survival was similar in SCD- or ECD-KTxR (P = 0.38). DCGS was better in SCD-KTxR versus ECD-KTxR (77.3% vs. 67.3%; P = 0.01). DCGS did not differ in either group experiencing IGF (P = 0.17) or DGF (P = 0.12). However, DCGS was worse in ECD-KTxR experiencing SGF (84.9% vs. 73.7%; P = 0.04). Predictors of DCGS were 1-year serum creatinine (hazard ratio, 1.03; P < 0.0001) and ΔeGFR > 30% between 1 and 12 months (Δ1-12eGFR) after transplantation (hazard ratio, 2.2; P = 0.02). In ECD-KTxR with IGF and more than 1-year follow-up, 10-year DCGS was better in those with Δ1-12eGFR ≤ 30% versus those with Δ1-12eGFR > 30% (83.8% vs. 53.6%; P = 0.01). Recipients of SCD or ECD kidneys with IGF or DGF had similar 10-year patient survival and DCGS. SGF had a worse impact on DCGS in ECD-KTxR. In addition to 1-year serum creatinine, Δ1-12eGFR > 30% is a negative predictor of DCGS. Larger studies should confirm if increasing the use of ECD, avoiding factors that contribute to SGF or DGF, and/or a decline in eGFR during the first year after transplantation may expand the donor pool and result in acceptable long-term outcomes.

The Effect of Donor Diabetes History on Graft Failure and Endothelial Cell Density Ten Years after Penetrating Keratoplasty

PubMed Central

Lass, Jonathan H.; Riddlesworth, Tonya D.; Gal, Robin L.; Kollman, Craig; Benetz, Beth A.; Price, Francis W.; Sugar, Alan; Terry, Mark A.; Soper, Mark; Beck, Roy W.

2014-01-01

Objective To examine the long term effect of donor diabetes history on graft failure and endothelial cell density (ECD) after penetrating keratoplasty (PKP) in the Cornea Donor Study Design Multi-center prospective, double-masked, controlled clinical trial Participants 1090 subjects undergoing PKP for a moderate risk condition, principally Fuchs’ dystrophy or pseudophakic/aphakic corneal edema (PACE), were enrolled by 105 surgeons from 80 clinical sites in the United States. Methods Corneas from donors 12 to 75 years old were assigned by 43 eye banks to participants without respect to recipient factors. Donor and recipient diabetes status was determined from existing medical records. Images of the central endothelium were obtained preoperatively (baseline) and at intervals for ten years postoperatively and analyzed by a central image analysis reading center to determine ECD. Main Outcome Measure(s) Time to graft failure (regraft or cloudy cornea for 3 consecutive months) and ECD. Results There was no statistically significant association of donor diabetes history with 10-year graft failure, baseline ECD, 10-year ECD or ECD values longitudinally over time in unadjusted analyses nor after adjusting for donor age and other significant covariates. The 10-year graft failure rate was 23% in the 199 cases receiving a cornea from a donor with diabetes versus 26% in the 891 cases receiving a cornea from a donor without diabetes (95% confidence interval for the difference: −10% to +6%; unadjusted p = 0.60). Baseline ECD (p=0.71), 10-year ECD (p>0.99), and changes in ECD over 10 years (p=0.86) were similar comparing donor diabetes and no-diabetes groups. Conclusions and Relevance The study results do not suggest an association between donor diabetes and PKP outcome. However, the assessment of donor diabetes was imprecise and based on historical data only. The increasing frequency of diabetes in the aging population in the United States affects the donor pool, thus the impact of donor diabetes on long term endothelial health after penetrating and/or endothelial keratoplasty warrants further study with more precise measures of diabetes and its complications. Trial Registration clinicaltrials.gov NCT00006411 PMID:25439611

A Comparison of Oxidative Lactate Metabolism in Traumatically Injured Brain and Control Brain.

PubMed

Jalloh, Ibrahim; Helmy, Adel; Howe, Duncan J; Shannon, Richard J; Grice, Peter; Mason, Andrew; Gallagher, Clare N; Murphy, Michael P; Pickard, John D; Menon, David K; Carpenter, T Adrian; Hutchinson, Peter J; Carpenter, Keri L H

2018-05-18

Metabolic abnormalities occur after traumatic brain injury (TBI). Glucose is conventionally regarded as the major energy substrate, although lactate can also be an energy source. We compared 3- 13 C lactate metabolism in TBI with "normal" control brain and muscle, measuring 13 C-glutamine enrichment to assess tricarboxylic acid (TCA) cycle metabolism. Microdialysis catheters in brains of nine patients with severe TBI, five non-TBI brain surgical patients, and five resting muscle (non-TBI) patients were perfused (24 h in brain, 8 h in muscle) with 8 mmol/L sodium 3- 13 C lactate. Microdialysate analysis employed ISCUS and nuclear magnetic resonance. In TBI, with 3- 13 C lactate perfusion, microdialysate glucose concentration increased nonsignificantly (mean +11.9%, p = 0.463), with significant increases (p = 0.028) for lactate (+174%), pyruvate (+35.8%), and lactate/pyruvate ratio (+101.8%). Microdialysate 13 C-glutamine fractional enrichments (median, interquartile range) were: for C4 5.1 (0-11.1) % in TBI and 5.7 (4.6-6.8) % in control brain, for C3 0 (0-5.0) % in TBI and 0 (0-0) % in control brain, and for C2 2.9 (0-5.7) % in TBI and 1.8 (0-3.4) % in control brain. 13 C-enrichments were not statistically different between TBI and control brain, showing both metabolize 3- 13 C lactate via TCA cycle, in contrast to muscle. Several patients with TBI exhibited 13 C-glutamine enrichment above the non-TBI control range, suggesting lactate oxidative metabolism as a TBI "emergency option."

Monitoring environmental pollutants by microchip capillary electrophoresis with electrochemical detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Gang; Lin, Yuehe; Wang, Joseph

2006-01-15

This is a review article. During the past decade, significant progress in the development of miniaturized microfluidic systems has Occurred due to the numerous advantages of microchip analysis. This review focuses on recent advances and the key strategies in microchip capillary electrophoresis (CE) with electrochemical detection (ECD) for separating and detecting a variety of environmental pollutants. The subjects covered include the fabrication of microfluidic chips, ECD, typical applications of microchip CE with ECD in environmental analysis, and future prospects. It is expected that microchip CE-ECD will become a powerful tool in the environmental field and will lead to the creationmore » of truly portable devices.« less

Effects of caffeine on the preterm brain: An observational study.

PubMed

Dix, Laura M L; van Bel, Frank; Baerts, Willem; Lemmers, Petra M A

2018-05-01

Caffeine improves neurodevelopmental outcome of preterm infants. This study analyses the effects of caffeine on the neonatal brain. We hypothesized that caffeine has a neuroprotective effect through an increase in oxygen metabolism; reflected by increased cerebral oxygen extraction, electrical function, and perfusion. Preterm infants <32 weeks gestation (GA) receiving their primary dose caffeine-base (10 mg/kg) were included. Ten minutes of stable monitoring were selected before, during, and every hour up to 6 h after caffeine. Near-infrared spectroscopy monitored regional cerebral oxygenation (rScO 2 ) and extraction (FTOE). Amplitude-integrated electroencephalogram (aEEG) monitored minimum, mean and maximum amplitudes. Spontaneous activity transients (SAT) rate and the interval between SATs (ISI) were calculated. Mean arterial blood pressure (MABP), heart rate (HR) and arterial oxygen saturation (SaO 2 ) were monitored. Arterial pCO 2 's were collected before and 4 h after caffeine. Brain perfusion was assessed 1 h before and 3 h after caffeine by Doppler-measured resistance-index (RI), peak systolic velocity (PSV) and end-diastolic velocity (EDV), in the anterior cerebral artery (ACA) and internal carotid artery (ICA). Results were presented in mean ± SD. 34 infants, mean GA 28.8 ± 2.1 wk, were included. rScO 2 significantly decreased from 69 ± 11 to 63 ± 12 1 h after caffeine, and recovered at 6 h (66 ± 10). FTOE increased correspondingly. MABP and HR increased significantly. PSV in the ACA decreased slightly. Other Doppler variables, aEEG parameters, and SaO 2 were unaffected. Caffeine increases oxygen extraction, suggesting a (transient) stimulating effect on brain metabolism. However, no substantial changes were found in brain perfusion and in electrical brain activity. Copyright © 2018 Elsevier B.V. All rights reserved.

Role of Brain Perfusion SPECT with 99mTc HMPAO in the Assessment of Response to Drug Therapy in Patients with Autoimmune Vasculitis: A Prospective Study

PubMed Central

Mauro, Liberatore; Manuela, Morreale; Valentina, Megna; Sara, Collorone; Chondrogiannis, Sotirios; Maria, Drudi Francesco; Christos, Anagnostou; Liana, Civitelli; Ada, Francia; Maffione, Anna Margherita; Marzola, Maria Cristina; Rubello, Domenico

2015-01-01

Background: The diagnosis of vasculitis in the brain remains a quite difficult achievement. To the best of our knowledge, there is no imaging method reported in literature which is capable of reaching to a diagnosis of vasculitis with very high sensitivity. Aim: The aim of this study was to determine whether perfusion brain single photon emission computed tomography (SPECT) can be usefully employed in monitoring the treatment of vasculitis, allowing treating only potentially responder patients and avoiding the side effects on patients who do not respond. Materials and Methods: Twenty patients (two males and 18 females) suffering from systemic lupus erythematosus (SLE; n = 5), Behcet's disease (BD; n = 5), undifferentiated vasculitis (UV; n = 5), and Sjogren's syndrome (SS; n = 5) were included in the study. All patients underwent a wide neurological anamnestic investigation, a complete objective neurological examination and SPECT of the brain with 99mTc-hexamethyl-propylene-aminoxime (HMPAO). The brain SPECT was then repeated after appropriate medical treatment. The neurological and neuropsychiatric follow-up was performed at 6 months after the start of the treatment. Results: Overall, the differences between the scintigraphic results obtained after and before the medical treatment indicated a statistically significant increase of the cerebral perfusion (CP). In 19 out of 200 regions of interest (ROI) studied, the difference between pre- and post treatment percentages had negative sign, indicating a worsening of CP. This latter event has occurred six times (five in the same patients) in the UV, 10 times (eight in the same patients) in the SLE, never in BD, and three times (two in the same patient) in the SS. Conclusion: The reported results seem to indicate the possibility of identifying, by the means of a brain SPECT, responder and nonresponder (unchanged or worsened CP) patients, affected by autoimmune vasculitis, to the therapy. PMID:25973400

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oborn, B. M.; Kolling, S.; Metcalfe, P. E.

Purpose: A potential side effect of inline MRI-linac systems is electron contamination focusing causing a high skin dose. In this work, the authors reexamine this prediction for an open bore 1 T MRI system being constructed for the Australian MRI-Linac Program. The efficiency of an electron contamination deflector (ECD) in purging electron contamination from the linac head is modeled, as well as the impact of a helium gas region between the deflector and phantom surface for lowering the amount of air-generated contamination. Methods: Magnetic modeling of the 1 T MRI was used to generate 3D magnetic field maps both withmore » and without the presence of an ECD located immediately below the MLC’s. Forty-seven different ECD designs were modeled and for each the magnetic field map was imported into Geant4 Monte Carlo simulations including the linac head, ECD, and a 30 × 30 × 30 cm{sup 3} water phantom located at isocenter. For the first generation system, the x-ray source to isocenter distance (SID) will be 160 cm, resulting in an 81.2 cm long air gap from the base of the ECD to the phantom surface. The first 71.2 cm was modeled as air or helium gas, with the latter encased between two windows of 50 μm thick high density polyethlyene. 2D skin doses (at 70 μm depth) were calculated across the phantom surface at 1 × 1 mm{sup 2} resolution for 6 MV beams of field size of 5 × 5, 10 × 10, and 20 × 20 cm{sup 2}. Results: The skin dose was predicted to be of similar magnitude as the generic systems modeled in previous work, 230% to 1400% ofD {sub max} for 5 × 5 to 20 × 20 cm{sup 2}, respectively. Inclusion of the ECD introduced a nonuniformity to the MRI imaging field that ranged from ∼20 to ∼140 ppm while the net force acting on the ECD ranged from ∼151 N to ∼1773 N. Various ECD designs were 100% efficient at purging the electron contamination into the ECD magnet banks; however, a small percentage were scattered back into the beam and continued to the phantom surface. Replacing a large portion of the extended air-column between the ECD and phantom surface with helium gas is a key element as it significantly minimized the air-generated contamination. When using an optimal ECD and helium gas region, the 70 μm skin dose is predicted to increase moderately inside a small hot spot over that of the case with no magnetic field present for the jaw defined square beams examined here. These increases include from 12% to 40% of D {sub max} for 5 × 5 cm{sup 2}, 18% to 55% of D {sub max} for 10 × 10 cm{sup 2}, and from 23% to 65% of D {sub max} for 20 × 20 cm{sup 2}. Conclusions: Coupling an efficient ECD and helium gas region below the MLCs in the 160 cm isocenter MRI-linac system is predicted to ameliorate the impact electron contamination focusing has on skin dose increases. An ECD is practical as its impact on the MRI imaging distortion is correctable, and the mechanical forces acting on it manageable from an engineering point of view.« less

Electron contamination modeling and reduction in a 1 T open bore inline MRI-linac system.

PubMed

Oborn, B M; Kolling, S; Metcalfe, P E; Crozier, S; Litzenberg, D W; Keall, P J

2014-05-01

A potential side effect of inline MRI-linac systems is electron contamination focusing causing a high skin dose. In this work, the authors reexamine this prediction for an open bore 1 T MRI system being constructed for the Australian MRI-Linac Program. The efficiency of an electron contamination deflector (ECD) in purging electron contamination from the linac head is modeled, as well as the impact of a helium gas region between the deflector and phantom surface for lowering the amount of air-generated contamination. Magnetic modeling of the 1 T MRI was used to generate 3D magnetic field maps both with and without the presence of an ECD located immediately below the MLC's. Forty-seven different ECD designs were modeled and for each the magnetic field map was imported into Geant4 Monte Carlo simulations including the linac head, ECD, and a 30 × 30 × 30 cm(3) water phantom located at isocenter. For the first generation system, the x-ray source to isocenter distance (SID) will be 160 cm, resulting in an 81.2 cm long air gap from the base of the ECD to the phantom surface. The first 71.2 cm was modeled as air or helium gas, with the latter encased between two windows of 50 μm thick high density polyethlyene. 2D skin doses (at 70 μm depth) were calculated across the phantom surface at 1 × 1 mm(2) resolution for 6 MV beams of field size of 5 × 5, 10 × 10, and 20 × 20 cm(2). The skin dose was predicted to be of similar magnitude as the generic systems modeled in previous work, 230% to 1400% of D(max) for 5 × 5 to 20 × 20 cm(2), respectively. Inclusion of the ECD introduced a nonuniformity to the MRI imaging field that ranged from ∼20 to ∼140 ppm while the net force acting on the ECD ranged from ∼151 N to ∼1773 N. Various ECD designs were 100% efficient at purging the electron contamination into the ECD magnet banks; however, a small percentage were scattered back into the beam and continued to the phantom surface. Replacing a large portion of the extended air-column between the ECD and phantom surface with helium gas is a key element as it significantly minimized the air-generated contamination. When using an optimal ECD and helium gas region, the 70 μm skin dose is predicted to increase moderately inside a small hot spot over that of the case with no magnetic field present for the jaw defined square beams examined here. These increases include from 12% to 40% of [Formula: see text] for 5 × 5 cm(2), 18% to 55% of D(max) for 10 × 10 cm(2), and from 23% to 65% of D(max) for 20 × 20 cm(2). Coupling an efficient ECD and helium gas region below the MLCs in the 160 cm isocenter MRI-linac system is predicted to ameliorate the impact electron contamination focusing has on skin dose increases. An ECD is practical as its impact on the MRI imaging distortion is correctable, and the mechanical forces acting on it manageable from an engineering point of view.

Arterial Spin Labeling - Fast Imaging with Steady-State Free Precession (ASL-FISP): A Rapid and Quantitative Perfusion Technique for High Field MRI

PubMed Central

Gao, Ying; Goodnough, Candida L.; Erokwu, Bernadette O.; Farr, George W.; Darrah, Rebecca; Lu, Lan; Dell, Katherine M.; Yu, Xin; Flask, Chris A.

2014-01-01

Arterial Spin Labeling (ASL) is a valuable non-contrast perfusion MRI technique with numerous clinical applications. Many previous ASL MRI studies have utilized either Echo-Planar Imaging (EPI) or True Fast Imaging with Steady-State Free Precession (True FISP) readouts that are prone to off-resonance artifacts on high field MRI scanners. We have developed a rapid ASL-FISP MRI acquisition for high field preclinical MRI scanners providing perfusion-weighted images with little or no artifacts in less than 2 seconds. In this initial implementation, a FAIR (Flow-Sensitive Alternating Inversion Recovery) ASL preparation was combined with a rapid, centrically-encoded FISP readout. Validation studies on healthy C57/BL6 mice provided consistent estimation of in vivo mouse brain perfusion at 7 T and 9.4 T (249±38 ml/min/100g and 241±17 ml/min/100g, respectively). The utility of this method was further demonstrated in detecting significant perfusion deficits in a C57/BL6 mouse model of ischemic stroke. Reasonable kidney perfusion estimates were also obtained for a healthy C57/BL6 mouse exhibiting differential perfusion in the renal cortex and medulla. Overall, the ASL-FISP technique provides a rapid and quantitative in vivo assessment of tissue perfusion for high field MRI scanners with minimal image artifacts. PMID:24891124

An experimental study and finite element modeling of head and neck cooling for brain hypothermia.

PubMed

Li, Hui; Chen, Roland K; Tang, Yong; Meurer, William; Shih, Albert J

2018-01-01

Reducing brain temperature by head and neck cooling is likely to be the protective treatment for humans when subjects to sudden cardiac arrest. This study develops the experimental validation model and finite element modeling (FEM) to study the head and neck cooling separately, which can induce therapeutic hypothermia focused on the brain. Anatomically accurate geometries based on CT images of the skull and carotid artery are utilized to find the 3D geometry for FEM to analyze the temperature distributions and 3D-printing to build the physical model for experiment. The results show that FEM predicted and experimentally measured temperatures have good agreement, which can be used to predict the temporal and spatial temperature distributions of the tissue and blood during the head and neck cooling process. Effects of boundary condition, perfusion, blood flow rate, and size of cooling area are studied. For head cooling, the cooling penetration depth is greatly depending on the blood perfusion in the brain. In the normal blood flow condition, the neck internal carotid artery temperature is decreased only by about 0.13°C after 60min of hypothermia. In an ischemic (low blood flow rate) condition, such temperature can be decreased by about 1.0°C. In conclusion, decreasing the blood perfusion and metabolic reduction factor could be more beneficial to cool the core zone. The results also suggest that more SBC researches should be explored, such as the optimization of simulation and experimental models, and to perform the experiment on human subjects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Electron capture dissociation of polypeptides using a 3 Tesla Fourier transform ion cyclotron resonance mass spectrometer.

PubMed

Polfer, Nicolas C; Haselmann, Kim F; Zubarev, Roman A; Langridge-Smith, Pat R R

2002-01-01

Electron capture dissociation (ECD) of polypeptides has been demonstrated using a commercially available 3 Tesla Fourier transform ion cyclotron resonance (FTICR) instrument. A conventional rhenium filament, designed for high-energy electron impact ionisation, was used to effect ECD of substance P, bee venom melittin and bovine insulin, oxidised B chain. A retarding field analysis of the effective electron kinetic energy distribution entering the ICR cell suggests that one of the most important parameters governing ECD for this particular instrument is the need to employ low trapping plate voltages. This is shown to maximise the abundance of low-energy electrons. The demonstration of ECD at this relatively low magnetic field strength could offer the prospect of more routine ECD analysis for the wider research community, given the reduced cost of such magnets and (at least theoretically) the greater ease of electron/ion cloud overlap at lower field. Copyright 2002 John Wiley & Sons, Ltd.

Further evidence of psychological factors underlying choice of elective cesarean delivery (ECD) by primigravidae.

PubMed

Matinnia, Nasrin; Haghighi, Mohammad; Jahangard, Leila; Ibrahim, Faisal B; Rahman, Hejar A; Ghaleiha, Ali; Holsboer-Trachsler, Edith; Brand, Serge

2018-01-01

Requests for elective cesarean delivery (ECD) have increased in Iran. While some sociodemographic and fear-related factors have been linked with this choice, psychological factors such as self-esteem, stress, and health beliefs are under-researched. A total of 342 primigravidae (mean age = 25 years) completed questionnaires covering psychological dimensions such as self-esteem, perceived stress, marital relationship quality, perceived social support, and relevant health-related beliefs. Of the sample, 214 (62.6%) chose to undergo ECD rather than vaginal delivery (VD). This choice was associated with lower self-esteem, greater perceived stress, belief in higher susceptibility to problematic birth and barriers to an easy birth, along with lower perceived severity of ECD, fewer perceived benefits from VD, lower self-efficacy and a lower feeling of preparedness. No differences were found for marital relationship quality or perceived social support. The pattern suggests that various psychological factors such as self-esteem, self-efficacy, and perceived stress underpin the decision by primigravidae to have an ECD.

Structural insights of ZIP4 extracellular domain critical for optimal zinc transport

NASA Astrophysics Data System (ADS)

Zhang, Tuo; Sui, Dexin; Hu, Jian

2016-06-01

The ZIP zinc transporter family is responsible for zinc uptake from the extracellular milieu or intracellular vesicles. The LIV-1 subfamily, containing nine out of the 14 human ZIP proteins, is featured with a large extracellular domain (ECD). The critical role of the ECD is manifested by disease-causing mutations on ZIP4, a representative LIV-1 protein. Here we report the first crystal structure of a mammalian ZIP4-ECD, which reveals two structurally independent subdomains and an unprecedented dimer centred at the signature PAL motif. Structure-guided mutagenesis, cell-based zinc uptake assays and mapping of the disease-causing mutations indicate that the two subdomains play pivotal but distinct roles and that the bridging region connecting them is particularly important for ZIP4 function. These findings lead to working hypotheses on how ZIP4-ECD exerts critical functions in zinc transport. The conserved dimeric architecture in ZIP4-ECD is also demonstrated to be a common structural feature among the LIV-1 proteins.

Cerebral perfusion imaging with bolus harmonic imaging (Honorable Mention Poster Award)

NASA Astrophysics Data System (ADS)

Kier, Christian; Toth, Daniel; Meyer-Wiethe, Karsten; Schindler, Angela; Cangur, Hakan; Seidel, Gunter; Aach, Til

2005-04-01

Fast visualisation of cerebral microcirculation supports diagnosis of acute stroke. However, the commonly used CT/MRI-based methods are time consuming, costly and not applicable to every patient. The bolus perfusion harmonic imaging (BHI) method is an ultrasound imaging technique which makes use of the fact, that ultrasound contrast agents unlike biological tissues resonate at harmonic frequencies. Exploiting this effect, the contrast between perfused and non-perfused areas can be improved. Thus, BHI overcomes the low signal-to-noise ratio of transcranial ultrasound and the high impedance of the skull. By analysing image sequences, visualising the qualitative characteristics of an US contrast agent bolus injection becomes possible. The analysis consists of calculating four perfusion-related parameters, Local Peak Intensity, Time To Peak, Area Under Curve, and Average Rising, from the time/intensity curve and providing them as colour-coded images. For calculating these parameters the fundamental assumption is that image intensity corresponds to contrast agent concentration which in turn shows the perfusion of the corresponding brain region. In a clinical study on patients suffering from acute ischemic stroke it is shown that some of the parameters correlate significantly to the infarction area. Thus, BHI becomes a less time-consuming and inexpensive bedside method for diagnosis of cerebral perfusion deficits.

Early Childhood Development through an Integrated Program: Evidence from the Philippines. Impact Evaluation Series No. 2. World Bank Policy Research Working Paper 3922-IE

ERIC Educational Resources Information Center

Armecin, Graeme; Behrman, Jere R.; Ghuman, Sharon; Gultiano, Socorro; King, Elizabeth M.; Lee, Nanette

2006-01-01

More attention and resources have been devoted in recent years to early childhood development (ECD) in low- and middle-income countries. Rigorous studies on the effectiveness of ECD-related programs for improving children's development in various dimensions in the developing world are scant. The authors evaluate an important ECD initiative of the…

Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma.

PubMed Central

Gamallo, C.; Palacios, J.; Suarez, A.; Pizarro, A.; Navarro, P.; Quintanilla, M.; Cano, A.

1993-01-01

Recently, a correlation has been suggested between a loss of E-cadherin (E-CD) and increased invasiveness of neoplastic cells. In this study, E-CD expression in breast cancer was investigated using an affinity-purified antibody (ECCD-2) in an immunoenzymatic (avidin-biotin-alkaline phosphatase) test. Intensity and extension of E-CD immunoreactivity were evaluated in 61 breast carcinomas and correlated with their histological type and grade, nodal involvement, and hormonal receptor status. Histological types were infiltrating ductal carcinoma of no special type (n = 54) and infiltrating lobular carcinoma (n = 7). All infiltrating ductal carcinomas of no special type except two grade 3 carcinomas showed positive immunoreactivity that was variable among different cases. Grade 1 breast carcinomas (n = 10) showed greater immunoreactivity than grade 2 (n = 25) and grade 3 (n = 19) carcinomas. E-CD immunoreactivity correlated positively with the degree of tubular formation and inversely with the mitoses number. None of the infiltrating lobular carcinomas expressed E-CD in their infiltrating cells, whereas they showed only weak immunostains in areas of atypical lobular hyperplasia and lobular carcinoma in situ. These results indicate that E-CD expression correlates with histological type and grade in breast carcinomas. Images Figure 1 Figure 2 Figure 3 PMID:7682767

Effect of laser peripheral iridotomy using argon and neodymium-YAG lasers on corneal endothelial cell density: 7-year longitudinal evaluation.

PubMed

Ono, Takashi; Iida, Masaharu; Sakisaka, Toshihiro; Minami, Keiichiro; Miyata, Kazunori

2018-03-01

To evaluate the changes in corneal endothelial cell density (ECD) over a 7-year period after laser peripheral iridotomy (LPI) using argon and neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers. Retrospective case series. Eyes that underwent prophylactic LPI using argon and Nd:YAG lasers were followed up for 7 years. Central corneal endothelial cells were observed by use of noncontact specular microscopy preoperatively and at 1 and 7 years postoperatively. Changes in ECD and the associations between preoperative ECD and the total energy of the Nd:YAG laser were evaluated. Fifty-one eyes of 51 patients were followed up for 7 years. The ECD significantly decreased after LPI (P < 0.049), and the reduction rate at 1 year after the surgery (1.69 ± 4.80%, 95% CI: 0.34%-3.04%) was significantly higher than the annual reduction rates after 1 year (0.17 ± 0.85%/y, P = 0.036, 95% CI: -0.07% to 0.41%). No association was found between the preoperative ECD and the total laser energy. Long-term evaluation indicated that the reduction in ECD after argon-Nd:YAG laser LPI was present but small during the initial year and was negligible after 1 year.

Mapping the dynamics of brain perfusion using functional ultrasound in a rat model of transient middle cerebral artery occlusion

PubMed Central

Brunner, Clément; Isabel, Clothilde; Martin, Abraham; Dussaux, Clara; Savoye, Anne; Emmrich, Julius; Montaldo, Gabriel; Mas, Jean-Louis; Urban, Alan

2015-01-01

Following middle cerebral artery occlusion, tissue outcome ranges from normal to infarcted depending on depth and duration of hypoperfusion as well as occurrence and efficiency of reperfusion. However, the precise time course of these changes in relation to tissue and behavioral outcome remains unsettled. To address these issues, a three-dimensional wide field-of-view and real-time quantitative functional imaging technique able to map perfusion in the rodent brain would be desirable. Here, we applied functional ultrasound imaging, a novel approach to map relative cerebral blood volume without contrast agent, in a rat model of brief proximal transient middle cerebral artery occlusion to assess perfusion in penetrating arterioles and venules acutely and over six days thanks to a thinned-skull preparation. Functional ultrasound imaging efficiently mapped the acute changes in relative cerebral blood volume during occlusion and following reperfusion with high spatial resolution (100 µm), notably documenting marked focal decreases during occlusion, and was able to chart the fine dynamics of tissue reperfusion (rate: one frame/5 s) in the individual rat. No behavioral and only mild post-mortem immunofluorescence changes were observed. Our study suggests functional ultrasound is a particularly well-adapted imaging technique to study cerebral perfusion in acute experimental stroke longitudinally from the hyper-acute up to the chronic stage in the same subject. PMID:26721392

Large enhancement of perfusion contribution on fMRI signal

PubMed Central

Wang, Xiao; Zhu, Xiao-Hong; Zhang, Yi; Chen, Wei

2012-01-01

The perfusion contribution to the total functional magnetic resonance imaging (fMRI) signal was investigated using a rat model with mild hypercapnia at 9.4 T, and human subjects with visual stimulation at 4 T. It was found that the total fMRI signal change could be approximated as a linear superposition of ‘true' blood oxygenation level-dependent (BOLD; T2/T2*) effect and the blood flow-related (T1) effect. The latter effect was significantly enhanced by using short repetition time and large radiofrequency pulse flip angle and became comparable to the ‘true' BOLD signal in response to a mild hypercapnia in the rat brain, resulting in an improved contrast-to-noise ratio (CNR). Bipolar diffusion gradients suppressed the intravascular signals but had no significant effect on the flow-related signal. Similar results of enhanced fMRI signal were observed in the human study. The overall results suggest that the observed flow-related signal enhancement is likely originated from perfusion, and this enhancement can improve CNR and the spatial specificity for mapping brain activity and physiology changes. The nature of mixed BOLD and perfusion-related contributions in the total fMRI signal also has implication on BOLD quantification, in particular, the BOLD calibration model commonly used to estimate the change of cerebral metabolic rate of oxygen. PMID:22395206

Radiographic absence of the posterior communicating arteries and the prediction of cognitive dysfunction after carotid endarterectomy.

PubMed

Sussman, Eric S; Kellner, Christopher P; Mergeche, Joanna L; Bruce, Samuel S; McDowell, Michael M; Heyer, Eric J; Connolly, E Sander

2014-09-01

Approximately 25% of patients exhibit cognitive dysfunction 24 hours after carotid endarterectomy (CEA). One of the purported mechanisms of early cognitive dysfunction (eCD) is hypoperfusion due to inadequate collateral circulation during cross-clamping of the carotid artery. The authors assessed whether poor collateral circulation within the circle of Willis, as determined by preoperative CT angiography (CTA) or MR angiography (MRA), could predict eCD. Patients who underwent CEA after preoperative MRA or CTA imaging and full neuropsychometric evaluation were included in this study (n = 42); 4 patients were excluded due to intraoperative electroencephalographic changes and subsequent shunt placement. Thirty-eight patients were included in the statistical analyses. Patients were stratified according to posterior communicating artery (PCoA) status (radiographic visualization of at least 1 PCoA vs of no PCoAs). Variables with p < 0.20 in univariate analyses were included in a stepwise multivariate logistic regression model to identify predictors of eCD after CEA. Overall, 23.7% of patients exhibited eCD. In the final multivariate logistic regression model, radiographic absence of both PCoAs was the only independent predictor of eCD (OR 9.64, 95% CI 1.43-64.92, p = 0.02). The absence of both PCoAs on preoperative radiographic imaging is predictive of eCD after CEA. This finding supports the evidence for an underlying ischemic etiology of eCD. Larger studies are justified to verify the findings of this study. Clinical trial registration no.: NCT00597883 ( http://www.clinicaltrials.gov ).

Early Childhood Diarrhea Predicts Cognitive Delays in Later Childhood Independently of Malnutrition

PubMed Central

Pinkerton, Relana; Oriá, Reinaldo B.; Lima, Aldo A. M.; Rogawski, Elizabeth T.; Oriá, Mônica O. B.; Patrick, Peter D.; Moore, Sean R.; Wiseman, Benjamin L.; Niehaus, Mark D.; Guerrant, Richard L.

2016-01-01

Understanding the complex relationship between early childhood infectious diseases, nutritional status, poverty, and cognitive development is significantly hindered by the lack of studies that adequately address confounding between these variables. This study assesses the independent contributions of early childhood diarrhea (ECD) and malnutrition on cognitive impairment in later childhood. A cohort of 131 children from a shantytown community in northeast Brazil was monitored from birth to 24 months for diarrhea and anthropometric status. Cognitive assessments including Test of Nonverbal Intelligence (TONI), coding tasks (WISC-III), and verbal fluency (NEPSY) were completed when children were an average of 8.4 years of age (range = 5.6–12.7 years). Multivariate analysis of variance models were used to assess the individual as well as combined effects of ECD and stunting on later childhood cognitive performance. ECD, height for age (HAZ) at 24 months, and weight for age (WAZ) at 24 months were significant univariate predictors of the studies three cognitive outcomes: TONI, coding, and verbal performance (P < 0.05). Multivariate models showed that ECD remained a significant predictor, after adjusting for the effect of 24 months HAZ and WAZ, for both TONI (HAZ, P = 0.029 and WAZ, P = 0.006) and coding (HAZ, P = 0.025 and WAZ, P = 0.036) scores. WAZ and HAZ were also significant predictors after adjusting for ECD. ECD remained a significant predictor of coding (WISC III) after number of household income was considered (P = 0.006). This study provides evidence that ECD and stunting may have independent effects on children's intellectual function well into later childhood. PMID:27601523

Cataract surgery in eyes with low corneal endothelial cell density.

PubMed

Hayashi, Ken; Yoshida, Motoaki; Manabe, Shin-ichi; Hirata, Akira

2011-08-01

To compare corneal endothelial damage after cataract surgery in eyes with low endothelial cell density (ECD) and eyes with normal ECD. Hayashi Eye Hospital, Fukuoka, Japan. Case-control study. Cataract surgery was performed in eyes with a low ECD (500 to 1000 cells/mm(2)) (low-density group) and control eyes with a normal ECD. The ECD and central corneal thickness (CCT) were measured preoperatively and 1 and 3 months postoperatively, and the percentage cell loss and increase in CCT were compared. The low-density group and control group each comprised 50 eyes. In the low-density group, 39 eyes had nonprogressive endothelial pathology and 11 had Fuchs dystrophy. The mean ECD was significantly less and the CCT significantly greater in the low-density group than in the control group throughout the follow-up (P ≤.0066). However, no significant difference in the percentage of cell loss was found between groups at 1 or 3 months (5.1%, low-density group; 4.2%, control group) (P ≥.1477). The percentage increase in CCT was significantly greater in the low-density group than in the control group at 1 month (P<.0001), although there was no significant difference at 3 months (0.4% and -0.4%, respectively) (P=.2172). Corneal endothelial damage after cataract surgery in eyes with low ECD was slight and comparable to that in healthy eyes, which suggests that cataract surgery alone (without corneal transplantation) should be performed first. Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Determination of the location of positive charges in gas-phase polypeptide polycations by tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Kjeldsen, Frank; Savitski, Mikhail M.; Adams, Christopher M.; Zubarev, Roman A.

2006-06-01

Location of protonated sites in electrospray-ionized gas-phase peptides and proteins was performed with tandem mass spectrometry using ion activation by both electron capture dissociation (ECD) and collisional activation dissociation (CAD). Charge-carrying sites were assigned based on the increment in the charge state of fragment ions compared to that of the previous fragment in the same series. The property of ECD to neutralize preferentially the least basic site was confirmed by the analysis of three thousand ECD mass spectra of doubly charged tryptic peptides. Multiply charged cations of bradykinin, neurotensin and melittin were studied in detail. For n+ precursors, ECD revealed the positions of (n - 1) most basic sites, while CAD could in principle locate alln charges. However, ECD introduced minimal proton mobilization and produced more conclusive data than CAD, for which N- and C-terminal data often disagreed. Consistent with the dominance of one charge conformer and its preservation in ECD, the average charge states of complementary fragments of n+ ions almost always added up to (n - 1)+, while the similar figure in CAD often deviated from n+, indicating extensive charge isomerization under collisional excitation. For bradykinin and neurotensin, the charge assignments were largely in agreement with the intrinsic gas-phase basicity of the respective amino acid residues. For melittin ions in higher charge states, ECD revealed the charging at both intrinsically basic as well as at less basic residues, which was attributed to charge sharing with other groups due to the presence of secondary and higher order structures in this larger polypeptide.

Normothermic Perfusion in the Assessment and Preservation of Declined Livers Before Transplantation: Hyperoxia and Vasoplegia—Important Lessons From the First 12 Cases

PubMed Central

Watson, Christopher J.E.; Kosmoliaptsis, Vasilis; Randle, Lucy V.; Gimson, Alexander E.; Brais, Rebecca; Klinck, John R.; Hamed, Mazin; Tsyben, Anastasia; Butler, Andrew J.

2017-01-01

Background A program of normothermic ex situ liver perfusion (NESLiP) was developed to facilitate better assessment and use of marginal livers, while minimizing cold ischemia. Methods Declined marginal livers and those offered for research were evaluated. Normothermic ex situ liver perfusion was performed using an erythrocyte-based perfusate. Viability was assessed with reference to biochemical changes in the perfusate. Results Twelve livers (9 donation after circulatory death [DCD] and 3 from brain-dead donors), median Donor Risk Index 2.15, were subjected to NESLiP for a median 284 minutes (range, 122-530 minutes) after an initial cold storage period of 427 minutes (range, 222-877 minutes). The first 6 livers were perfused at high perfusate oxygen tensions, and the subsequent 6 at near-physiologic oxygen tensions. After transplantation, 5 of the first 6 recipients developed postreperfusion syndrome and 4 had sustained vasoplegia; 1 recipient experienced primary nonfunction in conjunction with a difficult explant. The subsequent 6 liver transplants, with livers perfused at lower oxygen tensions, reperfused uneventfully. Three DCD liver recipients developed cholangiopathy, and this was associated with an inability to produce an alkali bile during NESLiP. Conclusions Normothermic ex situ liver perfusion enabled assessment and transplantation of 12 livers that may otherwise not have been used. Avoidance of hyperoxia during perfusion may prevent postreperfusion syndrome and vasoplegia, and monitoring biliary pH, rather than absolute bile production, may be important in determining the likelihood of posttransplant cholangiopathy. Normothermic ex situ liver perfusion has the potential to increase liver utilization, but more work is required to define factors predicting good outcomes. PMID:28437389

The extracellular domain of Her2 in serum as a biomarker of breast cancer.

PubMed

Perrier, Alexandre; Gligorov, Joseph; Lefèvre, Guillaume; Boissan, Mathieu

2018-02-28

Breast cancer is a major health problem worldwide. In ~15% of breast cancers, the epidermal growth factor receptor HER2, a transmembrane protein, is overexpressed. This HER2 overexpression is associated with an aggressive form of the disease and a poor clinical prognosis. The extracellular domain (ECD) of HER2 is released into the blood by a proteolytic mechanism known as "ECD shedding". This proteolytic shedding leaves a constitutively active truncated receptor in the membrane that is 10-100-fold more oncogenic than the full-length receptor and promotes the growth and survival of cancer cells. Shedding of the HER2 ECD is increased during metastasis: whereas 15% of primary breast cancer patients have elevated levels of serum HER2 ECD (sHER2 ECD), the levels reach 45% in patients with metastatic disease. Thus, sHER2 ECD has been proposed as a promising biomarker for cancer recurrence and for monitoring the disease status of patients overexpressing HER2. Nevertheless, in 2016, the American Society of Clinical Oncology advises clinicians not to use soluble HER2 levels to guide their choice of adjuvant therapy for patients with HER2-positive breast cancer, because the evidence was considered not strong enough. Currently, biomarkers such as carcinoembryonic antigen and cancer antigen 15-3 are widely used to monitor metastatic breast cancer disease even if the level of evidence of clinical impact of this monitoring is poor. In this article, we review the evidence that sHER2 ECD might be used in some situations as a biomarker for breast cancer. Although this serum biomarker will not replace the direct measurement of tumor HER2 status for diagnosis of early-stage tumors; it might be especially useful in metastatic disease for prognosis, as an indicator of cancer progression and of therapy response, particularly to anti-HER2 therapies. Owing to these data, sHER2 ECD should be considered as a promising biomarker to detect cancer recurrence and metastasis.

Estrogenic effect of leachates and soil extracts from lysimeters spiked with sewage sludge and reference endocrine disrupters.

PubMed

Dizer, Halim; Fischer, Birgit; Sepulveda, Isabel; Loffredo, Elisabetta; Senesi, Nicola; Santana, Fernando; Hansen, Peter-D

2002-01-01

Several experiments were conducted to evaluate the behavior and performance of some potential endocrine disrupters (ECDs). Two in vitro screening assays, one based on MCF7-cell proliferation (E-screen test) and the other on estrogenic receptor activity [enzyme-linked receptor assay (ELRA)], were used for the tests, which were done in lysimeters 80 cm in diameter with depth of 30 cm (shallow) or 90 cm (deep). A sandy soil was used to fill in all lysimeters, which were spiked on the surface with either: (a) a sewage sludge (SS) at a dose equivalent to 20 tons ha-1; (b) a mixture of reference ECDs, comprising 17 alpha- and 17 beta-estradiol (E2), nonylphenol, octylphenol, and bisphenol A at doses 100 times higher than the maximum concentrations respectively found in the applied SS; or (c) a mixture of ECDs and SS. After percolation of the lysimeters with rain and/or artificial water, five leachates were sampled from each lysimeter during a period of 210 days. Immediately after the lysimeter percolation experiments, four and six soil fractions were dissected from, respectively, the 30-cm and 90-cm lysimeters and extracted by water. Both the leachate and soil extract samples were analyzed for their estrogenicity using the assays indicated above. The E-screen assay was highly sensitive only for some leachate and extract samples but gave no response for most leachates and soil extracts. The results of the ELRA assay suggests a significantly higher estrogenicity of leachate samples from shallow lysimeters compared with that of leachates from deep lysimeters. In contrast, the estrogenic effect measured for soil extracts of shallow lysimeters was lower than that measured for soil extracts of deep lysimeters. The results of the E-screen assay suggests the occurrence of a fast mobilization of applied ECDs and a moderate retardation effect of native ECDs contained in applied SS in the sandy soil used in the lysimeters. In lysimeters spiked with a mixture of SS and ECDs, the washing-out effect of ECDs in the first leachate fraction decreased, but the distribution of ECDs in the lysimeters increased. The relatively high estrogenic impact measured for soil water extracts suggests that the ECDs were mostly associated with water-soluble fractions of organic matter and/or water-suspended fractions of the mineral soil matrix. The application of SS to agricultural and forest fields may determine the immobilization of ECDs in soil or their movement to surface and/or groundwater. Therefore, an endocrine risk of exposure exists for the water and soil organisms.

Amphetamine manipulates monoamine oxidase-A level and behavior using theranostic aptamers of transcription factors AP-1/NF-kB.

PubMed

Liu, Christina H; Ren, Jiaqian; Liu, Philip K

2016-02-03

Monoamine oxidase (MAO) enzymes play a critical role in controlling the catabolism of monoamine neurotransmitters and biogenic trace amines and behavior in humans. However, the mechanisms that regulate MAO are unclear. Several transcription factor proteins are proposed to modulate the transcription of MAO gene, but evidence supporting these hypotheses is controversial. We aimed to investigate the mechanism of gene transcription regulator proteins on amphetamine-induced behavior. We applied aptamers containing a DNA binding sequence, as well as a random sequence (without target) to study the modulation of amphetamine-induced MAO levels and hyperactivity in living mice. We pretreated in adult male C57black6 mice (Taconic Farm, Germantown, NY) (n ≥ 3 litters at a time), 2 to 3 months of age (23 ± 2 gm body weight) with double-stranded (ds) DNA aptamers with sequence specific to activator protein-1 (5ECdsAP1), nuclear factor-kappa beta (5ECdsNF-kB), special protein-1 (5ECdsSP-1) or cyclicAMP responsive element binding (5ECdsCreB) protein binding regions, 5ECdsRan [a random sequence without target], single-stranded AP-1 (5ECssAP-1) (8 nmol DNA per kg) or saline (5 μl, intracerebroventricular [icv] injection) control before amphetamine administration (4 mg/kg, i.p.). We then measured and analyzed locomotor activities and the level of MAO-A and MAO-B activity. In the pathological condition of amphetamine exposure, we showed here that pretreatment with 5ECdsAP1 and 5ECdsNF-kB reversed the decrease of MAO-A activity (p < 0.05, t test), but not activity of the B isomer (MAO-B), in the ventral tegmental area (VTA) and substantia nigra (SN) of C57black6 mice. The change in MAO-A level coincided with a reversed amphetamine-induced restless behavior of mice. Pretreatments with saline, 5ECdsCreB, 5ECdsSP-1, 5ECdsRan or 5ECssAP-1 had no effect. Our data lead us to conclude that elevation of AP-1 or NF-kB indirectly decreases MAO-A protein levels which, in turn, diminishes MAO-A ability in the VTA of the mesolimbic dopaminergic pathway that has been implicated in cells under stress especially in the SN and VTA. This study has implications for design for the treatment of drug exposure and perhaps Parkinson's dementia.

Clinical Phase IIB Trial of Oxycyte Perflurocarbon in Severe Human Traumatic Brain Injury

DTIC Science & Technology

2013-10-01

TERMS Penetrating ballistic brain injury, ischemia, hypoxia, perfluorocarbon , cell death, perfusion. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION...SUBTITLE The Role of Perfluorocarbons in Mitigating Traumatic Brain Injury 5a. CONTRACT NUMBER W81XWH-08-1-0419 5b. GRANT NUMBER 5c. PROGRAM...damage seems to be mediated by mechanisms that follow the initial injury (secondary mechanisms). Perfluorocarbons (PFCs) are one of the methods by which

Effects of Omega-3 Fatty Acids on Resting Cerebral Perfusion in Patients with Mild Cognitive Impairment: A Randomized Controlled Trial.

PubMed

Schwarz, C; Wirth, M; Gerischer, L; Grittner, U; Witte, A V; Köbe, T; Flöel, A

2018-01-01

Alteration of cerebral perfusion can be considered as a possible therapeutic target in mild cognitive impairment. This randomized, placebo-controlled, double-blind proof-of-concept study assessed effects of omega-3 fatty acids on cerebral perfusion in patients with mild cognitive impairment. In thirteen patients (omega:n=5; placebo:n=8) cerebral perfusion was measured before and after 26-weeks intervention within posterior cortical regions using magnetic resonance imaging. There was a medium effect of intervention on cerebral blood flow (η2=0.122) and blood volume (η2=0.098). The omega group showed an increase in blood flow (mean difference: 0.02 [corresponds to 26.1%], 95% confidence interval:0.00-0.05) and blood volume (mean difference: 0.08 [corresponds to 18.5%], 95% confidence interval:0.01-0.15), which was not observed in the placebo group. These preliminary findings suggest that omega-3 fatty acids supplementation may improve perfusion in cerebral regions typically affected in mild cognitive impairment.Regulation of perfusion may help to maintain brain structure and function and potentially delay conversion to dementia.

Simultaneous and Noninvasive Imaging of Cerebral Oxygen Metabolic Rate, Blood Flow and Oxygen Extraction Fraction in Stroke Mice

PubMed Central

Zhu, Xiao-Hong; Chen, James; Tu, Tsang-Wei; Chen, Wei; Song, Sheng-Kwei

2012-01-01

Many brain diseases have been linked to abnormal oxygen metabolism and blood perfusion; nevertheless, there is still a lack of robust diagnostic tools for directly imaging cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF), as well as the oxygen extraction fraction (OEF) that reflects the balance between CMRO2 and CBF. This study employed the recently developed in vivo 17O MR spectroscopic imaging to simultaneously assess CMRO2, CBF and OEF in the brain using a preclinical middle cerebral arterial occlusion mouse model with a brief inhalation of 17O-labeled oxygen gas. The results demonstrated high sensitivity and reliability of the noninvasive 17O-MR approach for rapidly imaging CMRO2, CBF and OEF abnormalities in the ischemic cortex of the MCAO mouse brain. It was found that in the ischemic brain regions both CMRO2 and CBF were substantially lower than that of intact brain regions, even for the mildly damaged brain regions that were unable to be clearly identified by the conventional MRI. In contrast, OEF was higher in the MCAO affected brain regions. This study demonstrates a promising 17O MRI technique for imaging abnormal oxygen metabolism and perfusion in the diseased brain regions. This 17O MRI technique is advantageous because of its robustness, simplicity, noninvasiveness and reliability: features that are essential to potentially translate it to human patients for early diagnosis and monitoring of treatment efficacy. PMID:23000789

Simultaneous and noninvasive imaging of cerebral oxygen metabolic rate, blood flow and oxygen extraction fraction in stroke mice.

PubMed

Zhu, Xiao-Hong; Chen, James M; Tu, Tsang-Wei; Chen, Wei; Song, Sheng-Kwei

2013-01-01

Many brain diseases have been linked to abnormal oxygen metabolism and blood perfusion; nevertheless, there is still a lack of robust diagnostic tools for directly imaging cerebral metabolic rate of oxygen (CMRO(2)) and cerebral blood flow (CBF), as well as the oxygen extraction fraction (OEF) that reflects the balance between CMRO(2) and CBF. This study employed the recently developed in vivo (17)O MR spectroscopic imaging to simultaneously assess CMRO(2), CBF and OEF in the brain using a preclinical middle cerebral arterial occlusion mouse model with a brief inhalation of (17)O-labeled oxygen gas. The results demonstrated high sensitivity and reliability of the noninvasive (17)O-MR approach for rapidly imaging CMRO(2), CBF and OEF abnormalities in the ischemic cortex of the MCAO mouse brain. It was found that in the ischemic brain regions both CMRO(2) and CBF were substantially lower than that of intact brain regions, even for the mildly damaged brain regions that were unable to be clearly identified by the conventional MRI. In contrast, OEF was higher in the MCAO affected brain regions. This study demonstrates a promising (17)O MRI technique for imaging abnormal oxygen metabolism and perfusion in the diseased brain regions. This (17)O MRI technique is advantageous because of its robustness, simplicity, noninvasiveness and reliability: features that are essential to potentially translate it to human patients for early diagnosis and monitoring of treatment efficacy. Copyright © 2012 Elsevier Inc. All rights reserved.

Iofetamine hydrochloride I 123: a new radiopharmaceutical for cerebral perfusion imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Druckenbrod, R.W.; Williams, C.C.; Gelfand, M.J.

1989-01-01

Iofetamine hydrochloride I-123 permits cerebral blood perfusion imaging with single photon emission computed tomography (SPECT). SPECT is more widely available than positron emission tomography, and complements anatomic visualization with X-ray computed tomography (CT) or magnetic resonance imaging. Iofetamine is an amphetamine analog that is rapidly taken up by the lungs, then redistributed principally to the liver and brain. The precise mechanism of localization has not been determined, but is believed to result from nonspecific receptor binding. Brain uptake peaks at 30 minutes postinjection and remains relatively constant through 60 minutes. The drug is metabolized and excreted in the urine, withmore » negligible activity remaining at 48 hours. When compared with CT in stroke patients, visualization may be performed sooner after symptom onset and a larger zone of involvement may be evident with iofetamine. Localization of seizure foci and diagnosis of Alzheimer's disease may also be possible. As CT has revolutionized noninvasive imaging of brain anatomy, SPECT with iofetamine permits routine cerebral blood flow imaging. 36 references.« less

A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment.

PubMed

Xie, Long; Dolui, Sudipto; Das, Sandhitsu R; Stockbower, Grace E; Daffner, Molly; Rao, Hengyi; Yushkevich, Paul A; Detre, John A; Wolk, David A

2016-01-01

Arterial spin labeled perfusion magnetic resonance imaging (ASL MRI) provides non-invasive quantification of cerebral blood flow, which can be used as a biomarker of brain function due to the tight coupling between cerebral blood flow (CBF) and brain metabolism. A growing body of literature suggests that regional CBF is altered in neurodegenerative diseases. Here we examined ASL MRI CBF in subjects with amnestic mild cognitive impairment (n = 65) and cognitively normal healthy controls (n = 62), both at rest and during performance of a memory-encoding task. As compared to rest, task-enhanced ASL MRI improved group discrimination, which supports the notion that physiologic measures during a cognitive challenge, or "stress test", may increase the ability to detect subtle functional changes in early disease stages. Further, logistic regression analysis demonstrated that ASL MRI and concomitantly acquired structural MRI provide complementary information of disease status. The current findings support the potential utility of task-enhanced ASL MRI as a biomarker in early Alzheimer's disease.

The Effect of Severe Carotid Occlusive Disease and Its Surgical Treatment on Cognitive Functions of the Brain

ERIC Educational Resources Information Center

Soinne, Lauri; Helenius, Johanna; Tikkala, Irene; Saimanen, Eija; Salonen, Oili; Hietanen, Marja; Lindsberg, Perttu J.; Kaste, Markku; Tatlisumak, Turgut

2009-01-01

Surgery of a high-grade carotid stenosis is evidence-based stroke prevention. Also cognitive effects are reported after carotid endarterectomy (CEA): both deterioration and improvement, the former attributed to perioperative complications and the latter often to learning effect. By imaging, brain perfusion and diffusion changes were shown in…

Neurotrophic Substances and Behavioral Recovery from Brain Damage.

DTIC Science & Technology

1983-07-01

intracerebral administration of this substance can increase choline acetyltransferase, an enzyme necessary for the production of neurotransmitter. This...from limbic system 1 Hefti, F., Dravid, A. and Hartikka, J. Chronic intraventricular injections of nerve growth factor elevate hippocampal choline ...testing, the animals were killed with an overdose of anesthetic (Nembutal) and perfused intracardially with saline-formalin solution. Their brains

A database for estimating organ dose for coronary angiography and brain perfusion CT scans for arbitrary spectra and angular tube current modulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rupcich, Franco; Badal, Andreu; Kyprianou, Iacovos

Purpose: The purpose of this study was to develop a database for estimating organ dose in a voxelized patient model for coronary angiography and brain perfusion CT acquisitions with any spectra and angular tube current modulation setting. The database enables organ dose estimation for existing and novel acquisition techniques without requiring Monte Carlo simulations. Methods: The study simulated transport of monoenergetic photons between 5 and 150 keV for 1000 projections over 360 Degree-Sign through anthropomorphic voxelized female chest and head (0 Degree-Sign and 30 Degree-Sign tilt) phantoms and standard head and body CTDI dosimetry cylinders. The simulations resulted in tablesmore » of normalized dose deposition for several radiosensitive organs quantifying the organ dose per emitted photon for each incident photon energy and projection angle for coronary angiography and brain perfusion acquisitions. The values in a table can be multiplied by an incident spectrum and number of photons at each projection angle and then summed across all energies and angles to estimate total organ dose. Scanner-specific organ dose may be approximated by normalizing the database-estimated organ dose by the database-estimated CTDI{sub vol} and multiplying by a physical CTDI{sub vol} measurement. Two examples are provided demonstrating how to use the tables to estimate relative organ dose. In the first, the change in breast and lung dose during coronary angiography CT scans is calculated for reduced kVp, angular tube current modulation, and partial angle scanning protocols relative to a reference protocol. In the second example, the change in dose to the eye lens is calculated for a brain perfusion CT acquisition in which the gantry is tilted 30 Degree-Sign relative to a nontilted scan. Results: Our database provides tables of normalized dose deposition for several radiosensitive organs irradiated during coronary angiography and brain perfusion CT scans. Validation results indicate total organ doses calculated using our database are within 1% of those calculated using Monte Carlo simulations with the same geometry and scan parameters for all organs except red bone marrow (within 6%), and within 23% of published estimates for different voxelized phantoms. Results from the example of using the database to estimate organ dose for coronary angiography CT acquisitions show 2.1%, 1.1%, and -32% change in breast dose and 2.1%, -0.74%, and 4.7% change in lung dose for reduced kVp, tube current modulated, and partial angle protocols, respectively, relative to the reference protocol. Results show -19.2% difference in dose to eye lens for a tilted scan relative to a nontilted scan. The reported relative changes in organ doses are presented without quantification of image quality and are for the sole purpose of demonstrating the use of the proposed database. Conclusions: The proposed database and calculation method enable the estimation of organ dose for coronary angiography and brain perfusion CT scans utilizing any spectral shape and angular tube current modulation scheme by taking advantage of the precalculated Monte Carlo simulation results. The database can be used in conjunction with image quality studies to develop optimized acquisition techniques and may be particularly beneficial for optimizing dual kVp acquisitions for which numerous kV, mA, and filtration combinations may be investigated.« less

How and How Much Molecular Conformation Affects Electronic Circular Dichroism: The Case of 1,1-Diarylcarbinols.

PubMed

Padula, Daniele; Pescitelli, Gennaro

2018-01-09

Chiroptical spectra such as electronic circular dichroism (ECD) are said to be much more sensitive to conformation than their non-chiroptical counterparts, however, it is difficult to demonstrate such a common notion in a clear-cut way. We run DFT and TDDFT calculations on two closely related 1,1-diarylmethanols which show mirror-image ECD spectra for the same absolute configuration. We demonstrate that the main reason for the different chiroptical response of the two compounds lies in different conformational ensembles, caused by a single hydrogen-to-methyl substitution. We conclude that two compounds, having the same configuration but different conformation, may exhibit mirror-image ECD signals, stressing the importance and impact of conformational factors on ECD spectra.

Headaches as a presenting symptom of linear morphea en coup de sabre.

PubMed

Polcari, Ingrid; Moon, Amanda; Mathes, Erin F; Gilmore, Elaine S; Paller, Amy S

2014-12-01

Linear morphea en coup de sabre (ECDS) is a form of localized scleroderma that predominantly affects the pediatric population, with a median age of 10 years at presentation. The existence of neurologic findings in association with ECDS has been well described in the literature. Here we describe 4 patients with ECDS who presented with headaches, which were typical migraines in 3 of the patients. The headaches preceded the onset of cutaneous findings by at least 6 months. Our patients' cases emphasize both the importance of recognizing headaches as a harbinger of ECDS and the necessity of performing thorough cutaneous examination in patients with unexplained headaches or other neurologic disease. Copyright © 2014 by the American Academy of Pediatrics.

First Comparison of Hypothermic Oxygenated PErfusion Versus Static Cold Storage of Human Donation After Cardiac Death Liver Transplants: An International-matched Case Analysis.

PubMed

Dutkowski, Philipp; Polak, Wojciech G; Muiesan, Paolo; Schlegel, Andrea; Verhoeven, Cornelia J; Scalera, Irene; DeOliveira, Michelle L; Kron, Philipp; Clavien, Pierre-Alain

2015-11-01

Exposure of donor liver grafts to prolonged periods of warm ischemia before procurement causes injuries including intrahepatic cholangiopathy, which may lead to graft loss. Due to unavoidable prolonged ischemic time before procurement in donation after cardiac death (DCD) donation in 1 participating center, each liver graft of this center was pretreated with the new machine perfusion "Hypothermic Oxygenated PErfusion" (HOPE) in an attempt to improve graft quality before implantation. HOPE-treated DCD livers (n = 25) were matched and compared with normally preserved (static cold preservation) DCD liver grafts (n = 50) from 2 well-established European programs. Criteria for matching included duration of warm ischemia and key confounders summarized in the balance of risk score. In a second step, perfused and unperfused DCD livers were compared with liver grafts from standard brain dead donors (n = 50), also matched to the balance of risk score, serving as baseline controls. HOPE treatment of DCD livers significantly decreased graft injury compared with matched cold-stored DCD livers regarding peak alanine-aminotransferase (1239 vs 2065 U/L, P = 0.02), intrahepatic cholangiopathy (0% vs 22%, P = 0.015), biliary complications (20% vs 46%, P = 0.042), and 1-year graft survival (90% vs 69%, P = 0.035). No graft failure due to intrahepatic cholangiopathy or nonfunction occurred in HOPE-treated livers, whereas 18% of unperfused DCD livers needed retransplantation. In addition, HOPE-perfused DCD livers achieved similar results as control donation after brain death livers in all investigated endpoints. HOPE seems to offer important benefits in preserving higher-risk DCD liver grafts.

Autonomic Impairment in Severe Traumatic Brain Injury: A Multimodal Neuromonitoring Study.

PubMed

Sykora, Marek; Czosnyka, Marek; Liu, Xiuyun; Donnelly, Joseph; Nasr, Nathalie; Diedler, Jennifer; Okoroafor, Francois; Hutchinson, Peter; Menon, David; Smielewski, Peter

2016-06-01

Autonomic impairment after acute traumatic brain injury has been associated independently with both increased morbidity and mortality. Links between autonomic impairment and increased intracranial pressure or impaired cerebral autoregulation have been described as well. However, relationships between autonomic impairment, intracranial pressure, impaired cerebral autoregulation, and outcome remain poorly explored. Using continuous measurements of heart rate variability and baroreflex sensitivity we aimed to test whether autonomic markers are associated with functional outcome and mortality independently of intracranial variables. Further, we aimed to evaluate the relationships between autonomic functions, intracranial pressure, and cerebral autoregulation. Retrospective analysis of a prospective database. Neurocritical care unit in a university hospital. Sedated patients with severe traumatic brain injury. Waveforms of intracranial pressure and arterial blood pressure, baseline Glasgow Coma Scale and 6 months Glasgow Outcome Scale were recorded. Baroreflex sensitivity was assessed every 10 seconds using a modified cross-correlational method. Frequency domain analyses of heart rate variability were performed automatically every 10 seconds from a moving 300 seconds of the monitoring time window. Mean values of baroreflex sensitivity, heart rate variability, intracranial pressure, arterial blood pressure, cerebral perfusion pressure, and impaired cerebral autoregulation over the entire monitoring period were calculated for each patient. Two hundred and sixty-two patients with a median age of 36 years entered the analysis. The median admission Glasgow Coma Scale was 6, the median Glasgow Outcome Scale was 3, and the mortality at 6 months was 23%. Baroreflex sensitivity (adjusted odds ratio, 0.9; p = 0.02) and relative power of a high frequency band of heart rate variability (adjusted odds ratio, 1.05; p < 0.001) were individually associated with mortality, independently of age, admission Glasgow Coma Scale, intracranial pressure, pressure reactivity index, or cerebral perfusion pressure. Baroreflex sensitivity showed no correlation with intracranial pressure or cerebral perfusion pressure; the correlation with pressure reactivity index was strong in older patients (age, > 60 yr). The relative power of high frequency correlated significantly with intracranial pressure and cerebral perfusion pressure, but not with pressure reactivity index. The relative power of low frequency correlated significantly with pressure reactivity index. Autonomic impairment, as measured by heart rate variability and baroreflex sensitivity, is significantly associated with increased mortality after traumatic brain injury. These effects, though partially interlinked, seem to be independent of age, trauma severity, intracranial pressure, or autoregulatory status, and thus represent a discrete phenomenon in the pathophysiology of traumatic brain injury. Continuous measurements of heart rate variability and baroreflex sensitivity in the neuromonitoring setting of severe traumatic brain injury may carry novel pathophysiological and predictive information.

Risk factors for donor endothelial loss in eye bank-prepared posterior lamellar corneal tissue for descemet stripping automated endothelial keratoplasty.

PubMed

Liu, Yu-Chi; Alvarez Paraz, Carisa M; Cajucom-Uy, Howard Yu; Agahari, Djoni; Sethuraman, Selvam; Tan, Donald T-H; Mehta, Jodhbir S

2014-07-01

The aim of this study was to investigate donor, tissue, and precut procedure risk factors for endothelial cell density (ECD) loss in posterior lamellar corneal tissue preparation by an eye bank for Descemet stripping automated endothelial keratoplasty. A total of 259 corneoscleral rims precut by the Singapore Eye Bank from October 2011 to August 2013 were evaluated. Donor characteristics, tissue characteristics, and precut procedure parameters were analyzed. The mean donor age was 57.18 ± 11.35 years, and the mean cutting transition time was 4.16 ± 0.75 seconds. The mean ECD was 2826 ± 225 and 2787 ± 224 cells per square millimeter before and after precutting, respectively, with an average ECD change of -1.38% ± 3.28%. The precutting procedure failure rate was 1.2%. Mutivariate regression analysis showed that an older donor age, a higher ECD before cutting, and a slower cutting transition speed were significant factors. Corneas with an ECD >2800 cells per square millimeter before precutting, cutting transition time >5.5 seconds, and corneas with donor age >65 years were significantly more likely to have greater than 5% ECD loss after precutting (odds ratio, 6.42, 1.66, and 1.62; 95% confidence interval, 1.44-29.43, 1.45-2.72, and 1.66-5.82, respectively). Donor source, death-to-preservation time (range, 0.67-10.88 hours), death-to-precutting time (range, 0-7 days), and graft thickness (range, 43-232 μm) were not statistically significant factors. The ECD loss in the precut tissue prepared by the eye bank was very low. The risk factors identified provide better understanding of how to improve the quality and safety profiles when preparing graft tissue for Descemet stripping automated endothelial keratoplasty.

AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges

PubMed Central

Gardner, Matthew R.; Kattenhorn, Lisa M.; Kondur, Hema R.; von Schaewen, Markus; Dorfman, Tatyana; Chiang, Jessica J.; Haworth, Kevin G.; Decker, Julie M.; Alpert, Michael D.; Bailey, Charles C.; Neale, Ernest S.; Fellinger, Christoph H.; Joshi, Vinita R.; Fuchs, Sebastian P.; Martinez-Navio, Jose M.; Quinlan, Brian D.; Yao, Annie Y.; Mouquet, Hugo; Gorman, Jason; Zhang, Baoshan; Poignard, Pascal; Nussenzweig, Michel C.; Burton, Dennis R.; Kwong, Peter D.; Piatak, Michael; Lifson, Jeffrey D.; Gao, Guangping; Desrosiers, Ronald C.; Evans, David T.; Hahn, Beatrice H.; Ploss, Alexander; Cannon, Paula M.; Seaman, Michael S.; Farzan, Michael

2015-01-01

Long-term in vivo expression of a broad and potent entry inhibitor could circumvent the need for a conventional vaccine for HIV-1. Adeno-associated virus (AAV) vectors can stably express HIV-1 broadly neutralizing antibodies (bNAbs)1,2. However even the best bNAbs neutralize 10–50% of HIV-1 isolates inefficiently (IC80 > 5 μg/ml), suggesting that high concentrations of these antibodies would be necessary to achieve general protection3–6. Here we show that eCD4-Ig, a fusion of CD4-Ig with a small CCR5-mimetic sulfopeptide, binds avidly and cooperatively to the HIV-1 envelope glycoprotein (Env) and is more potent than the best bNAbs (geometric mean IC50 < 0.05 μg/ml). Because eCD4-Ig binds only conserved regions of Env, it is also much broader than any bNAb. For example, eCD4-Ig efficiently neutralized 100% of a diverse panel of neutralization-resistant HIV-1, HIV-2, and SIV isolates, including a comprehensive set of isolates resistant to the CD4-binding site bNAbs VRC01, NIH45-46, and 3BNC117. Rhesus macaques inoculated with an AAV vector stably expressed 17 to 77 μg/ml of fully functional rhesus eCD4-Ig for 40 weeks, and these macaques were protected from multiple infectious challenges with SHIV-AD8. Rhesus eCD4-Ig was also markedly less immunogenic than rhesus forms of four well characterized bNAbs. Our data suggest that AAV-delivered eCD4-Ig can function like an effective HIV-1 vaccine. PMID:25707797

Thyrotropin Receptor Epitope and Human Leukocyte Antigen in Graves’ Disease

PubMed Central

Inaba, Hidefumi; De Groot, Leslie J.; Akamizu, Takashi

2016-01-01

Graves’ disease (GD) is an organ-specific autoimmune disease, and thyrotropin (TSH) receptor (TSHR) is a major autoantigen in this condition. Since the extracellular domain of human TSHR (TSHR-ECD) is shed into the circulation, TSHR-ECD is a preferentially immunogenic portion of TSHR. Both genetic factors and environmental factors contribute to development of GD. Inheritance of human leukocyte antigen (HLA) genes, especially HLA-DR3, is associated with GD. TSHR-ECD protein is endocytosed into antigen-presenting cells (APCs), and processed to TSHR-ECD peptides. These peptide epitopes bind to HLA-class II molecules, and subsequently the complex of HLA-class II and TSHR-ECD epitope is presented to CD4+ T cells. The activated CD4+ T cells secrete cytokines/chemokines that stimulate B-cells to produce TSAb, and in turn hyperthyroidism occurs. Numerous studies have been done to identify T- and B-cell epitopes in TSHR-ECD, including (1) in silico, (2) in vitro, (3) in vivo, and (4) clinical experiments. Murine models of GD and HLA-transgenic mice have played a pivotal role in elucidating the immunological mechanisms. To date, linear or conformational epitopes of TSHR-ECD, as well as the molecular structure of the epitope-binding groove in HLA-DR, were reported to be related to the pathogenesis in GD. Dysfunction of central tolerance in the thymus, or in peripheral tolerance, such as regulatory T cells, could allow development of GD. Novel treatments using TSHR antagonists or mutated TSHR peptides have been reported to be effective. We review and update the role of immunogenic TSHR epitopes and HLA in GD, and offer perspectives on TSHR epitope specific treatments. PMID:27602020

Early Childhood Diarrhea Predicts Cognitive Delays in Later Childhood Independently of Malnutrition.

PubMed

Pinkerton, Relana; Oriá, Reinaldo B; Lima, Aldo A M; Rogawski, Elizabeth T; Oriá, Mônica O B; Patrick, Peter D; Moore, Sean R; Wiseman, Benjamin L; Niehaus, Mark D; Guerrant, Richard L

2016-11-02

Understanding the complex relationship between early childhood infectious diseases, nutritional status, poverty, and cognitive development is significantly hindered by the lack of studies that adequately address confounding between these variables. This study assesses the independent contributions of early childhood diarrhea (ECD) and malnutrition on cognitive impairment in later childhood. A cohort of 131 children from a shantytown community in northeast Brazil was monitored from birth to 24 months for diarrhea and anthropometric status. Cognitive assessments including Test of Nonverbal Intelligence (TONI), coding tasks (WISC-III), and verbal fluency (NEPSY) were completed when children were an average of 8.4 years of age (range = 5.6-12.7 years). Multivariate analysis of variance models were used to assess the individual as well as combined effects of ECD and stunting on later childhood cognitive performance. ECD, height for age (HAZ) at 24 months, and weight for age (WAZ) at 24 months were significant univariate predictors of the studies three cognitive outcomes: TONI, coding, and verbal performance (P < 0.05). Multivariate models showed that ECD remained a significant predictor, after adjusting for the effect of 24 months HAZ and WAZ, for both TONI (HAZ, P = 0.029 and WAZ, P = 0.006) and coding (HAZ, P = 0.025 and WAZ, P = 0.036) scores. WAZ and HAZ were also significant predictors after adjusting for ECD. ECD remained a significant predictor of coding (WISC III) after number of household income was considered (P = 0.006). This study provides evidence that ECD and stunting may have independent effects on children's intellectual function well into later childhood. © The American Society of Tropical Medicine and Hygiene.

Outcomes of cataract surgery in eyes with a low corneal endothelial cell density.

PubMed

Yamazoe, Katsuya; Yamaguchi, Takefumi; Hotta, Kazuki; Satake, Yoshiyuki; Konomi, Kenji; Den, Seika; Shimazaki, Jun

2011-12-01

To evaluate the surgical outcomes of cataract surgery in eyes with a low preoperative corneal endothelial cell density (ECD) and analyze factors affecting the prognosis. Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan. Noncomparative case series. Eyes with a preoperative ECD of less than 1000 cells/mm(2) that had cataract surgery between 2006 and 2010 were identified. Standard phacoemulsification with intraocular lenses was performed using the soft-shell technique. The rate of endothelial cell loss, incidence of bullous keratopathy, and risk factors were retrospectively assessed. Sixty-one eyes (53 patients) with a low preoperative ECD were identified. Preoperative diagnoses or factors regarded as causing endothelial cell loss included Fuchs dystrophy (20 eyes), laser iridotomy (16 eyes), keratoplasty (10 eyes), traumatic injury (3 eyes), trabeculectomy (3 eyes), corneal endotheliitis (2 eyes), and other (7 eyes). The corrected distance visual acuity improved from 0.59 ± 0.49 logMAR preoperatively to 0.32 ± 0.48 logMAR postoperatively (P<.001). The mean ECD was 693 ± 172 cells/mm(2) and 611 ± 203 cells/mm(2), respectively (P=.001). The mean rate of endothelial cell loss was 11.5% ± 23.4%. Greater ECD loss was associated with a shorter axial length (AL) (<23.0 mm) and diabetes mellitus. Bullous keratopathy developed in 9 eyes (14.8%) and was associated with posterior capsule rupture. The results suggest that modern techniques for cataract surgery provide excellent visual rehabilitation in many patients with a low preoperative ECD. Shorter AL, diabetes mellitus, and posterior capsule rupture were risk factors for greater ECD loss and bullous keratopathy. Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Determination of 3-hydroxypropylmercapturic acid in urine by three column-switching high-performance liquid chromatography with electrochemical detection using a diamond electrode.

PubMed

Higashi, Kyohei; Shibasaki, Mana; Kuni, Kyoshiro; Uemura, Takeshi; Waragai, Masaaki; Uemura, Kenichi; Igarashi, Kazuei; Toida, Toshihiko

2017-09-29

A three column-switching high-performance liquid chromatography (HPLC) using an electrochemical detector (ECD) equipped with a diamond electrode was established to determine 3-hydroxypropylmercapturic acid (3-HPMA) in urine. An extracted urine sample was consecutively fractionated using a strong anion-exchange column (first column) and a C8 column (second column) via a switching valve before application on an Octa Decyl Silyl (ODS) column (third column), followed by ECD analysis. The% recovery of 3-HPMA standard throughout the three-column process and limit of detection (LOD) were 94±1% and 0.1pmol, respectively. A solid phase extraction step is required for the sensitive analysis of 3-HPMA in urine by column-switching HPLC-ECD despite a decreased% recovery (55%) of urine sample spiked with 100pmol of 3-HPMA. To test the utility of our column-switching HPLC-ECD method, 3-HPMA levels of 27 urine samples were determined, and the correlation between HPLC-ECD and LC-Electrospray ionization (ESI)-MS/MS method was examined. As a result, the median values of μmol 3-HPMA/g Creatinine (Cre) in urine obtained by column-switching HPLC-ECD and LC-MS/MS were 2.19±2.12μmol/g Cre and 2.13±3.38μmol/g Cre, respectively, and the calibration curve (y=1.5171x-1.007) exhibited good linearity within a defined range (r 2 =0.907). These results indicate that the combination of column-switching HPLC and ECD is a powerful tool for the specific, reliable detection of 3-HPMA in urine. Copyright © 2017 Elsevier B.V. All rights reserved.

Atypical behavior in the electron capture induced dissociation of biologically relevant transition metal ion complexes of the peptide hormone oxytocin

NASA Astrophysics Data System (ADS)

Kleinnijenhuis, Anne J.; Mihalca, Romulus; Heeren, Ron M. A.; Heck, Albert J. R.

2006-07-01

Doubly protonated ions of the disulfide bond containing nonapeptide hormone oxytocin and oxytocin complexes with different transition metal ions, that have biological relevance under physiological conditions, were subjected to electron capture dissociation (ECD) to probe their structural features in the gas phase. Although, all the ECD spectra were strikingly different, typical ECD behavior was observed for complexes of the nonapeptide hormone oxytocin with Ni2+, Co2+ and Zn2+, i.e., abundant c/z' and a'/y backbone cleavages and ECD characteristic S-S and S-C bond cleavages were observed. We propose that, although in the oxytocin-transition metal ion complexes the metal ions serve as the main initial capture site, the captured electron is transferred to other sites in the complex to form a hydrogen radical, which drives the subsequent typical ECD fragmentations. The complex of oxytocin with Cu2+ displayed noticeably different ECD behavior. The fragment ions were similar to fragment ions typically observed with low-energy collision induced dissociation (CID). We propose that the electrons captured by the oxytocin-Cu2+ complex might be favorably involved in reducing the Cu2+ metal ion to Cu+. Subsequent energy redistribution would explain the observed low-energy CID-type fragmentations. Electron capture resulted also in quite different specific cleavage sites for the complexes of oxytocin with Ni2+, Co2+ and Zn2+. This is an indication for structural differences in these complexes possibly linked to their significantly different biological effects on oxytocin-receptor binding, and suggests that ECD may be used to study subtle structural differences in transition metal ion-peptide complexes.

The impact of inter-fraction dose variations on biological equivalent dose (BED): the concept of equivalent constant dose.

PubMed

Zavgorodni, S

2004-12-07

Inter-fraction dose fluctuations, which appear as a result of setup errors, organ motion and treatment machine output variations, may influence the radiobiological effect of the treatment even when the total delivered physical dose remains constant. The effect of these inter-fraction dose fluctuations on the biological effective dose (BED) has been investigated. Analytical expressions for the BED accounting for the dose fluctuations have been derived. The concept of biological effective constant dose (BECD) has been introduced. The equivalent constant dose (ECD), representing the constant physical dose that provides the same cell survival fraction as the fluctuating dose, has also been introduced. The dose fluctuations with Gaussian as well as exponential probability density functions were investigated. The values of BECD and ECD calculated analytically were compared with those derived from Monte Carlo modelling. The agreement between Monte Carlo modelled and analytical values was excellent (within 1%) for a range of dose standard deviations (0-100% of the dose) and the number of fractions (2 to 37) used in the comparison. The ECDs have also been calculated for conventional radiotherapy fields. The analytical expression for the BECD shows that BECD increases linearly with the variance of the dose. The effect is relatively small, and in the flat regions of the field it results in less than 1% increase of ECD. In the penumbra region of the 6 MV single radiotherapy beam the ECD exceeded the physical dose by up to 35%, when the standard deviation of combined patient setup/organ motion uncertainty was 5 mm. Equivalently, the ECD field was approximately 2 mm wider than the physical dose field. The difference between ECD and the physical dose is greater for normal tissues than for tumours.

Development and implementation of a mobile device-based pediatric electronic decision support tool as part of a national practice standardization project.

PubMed

McCulloh, Russell J; Fouquet, Sarah D; Herigon, Joshua; Biondi, Eric A; Kennedy, Brandan; Kerns, Ellen; DePorre, Adrienne; Markham, Jessica L; Chan, Y Raymond; Nelson, Krista; Newland, Jason G

2018-06-07

Implementing evidence-based practices requires a multi-faceted approach. Electronic clinical decision support (ECDS) tools may encourage evidence-based practice adoption. However, data regarding the role of mobile ECDS tools in pediatrics is scant. Our objective is to describe the development, distribution, and usage patterns of a smartphone-based ECDS tool within a national practice standardization project. We developed a smartphone-based ECDS tool for use in the American Academy of Pediatrics, Value in Inpatient Pediatrics Network project entitled "Reducing Excessive Variation in the Infant Sepsis Evaluation (REVISE)." The mobile application (app), PedsGuide, was developed using evidence-based recommendations created by an interdisciplinary panel. App workflow and content were aligned with clinical benchmarks; app interface was adjusted after usability heuristic review. Usage patterns were measured using Google Analytics. Overall, 3805 users across the United States downloaded PedsGuide from December 1, 2016, to July 31, 2017, leading to 14 256 use sessions (average 3.75 sessions per user). Users engaged in 60 442 screen views, including 37 424 (61.8%) screen views that displayed content related to the REVISE clinical practice benchmarks, including hospital admission appropriateness (26.8%), length of hospitalization (14.6%), and diagnostic testing recommendations (17.0%). Median user touch depth was 5 [IQR 5]. We observed rapid dissemination and in-depth engagement with PedsGuide, demonstrating feasibility for using smartphone-based ECDS tools within national practice improvement projects. ECDS tools may prove valuable in future national practice standardization initiatives. Work should next focus on developing robust analytics to determine ECDS tools' impact on medical decision making, clinical practice, and health outcomes.

Serum levels of the extracellular domain of the epidermal growth factor receptor in individuals exposed to arsenic in drinking water in Bangladesh.

PubMed

Li, Y; Chen, Y; Slavkovic, V; Ahsan, H; Parvez, F; Graziano, J H; Brandt-Rauf, P W

2007-01-01

Epidermal growth factor receptor-dependent mechanisms have been implicated in growth signal transduction pathways that contribute to cancer development, including dermal carcinogenesis. Detection of the extracellular domain of the epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a potential biomarker for monitoring this effect in vivo. Arsenic is a known human carcinogen, producing skin and other malignancies in populations exposed through their drinking water. One such exposed population, which we have been studying for a number of years, is in Bangladesh. The purpose of this study was to examine the EGFR ECD as a potential biomarker of arsenic exposure and/or effect in this population. Levels of the EGFR ECD were determined by enzyme-linked immunosorbent assay in the serum samples from 574 individuals with a range of arsenic exposures from drinking water in the Araihazar area of Bangladesh. In multiple regression analysis, serum EGFR ECD was found to be positively associated with three different measures of arsenic exposure (well water arsenic, urinary arsenic and a cumulative arsenic index) at statistically significant levels (p

Large-area flexible monolithic ITO/WO3/Nb2O5/NiVOχ/ITO electrochromic devices prepared by using magnetron sputter deposition

NASA Astrophysics Data System (ADS)

Tang, Chien-Jen; Ye, Jia-Ming; Yang, Yueh-Ting; He, Ju-Liang

2016-05-01

Electrochromic devices (ECDs) have been applied in smart windows to control the transmission of sunlight in green buildings, saving up to 40-50% electricity consumption and ultimately reducing carbon dioxide emissions. However, the high manufacturing costs and difficulty of transportation of conventional massive large area ECDs has limited widespread applications. A unique design replacing the glass substrate commonly used in the ECD windows with inexpensive, light-weight and flexible polymeric substrate materials would accelerate EC adoption allowing them to be supplemented for regular windows without altering window construction. In this study, an ITO/WO3/Nb2O5/NiVOχ/ITO all-solid-state monolithic ECD with an effective area of 24 cm × 18 cm is successfully integrated on a PET substrate by using magnetron sputter deposition. The electrochromic performance and bending durability of the resultant material are also investigated. The experimental results indicate that the ultimate response times for the prepared ECD is 6 s for coloring at an applied voltage of -3 V and 5 s for bleaching at an applied voltage of +3 V, respectively. The optical transmittances for the bleached and colored state at a wavelength of 633 nm are 53% and 11%, respectively. The prepared ECD can sustain over 8000 repeated coloring and bleaching cycles, as well as tolerate a bending radius of curvature of 7.5 cm.

Assessment of the reliability of human corneal endothelial cell-density estimates using a noncontact specular microscope.

PubMed

Doughty, M J; Müller, A; Zaman, M L

2000-03-01

We sought to determine the variance in endothelial cell density (ECD) estimates for human corneal endothelia. Noncontact specular micrographs were obtained from white subjects without any history of contact lens wear, or major eye disease or surgery; subjects were within four age groups (children, young adults, older adults, senior citizens). The endothelial image was scanned, and the areas from > or =75 cells measured from an overlay by planimetry. The cell-area values were used to calculate the ECD repeatedly so that the intra- and intersubject variation in an average ECD estimate could be made by using different numbers of cells (5, 10, 15, etc.). An average ECD of 3,519 cells/mm2 (range, 2,598-5,312 cells/mm2) was obtained of counts of 75 cells/ endothelium from individuals aged 6-83 years. Average ECD estimates in each age group were 4,124, 3,457, 3,360, and 3,113 cells/mm2, respectively. Analysis of intersubject variance revealed that ECD estimates would be expected to be no better than +/-10% if only 25 cells were measured per endothelium, but approach +/-2% if 75 cells are measured. In assessing the corneal endothelium by noncontact specular microscopy, cell count should be given, and this should be > or =75/ endothelium for an expected variance to be at a level close to that recommended for monitoring age-, stress-, or surgery-related changes.

How to Perfuse: Concepts of Cerebral Protection during Arch Replacement

PubMed Central

Habertheuer, Andreas; Wiedemann, Dominik; Kocher, Alfred; Laufer, Guenther; Vallabhajosyula, Prashanth

2015-01-01

Arch surgery remains undoubtedly among the most technically and strategically challenging endeavors in cardiovascular surgery. Surgical interventions of thoracic aneurysms involving the aortic arch require complete circulatory arrest in deep hypothermia (DHCA) or elaborate cerebral perfusion strategies with varying degrees of hypothermia to achieve satisfactory protection of the brain from ischemic insults, that is, unilateral/bilateral antegrade cerebral perfusion (ACP) and retrograde cerebral perfusion (RCP). Despite sophisticated and increasingly individualized surgical approaches for complex aortic pathologies, there remains a lack of consensus regarding the optimal method of cerebral protection and circulatory management during the time of arch exclusion. Many recent studies argue in favor of ACP with various degrees of hypothermic arrest during arch reconstruction and its advantages have been widely demonstrated. In fact ACP with more moderate degrees of hypothermia represents a paradigm shift in the cardiac surgery community and is widely adopted as an emergent strategy; however, many centers continue to report good results using other perfusion strategies. Amidst this important discussion we review currently available surgical strategies of cerebral protection management and compare the results of recent European multicenter and single-center data. PMID:26713319

Use of intracranial and ocular thermography before and after arteriovenous malformation excision

NASA Astrophysics Data System (ADS)

Hwang, Peter Y. K.; Lewis, Philip M.; Maller, Jerome J.

2014-11-01

Excision of arteriovenous malformations (AVMs) is known to carry a risk of postoperative hemorrhage, postulated to be the result of normal perfusion pressure breakthrough. It is also possible that AVMs may cause a steal effect, reducing perfusion in nearby vessels. There is currently no simple method of visualizing the presence or absence of steal effect intraoperatively. We hypothesized that the infrared thermographic (heat sensitive) imaging of perilesional brain may be useful for detecting reduced perfusion due to steal. Moreover, we hypothesized that if steal effect was present, it could impact on ocular perfusion and thereby temperature. Our objective was, therefore, to investigate whether perilesional cortical and ocular temperature (OT) may be a marker of steal effect. We intraoperatively acquired conventional and thermal images of the surgical field and eyes bilaterally, pre- and post-excisions of a large left hemisphere AVM. We found OT asymmetry preoperatively, which was absent after the AVM was excised. Intraoperative thermal images showed an increase of perilesional temperature, although this could be confounded by generalized changes in cortical perfusion due to anesthetics or surgery.

A microfluidic brain slice perfusion chamber for multisite recording using penetrating electrodes.

PubMed

Blake, Alexander J; Rodgers, Frank C; Bassuener, Anna; Hippensteel, Joseph A; Pearce, Thomas M; Pearce, Timothy R; Zarnowska, Ewa D; Pearce, Robert A; Williams, Justin C

2010-05-30

To analyze the spatiotemporal dynamics of network activity in a brain tissue slice, it is useful to record simultaneously from multiple locations. When obtained from laminar structures such as the hippocampus or neocortex, multisite recordings also yield information about subcellular current distributions via current source density analysis. Multisite probes developed for in vivo recordings could serve these purposes in vitro, allowing recordings to be obtained from brain slices at sites deeper within the tissue than currently available surface recording methods permit. However, existing recording chambers do not allow for the insertion of lamina-spanning probes that enter through the edges of brain slices. Here, we present a novel brain slice recording chamber design that accomplishes this goal. The device provides a stable microfluidic perfusion environment in which tissue health is optimized by superfusing both surfaces of the slice. Multichannel electrodes can be inserted parallel to the surface of the slice, at any depth relative to the surface. Access is also provided from above for the insertion of additional recording or stimulating electrodes. We illustrate the utility of this recording configuration by measuring current sources and sinks during theta burst stimuli that lead to the induction of long-term potentiation in hippocampal slices. (c) 2010 Elsevier B.V. All rights reserved.

Rheological effects of drag-reducing polymers improve cerebral blood flow and oxygenation after traumatic brain injury in rats

PubMed Central

Kameneva, Marina V; Bragina, Olga A; Thomson, Susan; Statom, Gloria L; Lara, Devon A; Yang, Yirong; Nemoto, Edwin M

2016-01-01

Cerebral ischemia has been clearly demonstrated after traumatic brain injury (TBI); however, neuroprotective therapies have not focused on improvement of the cerebral microcirculation. Blood soluble drag-reducing polymers (DRP), prepared from high molecular weight polyethylene oxide, target impaired microvascular perfusion by altering the rheological properties of blood and, until our recent reports, has not been applied to the brain. We hypothesized that DRP improve cerebral microcirculation and oxygenation after TBI. DRP were studied in healthy and traumatized rat brains and compared to saline controls. Using in-vivo two-photon laser scanning microscopy over the parietal cortex, we showed that after TBI, nanomolar concentrations of intravascular DRP significantly enhanced microvascular perfusion and tissue oxygenation in peri-contusional areas, preserved blood–brain barrier integrity and protected neurons. The mechanisms of DRP effects were attributable to reduction of the near-vessel wall cell-free layer which increased near-wall blood flow velocity, microcirculatory volume flow, and number of erythrocytes entering capillaries, thereby reducing capillary stasis and tissue hypoxia as reflected by a reduction in NADH. Our results indicate that early reduction in CBF after TBI is mainly due to ischemia; however, metabolic depression of contused tissue could be also involved. PMID:28155574

A non-linear regression method for CT brain perfusion analysis

NASA Astrophysics Data System (ADS)

Bennink, E.; Oosterbroek, J.; Viergever, M. A.; Velthuis, B. K.; de Jong, H. W. A. M.

2015-03-01

CT perfusion (CTP) imaging allows for rapid diagnosis of ischemic stroke. Generation of perfusion maps from CTP data usually involves deconvolution algorithms providing estimates for the impulse response function in the tissue. We propose the use of a fast non-linear regression (NLR) method that we postulate has similar performance to the current academic state-of-art method (bSVD), but that has some important advantages, including the estimation of vascular permeability, improved robustness to tracer-delay, and very few tuning parameters, that are all important in stroke assessment. The aim of this study is to evaluate the fast NLR method against bSVD and a commercial clinical state-of-art method. The three methods were tested against a published digital perfusion phantom earlier used to illustrate the superiority of bSVD. In addition, the NLR and clinical methods were also tested against bSVD on 20 clinical scans. Pearson correlation coefficients were calculated for each of the tested methods. All three methods showed high correlation coefficients (>0.9) with the ground truth in the phantom. With respect to the clinical scans, the NLR perfusion maps showed higher correlation with bSVD than the perfusion maps from the clinical method. Furthermore, the perfusion maps showed that the fast NLR estimates are robust to tracer-delay. In conclusion, the proposed fast NLR method provides a simple and flexible way of estimating perfusion parameters from CT perfusion scans, with high correlation coefficients. This suggests that it could be a better alternative to the current clinical and academic state-of-art methods.

Fuels for urban transit buses: a cost-effectiveness analysis.

PubMed

Cohen, Joshua T; Hammitt, James K; Levy, Jonathan I

2003-04-15

Public transit agencies have begun to adopt alternative propulsion technologies to reduce urban transit bus emissions associated with conventional diesel (CD) engines. Among the most popular alternatives are emission controlled diesel buses (ECD), defined here to be buses with continuously regenerating diesel particle filters burning low-sulfur diesel fuel, and buses burning compressed natural gas (CNG). This study uses a series of simplifying assumptions to arrive at first-order estimates for the incremental cost-effectiveness (CE) of ECD and CNG relative to CD. The CE ratio numerator reflects acquisition and operating costs. The denominator reflects health losses (mortality and morbidity) due to primary particulate matter (PM), secondary PM, and ozone exposure, measured as quality adjusted life years (QALYs). We find that CNG provides larger health benefits than does ECD (nine vs six QALYs annually per 1000 buses) but that ECD is more cost-effective than CNG (dollar 270 000 per QALY for ECD vs dollar 1.7 million to dollar 2.4 million for CNG). These estimates are subject to much uncertainty. We identify assumptions that contribute most to this uncertainty and propose potential research directions to refine our estimates.

Imaging of cerebral blood flow in patients with severe traumatic brain injury in the neurointensive care.

PubMed

Rostami, Elham; Engquist, Henrik; Enblad, Per

2014-01-01

Ischemia is a common and deleterious secondary injury following traumatic brain injury (TBI). A great challenge for the treatment of TBI patients in the neurointensive care unit (NICU) is to detect early signs of ischemia in order to prevent further advancement and deterioration of the brain tissue. Today, several imaging techniques are available to monitor cerebral blood flow (CBF) in the injured brain such as positron emission tomography (PET), single-photon emission computed tomography, xenon computed tomography (Xenon-CT), perfusion-weighted magnetic resonance imaging (MRI), and CT perfusion scan. An ideal imaging technique would enable continuous non-invasive measurement of blood flow and metabolism across the whole brain. Unfortunately, no current imaging method meets all these criteria. These techniques offer snapshots of the CBF. MRI may also provide some information about the metabolic state of the brain. PET provides images with high resolution and quantitative measurements of CBF and metabolism; however, it is a complex and costly method limited to few TBI centers. All of these methods except mobile Xenon-CT require transfer of TBI patients to the radiological department. Mobile Xenon-CT emerges as a feasible technique to monitor CBF in the NICU, with lower risk of adverse effects. Promising results have been demonstrated with Xenon-CT in predicting outcome in TBI patients. This review covers available imaging methods used to monitor CBF in patients with severe TBI.

Imaging of Cerebral Blood Flow in Patients with Severe Traumatic Brain Injury in the Neurointensive Care

PubMed Central

Rostami, Elham; Engquist, Henrik; Enblad, Per

2014-01-01

Ischemia is a common and deleterious secondary injury following traumatic brain injury (TBI). A great challenge for the treatment of TBI patients in the neurointensive care unit (NICU) is to detect early signs of ischemia in order to prevent further advancement and deterioration of the brain tissue. Today, several imaging techniques are available to monitor cerebral blood flow (CBF) in the injured brain such as positron emission tomography (PET), single-photon emission computed tomography, xenon computed tomography (Xenon-CT), perfusion-weighted magnetic resonance imaging (MRI), and CT perfusion scan. An ideal imaging technique would enable continuous non-invasive measurement of blood flow and metabolism across the whole brain. Unfortunately, no current imaging method meets all these criteria. These techniques offer snapshots of the CBF. MRI may also provide some information about the metabolic state of the brain. PET provides images with high resolution and quantitative measurements of CBF and metabolism; however, it is a complex and costly method limited to few TBI centers. All of these methods except mobile Xenon-CT require transfer of TBI patients to the radiological department. Mobile Xenon-CT emerges as a feasible technique to monitor CBF in the NICU, with lower risk of adverse effects. Promising results have been demonstrated with Xenon-CT in predicting outcome in TBI patients. This review covers available imaging methods used to monitor CBF in patients with severe TBI. PMID:25071702

Fluorescence Imaging/Agents in Tumor Resection.

PubMed

Stummer, Walter; Suero Molina, Eric

2017-10-01

Intraoperative fluorescence imaging allows real-time identification of diseased tissue during surgery without being influenced by brain shift and surgery interruption. 5-Aminolevulinic acid, useful for malignant gliomas and other tumors, is the most broadly explored compound approved for fluorescence-guided resection. Intravenous fluorescein sodium has recently received attention, highlighting tumor tissue based on extravasation at the blood-brain barrier (defective in many brain tumors). Fluorescein in perfused brain, unselective extravasation in brain perturbed by surgery, and propagation with edema are concerns. Fluorescein is not approved but targeted fluorochromes with affinity to brain tumor cells, in development, may offer future advantages. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Optical guidance for stereotactic brain tumor biopsy procedures: preliminary clinical evaluation (Conference Presentation)

NASA Astrophysics Data System (ADS)

Haj-Hosseini, Neda; Richter, Johan; Milos, Peter; Hallbeck, Martin; Wârdell, Karin

2017-02-01

In the routine of stereotactic biopsy on suspected tumors located deep in the brain or patients with multiple lesions, tissue samples are harvested to determine the type of malignancy. Biopsies are taken from pre-calculated positions based on the preoperative radiologic images susceptible to brain shift. In such cases the biopsy procedure may need to be repeated leading to a longer operation time. To provide guidance for targeting diagnostic tumor tissue and to avoid vessel rupture on the insertion path of the tumor, an application specific fiber optic probe was developed. The setup incorporated spectroscopy for 5-aminolevulinic acid induced protopophyrin IX (PpIX) fluorescence in the tumor and laser Doppler for measuring microvascular blood flow which recorded backscattered light (TLI) at 780 nm and blood perfusion. The recorded signals were compared to the histopathologic diagnosis of the tissue samples (n=16) and to the preoperative radiologic images. All together 146 fluorescence and 276 laser Doppler signals were recorded along 5 trajectories in 4 patients. On all occasions strong PpIX fluorescence peaks were visible during real-time guidance. Comparing the gliotic tumor marginal zone with the tumor, the PpIX (51 vs. 528 a.u., [0-1790], p < 0.05) was higher and TLI (2.9 vs. 2.0 a.u., [0-4.1], p < 0.05) was lower in tumor. The autofluorescence (104 vs.70 a.u., [0-442], p > 0.05) and blood perfusion (8.3 vs. 17 a.u., [0-254], p > 0.05) were not significantly different. In conclusion, the optical guidance probe made real-time tumor detection and vessel tracking possible during the stereotactic biopsy procedures. Moreover, the fluorescence and blood perfusion in the tumor could be studied at controlled positions in the brain and the tumor.

Estimation of in-vivo neurotransmitter release by brain microdialysis: the issue of validity.

PubMed

Di Chiara, G.; Tanda, G.; Carboni, E.

1996-11-01

Although microdialysis is commonly understood as a method of sampling low molecular weight compounds in the extracellular compartment of tissues, this definition appears insufficient to specifically describe brain microdialysis of neurotransmitters. In fact, transmitter overflow from the brain into dialysates is critically dependent upon the composition of the perfusing Ringer. Therefore, the dialysing Ringer not only recovers the transmitter from the extracellular brain fluid but is a main determinant of its in-vivo release. Two types of brain microdialysis are distinguished: quantitative micro-dialysis and conventional microdialysis. Quantitative microdialysis provides an estimate of neurotransmitter concentrations in the extracellular fluid in contact with the probe. However, this information might poorly reflect the kinetics of neurotransmitter release in vivo. Conventional microdialysis involves perfusion at a constant rate with a transmitter-free Ringer, resulting in the formation of a steep neurotransmitter concentration gradient extending from the Ringer into the extracellular fluid. This artificial gradient might be critical for the ability of conventional microdialysis to detect and resolve phasic changes in neurotransmitter release taking place in the implanted area. On the basis of these characteristics, conventional microdialysis of neurotransmitters can be conceptualized as a model of the in-vivo release of neurotransmitters in the brain. As such, the criteria of face-validity, construct-validity and predictive-validity should be applied to select the most appropriate experimental conditions for estimating neurotransmitter release in specific brain areas in relation to behaviour.

γ-Aminobutyric acid (GABA) concentration inversely correlates with basal perfusion in human occipital lobe

PubMed Central

Donahue, Manus J; Rane, Swati; Hussey, Erin; Mason, Emily; Pradhan, Subechhya; Waddell, Kevin W; Ally, Brandon A

2014-01-01

Commonly used neuroimaging approaches in humans exploit hemodynamic or metabolic indicators of brain function. However, fundamental gaps remain in our ability to relate such hemo-metabolic reactivity to neurotransmission, with recent reports providing paradoxical information regarding the relationship among basal perfusion, functional imaging contrast, and neurotransmission in awake humans. Here, sequential magnetic resonance spectroscopy (MRS) measurements of the primary inhibitory neurotransmitter, γ-aminobutyric acid (GABA+macromolecules normalized by the complex N-acetyl aspartate-N-acetyl aspartyl glutamic acid: [GABA+]/[NAA–NAAG]), and magnetic resonance imaging (MRI) measurements of perfusion, fractional gray-matter volume, and arterial arrival time (AAT) are recorded in human visual cortex from a controlled cohort of young adult male volunteers with neurocognitive battery-confirmed comparable cognitive capacity (3 T; n=16; age=23±3 years). Regression analyses reveal an inverse correlation between [GABA+]/[NAA–NAAG] and perfusion (R=−0.46; P=0.037), yet no relationship between AAT and [GABA+]/[NAA–NAAG] (R=−0.12; P=0.33). Perfusion measurements that do not control for AAT variations reveal reduced correlations between [GABA+]/[NAA–NAAG] and perfusion (R=−0.13; P=0.32). These findings largely reconcile contradictory reports between perfusion and inhibitory tone, and underscore the physiologic origins of the growing literature relating functional imaging signals, hemodynamics, and neurotransmission. PMID:24398941

Biomarkers for visceral hypersensitivity identified by classification of electroencephalographic frequency alterations

NASA Astrophysics Data System (ADS)

Graversen, Carina; Brock, Christina; Mohr Drewes, Asbjørn; Farina, Dario

2011-10-01

Abdominal pain is frequently related to visceral hypersensitivity. This is associated with increased neuronal excitability in the central nervous system (CNS), which can be manifested as discrete electroencephalographic (EEG) alterations. In the current placebo-controlled study, visceral hypersensitivity was evoked by chemical irritation of the esophagus with acid and capsaicin perfusion. The resulting hyperexcitability of the CNS was evaluated by evoked brain potentials following painful electrical stimulations of a remote organ—the rectosigmoid colon. Alterations in individual EEG power distributions between baseline and after perfusion were quantified by extracting features from the evoked brain potentials using an optimized discrete wavelet transform. Visceral hypersensitivity was identified as increased EEG power in the delta, theta and alpha frequency bands. By applying a support vector machine in regression mode, the individual baseline corrected alterations after sensitization were discriminated from alterations caused by placebo perfusions. An accuracy of 91.7% was obtained (P < 0.01). The regression value representing the overall alteration of the EEG correlated with the degree of hyperalgesia (P = 0.03). In conclusion, this study showed that classification of EEG can be used to detect biomarkers reflecting central neuronal changes. In the future, this may be used in studies of pain physiology and pharmacological interventions.

Thirst-Dependent Activity of the Insular Cortex Reflects its Emotion-Related Subdivision: A Cerebral Blood Flow Study.

PubMed

Meier, Lea; Federspiel, Andrea; Jann, Kay; Wiest, Roland; Strik, Werner; Dierks, Thomas

2018-04-26

Recent studies investigating neural correlates of human thirst have identified various subcortical and telencephalic brain areas. The experience of thirst represents a homeostatic emotion and a state that slowly evolves over time. Therefore, the present study aims at systematically examining cerebral perfusion during the parametric progression of thirst. We measured subjective thirst ratings, serum parameters and cerebral blood flow in 20 healthy subjects across four different thirst stages: intense thirst, moderate thirst, subjective satiation and physiological satiation. Imaging data revealed dehydration-related perfusion differences in previously identified brain areas, such as the anterior cingulate cortex, the middle temporal gyrus and the insular cortex. However, significant differences across all four thirst stages (including the moderate thirst level), were exclusively found in the posterior insular cortex. The subjective thirst ratings over the different thirst stages, however, were associated with perfusion differences in the right anterior insula. These findings add to our understanding of the insular cortex as a key player in human thirst - both on the level of physiological dehydration and the level of the subjective thirst experience. Copyright © 2018. Published by Elsevier Ltd.

Non-contact tissue perfusion and oxygenation imaging using a LED based multispectral and a thermal imaging system, first results of clinical intervention studies

NASA Astrophysics Data System (ADS)

Klaessens, John H. G. M.; Nelisse, Martin; Verdaasdonk, Rudolf M.; Noordmans, Herke Jan

2013-03-01

During clinical interventions objective and quantitative information of the tissue perfusion, oxygenation or temperature can be useful for the surgical strategy. Local (point) measurements give limited information and affected areas can easily be missed, therefore imaging large areas is required. In this study a LED based multispectral imaging system (MSI, 17 different wavelengths 370nm-880nm) and a thermo camera were applied during clinical interventions: tissue flap transplantations (ENT), local anesthetic block and during open brain surgery (epileptic seizure). The images covered an area of 20x20 cm, when doing measurements in an (operating) room, they turned out to be more complicated than laboratory experiments due to light fluctuations, movement of the patient and limited angle of view. By constantly measuring the background light and the use of a white reference, light fluctuations and movement were corrected. Oxygenation concentration images could be calculated and combined with the thermal images. The effectively of local anesthesia of a hand could be predicted in an early stage using the thermal camera and the reperfusion of transplanted skin flap could be imaged. During brain surgery, a temporary hyper-perfused area was witnessed which was probably related to an epileptic attack. A LED based multispectral imaging system combined with thermal imaging provide complementary information on perfusion and oxygenation changes and are promising techniques for real-time diagnostics during clinical interventions.

Quantitative iodine-123 IMP imaging of brain perfusion in schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, M.B.; Lake, R.R.; Graham, L.S.

1989-10-01

Decreased perfusion in the frontal lobes of patients with chronic schizophrenia has been reported by multiple observes using a variety of techniques. Other observers have been unable to confirm this finding using similar techniques. In this study quantitative single photon emission computed tomography brain imaging was performed using p,5n ({sup 123}I)IMP in five normal subjects and ten chronically medicated patients with schizophrenia. The acquisition data were preprocessed with an image dependent Metz filter and reconstructed using a ramp filtered back projection technique. The uptake in each of 50 regions of interest in each subject was normalized to the uptake inmore » the cerebellum. There were no significant confirmed differences in the comparable ratios of normal subjects and patients with schizophrenia even at the p = 0.15 level. Hypofrontality was not observed.« less

Comparative study of anatomical normalization errors in SPM and 3D-SSP using digital brain phantom.

PubMed

Onishi, Hideo; Matsutake, Yuki; Kawashima, Hiroki; Matsutomo, Norikazu; Amijima, Hizuru

2011-01-01

In single photon emission computed tomography (SPECT) cerebral blood flow studies, two major algorithms are widely used statistical parametric mapping (SPM) and three-dimensional stereotactic surface projections (3D-SSP). The aim of this study is to compare an SPM algorithm-based easy Z score imaging system (eZIS) and a 3D-SSP system in the errors of anatomical standardization using 3D-digital brain phantom images. We developed a 3D-brain digital phantom based on MR images to simulate the effects of head tilt, perfusion defective region size, and count value reduction rate on the SPECT images. This digital phantom was used to compare the errors of anatomical standardization by the eZIS and the 3D-SSP algorithms. While the eZIS allowed accurate standardization of the images of the phantom simulating a head in rotation, lateroflexion, anteflexion, or retroflexion without angle dependency, the standardization by 3D-SSP was not accurate enough at approximately 25° or more head tilt. When the simulated head contained perfusion defective regions, one of the 3D-SSP images showed an error of 6.9% from the true value. Meanwhile, one of the eZIS images showed an error as large as 63.4%, revealing a significant underestimation. When required to evaluate regions with decreased perfusion due to such causes as hemodynamic cerebral ischemia, the 3D-SSP is desirable. In a statistical image analysis, we must reconfirm the image after anatomical standardization by all means.

Quantitative Changes in Cerebral Perfusion during Urinary Urgency in Women with Overactive Bladder

PubMed Central

Weissbart, Steven J.; Xu, Sihua; Bhavsar, Rupal; Rao, Hengyi

2017-01-01

Purpose To quantitatively measure changes in cerebral perfusion in select regions of interest in the brain during urinary urgency in women with overactive bladder (OAB) using arterial spin labeling (ASL). Methods Twelve women with OAB and 10 controls underwent bladder filling and rated urinary urgency (scale 0–10). ASL fMRI scans were performed (1) in the low urgency state after voiding and (2) high urgency state after drinking oral fluids. Absolute regional cerebral blood flow (rCBF) in select regions of interest was compared between the low and high urgency states. Results There were no significant differences in rCBF between the low and high urgency states in the control group. In the OAB group, rCBF (mean ± SE, ml/100 g/min) increased by 10–14% from the low to the high urgency state in the right anterior cingulate cortex (ACC) (44.56 ± 0.59 versus 49.52 ± 1.49, p < 0.05), left ACC (49.29 ± 0.85 versus 54.02 ± 1.46, p < 0.05), and left insula (50.46 ± 1.72 versus 54.99 ± 1.09, p < 0.05). Whole-brain analysis identified additional areas of activation in the right insula, right dorsolateral prefrontal cortex, and pons/midbrain area. Conclusions Urinary urgency is associated with quantitative increase in cerebral perfusion in regions of the brain associated with processing emotional response to discomfort. PMID:28904950

Decision-making deficit of a patient with axonal damage after traumatic brain injury.

PubMed

Yasuno, Fumihiko; Matsuoka, Kiwamu; Kitamura, Soichiro; Kiuchi, Kuniaki; Kosaka, Jun; Okada, Koji; Tanaka, Syohei; Shinkai, Takayuki; Taoka, Toshiaki; Kishimoto, Toshifumi

2014-02-01

Patients with traumatic brain injury (TBI) were reported to have difficulty making advantageous decisions, but the underlying deficits of the network of brain areas involved in this process were not directly examined. We report a patient with TBI who demonstrated problematic behavior in situations of risk and complexity after cerebral injury from a traffic accident. The Iowa gambling task (IGT) was used to reveal his deficits in the decision-making process. To examine underlying deficits of the network of brain areas, we examined T1-weighted structural MRI, diffusion tensor imaging (DTI) and Tc-ECD SPECT in this patient. The patient showed abnormality in IGT. DTI-MRI results showed a significant decrease in fractional anisotropy (FA) in the fasciculus between the brain stem and cortical regions via the thalamus. He showed significant decrease in gray matter volumes in the bilateral insular cortex, hypothalamus, and posterior cingulate cortex, possibly reflecting Wallerian degeneration secondary to the fasciculus abnormalities. SPECT showed significant blood flow decrease in the broad cortical areas including the ventromedial prefrontal cortex (VM). Our study showed that the patient had dysfunctional decision-making process. Microstructural abnormality in the fasciculus, likely from the traffic accident, caused reduced afferent feedback to the brain, resulting in less efficient decision-making. Our findings support the somatic-marker hypothesis (SMH), where somatic feedback to the brain influences the decision-making process. Copyright © 2013 Elsevier Inc. All rights reserved.

Increased Brain Perfusion Persists over the First Month of Life in Term Asphyxiated Newborns Treated with Hypothermia: Does it Reflect Activated Angiogenesis?

PubMed

Shaikh, Henna; Lechpammer, Mirna; Jensen, Frances E; Warfield, Simon K; Hansen, Anne H; Kosaras, Bela; Shevell, Michael; Wintermark, Pia

2015-06-01

Many asphyxiated newborns still develop brain injury despite hypothermia therapy. The development of brain injury in these newborns has been related partly to brain perfusion abnormalities. The purposes of this study were to assess brain hyperperfusion over the first month of life in term asphyxiated newborns and to search for some histopathological clues indicating whether this hyperperfusion may be related to activated angiogenesis following asphyxia. In this prospective cohort study, regional cerebral blood flow was measured in term asphyxiated newborns treated with hypothermia around day 10 of life and around 1 month of life using magnetic resonance imaging (MRI) and arterial spin labeling. A total of 32 MRI scans were obtained from 24 term newborns. Asphyxiated newborns treated with hypothermia displayed an increased cerebral blood flow in the injured brain areas around day 10 of life and up to 1 month of life. In addition, we looked at the histopathological clues in a human asphyxiated newborn and in a rat model of neonatal encephalopathy. Vascular endothelial growth factor (VEGF) was expressed in the injured brain of an asphyxiated newborn treated with hypothermia in the first days of life and of rat pups 24-48 h after the hypoxic-ischemic event, and the endothelial cell count increased in the injured cortex of the pups 7 and 11 days after hypoxia-ischemia. Our data showed that the hyperperfusion measured by imaging persisted in the injured areas up to 1 month of life and that angiogenesis was activated in the injured brain of asphyxiated newborns.

The effect of head size/shape, miscentering, and bowtie filter on peak patient tissue doses from modern brain perfusion 256-slice CT: How can we minimize the risk for deterministic effects?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perisinakis, Kostas; Seimenis, Ioannis; Tzedakis, Antonis

Purpose: To determine patient-specific absorbed peak doses to skin, eye lens, brain parenchyma, and cranial red bone marrow (RBM) of adult individuals subjected to low-dose brain perfusion CT studies on a 256-slice CT scanner, and investigate the effect of patient head size/shape, head position during the examination and bowtie filter used on peak tissue doses. Methods: The peak doses to eye lens, skin, brain, and RBM were measured in 106 individual-specific adult head phantoms subjected to the standard low-dose brain perfusion CT on a 256-slice CT scanner using a novel Monte Carlo simulation software dedicated for patient CT dosimetry. Peakmore » tissue doses were compared to corresponding thresholds for induction of cataract, erythema, cerebrovascular disease, and depression of hematopoiesis, respectively. The effects of patient head size/shape, head position during acquisition and bowtie filter used on resulting peak patient tissue doses were investigated. The effect of eye-lens position in the scanned head region was also investigated. The effect of miscentering and use of narrow bowtie filter on image quality was assessed. Results: The mean peak doses to eye lens, skin, brain, and RBM were found to be 124, 120, 95, and 163 mGy, respectively. The effect of patient head size and shape on peak tissue doses was found to be minimal since maximum differences were less than 7%. Patient head miscentering and bowtie filter selection were found to have a considerable effect on peak tissue doses. The peak eye-lens dose saving achieved by elevating head by 4 cm with respect to isocenter and using a narrow wedge filter was found to approach 50%. When the eye lies outside of the primarily irradiated head region, the dose to eye lens was found to drop to less than 20% of the corresponding dose measured when the eye lens was located in the middle of the x-ray beam. Positioning head phantom off-isocenter by 4 cm and employing a narrow wedge filter results in a moderate reduction of signal-to-noise ratio mainly to the peripheral region of the phantom. Conclusions: Despite typical peak doses to skin, eye lens, brain, and RBM from the standard low-dose brain perfusion 256-slice CT protocol are well below the corresponding thresholds for the induction of erythema, cataract, cerebrovascular disease, and depression of hematopoiesis, respectively, every effort should be made toward optimization of the procedure and minimization of dose received by these tissues. The current study provides evidence that the use of the narrower bowtie filter available may considerably reduce peak absorbed dose to all above radiosensitive tissues with minimal deterioration in image quality. Considerable reduction in peak eye-lens dose may also be achieved by positioning patient head center a few centimeters above isocenter during the exposure.« less

Insulin resistance is associated with lower arterial blood flow and reduced cortical perfusion in cognitively asymptomatic middle-aged adults

PubMed Central

Hoscheidt, Siobhan M; Kellawan, J Mikhail; Berman, Sara E; Rivera-Rivera, Leonardo A; Krause, Rachel A; Oh, Jennifer M; Beeri, Michal S; Rowley, Howard A; Wieben, Oliver; Carlsson, Cynthia M; Asthana, Sanjay; Johnson, Sterling C; Schrage, William G

2016-01-01

Insulin resistance (IR) is associated with poor cerebrovascular health and increased risk for dementia. Little is known about the unique effect of IR on both micro- and macrovascular flow particularly in midlife when interventions against dementia may be most effective. We examined the effect of IR as indexed by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) on cerebral blood flow in macro- and microvessels utilizing magnetic resonance imaging (MRI) among cognitively asymptomatic middle-aged individuals. We hypothesized that higher HOMA-IR would be associated with reduced flow in macrovessels and lower cortical perfusion. One hundred and twenty cognitively asymptomatic middle-aged adults (57 ± 5 yrs) underwent fasting blood draw, phase contrast-vastly undersampled isotropic projection reconstruction (PC VIPR) MRI, and arterial spin labeling (ASL) perfusion. Higher HOMA-IR was associated with lower arterial blood flow, particularly within the internal carotid arteries (ICAs), and lower cerebral perfusion in several brain regions including frontal and temporal lobe regions. Higher blood flow in bilateral ICAs predicted greater cortical perfusion in individuals with lower HOMA-IR, a relationship not observed among those with higher HOMA-IR. Findings provide novel evidence for an uncoupling of macrovascular blood flow and microvascular perfusion among individuals with higher IR in midlife. PMID:27488909

Dynamic spatio-temporal imaging of early reflow in a neonatal rat stroke model.

PubMed

Leger, Pierre-Louis; Bonnin, Philippe; Lacombe, Pierre; Couture-Lepetit, Elisabeth; Fau, Sebastien; Renolleau, Sylvain; Gharib, Abdallah; Baud, Olivier; Charriaut-Marlangue, Christiane

2013-01-01

The aim of the study was to better understand blood-flow changes in large arteries and microvessels during the first 15 minutes of reflow in a P7 rat model of arterial occlusion. Blood-flow changes were monitored by using ultrasound imaging with sequential Doppler recordings in internal carotid arteries (ICAs) and basilar trunk. Relative cerebral blood flow (rCBF) changes were obtained by using laser speckle Doppler monitoring. Tissue perfusion was measured with [(14)C]-iodoantipyrine autoradiography. Cerebral energy metabolism was evaluated by mitochondrial oxygen consumption. Gradual increase in mean blood-flow velocities illustrated a gradual perfusion during early reflow in both ICAs. On ischemia, the middle cerebral artery (MCA) territory presented a residual perfusion, whereas the caudal territory remained normally perfused. On reflow, speckle images showed a caudorostral propagation of reperfusion through anastomotic connections, and a reduced perfusion in the MCA territory. Autoradiography highlighted the caudorostral gradient, and persistent perfusion in ventral and medial regions. These blood-flow changes were accompanied by mitochondrial respiration impairment in the ipsilateral cortex. Collectively, these data indicate the presence of a primary collateral pathway through the circle of Willis, providing an immediate diversion of blood flow toward ischemic regions, and secondary efficient cortical anastomoses in the immature rat brain.

Modeling and optimization of Look-Locker spin labeling for measuring perfusion and transit time changes in activation studies taking into account arterial blood volume.

PubMed

Francis, S T; Bowtell, R; Gowland, P A

2008-02-01

This work describes a new compartmental model with step-wise temporal analysis for a Look-Locker (LL)-flow-sensitive alternating inversion-recovery (FAIR) sequence, which combines the FAIR arterial spin labeling (ASL) scheme with a LL echo planar imaging (EPI) measurement, using a multireadout EPI sequence for simultaneous perfusion and T*(2) measurements. The new model highlights the importance of accounting for the transit time of blood through the arteriolar compartment, delta, in the quantification of perfusion. The signal expected is calculated in a step-wise manner to avoid discontinuities between different compartments. The optimal LL-FAIR pulse sequence timings for the measurement of perfusion with high signal-to-noise ratio (SNR), and high temporal resolution at 1.5, 3, and 7T are presented. LL-FAIR is shown to provide better SNR per unit time compared to standard FAIR. The sequence has been used experimentally for simultaneous monitoring of perfusion, transit time, and T*(2) changes in response to a visual stimulus in four subjects. It was found that perfusion increased by 83 +/- 4% on brain activation from a resting state value of 94 +/- 13 ml/100 g/min, while T*(2) increased by 3.5 +/- 0.5%. (c) 2008 Wiley-Liss, Inc.

DECHLORINATION OF TRICHLOROETHYLENE USING ELECTROCHEMICAL METHODS

EPA Science Inventory

Electrochemical degradation (ECD) is used to decontaminate organic and inorganic contaminants through oxidative or reductive processes. The ECD of Trichloroethylene (TCE) dechlorinates TCE through electric reduction. TCE dechlorination presented in the literature utilized electro...

Neonatal Morbidity and Mortality After Elective Cesarean Delivery

PubMed Central

Signore, Caroline; Klebanoff, Mark

2008-01-01

As overall cesarean delivery rates have continued to rise, there has been growing interest in the rates of elective cesarean delivery (ECD), and its relative benefits and harms for the mother and neonate. This article explores the effects of elective cesarean delivery at term on neonatal morbidity and mortality. Available data are subject to a number of limitations, and do not provide conclusive evidence regarding the safety of planned elective cesarean versus planned vaginal delivery. Nevertheless, some data suggest an association between ECD and increased neonatal respiratory morbidity and lacerations, and possibly decreased central and peripheral nervous system injury. Potentially increased risks of neonatal mortality with ECD at term may be counterbalanced by risks of fetal demise in ongoing pregnancies. Patients and physicians considering ECD should carefully review competing risks and benefits; further research is needed to inform these discussions. PMID:18456074

Does endothelial cell density correlate with corneal diameter in a group of young adults?

PubMed

Giasson, Claude J; Gosselin, Lucie; Masella, Aviva; Forcier, Pierre

2008-07-01

In children, but not in the elderly, an association exists between corneal diameter and endothelial cell density (ECD). We tested whether such an association also held true in young adults. The eyes of 35 healthy subjects (mean age, 23.1 +/- 3.1 years) were photographed by using a video camera and a noncontact endothelial microscope. Both sets of images were analyzed with image software and the contour method to measure corneal diameter, ECD, and endothelial coefficients. Axial lengths, refractive errors, and corneal curvatures were measured by using an A-scan ultrasonic biometer and kerato-refractometer. Measurements, averaged for the right and left eyes, were analyzed depending on (1) use of contact lenses, (2) ametropia, and on whether (3) axial length or (4) corneal diameter was above or below group means. Differences were tested for statistical significance with independent t tests and association with the Pearson correlation coefficient. ECD, corneal diameter, and spherical equivalent refraction were 3022 +/- 262 cells/mm2, 12.0 +/- 0.5 mm, and -3.1 +/- 2.5 D, respectively. The only significant differences between wearers and nonwearers of contact lenses were the spherical refractive equivalent and axial length. There was no correlation between ECD and corneal diameter or axial length. As opposed to previously reported results in children, but as found in the elderly, there is no correlation between ECD and corneal diameter in young adults. Therefore, corneal size cannot be considered a determinant of ECD in young adults.

Dual Kidney Transplantation: Is It Worth It?

PubMed

Snanoudj, Renaud; Timsit, Marc-Olivier; Rabant, Marion; Tinel, Claire; Lazareth, Hélène; Lamhaut, Lionel; Martinez, Frank; Legendre, Christophe

2017-03-01

Use of expanded criteria donor (ECD) kidneys, which are associated with a reduced graft survival rate, has become widely adopted in elderly recipients in an old-to-old allocation system. However, the results are frequently unsatisfactory, and a high proportion of these ECD kidneys are discarded. Dual kidney transplantation (DKT) is an underused way to expand the pool of ECD kidneys and to rapidly transplant elderly patients with satisfactory results because of the transplantation of double the nephronic mass. In this overview, we summarize the results of the main studies on DKT. DKT suffers from a prejudice of heaviness and is considered to be useless by transplant centers that do not perform it. The literature is often biased by the heterogeneity of the criteria leading to a DKT and the common refusal of kidneys that are judged too marginal. In fact, we show that when strictly allocated according to reliable clinical or histological scores, dual and single ECD transplantations yield similar results in terms of patient and graft survival rates despite significant differences in donors' characteristics. DKTs are not associated with a higher proportion of surgical complications, except in some studies showing thrombosis of 1 of the 2 grafts. The benefits of dual transplantation are particularly evident for kidneys coming from most ECDs. There is still a need for more studies to find the best allocation criteria that would permit transplantation to the highest number of patients with similar outcomes in recipients of single and dual ECD kidneys.

Structural and Genetic Analyses of the Mycobacterium tuberculosis Protein Kinase B Sensor Domain Identify a Potential Ligand-binding Site.

PubMed

Prigozhin, Daniil M; Papavinasasundaram, Kadamba G; Baer, Christina E; Murphy, Kenan C; Moskaleva, Alisa; Chen, Tony Y; Alber, Tom; Sassetti, Christopher M

2016-10-28

Monitoring the environment with serine/threonine protein kinases is critical for growth and survival of Mycobacterium tuberculosis, a devastating human pathogen. Protein kinase B (PknB) is a transmembrane serine/threonine protein kinase that acts as an essential regulator of mycobacterial growth and division. The PknB extracellular domain (ECD) consists of four repeats homologous to penicillin-binding protein and serine/threonine kinase associated (PASTA) domains, and binds fragments of peptidoglycan. These properties suggest that PknB activity is modulated by ECD binding to peptidoglycan substructures, however, the molecular mechanisms underpinning PknB regulation remain unclear. In this study, we report structural and genetic characterization of the PknB ECD. We determined the crystal structures of overlapping ECD fragments at near atomic resolution, built a model of the full ECD, and discovered a region on the C-terminal PASTA domain that has the properties of a ligand-binding site. Hydrophobic interaction between this surface and a bound molecule of citrate was observed in a crystal structure. Our genetic analyses in M. tuberculosis showed that nonfunctional alleles were produced either by deletion of any of single PASTA domain or by mutation of individual conserved residues lining the putative ligand-binding surface of the C-terminal PASTA repeat. These results define two distinct structural features necessary for PknB signal transduction, a fully extended ECD and a conserved, membrane-distal putative ligand-binding site. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Feasibility study of a large-scale tuned mass damper with eddy current damping mechanism

NASA Astrophysics Data System (ADS)

Wang, Zhihao; Chen, Zhengqing; Wang, Jianhui

2012-09-01

Tuned mass dampers (TMDs) have been widely used in recent years to mitigate structural vibration. However, the damping mechanisms employed in the TMDs are mostly based on viscous dampers, which have several well-known disadvantages, such as oil leakage and difficult adjustment of damping ratio for an operating TMD. Alternatively, eddy current damping (ECD) that does not require any contact with the main structure is a potential solution. This paper discusses the design, analysis, manufacture and testing of a large-scale horizontal TMD based on ECD. First, the theoretical model of ECD is formulated, then one large-scale horizontal TMD using ECD is constructed, and finally performance tests of the TMD are conducted. The test results show that the proposed TMD has a very low intrinsic damping ratio, while the damping ratio due to ECD is the dominant damping source, which can be as large as 15% in a proper configuration. In addition, the damping ratios estimated with the theoretical model are roughly consistent with those identified from the test results, and the source of this error is investigated. Moreover, it is demonstrated that the damping ratio in the proposed TMD can be easily adjusted by varying the air gap between permanent magnets and conductive plates. In view of practical applications, possible improvements and feasibility considerations for the proposed TMD are then discussed. It is confirmed that the proposed TMD with ECD is reliable and feasible for use in structural vibration control.

High brain distribution of a new central nervous system drug candidate despite its P-glycoprotein-mediated efflux at the mouse blood-brain barrier.

PubMed

Taccola, Camille; Cartot-Cotton, Sylvaine; Valente, Delphine; Barneoud, Pascal; Aubert, Catherine; Boutet, Valérie; Gallen, Fabienne; Lochus, Murielle; Nicolic, Sophie; Dodacki, Agnès; Smirnova, Maria; Cisternino, Salvatore; Declèves, Xavier; Bourasset, Fanchon

2018-05-30

Efficacy of drugs aimed at treating central nervous system (CNS) disorders rely partly on their ability to cross the cerebral endothelium, also called the blood-brain barrier (BBB), which constitutes the main interface modulating exchanges of compounds between the brain and blood. In this work, we used both, conventional pharmacokinetics (PK) approach and in situ brain perfusion technique to study the blood and brain PK of PKRinh, an inhibitor of the double-stranded RNA-dependent protein kinase (PKR) activation, in mice. PKRinh showed a supra dose-proportional blood exposure that was not observed in the brain, and a brain to blood AUC ratio of unbound drug smaller than 1 at all tested doses. These data suggested the implication of an active efflux at the BBB. Using in situ brain perfusion technique, we showed that PKRinh has a very high brain uptake clearance which saturates with increasing concentrations. Fitting the data to a Michaelis-Menten equation revealed that PKRinh transport through the BBB is composed of a passive unsaturable flux and an active saturable protein-mediated efflux with a k m of ≅ 3 μM. We were able to show that the ATP-binding cassette (ABC) transporter P-gp (Abcb1), but not Bcrp (Abcg2), was involved in the brain to blood efflux of PKRinh. At the circulating PKRinh concentrations of this study, the P-gp was not saturated, in accordance with the linear brain PKRinh PK. Finally, PKRinh had high brain uptake clearance (14 μl/g/s) despite it is a good P-gp substrate (P-gp Efflux ratio ≅ 3.6), and reached similar values than the cerebral blood flow reference, diazepam, in P-gp saturation conditions. With its very unique brain transport properties, PKRinh improves our knowledge about P-gp-mediated efflux across the BBB for the development of new CNS directed drugs. Copyright © 2018. Published by Elsevier B.V.

Regulation of brain copper homeostasis by the brain barrier systems: Effects of Fe-overload and Fe-deficiency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monnot, Andrew D.; Behl, Mamta; Ho, Sanna

2011-11-15

Maintaining brain Cu homeostasis is vital for normal brain function. The role of systemic Fe deficiency (FeD) or overload (FeO) due to metabolic diseases or environmental insults in Cu homeostasis in the cerebrospinal fluid (CSF) and brain tissues remains unknown. This study was designed to investigate how blood-brain barrier (BBB) and blood-SCF barrier (BCB) regulated Cu transport and how FeO or FeD altered brain Cu homeostasis. Rats received an Fe-enriched or Fe-depleted diet for 4 weeks. FeD and FeO treatment resulted in a significant increase (+ 55%) and decrease (- 56%) in CSF Cu levels (p < 0.05), respectively; however,more » neither treatment had any effect on CSF Fe levels. The FeD, but not FeO, led to significant increases in Cu levels in brain parenchyma and the choroid plexus. In situ brain perfusion studies demonstrated that the rate of Cu transport into the brain parenchyma was significantly faster in FeD rats (+ 92%) and significantly slower (- 53%) in FeO rats than in controls. In vitro two chamber Transwell transepithelial transport studies using primary choroidal epithelial cells revealed a predominant efflux of Cu from the CSF to blood compartment by the BCB. Further ventriculo-cisternal perfusion studies showed that Cu clearance by the choroid plexus in FeD animals was significantly greater than control (p < 0.05). Taken together, our results demonstrate that both the BBB and BCB contribute to maintain a stable Cu homeostasis in the brain and CSF. Cu appears to enter the brain primarily via the BBB and is subsequently removed from the CSF by the BCB. FeD has a more profound effect on brain Cu levels than FeO. FeD increases Cu transport at the brain barriers and prompts Cu overload in the CNS. The BCB plays a key role in removing the excess Cu from the CSF.« less

Possible involvement of cationic-drug sensitive transport systems in the blood-to-brain influx and brain-to-blood efflux of amantadine across the blood-brain barrier.

PubMed

Suzuki, Toyofumi; Fukami, Toshiro; Tomono, Kazuo

2015-03-01

The purpose of this study was to characterize the brain-to-blood efflux transport of amantadine across the blood-brain barrier (BBB). The apparent in vivo efflux rate constant for [(3) H]amantadine from the rat brain (keff ) was found to be 1.53 × 10(-2) min(-1) after intracerebral microinjection using the brain efflux index method. The efflux of [(3) H]amantadine was inhibited by 1-methyl-4-phenylpyridinium (MPP(+) ), a cationic neurotoxin, suggesting that amantadine transport from the brain to the blood across the BBB potentially involves the rat plasma membrane monoamine transporter (rPMAT). On the other hand, other selected substrates for organic cation transporters (OCTs) and organic anion transporters (OATs), as well as inhibitors of P-glycoprotein (P-gp), did not affect the efflux transport of [(3) H]amantadine. In addition, in vitro studies using an immortalized rat brain endothelial cell line (GPNT) showed that the uptake and retention of [(3) H]amantadine by the cells was not changed by the addition of cyclosporin, which is an inhibitor of P-gp. However, cyclosporin affected the uptake and retention of rhodamine123. Finally, the initial brain uptake of [(3) H]amantadine was determined using an in situ mouse brain perfusion technique. Notably, the brain uptake clearance for [(3) H]amantadine was significantly decreased with the co-perfusion of quinidine or verapamil, which are cationic P-gp inhibitors, while MPP(+) did not have a significant effect. It is thus concluded that while P-gp is not involved, it is possible that rPMAT and the cationic drug-sensitive transport system participate in the brain-to-blood efflux and the blood-to-brain influx of amantadine across the BBB, respectively. Copyright © 2014 John Wiley & Sons, Ltd.

Tension-Type Headaches: Self-Care Measures for Relief

MedlinePlus

... Accessed July 6, 2015. Durazzo TC, et al. Comparison of regional brain perfusion levels in chronically smoking ... Healthy Living," and the triple-shield Mayo Clinic logo are trademarks of Mayo Foundation for Medical Education ...

The Influence of Maternal and Household Resources, and Parental Psychosocial Child Stimulation on Early Childhood Development: A Cross-Sectional Study of Children 36–59 Months in Honduras

PubMed Central

Urke, Helga Bjørnøy; Contreras, Mariela; Matanda, Dennis Juma

2018-01-01

Optimal early childhood development (ECD) is currently jeopardized for more than 250 million children under five in low- and middle-income countries. The Sustainable Development Goals has called for a renewed emphasis on children’s wellbeing, encompassing a holistic approach that ensures nurturing care to facilitate optimal child development. In vulnerable contexts, the extent of a family’s available resources can influence a child’s potential of reaching its optimal development. Few studies have examined these relationships in low- and middle-income countries using nationally representative samples. The present paper explored the relationships between maternal and paternal psychosocial stimulation of the child as well as maternal and household resources and ECD among 2729 children 36–59 months old in Honduras. Data from the Demographic and Health Surveys conducted in 2011–2012 was used. Adjusted logistic regression analyses showed that maternal psychosocial stimulation was positively and significantly associated with ECD in the full, rural, and lowest wealth quintile samples. These findings underscore the importance of maternal engagement in facilitating ECD but also highlight the role of context when designing tailored interventions to improve ECD. PMID:29735895

Hyperventilation, cerebral perfusion, and syncope.

PubMed

Immink, R V; Pott, F C; Secher, N H; van Lieshout, J J

2014-04-01

This review summarizes evidence in humans for an association between hyperventilation (HV)-induced hypocapnia and a reduction in cerebral perfusion leading to syncope defined as transient loss of consciousness (TLOC). The cerebral vasculature is sensitive to changes in both the arterial carbon dioxide (PaCO2) and oxygen (PaO2) partial pressures so that hypercapnia/hypoxia increases and hypocapnia/hyperoxia reduces global cerebral blood flow. Cerebral hypoperfusion and TLOC have been associated with hypocapnia related to HV. Notwithstanding pronounced cerebrovascular effects of PaCO2 the contribution of a low PaCO2 to the early postural reduction in middle cerebral artery blood velocity is transient. HV together with postural stress does not reduce cerebral perfusion to such an extent that TLOC develops. However when HV is combined with cardiovascular stressors like cold immersion or reduced cardiac output brain perfusion becomes jeopardized. Whether, in patients with cardiovascular disease and/or defect, cerebral blood flow cerebral control HV-induced hypocapnia elicits cerebral hypoperfusion, leading to TLOC, remains to be established.

Decreased Regional Cerebral Perfusion in Moderate-Severe Obstructive Sleep Apnoea during Wakefulness.

PubMed

Innes, Carrie R H; Kelly, Paul T; Hlavac, Michael; Melzer, Tracy R; Jones, Richard D

2015-05-01

To investigate gray matter volume and concentration and cerebral perfusion in people with untreated obstructive sleep apnea (OSA) while awake. Voxel-based morphometry to quantify gray matter concentration and volume. Arterial spin labeling perfusion imaging to quantify cerebral perfusion. Lying supine in a 3-T magnetic resonance imaging scanner in the early afternoon. 19 people with OSA (6 females, 13 males; mean age 56.7 y, range 41-70; mean AHI 18.5, range 5.2-52.8) and 19 controls (13 females, 6 males; mean age: 50.0 y, range 41-81). N/A. There were no differences in regional gray matter concentration or volume between participants with OSA and controls. Neither was there any difference in regional perfusion between controls and people with mild OSA (n = 11). However, compared to controls, participants with moderate-severe OSA (n = 8) had decreased perfusion (while awake) in three clusters. The largest cluster incorporated, bilaterally, the paracingulate gyrus, anterior cingulate gyrus, and subcallosal cortex, and the left putamen and left frontal orbital cortex. The second cluster was right-lateralized, incorporating the posterior temporal fusiform cortex, parahippocampal gyrus, and hippocampus. The third cluster was located in the right thalamus. There is decreased regional perfusion during wakefulness in participants with moderate-severe obstructive sleep apnea, and these are in brain regions which have shown decreased regional gray matter volume in previous studies in people with severe OSA. Thus, we hypothesize that cerebral perfusion changes are evident before (and possibly underlie) future structural changes. © 2015 Associated Professional Sleep Societies, LLC.

SU-E-QI-06: Design and Initial Validation of a Precise Capillary Phantom to Test Perfusion Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wood, R; Iacobucci, G; Khobragade, P

2014-06-15

Purpose: To design a precise perfusion phantom mimicking capillaries of the brain vasculature which could be used to test various perfusion protocols and algorithms which generate perfusion maps. Methods: A perfusion phantom was designed in Solidworks and built using additive manufacturing. The phantom was an overall cylindrical shape of diameter and height 20mm and containing capillaries of 200μm or 300μm which were parallel and in contact making up the inside volume where flow was allowed. We created a flow loop using a peristaltic pump and contrast agent was injected manually. Digital Subtraction Angiographic images and low contrast images with conemore » beam CT were acquired after the contrast was injected. These images were analyzed by our own code in LabVIEW software and Time-Density Curve, MTT and TTP was calculated. Results: Perfused area was visible in the cone beam CT images; however, individual capillaries were not distinguishable. The Time-Density Curve acquired was accurate, sensitive and repeatable. The parameters MTT, and TTP offered by the phantom were very sensitive to slight changes in the TDC shape. Conclusion: We have created a robust calibrating model for evaluation of existing perfusion data analysis systems. This approach is extremely sensitive to changes in the flow due to the high temporal resolution and could be used as a golden standard to assist developers in calibrating and testing of imaging perfusion systems and software algorithms. Supported by NIH Grant: 2R01EB002873 and an equipment grant from Toshiba Medical Systems Corporation.« less

Notch as a Diagnostic Marker and Therapeutic Target in Human Breast Cancer

DTIC Science & Technology

2008-05-01

JAG1. The soluble JAG1-ECD-FLAG was expressed in Chinese Hamster ovary K1 (CHO-K1) cells and then CHO clones were screened for their ability to... medium was collected from CHO-K1- hJAG1-ECD-Flag (clone14) grown in culture. The purification strategy to obtain hJAG1-ECD-Flag is as follows: 1) pre...expressed in Chinese hampster ovary K1 (CHO-K1) cells and then CHO clones were screened for their ability to express high levels of secreted JAG1-Flag

Accuracy of Computed Tomographic Perfusion in Diagnosis of Brain Death: A Prospective Cohort Study.

PubMed

Sawicki, Marcin; Sołek-Pastuszka, Joanna; Chamier-Ciemińska, Katarzyna; Walecka, Anna; Bohatyrewicz, Romuald

2018-05-04

BACKGROUND This study was designed to determine diagnostic accuracy of computed tomographic perfusion (CTP) compared to computed tomographic angiography (CTA) for the diagnosis of brain death (BD). MATERIAL AND METHODS Whole-brain CTP was performed in patients diagnosed with BD and in patients with devastating brain injury with preserved brainstem reflexes. CTA was derived from CTP datasets. Cerebral blood flow (CBF) and volume (CBV) were calculated in all brain regions. CTP findings were interpreted as confirming diagnosis of BD (positive) when CBF and CBV in all ROIs were below 10 mL/100 g/min and 1.0 mL/100 g, respectively. CTA findings were interpreted using a 4-point system. RESULTS Fifty brain-dead patients and 5 controls were included. In brain-dead patients, CTP results revealed CBF 0.00-9.98 mL/100 g/min and CBV 0.00-0.99 mL/100 g, and were thus interpreted as positive in all patients. CTA results suggested 7 negative cases, providing 86% sensitivity. In the non-brain-dead group, CTP results revealed CBF 2.37-37.59 mL/100 g/min and CBV 0.73-2.34 mL/100 g. The difference between values of CBF and CBV in the brain-dead and non-brain-dead groups was statistically significant (p=0.002 for CBF and p=0.001 for CBV). CTP findings in all non-brain-dead patients were interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31-1.00) for CTP in the diagnosis of BD. In all non-brain-dead patients, CTA revealed preserved intracranial filling and was interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31-1.00) for CTA in diagnosis of BD. CONCLUSIONS Whole-brain CTP seems to be a highly sensitive and specific method in diagnosis of BD.

Predictors of liver donation without kidney recovery in a cohort of expanded criteria donors: identifying opportunities to improve expanded criteria donor kidney utilization.

PubMed

White, S L; Leichtman, A B; O'Connor, K; Lipkowitz, G; Pietroski, R; Stoff, J S; Luskin, R S; Belcher, J; Meyer, K; Merion, R M; Port, F K; Delmonico, F L

2012-09-01

To maximize deceased donation, it is necessary to facilitate organ recovery from expanded criteria donors (ECDs). Utilization of donors meeting the kidney definition for ECDs increases access to kidney transplantation and reduces waiting times; however, ECDs often do not proceed to kidney recovery. Based on a prospective study of three Organ Procurement Organizations in the United States, we describe the characteristics of donors meeting the Organ Procurement and Transplant Network (OPTN) ECD kidney definition (donor age 60+ or donor age 50-60 years with two of the following: final serum creatinine > 1.5 mg/dL, history of hypertension, or death from cerebral vascular accident) who donated a liver without kidney recovery. ECDs with organs recovered between February 2003 and September 2005 by New England Organ Bank, Gift of Life Michigan, and LifeChoice Donor Services were studied (n = 324). All donors were declared dead by neurological criteria. Data on a wide range of donor characteristics were collected, including donor demographics, medical history, cause of death, donor status during hospitalization, serological status, and donor kidney quality. Logistic regression models were used to identify donor characteristics predictive of liver-alone donation. Seventy-four of the 324 donors fulfilling the ECD definition for kidneys donated a liver alone (23%). History of diabetes, final serum creatinine > 1.5 mg/dL, age 70+, and presence of proteinuria were associated with liver-alone donation in univariate models. On multivariate analysis, only final serum creatinine > 1.5 mg/dL and age 70+ were independently predictive of liver donation alone. Older age and elevated serum creatinine may be perceived as stronger contraindications to kidney donation than the remaining elements of the ECD definition. It is likely that at least a proportion of these liver-alone donors represent missed opportunities for kidney transplantation. Copyright © 2012 Elsevier Inc. All rights reserved.

Renal Transplants from Older Deceased Donors: Use of Preimplantation Biopsy and Differential Allocation to Dual or Single Kidney Transplant according to Histological Score Has No Advantages over Allocation to Single Kidney Transplant by Simple Clinical Indication.

PubMed

Casati, Costanza; Colombo, Valeriana Giuseppina; Perrino, Marialuisa; Rossetti, Ornella Marina; Querques, Marialuisa; Giacomoni, Alessandro; Binaggia, Agnese; Colussi, Giacomo

2018-01-01

Grafts from elderly donors (ECD) are increasingly allocated to single (SKT) or dual (DKT) kidney transplantation according to biopsy score. Indications and benefits of either procedure lack universal agreement. A total of 302 ECD-transplants in period from Jan 1, 2000, to Dec 31, 2015, were allocated to SKT (SKT pre ) on clinical grounds alone (before Dec 2010, pre-DKT era, n = 170) or according to a clinical-histological protocol (after Dec 2010, DKT era, n = 132) to DKT ( n = 48), SKT biopsy-based protocol ("high-risk", SKT hr , n = 51), or SKT clinically based protocol ("low-risk", SKT lr , n = 33). Graft and patient survival were compared between the two periods and between different transplant categories. Graft and overall survival in recipients from ECD in pre-DKT and DKT era did not differ (5-year graft survival 87.7% and 84.2%, resp.); equal survival in the 2 ECD periods was shown in both donor age ranges of 60-69 and >70-years, and in low-risk or high-risk ECD categories. Within the DKT protocol SKT hr showed worst graft and overall survival in the 60-69 donor age range; DKT did not result in significantly better outcome than SKT from ECD in either era. One-year posttransplant creatinine clearance in recipients did not differ between any ECD transplant category. At 3 and 5 years after transplantation there were significantly higher total dialysis-free recipient life years from an equal donor number in the pre-DKT era than in the DKT protocol. Use of a biopsy-based protocol to allocate grafts from aged donors to SKT or DKT did not result in better short term graft survival than a clinically based protocol with allocation only to SKT and reduced overall recipient dialysis-free life years in time.

Renal Transplants from Older Deceased Donors: Use of Preimplantation Biopsy and Differential Allocation to Dual or Single Kidney Transplant according to Histological Score Has No Advantages over Allocation to Single Kidney Transplant by Simple Clinical Indication

PubMed Central

Casati, Costanza; Colombo, Valeriana Giuseppina; Perrino, Marialuisa; Rossetti, Ornella Marina; Querques, Marialuisa; Giacomoni, Alessandro; Binaggia, Agnese

2018-01-01

Background Grafts from elderly donors (ECD) are increasingly allocated to single (SKT) or dual (DKT) kidney transplantation according to biopsy score. Indications and benefits of either procedure lack universal agreement. Methods A total of 302 ECD-transplants in period from Jan 1, 2000, to Dec 31, 2015, were allocated to SKT (SKTpre) on clinical grounds alone (before Dec 2010, pre-DKT era, n = 170) or according to a clinical-histological protocol (after Dec 2010, DKT era, n = 132) to DKT (n = 48), SKT biopsy-based protocol (“high-risk”, SKThr, n = 51), or SKT clinically based protocol (“low-risk”, SKTlr, n = 33). Graft and patient survival were compared between the two periods and between different transplant categories. Results Graft and overall survival in recipients from ECD in pre-DKT and DKT era did not differ (5-year graft survival 87.7% and 84.2%, resp.); equal survival in the 2 ECD periods was shown in both donor age ranges of 60–69 and >70-years, and in low-risk or high-risk ECD categories. Within the DKT protocol SKThr showed worst graft and overall survival in the 60–69 donor age range; DKT did not result in significantly better outcome than SKT from ECD in either era. One-year posttransplant creatinine clearance in recipients did not differ between any ECD transplant category. At 3 and 5 years after transplantation there were significantly higher total dialysis-free recipient life years from an equal donor number in the pre-DKT era than in the DKT protocol. Conclusions Use of a biopsy-based protocol to allocate grafts from aged donors to SKT or DKT did not result in better short term graft survival than a clinically based protocol with allocation only to SKT and reduced overall recipient dialysis-free life years in time. PMID:29862061

Hearing rehabilitation with a binaural cochlear implant in a patient with Erdheim-Chester disease.

PubMed

Querat, Charlotte; Thai-Van, Hung; Durand, Denis Vital; Cotton, François; Gallego, Stéphane; Truy, Eric

2015-09-01

Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis. This paper reports an exceptional case of bilateral neural involvement, responsible for profound hearing loss. Bilateral cochlear implantation was performed. We present a 57-year-old man affected by ECD with profound bilateral hearing loss. The patient underwent cochlear implantation with a binaural Digisonic(®) cochlear implant, 7 years after the initial diagnosis. Speech intelligibility rose to a plateau after about 6 months of cochlear implant use. The average outcome of speech intelligibility over time was 55% for dissyllabic words without lip reading, and 70% for sentences. Perception score decreased before the patient died from ECD. A description of the ECD and its otological manifestations is presented. This paper reports the effective hearing rehabilitation of profound bilateral hearing loss by the means of a binaural Digisonic(®) cochlear implant.

Regional cerebral blood flow assessed by single photon emission computed tomography (SPECT) in dogs with congenital portosystemic shunt and hepatic encephalopathy.

PubMed

Or, Matan; Peremans, Kathelijne; Martlé, Valentine; Vandermeulen, Eva; Bosmans, Tim; Devriendt, Nausikaa; de Rooster, Hilde

2017-02-01

Regional cerebral blood flow (rCBF) in eight dogs with congenital portosystemic shunt (PSS) and hepatic encephalopathy (HE) was compared with rCBF in eight healthy control dogs using single photon emission computed tomography (SPECT) with a 99m technetium-hexamethylpropylene amine oxime ( 99m Tc-HMPAO) tracer. SPECT scans were abnormal in all PSS dogs. Compared to the control group, rCBF in PSS dogs was significantly decreased in the temporal lobes and increased in the subcortical (thalamic and striatal) area. Brain perfusion imaging alterations observed in the dogs with PSS and HE are similar to those in human patients with HE. These findings suggest that dogs with HE and PSS have altered perfusion of mainly the subcortical and the temporal regions of the brain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantification of Load Dependent Brain Activity in Parametric N-Back Working Memory Tasks using Pseudo-continuous Arterial Spin Labeling (pCASL) Perfusion Imaging.

PubMed

Zou, Qihong; Gu, Hong; Wang, Danny J J; Gao, Jia-Hong; Yang, Yihong

2011-04-01

Brain activation and deactivation induced by N-back working memory tasks and their load effects have been extensively investigated using positron emission tomography (PET) and blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). However, the underlying mechanisms of BOLD fMRI are still not completely understood and PET imaging requires injection of radioactive tracers. In this study, a pseudo-continuous arterial spin labeling (pCASL) perfusion imaging technique was used to quantify cerebral blood flow (CBF), a well understood physiological index reflective of cerebral metabolism, in N-back working memory tasks. Using pCASL, we systematically investigated brain activation and deactivation induced by the N-back working memory tasks and further studied the load effects on brain activity based on quantitative CBF. Our data show increased CBF in the fronto-parietal cortices, thalamus, caudate, and cerebellar regions, and decreased CBF in the posterior cingulate cortex and medial prefrontal cortex, during the working memory tasks. Most of the activated/deactivated brain regions show an approximately linear relationship between CBF and task loads (0, 1, 2 and 3 back), although several regions show non-linear relationships (quadratic and cubic). The CBF-based spatial patterns of brain activation/deactivation and load effects from this study agree well with those obtained from BOLD fMRI and PET techniques. These results demonstrate the feasibility of ASL techniques to quantify human brain activity during high cognitive tasks, suggesting its potential application to assessing the mechanisms of cognitive deficits in neuropsychiatric and neurological disorders.

A comparative study of brain perfusion single-photon emission computed tomography and magnetic resonance imaging in patients with post-traumatic anosmia.

PubMed

Atighechi, Saeid; Salari, Hadi; Baradarantar, Mohammad Hossein; Jafari, Rozita; Karimi, Ghasem; Mirjali, Mehdi

2009-01-01

Loss of smell is a problem that can occur in up to 30% of patients with head trauma. The olfactory function investigation methods so far in use have mostly relied on subjective responses given by patients. Recently, some studies have used magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) to evaluate patients with post-traumatic anosmia. The present study seeks to detect post-traumatic anosmia and the areas in the brain that are related to olfactory impairment by using SPECT and MRI as imaging techniques. The study was conducted on 21 patients suffering from head injury and consequently anosmia as defined by an olfactory identification test. Two control groups (traumatic normosmic and nontraumatic healthy individuals) were selected. Brain MRI, qualitative and semiquantitative SPECT with 99mtc-ethyl-cysteinate-dimer were taken from all the patients. Then the brain SPECT and MRI were compared with each other. Semi-quantitative assessment of the brain perfusion SPECT revealed frontal, left parietal, and left temporal hypoperfusion as compared with the two control groups. Eighty-five percent of the anosmic patients had abnormal brain MRI. Regarding the MRI, the main abnormality proved to be in the anterior inferior region of the frontal lobes and olfactory bulbs. The findings of this study suggest that damage to the frontal lobes and olfactory bulbs as shown in the brain MRI and hypoperfusion in the frontal, left parietal, and left temporal lobes in the semiquantitative SPECT corresponds to post-traumatic anosmia. Further neurophysiological and imaging studies are definitely needed to set the idea completely.

Neurochemical Measurement of Adenosine in Discrete Brain Regions of Five Strains of Inbred Mice

PubMed Central

Pani, Amar K.; Jiao, Yun; Sample, Kenneth J.; Smeyne, Richard J.

2014-01-01

Adenosine (ADO), a non-classical neurotransmitter and neuromodulator, and its metabolites adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP), have been shown to play an important role in a number of biochemical processes. Although their signaling is well described, it has been difficult to directly, accurately and simultaneously quantitate these purines in tissue or fluids. Here, we describe a novel method for measuring adenosine (ADO) and its metabolites using high performance liquid chromatography with electrochemical detection (HPLC-ECD). Using this chromatographic technique, we examined baseline levels of ADO and ATP, ADP and AMP in 6 different brain regions of the C57BL/6J mouse: stratum, cortex, hippocampus, olfactory bulb, substantia nigra and cerebellum and compared ADO levels in 5 different strains of mice (C57BL/6J, Swiss-Webster, FVB/NJ, 129P/J, and BALB/c). These studies demonstrate that baseline levels of purines vary significantly among the brain regions as well as between different mouse strains. These dissimilarities in purine concentrations may explain the variable phenotypes among background strains described in neurological disease models. PMID:24642754

What role for the home learning environment and parenting in reducing the socioeconomic gradient in child development? Findings from the Millennium Cohort Study.

PubMed

Kelly, Y; Sacker, A; Del Bono, E; Francesconi, M; Marmot, M

2011-09-01

Early child health and development (ECD) is important for health in later life. Objectives were to (1) examine the extent of socioeconomic inequality in markers of ECD at ages 3 and 5 years; (2) examine whether the ECD-income gap widens between these ages; (3) assess the contribution of the home learning environment, family routines and psychosocial environment to observed inequalities in ECD. Data on socioemotional difficulties, and tests of cognitive ability in 3-year-old (n=15 382) and 5-year-old (n=15 042) children from the UK Millennium Cohort Study were used. Children in the highest income group were less likely to have socioemotional difficulties compared with those in the lowest income group at 3 and 5 years (2.4% vs 16.4% and 2.0% vs 15.9%, respectively) and had higher mean scores: age 3 'school readiness' 114 versus 99; verbal ability 54 versus 48, and age 5: verbal ability 60 versus 51, non-verbal ability 58 versus 54 and spatial ability 54 versus 48 (all p<0.001). The income gap in verbal ability scores widened between ages 3 and 5 (Wald test, p=0.04). Statistical adjustment for markers of home learning, family routines and psychosocial environments did more to explain the income gap in socioemotional difficulties than in cognitive test scores. Our results suggest that relationships between family income and markers of ECD are amenable to change. The role of home learning, family routines and psychosocial environmental factors are potentially important in closing income gaps in ECD.

A Mathematical Model to Predict Endothelial Cell Density Following Penetrating Keratoplasty With Selective Dropout From Graft Failure

PubMed Central

Riddlesworth, Tonya D.; Kollman, Craig; Lass, Jonathan H.; Patel, Sanjay V.; Stulting, R. Doyle; Benetz, Beth Ann; Gal, Robin L.; Beck, Roy W.

2014-01-01

Purpose. We constructed several mathematical models that predict endothelial cell density (ECD) for patients after penetrating keratoplasty (PK) for a moderate-risk condition (principally Fuchs' dystrophy or pseudophakic/aphakic corneal edema). Methods. In a subset (n = 591) of Cornea Donor Study participants, postoperative ECD was determined by a central reading center. Various statistical models were considered to estimate the ECD trend longitudinally over 10 years of follow-up. A biexponential model with and without a logarithm transformation was fit using the Gauss-Newton nonlinear least squares algorithm. To account for correlated data, a log-polynomial model was fit using the restricted maximum likelihood method. A sensitivity analysis for the potential bias due to selective dropout was performed using Bayesian analysis techniques. Results. The three models using a logarithm transformation yield similar trends, whereas the model without the transform predicts higher ECD values. The adjustment for selective dropout turns out to be negligible. However, this is possibly due to the relatively low rate of graft failure in this cohort (19% at 10 years). Fuchs' dystrophy and pseudophakic/aphakic corneal edema (PACE) patients had similar ECD decay curves, with the PACE group having slightly higher cell densities by 10 years. Conclusions. Endothelial cell loss after PK can be modeled via a log-polynomial model, which accounts for the correlated data from repeated measures on the same subject. This model is not significantly affected by the selective dropout due to graft failure. Our findings warrant further study on how this may extend to ECD following endothelial keratoplasty. PMID:25425307

Cerebral Perfusion Is Perturbed by Preterm Birth and Brain Injury.

PubMed

Mahdi, E S; Bouyssi-Kobar, M; Jacobs, M B; Murnick, J; Chang, T; Limperopoulos, C

2018-05-10

Early disturbances in systemic and cerebral hemodynamics are thought to mediate prematurity-related brain injury. However, the extent to which CBF is perturbed by preterm birth is unknown. Our aim was to compare global and regional CBF in preterm infants with and without brain injury on conventional MR imaging using arterial spin-labeling during the third trimester of ex utero life and to examine the relationship between clinical risk factors and CBF. We prospectively enrolled preterm infants younger than 32 weeks' gestational age and <1500 g and performed arterial spin-labeling MR imaging studies. Global and regional CBF in the cerebral cortex, thalami, pons, and cerebellum was quantified. Preterm infants were stratified into those with and without structural brain injury. We further categorized preterm infants by brain injury severity: moderate-severe and mild. We studied 78 preterm infants: 31 without brain injury and 47 with brain injury (29 with mild and 18 with moderate-severe injury). Global CBF showed a borderline significant increase with increasing gestational age at birth ( P = .05) and trended lower in preterm infants with brain injury ( P = .07). Similarly, regional CBF was significantly lower in the right thalamus and midpons ( P < .05) and trended lower in the midtemporal, left thalamus, and anterior vermis regions ( P < .1) in preterm infants with brain injury. Regional CBF in preterm infants with moderate-severe brain injury trended lower in the midpons, right cerebellar hemisphere, and dentate nuclei compared with mild brain injury ( P < .1). In addition, a significant, lower regional CBF was associated with ventilation, sepsis, and cesarean delivery ( P < .05). We report early disturbances in global and regional CBF in preterm infants following brain injury. Regional cerebral perfusion alterations were evident in the thalamus and pons, suggesting regional vulnerability of the developing cerebro-cerebellar circuitry. © 2018 by American Journal of Neuroradiology.

ELECTROCHEMICAL DEGRADATION OF PERSISTANCE POLLUTANTS IN GROUNDWATER AND SEDIMENTS

EPA Science Inventory

Electrochemical Degradation (ECD) utilizes redox potential at the anode and the cathode to oxidize and/or reduce organic contaminants. ECD of environmentally persistence pollutants such chlorinate solvents, PCBs, and PAHs, although theoretically possible, has not been experimenta...

The "Skull Flap" a new conceived device for decompressive craniectomy experimental study on dogs to evaluate the safety and efficacy in reducing intracranial pressure and subsequent impact on brain perfusion.

PubMed

Salvatore, Chibbaro; Fabrice, Vallee; Marco, Marsella; Leonardo, Tigan; Thomas, Lilin; Benoit, Lecuelle; Bernard, George; Pierre, Kehrli; Eric, Vicaut; Paolo, Diemidio

2013-10-01

Decompressive craniectomy (DC) is a procedure performed increasingly often in current neurosurgical practice. Significant perioperative morbidity may be associated to this procedure because of the large skull defect; also, later closure of the skull defect (cranioplasty) may be associated to post-operative morbidity as much as any other reconstructive operation. The authors present a newly conceived/developed device: The "Skull Flap" (SF). This system, placed at the time of the craniectomy, offers the possibility to provide cranial reconstruction sparing patients a second operation. In other words, DC and cranioplasty essentially take place at the same time and in addition, patients retain their own bone flap. The current study conducted on animal models, represents the logical continuation of a prior recent study, realized on cadaver specimens, to assess the efficacy and safety of this recently developed device. This is an experimental pilot study on dogs to assess both safety and efficacy of the SF device. Two groups of experimental raised intracranial pressure animal models underwent DC; in the first group of dogs, the bone flap was left in raised position above the skull defect using the SF device; on the second group the flap was discarded. All dogs underwent transcranial Doppler (TCD) to assess brain perfusion. Head computed tomography (CT) scan to determine flap position was also obtained in the group in which the SF device was placed. SF has proved to be a strong fixation device that allows satisfactory brain decompression by keeping the bone flap elevated from the swollen brain; later on, the SF allows cranial reconstruction in a simple way without requiring a second staged operation. In addition, it is relevant to note that brain perfusion was measured and found to be better in the group receiving the SF (while the flap being in a raised as well as in its natural position) comparing to the other group. The SF device has proved to be very easy to place, well-adaptable to a different type of flaps and ultimately very effective in maintaining satisfactory brain decompression and later on, making easy bone flap repositioning after brain swelling has subsided.

Computed Tomography Perfusion Improves Diagnostic Accuracy in Acute Posterior Circulation Stroke.

PubMed

Sporns, Peter; Schmidt, Rene; Minnerup, Jens; Dziewas, Rainer; Kemmling, André; Dittrich, Ralf; Zoubi, Tarek; Heermann, Philipp; Cnyrim, Christian; Schwindt, Wolfram; Heindel, Walter; Niederstadt, Thomas; Hanning, Uta

2016-01-01

Computed tomography perfusion (CTP) has a high diagnostic value in the detection of acute ischemic stroke in the anterior circulation. However, the diagnostic value in suspected posterior circulation (PC) stroke is uncertain, and whole brain volume perfusion is not yet in widespread use. We therefore studied the additional value of whole brain volume perfusion to non-contrast CT (NCCT) and CT angiography source images (CTA-SI) for infarct detection in patients with suspected acute ischemic PC stroke. This is a retrospective review of patients with suspected stroke in the PC in a database of our stroke center (n = 3,011) who underwent NCCT, CTA and CTP within 9 h after stroke onset and CT or MRI on follow-up. Images were evaluated for signs and pc-ASPECTS locations of ischemia. Three imaging models - A (NCCT), B (NCCT + CTA-SI) and C (NCCT + CTA-SI + CTP) - were compared with regard to the misclassification rate relative to gold standard (infarction in follow-up imaging) using the McNemar's test. Of 3,011 stroke patients, 267 patients had a suspected stroke in the PC and 188 patients (70.4%) evidenced a PC infarct on follow-up imaging. The sensitivity of Model C (76.6%) was higher compared with that of Model A (21.3%) and Model B (43.6%). CTP detected significantly more ischemic lesions, especially in the cerebellum, posterior cerebral artery territory and thalami. Our findings in a large cohort of consecutive patients show that CTP detects significantly more ischemic strokes in the PC than CTA and NCCT alone. © 2016 S. Karger AG, Basel.

Resting-State Hyperperfusion of the Supplementary Motor Area in Catatonia

PubMed Central

Schäppi, Lea; Federspiel, Andrea; Bohlhalter, Stephan; Wiest, Roland; Strik, Werner; Stegmayer, Katharina

2017-01-01

Abstract Catatonia is a psychomotor syndrome that not only frequently occurs in the context of schizophrenia but also in other conditions. The neural correlates of catatonia remain unclear due to small-sized studies. We therefore compared resting-state cerebral blood flow (rCBF) and gray matter (GM) density between schizophrenia patients with current catatonia and without catatonia and healthy controls. We included 42 schizophrenia patients and 41 controls. Catatonia was currently present in 15 patients (scoring >2 items on the Bush Francis Catatonia Rating Scale screening). Patients did not differ in antipsychotic medication or positive symptoms. We acquired whole-brain rCBF using arterial spin labeling and GM density. We compared whole-brain perfusion and GM density over all and between the groups using 1-way ANCOVAs (F and T tests). We found a group effect (F test) of rCBF within bilateral supplementary motor area (SMA), anterior cingulate cortex, dorsolateral prefrontal cortex, left interior parietal lobe, and cerebellum. T tests indicated 1 cluster (SMA) to be specific to catatonia. Moreover, catatonia of excited and retarded types differed in SMA perfusion. Furthermore, increased catatonia severity was associated with higher perfusion in SMA. Finally, catatonia patients had a distinct pattern of GM density reduction compared to controls with prominent GM loss in frontal and insular cortices. SMA resting-state hyperperfusion is a marker of current catatonia in schizophrenia. This is highly compatible with a dysregulated motor system in catatonia, particularly affecting premotor areas. Moreover, SMA perfusion was differentially altered in retarded and excited catatonia subtypes, arguing for distinct pathobiology. PMID:27729486

Changes in body temperature of the unanaesthetized monkey produced by sodium and calcium ions perfused through the cerebral ventricles

PubMed Central

Myers, R. D.; Veale, W. L.; Yaksh, T. L.

1971-01-01

1. In the unanaesthetized Rhesus monkey, solutions containing sodium, calcium, potassium or magnesium in excess of the normal concentration of extracellular fluid were perfused from a lateral to the fourth ventricle through chronically implanted cannulae. 2. Sodium (11·0-88·0 mM in excess of the physiological concentration) perfused through the ventricles, caused an immediate rise in body temperature which was accompanied by vasoconstriction, piloerection and shivering. The latency of the hyperthermia was related directly to the rate of perfusion and the concentration of sodium, whereas the magnitude of the response depended upon the concentration only. When the perfusion was terminated, shivering ceased and the temperature of the monkey returned to the base line level. 3. When calcium ions were perfused in concentrations 2·5-47·9 mM in excess of that of extracellular fluid, a fall in the temperature of the animal occurred. The magnitude of the decreases depended upon the concentration of calcium in the perfusion fluid. Vasodilatation, sedation and a reduction in withdrawal reflexes accompanied the calcium-induced hypothermia. After the perfusion ended, the temperature continued to fall until the monkey began to shiver and vasoconstriction was observed in many skin areas. 4. The perfusion through the cerebral ventricles with modified Krebs solution alone or with the Krebs solution which contained potassium or magnesium ions in concentrations five to ten times normal had virtually no effect on the temperature of the monkey. 5. Since the temperature of the monkey was unchanged as long as the physiological ratio of sodium to calcium in the perfusion fluid remained constant, we conclude that the balance between these two essential cations within the brain stem could determine the neural mechanism whereby the set-point for body temperature of the primate is established. PMID:4999638

Models of Cerebral-Body Perfusion and Cerebral Chemical Transport.

DTIC Science & Technology

1988-03-01

Pressure Waves 22 Conchusion 23 References 36 A Compartmental Brain Model for Chemical Transport and CO2 Controlled Blood Flow Abstract 37 Introduction 38...surrounding the body, e.g., atmospheric pressure , pressure al high and low altitudes, high underwater pressure , vacuum and excessive gravity acceleration...Resistance of the AreriolarNenous capillary, accounting for the pressure drop observed between them. RCB Resistance of the Blood -Brain barrier (between

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lewis, M.E.; Khachaturian, H.; Watson, S.J.

Using adjacent section autoradiography-immunocytochemistry, the distribution of (TH)naloxone binding sites was studied in relation to neuronal systems containing (Leu)enkephalin, dynorphin A, or beta-endorphin immunoreactivity in rat brain. Brain sections from formaldehyde-perfused rats show robust specific binding of (TH)naloxone, the pharmacological (mu-like) properties of which appear unaltered. In contrast, specific binding of the delta ligand (TH)D-Ala2,D-Leu5-enkephalin was virtually totally eliminated as a result of formaldehyde perfusion. Using adjacent section analysis, the authors have noted associations between (TH)naloxone binding sites and one, two, or all three opioid systems in different brain regions; however, in some areas, no apparent relationship could be observed.more » Within regions, the relationship was complex. The complexity of the association between (TH)naloxone binding sites and the multiple opioid systems, and previous reports of co-localization of mu and kappa receptors in rat brain, are inconsistent with a simple-one-to-one relationship between a given opioid precursor and opioid receptor subtype. Instead, since differential processing of the three precursors gives rise to peptides of varying receptor subtype potencies and selectivities, the multiple peptide-receptor relationships may point to a key role of post-translational processing in determining the physiological consequences of opioid neurotransmission.« less

Optimization of the method for assessment of brain perfusion in humans using contrast-enhanced reflectometry: multidistance time-resolved measurements

NASA Astrophysics Data System (ADS)

Milej, Daniel; Janusek, Dariusz; Gerega, Anna; Wojtkiewicz, Stanislaw; Sawosz, Piotr; Treszczanowicz, Joanna; Weigl, Wojciech; Liebert, Adam

2015-10-01

The aim of the study was to determine optimal measurement conditions for assessment of brain perfusion with the use of optical contrast agent and time-resolved diffuse reflectometry in the near-infrared wavelength range. The source-detector separation at which the distribution of time of flights (DTOF) of photons provided useful information on the inflow of the contrast agent to the intracerebral brain tissue compartments was determined. Series of Monte Carlo simulations was performed in which the inflow and washout of the dye in extra- and intracerebral tissue compartments was modeled and the DTOFs were obtained at different source-detector separations. Furthermore, tests on diffuse phantoms were carried out using a time-resolved setup allowing the measurement of DTOFs at 16 source-detector separations. Finally, the setup was applied in experiments carried out on the heads of adult volunteers during intravenous injection of indocyanine green. Analysis of statistical moments of the measured DTOFs showed that the source-detector separation of 6 cm is recommended for monitoring of inflow of optical contrast to the intracerebral brain tissue compartments with the use of continuous wave reflectometry, whereas the separation of 4 cm is enough when the higher-order moments of DTOFs are available.

Effects of endogenous pyrogen and prostaglandin E2 on hypothalamic neurons in rat brain slices.

PubMed

Watanabe, T; Morimoto, A; Murakami, N

1987-06-01

We investigated the effects of endogenous pyrogen and prostaglandin E2 (PGE2) on the preoptic and anterior hypothalamic (POAH) neurons using brain slice preparations from the rat. Partially purified endogenous pyrogen did not change the activities of most of the neurons in the POAH region when applied locally through a micropipette attached to the recording electrode in proximity to the neurons. This indicates that partially purified endogenous pyrogen does not act directly on the neuronal activity in the POAH region. The partially purified endogenous pyrogen, applied into a culture chamber containing a brain slice, facilitated the activities in 24% of the total neurons tested, regardless of the thermal specificity of the neurons. Moreover, PGE2 added to the culture chamber facilitated 48% of the warm-responsive, 33% of the cold-responsive, and 29% of the thermally insensitive neurons. The direction of change in neuronal activity induced by partially purified endogenous pyrogen appears to be almost the same as that induced by PGE2 when these substances were applied by perfusion to the same neuron in the culture chamber. These results suggest that partially purified pyrogen applied to the perfusate of the culture chamber stimulates some constituents of brain tissue to synthesize and release prostaglandin, which in turn affects the neuronal activity of the POAH region.

[How can we determine the best cerebral perfusion pressure in pediatric traumatic brain injury?].

PubMed

Vuillaume, C; Mrozek, S; Fourcade, O; Geeraerts, T

2013-12-01

The management of cerebral perfusion pressure (CPP) is the one of the main preoccupation for the care of paediatric traumatic brain injury (TBI). The physiology of cerebral autoregulation, CO2 vasoreactivity, cerebral metabolism changes with age as well as the brain compliance. Low CPP leads to high morbidity and mortality in pediatric TBI. The recent guidelines for the management of CPP for the paediatric TBI indicate a CPP threshold 40-50 mmHg (infants for the lower and adolescent for the upper). But we must consider the importance of age-related differences in the arterial pressure and CPP. The best CPP is the one that allows to avoid cerebral ischaemia and oedema. In this way, the adaptation of optimal CPP must be individual. To assess this objective, interesting tools are available. Transcranial Doppler can be used to determine the best level of CPP. Other indicators can predict the impairment of autoregulation like pressure reactivity index (PRx) taking into consideration the respective changes in ICP and CPP. Measurement of brain tissue oxygen partial pressure is an other tool that can be used to determine the optimal CPP. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Heart and brain interaction in patients with heart failure: overview and proposal for a taxonomy. A position paper from the Study Group on Heart and Brain Interaction of the Heart Failure Association.

PubMed

Doehner, Wolfram; Ural, Dilek; Haeusler, Karl Georg; Čelutkienė, Jelena; Bestetti, Reinaldo; Cavusoglu, Yuksel; Peña-Duque, Marco A; Glavas, Duska; Iacoviello, Massimo; Laufs, Ulrich; Alvear, Ricardo Marmol; Mbakwem, Amam; Piepoli, Massimo F; Rosen, Stuart D; Tsivgoulis, Georgios; Vitale, Cristiana; Yilmaz, M Birhan; Anker, Stefan D; Filippatos, Gerasimos; Seferovic, Petar; Coats, Andrew J S; Ruschitzka, Frank

2018-02-01

Heart failure (HF) is a complex clinical syndrome with multiple interactions between the failing myocardium and cerebral (dys-)functions. Bi-directional feedback interactions between the heart and the brain are inherent in the pathophysiology of HF: (i) the impaired cardiac function affects cerebral structure and functional capacity, and (ii) neuronal signals impact on the cardiovascular continuum. These interactions contribute to the symptomatic presentation of HF patients and affect many co-morbidities of HF. Moreover, neuro-cardiac feedback signals significantly promote aggravation and further progression of HF and are causal in the poor prognosis of HF. The diversity and complexity of heart and brain interactions make it difficult to develop a comprehensive overview. In this paper a systematic approach is proposed to develop a comprehensive atlas of related conditions, signals and disease mechanisms of the interactions between the heart and the brain in HF. The proposed taxonomy is based on pathophysiological principles. Impaired perfusion of the brain may represent one major category, with acute (cardio-embolic) or chronic (haemodynamic failure) low perfusion being sub-categories with mostly different consequences (i.e. ischaemic stroke or cognitive impairment, respectively). Further categories include impairment of higher cortical function (mood, cognition), of brain stem function (sympathetic over-activation, neuro-cardiac reflexes). Treatment-related interactions could be categorized as medical, interventional and device-related interactions. Also interactions due to specific diseases are categorized. A methodical approach to categorize the interdependency of heart and brain may help to integrate individual research areas into an overall picture. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Time Is Brain: The Stroke Theory of Relativity.

PubMed

Gomez, Camilo R

2018-04-25

Since the introduction of the philosophical tenet "Time is Brain!," multiple lines of research have demonstrated that other factors contribute to the degree of ischemic injury at any one point in time, and it is now clear that the therapeutic window of acute ischemic stroke is more protracted than it was first suspected. To define a more realistic relationship between time and the ischemic process, we used computational modeling to assess how these 2 variables are affected by collateral circulatory competence. Starting from the premise that the expression "Time=Brain" is mathematically false, we reviewed the existing literature on the attributes of cerebral ischemia over time, with particular attention to relevant clinical parameters, and the effect of different variables, particularly collateral circulation, on the time-ischemia relationship. We used this information to construct a theoretical computational model and applied it to categorically different yet abnormal cerebral perfusion scenarios, allowing comparison of their behavior both overall (i.e., final infarct volume) and in real-time (i.e., instantaneous infarct growth rate). Optimal collateral circulatory competence was predictably associated with slower infarct growth rates and prolongation of therapeutic window. Modeling of identifiable specific types of perfusion maps allows forecasting of the fate of the ischemic process over time. Distinct cerebral perfusion map patterns can be readily identified in patients with acute ischemic stroke. These patterns have inherently different behaviors relative to the time-ischemia construct, allowing the possibility of improving parsing and treatment allocation. It is clearly evident that the effect of time on the ischemic process is relative. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Butorphanol suppression of histamine itch is mediated by nucleus accumbens and septal nuclei: a pharmacological fMRI study.

PubMed

Papoiu, Alexandru D P; Kraft, Robert A; Coghill, Robert C; Yosipovitch, Gil

2015-02-01

Opioid receptors in the central nervous system are important modulators of itch transmission. In this study, we examined the effect of mixed-action opioid butorphanol on histamine itch, cowhage itch, and heat pain in healthy volunteers. Using functional MRI, we investigated significant changes in cerebral perfusion to identify the critical brain centers mediating the antipruritic effect of butorphanol. Butorphanol suppressed the itch induced experimentally with histamine, reduced the intensity of cowhage itch by approximately 35%, and did not affect heat pain sensitivity. In comparison with the placebo, butorphanol produced a bilateral deactivation of claustrum, insula, and putamen, areas activated during itch processing. Analysis of cerebral perfusion patterns of brain processing of itch versus itch inhibition under the effect of the drug revealed that the reduction in cowhage itch by butorphanol was correlated with changes in cerebral perfusion in the midbrain, thalamus, S1, insula, and cerebellum. The suppression of histamine itch by butorphanol was paralleled by the activation of nucleus accumbens and septal nuclei, structures expressing high levels of kappa opioid receptors. In conclusion, important relays of the mesolimbic circuit were involved in the inhibition of itch by butorphanol and could represent potential targets for the development of antipruritic therapy.

Regional reliability of quantitative signal targeting with alternating radiofrequency (STAR) labeling of arterial regions (QUASAR).

PubMed

Tatewaki, Yasuko; Higano, Shuichi; Taki, Yasuyuki; Thyreau, Benjamin; Murata, Takaki; Mugikura, Shunji; Ito, Daisuke; Takase, Kei; Takahashi, Shoki

2014-01-01

Quantitative signal targeting with alternating radiofrequency labeling of arterial regions (QUASAR) is a recent spin labeling technique that could improve the reliability of brain perfusion measurements. Although it is considered reliable for measuring gray matter as a whole, it has never been evaluated regionally. Here we assessed this regional reliability. Using a 3-Tesla Philips Achieva whole-body system, we scanned four times 10 healthy volunteers, in two sessions 2 weeks apart, to obtain QUASAR images. We computed perfusion images and ran a voxel-based analysis within all brain structures. We also calculated mean regional cerebral blood flow (rCBF) within regions of interest configured for each arterial territory distribution. The mean CBF over whole gray matter was 37.74 with intraclass correlation coefficient (ICC) of .70. In white matter, it was 13.94 with an ICC of .30. Voxel-wise ICC and coefficient-of-variation maps showed relatively lower reliability in watershed areas and white matter especially in deeper white matter. The absolute mean rCBF values were consistent with the ones reported from PET, as was the relatively low variability in different feeding arteries. Thus, QUASAR reliability for regional perfusion is high within gray matter, but uncertain within white matter. © 2014 The Authors. Journal of Neuroimaging published by the American Society of Neuroimaging.

Regional Reliability of Quantitative Signal Targeting with Alternating Radiofrequency (STAR) Labeling of Arterial Regions (QUASAR)

PubMed Central

Tatewaki, Yasuko; Higano, Shuichi; Taki, Yasuyuki; Thyreau, Benjamin; Murata, Takaki; Mugikura, Shunji; Ito, Daisuke; Takase, Kei; Takahashi, Shoki

2014-01-01

BACKGROUND AND PURPOSE Quantitative signal targeting with alternating radiofrequency labeling of arterial regions (QUASAR) is a recent spin labeling technique that could improve the reliability of brain perfusion measurements. Although it is considered reliable for measuring gray matter as a whole, it has never been evaluated regionally. Here we assessed this regional reliability. METHODS Using a 3-Tesla Philips Achieva whole-body system, we scanned four times 10 healthy volunteers, in two sessions 2 weeks apart, to obtain QUASAR images. We computed perfusion images and ran a voxel-based analysis within all brain structures. We also calculated mean regional cerebral blood flow (rCBF) within regions of interest configured for each arterial territory distribution. RESULTS The mean CBF over whole gray matter was 37.74 with intraclass correlation coefficient (ICC) of .70. In white matter, it was 13.94 with an ICC of .30. Voxel-wise ICC and coefficient-of-variation maps showed relatively lower reliability in watershed areas and white matter especially in deeper white matter. The absolute mean rCBF values were consistent with the ones reported from PET, as was the relatively low variability in different feeding arteries. CONCLUSIONS Thus, QUASAR reliability for regional perfusion is high within gray matter, but uncertain within white matter. PMID:25370338

Organ-specific physiological responses to acute physical exercise and long-term training in humans.

PubMed

Heinonen, Ilkka; Kalliokoski, Kari K; Hannukainen, Jarna C; Duncker, Dirk J; Nuutila, Pirjo; Knuuti, Juhani

2014-11-01

Virtually all tissues in the human body rely on aerobic metabolism for energy production and are therefore critically dependent on continuous supply of oxygen. Oxygen is provided by blood flow, and, in essence, changes in organ perfusion are also closely associated with alterations in tissue metabolism. In response to acute exercise, blood flow is markedly increased in contracting skeletal muscles and myocardium, but perfusion in other organs (brain and bone) is only slightly enhanced or is even reduced (visceral organs). Despite largely unchanged metabolism and perfusion, repeated exposures to altered hemodynamics and hormonal milieu produced by acute exercise, long-term exercise training appears to be capable of inducing effects also in tissues other than muscles that may yield health benefits. However, the physiological adaptations and driving-force mechanisms in organs such as brain, liver, pancreas, gut, bone, and adipose tissue, remain largely obscure in humans. Along these lines, this review integrates current information on physiological responses to acute exercise and to long-term physical training in major metabolically active human organs. Knowledge is mostly provided based on the state-of-the-art, noninvasive human imaging studies, and directions for future novel research are proposed throughout the review. ©2014 Int. Union Physiol. Sci./Am. Physiol. Soc.

A Perfusion MRI Study of Emotional Valence and Arousal in Parkinson's Disease

PubMed Central

Limsoontarakul, Sunsern; Campbell, Meghan C.; Black, Kevin J.

2011-01-01

Background. Brain regions subserving emotion have mostly been studied using functional magnetic resonance imaging (fMRI) during emotion provocation procedures in healthy participants. Objective. To identify neuroanatomical regions associated with spontaneous changes in emotional state over time. Methods. Self-rated emotional valence and arousal scores, and regional cerebral blood flow (rCBF) measured by perfusion MRI, were measured 4 or 8 times spanning at least 2 weeks in each of 21 subjects with Parkinson's disease (PD). A random-effects SPM analysis, corrected for multiple comparisons, identified significant clusters of contiguous voxels in which rCBF varied with valence or arousal. Results. Emotional valence correlated positively with rCBF in several brain regions, including medial globus pallidus, orbital prefrontal cortex (PFC), and white matter near putamen, thalamus, insula, and medial PFC. Valence correlated negatively with rCBF in striatum, subgenual cingulate cortex, ventrolateral PFC, and precuneus—posterior cingulate cortex (PCC). Arousal correlated positively with rCBF in clusters including claustrum-thalamus-ventral striatum and inferior parietal lobule and correlated negatively in clusters including posterior insula—mediodorsal thalamus and midbrain. Conclusion. This study demonstrates that the temporal stability of perfusion MRI allows within-subject investigations of spontaneous fluctuations in mental state, such as mood, over relatively long-time intervals. PMID:21969917

Extended Criteria Donors in Liver Transplantation.

PubMed

Vodkin, Irine; Kuo, Alexander

2017-05-01

Mortality rates on the liver transplant waiting list are increasing. The shortage of organs has resulted in higher utilization of extended criteria donors (ECDs), with centers pushing the limits of what is acceptable for transplantation. Donor quality is more appropriately represented as a continuum of risk, and careful selection and matching of ECD grafts with recipients may lead to excellent outcomes. Although there is no precise definition for what constitutes an ECD liver, this review focuses on frequently cited characteristics, including donor age, steatosis, donation after cardiac death, and donors with increased risk of disease transmission. Copyright © 2016 Elsevier Inc. All rights reserved.

[In-situ measurement of background atmospheric HCFC-142b using GC-MS and GC-ECD method].

PubMed

Guo, Li-feng; Yao, Bo; Zhou, Ling-xi; Li, Pei-chang; Xu, Lin

2013-05-01

Custom-made GC-MS and GC-ECD in-situ measurement systems were established at the Shangdianzi GAW Regional station. From May 2010 to May 2011, the precisions for GC-MS and GC-ECD systems were 0.23% and 0.88%, respectively, and the HCFC-142b mole fraction during the observation period ranged from 21 x 10(-12) to 355 x 10(-12). The result of the independent-sample T test was P > 0.05, and there was no significant difference in HCFC-142b mole fraction measured by the two systems. The small difference of HCFC-142b mole fraction measured by GC-MS and GC-ECD might be associated with the different sampling time and precision of the two systems. A statistical filter of "robust local regression" was applied to separate HCFC-142b background and pollution data. The mean difference, median difference, 25 and 75 percent difference of background data measured by GC-MS and GC-ECD were all within the precisions. The pollution events captured by the two systems showed similar characters. Results from both systems showed a higher HCFC-142b level in summer and autumn than in winter. The pollution mole fraction of the two systems showed similar seasonal changes.

Early childhood development in Africa: interrogating constraints of prevailing knowledge bases.

PubMed

Pence, Alan R; Marfo, Kofi

2008-04-01

The past two decades have been characterized by renewed attention to the importance of early childhood development (ECD) policies and services in the world's richest and most industrialized countries. During the same period, we have witnessed unprecedented efforts to place ECD policies on the national development planning agenda of the economically less advantaged countries of the Majority World. This paper is premised on the concern that the purposes that have led bilateral and multilateral international agencies to promote and support ECD services in Africa may also be paving the way for uncritical adoption of program and service delivery models grounded in value systems and knowledge bases that may not be appropriate for the continent. We present two critiques to highlight the dangers of ignoring the sociocultural contexts of the knowledge bases that inform ECD policies and practices. We describe one capacity-building effort, under the auspices of the Early Childhood Development Virtual University (ECDVU), to promote culturally relevant knowledge and prepare leadership personnel for Africa's emerging ECD movement. Finally, based on an exercise designed for an ECDVU cohort to engage and reflect on critiques of mainstream research and theorizing on child development, we share insights that are suggestive of the ways in which African perspectives can contribute to and enrich a global knowledge base on child development.

Crystal Structure of the PAC1R Extracellular Domain Unifies a Consensus Fold for Hormone Recognition by Class B G-Protein Coupled Receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Shiva; Pioszak, Augen; Zhang, Chenghai

2012-02-21

Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the PACAP/glucagon family of peptide hormones, which controls many physiological functions in the immune, nervous, endocrine, and muscular systems. It activates adenylate cyclase by binding to its receptor, PAC1R, a member of class B G-protein coupled receptors (GPCR). Crystal structures of a number of Class B GPCR extracellular domains (ECD) bound to their respective peptide hormones have revealed a consensus mechanism of hormone binding. However, the mechanism of how PACAP binds to its receptor remains controversial as an NMR structure of the PAC1R ECD/PACAP complex reveals a different topology ofmore » the ECD and a distinct mode of ligand recognition. Here we report a 1.9 {angstrom} crystal structure of the PAC1R ECD, which adopts the same fold as commonly observed for other members of Class B GPCR. Binding studies and cell-based assays with alanine-scanned peptides and mutated receptor support a model that PAC1R uses the same conserved fold of Class B GPCR ECD for PACAP binding, thus unifying the consensus mechanism of hormone binding for this family of receptors.« less

Rabbit antithymocyte globulin is more beneficial in standard kidney than in extended donor recipients.

PubMed

Hardinger, Karen L; Brennan, Daniel C; Schnitzler, Mark A

2009-05-15

In a randomized, international study comparing rabbit antithymocyte globulin (TMG) and basiliximab (BAS) induction in renal transplant recipients at risk for delayed graft function or acute rejection (n=278), TMG was associated with less acute rejection at 1 year. This study analyzed outcomes stratified by standard criteria donor (SCD), extended criteria donor (ECD), and hypertensive donor. Data-capture limitations necessitated defining ECD as donor age more than 60 years or 50 to 60 years with hypertension and renal insufficiency. Seventy-five recipients received ECD-kidneys (28.4% TMG vs. 25.6% BAS, P=NS) and 203 recipients received SCD-kidneys (72.6% TMG vs. 74.4% BAS, P=NS). Recipients of an ECD or hypertensive donor-kidney had similar outcomes between treatment groups. Recipients of an SCD-kidney treated with TMG had less rejection (odds ratio [OR] 0.48). Recipients of a normotensive donor-kidney treated with TMG had less rejection (OR 0.56). Recipients of a normotensive, SCD-kidney treated with TMG had less rejection (OR 0.47) and death (OR 0.17) than their counterparts treated with BAS. Contrary to its perceived niche in recipients of ECD-kidneys, TMG was most beneficial in patients who received a normotensive, deceased SCD kidney.

X-ray crystallographic studies of the extracellular domain of the first plant ATP receptor, DORN1, and the orthologous protein from Camelina sativa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zhijie; Chakraborty, Sayan; Xu, Guozhou

Does not respond to nucleotides 1 (DORN1) has recently been identified as the first membrane-integral plant ATP receptor, which is required for ATP-induced calcium response, mitogen-activated protein kinase activation and defense responses inArabidopsis thaliana. In order to understand DORN1-mediated ATP sensing and signal transduction, crystallization and preliminary X-ray studies were conducted on the extracellular domain of DORN1 (atDORN1-ECD) and that of an orthologous protein,Camelina sativalectin receptor kinase I.9 (csLecRK-I.9-ECD or csI.9-ECD). A variety of deglycosylation strategies were employed to optimize the glycosylated recombinant atDORN1-ECD for crystallization. In addition, the glycosylated csI.9-ECD protein was crystallized at 291 K. X-ray diffraction datamore » were collected at 4.6 Å resolution from a single crystal. The crystal belonged to space groupC222 orC222 1, with unit-cell parametersa= 94.7,b= 191.5,c= 302.8 Å. These preliminary studies have laid the foundation for structural determination of the DORN1 and I.9 receptor proteins, which will lead to a better understanding of the perception and function of extracellular ATP in plants.« less

The Influence of Maternal and Household Resources, and Parental Psychosocial Child Stimulation on Early Childhood Development: A Cross-Sectional Study of Children 36⁻59 Months in Honduras.

PubMed

Urke, Helga Bjørnøy; Contreras, Mariela; Matanda, Dennis Juma

2018-05-07

Optimal early childhood development (ECD) is currently jeopardized for more than 250 million children under five in low- and middle-income countries. The Sustainable Development Goals has called for a renewed emphasis on children’s wellbeing, encompassing a holistic approach that ensures nurturing care to facilitate optimal child development. In vulnerable contexts, the extent of a family’s available resources can influence a child’s potential of reaching its optimal development. Few studies have examined these relationships in low- and middle-income countries using nationally representative samples. The present paper explored the relationships between maternal and paternal psychosocial stimulation of the child as well as maternal and household resources and ECD among 2729 children 36⁻59 months old in Honduras. Data from the Demographic and Health Surveys conducted in 2011⁻2012 was used. Adjusted logistic regression analyses showed that maternal psychosocial stimulation was positively and significantly associated with ECD in the full, rural, and lowest wealth quintile samples. These findings underscore the importance of maternal engagement in facilitating ECD but also highlight the role of context when designing tailored interventions to improve ECD.

An evaluation of kurtosis beamforming in magnetoencephalography to localize the epileptogenic zone in drug resistant epilepsy patients.

PubMed

Hall, Michael B H; Nissen, Ida A; van Straaten, Elisabeth C W; Furlong, Paul L; Witton, Caroline; Foley, Elaine; Seri, Stefano; Hillebrand, Arjan

2018-06-01

Kurtosis beamforming is a useful technique for analysing magnetoencephalograpy (MEG) data containing epileptic spikes. However, the implementation varies and few studies measure concordance with subsequently resected areas. We evaluated kurtosis beamforming as a means of localizing spikes in drug-resistant epilepsy patients. We retrospectively applied kurtosis beamforming to MEG recordings of 22 epilepsy patients that had previously been analysed using equivalent current dipole (ECD) fitting. Virtual electrodes were placed in the kurtosis volumetric peaks and visually inspected to select a candidate source. The candidate sources were compared to the ECD localizations and resection areas. The kurtosis beamformer produced interpretable localizations in 18/22 patients, of which the candidate source coincided with the resection lobe in 9/13 seizure-free patients and in 3/5 patients with persistent seizures. The sublobar accuracy of the kurtosis beamformer with respect to the resection zone was higher than ECD (56% and 50%, respectively), however, ECD resulted in a higher lobar accuracy (75%, 67%). Kurtosis beamforming may provide additional value when spikes are not clearly discernible on the sensors and support ECD localizations when dipoles are scattered. Kurtosis beamforming should be integrated with existing clinical protocols to assist in localizing the epileptogenic zone. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

A wide linear range Eddy Current Displacement Sensor equipped with dual-coil probe applied in the Magnetic Suspension Flywheel.

PubMed

Fang, Jiancheng; Wen, Tong

2012-01-01

The Eddy Current Displacement Sensor (ECDS) is widely used in the Magnetic Suspension Flywheel (MSFW) to measure the tiny clearance between the rotor and the magnetic bearings. The linear range of the ECDS is determined by the diameter of its probe coil. Wide clearances must be measured in some new MSFWs recently designed for the different space missions, but the coil diameter is limited by some restrictions. In this paper, a multi-channel ECDS equipped with dual-coil probes is proposed to extend the linear range to satisfy the demands of such MSFWs. In order to determine the best configuration of the dual-coil probe, the quality factors of the potential types of the dual-coil probes, the induced eddy current and the magnetic intensity on the surface of the measuring object are compared with those of the conventional single-coil probe. The linear range of the ECDS equipped with the selected dual-coil probe is extended from 1.1 mm to 2.4 mm under the restrictions without adding any cost for additional compensation circuits or expensive coil materials. The effectiveness of the linear range extension ability and the dynamic response of the designed ECDS are confirmed by the testing and the applications in the MSFW.

Pathological Laughing: Brain SPECT Findings.

PubMed

Morland, David; Wolff, Valérie; Blondet, Cyrille; Marescaux, Christian; Namer, Izzie Jacques

2015-09-01

We present the case of a 40-year-old man consulting for uncontrollable episodes of laughing related to emotional lability and not systematically linked to feelings of happiness. Seven months earlier he had presented a pontine ischemic stroke related to an occlusion of the basilar and left vertebral arteries. No epileptic activity or new MRI brain lesions were found. Brain perfusion SPECT performed showed marked hypoperfusion in the right frontal inferior and temporoinsular regions, suggesting a diaschisis phenomenon caused by pontine lesions and highlighted laughing regulation pathways. The patient was successfully treated with a serotonergic reuptake inhibitor, fluoxetine.

Hypertonic sodium lactate reverses brain oxygenation and metabolism dysfunction after traumatic brain injury.

PubMed

Millet, A; Cuisinier, A; Bouzat, P; Batandier, C; Lemasson, B; Stupar, V; Pernet-Gallay, K; Crespy, T; Barbier, E L; Payen, J F

2018-06-01

The mechanisms by which hypertonic sodium lactate (HSL) solution act in injured brain are unclear. We investigated the effects of HSL on brain metabolism, oxygenation, and perfusion in a rodent model of diffuse traumatic brain injury (TBI). Thirty minutes after trauma, anaesthetised adult rats were randomly assigned to receive a 3 h infusion of either a saline solution (TBI-saline group) or HSL (TBI-HSL group). The sham-saline and sham-HSL groups received no insult. Three series of experiments were conducted up to 4 h after TBI (or equivalent) to investigate: 1) brain oedema using diffusion-weighted magnetic resonance imaging and brain metabolism using localized 1 H-magnetic resonance spectroscopy (n = 10 rats per group). The respiratory control ratio was then determined using oxygraphic analysis of extracted mitochondria, 2) brain oxygenation and perfusion using quantitative blood-oxygenation-level-dependent magnetic resonance approach (n = 10 rats per group), and 3) mitochondrial ultrastructural changes (n = 1 rat per group). Compared with the TBI-saline group, the TBI-HSL and the sham-operated groups had reduced brain oedema. Concomitantly, the TBI-HSL group had lower intracellular lactate/creatine ratio [0.049 (0.047-0.098) vs 0.097 (0.079-0.157); P < 0.05], higher mitochondrial respiratory control ratio, higher tissue oxygen saturation [77% (71-79) vs 66% (55-73); P < 0.05], and reduced mitochondrial cristae thickness in astrocytes [27.5 (22.5-38.4) nm vs 38.4 (31.0-47.5) nm; P < 0.01] compared with the TBI-saline group. Serum sodium and lactate concentrations and serum osmolality were higher in the TBI-HSL than in the TBI-saline group. These findings indicate that the hypertonic sodium lactate solution can reverse brain oxygenation and metabolism dysfunction after traumatic brain injury through vasodilatory, mitochondrial, and anti-oedema effects. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

The Role of Multimodal Invasive Monitoring in Acute Traumatic Brain Injury.

PubMed

Lazaridis, Christos; Robertson, Claudia S

2016-10-01

This article reviews the role of modalities that directly monitor brain parenchyma in patients with severe traumatic brain injury. The physiology monitored involves compartmental and perfusion pressures, tissue oxygenation and metabolism, quantitative blood flow, pressure autoregulation, and electrophysiology. There are several proposed roles for this multimodality monitoring, such as to track, prevent, and treat the cascade of secondary brain injury; monitor the neurologically injured patient; integrate various data into a composite, patient-specific, and dynamic picture; apply protocolized, pathophysiology-driven intensive care; use as a prognostic marker; and understand pathophysiologic mechanisms involved in secondary brain injury to develop preventive and abortive therapies, and to inform future clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

Successful Dual Kidney Transplantation After Hypothermic Oxygenated Perfusion of Discarded Human Kidneys

PubMed Central

Ravaioli, Matteo; De Pace, Vanessa; Comai, Giorgia; Busutti, Marco; Gaudio, Massimo Del; Amaduzzi, Annalisa; Cucchetti, Alessandro; Siniscalchi, Antonio; La Manna, Gaetano; D’Errico, Antonietta A.D.; Pinna, Antonio Daniele

2017-01-01

Patient: Female, 58 Final Diagnosis: Nephroangiosclerosis Symptoms: Renal failure Medication: — Clinical Procedure: Resuscitation of grafts by hypothermic oxygenated perfusion Specialty: Transplantology Objective: Challenging differential diagnosis Background: The recovery of discarded human kidneys has increased in recent years and impels to use of unconventional organ preservation strategies that improve graft function. We report the first case of human kidneys histologically discarded and transplanted after hypothermic oxygenated perfusion (HOPE). Case Report: Marginal kidneys from a 78-year-old woman with brain death were declined by Italian transplant centers due to biopsy score (right kidney: 6; left kidney: 7). We recovered and preserved both kidneys through HOPE and we revaluated their use for transplantation by means of perfusion parameters. The right kidney was perfused for 1 h 20 min and the left kidney for 2 h 30 min. During organ perfusion, the renal flow increased progressively. We observed an increase of 34% for the left kidney (median flow 52 ml/min) and 50% for the right kidney (median flow 24 ml/min). Both kidneys had low perfusate’s lactate levels. We used perfusion parameters as important determinants of the organ discard. Based on our previous organ perfusion experience, the increase of renal flow and the low level of lactate following 1 h of HOPE lead us to declare both kidneys as appropriate for dual kidney transplantation (DKT). No complications were reported during the transplant and in the post-transplant hospital stay. The recipient had immediate graft function and serum creatinine value of 0.95 mg/dL at 3 months post-transplant. Conclusions: HOPE provides added information in the organ selection process and may improve graft quality of marginal kidneys. PMID:28928357

Modeling the Complexities of Water and Hygiene in Limpopo Province South Africa

NASA Astrophysics Data System (ADS)

Mellor, J. E.; Smith, J. A.; Learmonth, G.; Netshandama, V.; Dillingham, R.

2012-12-01

Access to sustainable water and sanitation services is one of the biggest challenges the developing world faces as an increasing number of people inhabit those areas. Inadequate access to water and sanitation infrastructure often leads children to drink poor quality water which can result in early childhood diarrhea (ECD). Repeated episodes of ECD can cause serious problems such as growth stunting, cognitive impairment, and even death. Although researchers have long studied the connection between poor access to water and hygiene facilities and ECD, most studies have relied on intervention-control methods to study the effects of singular interventions. Such studies are time-consuming, costly, and fail to acknowledge that the causes and prevention strategies for ECD are numerous and complex. An alternate approach is to think of a community as a complex system in which the engineered, natural and social environments interact in ways that are not easily predicted. Such complex systems have no central or coordinating mechanism and may exhibit emergent behavior which can be counterintuitive and lead to valuable insights. The goal of this research is to develop a robust, quantitative understanding of the complex pathogen transmission chain that leads to ECD. To realize this goal, we have developed an Agent-Based Model (ABM) which simulates individual community member behavior. We have validated this transdisciplinary model with four years of field data from a community in Limpopo Province, South Africa. Our model incorporates data such as household water source preferences, collection habits, household- and source-water quality, water-source reliability and biological regrowth. Our outcome measures are household water quality, ECD incidences, and child growth stunting. This technique allows us to test hypotheses on the computer. Future researchers can implement promising interventions with our partner institution, the University of Venda, and the model can be refined as the results of those interventions become available. Our model accurately reproduces current pathogen transport through the communities and child growth stunting. An intensive sensitivity analysis found that biological regrowth, biofilm layers and collection habits are all factors in pathogen transmission. We also report on the effects of multiple interventions and our exploration of emergent behavior. Our results indicate that the dominant source of fecal-oral transmission is through the contamination of drinking water after collection, but before consumption. Furthermore sub-optimal interventions such as improved, but still inconsistent water treatment have little protective effect against ECD. Finally, interventions such as the introduction of point-of-use water treatment technologies or improved water-storage practices are the best ECD prevention strategies. The complexities of the causes and prevention strategies of pathogen loading and ECD in the developing world are poorly understood. This project goes beyond previous studies through its ability to model the complex engineered/natural/social pathogen transmission chain using an ABM informed by field data. We hope that this and similar tools may be used by scientists, policy-makers and humanitarian organizations when designing community-level interventions to prevent ECD in similar settings around the world.

Tissue quality of eye-bank-prepared precut corneas for Descemet's stripping automated endothelial keratoplasty.

PubMed

Nelson, Brian A; Ritenour, Rusty J

2014-02-01

To evaluate endothelial cell density (ECD) of eye-bank-prepared tissue for use in Descemet's stripping automated endothelial keratoplasty (DSAEK). Prospective case series of consecutive corneal tissue prepared for DSAEK surgery. Sixty-seven sequential corneal-scleral tissue specimens representing 48 human donors processed for use in DSAEK surgery by the Regional Tissue Bank (Halifax, Nova Scotia). Corneal-scleral donor tissue was obtained by in situ recovery. ECD was recorded using the EB-3000 XYZ (HAI Laboratories Inc, Lexington, MA) specular microscope within 24 hours of preservation. Before the tissue was dissected, the corneal thickness was measured using the DGH-550 PACHETTE 2 (DGH Technology, Exton, PA) ultrasound pachymeter. The dissection was performed using a 300-μm Moria ALTK model microkeratome (Moria Inc). The posterior bed thickness was measured, and the anterior flap was replaced. Endothelial cell count density was obtained after re-preservation. Complete measurements were obtained for 42 of 67 corneas. In 25 corneas it was not possible to obtain a postdissection ECD measurement. The mean ECD before dissection was 2806 ± 317 cells/mm(2). The mean ECD after dissection was 2772 ± 318 cells/mm(2). There was an average loss of 34 cells/mm(2) (95% CI -110 to 40 cells/mm(2), p = 0.3). This case series confirms that ECD is preserved when DSAEK tissue is prepared in advance of surgery by trained eye-bank technicians in a low-volume Canadian eye bank. It was difficult to obtain clear images of the endothelial cell layer postdissection, possibly because of tissue swelling or distortion. Sixty-six of 67 corneas included in the study were used for surgery. © 2013 Canadian Ophthalmological Society Published by Canadian Ophthalmological Society All rights reserved.

Development of a clinical static and dynamic standing balance measurement tool appropriate for use in adolescents.

PubMed

Emery, Carolyn A; Cassidy, J David; Klassen, Terry P; Rosychuk, Rhonda J; Rowe, Brian B

2005-06-01

There is a need in sports medicine for a static and dynamic standing balance measure to quantify balance ability in adolescents. The purposes of this study were to determine the test-retest reliability of timed static (eyes open) and dynamic (eyes open and eyes closed) unipedal balance measurements and to examine factors associated with balance. Adolescents (n=123) were randomly selected from 10 Calgary high schools. This study used a repeated-measures design. One rater measured unipedal standing balance, including timed eyes-closed static (ECS), eyes-open dynamic (EOD), and eyes-closed dynamic (ECD) balance at baseline and 1 week later. Dynamic balance was measured on a foam surface. Reliability was examined using both intraclass correlation coefficients (ICCs) and Bland and Altman statistical techniques. Multiple linear regressions were used to examine other potentially influencing factors. Based on ICCs, test-retest reliability was adequate for ECS, EOD, and ECD balance (ICC=.69, .59, and .46, respectively). The results of Bland and Altman methods, however, suggest that caution is required in interpreting reliability based on ICCs alone. Although both ECS balance and ECD balance appear to demonstrate adequate test-retest reliability by ICC, Bland and Altman methods of agreement demonstrate sufficient reliability for ECD balance only. Thirty percent of the subjects reached the 180-second maximum on EOD balance, suggesting that this test is not appropriate for use in this population. Balance ability (ECS and ECD) was better in adolescents with no past history of lower-extremity injury. Timed ECD balance is an appropriate and reliable clinical measurement for use in adolescents and is influenced by previous injury.

N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor Significantly Increases Peptide Hormone Affinity.

PubMed

Lee, Sang-Min; Booe, Jason M; Gingell, Joseph J; Sjoelund, Virginie; Hay, Debbie L; Pioszak, Augen A

2017-07-05

The calcitonin receptor (CTR) is a class B G protein-coupled receptor that is activated by the peptide hormones calcitonin and amylin. Calcitonin regulates bone remodeling through CTR, whereas amylin regulates blood glucose and food intake by activating CTR in complex with receptor activity-modifying proteins (RAMPs). These receptors are targeted clinically for the treatment of osteoporosis and diabetes. Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays. N-Glycan-free CTR ECD produced in Escherichia coli exhibited ∼10-fold lower peptide affinity than CTR ECD produced in HEK293T cells, which yield complex N-glycans, or in HEK293S GnTI - cells, which yield core N-glycans (Man 5 GlcNAc 2 ). PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding. Similar results were observed for an amylin receptor RAMP2-CTR ECD complex. Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement. Molecular modeling suggested that this GlcNAc functions through an allosteric mechanism rather than by directly contacting the peptide. These results reveal an important role for N-linked glycosylation in the peptide hormone binding of a clinically relevant class B GPCR.

Structural Basis for Hormone Recognition by the Human CRFR2[alpha] G Protein-coupled Receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pal, Kuntal; Swaminathan, Kunchithapadam; Xu, H. Eric

2012-05-09

The mammalian corticotropin releasing factor (CRF)/urocortin (Ucn) peptide hormones include four structurally similar peptides, CRF, Ucn1, Ucn2, and Ucn3, that regulate stress responses, metabolism, and cardiovascular function by activating either of two related class B G protein-coupled receptors, CRFR1 and CRFR2. CRF and Ucn1 activate both receptors, whereas Ucn2 and Ucn3 are CRFR2-selective. The molecular basis for selectivity is unclear. Here, we show that the purified N-terminal extracellular domains (ECDs) of human CRFR1 and the CRFR2{alpha} isoform are sufficient to discriminate the peptides, and we present three crystal structures of the CRFR2{alpha} ECD bound to each of the Ucn peptides.more » The CRFR2{alpha} ECD forms the same fold observed for the CRFR1 and mouse CRFR2{beta} ECDs but contains a unique N-terminal {alpha}-helix formed by its pseudo signal peptide. The CRFR2{alpha} ECD peptide-binding site architecture is similar to that of CRFR1, and binding of the {alpha}-helical Ucn peptides closely resembles CRF binding to CRFR1. Comparing the electrostatic surface potentials of the ECDs suggests a charge compatibility mechanism for ligand discrimination involving a single amino acid difference in the receptors (CRFR1 Glu104/CRFR2{alpha} Pro-100) at a site proximate to peptide residue 35 (Arg in CRF/Ucn1, Ala in Ucn2/3). CRFR1 Glu-104 acts as a selectivity filter preventing Ucn2/3 binding because the nonpolar Ala-35 is incompatible with the negatively charged Glu-104. The structures explain the mechanisms of ligand recognition and discrimination and provide a molecular template for the rational design of therapeutic agents selectively targeting these receptors.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jiang; Malmirchegini, G. Reza; Clubb, Robert T.

Native mass spectrometry (MS) has become an invaluable tool for the characterization of proteins and non-covalent protein complexes under near physiological solution conditions. Here we report the structural characterization of human hemoglobin (Hb), a 64 kDa oxygen-transporting protein complex, by high resolution native top-down mass spectrometry using electrospray ionization (ESI) and a 15-Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Native MS preserves the non-covalent interactions between the globin subunits, and electron capture dissociation (ECD) produces fragments directly from the intact Hb complex without dissociating the subunits. Using activated ion ECD, we observe the gradual unfolding process of themore » Hb complex in the gas phase. Without protein ion activation, the native Hb shows very limited ECD fragmentation from the N-termini, suggesting a tightly packed structure of the native complex and therefore low fragmentation efficiency. Precursor ion activation allows steady increase of N-terminal fragment ions, while the C-terminal fragments remain limited (38 c ions and 4 z ions on the α chain; 36 c ions and 2 z ions on the β chain). This ECD fragmentation pattern suggests that upon activation, the Hb complex starts to unfold from the N-termini of both subunits, whereas the C-terminal regions and therefore the potential regions involved in the subunit binding interactions remain intact. ECD-MS of the Hb dimer show similar fragmentation patterns as the Hb tetramer, providing further evidence for the hypothesized unfolding process of the Hb complex in the gas phase. Native top-down ECD-MS allows efficient probing of the Hb complex structure and the subunit binding interactions in the gas phase. Finally, it may provide a fast and effective means to probe the structure of novel protein complexes that are intractable to traditional structural characterization tools.« less

Structural Heterogeneity of Doubly-Charged Peptide b-Ions

NASA Astrophysics Data System (ADS)

Li, Xiaojuan; Huang, Yiqun; O'Connor, Peter B.; Lin, Cheng

2011-02-01

Performing collisionally activated dissociation (CAD) and electron capture dissociation (ECD) in tandem has shown great promise in providing comprehensive sequence information that was otherwise unobtainable by using either fragmentation method alone or in duet. However, the general applicability of this MS3 approach in peptide sequencing may be undermined by the formation of non-direct sequence ions, as sometimes observed under CAD, particularly when multiple stages of CAD are involved. In this study, varied-sized doubly-charged b-ions from three tachykinin peptides were investigated by ECD. Sequence scrambling was observed in ECD of all b-ions from neurokinin A (HKTDSFVGLM-NH2), suggesting the presence of N- and C-termini linked macro-cyclic conformers. On the contrary, none of the b-ions from eledoisin (pEPSKDAFIGLM-NH2) produced non-direct sequence ions under ECD, as it does not contain a free N-terminal amino group. ECD of several b-ions from Substance P (RPKPQQFFGLM-NH2) showed series of cm-Lys fragment ions which suggested that the macro-cyclic structure may also be formed by connecting the C-terminal carbonyl group and the ɛ-amino group of the lysine side chain. Theoretical investigation of selected Substance P b-ions revealed several low energy conformers, including both linear oxazolones and macro-ring structures, in corroboration with the experimental observation. This study showed that a b-ion may exist as a mixture of several forms, with their propensities influenced by its N-terminus, length, and certain side-chain groups. Further, the presence of several macro-cyclic structures may result in erroneous sequence assignment when the combined CAD and ECD methods are used in peptide sequencing.

Structural Heterogeneity of Doubly-Charged Peptide b-Ions

PubMed Central

Li, Xiaojuan; Huang, Yiqun; O’Connor, Peter B.; Lin, Cheng

2011-01-01

Performing collisionally activated dissociation (CAD) and electron capture dissociation (ECD) in tandem has shown great promise in providing comprehensive sequence information that was otherwise unobtainable by using either fragmentation method alone or in duet. However, the general applicability of this MS3 approach in peptide sequencing may be undermined by the formation of non-direct sequence ions, as sometimes observed under CAD, particularly when multiple stages of CAD are involved. In this study, varied-sized doubly-charged b-ions from three tachykinin peptides were investigated by ECD. Sequence scrambling was observed in ECD of all b-ions from neurokinin A (HKTDSFVGLM-NH2), suggesting the presence of N- and C-termini linked macro-cyclic conformers. On the contrary, none of the b-ions from eledoisin (pEPSKDAFIGLM-NH2) produced non-direct sequence ions under ECD, as it does not contain a free N-terminal amino group. ECD of several b-ions from Substance P (RPKPQQFFGLM-NH2) showed series of cm-Lys fragment ions which suggested that the macro-cyclic structure may also be formed by connecting the C-terminal carbonyl group and the ε-amino group of the lysine side chain. Theoretical investigation of selected Substance P b-ions revealed several low energy conformers, including both linear oxazolones and macro-ring structures, in corroboration with the experimental observation. This study showed that a b-ion may exist as a mixture of several forms, with their propensities influenced by its N-terminus, length, and certain side-chain groups. Further, the presence of several macro-cyclic structures may result in erroneous sequence assignment when the combined CAD and ECD methods are used in peptide sequencing. PMID:21472584

Early Childhood Development and Iranian Parents' Knowledge: A Qualitative Study.

PubMed

Habibi, Elham; Sajedi, Firouzeh; Afzali, Hosein Malek; Hatamizadeh, Nikta; Shahshahanipour, Soheila; Glascoe, Frances Page

2017-01-01

Early childhood is the most important step throughout the lifespan and it is a critical period continuing to the end of 8-year-old. Mothers' knowledge is one of the important aspects of child development. The goals of this study were to determine the situation of knowledge in Iranian parents about the concept and the importance of early childhood development (ECD) and determining the sources of parental knowledge about ECD from the perspective of parents and grandparents. This qualitative study was conducted based on the directional content analysis in 2016. The purposive sampling method is utilized to select 24 participants among parents and grandparents in Tehran. The inclusion criteria consisted of speaking in Persian and having a child or grandchild <3-year-old. Data were collected through four focus group discussions and four individual interviews. Iranian parental knowledge about integrative ECD is not enough, their knowledge about motor development and speech and language are relatively better, about cognitive development is little and socialemotional is very little. They said parents and other caregivers influence the process of children's development. Parents' knowledge resources about ECD included human resources, physical resources, virtual space, and the media. According to the majority of participants, "pediatricians are the most reliable source of parents' knowledge about ECD" even though the main focus of pediatricians is on treating diseases, physical health, and growth of children. According to the results, the knowledge of Iranian parent is not enough about ECD; therefore, actions must be taken to increase their knowledge in these domains. Parents look for reliable and valid sources to enhance their knowledge and they rely the most on pediatricians in this regard. Therefore, more studies on assessing parents' knowledge in community and the practical methods for knowledge promotion in this field is recommended.

Creating leptin-like biofunctions by active immunization against chicken leptin receptor in growing chickens.

PubMed

Lei, M M; Wu, S Q; Shao, X B; Li, X W; Chen, Z; Ying, S J; Shi, Z D

2015-01-01

In this study, immunization against chicken leptin receptor (cLEPR) extracellular domain (ECD) was applied to investigate leptin regulation and LEPR biofunction in growing chicken pullets. A recombinant protein (cLEPR ECD) based on the cLEPR complemenary DNA sequence corresponding to the 582nd to 796th amino acid residues of cLEPR mature peptide was prepared and used as antigen. Immunization against cLEPR ECD in growing chickens increased anti-cLEPR ECD antibody titers in blood, enhanced proportions of phosphorylated janus kinase 2 (JAK2) and served as signal transducer and activator of transcription 3 (STAT3) protein in liver tissue. Chicken live weight gain and abdominal fat mass were significantly decreased (P < 0.05), but feed intake was stimulated by cLEPR ECD immunization (P < 0.05). The treatment also upregulated the gene expression levels of lepR, AMP-activated protein kinase (AMPK), acetyl CoA carboxylase-2 (ACC2), and uncoupling protein 3 (UCP3) in liver, abdominal fat, and breast muscle (P < 0.05) but decreased fasn expression levels (P < 0.01). Apart from that of lepR, the expression of appetite-regulating genes, such as orexigenic genes, agouti-related peptide (AgRP) and neuropeptide Y (NPY), were upregulated (P < 0.01), whereas the anorexigenic gene proopiomelanocortin (POMC) was downregulated in the hypothalamic tissue of cLEPR-immunized pullets (P < 0.01). Blood concentrations of metabolic molecules, such as glucose, triglycerides, and very-low-density lipoprotein, were significantly decreased in cLEPR-immunized pullets but those of cholesterol, high-density lipoprotein, and low-density lipoprotein increased. These results demonstrate that antibodies to membrane proximal cLEPR ECD enhance cLEPR signal transduction, which stimulates metabolism and reduces fat deposition in chickens. Copyright © 2015 Elsevier Inc. All rights reserved.

Influence of metallic artifact filtering on MEG signals for source localization during interictal epileptiform activity

NASA Astrophysics Data System (ADS)

Migliorelli, Carolina; Alonso, Joan F.; Romero, Sergio; Mañanas, Miguel A.; Nowak, Rafał; Russi, Antonio

2016-04-01

Objective. Medical intractable epilepsy is a common condition that affects 40% of epileptic patients that generally have to undergo resective surgery. Magnetoencephalography (MEG) has been increasingly used to identify the epileptogenic foci through equivalent current dipole (ECD) modeling, one of the most accepted methods to obtain an accurate localization of interictal epileptiform discharges (IEDs). Modeling requires that MEG signals are adequately preprocessed to reduce interferences, a task that has been greatly improved by the use of blind source separation (BSS) methods. MEG recordings are highly sensitive to metallic interferences originated inside the head by implanted intracranial electrodes, dental prosthesis, etc and also coming from external sources such as pacemakers or vagal stimulators. To reduce these artifacts, a BSS-based fully automatic procedure was recently developed and validated, showing an effective reduction of metallic artifacts in simulated and real signals (Migliorelli et al 2015 J. Neural Eng. 12 046001). The main objective of this study was to evaluate its effects in the detection of IEDs and ECD modeling of patients with focal epilepsy and metallic interference. Approach. A comparison between the resulting positions of ECDs was performed: without removing metallic interference; rejecting only channels with large metallic artifacts; and after BSS-based reduction. Measures of dispersion and distance of ECDs were defined to analyze the results. Main results. The relationship between the artifact-to-signal ratio and ECD fitting showed that higher values of metallic interference produced highly scattered dipoles. Results revealed a significant reduction on dispersion using the BSS-based reduction procedure, yielding feasible locations of ECDs in contrast to the other two approaches. Significance. The automatic BSS-based method can be applied to MEG datasets affected by metallic artifacts as a processing step to improve the localization of epileptic foci.

Impact of playing American professional football on long-term brain function.

PubMed

Amen, Daniel G; Newberg, Andrew; Thatcher, Robert; Jin, Yi; Wu, Joseph; Keator, David; Willeumier, Kristen

2011-01-01

The authors recruited 100 active and former National Football League players, representing 27 teams and all positions. Players underwent a clinical history, brain SPECT imaging, qEEG, and multiple neuropsychological measures, including MicroCog. Relative to a healthy-comparison group, players showed global decreased perfusion, especially in the prefrontal, temporal, parietal, and occipital lobes, and cerebellar regions. Quantitative EEG findings were consistent, showing elevated slow waves in the frontal and temporal regions. Significant decreases from normal values were found in most neuropsychological tests. This is the first large-scale brain-imaging study to demonstrate significant differences consistent with a chronic brain trauma pattern in professional football players.

Cardiovascular alterations and multi organ dysfunction after birth asphyxia

PubMed Central

Polglase, Graeme R.; Ong, Tracey; Hillman, Noah H

2016-01-01

Synopsis The cardiovascular response to asphyxia involves redistribution of cardiac output to maintain oxygen delivery to critical organs such as the adrenal gland, heart and brain, at the expense of other organs such as the gut, kidneys and skin. This results in reduced perfusion and localized hypoxia/ischemia in these organs, which if severe, can result in multi-organ failure. Liver injury, coagulopathy, bleeding, thrombocytopenia, renal dysfunction, pulmonary and gastrointestinal injury all result from hypoxia, under-perfusion or both. Current clinical therapies need to be considered together with therapeutic hypothermia and cardiovascular recovery. PMID:27524448

Perfusion deficits detected by arterial spin-labeling in patients with TIA with negative diffusion and vascular imaging.

PubMed

Qiao, X J; Salamon, N; Wang, D J J; He, R; Linetsky, M; Ellingson, B M; Pope, W B

2013-01-01

A substantial portion of clinically diagnosed TIA cases is imaging-negative. The purpose of the current study is to determine if arterial spin-labeling is helpful in detecting perfusion abnormalities in patients presenting clinically with TIA. Pseudocontinuous arterial spin-labeling with 3D background-suppressed gradient and spin-echo was acquired on 49 patients suspected of TIA within 24 hours of symptom onset. All patients were free of stroke history and had no lesion-specific findings on general MR, DWI, and MRA sequences. The calculated arterial spin-labeling CBF maps were scored from 1-3 on the basis of presence and severity of perfusion disturbance by 3 independent observers blinded to patient history. An age-matched cohort of 36 patients diagnosed with no cerebrovascular events was evaluated as a control. Interobserver agreement was assessed by use of the Kendall concordance test. Scoring of perfusion abnormalities on arterial spin-labeling scans of the TIA cohort was highly concordant among the 3 observers (W = 0.812). The sensitivity and specificity of arterial spin-labeling in the diagnosis of perfusion abnormalities in TIA was 55.8% and 90.7%, respectively. In 93.3% (70/75) of the arterial spin-labeling CBF map readings with positive scores (≥2), the brain regions where perfusion abnormalities were identified by 3 observers matched with the neurologic deficits at TIA onset. In this preliminary study, arterial spin-labeling showed promise in the detection of perfusion abnormalities that correlated with clinically diagnosed TIA in patients with otherwise normal neuroimaging results.

ELECTROCHEMICAL DECHLORINATION OF TRICHLOROETHYLENE USING GRANULAR-GRAPHITE ELECTRODES: IDENTIFICATION AND QUANTIFICATION OF DECHLORINATION PRODUCTS

EPA Science Inventory

Electrochemical degradation (ECD) utilizes high redox potential at the anode and low redox potential at the cathode to oxidize and/or reduce organic and inorganic contaminants. ECD of Trichloroethylene (TCE), although theoretically possible, has not been experimentally proven. Th...

Conformational states of the full-length glucagon receptor

PubMed Central

Yang, Linlin; Yang, Dehua; de Graaf, Chris; Moeller, Arne; West, Graham M.; Dharmarajan, Venkatasubramanian; Wang, Chong; Siu, Fai Y.; Song, Gaojie; Reedtz-Runge, Steffen; Pascal, Bruce D.; Wu, Beili; Potter, Clinton S.; Zhou, Hu; Griffin, Patrick R.; Carragher, Bridget; Yang, Huaiyu; Wang, Ming-Wei; Stevens, Raymond C.; Jiang, Hualiang

2015-01-01

Class B G protein-coupled receptors are composed of an extracellular domain (ECD) and a seven-transmembrane (7TM) domain, and their signalling is regulated by peptide hormones. Using a hybrid structural biology approach together with the ECD and 7TM domain crystal structures of the glucagon receptor (GCGR), we examine the relationship between full-length receptor conformation and peptide ligand binding. Molecular dynamics (MD) and disulfide crosslinking studies suggest that apo-GCGR can adopt both an open and closed conformation associated with extensive contacts between the ECD and 7TM domain. The electron microscopy (EM) map of the full-length GCGR shows how a monoclonal antibody stabilizes the ECD and 7TM domain in an elongated conformation. Hydrogen/deuterium exchange (HDX) studies and MD simulations indicate that an open conformation is also stabilized by peptide ligand binding. The combined studies reveal the open/closed states of GCGR and suggest that glucagon binds to GCGR by a conformational selection mechanism. PMID:26227798

Evidence of second-trimester changes in head biometry and brain perfusion in fetuses with congenital heart disease.

PubMed

Masoller, N; Martínez, J M; Gómez, O; Bennasar, M; Crispi, F; Sanz-Cortés, M; Egaña-Ugrinovic, G; Bartrons, J; Puerto, B; Gratacós, E

2014-08-01

To evaluate the associations between congenital heart disease (CHD) and head biometry and cerebrovascular blood flow dynamics at the time of diagnosis of CHD in the second trimester of pregnancy. This was a study of 95 consecutive fetuses diagnosed with CHD. At the time of diagnosis, fetal biometry was performed and brain perfusion was assessed by middle cerebral artery pulsatility index (MCA-PI), cerebroplacental ratio (CPR) and fractional moving blood volume (FMBV). The results were compared with those of 95 normal fetuses matched for gestational age. Median gestational age at diagnosis was 22 + 3 (range, 20 + 0 to 23 + 5) weeks. Fetuses with CHD showed significantly lower MCA-PI and CPR Z-scores (-0.23 vs 0.34 and -0.37 vs 0.30, respectively; both P < 0.001) and higher FMBV Z-scores (2.35 vs 0.15; P < 0.001). FMBV > 95(th) percentile was observed in 81.1% of cases as compared with 10.5% in controls (P < 0.001). Moreover, cases showed significantly smaller biparietal diameter (BPD) and head circumference (HC) Z-scores (-1.61 vs -0.43 and -0.89 vs 0.09, respectively; both P < 0.001), with a higher proportion of BPD and HC measurements below the 5(th) percentile compared with controls (51.6% vs 13.7% and 26.3% vs 4.2%, respectively; both P < 0.001). These findings were more pronounced in those cases with types of CHD associated with compromised oxygenated blood delivery to the brain, such as left outflow tract obstruction and transposition of the great arteries. A high proportion of fetuses with CHD have a smaller head and increased brain perfusion already in the second trimester, suggesting an early onset of the mechanisms leading to poorer neurodevelopment later in life. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Differentiation of brain abscesses from glioblastomas and metastatic brain tumors: comparisons of diagnostic performance of dynamic susceptibility contrast-enhanced perfusion MR imaging before and after mathematic contrast leakage correction.

PubMed

Toh, Cheng Hong; Wei, Kuo-Chen; Chang, Chen-Nen; Ng, Shu-Hang; Wong, Ho-Fai; Lin, Ching-Po

2014-01-01

To compare the diagnostic performance of dynamic susceptibility contrast-enhanced perfusion MRI before and after mathematic contrast leakage correction in differentiating pyogenic brain abscesses from glioblastomas and/or metastatic brain tumors. Cerebral blood volume (CBV), leakage-corrected CBV and leakage coefficient K2 were measured in enhancing rims, perifocal edema and contralateral normal appearing white matter (NAWM) of 17 abscesses, 19 glioblastomas and 20 metastases, respectively. The CBV and corrected CBV were normalized by dividing the values in the enhancing rims or edema to those of contralateral NAWM. For each study group, a paired t test was used to compare the K2 of the enhancing rims or edema with those of NAWM, as well as between CBV and corrected CBV of the enhancing rims or edema. ANOVA was used to compare CBV, corrected CBV and K2 among three lesion types. The diagnostic performance of CBV and corrected CBV was assessed with receiver operating characteristic (ROC) curve analysis. The CBV and correction CBV of enhancing rim were 1.45±1.17 and 1.97±1.01 for abscesses, 3.85±2.19 and 4.39±2.33 for glioblastomas, and 2.39±0.90 and 2.97±0.78 for metastases, respectively. The CBV and corrected CBV in the enhancing rim of abscesses were significantly lower than those of glioblastomas and metastases (P = 0.001 and P = 0.007, respectively). In differentiating abscesses from glioblastomas and metastases, the AUC values of corrected CBV (0.822) were slightly higher than those of CBV (0.792). Mathematic leakage correction slightly increases the diagnostic performance of CBV in differentiating pyogenic abscesses from necrotic glioblastomas and cystic metastases. Clinically, DSC perfusion MRI may not need mathematic leakage correction in differentiating abscesses from glioblastomas and/or metastases.

Association of Severe Traumatic Brain Injury Patient Outcomes With Duration of Cerebrovascular Autoregulation Impairment Events.

PubMed

Preiksaitis, Aidanas; Krakauskaite, Solventa; Petkus, Vytautas; Rocka, Saulius; Chomskis, Romanas; Dagi, Teodoro Forcht; Ragauskas, Arminas

2016-07-01

Cerebrovascular autoregulation (CA) is an important hemodynamic mechanism that protects the brain against inappropriate fluctuations in cerebral blood flow in the face of changing cerebral perfusion pressure. Temporal CA failure is associated with worse outcomes in various acute neurological diseases. An integrative approach is presently used according to the existing paradigm for the association of series of temporal CA impairments with the outcomes of patients with traumatic brain injury (TBI). To explore the influence of the duration of CA impairment events on severe TBI patient outcomes. Patient age was also included in the analysis of the prospectively collected clinical data. CA monitoring included 33 prospective severe TBI patients. The pressure reactivity index [PRx(t)] was continuously monitored to collect information on the dynamics of CA status and to analyze associations between the duration of the longest CA impairment event and patient outcomes. The Glasgow outcome scale and the duration of the longest CA impairment were negatively correlated. The duration of autoregulation impairment significantly correlated with worse outcomes. Multidimensional representation of Glasgow outcome scale plots showed that better outcomes were obtained for younger patients (age < 47 years) and those whose longest CA impairment event was shorter than 40 minutes if PRx(t) was above 0.7 in the CA impairment event. Unfavorable outcomes for TBI patients are more significantly associated with the duration of the single longest CA impairment episode at a high PRx(t) value, rather than with averaged PRx(t) values or the average time of all CA impairment episodes. ABP, arterial blood pressureABP(t), continuous reference arterial blood pressureCA, cerebrovascular autoregulationCBF, cerebral blood flowCPP, cerebral perfusion pressureGOS, Glasgow outcome scaleGOSHD, Glasgow outcome scale after hospital dischargeGOS6M, Glasgow outcome scale at 6 months after dischargeICP, intracranial pressureICP(t), continuously monitored intracranial pressureLCAI, longest CA impairmentoptCPP, optimal cerebral perfusion pressurePRx(t), pressure reactivity indexTBI, traumatic brain injury.

Mid-gestation brain Doppler and head biometry in fetuses with congenital heart disease predict abnormal brain development at birth.

PubMed

Masoller, N; Sanz-CortéS, M; Crispi, F; Gómez, O; Bennasar, M; Egaña-Ugrinovic, G; Bargalló, N; Martínez, J M; Gratacós, E

2016-01-01

Fetuses with congenital heart disease (CHD) show evidence of abnormal brain development before birth, which is thought to contribute to adverse neurodevelopment during childhood. Our aim was to evaluate whether brain development in late pregnancy can be predicted by fetal brain Doppler, head biometry and the clinical form of CHD at the time of diagnosis. This was a prospective cohort study including 58 fetuses with CHD, diagnosed at 20-24 weeks' gestation, and 58 normal control fetuses. At the time of diagnosis, we recorded fetal head circumference (HC), biparietal diameter, middle cerebral artery pulsatility index (MCA-PI), cerebroplacental ratio (CPR) and brain perfusion by fractional moving blood volume. We classified cases into one of two clinical types defined by the expected levels (high or low) of placental (well-oxygenated) blood perfusion, according to the anatomical defect. All fetuses underwent subsequent 3T-magnetic resonance imaging (MRI) at 36-38 weeks' gestation. Abnormal prenatal brain development was defined by a composite score including any of the following findings on MRI: total brain volume <  10(th) centile, parietoccipital or cingulate fissure depth <  10(th) centile or abnormal metabolic profile in the frontal lobe. Logistic regression analysis demonstrated that MCA-PI (odds ratio (OR), 12.7; P = 0.01), CPR (OR, 8.7; P = 0.02) and HC (OR, 6.2; P = 0.02) were independent predictors of abnormal neurodevelopment; however, the clinical type of CHD was not. Fetal brain Doppler and head biometry at the time of CHD diagnosis are independent predictors of abnormal brain development at birth, and could be used in future algorithms to improve counseling and targeted interventions. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

The role of corneal endothelial morphology in graft assessment and prediction of endothelial cell loss during organ culture of human donor corneas.

PubMed

Hermel, Martin; Salla, Sabine; Fuest, Matthias; Walter, Peter

2017-03-01

Endothelial assessment is crucial in the release of corneas for grafting. We retrospectively analysed the role of endothelial morphology parameters in predicting endothelial cell loss during organ culture. Human donor corneas were cultured in minimal essential medium with 2% fetal calf serum and antibiotics. Initial endothelial morphology was assessed microscopically using score parameters polymegethism (POL), pleomorphism (PLE), granulation (GRA), vacuolization (VAC), segmentation of cell membranes (SEG), Descemet's folds (DF), trypan blue-positive cells (TBPC) and endothelial cell-free areas (ECFA). Some corneas were primarily rejected based on endothelial assessment. Endothelial cell density (ECD) was assessed at the beginning (I-ECD) and end of culture. Corneas were then placed in dehydration medium (as above + 5% dextran 500). In a subgroup, ECD was reassessed after dehydration. Endothelial cell loss during culture (ECL@Culture) and culture+dehydration (ECL-Culture&Dehydration) were calculated. Data were given as mean ± SD and analysed using multiple linear and logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. I-ECD was 2812 ± 360/mm 2 (n = 2356). The decision to reject a cornea due to endothelial assessment was associated negatively with I-ECD (OR = 0.77/100 cells, CI 0.7-0.82) and positively with ECFA (OR = 2.7, CI 1.69-4.35), SEG (OR =1.3, CI 1.01-1.68) and donor age (OR = 1.26/decade, CI 1.33-1.41). ECL@Culture was 153 ± 201/mm 2 (n = 1277), ECL@Culture&Dehydration was 169 ± 183/mm 2 (n = 918). ECL@Culture was associated positively with donor age, I-ECD, GRA and TBPC, and negatively with PLE, and DF. ECL@Culture&Dehydration was associated positively with age, sex, initial ECD, POL, PLE, VAC and TBPC. Morphological parameters displayed associations with the exclusion of corneas from culture and with endothelial cell loss. Appropriate parameter selection for screening purposes may help improve graft quality. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Structural and functional characterizations of activin type 2B receptor (acvr2b) ortholog from the marine fish, gilthead sea bream, Sparus aurata: evidence for gene duplication of acvr2b in fish.

PubMed

Funkenstein, Bruria; Krol, Ekaterina; Esterin, Elena; Kim, Yong-Soo

2012-12-01

Myostatin (MSTN), a negative regulator of muscle growth and a member of the transforming growth factor-β superfamily, can bind the two activin type 2 receptors (ACVR2). It has been previously shown that WT mice injected with ACVR2B extracellular domain (ACVR2B-ECD) had higher muscle mass. Likewise, fish larvae immersed in Pichia pastoris culture supernatant, containing goldfish Acvr2b-ECD, showed enhanced larval growth. However, it is not clear whether fish Mstn1 and Mstn2 signal through the same receptor and whether fish express more than one acvr2b gene. In the current study, three cDNAs encoding acvr2b (saacvr2b-1, saacvr2b-2a, and saacvr2b-2b) were cloned from gilthead sea bream. All three contain the short extracellular binding domain, a short transmembrane region, and a conserved catalytic domain of serine/threonine protein kinase. Bioinformatics analysis provided evidence for the existence of two acvr2b genes (acvr2b-1 and acvr2b-2) in several other fish species as well, probably as a result of gene or genome duplication. The two isoforms differ in their amino acid sequences. The direct inhibitory effect of Acvr2b-ECD on Mstn activity was tested in vitro. The saAcvr2b-1-ECD was expressed in the yeast P. pastoris. Evidence is provided for N-glycosylation of Acvr2b-1-ECD. The affinity-purified Acvr2b-1-ECD inhibited recombinant mouse/rat/human mature MSTN activity when determined in vitro using the CAGA-luciferase assay in A204 cells. A lower inhibitory activity was obtained when unprocessed purified, furin-digested, and activated saMstn1 was used. Results of this study demonstrate for the first time the existence of two acvr2b genes in fish. In addition, the study shows that bioactive fish Acvr2b-ECD can be produced from P. pastoris.

Central Artery Stiffness, Baroreflex Sensitivity, and Brain White Matter Neuronal Fiber Integrity in Older Adults

PubMed Central

Tarumi, Takashi; de Jong, Daan L.K.; Zhu, David C.; Tseng, Benjamin Y.; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B.; Kerwin, Diana R.; Lu, Hanzhang; Cullum, C. Munro; Zhang, Rong

2015-01-01

Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65±6 years) with normal cognitive function or mild cognitive impairment (MCI) were tested. The neuronal fiber integrity of brain WM was assessed from diffusion metrics acquired by diffusion tensor imaging. BRS was measured in response to acute changes in blood pressure induced by bolus injections of vasoactive drugs. Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). The WM diffusion metrics including fractional anisotropy (FA) and radial (RD) and axial (AD) diffusivities, BRS, and cfPWV were not different between the control and MCI groups. Thus, the data from both groups were combined for subsequent analyses. Across WM, fiber tracts with decreased FA and increased RD were associated with lower BRS and higher cfPWV, with many of the areas presenting spatial overlap. In particular, the BRS assessed during hypotension was strongly correlated with FA and RD when compared with hypertension. Executive function performance was associated with FA and RD in the areas that correlated with cfPWV and BRS. These findings suggest that baroreflex-mediated control of systemic arterial perfusion, especially during hypotension, may play a crucial role in maintaining neuronal fiber integrity of brain WM in older adults. PMID:25623500

The structure of the perivascular compartment in the old canine brain: a case study.

PubMed

Criswell, Theodore P; Sharp, Matthew MacGregor; Dobson, Howard; Finucane, Ciara; Weller, Roy O; Verma, Ajay; Carare, Roxana O

2017-11-15

Dilatation of periarteriolar spaces in MRI of the ageing human brains occurs in white matter (WM), basal ganglia and midbrain but not in cerebral cortex. Perivenous collagenous occurs in periventricular but not in subcortical WM.Here we test the hypotheses that (a) the capacity for dilatation of periarteriolar spaces correlates with the anatomical distribution of leptomeningeal cells coating intracerebral arteries and (b) the regional development of perivenous collagenous in the WM correlates with the population of intramural cells in the walls of veins.The anatomical distribution of leptomeningeal and intramural cells related to cerebral blood vessels is best documented by electron microscopy, requiring perfusion-fixed tissue not available in human material. We therefore analysed perfusion-fixed brain from a 12-year-old Beagle dog as the canine brain represents the anatomical arrangement in the human brain. Results showed regional variation in the arrangement of leptomeningeal cells around blood vessels. Arterioles are enveloped by one complete layer of leptomeninges often with a second incomplete layer in the WM. Venules showed incomplete layers of leptomeningeal cells. Intramural cell expression was higher in the post-capillary venules of the subcortical WM when compared with periventricular WM, suggesting that periventricular collagenosis around venules may be due to a lower resistance in the venular walls. It appears that the regional variation in the capacity for dilatation of arteriolar perivascular spaces in the white WM may be related to the number of perivascular leptomeningeal cells surrounding vessels in different areas of the brain. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Mortality and Outcome Comparison Between Brain Tissue Oxygen Combined with Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy and Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy in Traumatic Brain Injury: A Meta-Analysis.

PubMed

Xie, Qiang; Wu, Hai-Bing; Yan, Yu-Feng; Liu, Meng; Wang, Er-Song

2017-04-01

The combination of brain tissue oxygen and standard intracranial pressure (ICP)/cerebral perfusion pressure (CPP)-guided therapy is thought to improve traumatic brain injury (TBI) prognosis compared with standard ICP/CPP-guided therapy. However, related results of previous observational studies and recently published cohort studies and randomized controlled trials (RCTs) remain controversial. The objective of this study was to compare the effect of the combined therapy with that of standard ICP/CPP-guided therapy on mortality rate, favorable outcome, ICP/CPP, and length of stay (LOS). We systematically searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Web of Science in July 2016 for studies comparing the combined therapy and standard ICP/CPP-guided therapy. Random-effect and fixed-effect models were used for pooled analyses. After screening 362 studies, 8 cohort studies and 1 RCT were included. Primary outcomes were mortality and favorable outcome. The overall mortality risk ratio showed no obvious advantages between the 2 groups (risk ratio [RR], 0.76; 95% confidence interval [CI], 0.54-1.06) and discharge mortality (RR, 1.01; 95% CI, 0.80-1.26) and 3-month mortality (RR, 0.77; 95% CI, 0.53-1.12). Compared with the ICP/CPP group, the combined group was more likely to achieve better outcome during the 6 months after TBI (RR, 1.26; 95% CI, 1.04-1.52) or exactly at 6 months (RR, 1.34; 95% CI, 1.07-1.68), whereas ICP (standardized mean difference [SMD], -0.19; 95% CI, -0.43 to 0.05), CPP (SMD, 0.13; 95% CI, -0.09 to 0.35), and LOS (SMD, 0.13; 95% CI, -0.11 to 0.37) showed no obvious differences. Compared with standard ICP/CPP-guided therapy, brain tissue oxygen combined with ICP/CPP-guided therapy improved long-term outcomes without any effects on mortality, ICP/CPP, or LOS. Copyright © 2016 Elsevier Inc. All rights reserved.

The distribution of the anti-HIV drug, 2'3'-dideoxycytidine (ddC), across the blood-brain and blood-cerebrospinal fluid barriers and the influence of organic anion transport inhibitors.

PubMed

Gibbs, J E; Thomas, S A

2002-02-01

The brain and CSF distribution of the HIV reverse transcriptase inhibitor, 2'3'-dideoxycytidine (ddC), was investigated by the in situ brain perfusion and isolated incubated choroid plexus methods in the guinea pig. Multiple-time brain perfusions indicated that the distribution of [3H]ddC to the brain and CSF was low and the unidirectional rate constant (K(in)) for the brain uptake of this nucleoside analogue (0.52 +/- 0.10 microL/min/g) was not significantly different to that for the vascular marker, [14C]mannitol (0.44 +/- 0.09 microL/min/g). The influence of unlabelled ddC, six organic anion transport inhibitors and 3'-azido 3'-deoxythymidine (AZT) on the CNS uptake of [3H]ddC was examined in situ and in vitro. ddC, probenecid and 2,4-dichlorophenoxyacetic acid altered the distribution of [3H]ddC into the brain and choroid plexuses, indicating that the limited distribution of [3H]ddC was a result of an organic anion efflux transporter, in addition to the low lipophilicity of this drug (octanol-saline partition coefficient, 0.047 +/- 0.001). The CNS distribution was also sensitive to p-aminohippurate and deltorphin II, but not digoxin, suggesting the involvement of organic anion transporters (OAT1/OAT3-like) and organic anion transporting polypeptides (OATP1/OATPA-like). AZT did not effect the accumulation of [3H]ddC, indicating that when these nucleoside analogues are used in anti-HIV combination therapy, the CNS distribution of ddC is unchanged.

Multimodality Monitoring for Cerebral Perfusion Pressure Optimization in Comatose Patients with Intracerebral Hemorrhage

PubMed Central

Ko, Sang-Bae; Choi, H. Alex; Parikh, Gunjan; Helbok, Raimund; Schmidt, J. Michael; Lee, Kiwon; Badjatia, Neeraj; Claassen, Jan; Connolly, E. Sander; Mayer, Stephan A.

2011-01-01

Background and Purpose Limited data exists to recommend specific cerebral perfusion pressure (CPP) targets in patients with intracerebral hemorrhage (ICH). We sought to determine the feasibility of brain multimodality monitoring (MMM) for optimizing CPP and potentially reducing secondary brain injury after ICH. Methods We retrospectively analyzed brain MMM data targeted at perihematomal brain tissue in 18 comatose ICH patients (median monitoring: 164 hours). Physiological measures were averaged over one-hour intervals corresponding to each microdialysis sample. Metabolic crisis (MC) was defined as a lactate/pyruvate ratio (LPR) >40 with a brain glucose concentration <0.7 mmol/L. Brain tissue hypoxia (BTH) was defined as PbtO2 <15 mm Hg. Pressure reactivity index (PRx) and oxygen reactivity index (ORx) were calculated. Results Median age was 59 years, median GCS score 6, and median ICH volume was 37.5 ml. The risk of BTH, and to a lesser extent MC, increased with lower CPP values. Multivariable analyses showed that CPP <80 mm Hg was associated with a greater risk of BTH (OR 1.5, 95% CI 1.1–2.1, P=0.01) compared to CPP >100 mm Hg as a reference range. Six patients died (33%). Survivors had significantly higher CPP and PbtO2 and lower ICP values starting on post-bleed day 4, whereas LPR and PRx values were lower, indicating preservation of aerobic metabolism and pressure autoregulation. Conclusions PbtO2 monitoring can be used to identify CPP targets for optimal brain tissue oxygenation. In patients who do not undergo MMM, maintaining CPP >80 mm Hg may reduce the risk of BTH. PMID:21852615

Assignment of absolute stereostructures through quantum mechanics electronic and vibrational circular dichroism calculations.

PubMed

Dai, Peng; Jiang, Nan; Tan, Ren-Xiang

2016-01-01

Elucidation of absolute configuration of chiral molecules including structurally complex natural products remains a challenging problem in organic chemistry. A reliable method for assigning the absolute stereostructure is to combine the experimental circular dichroism (CD) techniques such as electronic and vibrational CD (ECD and VCD), with quantum mechanics (QM) ECD and VCD calculations. The traditional QM methods as well as their continuing developments make them more applicable with accuracy. Taking some chiral natural products with diverse conformations as examples, this review describes the basic concepts and new developments of QM approaches for ECD and VCD calculations in solution and solid states.

Quantitative fluorescence angiography for neurosurgical interventions.

PubMed

Weichelt, Claudia; Duscha, Philipp; Steinmeier, Ralf; Meyer, Tobias; Kuß, Julia; Cimalla, Peter; Kirsch, Matthias; Sobottka, Stephan B; Koch, Edmund; Schackert, Gabriele; Morgenstern, Ute

2013-06-01

Present methods for quantitative measurement of cerebral perfusion during neurosurgical operations require additional technology for measurement, data acquisition, and processing. This study used conventional fluorescence video angiography--as an established method to visualize blood flow in brain vessels--enhanced by a quantifying perfusion software tool. For these purposes, the fluorescence dye indocyanine green is given intravenously, and after activation by a near-infrared light source the fluorescence signal is recorded. Video data are analyzed by software algorithms to allow quantification of the blood flow. Additionally, perfusion is measured intraoperatively by a reference system. Furthermore, comparing reference measurements using a flow phantom were performed to verify the quantitative blood flow results of the software and to validate the software algorithm. Analysis of intraoperative video data provides characteristic biological parameters. These parameters were implemented in the special flow phantom for experimental validation of the developed software algorithms. Furthermore, various factors that influence the determination of perfusion parameters were analyzed by means of mathematical simulation. Comparing patient measurement, phantom experiment, and computer simulation under certain conditions (variable frame rate, vessel diameter, etc.), the results of the software algorithms are within the range of parameter accuracy of the reference methods. Therefore, the software algorithm for calculating cortical perfusion parameters from video data presents a helpful intraoperative tool without complex additional measurement technology.

Implications of Evidence-Centered Design for Educational Testing

ERIC Educational Resources Information Center

Mislevy, Robert J.; Haertel, Geneva D.

2006-01-01

Evidence-centered assessment design (ECD) provides language, concepts, and knowledge representations for designing and delivering educational assessments, all organized around the evidentiary argument an assessment is meant to embody. This article describes ECD in terms of layers for analyzing domains, laying out arguments, creating schemas for…

MEASUREMENT OF DIBROMOACETIC ACID IN RAT BLOOD BY GC/ECD

EPA Science Inventory

Measurement of Dibromoacetic Acid in Rat Blood by GC/ECD

M. Leonard Mole, MD 67, Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, USEPA, Research Triangle Park, NC 27711; Phone: 919-541-2680, FAX: 919-541-4017, e-mail: mole.l...

Successful outcome of transplant of kidneys recovered from a brain-dead liver transplant recipient: case report.

PubMed

Domagała, Piotr; Kwiatkowski, Artur; Drozdowski, Jakub; Ostrowski, Krzysztof; Wszola, Michal; Diuwe, Piotr; Durlik, Magdalena; Paczek, Leszek; Chmura, Andrzej

2012-12-01

Few reports describing the use of organs donated by transplant recipients have been published. In this case report, kidneys procured from a brain-dead liver recipient were transplanted successfully. A 21-year-old man was referred for liver transplant after an overdose of acetaminophen. The patient's kidney function was initially normal, with proper urine production and normal kidney laboratory parameters. On the third day after admission, the patient's kidney laboratory parameters became elevated and hepatic encephalopathy requiring mechanical ventilation developed. An orthotopic liver transplant was performed the next day. The patient did not recover consciousness, and brain death was diagnosed on the third day after the liver transplant surgery. The maximum serum concentration of creatinine was 5.8 mg/dL (513 μmol/L) before kidney recovery, and urine production was normal. The kidneys were recovered with organ-perfusion support and were preserved by using machine perfusion. The kidneys were transplanted into 2 male recipients. Twelve months after transplant, the recipients remained in good health with satisfactory kidney function. This case demonstrates that transplanting kidneys recovered from liver transplant recipients is possible and beneficial, thus expanding the pool of potential donors.

Precut cornea for Descemet's stripping endothelial keratoplasty: experience at a single eye bank.

PubMed

Mohamed, Ashik; Chaurasia, Sunita; Chandragiri, Venkataswamy; Kandhibanda, Srinivas; Gunnam, Srinivas; Garg, Prashant

2017-06-01

The aim of the study is to describe the experience with precut facility for endothelial keratoplasty at a single eye bank affiliated to a tertiary eye care center in India. Data on precut tissues from Nov 2012 to Dec 2014 were retrospectively reviewed from the electronic database of the eye bank of a tertiary eye care center in South India. Donor characteristic data including donor age, precut and postcut endothelial cell density (ECD), recipient age, and thickness of graft were collected. The number of precuts increased from 42 in 2012 (Nov and Dec) and 422 in 2013 to 584 in 2014. Of the total of 1048 precuts, seven (0.67 %) were miscut and could not be utilized for transplants. The donor age ranged from 2 to 89 years. A mean change of 43.6 ± 325.2 cells/mm 2 in ECD was noted after cut, proportional increase in mean being 1.9 %. The change in ECD after cut was negatively correlated with ECD before cut. The recipient age ranged from 1 to 89 years. The median thickness of donor lenticule after cut was 148 µm (interquartile range 131-166 µm). Analysis of precut donor corneas from a single eye bank shows that the ECD of the processed tissues was excellent for transplantation. The tissue wastage in the hands of eye bank personal was minimal.

Effect of Range and Angular Velocity of Passive Movement on Somatosensory Evoked Magnetic Fields.

PubMed

Sugawara, Kazuhiro; Onishi, Hideaki; Yamashiro, Koya; Kojima, Sho; Miyaguchi, Shota; Kotan, Shinichi; Tsubaki, Atsuhiro; Kirimoto, Hikari; Tamaki, Hiroyuki; Shirozu, Hiroshi; Kameyama, Shigeki

2016-09-01

To clarify characteristics of each human somatosensory evoked field (SEF) component following passive movement (PM), PM1, PM2, and PM3, using high spatiotemporal resolution 306-channel magnetoencephalography and varying PM range and angular velocity. We recorded SEFs following PM under three conditions [normal range-normal velocity (NN), small range-normal velocity (SN), and small range-slow velocity (SS)] with changing movement range and angular velocity in 12 participants and calculated the amplitude, equivalent current dipole (ECD) location, and the ECD strength for each component. All components were observed in six participants, whereas only PM1 and PM3 in the other six. Clear response deflections at the ipsilateral hemisphere to PM side were observed in seven participants. PM1 amplitude was larger under NN and SN conditions, and mean ECD location for PM1 was at primary motor area. PM3 amplitude was larger under SN condition and mean ECD location for PM3 under SS condition was at primary somatosensory area. PM1 amplitude was dependent on the angular velocity of PM, suggesting that PM1 reflects afferent input from muscle spindle, whereas PM3 amplitude was dependent on the duration. The ECD for PM3 was located in the primary somatosensory cortex, suggesting that PM3 reflects cutaneous input. We confirmed the hypothesis for locally distinct generators and characteristics of each SEF component.

Viral transduction of the HER2-extracellular domain expands trastuzumab-based photoimmunotherapy for HER2-negative breast cancer cells.

PubMed

Shimoyama, Kyoko; Kagawa, Shunsuke; Ishida, Michihiro; Watanabe, Shinichiro; Noma, Kazuhiro; Takehara, Kiyoto; Tazawa, Hiroshi; Hashimoto, Yuuri; Tanabe, Shunsuke; Matsuoka, Junji; Kobayashi, Hisataka; Fujiwara, Toshiyoshi

2015-02-01

The prognosis of HER2-positive breast cancer has been improved by trastuzumab therapy, which features high specificity and limited side effects. However, trastuzumab-based therapy has shortcomings. Firstly, HER2-targeted therapy is only applicable to HER2-expressing tumors, which comprise only 20-25% of primary breast cancers. Secondly, many patients who initially respond to trastuzumab ultimately develop disease progression. To overcome these problems, we employed virus-mediated HER2 transduction and photoimmunotherapy (PIT) which involves trastuzumab conjugated with a photosensitizer, trastuzumab-IR700, and irradiation of near-infrared light. We hypothesized that the gene transduction technique together with PIT would expand the range of tumor entities suitable for trastuzumab-based therapy and improve its antitumor activity. The HER2-extracellular domain (ECD) was transduced by the adenoviral vector, Ad-HER2-ECD, and PIT with trastuzumab-IR700 was applied in the HER2-negative cancer cells. Ad-HER2-ECD can efficiently transduce HER2-ECD into HER2-negative human cancer cells. PIT with trastuzumab-IR700 induced direct cell membrane destruction of Ad-HER2-ECD-transduced HER2-negative cancer cells. Novel combination of viral transduction of a target antigen and an antibody-based PIT would expand and potentiate molecular-targeted therapy even for target-negative or attenuated cancer cells.

Early Support of Intracranial Perfusion

DTIC Science & Technology

2009-10-01

outcomes after traumatic brain injury: A multicenter analysis. Archives of Physical Medicine and Rehabilitation, 84(10), 1441- 1448. Cremer , O. L...Kolesnik Research Assistant 67.5 Sean Jordan Research Assistant 44.5 Sara Wade Research Assistant 90 David Prakash Research Assistant 63.6 Scott Berry

Clinical application of 3D arterial spin-labeled brain perfusion imaging for Alzheimer disease: comparison with brain perfusion SPECT.

PubMed

Takahashi, H; Ishii, K; Hosokawa, C; Hyodo, T; Kashiwagi, N; Matsuki, M; Ashikaga, R; Murakami, T

2014-05-01

Alzheimer disease is the most common neurodegenerative disorder with dementia, and a practical and economic biomarker for diagnosis of Alzheimer disease is needed. Three-dimensional arterial spin-labeling, with its high signal-to-noise ratio, enables measurement of cerebral blood flow precisely without any extrinsic tracers. We evaluated the performance of 3D arterial spin-labeling compared with SPECT, and demonstrated the 3D arterial spin-labeled imaging characteristics in the diagnosis of Alzheimer disease. This study included 68 patients with clinically suspected Alzheimer disease who underwent both 3D arterial spin-labeling and SPECT imaging. Two readers independently assessed both images. Kendall W coefficients of concordance (K) were computed, and receiver operating characteristic analyses were performed for each reader. The differences between the images in regional perfusion distribution were evaluated by means of statistical parametric mapping, and the incidence of hypoperfusion of the cerebral watershed area, referred to as "borderzone sign" in the 3D arterial spin-labeled images, was determined. Readers showed K = 0.82/0.73 for SPECT/3D arterial spin-labeled imaging, and the respective areas under the receiver operating characteristic curve were 0.82/0.69 for reader 1 and 0.80/0.69 for reader 2. Statistical parametric mapping showed that the perisylvian and medial parieto-occipital perfusion in the arterial spin-labeled images was significantly higher than that in the SPECT images. Borderzone sign was observed on 3D arterial spin-labeling in 70% of patients misdiagnosed with Alzheimer disease. The diagnostic performance of 3D arterial spin-labeling and SPECT for Alzheimer disease was almost equivalent. Three-dimensional arterial spin-labeled imaging was more influenced by hemodynamic factors than was SPECT imaging. © 2014 by American Journal of Neuroradiology.

Carotid Artery Stenting and Blood-Brain Barrier Permeability in Subjects with Chronic Carotid Artery Stenosis.

PubMed

Szarmach, Arkadiusz; Halena, Grzegorz; Kaszubowski, Mariusz; Piskunowicz, Maciej; Studniarek, Michal; Lass, Piotr; Szurowska, Edyta; Winklewski, Pawel J

2017-05-08

Failure of the blood-brain barrier (BBB) is a critical event in the development and progression of diseases such as acute ischemic stroke, chronic ischemia or small vessels disease that affect the central nervous system. It is not known whether BBB breakdown in subjects with chronic carotid artery stenosis can be restrained with postoperative recovery of cerebral perfusion. The aim of the study was to assess the short-term effect of internal carotid artery stenting on basic perfusion parameters and permeability surface area-product (PS) in such a population. Forty subjects (23 males) with stenosis of >70% within a single internal carotid artery and neurological symptoms who underwent a carotid artery stenting procedure were investigated. Differences in the following computed tomography perfusion (CTP) parameters were compared before and after surgery: global cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP) and PS. PS acquired by CTP is used to measure the permeability of the BBB to contrast material. In all baseline cases, the CBF and CBV values were low, while MTT and TTP were high on both the ipsi- and contralateral sides compared to reference values. PS was approximately twice the normal value. CBF was higher (+6.14%), while MTT was lower (-9.34%) on the contralateral than on the ipsilateral side. All perfusion parameters improved after stenting on both the ipsilateral (CBF +22.66%; CBV +18.98%; MTT -16.09%, TTP -7.62%) and contralateral (CBF +22.27%, CBV +19.72%, MTT -14.65%, TTP -7.46%) sides. PS decreased by almost half: ipsilateral -48.11%, contralateral -45.19%. The decline in BBB permeability was symmetrical on the ipsi- and contralateral sides to the stenosis. Augmented BBB permeability can be controlled by surgical intervention in humans.

Relations of Blood Pressure and Head Injury to Regional Cerebral Blood Flow

PubMed Central

Allen, Allyssa J.; Katzel, Leslie I.; Wendell, Carrington R.; Siegel, Eliot L.; Lefkowitz, David; Waldstein, Shari R.

2016-01-01

Hypertension confers increased risk for cognitive decline, dementia, and cerebrovascular disease. These associations have been attributed, in part, to cerebral hypoperfusion. Here we posit that relations of higher blood pressure to lower levels of cerebral perfusion may be potentiated by a prior head injury. Participants were 87 community-dwelling older adults -69% men, 90% white, mean age= 66.9 years, 27.6% with a history of mild traumatic brain injury (mTBI) defined as a loss of consciousness

Resting-State Hyperperfusion of the Supplementary Motor Area in Catatonia.

PubMed

Walther, Sebastian; Schäppi, Lea; Federspiel, Andrea; Bohlhalter, Stephan; Wiest, Roland; Strik, Werner; Stegmayer, Katharina

2017-09-01

Catatonia is a psychomotor syndrome that not only frequently occurs in the context of schizophrenia but also in other conditions. The neural correlates of catatonia remain unclear due to small-sized studies. We therefore compared resting-state cerebral blood flow (rCBF) and gray matter (GM) density between schizophrenia patients with current catatonia and without catatonia and healthy controls. We included 42 schizophrenia patients and 41 controls. Catatonia was currently present in 15 patients (scoring >2 items on the Bush Francis Catatonia Rating Scale screening). Patients did not differ in antipsychotic medication or positive symptoms. We acquired whole-brain rCBF using arterial spin labeling and GM density. We compared whole-brain perfusion and GM density over all and between the groups using 1-way ANCOVAs (F and T tests). We found a group effect (F test) of rCBF within bilateral supplementary motor area (SMA), anterior cingulate cortex, dorsolateral prefrontal cortex, left interior parietal lobe, and cerebellum. T tests indicated 1 cluster (SMA) to be specific to catatonia. Moreover, catatonia of excited and retarded types differed in SMA perfusion. Furthermore, increased catatonia severity was associated with higher perfusion in SMA. Finally, catatonia patients had a distinct pattern of GM density reduction compared to controls with prominent GM loss in frontal and insular cortices. SMA resting-state hyperperfusion is a marker of current catatonia in schizophrenia. This is highly compatible with a dysregulated motor system in catatonia, particularly affecting premotor areas. Moreover, SMA perfusion was differentially altered in retarded and excited catatonia subtypes, arguing for distinct pathobiology. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

CBF tomograms with (/sup 99m/Tc-HM-PAO in patients with dementia (Alzheimer type and HIV) and Parkinson's disease--initial results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Costa, D.C.; Ell, P.J.; Burns, A.

1988-12-01

We present preliminary data on the utility of functional brain imaging with (99mTc)-d,l-HM-PAO and single photon emission computed tomography (SPECT) in the study of patients with dementia of the Alzheimer type (DAT), HIV-related dementia syndrome, and the on-off syndrome of Parkinson's disease. In comparison with a group of age-matched controls, the DAT patients revealed distinctive bilateral temporal and posterior parietal deficits, which correlate with detailed psychometric evaluation. Patients with amnesia as the main symptom (group A) showed bilateral mesial temporal lobe perfusion deficits (p less than 0.02). More severely affected patients (group B) with significant apraxia, aphasia, or agnosia exhibitedmore » patterns compatible with bilateral reduced perfusion in the posterior parietal cortex, as well as reduced perfusion to both temporal lobes, different from the patients of the control group (p less than 0.05). SPECT studies of HIV patients with no evidence of intracraneal space occupying pathology showed marked perfusion deficits. Patients with Parkinson's disease and the on-off syndrome studied during an on phase (under levodopa therapy) and on another occasion after withdrawal of levodopa (off) demonstrated a significant change in the uptake of (99mTc)-d,l-HM-PAO in the caudate nucleus (lower on off) and thalamus (higher on off). These findings justify the present interest in the functional evaluation of the brain of patients with dementia. (99mTc)-d,l-HM-PAO and regional cerebral blood flow (rCBF)/SPECT appear useful and highlight individual disorders of flow in a variety of neuropsychiatric conditions.« less

[Analysis of brain hemometabolism behavior during carotid endarterectomy with temporary clamping.].

PubMed

Duval Neto, Gastão Fernandes; Niencheski, Augusto H

2004-04-01

Carotid endarterectomy with temporary clamping changes cerebral blood flow and cerebral metabolic oxygen demand ratio with consequent oligemic hypoxia or hemometabolic uncoupling. This study aimed at identifying changes in brain hemometabolism, evaluated through changes in oxyhemoglobin saturation in internal jugular vein bulb (SvjO2) during carotid endarterectomy with clamping, and at correlating these changes with potentially interfering factors, mainly end tidal CO2 pressure (P ET CO2) and cerebral perfusion pressure (CPP). Sixteen patients with unilateral carotid stenotic disease scheduled to carotid endarterectomy with carotid arterial clamping were enrolled in this study. Parameters including internal jugular bulb oxyhemoglobin saturation, stump pressure and end tidal CO2 pressure were measured at the following moments: M1 - pre-clamping; M2 - 3 minutes after clamping; M3 - pre-unclamping; M4 - post-unclamping). The comparison among SvjO2 (%, mean +/- SD) in all studied periods has shown differences between those recorded in moments M1 (52.25 +/- 7.87) and M2 (47.43 +/- 9.19). This initial decrease stabilized during temporary clamping, showing decrease in the comparison between M2 and M3 (46.56 +/- 9.25), without statistical significance (p = ns). At post-unclamping, M4 (47.68 +/- 9.12), SvjO2 was increased as compared to M2 and M3 clamping stages, however it was still lower than that of pre-clamping stage M1.(M4 x M1 - p < 0.04) This SvjO2 decrease was followed by significant cerebral perfusion pressure (stump pressure) decrease. Factors influencing this brain hemometabolic uncoupling trend were correlated to P ET CO2. The comparison between CPP and SvjO2 showed weak correlation devoid of statistical significance. In the conditions of our study, SvjO2 measurement is a fast and effective way of clinically monitoring changes in CBF/CMRO2 ratio. Temporary carotid clamping implies in a trend towards brain hemometabolic uncoupling and, as a consequence, to oligemic ischemia; cerebral perfusion pressure does not assesses brain hemometabolic status (CBF and CMRO2 ratio); hypocapnia, may lead to brain hemometabolic uncoupling; P ET CO2 monitoring is an innocuous and efficient way to indirectly monitor PaCO2 preventing inadvertent hypocapnia and its deleterious effects on CBF/CMRO2 ratio during temporary carotid clamping.

Whole-brain background-suppressed pCASL MRI with 1D-accelerated 3D RARE Stack-Of-Spirals readout

PubMed Central

Vidorreta, Marta; Wang, Ze; Chang, Yulin V.; Wolk, David A.; Fernández-Seara, María A.; Detre, John A.

2017-01-01

Arterial Spin Labeled (ASL) perfusion MRI enables non-invasive, quantitative measurements of tissue perfusion, and has a broad range of applications including brain functional imaging. However, ASL suffers from low signal-to-noise ratio (SNR), limiting image resolution. Acquisitions using 3D readouts are optimal for background-suppression of static signals, but can be SAR intensive and typically suffer from through-plane blurring. In this study, we investigated the use of accelerated 3D readouts to obtain whole-brain, high-SNR ASL perfusion maps and reduce SAR deposition. Parallel imaging was implemented along the partition-encoding direction in a pseudo-continuous ASL sequence with background-suppression and 3D RARE Stack-Of-Spirals readout, and its performance was evaluated in three small cohorts. First, both non-accelerated and two-fold accelerated single-shot versions of the sequence were evaluated in healthy volunteers during a motor-photic task, and the performance was compared in terms of temporal SNR, GM-WM contrast, and statistical significance of the detected activation. Secondly, single-shot 1D-accelerated imaging was compared to a two-shot accelerated version to assess benefits of SNR and spatial resolution for applications in which temporal resolution is not paramount. Third, the efficacy of this approach in clinical populations was assessed by applying the single-shot 1D-accelerated version to a larger cohort of elderly volunteers. Accelerated data demonstrated the ability to detect functional activation at the subject level, including cerebellar activity, without loss in the perfusion signal temporal stability and the statistical power of the activations. The use of acceleration also resulted in increased GM-WM contrast, likely due to reduced through-plane partial volume effects, that were further attenuated with the use of two-shot readouts. In a clinical cohort, image quality remained excellent, and expected effects of age and sex on cerebral blood flow could be detected. The sequence is freely available upon request for academic use and could benefit a broad range of cognitive and clinical neuroscience research. PMID:28837640

The effect of sildenafil citrate (Viagra) on cerebral blood flow in patients with cerebrovascular risk factors.

PubMed

Lorberboym, M; Mena, I; Wainstein, J; Boaz, M; Lampl, Y

2010-06-01

Sildenafil citrate is widely used for erectile dysfunction. The present study examined the short-term effects of sildenafil administration in individuals with cerebrovascular risk factors, including patients with a history of stroke. Twenty-five consecutive male patients with erectile dysfunction and vascular risk factors were included in the study. A perfusion brain SPECT study was performed at baseline and 1 h after the oral administration of sildenafil. Associations between any of the risk factors and the perfusion scores were not detected, with the exception of stroke. Stroke patients showed significantly more areas with diminished perfusion after sildenafil administration compared to baseline. In patients with diabetes or hypertension, a dose of 50 mg sildenafil does not appear to produce detrimental effects on cerebral blood flow. However, patients with a history of stroke may be at increased risk of hemodynamic impairment after the use of sildenafil.

N-isopropyl-(/sup 123/I)p-iodoamphetamine: single-pass brain uptake and washout; binding to brain synaptosomes; and localization in dog and monkey brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Winchell, H.S.; Horst, W.D.; Braun, L.

1980-10-01

The kinetics of N-isopropyl-p-(/sup 123/I)iodoamphetamine in rat brains were determined by serial measurements of brain uptake index (BUI) after intracarotid injection; also studied were its effects on amine uptake and release in rat's brain cortical synaptosomes; and its in vivo distribution in the dog and monkey. No specific localization in brain nuclei of the dog was seen, but there was progressive accumulation in the eyes. Rapid initial brain uptake in the ketamine-sedated monkey was noted, and further slow brain uptake occurred during the next 20 min but without retinal localization. High levels of brain activity were maintained for several hours.more » The quantitative initial single-pass clearance of the agent in the brain suggests its use in evaluation of regional brain perfusion. Its interaction with brain amine-binding sites suggests its possible application in studies of cerebral amine metabolism.« less

Acute Effects of an Alternative Electronic-Control-Device Waveform in Swine

DTIC Science & Technology

2009-03-01

sequences in a normal individual. Bozeman [32] suggested that lethality due to ECD impact could be due to hyperkalemia related to muscle contraction...and our previous investigations [1, 2], there may be a wide margin of safety, relative to hyperkalemia , for most ECD applications. The increase in

Assessment Of The Functionality Of A Pilot-Scale Reactor And Its Potential For Electrochemical Degradation Of Calmagite, A Sulfonated Azo-Dye

EPA Science Inventory

Electrochemical degradation (ECD) is a promising technology for in situ remediation of diversely contaminated environmental matrices by application of a low level electric potential gradient. This investigation, prompted by successful bench-scale ECD of trichloroethylene,...

A novel cardanol-based antioxidant and its application in vegetable oils and biodiesel

USDA-ARS?s Scientific Manuscript database

A novel antioxidant, epoxidized cardanol (ECD), derived from cardanol has been synthesized and characterized by FT-IR, 1H-NMR and 13C-NMR. Oxidative stability of ECD in vegetable oils and biodiesel was evaluated by the pressurized differential scanning calorimetry and Rancimat methods, respectively....

Synthesis of epoxidized cardanol and its antioxidative properties for vegetable oils and biodiesel

USDA-ARS?s Scientific Manuscript database

A novel antioxidant epoxidized cardanol (ECD), derived from cardanol, was synthesized and characterized by FT-IR, 1H-NMR and 13C-NMR. Oxidative stability of ECD used in vegetable oils and biodiesel was evaluated by pressurized differential scanning calorimetry (PDSC) and the Rancimat method, respect...

Design and Discovery in Educational Assessment: Evidence-Centered Design, Psychometrics, and Educational Data Mining

ERIC Educational Resources Information Center

Mislevy, Robert J.; Behrens, John T.; Dicerbo, Kristen E.; Levy, Roy

2012-01-01

"Evidence-centered design" (ECD) is a comprehensive framework for describing the conceptual, computational and inferential elements of educational assessment. It emphasizes the importance of articulating inferences one wants to make and the evidence needed to support those inferences. At first blush, ECD and "educational data…

78 FR 67020 - Airworthiness Directives; Eurocopter Deutschland GmbH (ECD) Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-08

... Airworthiness Directives; Eurocopter Deutschland GmbH (ECD) Helicopters AGENCY: Federal Aviation Administration... the AD Docket at http://www.regulations.gov . (h) Subject Joint Aircraft Service Component (JASC) Code..., of Eurocopter Deutschland GmbH Flight Manual BO 105 C/CS, Revision 5, dated March 12, 2010. (ii...

Effects of an alveolar recruitment maneuver on subdural pressure, brain swelling, and mean arterial pressure in patients undergoing supratentorial tumour resection: a randomized crossover study.

PubMed

Flexman, Alana M; Gooderham, Peter A; Griesdale, Donald E; Argue, Ruth; Toyota, Brian

2017-06-01

Although recruitment maneuvers have been advocated as part of a lung protective ventilation strategy, their effects on cerebral physiology during elective neurosurgery are unknown. Our objectives were to determine the effects of an alveolar recruitment maneuver on subdural pressure (SDP), brain relaxation score (BRS), and cerebral perfusion pressure among patients undergoing supratentorial tumour resection. In this prospective crossover study, patients scheduled for resection of a supratentorial brain tumour were randomized to undergo either a recruitment maneuver (30 cm of water for 30 sec) or a "sham" maneuver (5 cm of water for 30 sec), followed by the alternative intervention after a 90-sec equilibration period. Subdural pressure was measured through a dural perforation following opening of the cranium. Subdural pressure and mean arterial pressure (MAP) were recorded continuously. The blinded neurosurgeon provided a BRS at baseline and at the end of each intervention. During each treatment, the changes in SDP, BRS, and MAP were compared. Twenty-one patients underwent the study procedure. The increase in SDP was higher during the recruitment maneuver than during the sham maneuver (difference, 3.9 mmHg; 95% confidence interval [CI], 2.2 to 5.6; P < 0.001). Mean arterial pressure decreased further in the recruitment maneuver than in the sham maneuver (difference, -9.0 mmHg; 95% CI, -12.5 to -5.6; P < 0.001). Cerebral perfusion pressure decreased 14 mmHg (95% CI, 4 to 24) during the recruitment maneuver. The BRS did not change with either maneuver. Our results suggest that recruitment maneuvers increase subdural pressure and reduce cerebral perfusion pressure, although the clinical importance of these findings is thus far unknown. This trial was registered with ClinicalTrials.gov, NCT02093117.

Magnetic Particle Imaging for Real-Time Perfusion Imaging in Acute Stroke.

PubMed

Ludewig, Peter; Gdaniec, Nadine; Sedlacik, Jan; Forkert, Nils D; Szwargulski, Patryk; Graeser, Matthias; Adam, Gerhard; Kaul, Michael G; Krishnan, Kannan M; Ferguson, R Matthew; Khandhar, Amit P; Walczak, Piotr; Fiehler, Jens; Thomalla, Götz; Gerloff, Christian; Knopp, Tobias; Magnus, Tim

2017-10-24

The fast and accurate assessment of cerebral perfusion is fundamental for the diagnosis and successful treatment of stroke patients. Magnetic particle imaging (MPI) is a new radiation-free tomographic imaging method with a superior temporal resolution, compared to other conventional imaging methods. In addition, MPI scanners can be built as prehospital mobile devices, which require less complex infrastructure than computed tomography (CT) and magnetic resonance imaging (MRI). With these advantages, MPI could accelerate the stroke diagnosis and treatment, thereby improving outcomes. Our objective was to investigate the capabilities of MPI to detect perfusion deficits in a murine model of ischemic stroke. Cerebral ischemia was induced by inserting of a microfilament in the internal carotid artery in C57BL/6 mice, thereby blocking the blood flow into the medial cerebral artery. After the injection of a contrast agent (superparamagnetic iron oxide nanoparticles) specifically tailored for MPI, cerebral perfusion and vascular anatomy were assessed by the MPI scanner within seconds. To validate and compare our MPI data, we performed perfusion imaging with a small animal MRI scanner. MPI detected the perfusion deficits in the ischemic brain, which were comparable to those with MRI but in real-time. For the first time, we showed that MPI could be used as a diagnostic tool for relevant diseases in vivo, such as an ischemic stroke. Due to its shorter image acquisition times and increased temporal resolution compared to that of MRI or CT, we expect that MPI offers the potential to improve stroke imaging and treatment.

Critical cerebral perfusion pressure at high intracranial pressure measured by induced cerebrovascular and intracranial pressure reactivity.

PubMed

Bragin, Denis E; Statom, Gloria L; Yonas, Howard; Dai, Xingping; Nemoto, Edwin M

2014-12-01

The lower limit of cerebral blood flow autoregulation is the critical cerebral perfusion pressure at which cerebral blood flow begins to fall. It is important that cerebral perfusion pressure be maintained above this level to ensure adequate cerebral blood flow, especially in patients with high intracranial pressure. However, the critical cerebral perfusion pressure of 50 mm Hg, obtained by decreasing mean arterial pressure, differs from the value of 30 mm Hg, obtained by increasing intracranial pressure, which we previously showed was due to microvascular shunt flow maintenance of a falsely high cerebral blood flow. The present study shows that the critical cerebral perfusion pressure, measured by increasing intracranial pressure to decrease cerebral perfusion pressure, is inaccurate but accurately determined by dopamine-induced dynamic intracranial pressure reactivity and cerebrovascular reactivity. Cerebral perfusion pressure was decreased either by increasing intracranial pressure or decreasing mean arterial pressure and the critical cerebral perfusion pressure by both methods compared. Cortical Doppler flux, intracranial pressure, and mean arterial pressure were monitored throughout the study. At each cerebral perfusion pressure, we measured microvascular RBC flow velocity, blood-brain barrier integrity (transcapillary dye extravasation), and tissue oxygenation (reduced nicotinamide adenine dinucleotide) in the cerebral cortex of rats using in vivo two-photon laser scanning microscopy. University laboratory. Male Sprague-Dawley rats. At each cerebral perfusion pressure, dopamine-induced arterial pressure transients (~10 mm Hg, ~45 s duration) were used to measure induced intracranial pressure reactivity (Δ intracranial pressure/Δ mean arterial pressure) and induced cerebrovascular reactivity (Δ cerebral blood flow/Δ mean arterial pressure). At a normal cerebral perfusion pressure of 70 mm Hg, 10 mm Hg mean arterial pressure pulses had no effect on intracranial pressure or cerebral blood flow (induced intracranial pressure reactivity = -0.03 ± 0.07 and induced cerebrovascular reactivity = -0.02 ± 0.09), reflecting intact autoregulation. Decreasing cerebral perfusion pressure to 50 mm Hg by increasing intracranial pressure increased induced intracranial pressure reactivity and induced cerebrovascular reactivity to 0.24 ± 0.09 and 0.31 ± 0.13, respectively, reflecting impaired autoregulation (p < 0.05). By static cerebral blood flow, the first significant decrease in cerebral blood flow occurred at a cerebral perfusion pressure of 30 mm Hg (0.71 ± 0.08, p < 0.05). Critical cerebral perfusion pressure of 50 mm Hg was accurately determined by induced intracranial pressure reactivity and induced cerebrovascular reactivity, whereas the static method failed.

Recording and Modulation of Epileptiform Activity in Rodent Brain Slices Coupled to Microelectrode Arrays.

PubMed

Panuccio, Gabriella; Colombi, Ilaria; Chiappalone, Michela

2018-05-15

Temporal lobe epilepsy (TLE) is the most common partial complex epileptic syndrome and the least responsive to medications. Deep brain stimulation (DBS) is a promising approach when pharmacological treatment fails or neurosurgery is not recommended. Acute brain slices coupled to microelectrode arrays (MEAs) represent a valuable tool to study neuronal network interactions and their modulation by electrical stimulation. As compared to conventional extracellular recording techniques, they provide the added advantages of a greater number of observation points and a known inter-electrode distance, which allow studying the propagation path and speed of electrophysiological signals. However, tissue oxygenation may be greatly impaired during MEA recording, requiring a high perfusion rate, which comes at the cost of decreased signal-to-noise ratio and higher oscillations in the experimental temperature. Electrical stimulation further stresses the brain tissue, making it difficult to pursue prolonged recording/stimulation epochs. Moreover, electrical modulation of brain slice activity needs to target specific structures/pathways within the brain slice, requiring that electrode mapping be easily and quickly performed live during the experiment. Here, we illustrate how to perform the recording and electrical modulation of 4-aminopyridine (4AP)-induced epileptiform activity in rodent brain slices using planar MEAs. We show that the brain tissue obtained from mice outperforms rat brain tissue and is thus better suited for MEA experiments. This protocol guarantees the generation and maintenance of a stable epileptiform pattern that faithfully reproduces the electrophysiological features observed with conventional field potential recording, persists for several hours, and outlasts sustained electrical stimulation for prolonged epochs. Tissue viability throughout the experiment is achieved thanks to the use of a small-volume custom recording chamber allowing for laminar flow and quick solution exchange even at low (1 mL/min) perfusion rates. Quick MEA mapping for real-time monitoring and selection of stimulating electrodes is performed by a custom graphic user interface (GUI).

The FTD-like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism.

PubMed

Kleinberger, Gernot; Brendel, Matthias; Mracsko, Eva; Wefers, Benedikt; Groeneweg, Linda; Xiang, Xianyuan; Focke, Carola; Deußing, Maximilian; Suárez-Calvet, Marc; Mazaheri, Fargol; Parhizkar, Samira; Pettkus, Nadine; Wurst, Wolfgang; Feederle, Regina; Bartenstein, Peter; Mueggler, Thomas; Arzberger, Thomas; Knuesel, Irene; Rominger, Axel; Haass, Christian

2017-07-03

Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk for several neurodegenerative diseases including Alzheimer's disease and frontotemporal dementia (FTD). Homozygous TREM2 missense mutations, such as p.T66M, lead to the FTD-like syndrome, but how they cause pathology is unknown. Using CRISPR/Cas9 genome editing, we generated a knock-in mouse model for the disease-associated Trem2 p.T66M mutation. Consistent with a loss-of-function mutation, we observe an intracellular accumulation of immature mutant Trem2 and reduced generation of soluble Trem2 similar to patients with the homozygous p.T66M mutation. Trem2 p.T66M knock-in mice show delayed resolution of inflammation upon in vivo lipopolysaccharide stimulation and cultured macrophages display significantly reduced phagocytic activity. Immunohistochemistry together with in vivo TSPO small animal positron emission tomography (μPET) demonstrates an age-dependent reduction in microglial activity. Surprisingly, perfusion magnetic resonance imaging and FDG-μPET imaging reveal a significant reduction in cerebral blood flow and brain glucose metabolism. Thus, we demonstrate that a TREM2 loss-of-function mutation causes brain-wide metabolic alterations pointing toward a possible function of microglia in regulating brain glucose metabolism. © 2017 The Authors.

High-cervical spinal cord electrical stimulation in brain low perfusion syndromes: experimental basis and preliminary clinical report.

PubMed

Broseta, J; García-March, G; Sánchez-Ledesma, M J; Gonçalves, J; Silva, I; Barcia, J A; Llácer, J L; Barcia-Salorio, J L

1994-01-01

Previous studies of our group showed that C1-C2 spinal cord stimulation increases carotid and brain blood flow in normal conditions in the goat and dog and it has a beneficial vasomotor effect in a model of vasospasm in the rat. For further clinical application it seemed rational to investigate the possible vascular changes mediated by this technique in experimental brain infarction. To this aim, 45 New Zealand rabbits were used. Brain infarction was produced by bilateral carotid ligation in 15, unilateral microcoagulation of the middle cerebral artery in 15 and by microcoagulation of the vertebral artery at the craniocervical junction in the other 15. One week later, following daily clinical scoring and cortical and posterior fossa blood flow readings by laser Doppler, a period of 120 min of right C1-C2 spinal cord electric stimulation was performed. A mean of 27% increase in previous blood flow recordings was obtained at the right hemisphere and a mean of 32% in the posterior fossa. This procedure was used in 10 patients presenting with various cerebral low perfusion syndromes. Though not constant, an increase in alertness, retention, speech, emotional lability and performance in skilled acts was achieved. No MR changes were observed, though SPECT readings showed an increase in blood flow in the penumbral perilesional area.

Specific cerebral perfusion patterns in three schizophrenia symptom dimensions.

PubMed

Stegmayer, Katharina; Strik, Werner; Federspiel, Andrea; Wiest, Roland; Bohlhalter, Stephan; Walther, Sebastian

2017-12-01

Dimensional concepts such as the Research Domain Criteria initiative have been proposed to disentangle the heterogeneity of schizophrenia. One model introduced three neurobiologically informed behavioral dimensions: language, affectivity and motor behavior. To study the brain-behavior associations of these three dimensions, we investigated whether current behavioral alterations were linked to resting state perfusion in distinct brain circuits in schizophrenia. In total, 47 patients with schizophrenia spectrum disorders and 44 healthy controls were included. Psychopathology was assessed with the Positive And Negative Syndrome Scale and the Bern Psychopathology scale (BPS). The BPS provides severity ratings of three behavioral dimensions (language, affectivity and motor). Patients were classified according to the severity of alterations (severe, mild, no) in each dimension. Whole brain resting state cerebral blood flow (CBF) was compared between patient subgroups and controls. Two symptom dimensions were associated with distinct CBF changes. Behavioral alterations in the language dimension were linked to increased CBF in Heschl's gyrus. Altered affectivity was related to increased CBF in amygdala. The ratings of motor behavior instead were not specifically associated with CBF. Investigating behavioral alterations in three schizophrenia symptom dimensions identified distinct regional CBF changes in the language and limbic brain circuits. The results demonstrate a hitherto unknown segregation of pathophysiological pathways underlying a limited number of specific symptom dimensions in schizophrenia. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Fluorescein isothiocyanate (FITC)-Dextran Extravasation as a Measure of Blood-Brain Barrier Permeability

PubMed Central

Natarajan, Reka; Northrop, Nicole

2017-01-01

The blood-brain barrier (BBB) is formed in part by vascular endothelial cells that constitute the capillaries and microvessels of the brain. The function of this barrier is to maintain homeostasis within the brain microenvironment and buffer the brain from changes in the periphery. A dysfunction of the BBB would permit circulating molecules and pathogens typically restricted to the periphery to enter the brain and interfere with normal brain function. As increased permeability of the BBB is associated with several neuropathologies, it is important to have a reliable and sensitive method that determines BBB permeability and the degree of BBB disruption. A detailed protocol is presented for assessing the integrity of the BBB by transcardial perfusion of a 10,000 Da FITC labeled dextran molecule and its visualization to determine the degree of extravasation from brain microvessels. PMID:28398646

Brain dead or not? CT angiogram yielding false-negative result on brain death confirmation.

PubMed

Johnston, Robyn; Kaliaperumal, Chandrasekaran; Wyse, Gerald; Kaar, George

2013-01-08

We describe a case of severe traumatic brain injury with multiple facial and skull fractures where CT angiogram (CTA) failed to yield a definite result of brain death as an ancillary test. A 28-year-old man was admitted following a road traffic accident with a Glasgow Coma Score (GCS) of 3/15 and fixed pupils. CT brain revealed uncal herniation and diffuse cerebral oedema with associated multiple facial and skull fractures. 72 h later, his clinical condition remained the same with high intracranial pressure refractory to medical management. Clinical confirmation on brain death was not feasible owing to facial injuries. A CTA, performed to determine brain perfusion, yielded a 'false-negative' result. Skull fractures have possibly led to venous prominence in the cortical and deep venous drainage system. This point needs to be borne in mind while considering CTA as an ancillary test to confirm brain death.

Brain dead or not? CT angiogram yielding false-negative result on brain death confirmation

PubMed Central

Johnston, Robyn; Kaliaperumal, Chandrasekaran; Wyse, Gerald; Kaar, George

2013-01-01

We describe a case of severe traumatic brain injury with multiple facial and skull fractures where CT angiogram (CTA) failed to yield a definite result of brain death as an ancillary test. A 28-year-old man was admitted following a road traffic accident with a Glasgow Coma Score (GCS) of 3/15 and fixed pupils. CT brain revealed uncal herniation and diffuse cerebral oedema with associated multiple facial and skull fractures. 72 h later, his clinical condition remained the same with high intracranial pressure refractory to medical management. Clinical confirmation on brain death was not feasible owing to facial injuries. A CTA, performed to determine brain perfusion, yielded a ‘false-negative’ result. Skull fractures have possibly led to venous prominence in the cortical and deep venous drainage system. This point needs to be borne in mind while considering CTA as an ancillary test to confirm brain death. PMID:23302550

Direct reperfusion of the right common carotid artery prior to cardiopulmonary bypass in patients with brain malperfusion complicated with acute aortic dissection.

PubMed

Okita, Yutaka; Matsumori, Masamichi; Kano, Hiroya

2016-04-01

The cases of 3 patients with brain malperfusion secondary to acute aortic dissection who underwent preoperative perfusion of the right common carotid artery are presented. The patients were 64, 65 and 72 years old and 2 were female. All were in a comatose or semi-comatose state with left hemiplegia. The right common carotid artery was exposed and directly cannulated, using a 12-Fr paediatric arterial cannula. The right common femoral artery was chosen for arterial drainage, using a 14-Fr double-lumen cannula. The circuit contained a small roller pump and heat exchanger coil. Target flow was set at 90 ml/min and blood temperature at 30 °C. Durations of right carotid perfusion were 120, 100 and 45 min, respectively. All underwent partial arch replacement and survived. Postoperative neurological sequelae were minimal in all cases. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

[Brain oedema and acute liver failure].

PubMed

Spahr, L

2003-04-01

Brain oedema leading to intracranial hypertension occurs in a significant proportion of patients with acute liver failure in whom it is a leading cause of death. Although precise pathogenic mechanisms associated to this severe complication remain incompletely understood, increasing evidence points to gut-derived neurotoxins including ammonia as key mediators in cerebral osmotic and perfusion disturbances. The management of brain oedema and intracranial hypertension requires a multidisciplinar approach in a center where liver transplantation is available, as this option is the only treatment modality that provides improvement in outcome. This article reviews the most common causes of acute liver failure and the standard of supportive care management, and describes future potential therapeutic aspects of brain oedema and intracranial hypertension.

Native MS and ECD Characterization of a Fab-Antigen Complex May Facilitate Crystallization for X-ray Diffraction

NASA Astrophysics Data System (ADS)

Zhang, Ying; Cui, Weidong; Wecksler, Aaron T.; Zhang, Hao; Molina, Patricia; Deperalta, Galahad; Gross, Michael L.

2016-07-01

Native mass spectrometry (MS) and top-down electron-capture dissociation (ECD) combine as a powerful approach for characterizing large proteins and protein assemblies. Here, we report their use to study an antibody Fab (Fab-1)-VEGF complex in its near-native state. Native ESI with analysis by FTICR mass spectrometry confirms that VEGF is a dimer in solution and that its complex with Fab-1 has a binding stoichiometry of 2:2. Applying combinations of collisionally activated dissociation (CAD), ECD, and infrared multiphoton dissociation (IRMPD) allows identification of flexible regions of the complex, potentially serving as a guide for crystallization and X-ray diffraction analysis.

Ex Vivo Lung Perfusion: Establishment and Operationalization in Iran.

PubMed

Shafaghi, Shadi; Abbasi Dezfuli, Azizollah; Ansari Aval, Zahra; Sheikhy, Kambiz; Farzanegan, Behrooz; Mortaz, Esmaeil; Emami, Habib; Aigner, Clemens; Hosseini-Baharanchi, Fatemeh Sadat; Najafizadeh, Katayoun

2017-02-01

Although the number of lung transplants is limited because of general shortage of organ donors, ex vivo lung perfusion is a novel method with 2 main benefits, including better evaluation of lung potential and recovery of injured lungs. The main aim of this study was to establish and operationalize ex vivo lung perfusion as the first experience in Iran. This was a prospective operational research study on 5 cases, including 1 pig from Vienna Medical University and 4 patients from Masih Daneshvari Hospital. All organ donations from brain dead donors were evaluated according to lung transplant or ex vivo lung perfusion criteria from May 2013 to July 2015 in Tehran, Iran. If a donor did not have any sign of severe chest trauma or pneumonia but had poor oxygenation due to possible atelectasis or neurogenic pulmonary edema, their lungs were included for ex vivo lung perfusion. A successful trend in the difference between the pulmonary arterial Po2 and the left atrial Po2 was observed, as well as an increasing pattern in other functional parameters, including dynamic lung compliance and a decreasing trend in pulmonary vascular resistance. These initial trials indicate that ex vivo lung perfusion can lead to remarkable progress in lung transplant in Iran. They also provide several important pieces of guidance for successful ex vivo lung perfusion, including the necessity of following standard lung retrieval procedures and monitoring temperature and pressure precisely. The development of novel methods can provide opportunities for further research studies on lungs of deceased donors and lead to undiscovered findings. By keeping this science up to date in Iran and developing such new and creative methods, we can reveal effective strategies to promote the quality of donor lungs to support patients on transplant wait lists.

Microfluidic engineered high cell density three-dimensional neural cultures

NASA Astrophysics Data System (ADS)

Cullen, D. Kacy; Vukasinovic, Jelena; Glezer, Ari; La Placa, Michelle C.

2007-06-01

Three-dimensional (3D) neural cultures with cells distributed throughout a thick, bioactive protein scaffold may better represent neurobiological phenomena than planar correlates lacking matrix support. Neural cells in vivo interact within a complex, multicellular environment with tightly coupled 3D cell-cell/cell-matrix interactions; however, thick 3D neural cultures at cell densities approaching that of brain rapidly decay, presumably due to diffusion limited interstitial mass transport. To address this issue, we have developed a novel perfusion platform that utilizes forced intercellular convection to enhance mass transport. First, we demonstrated that in thick (>500 µm) 3D neural cultures supported by passive diffusion, cell densities <=5.0 × 103 cells mm-3 were required for survival. In 3D neuronal and neuronal-astrocytic co-cultures with increased cell density (>=104 cells mm-3), continuous medium perfusion at 2.0-11.0 µL min-1 improved viability compared to non-perfused cultures (p < 0.01), which exhibited widespread cell death and matrix degradation. In perfused cultures, survival was dependent on proximity to the perfusion source at 2.00-6.25 µL min-1 (p < 0.05); however, at perfusion rates of 10.0-11.0 µL min-1 survival did not depend on the distance from the perfusion source, and resulted in a preservation of cell density with >90% viability in both neuronal cultures and neuronal-astrocytic co-cultures. This work demonstrates the utility of forced interstitial convection in improving the survival of high cell density 3D engineered neural constructs and may aid in the development of novel tissue-engineered systems reconstituting 3D cell-cell/cell-matrix interactions.