Autoregulation Index Research Articles

Cerebral Haemodynamics following Acute Ischaemic Stroke: Effects of Stroke Severity and Stroke Subtype

Background: Acute ischaemic stroke (AIS) patients often show impaired cerebral autoregulation (CA). We tested the hypothesis that CA impairment and other alterations in cerebral haemodynamics are associated with stroke subtype and severity. Methods: AIS patients (n = 143) were amalgamated from similar studies. Data from baseline (< 48 h stroke onset) physiological recordings (beat-to-beat blood pressure [BP], cerebral blood flow velocity (CBFV) from bilateral insonation of the middle cerebral arteries) were calculated for mean values and autoregulation index (ARI). Differences were assessed between stroke subtype (Oxfordshire Community Stroke Project [OCSP] classification) and severity (National Institutes of Health Stroke Scale [NIHSS] score < 5 and 5–25). Correlation coefficients assessed associations between NIHSS and physiological measurements. Results: Thirty-two percent of AIS patients had impaired CA (ARI < 4) in affected hemisphere (AH) that was similar between stroke subtypes and severity. CBFV in AH was comparable between stroke subtype and severity. In unaffected hemisphere (UH), differences existed in mean CBFV between lacunar and total anterior circulation OCSP subtypes (42 vs. 56 cm•s^–1, p < 0.01), and mild and moderate-to-severe stroke severity (45 vs. 51 cm•s^–1, p = 0.04). NIHSS was associated with peripheral (diastolic and mean arterial BP) and cerebral haemodynamic parameters (CBFV and ARI) in the UH. Conclusions: AIS patients with different OCSP subtypes and severity have homogeneity in CA capability. Cerebral haemodynamic measurements in the UH were distinguishable between stroke subtype and severity, including the association between deteriorating ARI in UH with stroke severity. More studies are needed to determine their clinical significance and to understand the determinants of CA impairment in AIS patients.

Incomplete recovery of cerebral blood flow dynamics in sufficiently treated high blood pressure.

Objective:Whether cerebrovascular regulation is different in patients with controlled high blood pressure (HBP) with and without small vessel disease (SVD).Methods:Sixty-seven healthy controls (mean age ± SD, 45 ± 16 years; 30 women, 37 men) and 40 patients (mean age, 64 ± 13 years; 14 women, 26 men) with HBP and different stages of SVD, underwent simultaneous recordings of the spontaneous fluctuations of BP, blood flow velocity (CBFV) in both middle cerebral arteries (MCA), and of end-tidal CO2 (ETCO2). Coherence and transfer function gain and phase between BP and CBFV were assessed in the frequency ranges of VLF (0.02–0.07 Hz), low frequency (0.07–0.15), and high frequency (>0.15). BP SD indicated BP variability (BPV).Results:In controls (BP, 86 ± 13 mmHg; ETCO2, 39 ± 4 mmHg; BPV, 15 ± 6 mmHg), gain, phase and coherence were not age-dependent in simple or a multiple regression models. BPV correlated significantly in both MCAs with gain in low frequency and high frequency, and with phase in VLF and high frequency. In patients (BP, 91 ± 16 mmHg, ETCO2, 39 ± 4 mmHg, BPV 18 ± 5 mmHg), only gain showed some differences between different SVD groups. Comparing all patients with 25 controls of similar age and sex, patients exhibited significantly (P < 0.05–P < 0.005): increased coherence and gain in VLF, decreased phase in VLF and low frequency, correlations between BPV with phase in low frequency (left) and with gain in VLF (left) and in high frequency (left and right).Conclusion:Phase seems an age independent autoregulatory index. In controlled HBP, CBF regulation is degraded at longlasting CBF changes; BPV effects lose their physiological bilateral distribution.

Directional sensitivity of dynamic cerebral autoregulation in squat-stand maneuvers.

Dynamic cerebral autoregulation (CA), the transient response of cerebral blood flow (CBF) to rapid changes in arterial blood pressure (BP), is usually modeled as a linear mechanism. We tested the hypothesis that dynamic CA can display nonlinear behavior resulting from differential efficiency dependent on the direction of BP changes. Cerebral blood velocity (CBV) (transcranial Doppler), heart rate (HR) (three-lead ECG), continuous BP (Finometer), and end-tidal CO2 (capnograph) were measured in 10 healthy young subjects during 15 squat-stand maneuvers (SSM) with a frequency of 0.05 Hz. The protocol was repeated with a median (interquartile range) of 44 (35-64) days apart. Dynamic CA was assessed with the autoregulation index (ARI) obtained from CBV step responses estimated with an autoregressive moving-average model. Mean BP, HR, and CBV were different (all P < 0.001) between squat and stand, regardless of visits. ARI showed a strong interaction ( P < 0.001) of SSM with the progression of transients; in general, the mean ARI was higher for the squat phase compared with standing. The changes in ARI were partially explained by concomitant changes in CBV ( P = 0.023) and pulse pressure ( P < 0.001), but there was no evidence that ARI differed between visits ( P = 0.277). These results demonstrate that dynamic CA is dependent on the direction of BP change, but further work is needed to confirm if this finding can be generalized to other physiological conditions and also to assess its dependency on age, sex and pathology.

The Effects of Induction and Treatment of Intracranial Hypertension on Cerebral Autoregulation: An Experimental Study.

Background This study aimed to analyse cerebral autoregulation (CA) during induction and treatment of intracranial hypertension (ICH) in an experimental model. Materials and Methods Landrace and Duroc piglets were divided into mild and severe ICH groups. Four or seven millilitres of saline solution was infused into paediatric bladder catheter inserted in the parietal lobe (balloon inflation). After 1.5 h, a 3% saline solution was infused via venous catheter, and 30 min later, the bladder catheter balloon was deflated (surgery). The cerebral static autoregulation (sCA) index was evaluated using cerebral blood flow velocities (CBFV) obtained with Doppler ultrasound. Results Balloon inflation increased ICP in both groups. The severe ICH group showed significantly lower sCA index values (p=0.001, ANOVA) after balloon inflation (ICH induction) and a higher sCA index after saline injection (p=0.02) and after surgery (p=0.04). ICP and the sCA index were inversely correlated (r=−0.68 and p<0.05). CPP and the sCA index were directly correlated (r=0.74 and p<0.05). Conclusion ICH was associated with local balloon expansion, which triggered CA impairment, particularly in the severe ICH group. Moreover, ICP-reducing treatments were associated with improved CA in subjects with severe ICH.

Modelling the cerebral haemodynamic response in the physiological range of PaCO2

Objective: Arterial CO2 (PaCO2) has a strong effect on cerebral blood flow (CBF), but its influence on CBF regulatory mechanisms and circulatory systemic variables has not been fully described over the entire physiological range of PaCO2. Approach: CBF velocity (CBFV, transcranial Doppler), blood pressure (BP, Finometer) and end-tidal CO2 (EtCO2, capnography) were measured in 45 healthy volunteers (19 male, mean age 37.5 years, range 21–71) at baseline, and in response to hypo- (−5 mm Hg and −10 mm Hg below baseline) and hypercapnia (5% and 8% CO2), applied in random order. Main results: CBFV, cerebral dynamic autoregulation index (ARI), heart rate (HR), arterial blood pressure (ABP), critical closing pressure (CrCP) and resistance-area product (RAP) changed significantly (all p < 0.0001) for hypo- and hyper-capnia. These parameters were shown to follow a logistic curve relationship representing a ‘dose-response’ curve for the effects of PaCO2 on the cerebral and systemic circulations. The four logistic model parameters describing each ‘dose-response’ curve were specific to each of the modelled variables (ANOVA p < 0.0001). Significance: The ability to model the CBFV, ARI, HR, ABP, CrCP and RAP dependency of PaCO2 over its entire physiological range is a powerful tool for physiological and clinical studies, including the need to perform adjustments in disease populations with differing values of baseline PaCO2.

Dynamic Regulation of Cerebral Blood Flow in Patients With Alzheimer Disease.

Cerebral autoregulation and baroreflex sensitivity are key mechanisms that maintain cerebral blood flow. This study assessed whether these control mechanisms are affected in patients with dementia and mild cognitive impairment due to Alzheimer disease, as this would increase the risks of antihypertensive treatment. We studied 53 patients with dementia (73.1 years [95% confidence interval (CI), 71.4-74.8]), 37 patients with mild cognitive impairment (69.2 years [95% CI, 66.4-72.0]), and 47 controls (69.4 years [95% CI, 68.3-70.5]). Beat-to-beat blood pressure (photoplethysmography), heart rate, and cerebral blood flow velocity (transcranial Doppler) were measured during 5-minute rest (sitting) and 5 minutes of orthostatic challenges, using repeated sit-to-stand maneuvers. Cerebral autoregulation was assessed using transfer function analysis and the autoregulatory index. Baroreflex sensitivity was estimated with transfer function analysis and by calculating the heart rate response to blood pressure changes during the orthostatic challenges. Dementia patients had the lowest cerebral blood flow velocity (P=0.004). During rest, neither transfer function analysis nor the autoregulatory index indicated impairments in cerebral autoregulation. During the orthostatic challenges, higher autoregulatory index (P=0.011) and lower transfer function gain (P=0.017), indicating better cerebral autoregulation, were found in dementia (4.56 arb. unit [95% CI, 4.14-4.97]; 0.59 cm/s per mm Hg [95% CI, 0.51-0.66]) and mild cognitive impairment (4.59 arb. unit [95% CI, 4.04-5.13]; 0.51 cm/s per mm Hg [95% CI, 0.44-0.59]) compared with controls (3.71 arb. unit [95% CI, 3.35-4.07]; 0.67 cm/s per mm Hg [95% CI, 0.59-0.74]). Baroreflex sensitivity measures did not differ between groups. In conclusion, the key mechanisms to control blood pressure and cerebral blood flow are not reduced in 2 stages of Alzheimer disease compared with controls, both in rest and during orthostatic changes that reflect daily life challenges.

Cerebral Autoregulation in the Prediction of Delayed Cerebral Ischemia and Clinical Outcome in Poor-Grade Aneurysmal Subarachnoid Hemorrhage Patients.

Pressure reactivity index and oxygen reactivity index are used to assess cerebral autoregulation after acute brain injury. The value of autoregulation indices in the prediction of delayed cerebral ischemia and outcome in patients with subarachnoid hemorrhage is still inconclusive. In this study, we aimed to focus on the predictive value of the first 72 hours commonly referred to as "early brain injury" in comparison to the overall monitoring period. Retrospective observational cohort study. Neurocritical care unit at a tertiary academic medical center. Forty-three consecutive poor-grade patients with nontraumatic subarachnoid hemorrhage admitted between 2012 and 2016 undergoing continuous high-frequency monitoring. High-frequency monitoring includes arterial blood pressure, intracranial pressure, and brain tissue oxygen tension. Pressure reactivity index and oxygen reactivity index were evaluated as moving correlation coefficient between mean arterial pressure/intracranial pressure and cerebral perfusion pressure/brain tissue oxygen tension, respectively. Median autoregulation monitoring time was 188 ± 91 hours per patient. Initial pressure reactivity index was 0.31 ± 0.02 and decreased significantly to 0.01 ± 0.01 (p < 0.001) 3 days after admission with a second peak 10 days after admission (0.18 ± 0.14; p = 0.001). Admission oxygen reactivity index was high, 0.25 ± 0.03, and decreased to a minimum of 0.11 ± 0.02 eight days after admission (p = 0.008). Patients with delayed cerebral ischemia had significantly higher overall mean pressure reactivity index values (p < 0.04), which were more pronounced during the first 72 hours, reflecting early brain injury (p < 0.02). High pressure reactivity index during the first 72 hours was associated with poor functional outcome (p < 0.001). No association between oxygen reactivity index and delayed cerebral ischemia or clinical outcome was observed (p = 0.8/0.78). High initial pressure reactivity index, presumably reflecting early brain injury, but not oxygen reactivity index, was associated with delayed cerebral ischemia and worse clinical outcome in poor-grade subarachnoid hemorrhage patients. Our data indicate that autoregulation indices should be interpreted cautiously when used in these patients and that timing is crucial when autoregulation indices are evaluated as predictor for delayed cerebral ischemia and outcome.

Dynamic cerebral autoregulation is impaired during submaximal isometric handgrip in patients with heart failure.

The incidence of neurological complications, including stroke and cognitive dysfunction, is elevated in patients with heart failure (HF) with reduced ejection fraction. We hypothesized that the cerebrovascular response to isometric handgrip (iHG) is altered in patients with HF. Adults with HF and healthy volunteers were included. Cerebral blood velocity (CBV; transcranial Doppler, middle cerebral artery) and arterial blood pressure (BP; Finometer) were continuously recorded supine for 6 min, corresponding to 1 min of baseline and 3 min of iHG exercise, at 30% maximum voluntary contraction, followed by 2 min of recovery. The resistance-area product was calculated from the instantaneous BP-CBV relationship. Dynamic cerebral autoregulation (dCA) was assessed with the time-varying autoregulation index estimated from the CBV step response derived by an autoregressive moving-average time-domain model. Forty patients with HF and 23 BP-matched healthy volunteers were studied. Median left ventricular ejection fraction was 38.5% (interquartile range: 0.075%) in the HF group. Compared with control subjects, patients with HF exhibited lower time-varying autoregulation index during iHG, indicating impaired dCA ( P < 0.025). During iHG, there were steep rises in CBV, BP, and heart rate in control subjects but with different temporal patterns in HF, which, together with the temporal evolution of resistance-area product, confirmed the disturbance in dCA in HF. Patients with HF were more likely to have impaired dCA during iHG compared with age-matched control subjects. Our results also suggest an impairment of myogenic, neurogenic, and metabolic control mechanisms in HF. The relationship between impaired dCA and neurological complications in patients with HF during exercise deserves further investigation. NEW & NOTEWORTHY Our findings provide the first direct evidence that cerebral blood flow regulatory mechanisms can be affected in patients with heart failure during isometric handgrip exercise. As a consequence, eventual blood pressure modulations are buffered less efficiently and metabolic demands may not be met during common daily activities. These deficits in cerebral autoregulation are compounded by limitations of the systemic response to isometric exercise, suggesting that patients with heart failure may be at greater risk for cerebral events during exercise.

TNFα Impairs Cerebral Blood Flow Autoregulation in Pregnant Rats

Neurological symptoms are often reported among preeclamptic patients and cerebrovascular events account for ~40% of all preeclamptic/eclamptic‐related deaths. While cerebral blood flow (CBF) autoregulation is impaired in preeclamptic (PE) women as well as in placental ischemic rats which develop a PE‐like syndrome, the underlying mechanisms responsible for abnormal CBF autoregulation are unclear. Placental ischemic rats have higher levels of circulating cytokines, and we previously reported that tumor necrosis factor – alpha (TNFα), at levels that mimic TNFα in human preeclampsia, increases blood brain barrier (BBB) permeability and cerebral edema in pregnant rats. Therefore, we tested the hypothesis that TNFα alters CBF autoregulation in pregnant rats. To test this hypothesis, normal pregnant Sprague Dawley rats were infused with TNFα (200ng/day) and cerebral blood flow was measured by laser Doppler flowmetry under anesthesia. Rats were intubated and ventilated in order to maintain constant blood gasses and mean arterial pressure was elevated step‐wise from 100–190 mmHg by infusion of phenylephrine to determine changes in CBF. TNFα was found to impair CBF autoregulation in pregnant rats where CBF was significantly increased in TNFα‐infused rats at 180 mmHg (225±13 vs 173±8) and 190 mmHg (253±17 vs 188±9) compared to normal pregnant rats with no significant difference in peak CO2 between the two groups at 180 mmHg (44.9±0.8 vs 45.4±0.9 mmHg) or 190 mmHg (43±0.8 vs 45.3±0.9). Autoregulatory index (percent change in blood flow divided by percent change in perfusion pressure) was also significantly increased in TNFα‐infused rats at 180 mmHg (1.56±0.17 vs 0.91±0.11) and 190 mmHg (1.7±0.07 vs 0.99±0.11) compared to normal pregnant rats. These data suggest that circulating TNFα from the ischemic placenta could contribute to cerebrovascular complications during pregnancy and postpartum. TNFα could serve as a novel pharmacological target to ameliorate CBF autoregulation in preeclampsia.Support or Funding InformationThis study was supported by National Institutes of Health Grants, HLHL51971, HL136684‐A0, and an NRSA Institutional Training Grant, T32HL105324.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Defective renal autoregulation in the chronic bile duct ligation model of liver failure.

Cirrhosis of the liver is often associated with an impairment of renal function that is usually not associated with consistent structural abnormalities of the renal parenchyma, but is thought to be the functional consequence of arterial underfilling and reduced arterial blood pressure. We have used the cirrhosis model of chronic bile duct ligation (BDL) to assess the response of renal blood flow to a change of blood pressure. We have measured renal haemodynamics in BDL rats. Three weeks after BDL, rats showed elevated levels of total bilirubin, AST, and ALT as well as reduced arterial blood pressure. Creatinine clearance was significantly reduced, and plasma creatinine and urea nitrogen were elevated. Renal blood flow at baseline blood pressure was significantly lower in the BDL group than in the sham group. Clamp-induced reductions of renal perfusion pressure caused significantly greater changes of renal blood flow in BDL than control rats. The autoregulatory index over a comparable blood pressure range averaged 0.28 ± 0.35 in control rats and 1.26 ± 0.6 in BDL rats (p = 0.0004) indicating impairment of renal autoregulation in liver cirrhosis. Tubuloglomerular feedback (TGF) responses were significantly attenuated in BDL rats, especially in the subnormal flow range. Impairment of renal blood flow autoregulation, to some extent mediated by reduced TGF-mediated vasodilatation, may contribute to the renal vascular constrictor state in liver cirrhosis by preventing the full dilatory response to the blood pressure reduction.

Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage (BREATHE-ICH) study: a protocol for an experimental interventional study

IntroductionCerebral autoregulation (CA) is impaired in a multitude of neurological conditions. Increasingly, clinical studies are correlating the nature of this impairment with prognostic markers. In acute intracerebral haemorrhage (ICH), impairment...

Impaired cerebral microcirculation induced by ammonium chloride in rats is due to cortical adenosine release

Liver failure results in hyperammonaemia, impaired regulation of cerebral microcirculation, encephalopathy, and death. However, the key mediator that alters cerebral microcirculation remains unidentified. In this study we show that topically applied ammonium significantly increases periarteriolar adenosine tone on the brain surface of healthy rats and is associated with a disturbed microcirculation. Cranial windows were prepared in anaesthetized Wistar rats. The flow velocities were measured by speckle contrast imaging and compared before and after 30 min of exposure to 10 mM ammonium chloride applied on the brain surface. These flow velocities were compared with those for control groups exposed to artificial cerebrospinal fluid or ammonium plus an adenosine receptor antagonist. A flow preservation curve was obtained by analysis of flow responses to a haemorrhagic hypotensive challenge and during stepwise exsanguination. The periarteriolar adenosine concentration was measured with enzymatic biosensors inserted in the cortex. After ammonium exposure the arteriolar flow velocity increased by a median (interquartile range) of 21.7% (23.4%) vs. 7.2% (10.2%) in controls (n = 10 and n = 6, respectively, p <0.05), and the arteriolar surface area increased. There was a profound rise in the periarteriolar adenosine concentration. During the hypotensive challenge the flow decreased by 27.8% (14.9%) vs. 9.2% (14.9%) in controls (p <0.05). The lower limit of flow preservation remained unaffected, 27.7 (3.9) mmHg vs. 27.6 (6.4) mmHg, whereas the autoregulatory index increased, 0.29 (0.33) flow units per millimetre of mercury vs. 0.03 (0.21) flow units per millimetre of mercury (p <0.05). When ammonium exposure was combined with topical application of an adenosine receptor antagonist, the autoregulatory index was normalized. Vasodilation of the cerebral microcirculation during exposure to ammonium chloride is associated with an increase in the adenosine tone. Application of a specific adenosine receptor antagonist restores the regulation of the microcirculation. This indicates that adenosine could be a key mediator of the brain dysfunction seen during hyperammonaemia and is a potential therapeutic target. In patients with liver failure, disturbances in brain function are caused in part by ammonium toxicity. In our project we studied how ammonia, through adenosine release, affects the blood flow in the brain of rats. In our experimental model we demonstrated that the detrimental effect of ammonia on blood flow regulation was counteracted by blocking the adenosine receptors in the brain. With this observation we identified a novel potential treatment target. If we can confirm our findings in a future clinical study, this might help patients with liver failure and the severe condition called hepatic encephalopathy.

Intracranial and Extracranial Injury Burden as Drivers of Impaired Cerebrovascular Reactivity in Traumatic Brain Injury.

Impaired cerebrovascular reactivity has been associated with outcome following traumatic brain injury (TBI), but it is unknown how it is affected by trauma severity. Thus, we aimed to explore the relationship between intracranial (IC) and extracranial (EC) injury burden and cerebrovascular reactivity in TBI patients. We retrospectively included critically ill TBI patients. IC injury burden included detailed lesion and computerized tomography (CT) scoring (i.e., Marshall, Rotterdam, Helsinki, and Stockholm Scores) on admission. EC injury burden was characterized using the injury severity score (ISS) and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC were used to assess autoregulation/cerebrovascular reactivity. We used univariate and multi-variate logistic regression techniques to explore relationships between IC and EC injury burden and autoregulation indices. A total of 358 patients were assessed. ISS and all IC CT scoring systems were poor predictors of impaired cerebrovascular reactivity. Only subdural hematomas and thickness of subarachnoid hemorrhage (SAH; p < 0.05, respectively) were consistently associated with dysfunctional cerebrovascular reactivity. High age (p < 0.01 for all) and admission APACHE II scores (p < 0.05 for all) were the two variables most strongly associated with abnormal cerebrovascular reactivity. In summary, diffuse IC injury markers (thickness of SAH and the presence of a subdural hematoma) and APACHE II were most associated with dysfunction in cerebrovascular reactivity after TBI. Standard CT scoring systems and evidence of macroscopic parenchymal damage are poor predictors, implicating potentially both microscopic injury patterns and host response as drivers of dysfunctional cerebrovascular reactivity. Age remains a major variable associated with cerebrovascular reactivity.

Does gradual change in head positioning affect cerebrovascular physiology?

We studied cerebral blood velocity (CBV), and associated hemodynamic parameters during gradual changes in head positioning in a nonstroke group. CBV (transcranial Doppler ultrasound), beat‐to‐beat blood pressure (BP, Finometer), and end‐tidal carbon dioxide (ETCO 2, capnography) were recorded between lying flat (0°) and sitting up (30°) head positions, in 18 volunteers (10 female, mean age, 57 ± 16 years), at two visits (12 ± 8 days). A significant reduction was found between 5‐min FLAT (0°) and 5‐min SIT (30°) positions in CBV (visit 1: 4.5 ± 3.3%, P = 0.006; visit 2: 4.1 ± 3.5%, P = 0.003), critical closing pressure (CrCP; visit 1: 15.5 ± 14.0%, P = 0.0002; visit 2: 14.1 ± 7.8%, P = 0.009) and BP (visit 1: 8.3 ± 7.4%, P = 0.001; visit 2: 11.0 ± 11.3%, P < 0.001). For 5 min segments of data, the autoregulation index and other hemodynamic parameters did not show differences either due to head position or visit. For 30 sec time intervals, significant differences were observed in the following: (BP, P < 0.001; dominant hemisphere (DH) CBV, P < 0.005; nondominant hemisphere (NDH) CBV, P < 0.005; DH CrCP, P < 0.001; NDH CrCP, P < 0.001; DH resistance area product (RAP), P = 0.002; NDH RAP, P = 0.033). Significant static changes in BP, CBV and CrCP, and large transient changes in key hemodynamic parameters occur during 0° to 30°, and vice versa, with reproducible results. Further studies are needed following acute ischemic stroke to determine if a similar responses is present.

Non-linear models for the detection of impaired cerebral blood flow autoregulation.

The ability to discriminate between normal and impaired dynamic cerebral autoregulation (CA), based on measurements of spontaneous fluctuations in arterial blood pressure (BP) and cerebral blood flow (CBF), has considerable clinical relevance. We studied 45 normal subjects at rest and under hypercapnia induced by breathing a mixture of carbon dioxide and air. Non-linear models with BP as input and CBF velocity (CBFV) as output, were implemented with support vector machines (SVM) using separate recordings for learning and validation. Dynamic SVM implementations used either moving average or autoregressive structures. The efficiency of dynamic CA was estimated from the model’s derived CBFV response to a step change in BP as an autoregulation index for both linear and non-linear models. Non-linear models with recurrences (autoregressive) showed the best results, with CA indexes of 5.9 ± 1.5 in normocapnia, and 2.5 ± 1.2 for hypercapnia with an area under the receiver-operator curve of 0.955. The high performance achieved by non-linear SVM models to detect deterioration of dynamic CA should encourage further assessment of its applicability to clinical conditions where CA might be impaired.

Abstract TP211: Gray and White Matter Hemodynamics and Metabolism Measured Using Magnetic Resonance Imaging

Background: Reliable methods used to measure cerebral hemodynamics, metabolism and autoregulation are time-consuming and invasive. Objectives: We sought to measure cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ), in the whole brain, gray and white matter and detect physiological changes in humans under normal and ≈10% reductions in mean arterial pressure (MAP). Methods: CBF was measured using pseudo continuous arterial spin labeling (pCASL). OEF was measured using a MRI asymmetric spin echo-planar imaging (EPI). The arterial content of oxygen (CaO 2 ) was computed. CMRO 2 was calculated using the equation CMRO 2 =CaO 2 xCBFxOEF. Cerebral autoregulation was determined by measuring changes in CBF, OEF and CMRO 2 in response to ≈10% reductions in MAP in stroke-free controls induced by IV Nicardipine infusion. Autoregulation was measured in the whole brain, gray matter and white matter. Autoregulatory Index (AI) was computed using the equation AI = %CBF change/% MAP change supplemented by CBF associated OEF changes. Results: A total of 30 subjects were consented (Mean age 31, 93% male, 40% white, 43% black and 17% others). At baseline, CBF was measured in the whole brain (52.5±9.5 ml/100g/min), gray matter (72.0±13.0 ml/100g/min) and white matter (30.2±8.4 ml/100g/min). OEF was measured in the whole brain (0.32±0.02), gray matter (0.33±0.02) and white matter (0.30±0.01). CMRO 2 was measured in the whole brain (3.2±0.8 ml/100g/min), gray matter (4.6±1.1 ml/100g/min) and white matter (1.8±0.5 ml/100g/min). A target of 10% MAP lowering was successfully achieved in 18 subjects, resulting in a change of mean CBF in the whole brain (52 vs. 50, p=0.1), gray matter (72 vs. 69, p=0.2) and white matter (30 vs. 28, p=0.08). This translated to a AI of 0.3 ± 0.9 in the whole brain, 0.2±1.0 in the gray matter and 0.5±1.7 in the white matter. These CBF changes corroborated with no significant changes in OEF and CMRO 2 . Conclusions: MR measurement of CBF, OEF and CMRO 2 , in the whole brain, gray and white matter was comparable to measures obtained by invasive methods. Differences in these measures, as well as AI in the gray and white matter, may help understand cerebrovascular diseases that affect white matter such as lacunar strokes.

Abstract TP403: Effect of Hypercapnia on Dynamic Cerebral Autoregulation During Transient Hypotension

Background and Purpose: Hypercapnia leads to increased cerebral blood flow and impaired autoregulation by changing the cerebrovascular resistance (CVR). We studied the effect of hypercapnia on critical closing pressure (CCP) and resistance area product (RAP) which effectively reflects the role of vascular tone and resistance respectively in altering cerebrovascular resistance and maintaining cerebral autoregulation during transient hypotension. Methods: –26 healthy subjects had continuous cerebral blood flow velocity and arterial blood pressure recording. Transient hypotension was induced by sudden release of thigh cuff after suprasystolic inflation for 3 minutes. 3 trials of thigh cuff maneuver were performed with normal breathing, 3% CO 2 breathing and 5% CO 2 breathing. CO 2 inhalation was given for last 45 seconds of thigh cuff maneuver and continued for 90 seconds after release. Autoregulatory Index (ARI) was calculated for each trial with Tieck’s model. CCP and RAP were computed for 10 seconds’ window each at 1 minute after inflation (Baseline), immediately before release (Prerelease) and immediately after release (Release) of inflated thigh cuff. Results: –ARI values decreased significantly (p &lt; 0.0001) from 5.46 ± 1.47 to 2.0 ± 1.35 and 1.63 ± 1.09 during 3% CO 2 and 5% CO 2 trial respectively. No significant changes were observed in CCP value during thigh cuff release with all three trials. RAP significantly dropped from prerelease value after thigh cuff release in all 3 trials. Drop in RAP attenuated during hypercapnia trial and had significant (p &lt; 0.0001) difference between RAP Prerelease – Release ( d RAP) for Normal breathing (0.20 ± 0.12) and 3% and 5 % CO 2 trials (0.089 ± 0.090, 0.081 ± 0.093). d RAP was significantly correlated (Spearmen r = 0.42, p = 0.0004) with the ARI values where higher d RAP had better autoregulation. Conclusion: – Cerebral autoregulation during transient hypotension acts by changing vascular resistance i.e. RAP without any effect on vascular tone i.e. CCP and had been suggested to reflect myogenic component of autoregulation to blood pressure changes. We concluded that hypercapnia leads to impairment of myogenic component of autoregulation during transient arterial blood pressure changes as suggested by attenuated d RAP.

Comparing Models of Spontaneous Variations, Maneuvers and Indexes to Assess Dynamic Cerebral Autoregulation.

We analyzed the performance of linear and nonlinear models to assess dynamic cerebral autoregulation (dCA) from spontaneous variations in healthy subjects and compared it with the use of two known maneuvers to abruptly change arterial blood pressure (BP): thigh cuffs and sit-to-stand. Cerebral blood flow velocity and BP were measured simultaneously at rest and while the maneuvers were performed in 20 healthy subjects. To analyze the spontaneous variations, we implemented two types of models using support vector machine (SVM): linear and nonlinear finite impulse response models. The classic autoregulation index (ARI) and the more recently proposed model-free ARI (mfARI) were used as measures of dCA. An ANOVA analysis was applied to compare the different methods and the coefficient of variation was calculated to evaluate their variability. There are differences between indexes, but not between models and maneuvers. The mfARI index with the sit-to-stand maneuver shows the least variability. Support vector machine modeling of spontaneous variation with the mfARI index could be used for the assessment of dCA as an alternative to maneuvers to introduce large BP fluctuations.

KidsBrainIT: A New Multi-centre, Multi-disciplinary, Multi-national Paediatric Brain Monitoring Collaboration.

Validated optimal cerebral perfusion pressure (CPP) treatment thresholds in children do not exist. To improve the intensive care unit (ICU) management of the paediatric traumatic brain injury (TBI) population, we are forming a new paediatric multi-centre collaboration to recruit standardised ICU data for running and reporting upon models for assessing autoregulation and optimal CCP (CPPopt). We are adapting the adult BrainIT group's approach to develop a new Paediatric Brain Monitoring and Information Technology Group (KidsBrainIT), which will include a repository to store prospectively collected high-resolution physiological, clinical, and outcome data. In the first phase of this project there are 7 UK Paediatric Intensive Care Units, 1 Spanish, 1 Belgium, and 1 Romanian Centre interested in participating. In subsequent phases, we plan to open recruitment to other centres both within Europe, US and abroad. We are collaborating with the Leuven Group and plan to use their LAx (low-frequency autoregulation index), DATACAR (dynamic adaptive target of active cerebral autoregulation), CPPopt and visualisation methodologies. We also plan to use the continuous diffuse optical monitoring and tomography technology developed in Barcelona as an acute surrogate end-point for optimising brain perfusion. This technology allows non-invasive continuous monitoring of deep tissue perfusion and oxygenation in adults but its clinical application in infants and children with TBI has not been studied previously. We report on the current status of setting up this new collaboration and also on pilot analyses in two centres which are the basis of our rationale for the need for a prospective validation study of CPPopt in children. Specifically, we demonstrated that CPPopt varied with time for each patient during their paediatric intensive care unit (PICU) stay, and the median overall CPPopt levels for children aged 2-6 years, 7-11 years and 12-16 years were 68.83, 68.09, and 72.17 mmHg respectively. Among survivors and patients with favourable outcome (GOS 4 and 5), there were significantly higher proportions with CPP monitoring time within CPPopt (p = 0.04 and p = 0.01 respectively). There is a need and an interest in forming a multi-centre PICU collaboration for acquiring data and performing analyses for determining validated CPPopt thresholds in the paediatric TBI population. KidsBrainIT is being formed to meet that need.

Dynamic autoregulation of cerebral blood flow measured non-invasively with fast diffuse correlation spectroscopy

Cerebral autoregulation (CA) maintains cerebral blood flow (CBF) in the presence of systemic blood pressure changes. Brain injury can cause loss of CA and resulting dysregulation of CBF, and the degree of CA impairment is a functional indicator of cerebral tissue health. Here, we demonstrate a new approach to noninvasively estimate cerebral autoregulation in healthy adult volunteers. The approach employs pulsatile CBF measurements obtained using high-speed diffuse correlation spectroscopy (DCS). Rapid thigh-cuff deflation initiates a chain of responses that permits estimation of rates of dynamic autoregulation in the cerebral microvasculature. The regulation rate estimated with DCS in the microvasculature (median: 0.26 s−1, inter quartile range: 0.19 s−1) agrees well (R = 0.81, slope = 0.9) with regulation rates measured by transcranial Doppler ultrasound (TCD) in the proximal vasculature (median: 0.28 s−1, inter quartile range: 0.10 s−1). We also obtained an index of systemic autoregulation in concurrently measured scalp microvasculature. Systemic autoregulation begins later than cerebral autoregulation and exhibited a different rate (0.55 s−1, inter quartile range: 0.72 s−1). Our work demonstrates the potential of diffuse correlation spectroscopy for bedside monitoring of cerebral autoregulation in the microvasculature of patients with brain injury.