Reduction In Cerebral Blood Volume Research Articles

Brief neuronal afterdischarges in the rat hippocampus lead to transient changes in oscillatory activity and to a very long-lasting decline in BOLD signals without inducing a hypoxic state

The effects of hippocampal neuronal afterdischarges (nAD) on hemodynamic parameters, such as blood-oxygen-level-dependent (BOLD) signals) and local cerebral blood volume (CBV) changes, as well as neuronal activity and metabolic parameters in the dentate gyrus, was investigated in rats by combining in vivo electrophysiology with functional magnetic resonance imaging (fMRI) or 1H-nuclear magnetic resonance spectroscopy (1H-NMRS). Brief electrical high-frequency pulse-burst stimulation of the right perforant pathway triggered nAD, a seizure-like activity, in the right dentate gyrus with a high incidence, a phenomenon that in turn caused a sustained decrease in BOLD signals for more than 30 min. The decrease was associated with a reduction in CBV but not with signs of hypoxic metabolism. nAD also triggered transient changes mainly in the low gamma frequency band that recovered within 20 min, so that the longer-lasting altered hemodynamics reflected a switch in blood supply rather than transient changes in ongoing neuronal activity. Even in the presence of reduced baseline BOLD signals, neurovascular coupling mechanisms remained intact, making long-lasting vasospasm unlikely. Subsequently generated nAD did not further alter the baseline BOLD signals. Similarly, nAD did not alter baseline BOLD signals when acetaminophen was previously administered, because acetaminophen alone had already caused a similar decrease in baseline BOLD signals as observed after the first nAD. Thus, at least two different blood supply states exist for the hippocampus, one low and one high, with both states allowing similar neuronal activity. Both acetaminophen and nAD switch from the high to the low blood supply state. As a result, the hemodynamic response function to an identical stimulus differed after nAD or acetaminophen, although the triggered neuronal activity was similar.

Delayed perihematomal hypoperfusion is associated with poor outcome in intracerebral haemorrhage.

The aim of this study was to characterize the temporal evolution and prognostic significance of perihematomal perfusion in acute intracerebral haemorrhage (ICH). A single-centre prospective cohort of patients with primary spontaneous ICH receives computed tomography perfusion (CTP) within 6h from onset (T0) and at 7days (T7). Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the manually outlined perihematomal low-density area. Poor functional prognosis (modified Rankin Scale 3-6) at 90days was the outcome of interest, and predictors were explored with multivariable logistic regression. A total of 150 patients were studied, of whom 52 (34.7%) had a mRS 3-6 at 90days. Perihematomal perfusion decreased from T0 to T7 in all patients, but the magnitude of CBF and CBV reduction was larger in patients with unfavourable outcome (median CBF change -7.8 vs. -6.0ml/100g/min, p<.001, and median CBV change -0.5 vs. -0.4ml/100g, p=.010, respectively). This finding remained significant after adjustment for confounders (odds ratio [OR] for 1ml/100g/min CBF reduction: 1.33, 95% confidence interval [CI] (1.15-1.55), p<.001; OR for 0.1ml/100g CBV reduction: 1.67, 95% CI 1.18-2.35, p=.004). The presence of CBF<20ml/100g/min at T7 was then demonstrated as an independent predictor of poor functional outcome (adjusted OR: 2.45, 95% CI 1.08-5-54, p=.032). Perihaemorrhagic hypoperfusion becomes more severe in the days following acute ICH and is independently associated with poorer outcome. Understanding the underlying biological mechanisms responsible for delayed decrease in perihematomal perfusion is a necessary step towards outcome improvement in patients with ICH.

Characteristics of cerebral perfusion and diffusion associated with crossed cerebellar diaschisis after acute ischemic stroke.

We aimed to investigate the possible factors associated with the occurrence of crossed cerebellar diaschisis (CCD) at the hyperacute stage of ischemic stroke using whole-brain volume perfusion CT (VPCT) combined with magnetic resonance imaging (MRI). We retrospectively analyzed 108 patients with ischemic stroke within 6h of onset. The VPCT findings of the patients showed a unilateral perfusion deficit in the supratentorial territory. Follow-up MRI examinations were performed within 24h after onset. The effects of the supratentorial cerebral ischemia, the location distribution, the final infarct volume and the apparent diffusion coefficient (ADC) value on the occurrence and severity of CCD were analyzed. Among 108 patients with hyperacute cerebral ischemia, 62 (57.4%) demonstrated a contralateral cerebellar perfusion deficit on the VPCT maps. The occurrence of CCD was related to a reduction in cerebral blood volume (CBV) and prolongation of the mean transit time (MTT). Notably, the decrease in the ADC value in the infarct based on follow-up MRI was closely related to the occurrence and severity of CCD. The occurrence and severity of CCD are related to the degree of low supratentorial perfusion and the decrease in the ADC value of infarct focus.

Abstract WP79: Combination of Tmax and Relative CBV Perfusion Parameters More Accurately Predicts CTA Collaterals Than a Single Perfusion Parameter in DEFUSE 3

Introduction: Perfusion abnormalities that have been associated with collateral status include the hypoperfusion intensity ratio (HIR) and reduction of cerebral blood volume within the ischemic lesion (CBV index). We hypothesized that assessment of both of these parameters would predict poor CTA collaterals with greater accuracy than a single parameter. This hypothesis was assessed among patients enrolled in the DEFUSE 3 trial that evaluated the efficacy of thrombectomy in patients with imaging evidence of salvageable tissue in the late 6-16 hour window. Methods: Patients were eligible for this analysis if they had adequate quality CTA and CT perfusion. An expert neuroradiologist assessed collateral status on CTA using the Tan scale. The HIR index (fraction of Tmax&gt;10s delay within the Tmax&gt;6s lesion) and the CBV index (mean CBV within the Tmax&gt;6s lesion relative to normal CBV) were automatically calculated by RAPID software. ROC curve analysis was used to identify thresholds for both indices that predicted presence of poor collaterals on CTA. Proportions were compared using χ 2 and McNemar tests. Results: Of the 128 cases eligible for this analysis, 26% had poor collaterals on CTA. HIR ≥0.39 and CBV index ≤0.77 were the optimal thresholds for predicting poor collaterals on CTA. Good collaterals were present on CTA in 87% when neither of the perfusion indices were unfavorable, 77% when a single index was unfavorable, and 54% when both were unfavorable (p=0.001 for none vs both and p=0.029 for single vs both). Sensitivity for predicting poor CTA collaterals was 0.70 (95% CI 0.51-0.84) with HIR ≥0.39, 0.61 (0.42-0.77) with CBV index ≤0.77, and 0.82 (0.64-0.92) for the combined criteria of ‘either index unfavorable’ (p=0.016 for ‘either’ criteria vs CBV index alone). The presence of unfavorable criteria on both indices produced a higher specificity of 0.80 (0.70-0.87) vs. HIR alone 0.59 (0.48-0.69) or CBV alone 0.62 (0.52-0.72), both p&lt;0.001. Conclusion: The combination of 2 fully automated perfusion parameters were more accurate for predicting CTA collaterals than a single perfusion parameter in the DEFUSE 3 population. Automated perfusion parameters do not require an expert neuroradiologist for interpretation and have no concerns regarding inter-rater agreement.

A brain-wide functional map of the serotonergic responses toacute stress and fluoxetine

Central serotonin (5-HT) orchestrates myriad cognitive processes andlies at the core of many stress-related psychiatric illnesses. However, the basicrelationship between its brain-wide axonal projections and functional dynamics isnot known. Here we combine optogenetics and fMRI to produce a brain-wide 5-HT evokedfunctional map. We find that DRN photostimulation leads to an increase in thehemodynamic response in the DRN itself, while projection areas predominately exhibita reduction of cerebral blood volume mirrored by suppression of cortical deltaoscillations. We find that the regional distribution of post-synaptically expressed5-HT receptors better correlates with DRN 5-HT functional connectivity thananatomical projections. Our work suggests that neuroarchitecture is not the primarydeterminant of function for the DRN 5-HT. With respect to two 5-HT elevatingstimuli, we find that acute stress leads to circuit-wide blunting of the DRN output,while the SSRI fluoxetine noticeably enhances DRN functional connectivity. Thesedata provide fundamental insight into the brain-wide functional dynamics of the 5-HTprojection system.

Hypothermia for Increased Intracranial Pressure: Is It Dead?

Mild to moderate therapeutic hypothermia (HT) has been used to alleviate intracranial hypertension in traumatic brain injury (TBI). Its main contribution is thought to be via reduction in cerebral metabolic requirement leading both to favorable oxygen/metabolic delivery-demand ratios as well as a reduction of cerebral blood volume resulting in decreased ICP. Nevertheless, HT is a clinically complex, labor-intensive procedure with numerous potential adverse effects. Furthermore, randomized controlled trials suggest either no effect or harm. These facts challenge the role of HT in TBI. We address this challenge by posing three questions that relate to the overarching value of controlling ICP, the effectiveness of HT in reducing ICP, and the benefit-risk ratio of the intervention. We conclude that HT should not be used as an "early" intervention unless as a part of a clinical trial, although it may still have a role in patients with refractory intracranial hypertension.

Perfusion reduction in the absence of structural differences in cognitively impaired versus unimpaired RRMS patients

Background: Cognitive impairment affects 40%–68% of relapsing-remitting multiple sclerosis (RRMS) patients. Gray matter (GM) demyelination is complicit in cognitive impairment, yet cortical lesions are challenging to image clinically. We wanted to determine whether cortical cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) differences exist between cognitively impaired (CI) and unimpaired (NI) RRMS. Methods: Prospective study of healthy controls (n = 19), CI (n = 20), and NI (n = 19) undergoing magnetic resonance imaging (MRI) and cognitive testing <1 week apart. White matter (WM) T2 hyperintense lesions and T1 black holes were traced. General linear regression assessed the relationship between lobar WM volume and cortical and WM CBF, CBV, and MTT. Relationship between global and lobar cortical CBF, CBV, and MTT and cognitive impairment was tested using a generalized linear model. Adjusted Bonferroni p < 0.005 was considered significant. Results: No significant differences for age, gender, disease duration, and any fractional brain or lesion volume were demonstrated for RRMS subgroups. Expanded Disability Status Scale (EDSS) and Hospital Anxiety and Depression Scale–Depression (HADS-D) were higher in CI. Lobar cortical CBF and CBV were associated with cognitive impairment (p < 0.0001) after controlling for confounders. Cortical CBV accounted for 7.2% of cognitive impairment increasing to 8.7% with cortical CBF (p = 0.06), while WM and cortical CBF accounted for 8.2% of variance (p = 0.04). Conclusion: Significant cortical CBF and CBV reduction was present in CI compared to NI in the absence of structural differences.

Abstract TMP56: Mapping the Dynamics of Brain Perfusion During and Following Transient Middle Cerebral Artery Occlusion (tMCAo) in the Rat Using Functional Ultrasound (fUS)

Introduction: Following MCAo, tissue outcome varies depending on depth and duration of hypoperfusion and efficiency of reperfusion. However, the precise time-course of these events in relation to tissue and behavioral outcome remains unsettled due to lack of a wide field-of-view quantitative imaging technique able to map perfusion in the rodent brain at high spatiotemporal resolution. Here we used fUS, a novel approach to map cerebral blood volume (CBV) without contrast agent. Hypothesis: fUS will allow quantitative, near real-time mapping of CVB during and after tMCAo. Methods: 45min filament tMCAo was induced in adult SD rats; sham rats were also used. fUS was used to map the penetrating arterioles and venules of the ipsi- and contra-lateral motor (M1-2) and somatosensory (S1) cortex in coronal sections across the MCA territory at 80μm resolution. Three-min coronal scans were taken at different levels before, during and immediately after MCAo, and at 3 and 6 days thanks to a thinned-skull preparation. CBV was expressed relative to mirror ROI. In addition, a 1-hr movie (one frame/5s) was taken starting a few mins after reperfusion. Serial Neuroscore and 2 sensorimotor tasks were given over 3w post-MCAo, and then NeuN, IBa1 and GFAP immunofluorescence (IF) at post-mortem. Results: fUS showed a ∼80% CBV reduction in S1 during occlusion (p&lt;0.001; n=7), with partial (∼60%, p&lt;0.001) return of CBV on reperfusion, followed by a full return at days 3 and 6. As expected for this model, similar but less conspicuous CBV changes prevailed in M1-2. Continuous reperfusion was depicted in 5/7 rats (slope range: 8-25%/hr relative to prior CBV), but not in 2 rats. There were no significant changes in behavior relative to the sham group (n=4), and IF showed no infarction but marked selective neuronal loss (SNL) in the striatum in 5/7 rats and milder cortical SNL in 4/7 rats. Conclusions: fUS efficiently mapped the acute changes in CBV during occlusion and following reperfusion with high spatio-temporal resolution, allowing the charting of fine tissue reperfusion dynamics in the individual rat. fUS is ideal to longitudinally map real-time cerebral perfusion in experimental stroke from the hyper-acute through to the chronic stage.

CT perfusion cerebral blood volume does not always predict infarct core in acute ischemic stroke.

We investigated the practical clinical utility of the CT perfusion (CTP) cerebral blood volume (CBV) parameter for differentiating salvageable from non-salvageable tissue in acute ischemic stroke (AIS). Fifty-five patients with AIS were imaged within 6 h from onset using CTP. Admission CBV defect (CBVD) volume was outlined using previously established gray and white matter CBV thresholds for infarct core. Admission cerebral blood flow (CBF) hypoperfusion and CBF/CBV mismatch were visually evaluated. Truncation of the ischemic time-density curve (ITDC) and hypervolemia status at admission, recanalization at 24-h CT angiography, hemorrhagic transformation (HT) at 24 h and/or 7-day non-contrast CT (NCCT), final infarct volume as indicated by 3-month NCCT defect (NCCTD) and 3-month modified Rankin Score were determined. Patients with recanalization and no truncation had the highest correlation (R = 0.81) and regression slope (0.80) between CBVD and NCCTD. Regression slopes were close to zero for patients with admission hypervolemia with/without recanalization. Hypervolemia underestimated (p = 0.02), while recanalization and ITDC truncation overestimated (p = 0.03) the NCCTD. Among patients with confirmed recanalization at 24 h, 38 % patients had an admission CBF/CBV mismatch within normal appearing areas on respective NCCT. 83 % of these patients developed infarction in admission hypervolemic CBF/CBV mismatch tissue. A reduction in CBV is a valuable predictor of infarct core when the acquisition of ITDC data is complete and hypervolemia is absent within the tissue destined to infarct. Raised or normal CBV is not always indicative of salvageable tissue, contrary to the current definition of penumbra.

Diagnostic and Prognostic Impact of pc-ASPECTS Applied to Perfusion CT in the Basilar Artery International Cooperation Study.

The posterior circulation Acute Stroke Prognosis Early CT Score (pc-APECTS) applied to CT angiography source images (CTA-SI) predicts the functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). We assessed the diagnostic and prognostic impact of pc-ASPECTS applied to perfusion CT (CTP) in the BASICS registry population. We applied pc-ASPECTS to CTA-SI and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and CTP studies performed. Hypoattenuation on CTA-SI, relative reduction in CBV or CBF, or relative increase in MTT were rated as abnormal. CTA and CTP were available in 27/592 BASICS patients (4.6%). The proportion of patients with any perfusion abnormality was highest for MTT (93%; 95% confidence interval [CI], 76%-99%), compared with 78% (58%-91%) for CTA-SI and CBF, and 46% (27%-67%) for CBV (P < .001). All 3 patients with a CBV pc-ASPECTS < 8 compared to 6/23 patients with a CBV pc-ASPECTS ≥ 8 had died at 1 month (RR 3.8; 95% CI, 1.9-7.6). CTP was performed in a minority of the BASICS registry population. Perfusion disturbances in the posterior circulation were most pronounced on MTT parameter maps. CBV pc-ASPECTS < 8 may indicate patients with high case fatality.

Whole-Brain Perfusion CT Using a Toggling Table Technique to Predict Final Infarct Volume in Acute Ischemic Stroke

To evaluate how accurately final infarct volume in acute ischemic stroke can be predicted with perfusion CT (PCT) using a 64-MDCT unit and the toggling table technique. Retrospective analysis of 89 patients with acute ischemic stroke who underwent CCT, CT angiography (CTA) and PCT using the "toggling table" technique within the first three hours after symptom onset. In patients with successful thrombolytic therapy (n = 48) and in those without effective thrombolytic therapy (n = 41), the infarct volume and the volume of the penumbra on PCT were compared to the infarct size on follow-up images (CT or MRI) performed within 8 days. The feasibility of complete infarct volume prediction by 8 cm cranio-caudal coverage was evaluated. The correlation between the volume of hypoperfusion on PCT defined by cerebral blood volume reduction and final infarct volume was strongest in patients with successful thrombolytic therapy with underestimation of the definite infarct volume by 8.5 ml on average. The CBV map had the greatest prognostic value. In patients without successful thrombolytic therapy, the final infarct volume was overestimated by 12.1 ml compared to the MTT map on PCT. All infarcts were detected completely. There were no false-positive or false-negative results. Using PCT and the "toggling table" technique in acute stroke patients is helpful for the rapid and accurate quantification of the minimal final infarct and is therefore a prognostic parameter which has to be evaluated in further studies to assess its impact on therapeutic decision. ▶ Using PCT and the “toggling table technique” allows accurate quantification of the infarct core and penumbra. ▶ It is possible to record dynamic perfusion parameters quickly and easily of almost the entire supratentorial brain volume on a 64-slice MDCT unit. ▶ The technique allows identification of those patients who could profit from thrombolytic therapy outside the established time intervals.

Imaging Patients with Psychosis and a Mouse Model Establishes a Spreading Pattern of Hippocampal Dysfunction and Implicates Glutamate as a Driver

The hippocampus in schizophrenia is characterized by both hypermetabolism and reduced size. It remains unknown whether these abnormalities are mechanistically linked. Here we addressed this question by using MRI tools that can map hippocampal metabolism and structure in patients and mouse models. In at-risk patients, hypermetabolism was found to begin in CA1 and spread to the subiculum after psychosis onset. CA1 hypermetabolism at baseline predicted hippocampal atrophy, which occurred during progression to psychosis, most prominently in similar regions. Next, we used ketamine to model conditions of acute psychosis in mice. Acute ketamine reproduced a similar regional pattern of hypermetabolism, while repeated exposure shifted the hippocampus to a hypermetabolic basal state with concurrent atrophy and pathology in parvalbumin-expressing interneurons. Parallel invivo experiments using the glutamate-reducing drug LY379268 and direct measurements of extracellular glutamate showed that glutamate drives both neuroimaging abnormalities. These findings show that hippocampal hypermetabolism leads to atrophy in psychotic disorder and suggest glutamate as a pathogenic driver.

Abstract 2972: Perfusion CT in Patients with Basilar Artery Occlusion: Diagnostic and Prognostic Value in the Basilar Artery International Cooperation Study

Background: The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) applied to CT angiography source images (CTA-SI) predicts the functional outcome of patients with basilar artery occlusion (BAO). Compared with CTA-SI, perfusion CT (CTP) may provide added information. We assessed the diagnostic and prognostic impact of CTP compared with CTA-SI among patients in the Basilar Artery International Cooperation Study (BASICS) Methods: BASICS was a prospective observational registry of consecutive patients with acute symptomatic BAO. We applied pc-ASPECTS to CTA-SI and cerebral blood volume (CBV), cerebral blood flow (CBF), time-to-peak (TTP) and mean-transit-time (MTT) parameter maps in a 3-reader-consensus with readers blinded to clinical data. Hypoattenuation on CTA-SI, a relative reduction in CBV or CBF, or relative increase in MTT or TTP was rated as abnormal. Clinical outcome was measured with the modified Rankin Scale (mRS) score at 1 month. Results: Among 592 patients in the BASICS registry, 27 patients (4.6%) had CTP studies performed. Median (interquartile-range) pc-ASPECTS values on TTP/MTT, CTA-SI, CBF and CBV were 6 (5-8), 7 (5-9), 8 (6-9) and 10 (8.75-10), respectively (p&lt;0.001). The proportion of patients with any perfusion abnormalities in the posterior circulation was highest for TTP/MTT (93%; CI 95% 74% to 99%), compared with 78% (CI 95% 57% to 91%) for both CTA-SI and CBF and 46% (CI 95% 27% to 66%) for CBV (p&lt;0.001). At 1 month, 9 patients (33%) had a favourable outcome (mRS scores 0-3), 8 patients (30%) had an unfavourable outcome (mRS scores 4-5) and 10 patients (37%) were deceased. In univariate analysis, pc-ASPECTS scores did not correlate with outcome mRS scores for all imaging modalities (Spearman’s Rho, p&gt;0.1 for all). All three patients (100%) with a CBV pc-ASPECTS &lt;8 compared to 6 of 23 patients (26%) with a CBV pc-ASPECTS &gt;8 died (p=0.03). Conclusion: CTP was performed in a minority of patients in the BASICS registry population. Perfusion disturbances in the posterior circulation were most frequent and most pronounced on TTP and MTT parameter maps. Extensive reduction of CBV, defined as a pc-ASPECTS &lt;8, may indicate patients with a high case fatality.

Chapter 15. Analgesics, sedatives, and neuromuscular blockade

Chapter 15. Analgesics, sedatives, and neuromuscular blockade

Comment to: Parametric Response Map as an Imaging Biomarker to Distinguish Progression from Pseudoprogression in High-Grade Glioma: Pitfalls in Perfusion MRI in Brain Tumors

Pseudoprogression is a recently recognized phenomenon which occurs mainly within the first 3 months after resection and radiochemotherapy of glioblastomas in up to 30% of cases. It refers to contrast enhancement with or without clinical deterioration which spontaneously resolves and which is not regarded as being related to tumor growth. Even with advanced imaging techniques it is not yet possible to distinguish reliably between true tumor progression and pseudoprogression in patients with high-grade glioma who received radiochemotherapy. Tsien et al. performed magnetic resonance imaging (MRI) dynamic susceptibility contrast (DSC) perfusion on 27 patients with high-grade glioma before radiochemotherapy and at week 1 and 3 during treatment. Clinical and conventional magnetic resonance (MR) parameters, including average percent change of cerebral blood volume (CBV) and cerebral blood flow (CBF), were evaluated as potential predictors of pseudoprogression and progression, respectively. In addition, a new postprocessing tool called parametric response map, which uses a voxel-by-voxel method of image analysis, was used to evaluate CBV and CBF. Given significant tumor heterogeneity after radiochemotherapy, Tsien et al. hypothesized that a voxel approach may be more sensitive than referring to the mean tumor average of CBV and CBF as it is done in standard whole-tumor statistical methods. Using the “parametric response map”, Tsien et al. found a reduction in CBV at 3 weeks after therapy to be a potential biomarker for true tumor progression, whereas all other parameters failed to differentiate between progression and pseudoprogression.

Perfusion Deficit in Schizophrenia and Correlation with Psychopathological Symptoms

Perfusion Deficit in Schizophrenia and Correlation with Psychopathological Symptoms

Effect of ventilation on cerebral oxygenation during exercise: Insights from canonical correlation

We tested hypothesis that cerebral deoxygenation near maximal exercise intensity is mediated by hyperventilation, via hypocapnia-induced reductions in cerebral blood flow, by utilizing canonical correlation analysis (CCA) to determine the relative influence of cardiopulmonary changes on cerebral oxygenation, as assessed by near infrared spectroscopy (NIRS). Twenty-three subjects performed incremental exercise tests under normoxic and hypoxic conditions. Changes in ventilation (V (E)) were strongly correlated with end-tidal CO(2) (P(ET)(CO)(2)) and NIRS after the respiratory compensation point (RCP) (r(2)>0.97). However, in contrast to our expectations, CBF velocity (CBFv) shared the least amount of variance with NIRS measurements (r(2)<0.56) and the reduction in CBFv was not accompanied by a reduction in cerebral blood volume. These results demonstrate that while cerebral deoxygenation was associated with hyperventilation, it was not solely explained by hypocapnia-induced reductions in CBFv. CCA revealed that a relative increase in the venous contribution to NIRS explained a larger amount of variation in cerebral oxygenation than reductions CBFv.

Changes in cerebral hemodynamics and amplitude integrated EEG in an asphyxiated newborn during and after cool cap treatment

Amplitude integrated EEG (aEEG) and Near Infrared Spectroscopy (NIRS) were applied in a newborn with a moderate hypoxic–ischemic encephalopathy before, during and after brain cooling. At 2 h of life a selective head cooling with mild systemic hypothermia was started and maintained for 72 h. aEEG background pattern improved from severely abnormal to normal during the first 17 h of life. NIRS revealed a reduction in cerebral blood volume (CBV) during hypothermia that recovered during the rewarming period, whereas brain oxygenation remained stable. As brain cooling is supposed to reduce delayed hyperemia and help to maintain neuronal metabolism following cerebral insults, aEEG and NIRS monitoring may be useful during hypothermic treatment in order to document changes in CBV and brain oxygenation possibly reflecting the efficacy of hypothermia.

Effects of surgical repair of congenital diaphragmatic hernia on cerebral hemodynamics evaluated by near-infrared spectroscopy

Background Cardiorespiratory stabilization is recommended before surgical repair of congenital diaphragmatic hernia (CDH) because surgery may induce a transitory deterioration of chest compliance and gas exchange. It is not known if surgical intervention can affect cerebral circulation and oxygenation. Aim The aim of the study was to assess noninvasively, by near-infrared spectroscopy, the possible changes in cerebral hemodynamics and oxygenation associated with surgical repair of CDH. Subjects Twenty-five newborns with severe CDH (birth weight, 3057 ± 354 g; gestational age, 37.8 ± 1.8 weeks; male/female newborns, 15/10; left/right CDH, 19/6) were sedated, paralyzed, and mechanically ventilated by conventional gentle ventilation and surgically corrected at a median age of 2.7 days (min-max, 2-14 days) after cardiorespiratory stabilization. Methods Heart rate (HR [beats per minute]), preductal transcutaneous oxygen saturation (tcSa o 2 [%]), carbon dioxide tension (tcP co 2 [Torr]), and mean arterial blood pressure (mm Hg) were continuously monitored. Inspired fractional oxygen concentration (F io 2) was adjusted to maintain and preductal tcSa o 2 of greater than 80%, whereas the ventilator's settings were kept unchanged throughout the surgical procedure. Cerebral hemodynamics was assessed by near-infrared spectroscopy (NIRO 300, Hamamatsu Photonics, Japan), recording continuously and noninvasively the relative changes in concentration of oxygenated ( ΔO 2Hb [ μmol/L]), deoxygenated ( ΔHHb [ μmol/L]), and total ( ΔtHb [ μmol/L]) hemoglobin; the tissue oxygenation index (TOI [%]) was also calculated (TOI = O 2Hb/O 2Hb + HHb). Total hemoglobin concentration is considered to be representative of cerebral blood volume. Arterial blood gases were also measured at the beginning ( T 1) and at the end of surgery ( T 2). For all measurements, results at T 1 and at T 2, as well as the differences between T 1 and T 2, have been expressed as means or medians and SDs or 95% confidence intervals or ranges. The differences between T 1 and T 2 were considered statistically significant for a P value of less than .05 by the Student t test for paired values. Results At T 1, mean tcSa o 2% was 94.1 % (SD, 4.6) with a F io 2 of 0.25 (SD, 0.1); at T 2, to obtain similar values of tcSa o 2 (93.4%; SD, 4.4), it was necessary to increase the F io 2 to 0.37 (SD, 0.14; P < .001). Mean HR at T 1 was 149.5 beats per minute (SD, 9.1) and increased significantly ( P < .05) at T 2 (165.2 beats per minute; SD, 14.2). Mean arterial blood pressure was 54.7 mm Hg (SD, 7.7) at T 1 and did not change appreciably at T 2 (55.6 mm Hg; SD, 8.1). Moreover, tcP co 2 did not change significantly during the procedure (mean tcP co 2 = 49.9 Torr [SD, 12.8] at T 1 and 57.3 mm Hg [SD, 17.9] at T 2). O 2Hb and tHb decreased ( P < .001 and <.005) and HHb increased ( P < .05) significantly during the surgical procedure (mean Δ [SD]: ΔO 2Hb= −10.9 μmol/L [9.7], ΔtHb = −7.5 μmol/L [11.7], and ΔHHb = −3.5 μmol/L [6.8]). Mean TOI was 70% at T 1 (normal values >60%) and decreased significantly at T 2 (mean ΔTOI = −6.1% [SD, 10.6]). In all infants, the greatest changes occurred when the viscera were positioned into the abdomen. Conclusions Notwithstanding the initial cardiorespiratory stabilization, surgical repair of CDH was associated with a rise in HR and oxygen requirement and a drop in cerebral tHb and O 2Hb, suggesting a reduction in cerebral blood volume and oxygenation. These events were probably due to the combined effects of an increase in right to left shunting (as indicated by the increased oxygen requirement) and a decrease in venous return (possibly due to compression of the inferior vena cava by the viscera positioned into the abdomen). These preliminary results reinforce the importance of achieving a good cardiorespiratory stability before undertaking surgical correction of CDH to minimize the possible interference of the procedure with cerebral circulation and oxygenation.

Effect of cardiopulmonary bypass on cortical cerebral oxygenation during coronary artery bypass grafting.

To investigate the changes in cerebral oxygenation during coronary artery bypass grafting (CABG) with normothermic cardiopulmonary bypass (CPB) using near infrared spectroscopy. Measurement of cerebral cortical oxygenation changes included concentration of deoxygenated haemoglobin [HHb], oxygenated haemoglobin [O(2)Hb], changes in the redox status of the cytochrome c oxidase [Cyt-Ox], cerebral saturation as expressed by the tissue oxygenation index (TOI), and cerebral blood volume (CBV) as expressed by tissue haemoglobin index (THI). Measurements were performed in 19 consecutive patients undergoing normothermic (34-36 degrees C) CPB. Data were recorded at 0.5s intervals and averaged into 30 s epochs. Data analysis was carried at baseline, 1, 20, and 40 min after start of CPB, at rewarming, on weaning from CPB, and at closing of chest. There were no in-hospital death, neurological deficits, or myocardial infarcts. Compared to baseline, during the entire CPB duration, there was a marked reduction in [O(2)Hb] and CBV which reached their worst level 40 min after initiation of CPB (from -3.03+/-5.1 to -9.25+/-7.20 micromol/l for [O(2)Hb], and a 24% reduction for CBV (both P<0.0001). The deterioration in [O(2)Hb] was recovered by the end of surgery, while the changes in CBV persisted. No significant changes occurred with respect to [HHb], [Cyt-Ox], and TOI. Conventional CABG is responsible for deterioration in [O(2)Hb], and CBV, which peak at 40-60 min following initiation of CPB. The changes in [O(2)Hb] are reversible whereas the reduction of CBV persists to the end of the surgery. This suggests a transient impairment in the autoregulatory mechanisms controlling cerebral blood flow following discontinuation of cardiopulmonary bypass.