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CBF
Terms modified by CBF Selected AbstractsPerfusion-based functional magnetic resonance imaging,CONCEPTS IN MAGNETIC RESONANCE, Issue 1 2003Afonso C. Silva Abstract The measurement of cerebral blood flow (CBF) is a very important way of assessing tissue viability, metabolism, and function. CBF can be measured noninvasively with magnetic resonance imaging (MRI) by using arterial water as a perfusion tracer. Because of the tight coupling between neural activity and CBF, functional MRI (fMRI) techniques are having a large impact in defining regions of the brain that are activated due to specific stimuli. Among the different fMRI techniques, CBF-based fMRI has the advantages of being specific to tissue signal change, a critical feature for quantitative measurements within and across subjects, and for high-resolution functional mapping. Unlike the conventional blood oxygenation level dependent (BOLD) technique, the CBF change is an excellent index of the magnitude of neural activity change. Thus, CBF-based fMRI is the tool of choice for longitudinal functional imaging studies. A review of the principles and theoretical backgrounds of both continuous and pulsed arterial spin labeling methods for measuring CBF is presented, and a general overview of their current applications in the field of functional brain mapping is provided. In particular, examples of the use of CBF-based fMRI to investigate the fundamental hemodynamic responses induced by neural activity and to determine the signal source of the most commonly used BOLD functional imaging are reviewed. © 2003 Wiley Periodicals, Inc. Concepts Magn Reson 16A: 16,27, 2003 [source] Cerebral oxygenation is reduced during hyperthermic exercise in humansACTA PHYSIOLOGICA, Issue 1 2010P. Rasmussen Abstract Aim:, Cerebral mitochondrial oxygen tension (PmitoO2) is elevated during moderate exercise, while it is reduced when exercise becomes strenuous, reflecting an elevated cerebral metabolic rate for oxygen (CMRO2) combined with hyperventilation-induced attenuation of cerebral blood flow (CBF). Heat stress challenges exercise capacity as expressed by increased rating of perceived exertion (RPE). Methods:, This study evaluated the effect of heat stress during exercise on PmitoO2 calculated based on a Kety-Schmidt-determined CBF and the arterial-to-jugular venous oxygen differences in eight males [27 ± 6 years (mean ± SD) and maximal oxygen uptake (VO2max) 63 ± 6 mL kg,1 min,1]. Results:, The CBF, CMRO2 and PmitoO2 remained stable during 1 h of moderate cycling (170 ± 11 W, ,50% of VO2max, RPE 9,12) in normothermia (core temperature of 37.8 ± 0.4 °C). In contrast, when hyperthermia was provoked by dressing the subjects in watertight clothing during exercise (core temperature 39.5 ± 0.2 °C), PmitoO2 declined by 4.8 ± 3.8 mmHg (P < 0.05 compared to normothermia) because CMRO2 increased by 8 ± 7% at the same time as CBF was reduced by 15 ± 13% (P < 0.05). During exercise with heat stress, RPE increased to 19 (19,20; P < 0.05); the RPE correlated inversely with PmitoO2 (r2 = 0.42, P < 0.05). Conclusion:, These data indicate that strenuous exercise in the heat lowers cerebral PmitoO2, and that exercise capacity in this condition may be dependent on maintained cerebral oxygenation. [source] Twenty-four-hour non-invasive monitoring of systemic haemodynamics and cerebral blood flow velocity in healthy humansACTA PHYSIOLOGICA, Issue 1 2002M. DIAMANT ABSTRACT Acute short-term changes in blood pressure (BP) and cardiac output (CO) affect cerebral blood flow (CBF) in healthy subjects. As yet, however, we do not know how spontaneous fluctuations in BP and CO influence cerebral circulation throughout 24 h. We performed simultaneous monitoring of BP, systemic haemodynamic parameters and blood flow velocity in the middle cerebral artery (MCAV) in seven healthy subjects during a 24-h period. Finger BP was recorded continuously during 24 h by Portapres and bilateral MCAV was measured by transcranial Doppler (TCD) during the first 15 min of every hour. The subjects remained supine during TCD recordings and during the night, otherwise they were seated upright in bed. Stroke volume (SV), CO and total peripheral resistance (TPR) were determined by Modelflow analysis. The 15 min mean value of each parameter was assumed to represent the mean of the corresponding hour. There were no significant differences between right vs. left, nor between mean daytime vs. night time MCAV. Intrasubject comparison of the twenty-four 15-min MCAV recordings showed marked variations (P < 0.001). Within each single 15-min recording period, however, MCAV was stable whereas BP showed significant short-term variations (P < 0.01). A day,night difference in BP was only observed when daytime BP was evaluated from recordings in the seated position (P < 0.02), not in supine recordings. Throughout 24 h, MCAV was associated with SV and CO (P < 0.001), to a lesser extent with mean arterial pressure (MAP; P < 0.005), not with heart rate (HR) or TPR. These results indicate that in healthy subjects MCAV remains stable when measured under constant supine conditions but shows significant variations throughout 24 h because of activity. Moreover, changes in SV and CO, and to a lesser extent BP variations, affect MCAV throughout 24 h. [source] Brain Blood-flow Alterations Induced by Therapeutic Vagus Nerve Stimulation in Partial Epilepsy: II.EPILEPSIA, Issue 9 2004Low Levels of Stimulation, Prolonged Effects at High Summary:,Purpose: To measure vagus nerve stimulation (VNS)-induced cerebral blood flow (CBF) effects after prolonged VNS and to compare these effects with immediate VNS effects on CBF. Methods: Ten consenting partial epilepsy patients had positron emission tomography (PET) with intravenous [15O]H2O. Each had three control scans without VNS and three scans during 30 s of VNS, within 20 h after VNS began (immediate-effect study), and repeated after 3 months of VNS (prolonged study). After intrasubject subtraction of control from stimulation scans, images were anatomically transformed for intersubject averaging and superimposed on magnetic resonance imaging (MRI) for anatomic localization. Changes on t-statistical maps were considered significant at p < 0.05 (corrected for multiple comparisons). Results: During prolonged studies, CBF changes were not observed in any regions that did not have CBF changes during immediate-effect studies. During both types of studies, VNS-induced CBF increases were similarly located in the bilateral thalami, hypothalami, inferior cerebellar hemispheres, and right postcentral gyrus. During immediate-effect studies, VNS decreased bilateral hippocampal, amygdalar, and cingulate CBF and increased bilateral insular CBF; no significant CBF changes were observed in these regions during prolonged studies. Mean seizure frequency decreased by 25% over a 3-month period between immediate and prolonged PET studies, compared with 3 months before VNS began. Conclusions: Seizure control improved during a period over which some immediate VNS-induced CBF changes declined (mainly over cortical regions), whereas other VNS-induced CBF changes persisted (mainly over subcortical regions). Altered synaptic activities at sites of persisting VNS-induced CBF changes may reflect antiseizure actions. [source] Dynamic Variations of Local Cerebral Blood Flow in Maximal Electroshock Seizures in the RatEPILEPSIA, Issue 10 2002Véronique André Summary: ,Purpose: Measurement of cerebral blood flow is routinely used to locate the areas involved in generation and spread of seizures in epilepsy patients. Because the nature of the hyperperfused regions varies with the timing of injection of tracer, in this study, we used a rat model of maximal electroshock seizures to follow up the time-dependent changes in the distribution of seizure-induced cerebral blood flow (CBF) changes. Methods: CBF was measured by the quantitative autoradiographic [14C]iodoantipyrine technique over a 30-s duration. The tracer was injected either at 15 s before seizure induction, simultaneous with the application of the electroshock (tonic phase), at the onset of the clonic phase, or at 3 and 6 min after the seizure (postictal phase). Results: Rates of CBF underwent dynamic changes during the different phases of seizure activity and largely increased over control levels (,400%) in the 45 regions studied during all phases of the seizure (first 3 times). CBF remained higher than control levels in 35 and 15 areas at 3 and 6 min after the seizure, respectively. Conclusions: The distribution of maximal CBF increases showed a good correlation with their known involvement in the circuits underlying the clinical expression of the different types of seizure activity, tonic versus clonic. [source] Mixed-lineage eosinophil/basophil crisis in MDS: a rare form of progressionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2008F. Wimazal ABSTRACT Background, Basophilic crisis and eosinophilia are well recognized features of advanced chronic myeloid leukaemia. In other myeloid neoplasms, however, transformation with marked basophilia and eosinophilia is considered unusual. Design, We examined the long-term follow-up of 322 patients with de novo myelodysplastic syndromes (MDS) to define the frequency of basophilic, eosinophilic and mixed lineage (basophilic and eosinophilic) transformation. Results, Of all patients, only one developed mixed lineage crisis (, 20% basophils and , 20% eosinophils). In this patient, who initially suffered from chronic myelomonocytic leukaemia, basophils increased to 48% and eosinophils up to 31% at the time of progression. Mixed lineage crisis was not accompanied by an increase in blast cells or organomegaly. The presence of BCR/ABL and other relevant fusion gene products (FIP1L1/PDGFRA, AML1/ETO, PML/RAR,, CBF,/MYH11) were excluded by PCR. Myelomastocytic transformation/myelomastocytic leukaemia and primary mast cell disease were excluded by histology, KIT mutation analysis, electron microscopy and immunophenotyping. Basophils were thus found to be CD123+, CD203c+, BB1+, KIT- cells, and to express a functional IgE-receptor. Among the other patients with MDS examined, 4(1·2%) were found to have marked basophilia (, 20%) and 7(2·1%) were found to have massive eosinophilia ( , 20%), whereas mixed-lineage crisis was detected in none of them. Conclusions, Mixed basophil/eosinophil crisis may develop in patients with MDS but is an extremely rare event. [source] Cerebral perfusion in the elderly with nocturnal blood pressure fallEUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2007A. Siennicki-Lantz Cerebrovascular disease may be linked with vascular autoregulation in aging. The aim of this study was to examine relation between nocturnal blood pressure (BP) fall and cerebral blood flow (CBF) changes in elderly men. The prospective ,Men born in 1914' cohort study has been in progress since 1968 and included 809 subjects. After 14 years from the last follow up, 97 subjects reached the age of 82 and underwent CBF measurement and 24 h ambulatory blood pressure monitoring. Diastolic BP at night decreased in 84 subjects with median 12.7% and increased in 13 subjects with median 3.7%. Relative diastolic BP fall at night was negatively associated to CBF in temporal and infero-parietal areas. Higher proportion of subjects with increasing systolic BP during the 14-year period was observed in the subgroup with extreme nocturnal diastolic BP dip, irrespectively of BP values or prevalence of hypertension. Extreme nocturnal diastolic BP fall in a cohort of elderly men is correlated with focal changes in CBF. Further studies could explain if increasing BP in the elderly is a cause or result of pathological autoregulation, and if antihypertensive treatment increases nocturnal BP dip. [source] Effects of physiological aging and cerebrovascular risk factors on the hemodynamic response to brain activation: a functional transcranial Doppler studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2007K. Gröschel The influence of the vascular system on the coupling of cerebral blood flow (CBF) to focal brain activation during aging is incompletely understood. Using functional transcranial Doppler sonography and a hypercapnic challenge as a marker of intact cerebral vasoreactivity, we determined CBF velocity (CBFV) changes in response to a language and arithmetic task in a group of 43 healthy young subjects (mean age 32 ± 8.6 years), 18 healthy old subjects (mean age 64 ± 9.8 years) and 29 old subjects with risk factors for an atherosclerosis (mean age 69 ± 8.4 years). Despite a similar performance during the cognitive tasks the CBFV changes were significantly lower in the group of old subjects with vascular risk factors compared with the healthy young and old subjects. Similarly, the CBFV changes during hypercapnia were significantly lower in the group of old subjects with vascular risk factors compared with the healthy young and old subjects. In contrast, both cognitive tasks and hypercapnia produced comparable CBFV changes in the group of healthy young and old subjects. These results suggest that the hemodynamic response to neuronal activation is unaffected by aging alone, whereas the presence of cardiovascular risk factors significantly diminishes the capability of cerebral vessels to react to vasodilating stimuli. [source] Regulation of cerebral blood flow in mammals during chronic hypoxia: a matter of balanceEXPERIMENTAL PHYSIOLOGY, Issue 2 2010Philip N. Ainslie Respiratory-induced changes in the partial pressures of arterial carbon dioxide and oxygen play a major role in cerebral blood flow (CBF) regulation. Elevations in (hypercapnia) lead to vasodilatation and increases in CBF, whereas reductions in (hypocapnia) lead to vasoconstriction and decreases in CBF. A fall in (hypoxia) below a certain threshold (<40,45 mmHg) also produces cerebral vasodilatation. Upon initial exposure to hypoxia, CBF is elevated via a greater relative degree of hypoxia compared with hypocapnia. At this point, hypoxia-induced elevations in blood pressure and loss of cerebral autoregulation, stimulation of neuronal pathways, angiogenesis, release of adenosine, endothelium-derived NO and a variety of autocoids and cytokines are additional factors acting to increase CBF. Following 2,3 days, however, the process of ventilatory acclimatization results in a progressive rise in ventilation, which increases and reduces , collectively acting to attenuate the initial rise in CBF. Other factors acting to lower CBF include elevations in haematocrit, sympathetic nerve activity and local and endothelium-derived vasoconstrictors. Hypoxia-induced alterations of cerebrovascular reactivity, autoregulation and pulmonary vascular tone may also affect CBF. Thus, the extent of change in CBF during exposure to hypoxia is dependent on the balance between the myriad of vasodilators and constrictors derived from the endothelium, neuronal innervations and perfusion pressure. This review examines the extent and mechanisms by which hypoxia regulates CBF. Particular focus will be given to the marked influence of hypoxia associated with exposure to high altitude and chronic lung disease. The associated implications of these hypoxia-induced integrative alterations for the regulation of CBF are discussed, and future avenues for research are proposed. [source] Changes in Cerebral Blood Flow During and After 48 H of Both Isocapnic and Poikilocapnic Hypoxia in HumansEXPERIMENTAL PHYSIOLOGY, Issue 5 2002Marc J. Poulin During acclimatization to the hypoxia of altitude, the cerebral circulation is exposed to arterial hypoxia and hypocapnia, two stimuli with opposing influences on cerebral blood flow (CBF). In order to understand the resultant changes in CBF, this study examined the responses of CBF during a period of constant mild hypoxia both with and without concomitant regulation of arterial PCO2. Nine subjects were each exposed to two protocols in a purpose-built chamber: (1) 48 h of isocapnic hypoxia (Protocol I), where end-tidal PO2 (PET,O2) was held at 60 Torr and end-tidal PCO2 (PET,CO2) at the subject's resting value prior to experimentation; and (2) 48 h of poikilocapnic hypoxia (Protocol P), where PET,O2 was held at 60 Torr and PET,CO2 was uncontrolled. Transcranial Doppler ultrasound was used to assess CBF. At 24 h intervals during and after the hypoxic exposure CBF was measured and the sensitivity of CBF to acute variations in PO2 and PCO2 was determined. During Protocol P, PET,CO2 decreased by 13% (P < 0.001) and CBF decreased by 6% (P < 0.05), whereas during Protocol I, PET,CO2 and CBF remained unchanged. The sensitivity of CBF to acute variations in PO2 and PCO2 increased by 103% (P < 0.001) and 28% (P < 0.01), respectively, over the 48 h period of hypoxia. These changes did not differ between protocols. In conclusion, CBF decreases during mild poikilocapnic hypoxia, indicating that there is a predominant effect on CBF of the associated arterial hypocapnia. This fall occurs despite increases in the sensitivity of CBF to acute variations in PO2/PCO2 arising directly from the hypoxic exposure. [source] PRDX4, a member of the peroxiredoxin family, is fused to AML1 (RUNX1) in an acute myeloid leukemia patient with a t(X;21)(p22;q22)GENES, CHROMOSOMES AND CANCER, Issue 4 2004Yanming Zhang The AML1 gene (also known as RUNX1) at 21q22 codes for core binding factor (CBF) ,, which forms a heterodimer with CBF , that acts as a transcriptional activating factor. CBF is a critical regulator in the generation and differentiation of definitive hematopoietic stem cells and is frequently disrupted in leukemia through chromosome translocations. We cloned a novel AML1 partner gene, PRDX4, in an X;21 translocation in a 74-year-old male patient diagnosed with acute myeloid leukemia,M2. Chromosome analysis detected a t(X;21)(p22;q22) as the sole abnormality in bone marrow samples. The involvement of AML1 was confirmed by fluorescence in situ hybridization studies. Using 3, RACE-PCR, we cloned a fusion between exon 5 of AML1 and exon 2 of PRDX4. RT-PCR confirmed the fusion and detected another fusion between exon 6 of AML1 and exon 2 of PRDX4, indicating alternative splicing of exon 6 of AML1 in the fusion transcripts. PRDX4 is one of six peroxiredoxin-family genes that are highly conserved in eukaryotes and prokaryotes and are ubiquitously expressed. Peroxiredoxin genes exhibit thioredoxin-dependent peroxidase activity and have been implicated in a number of other cellular functions such as cell proliferation and differentiation. PRDX4 plays a regulatory role in the activation of the transcription factor NF-,B and is significantly down-regulated in acute promyelocytic leukemia. This is the first example of antioxidant enzyme involvement in a chromosome translocation in leukemia. © 2004 Wiley-Liss, Inc. [source] The effect of daily caffeine use on cerebral blood flow: How much caffeine can we tolerate?HUMAN BRAIN MAPPING, Issue 10 2009Merideth A. Addicott Abstract Caffeine is a commonly used neurostimulant that also produces cerebral vasoconstriction by antagonizing adenosine receptors. Chronic caffeine use results in an adaptation of the vascular adenosine receptor system presumably to compensate for the vasoconstrictive effects of caffeine. We investigated the effects of caffeine on cerebral blood flow (CBF) in increasing levels of chronic caffeine use. Low (mean = 45 mg/day), moderate (mean = 405 mg/day), and high (mean = 950 mg/day) caffeine users underwent quantitative perfusion magnetic resonance imaging on four separate occasions: twice in a caffeine abstinent state (abstained state) and twice in a caffeinated state following their normal caffeine use (native state). In each state, there were two drug conditions: participants received either caffeine (250 mg) or placebo. Gray matter CBF was tested with repeated-measures analysis of variance using caffeine use as a between-subjects factor, and correlational analyses were conducted between CBF and caffeine use. Caffeine reduced CBF by an average of 27% across both caffeine states. In the abstained placebo condition, moderate and high users had similarly greater CBF than low users; but in the native placebo condition, the high users had a trend towards less CBF than the low and moderate users. Our results suggest a limited ability of the cerebrovascular adenosine system to compensate for high amounts of daily caffeine use. Hum Brain Mapp 2009. © 2009 Wiley-Liss, Inc. [source] Imaging brain activity during natural vision using CASL perfusion fMRIHUMAN BRAIN MAPPING, Issue 7 2007Hengyi Rao Abstract Functional MRI (fMRI) has begun to be used to explore human brain activity during ecological and natural conditions. Arterial spin labeling (ASL) perfusion fMRI provides an appealing approach for imaging sustained brain activity during natural conditions because of its long-term temporal stability and ability to noninvasively quantify absolute cerebral blood flow (CBF). The present study used ASL perfusion fMRI to measure brain activation patterns associated with natural vision by concurrently recording CBF and blood oxygen level-dependent (BOLD) contrasts while subjects were freely viewing a cartoon movie. Reliable quantitative whole-brain CBF values (,60 mL/100g/min) as well as regional CBF values (45,80 mL/100g/min) were measured during movie viewing and resting states. The perfusion contrast revealed CBF increases in multiple visual pathway areas and frontal areas, and CBF decreases in ventromedial frontal cortex and superior temporal cortex during movie viewing compared to resting states. Concurrent BOLD contrast revealed similar but weaker activation and deactivation patterns. Regression analyses of both CBF data and BOLD data showed significant associations between activation in the middle temporal (MT) region and subjects' perception of motion. Region of interest analysis based on a priori literature-defined MT demonstrated significant monotonic stepwise associations between the intensity of motion perception and the CBF and BOLD signal changes. These results demonstrate the feasibility of using ASL perfusion fMRI for imaging both sustained and dynamic effects in neural activation during natural and ecologically valid situations, and support the notion of maintained functional segregation and specialization during natural vision. Hum Brain Mapp, 2006. © 2006 Wiley-Liss, Inc. [source] Regional cerebral blood flow responses to hyperventilation during sevoflurane anaesthesia studied with PETACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2010L. SCHLÜNZEN Background: Arterial carbon dioxide tension (PaCO2) is an important factor controlling cerebral blood flow (CBF) in neurosurgical patients. It is still unclear whether the hypocapnia-induced decrease in CBF is a general effect on the brain or rather linked to specific brain regions. We evaluated the effects of hyperventilation on regional cerebral blood flow (rCBF) in healthy volunteers during sevoflurane anaesthesia measured with positron emission tomography (PET). Methods: Eight human volunteers were anaesthetized with sevoflurane 1 MAC, while exposed to hyperventilation. During 1 MAC sevoflurane at normocapnia and 1 MAC sevoflurane at hypocapnia, one H215O scan was performed. Statistical parametric maps and conventional regions of interest analysis were used for estimating rCBF differences. Results: Cardiovascular parameters were maintained constant over time. During hyperventilation, the mean PaCO2 was decreased from 5.5 ± 0.7 to 3.8 ± 0.9 kPa. Total CBF decreased during the hypocapnic state by 44%. PET revealed wide variations in CBF between regions. The greatest values of vascular responses during hypocapnia were observed in the thalamus, medial occipitotemporal gyrus, cerebellum, precuneus, putamen and insula regions. The lowest values were observed in the superior parietal lobe, middle and inferior frontal gyrus, middle and inferior temporal gyrus and precentral gyrus. No increases in rCBF were observed. Conclusions: This study reports highly localized and specific changes in rCBF during hyperventilation in sevoflurane anaesthesia, with the most pronounced decreases in the sub cortical grey matter. Such regional heterogeneity of the cerebral vascular response should be considered in the assessment of cerebral perfusion reserve during hypocapnia. [source] Ferritin ferroxidase activity: A potent inhibitor of osteogenesisJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2010Abolfazl Zarjou Abstract Hemochromatosis is a known cause of osteoporosis, and iron overload has deleterious effects on bone. Although iron overload and its association with osteoporosis has long been recognized, the pathogenesis and exact role of iron have been undefined. Bone is an active tissue with constant remodeling capacity. Osteoblast (OB) development and maturation are under the influence of core binding factor ,-1 (CBF-,1), which induces expression of OB-specific genes, including alkaline phosphatase, an important enzyme in early osteogenesis, and osteocalcin, a noncollagenous protein deposited within the osteoid. This study investigates the mechanism by which iron inhibits human OB activity, which in vivo may lead to decreased mineralization, osteopenia, and osteoporosis. We demonstrate that iron-provoked inhibition of OB activity is mediated by ferritin and its ferroxidase activity. We confirm this notion by using purified ferritin H-chain and ceruloplasmin, both known to possess ferroxidase activity that inhibited calcification, whereas a site-directed mutant of ferritin H-chain lacking ferroxidase activity failed to provide any inhibition. Furthermore, we are reporting that such suppression is not restricted to inhibition of calcification, but OB-specific genes such as alkaline phosphatase, osteocalcin, and CBF-,1 are all downregulated by ferritin in a dose-responsive manner. This study corroborates that iron decreases mineralization and demonstrates that this suppression is provided by iron-induced upregulation of ferritin. In addition, we conclude that inhibition of OB activity, mineralization, and specific gene expression is attributed to the ferroxidase activity of ferritin. © 2010 American Society for Bone and Mineral Research [source] Butterfat fatty acids differentially regulate growth and differentiation in Jurkat T-cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2005Paolo Bergamo Abstract Synthetic Conjugated Linoleic Acid mixture (CLA; c9,t11; t10,c12-18:2) has been previously shown to inhibit growth, and enhance apoptosis and IL-2 mRNA synthesis in human lymphoblastic Jurkat T-cells. In this study, two different butterfat types were evaluated and compared for their effects on Jurkat cell viability, oxidative stress, pro-apoptotic activity, and cytokine synthesis: the conventionally produced butterfat (CBF), and organic butterfat (OBF) containing significantly higher amounts of c9,t11 (Rumenic Acid, RA), trans-vaccenic acid (VA; t11-18:1), ,-linolenic acid (ALA), and lower levels of linoleic acid (LA). Results from cell treatment with both butterfat mixtures showed comparable oxidative stress (superoxide production, intracellular GSH depletion,and lipid peroxides yield), NADPH oxidase activation, cytotoxicity (LDH release), and IL-2 transcript level, whereas the effects of enhanced growth-inhibitory and pro-apoptotic activities were associated with OBF treatment. To then investigate each butterfat-induced effect caused by RA, VA, LA, and ALA, cells were exposed to synthetic FA concentrations similar to those from the different butterfats. Higher oxidative stress (superoxide production, intracellular GSH depletion) was induced by ,-linolenic (ALA) and linoleic (LA) incubation (P,<,0.01) and superoxide production was suppressed by specific PKC, inhibitor (Gö 6976) and linked to increased toxicity and IL-2 synthesis inhibition. By contrast, cell treatment with RA increased apoptosis and IL-2 synthesis. These results suggest that a supply of ALA and LA is responsible for BF-induced oxidative stress via PKC,-NADPH oxidase pathway, and that enhanced antiproliferative effects in OBF treated cells is essentially determined by RA-induced pro-apoptotic activity. © 2005 Wiley-Liss, Inc. [source] In vivo vascular hallmarks of diffuse leukoaraiosisJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2010Jinsoo Uh PhD Abstract Purpose: To characterize multiple patterns of vascular changes in leukoaraiosis using in vivo magnetic resonance imaging (MRI) techniques. Materials and Methods: We measured cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and blood,brain-barrier (BBB) leakage in a group of 33 elderly subjects (age: 72.3 ± 6.8 years, 17 males, 16 females). Leukoaraiosis brain regions were identified in each subject using fluid-attenuated inversion-recovery (FLAIR) MRI. Vascular parameters in the leukoaraiosis regions were compared to those in the normal-appearing white matter (NAWM) regions. Vascular changes in leukoaraiosis were also compared to structural damage as assessed by diffusion tensor imaging. Results: CBF and CVR in leukoaraiosis regions were found to be 39.7 ± 5.2% (P < 0.001) and 52.5 ± 11.6% (P = 0.005), respectively, of those in NAWM. In subjects who did not have significant leukoaraiosis, CBF and CVR in regions with high risk for leukoaraiosis showed a slight reduction compared to the other white matter regions. Significant BBB leakage was also detected (P = 0.003) in leukoaraiosis and the extent of BBB leakage was positively correlated with mean diffusivity. In addition, CVR in NAWM was lower than that in white matter of subjects without significant leukoaraiosis. Conclusion: Leukoaraiosis was characterized by reduced CBF, CVR, and a leakage in the BBB. J. Magn. Reson. Imaging 2010;32:184,190. © 2010 Wiley-Liss, Inc. [source] Perfusion parameters derived from bolus-tracking perfusion imaging are immune to tracer recirculation,JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 3 2010Jayme Cameron Kosior PhD Abstract Purpose: To investigate the impact of tracer recirculation on estimates of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). Materials and Methods: The theoretical model used to derive CBF, CBV, and MTT was examined. CBF and CBV estimates with and without tracer recirculation were compared in computer simulations to examine the effects of tracer recirculation. Results: The equations used to derive CBF, CBV, and MTT assume that the arterial input function and tissue tracer signals define the input and output signals, respectively, of a linear time-invariant system. As a result of the principle of superposition, these perfusion parameters are immune to tracer recirculation, which was confirmed by computer simulation. However, limited acquisition durations can lead to CBV and CBF errors of up to 50%. Conclusion: Tracer recirculation does not impact estimation of CBF, CBV, or MTT. However, previous approaches used to remove recirculation effects may be beneficial when used to compensate for limited acquisition durations in which the passage of the bolus is not adequately captured. J. Magn. Reson. Imaging 2010;31:753,756. © 2010 Wiley-Liss, Inc. [source] Measurement of deep gray matter perfusion using a segmented true,fast imaging with steady-state precession (True-FISP) arterial spin-labeling (ASL) method at 3TJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2009Elan J. Grossman MS Abstract Purpose To study the feasibility of using the MRI technique of segmented true,fast imaging with steady-state precession arterial spin-labeling (True-FISP ASL) for the noninvasive measurement and quantification of local perfusion in cerebral deep gray matter at 3T. Materials and Methods A flow-sensitive alternating inversion-recovery (FAIR) ASL perfusion preparation was used in which the echo-planar imaging (EPI) readout was replaced with a segmented True-FISP data acquisition strategy. The absolute perfusion for six selected regions of deep gray matter (left and right thalamus, putamen, and caudate) were calculated in 11 healthy human subjects (six male, five female; mean age = 35.5 years ± 9.9). Results Preliminary measurements of the average absolute perfusion values at the six selected regions of deep gray matter are in agreement with published values for mean absolute cerebral blood flow (CBF) baselines acquired from healthy volunteers using positron emission tomography (PET). Conclusion Segmented True-FISP ASL is a practical and quantitative technique suitable to measure local tissue perfusion in cerebral deep gray matter at a high spatial resolution without the susceptibility artifacts commonly associated with EPI-based methods of ASL. J. Magn. Reson. Imaging 2009;29:1425,1431. © 2009 Wiley-Liss, Inc. [source] CBF, BOLD, CBV, and CMRO2 fMRI signal temporal dynamics at 500-msec resolutionJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 3 2008Qiang Shen PhD Abstract Purpose To investigate the temporal dynamics of blood oxygenation level-dependent (BOLD), cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO2) changes due to forepaw stimulation with 500-msec resolution in a single setting. Materials and Methods Forepaw stimulation and hypercapnic challenge on rats were studied. CBF and BOLD functional MRI (fMRI) were measured using the pseudo-continuous arterial spin-labeling technique at 500-msec resolution. CBV fMRI was measured using monocrystalline iron-oxide particles following CBF and BOLD measurements in the same animals. CMRO2 change was estimated via the biophysical BOLD model with hypercapnic calibration. Percent changes and onset times were analyzed for the entire forepaw somatosensory cortices and three operationally defined cortical segments, denoted Layers I,III, IV,V, and VI. Results BOLD change was largest in Layers I,III, whereas CBF, CBV, and CMRO2 changes were largest in Layers IV,V. Among all fMRI signals in all layers, only the BOLD signal in Layers I,III showed a poststimulus undershoot. CBF and CBV dynamics were similar. Closer inspection showed that CBV increased slightly first (P < 0.05), but was slow to peak. CBF increased second, but peaked first. BOLD significantly lagged both CBF and CBV (P < 0.05). Conclusion This study provides important temporal dynamics of multiple fMRI signals at high temporal resolution in a single setting. J. Magn. Reson. Imaging 2008. © 2008 Wiley-Liss, Inc. [source] Absolute quantification of cerebral blood flow in normal volunteers: Correlation between Xe-133 SPECT and dynamic susceptibility contrast MRIJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2007Linda Knutsson PhD Abstract Purpose To compare absolute cerebral blood flow (CBF) estimates obtained by dynamic susceptibility contrast MRI (DSC-MRI) and Xe-133 SPECT. Materials and Methods CBF was measured in 20 healthy volunteers using DSC-MRI at 3T and Xe-133 SPECT. DSC-MRI was accomplished by gradient-echo EPI and CBF was calculated using a time-shift-insensitive deconvolution algorithm and regional arterial input functions (AIFs). To improve the reproducibility of AIF registration the time integral was rescaled by use of a venous output function. In the Xe-133 SPECT experiment, Xe-133 gas was inhaled over 8 minutes and CBF was calculated using a biexponential analysis. Results The average whole-brain CBF estimates obtained by DSC-MRI and Xe-133 SPECT were 85 ± 23 mL/(min 100 g) and 40 ± 8 mL/(min 100 g), respectively (mean ± SD, n = 20). The linear CBF relationship between the two modalities showed a correlation coefficient of r = 0.76 and was described by the equation CBF(MRI) = 2.4 · CBF(Xe),7.9 (CBF in units of mL/(min 100 g)). Conclusion A reasonable positive linear correlation between MRI-based and SPECT-based CBF estimates was observed after AIF time-integral correction. The use of DSC-MRI typically results in overestimated absolute perfusion estimates and the present study indicates that this trend is further enhanced by the use of high magnetic field strength (3T). J. Magn. Reson. Imaging 2007;26:913,920. © 2007 Wiley-Liss, Inc. [source] Improved dynamic susceptibility contrast (DSC)-MR perfusion estimates by motion correctionJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2007Robert K. Kosior BSc Abstract Purpose To investigate the effect of patient motion on quantitative cerebral blood flow (CBF) maps in ischemic stroke patients and to evaluate the efficacy of a motion-correction scheme. Materials and Methods Perfusion data from 25 ischemic stroke patients were selected for analysis. Two motion profiles were applied to a digital anthropomorphic brain phantom to estimate accuracy. CBF images were generated for motion-corrupted and motion-corrected data. To correct for motion, rigid-body registration was performed. The realignment parameters and mean CBF in regions of interest were recorded. Results All patient data with motion exhibited visibly reduced intervolume misalignment after motion correction. Improved flow delineation between different tissues and a more clearly defined ischemic lesion (IL) were achieved in the motion-corrected CBF. A significant difference occurred in the IL (P < 0.05) for patients with severe motion with an average difference between corrupted and corrected data of 4.8 mL/minute/100 g. The phantom data supported the patient results with better CBF accuracy after motion correction and high registration accuracy (<1 mm translational and <1° rotational error). Conclusion Motion degrades flow differentiation between adjacent tissues in CBF maps and can cause ischemic severity to be underestimated. A registration motion correction scheme improves dynamic susceptibility contrast (DSC)-MR perfusion estimates. J. Magn. Reson. Imaging 2007;26:1167,1172. © 2007 Wiley-Liss, Inc. [source] Reexamining the quantification of perfusion MRI data in the presence of bolus dispersion,JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 3 2007Linda Ko BSc Abstract Purpose To determine the true impact of dispersion upon cerebral blood flow (CBF) quantification by removing an algorithm implementation-induced systematic error. Materials and Methods The impact of dispersion on the arterial input function (AIF) between measurement and entry into the tissue of interest on CBF estimates was simulated assuming: 1) contralateral circulation flow that introduces a true arterial tissue delay (ATD)-related dispersive component; and 2) the presence of an arterial stenosis that disperses and shifts the AIF peak entering the tissue; increasing the apparent ATD relative to the original AIF. Results Previously reported CBF estimates for the stenosis dispersion model were found to be a mixture of true dispersive effects and an algorithm implementation-induced systematic error. The true CBFMEASURED/CBFNO-DISPERSION ratios for short mean transit times (MTT) (normal) and long MTT (infarcted) tissue were similar for both dispersion models evaluated; this was an unanticipated result. The CBF quantification inaccuracies induced through the dispersion model truly related to ATD were lower than for the local stenosis-based dispersion for small ATD values. Conclusion Correcting the systematic error present in a previous deconvolution study removes the reported ATD-related impact on CBF quantification. The impact of dispersion was smaller than half that reported in previous simulation studies. J. Magn. Reson. Imaging 2007;25:639,643. © 2007 Wiley-Liss, Inc. [source] Method for improving the accuracy of quantitative cerebral perfusion imaging,JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 5 2005Ken E. Sakaie PhD Abstract Purpose To improve the accuracy of dynamic susceptibility contrast (DSC) measurements of cerebral blood flow (CBF) and volume (CBV). Materials and Methods In eight volunteers, steady-state CBV (CBVSS) was measured using TrueFISP readout of inversion recovery (IR) before and after injection of a bolus of contrast. A standard DSC (STD) perfusion measurement was performed by echo-planar imaging (EPI) during passage of the bolus and subsequently used to calculate the CBF (CBFDSC) and CBV (CBVDSC). The ratio of CBVSS to CBVDSC was used to calibrate measurements of CBV and CBF on a subject-by-subject basis. Results Agreement of values of CBV (1.77 ± 0.27 mL/100 g in white matter (WM), 3.65 ± 1.04 mL/100 g in gray matter (GM)), and CBF (23.6 ± 2.4 mL/(100 g min) in WM, 57.3 ± 18.2 mL/(100 g min) in GM) with published gold-standard values shows improvement after calibration. An F-test comparison of the coefficients of variation of the CBV and CBF showed a significant reduction, with calibration, of the variability of CBV in WM (P< 0.001) and GM (P < 0.03), and of CBF in WM (P < 0.0001). Conclusion The addition of a CBVSS measurement to an STD measurement of cerebral perfusion improves the accuracy of CBV and CBF measurements. The method may prove useful for assessing patients suffering from acute stroke. J. Magn. Reson. Imaging 2005;21:512,519. © 2005 Wiley-Liss, Inc. [source] Regional dynamics of the fMRI-BOLD signal response to hypoxia-hypercapnia in the rat brainJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2003Sridhar S. Kannurpatti PhD Abstract Purpose To examine the regional blood oxygenation level-dependent (BOLD) signal response to rapid changes in arterial oxygen tension. Materials and Methods Functional MR imaging (fMRI) was carried out in five male Sprague-Dawley rats anesthetized with Sodium Pentobarbital. Rats were subjected to different durations of apnea as a rapid, graded, and reversible hypoxic-hypercapnic stimulus. Dynamics of the BOLD signal response were studied on a pixel-by-pixel basis in the cerebral cortex, hippocampus, third ventricle, and thalamus in the rat brain. Results Apnea induced a BOLD signal drop in all the brain regions studied, the magnitude of which increased with longer durations of the stimulus. The signal recovered to preapnic baseline levels after resumption of normal ventilation. Regional variation in the BOLD signal dynamics was observed with the magnitude of the BOLD signal change in the hippocampus being the least, followed by a relatively larger change in the thalamus, cerebral cortex, and third ventricle. The time (t0) for the signal change after the onset of the stimulus was estimated for every pixel. Time delay maps generated show the highest onset time values in the hippocampus followed by the thalamus, cerebral cortex, and third ventricle. Conclusion The regional dynamics of the BOLD signal in the brain in response to apnea may vary depending on the rate of oxygen metabolism in addition to cerebral blood flow (CBF). J. Magn. Reson. Imaging 2003;17:641,647. © 2003 Wiley-Liss, Inc. [source] Effects of indomethacin on cerebral blood flow at rest and during hypercapnia: An arterial spin tagging study in humans,JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2002Keith S. St. Lawrence PhD Abstract Purpose To investigate using an arterial spin tagging (AST) approach the effect of indomethacin on the cerebral blood flow (CBF) response to hypercapnia. Materials and Methods Subjects inhaled a gas mixture containing 6% CO2 for two 5-minute periods, which were separated by a 10-minute interval, in which subjects inhaled room air. In six subjects, indomethacin (i.v., 0.2 mg/kg) was infused in the normocapnic interval between the two hypercapnic periods. Results Indomethacin reduced normocapnic gray matter CBF by 36 ± 5% and reduced the CBF increase during hypercapnia from 43 ± 9% to 16 ± 5% in gray matter (P < 0.001) and from 48 ± 11% to 35 ± 9% in white matter (P < 0.025). Conclusion The results demonstrate that an AST approach can measure the effects of indomethacin on global CBF increases during hypercapnia and suggest that an AST approach could be used to investigate pharmacological effects on focal CBF increases during functional activation. J. Magn. Reson. Imaging 2002;15:628,635. Published 2002 Wiley-Liss, Inc. [source] Methodology of brain perfusion imagingJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2001Emmanuel L. Barbier PhD Abstract Numerous techniques have been proposed in the last 15 years to measure various perfusion-related parameters in the brain. In particular, two approaches have proven extremely successful: injection of paramagnetic contrast agents for measuring cerebral blood volumes (CBV) and arterial spin labeling (ASL) for measuring cerebral blood flows (CBF). This review presents the methodology of the different magnetic resonance imaging (MRI) techniques in use for CBV and CBF measurements and briefly discusses their limitations and potentials. J. Magn. Reson. Imaging 2001;13:496,520. © 2001 Wiley-Liss, Inc. [source] Cerebral blood flow and oxygen metabolism measured with the Kety,Schmidt method using nitrous oxideACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2009S. TAUDORF Background: The Kety,Schmidt method is the reference method for measuring global cerebral blood flow (CBF), cerebral metabolic rates (CMR) and flux, especially where scanners are unavailable or impractical. Our primary objective was to assess the repeatability of the Kety,Schmidt method in a variety of different approaches using inhaled nitrous oxide (N2O) as the tracer, combined with photoacoustic spectrometry. A secondary objective was to assess the impact of this tracer on the systemic vascular concentration of nitrite (NO2,). Methods: Twenty-nine healthy male volunteers underwent 61 CBF measurements by breathing a normoxic gas mixture containing 5% N2O until tension equilibrium. Paired blood samples were collected from an arterial and a jugular bulb catheter in the saturation or desaturation phase, by continuous or the discontinuous sampling. N2O concentration was measured with photoacoustic spectrometry after equilibration of blood samples with air. CBF was calculated by the Kety,Schmidt equation. CMR of oxygen (CMRO2) was determined by the Fick principle. NO2, in plasma and red blood cells (RBC) was measured by ozone-based chemiluminescence. Results: The most robust approach for CBF measurement was achieved by discontinuous sampling in the desaturation phase [CBF, 64 (95% confidence interval, 59,71 ml)] 100 g/min; CMRO2 1.8 (1.7,2.0) ,mol/g/min). The tracer did not influence plasma or RBC NO2, (P>0.05 vs. baseline). Conclusion: These findings confirm the reliability and robustness of the Kety,Schmidt method using inhaled N2O for the measurement of global CBF and CMR. At the low tracer concentration used, altered NO metabolism is unlikely to have affected cerebral haemodynamic function. [source] An angiotensin II type 1 receptor blocker can preserve endothelial function and attenuate brain ischemic damage in spontaneously hypertensive ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 13 2010Naoki Oyama Abstract Hypertension reduces endothelial nitric oxide synthase (eNOS) expression and leads to endothelial dysfunction. However, few studies have demonstrated the influences of hypertension on eNOS function in the cerebral cortex. The present study investigates the influences of hypertension on endothelial function in the cerebral cortex and the protective effects of antihypertensive agents against brain ischemia through the preservation of endothelial function. Five- and ten-week-old male Wistar rats and spontaneously hypertensive rats (SHR) were used for experiments. Five-week-old SHR received olmesartan, hydralazine, or vehicle for 5 weeks in drinking water. eNOS activation in the cerebral cortex was evaluated by analyzing levels of total and Ser1177 -phosphorylated eNOS protein by Western blot. Blood pressure of 10-week-old SHR without treatment was clearly high, and the ratio of phospho-eNOS/total eNOS protein was significantly low. Five-week treatment with olmesartan or hydralazine suppressed the elevation of blood pressure and the reduction of phosphorylated eNOS-Ser1177 in SHR, and olmesartan was more effective in maintaining phosphorylation of eNOS-Ser1177 than hydralazine. To assess the contribution of eNOS to maintaining cerebral blood flow (CBF), we monitored CBF by laser-Doppler flowmetry after L-N5 -(1-iminoethyl)ornithine (L-NIO) infusion. CBF response to L-NIO was preserved in olmesartan-treated SHR but not in hydralazine-treated SHR. Furthermore, infarct volume 48 hr after transient focal brain ischemia in olmesartan-treated SHR was significantly reduced compared with vehicle-treated SHR. These findings indicate that chronic prehypertensive treatment with olmesartan could attenuate brain ischemic injury through the maintenance of endothelial function in the cerebral cortex in SHR. © 2010 Wiley-Liss, Inc. [source] Effects of EP1 receptor on cerebral blood flow in the middle cerebral artery occlusion model of stroke in miceJOURNAL OF NEUROSCIENCE RESEARCH, Issue 11 2007Sofiyan Saleem Abstract The lipid mediator prostaglandin E2 (PGE2) exhibits diverse biologic activity in a variety of tissues. Four PGE2 receptor subtypes (EP1,4) are involved in various physiologic and pathophysiologic conditions, but differ in tissue distribution, ligand-binding affinity, and coupling to intracellular signaling pathways. To characterize the role of the EP1 receptor, physiologic parameters (mean arterial blood pressure, pH, blood gases PaO2 and PaCO2, and body temperature), cerebral blood flow (CBF), and neuronal cell death were studied in a middle cerebral artery occlusion model of ischemic stroke in wild-type (WT) and EP1 knockout (EP1,/,) mice. The right middle cerebral artery was occluded for 60 min, and absolute CBF was measured by [14C] iodoantipyrine autoradiography. The effect of EP1 receptor on oxidative stress in neuronal cultures was investigated. Although no differences were observed in the physiologic parameters, CBF was significantly (P < 0.01) higher in EP1,/, mice than in WT mice, suggesting a role for this receptor in physiologic and pathophysiologic control of vascular tone. Similarly, neuronal cultures derived from EP1,/, mice were more resistant (90.6 ± 5.8% viability) to tert -butyl hydroperoxide-induced oxidative stress than neurons from WT mice (39.6 ± 17.2% viability). The EP1 receptor antagonist SC-51089 and calcium channel blocker verapamil each attenuated the neuronal cell death induced by PGE2. Thus, the prostanoid EP1 receptor plays a significant role in regulating CBF and neuronal cell death. These findings suggest that pharmacologic modulation of the EP1 receptor might be a means to improve CBF and neuronal survival during ischemic stroke. © 2007 Wiley-Liss, Inc. [source] |