This study assesses the utility of a hybrid optical instrument for noninvasive transcranial monitoring in the neurointensive care unit. The instrument is based on diffuse correlation spectroscopy (DCS) for measurement of cerebral blood flow (CBF), and near-infrared spectroscopy (NIRS) for measurement of oxy- and deoxy-hemoglobin concentration. DCS/NIRS measurements of CBF and oxygenation from frontal lobes are compared with concurrent xenon-enhanced computed tomography (XeCT) in patients during induced blood pressure changes and carbon dioxide arterial partial pressure variation.
Seven neurocritical care patients were included in the study. Relative CBF measured by DCS (rCBFDCS), and changes in oxy-hemoglobin (ΔHbO2), deoxy-hemoglobin (ΔHb), and total hemoglobin concentration (ΔTHC), measured by NIRS, were continuously monitored throughout XeCT during a baseline scan and a scan after intervention. CBF from XeCT regions-of-interest (ROIs) under the optical probes were used to calculate relative XeCT CBF (rCBFXeCT) and were then compared to rCBFDCS. Spearman’s rank coefficients were employed to test for associations between rCBFDCS and rCBFXeCT, as well as between rCBF from both modalities and NIRS parameters.
rCBFDCS and rCBFXeCT showed good correlation (rs = 0.73, P = 0.010) across the patient cohort. Moderate correlations between rCBFDCS and ΔHbO2/ΔTHC were also observed. Both NIRS and DCS distinguished the effects of xenon inhalation on CBF, which varied among the patients.
DCS measurements of CBF and NIRS measurements of tissue blood oxygenation were successfully obtained in neurocritical care patients. The potential for DCS to provide continuous, noninvasive bedside monitoring for the purpose of CBF management and individualized care is demonstrated.
Near-infrared spectroscopy; Diffuse correlation spectroscopy; Cerebral blood flow; Xenon CT; Neurocritical care
Individualizing arterial blood pressure (ABP) targets during cardiopulmonary bypass (CPB) based on cerebral blood flow (CBF) autoregulation monitoring may provide a more effective means for preventing cerebral hypoperfusion than the current standard of care. Autoregulation can be monitored in real-time with transcranial Doppler (TCD). We have previously demonstrated that near infrared spectroscopy (NIRS) derived regional cerebral oxygen saturation (rScO2) provides a clinically suitable surrogate of CBF for autoregulation monitoring. The purpose of this study was to determine the accuracy of a stand-alone “plug-and-play” investigational system for autoregulation monitoring that uses a commercially available NIRS monitor with TCD methods.
TCD monitoring of middle cerebral artery CBF velocity and NIRS monitoring was performed in 70 patients during CPB. Indices of autoregulation were computed by both a personal computer-based system and an investigational prototype NIRS-based monitor. A moving linear correlation coefficient between slow waves of ABP and CBF velocity (mean velocity index, M×) and between ABP and rScO2 (cerebral oximetry index, CO×) were calculated. When CBF is autoregulated, there is no correlation between CBF and ABP; when CBF is dysregulated, M× and CO× approach 1 (i.e., CBF and ABP are correlated). Linear regression and bias analysis was performed between time-averaged values of M× and CO× derived from the personal computer-based system and from CO× measured with the prototype monitor. Values for M× and CO× were categorized in 5 mmHg bins of ABP for each patient. The lower limit of CBF autoregulation) was defined as the ABP where M× incrementally increased to ≥ 0.4.
There was correlation and good agreement between CO× derived from the prototype monitor and M× (r=0.510, 95% confidence interval [CI], 0.414 to 0.595, p<0.001; bias -0.07 ± 0.19). The correlation and bias between the personal computer-based CO× and CO× from the prototype NIRS monitor were r=0.957, 95% CI, 0.945 to 0.966, p<0.001 and 0.06±0.06, respectively. The average ABP at the lower limit of autoregulation was 63 ± 11 mmHg (95% prediction interval, 52 to 74 mmHg mmHg). While the mean ABP at the CO×-determined lower limit of autoregulation determined with the prototype monitor was statistically different from that determined by M× (59 ± 9 mmHg, 95% prediction interval, 50 to 68 mmHg, p=0.026), the difference is not likely clinically meaningful.
Monitoring CBF autoregulation with an investigational stand-alone NIRS monitor is correlated and in good agreement with TCD based methods. Availability of such a device would allow wide-spread autoregulation monitoring as a means of individualizing ABP targets during CPB.
Impaired cerebral autoregulation may predispose patients to cerebral hypoperfusion during cardiopulmonary bypass (CPB). The purpose of this study was to identify risk factors for impaired autoregulation during coronary artery bypass graft, valve surgery with CPB, or both and to evaluate whether near-infrared spectroscopy (NIRS) autoregulation monitoring could be used to identify this condition.
Two hundred and thirty-four patients were monitored with transcranial Doppler and NIRS. A continuous, moving Pearson's correlation coefficient was calculated between mean arterial pressure (MAP) and cerebral blood flow (CBF) velocity, and between MAP and NIRS data, to generate the mean velocity index (Mx) and cerebral oximetry index (COx), respectively. Functional autoregulation is indicated by an Mx and COx that approach zero (no correlation between CBF and MAP); impaired autoregulation is indicated by an Mx and COx approaching 1. Impaired autoregulation was defined as an Mx ≥0.40 at all MAPs during CPB.
Twenty per cent of patients demonstrated impaired autoregulation during CPB. Based on multivariate logistic regression analysis, time-averaged COx during CPB, male gender, , CBF velocity, and preoperative aspirin use were independently associated with impaired CBF autoregulation. Perioperative stroke occurred in six of 47 (12.8%) patients with impaired autoregulation compared with five of 187 (2.7%) patients with preserved autoregulation (P=0.011).
Impaired CBF autoregulation occurs in 20% of patients during CPB. Patients with impaired autoregulation are more likely than those with functional autoregulation to have perioperative stroke. Non-invasive monitoring autoregulation may provide an accurate means to predict impaired autoregulation.
Clinical trials registration. www.clinicaltrials.gov (NCT00769691).
cardiac surgery; cardiopulmonary bypass; cerebral autoregulation; stroke
To compare cerebral blood flow (CBF) autoregulation in patients undergoing continuous flow left ventricular assist device (LVAD) implantation with that in patients undergoing coronary artery bypass graft (CABG) surgery.
Prospective, observational, controlled study.
Academic medical center.
Fifteen patients undergoing LVAD insertion and 10 patients undergoing CABG surgery.
Measurements and Main Results
Cerebral autoregulation was monitored with transcranial Doppler and near-infrared spectroscopy (NIRS). A continuous, Pearson's correlation coefficient was calculated between mean arterial pressure (MAP) and CBF velocity, and between MAP and NIRS data rendering the variables mean velocity index (Mx) and cerebral oximetry index (COx), respectively. Mx and COx approach zero when autoregulation is intact (no correlation between CBF and MAP), but approach 1 when autoregulation is impaired. Mx was lower during and immediately after cardiopulmonary bypass (CPB) in the LVAD group than it was in the CABG surgery patients, indicating better preserved autoregulation. Based on COx monitoring, autoregulation tended to be better preserved in the LVAD group than in the CABG group immediately after surgery (p=0.0906). On postoperative day 1, COx was lower in LVAD patients than in CABG surgery patients, again indicating preserved CBF autoregulation (p=0.0410). Based on COx monitoring, 3 (30%) of the CABG patients had abnormal autoregulation (COx ≥ 0.3) on the first postoperative day but none of the LVAD patients had this abnormality (p=0.037).
These data suggest that CBF autoregulation is preserved during and immediately after surgery in patients undergoing LVAD insertion.
Clinical monitoring of cerebral blood flow (CBF) autoregulation in patients undergoing liver transplantation may provide a means for optimizing blood pressure to reduce the risk of brain injury. The purpose of this pilot project is to test the feasibility of autoregulation monitoring with transcranial Doppler (TCD) and near infrared spectroscopy (NIRS) in patients undergoing liver transplantation and to assess changes that may occur perioperatively.
We performed a prospective observational study in 9 consecutive patients undergoing orthotopic liver transplantation. Patients were monitored with TCD and NIRS. A continuous Pearson’s correlation coefficient was calculated between mean arterial pressure (MAP) and CBF velocity and between MAP and NIRS data, rendering the variables mean velocity index (Mx) and cerebral oximetry index (COx), respectively. Both Mx and COx were averaged and compared during the dissection phase, anhepatic phase, first 30 mins of reperfusion, and remaining reperfusion phase. Impaired autoregulation was defined as Mx ≥ 0.4.
Autoregulation was impaired in one patient during all phases of surgery, in two patients during the anhepatic phase, and in one patient during reperfusion. Impaired autoregulation was associated with a MELD score > 15 (p=0.015) and postoperative seizures or stroke (p<0.0001). Analysis of Mx categorized in 5-mmHg bins revealed that MAP at the lower limit of autoregulation (MAP when Mx increased to ≥ 0.4) ranged between 40 and 85 mmHg. Average Mx and average COx were significantly correlated (p=0.0029). The relationship between COx and Mx remained when only patients with bilirubin > 1.2 mg/dL were evaluated (p=0.0419). There was no correlation between COx and baseline bilirubin (p=0.2562) but MELD score and COx were correlated (p=0.0458). Average COx was higher for patients with a MELD score > 15 (p=0.073) and for patients with a neurologic complication than for patients without neurologic complications (p=0.0245).
These results suggest that autoregulation is impaired in patients undergoing liver transplantation, even in the absence of acute, fulminant liver failure. Identification of patients at risk for neurologic complications after surgery may allow for prompt neuroprotective interventions, including directed pressure management.
Acetazolamide (ACZ) was used to stimulate the cerebral vasculature on ten healthy volunteers to assess the cerebral vasomotor reactivity (CVR). We have combined near infrared spectroscopy (NIRS), diffuse correlation spectroscopy (DCS) and transcranial Doppler (TCD) technologies to non-invasively assess CVR in real-time by measuring oxy- and deoxy-hemoglobin concentrations, using NIRS, local cerebral blood flow (CBF), using DCS, and blood flow velocity (CBFV) in the middle cerebral artery, using TCD. Robust and persistent increases in oxy-hemoglobin concentration, CBF and CBFV were observed. A significant agreement was found between macro-vascular (TCD) and micro-vascular (DCS) hemodynamics, between the NIRS and TCD data, and also within NIRS and DCS results. The relative cerebral metabolic rate of oxygen, rCMRO2, was also determined, and no significant change was observed. Our results showed that the combined diffuse optics-ultrasound technique is viable to follow (CVR) and rCMRO2 changes in adults, continuously, at the bed-side and in real time.
(170.3660) Light propagation in tissues; (170.3890) Medical optics instrumentation; (170.6480) Spectroscopy, speckle; (170.7170) Ultrasound; (290.4210) Multiple scattering
Near-infrared spectroscopy (NIRS) is a non-invasive, real-time bedside modality sensitive to changes in cerebral perfusion and oxygenation and is highly sensitive to physiological oscillations at different frequencies. However, the clinical feasibility of NIRS remains limited, partly due to concerns regarding NIRS signal quantification, which relies on mostly arbitrary assumptions on hemoglobin concentrations and tissue layers. In this pilot study comparing stroke patients to healthy controls, we explored the utility of the interhemispheric correlation coefficient (IHCC) during physiological oscillations in detecting asymmetry in hemispheric microvascular hemodynamics.
Using bi-hemispheric continuous-wave NIRS, 12 patients with hemispheric strokes and 9 controls were measured prospectively. NIRS signal was band-pass filtered to isolate cardiac (0.7–3 Hz) and respiratory (0.15–0.7 Hz) oscillations. IHCCs were calculated in both oscillation frequency bands. Using Fisher’s Z-transform for non-Gaussian distributions, the IHCC during cardiac and respiratory oscillations were compared between both groups.
Nine patients and nine controls had data of sufficient quality to be included in the analysis. The IHCCs during cardiac and respiratory oscillations were significantly different between patients versus controls (cardiac 0.79 ± 0.18 vs. 0.94 ± 0.07, P = 0.025; respiratory 0.24 ± 0.28 vs. 0.59 ± 0.3; P = 0.016).
Computing the IHCC during physiological cardiac and respiratory oscillations may be a new NIRS analysis technique to quantify asymmetric microvascular hemodynamics in stroke patients in the neurocritical care unit. It allows each subject to serve as their own control obviating the need for arbitrary assumptions on absolute hemoglobin concentration. Future clinical applications may include rapid identification of patients with ischemic brain injury in the pre-hospital setting. This promising new analysis technique warrants further validation.
Near-infrared spectroscopy; Cerebrovascular disease; Stroke; Critical care
Functional near infrared spectroscopy (NIRS) is a non-invasive optical imaging technique used to monitor cerebral blood flow (CBF) and by proxy neuronal activation. The use of NIRS in nutritional intervention studies is a relatively novel application of this technique, with only a small, but growing, number of trials published to date. These trials—in which the effects on CBF following administration of dietary components such as caffeine, polyphenols and omega-3 polyunsaturated fatty acids are assessed—have successfully demonstrated NIRS as a sensitive measure of change in hemodynamic response during cognitive tasks in both acute and chronic treatment intervention paradigms. The existent research in this area has been limited by the constraints of the technique itself however advancements in the measurement technology, paired with studies endeavoring increased sophistication in number and locations of channels over the head should render the use of NIRS in nutritional interventions particularly valuable in advancing our understanding of the effects of nutrients and dietary components on the brain.
NIRS; nutrition; cognition; neuroimaging; intervention studies
A primary focus of neurointensive care is the prevention of secondary brain injury, mainly caused by ischemia. A noninvasive bedside technique for continuous monitoring of cerebral blood flow (CBF) could improve patient management by detecting ischemia before brain injury occurs. A promising technique for this purpose is diffuse correlation spectroscopy (DCS) since it can continuously monitor relative perfusion changes in deep tissue. In this study, DCS was combined with a time-resolved near-infrared technique (TR-NIR) that can directly measure CBF using indocyanine green as a flow tracer. With this combination, the TR-NIR technique can be used to convert DCS data into absolute CBF measurements. The agreement between the two techniques was assessed by concurrent measurements of CBF changes in piglets. A strong correlation between CBF changes measured by TR-NIR and changes in the scaled diffusion coefficient measured by DCS was observed (R2 = 0.93) with a slope of 1.05 ± 0.06 and an intercept of 6.4 ± 4.3% (mean ± standard error).
(170.1470) Blood or tissue constituent monitoring; (170.3660) Light propagation in tissues; (170.3890) Medical optics instrumentation
Animal studies have suggested that the reduction in stroke risk observed with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) therapy is owing to an increase in basal cerebral blood flow (CBF). The purpose of the study was to determine if statin therapy was associated with increased CBF in humans with cerebrovascular atherosclerotic disease. Quantitative measurements of CBF were obtained on study entry in 97 patients with carotid artery occlusion enrolled in a prospective study of cerebral hemodynamics and stroke risk. This study represents a post hoc analysis of CBF measurements based on whether patients were receiving statin therapy at the time of CBF measurement. Global and regional CBF (including hemispheric, basal ganglia, and arterial borderzones), and baseline clinical, epidemiologic, and laboratory stroke risk factors were compared between the two groups. Nineteen of the 97 patients were on a statin agent on study entry. The statin group was younger, had significantly lower LDL levels and included more women. Statin therapy was not associated with higher baseline values of CBF in global or regional analyses. Mean middle cerebral artery territory CBF (±s.d.) ipsilateral to the occluded carotid artery was 37.6±12.7 mL/100 g min for the statin group (n = 19) compared with 38.6±12.7 mL/100 g min for the nonstatin group (n = 78). Contralateral values were 42.9±13.5 and 44.2±13.3 mL/100 g min for the statin and nonstatin groups, respectively. We conclude that the stroke risk reduction observed with statin therapy in humans likely involves mechanisms other than an increased basal CBF.
atherosclerosis; CBF measurements; cerebral hemodynamics; cerebrovascular disease
Mean arterial blood pressure (MAP) targets are empirically chosen during cardiopulmonary bypass (CPB). We have previously shown that near-infrared spectroscopy (NIRS) can be used clinically for monitoring cerebral blood flow autoregulation. The hypothesis of this study was that real-time autoregulation monitoring using NIRS-based methods is more accurate for delineating the MAP at the lower limit of autoregulation (LLA) during CPB than empiric determinations based on age, preoperative history, and preoperative blood pressure.
Two hundred thirty-two patients undergoing coronary artery bypass graft and/or valve surgery with CPB underwent transcranial Doppler monitoring of the middle cerebral arteries and NIRS monitoring. A continuous, moving Pearson's correlation coefficient was calculated between MAP and cerebral blood flow velocity, and between MAP and NIRS data to generate mean velocity index and cerebral oximeter index. When autoregulated, there is no correlation between cerebral blood flow and MAP (i.e., mean velocity and cerebral oximetry indices approach 0); when MAP is below the LLA, mean velocity and cerebral oximetry indices approach 1. The LLA was defined as the MAP where mean velocity index increased with declining MAP to ≥ 0.4. Linear regression was performed to assess the relation between preoperative systolic blood pressure, MAP, MAP in 10% decrements from baseline, and average cerebral oximetry index with MAP at the LLA.
The MAP at the LLA was 66 mmHg (95% prediction interval, 43 to 90 mmHg) for the 225 patients in which this limit was observed. There was no relationship between preoperative MAP and the LLA (p = 0.829) after adjusting for age, gender, prior stroke, diabetes, and hypertension, but a cerebral oximetry index value of >0.5 was associated with the LLA (p=0.022). The LLA could be identified with cerebral oximetry index in 219 (94.4%) patients. The mean difference in the LLA for mean velocity index versus cerebral oximetry index was −0.2±10.2 mmHg (95%CI, −1.5 to 1.2 mmHg). Preoperative systolic blood pressure was associated with a higher LLA (p=0.046) but only for those with systolic blood pressure ≤160 mmHg.
There is a wide range of MAP at the LLA in patients during CPB making estimating this target difficult. Real-time monitoring of autoregulation with cerebral oximetry index may provide a more rational means for individualizing MAP during CPB.
Hemodynamic responses evoked by transcranial magnetic stimulation (TMS) can be measured with near-infrared spectroscopy (NIRS). This study demonstrates that cerebral neuronal activity is not their sole contributor. We compared bilateral NIRS responses following brain stimulation to those from the shoulders evoked by shoulder stimulation and contrasted them with changes in circulatory parameters. The left primary motor cortex of ten subjects was stimulated with 8-s repetitive TMS trains at 0.5, 1, and 2 Hz at an intensity of 75% of the resting motor threshold. Hemoglobin concentration changes were measured with NIRS on the stimulated and contralateral hemispheres. The photoplethysmograph (PPG) amplitude and heart rate were recorded as well. The left shoulder of ten other subjects was stimulated with the same protocol while the hemoglobin concentration changes in both shoulders were measured. In addition to PPG amplitude and heart rate, the pulse transit time was recorded. The brain stimulation reduced the total hemoglobin concentration (HbT) on the stimulated and contralateral hemispheres. The shoulder stimulation reduced HbT on the stimulated shoulder but increased it contralaterally. The waveforms of the HbT responses on the stimulated hemisphere and shoulder correlated strongly with each other (r = 0.65–0.87). All circulatory parameters were also affected. The results suggest that the TMS-evoked NIRS signal includes components that do not result directly from cerebral neuronal activity. These components arise from local effects of TMS on the vasculature. Also global circulatory effects due to arousal may affect the responses. Thus, studies involving TMS-evoked NIRS responses should be carefully controlled for physiological artifacts and effective artifact removal methods are needed to draw inferences about TMS-evoked brain activity.
Traumatic brain injury (TBI) causes an early reduction of cerebral blood flow (CBF). The purpose was to study cerebrovascular endothelial function by examining the reactivity of cerebral vessels to L-arginine.
Fifty-one patients with severe TBI were prospectively studied by measuring cerebral hemodynamics before and after the administration of L-arginine, 300 mg/kg at 12 hrs and at 48 hrs after injury. These hemodynamic measurements, using transcranial Doppler techniques, included internal carotid flow volume as an estimate of hemispheric cerebral blood flow, flow velocity in intracranial vessels, CO2 reactivity, and dynamic pressure autoregulation using thigh cuff deflation and carotid compression methods. Changes in the hemodynamics with L-arginine administration were analyzed using a general linear mixed model.
L-arginine produced no change in mean arterial pressure, intracranial pressure, or brain oxygenation. Overall, L-arginine induced an 11.3% increase in internal carotid artery flow volume (p= .0190). This increase was larger at 48 hrs than at 12 hrs (p= .0045), and tended to be larger in the less injured hemisphere at both time periods. The response of flow velocity in the intracranial vessels was similar, but smaller differences with administration of L-arginine were observed. There was a significant improvement in CO2 reactivity with L-arginine, but no change in dynamic pressure autoregulation.
The low response of the cerebral vessels to L-arginine at 12 hrs post-injury with improvement at 48hrs suggests that dysfunction of cerebrovascular endothelium plays a role in the reduced CBF observed after TBI.
cerebral autoregulation; endothelial dysfunction; L-arginine; nitric oxide; traumatic brain injury
Changes in cerebral blood flow (CBF) and cerebral metabolic rates (CMRO2) have been used as indices for changes in neuronal activity. Near-infrared spectroscopy (NIRS) can also measure cerebral haemodynamics and metabolic changes, enabling the possible use of multichannel recording of NIRS for functional optical imaging of human brain activity. Spatio-temporal variations of brain regions were demonstrated during various mental tasks. Non-synchronous behaviour of cerebral haemodynamics during the neuronal activation was observed. Gender- and handedness-dependent lateralization of the function between right and left hemispheres was demonstrated by simultaneous measurement using two NIR instruments during the mirror-drawing task. A lack of interhemispheric integration was observed with schizophrenic patients. These observations suggest an application for NIRS in psychiatric disease management, as an addition to clinical monitoring at the bedside. A time resolved 64-channel optical imaging system was constructed. This consisted of three picosecond laser diodes and 64 channels of TAC and CFD systems. Image reconstruction for phantom model systems was performed. Time-resolved quantitative optical imaging will become real in the very near future.
Cerebrovascular autoregulation after resuscitation has not been well studied in an experimental model of pediatric cardiac arrest. Furthermore, developing noninvasive methods of monitoring autoregulation using near-infrared spectroscopy (NIRS) would be clinically useful in guiding neuroprotective hemodynamic management after pediatric cardiac arrest. We tested the hypotheses that the lower limit of autoregulation (LLA) would shift to a higher arterial blood pressure between 1 and 2 days of recovery after cardiac arrest and that the LLA would be detected by NIRS-derived indices of autoregulation in a swine model of pediatric cardiac arrest. We also tested the hypothesis that autoregulation with hypertension would be impaired after cardiac arrest.
Data on LLA were obtained from neonatal piglets that had undergone hypoxic-asphyxic cardiac arrest and recovery for 1 day (n=8) or 2 days (n=8), or that had undergone sham surgery with 2 days of recovery (n=8). Autoregulation with hypertension was examined in a separate cohort of piglets that underwent hypoxic-asphyxic cardiac arrest (n=5) or sham surgery (n=5) with 2 days of recovery. After the recovery period, piglets were reanesthetized, and autoregulation was monitored by standard laser-Doppler flowmetry and autoregulation indices derived from NIRS (the cerebral oximetry [COx] and hemoglobin volume [HVx] indices). The LLA was determined by decreasing blood pressure through inflation of a balloon catheter in the inferior vena cava. Autoregulation during hypertension was evaluated by inflation of an aortic balloon catheter.
The LLAs were similar between sham-operated piglets and piglets that recovered for 1 or 2 days after arrest. The NIRS-derived indices accurately detected the LLA determined by laser-Doppler flowmetry. The area under the curve of the receiver operator characteristic curve for cerebral oximetry index was 0.91 at 1 day and 0.92 at 2 days after arrest. The area under the curve for hemoglobin volume index was 0.92 and 0.89 at the respective time points. During induced hypertension, the static rate of autoregulation, defined as the percent change in cerebrovascular resistance divided by the percent change in cerebral perfusion pressure, was not different between postarrest and sham-operated piglets. At 2 days recovery from arrest, piglets exhibited neurobehavioral deficits and histologic neuronal injury.
In a swine model of pediatric hypoxic-asphyxic cardiac arrest with confirmed brain damage, the LLA did not differ 1 and 2 days after resuscitation. The NIRS-derived indices accurately detected the LLA compared to laser-Doppler flow measurements at those time points. Autoregulation remained functional during hypertension.
Absent outcome data from randomized clinical trials, management of hypertension in acute ischaemic stroke remains controversial. Data from human participants have failed to resolve the question whether cerebral blood flow (CBF) in the peri-infarct region will decrease due to impaired autoregulation when systemic mean arterial pressure (MAP) is rapidly reduced.
Nine participants, 1–11 days after hemispheric ischaemic stroke, with systolic blood pressure more than 145 mmHg, underwent baseline PET measurements of regional CBF. Intravenous nicardipine infusion was then used to rapidly reduce mean arterial pressure 16 ± 7 mmHg and CBF measurement was repeated.
Compared with the contralateral hemisphere, there were no significant differences in the percent change in CBF in the infarct (P = 0.43), peri-infarct region (P = 1.00) or remainder of the ipsilateral hemisphere (P = 0.50). Two participants showed CBF reductions of greater than 19% in both hemispheres.
In this study, selective regional impairment of CBF autoregulation in the infarcted hemisohere to reduced systemic blood pressure was not a characteristic of acute cerebral infarction. Reductions in CBF did occur in some individuals, but it was bihemispheric phenomenon that likely was due to an upward shift of the autoregulatory curve as a consequence of chronic hypertension. These results indicate individual monitoring of changes in global CBF, such as with bedside transcranial Doppler, may be useful to determine individual safe limits when MAP is lowered in the setting of acute ischaemic stroke. The benefit of such an approach can only be demonstrated by clinical trials demonstrating improved patient outcome.
autoregulation; blood pressure; cerebral infarction; cerebrovascular circulation
Age is an important risk factor for perioperative cerebral complications such as stroke, postoperative cognitive dysfunction, and delirium. We explored the hypothesis that intraoperative cerebrovascular autoregulation is less efficient and brain tissue oxygenation lower in elderly patients, thus, increasing the vulnerability of elderly brains to systemic insults such as hypotension.
We monitored intraoperative cerebral perfusion in 50 patients aged 18–40 and 77 patients >65 yr at two Swiss university hospitals. Mean arterial pressure (MAP) was measured continuously using a plethysmographic method. An index of cerebrovascular autoregulation (Mx) was calculated based on changes in transcranial Doppler flow velocity due to changes in MAP. Cerebral oxygenation was assessed by the tissue oxygenation index (TOI) using near-infrared spectroscopy. End-tidal CO2, O2, and sevoflurane concentrations and peripheral oxygen saturation were recorded continuously. Standardized anaesthesia was administered in all patients (thiopental, sevoflurane, fentanyl, atracurium).
Autoregulation was less efficient in patients aged >65 yr [by 0.10 (se 0.04; P=0.020)] in a multivariable linear regression analysis. This difference was not attributable to differences in MAP, end-tidal CO2, or higher doses of sevoflurane. TOI was not significantly associated with age, sevoflurane dose, or Mx but increased with increasing flow velocity [by 0.09 (se 0.04; P=0.028)] and increasing MAP [by 0.11 (se 0.05; P=0.043)].
Our results do not support the hypothesis that older patients' brains are more vulnerable to systemic insults. The difference of autoregulation between the two groups was small and most likely clinically insignificant.
age groups; anaesthesia; cerebrovascular circulation
To investigate relationships between hemodynamic responses and neural activities in the somatosensory cortices, hemodynamic responses by near infrared spectroscopy (NIRS) and electroencephalograms (EEGs) were recorded simultaneously while subjects received electrical stimulation in the right median nerve. The statistical significance of the hemodynamic responses was evaluated by a general linear model (GLM) with the boxcar design matrix convoluted with Gaussian function. The resulting NIRS and EEGs data were stereotaxically superimposed on the reconstructed brain of each subject. The NIRS data indicated that changes in oxy-hemoglobin concentration increased at the contralateral primary somatosensory (SI) area; responses then spread to the more posterior and ipsilateral somatosensory areas. The EEG data indicated that positive somatosensory evoked potentials peaking at 22 ms latency (P22) were recorded from the contralateral SI area. Comparison of these two sets of data indicated that the distance between the dipoles of P22 and NIRS channels with maximum hemodynamic responses was less than 10 mm, and that the two topographical maps of hemodynamic responses and current source density of P22 were significantly correlated. Furthermore, when onset of the boxcar function was delayed 5–15 s (onset delay), hemodynamic responses in the bilateral parietal association cortices posterior to the SI were more strongly correlated to electrical stimulation. This suggests that GLM analysis with onset delay could reveal the temporal ordering of neural activation in the hierarchical somatosensory pathway, consistent with the neurophysiological data. The present results suggest that simultaneous NIRS and EEG recording is useful for correlating hemodynamic responses to neural activity.
SEP; NIRS; EEG; Dipole; Hemodynamic responses
Advances in medical and surgical care of the high-risk neonate have led to increased survival. A significant number of these neonates suffer from neurodevelopmental delays and failure in school. The focus of clinical research has shifted to understanding events contributing to neurological morbidity in these patients. Assessing changes in cerebral oxygenation and regulation of cerebral blood flow (CBF) is important in evaluating the status of the central nervous system. Traditional CBF imaging methods fail for both ethical and logistical reasons. Optical near infrared spectroscopy (NIRS) is increasingly being used for bedside monitoring of cerebral oxygenation and blood volume in both very low birth weight infants and neonates with congenital heart disease. Although trends in CBF may be inferred from changes in cerebral oxygenation and/or blood volume, NIRS does not allow a direct measure of CBF in these populations. Two relatively new modalities, arterial spin-labeled perfusion magnetic resonance imaging and optical diffuse correlation spectroscopy, provide direct, noninvasive measures of cerebral perfusion suitable for the high-risk neonates. Herein we discuss the instrumentation, applications, and limitations of these noninvasive imaging techniques for measuring and/or monitoring CBF.
infant cerebral blood flow; CBF; arterial spin labeled perfusion; MRI; PVL; optical spectroscopy
With the causes of perinatal brain injuries still unclear and the probable role of hemodynamic instability in their etiology, bedside monitoring of neonatal cerebral hemodynamics with standard values as a function of age are needed. In this study, we combined quantitative frequency domain near infrared spectroscopy (FD-NIRS) measures of cerebral tissue oxygenation (StO2) and cerebral blood volume (CBV) with diffusion correlation spectroscopy (DCS) measures of a cerebral blood flow index (CBFix) to test the validity of the CBV-CBF relationship in premature neonates and to estimate cerebral metabolic rate of oxygen (rCMRO2) with or without the CBFix measurement. We measured 11 premature neonates (28–34 weeks gestational age) without known neurological issues, once a week from one to six weeks of age. In nine patients, cerebral blood velocities from the middle cerebral artery were collected by transcranial Doppler (TCD) and compared with DCS values. Results show a steady decrease in StO2 during the first six weeks of life while CBV remains stable, and a steady increase in CBFix. rCMRO2 estimated from FD-NIRS remains constant but shows wide interindividual variability. rCMRO2 calculated from FD-NIRS and DCS combined increased by 40% during the first six weeks of life with reduced interindividual variability. TCD and DCS values are positively correlated. In conclusion, FD-NIRS combined with DCS offers a safe and quantitative bedside method to assess CBV, StO2, CBF, and rCMRO2 in the premature brain, facilitating individual follow-up and comparison among patients. A stable CBV-CBF relationship may not be valid for premature neonates.
premature neonates; brain hemodynamics; near-infrared spectroscopy; diffuse correlation spectroscopy; cerebral blood flow; cerebral oxygen consumption; brain development
Many studies have reported beneficial effects from the application of near-infrared (NIR) light photobiomodulation (PBM) to the body, and one group has reported beneficial effects applying it to the brain in stroke patients. We have reported that the measurement of a patient's left and right hemispheric emotional valence (HEV) may clarify data and guide lateralized treatments. We sought to test whether a NIR treatment could 1. improve the psychological status of patients, 2. show a relationship between immediate psychological improvements when HEV was taken into account, and 3. show an increase in frontal pole regional cerebral blood flow (rCBF), and 4. be applied without side effects.
We gave 10 patients, (5 M/5 F) with major depression, including 9 with anxiety, 7 with a past history of substance abuse (6 with an opiate abuse and 1 with an alcohol abuse history), and 3 with post traumatic stress disorder, a baseline standard diagnostic interview, a Hamilton Depression Rating Scale (HAM-D), a Hamilton Anxiety Rating Scale (HAM-A), and a Positive and Negative Affect Scale (PANAS). We then gave four 4-minute treatments in a random order: NIR to left forehead at F3, to right forehead at F4, and placebo treatments (light off) at the same sites. Immediately following each treatment we repeated the PANAS, and at 2-weeks and at 4-weeks post treatment we repeated all 3 rating scales. During all treatments we recorded total hemoglobin (cHb), as a measure of rCBF with a commercial NIR spectroscopy device over the left and the right frontal poles of the brain.
At 2-weeks post treatment 6 of 10 patients had a remission (a score ≤ 10) on the HAM-D and 7 of 10 achieved this on the HAM-A. Patients experienced highly significant reductions in both HAM-D and HAM-A scores following treatment, with the greatest reductions occurring at 2 weeks. Mean rCBF across hemispheres increased from 0.011 units in the off condition to 0.043 units in the on condition, for a difference of 0.032 (95% CI: -0.016, 0.080) units, though this result did not reach statistical significance. Immediately after treatment the PANAS improved to a significantly greater extent with NIR "on" relative to NIR "off" when a hemisphere with more positive HEV was treated than when one with more negative HEV was treated. We observed no side effects.
This small feasibility study suggests that NIR-PBM may have utility for the treatment of depression and other psychiatric disorders and that double blind randomized placebo-controlled trials are indicated.
ClinicalTrials.gov Identifier: NCT00961454
To determine whether mean arterial blood pressure (MAP) excursions below the lower limit of cerebral blood flow (CBF) autoregulation during cardiopulmonary bypass (CPB) are associated with acute kidney injury (AKI) after surgery.
Tertiary care medical center.
Four hundred ten patients undergoing cardiac surgery with CPB.
Prospective observational study.
Measurements and Main Results
Autoregulation was monitored during CPB by calculating a continuous, moving Pearson’s correlation coefficient between MAP and processed near-infrared spectroscopy signals to generate the variable cerebral oximetry index (COx). When MAP is below the lower limit of autoregulation, COx approaches 1, because CBF is pressure passive. An identifiable lower limit of autoregulation was ascertained in 348 patients. Based on the RIFLE criteria, AKI developed within 7 days of surgery in 121 (34.8%) of these patients. Although the average MAP during CPB did not differ, the MAP at the limit of autoregulation and the duration and degree to which MAP was below the autoregulation threshold (mmHg × min/hr of CPB) were both higher in patients with AKI than in those without AKI. Excursions of MAP below the lower limit of autoregulation (relative risk, 1.02, 95% confidence interval, 1.01 to 1.03, p<0.0001) and diabetes (relative risk, 1.78, 95% confidence interval, 1.27 to 2.50, p=0.001) were independently associated with for AKI.
Excursions of MAP below the limit of autoregulation and not absolute MAP are independently associated with for AKI. Monitoring COx may provide a novel method for precisely guiding MAP targets during CPB.
Cerebral autoregulation; blood pressure; cardiac surgery; acute kidney injury
Breath – holding (BH) is a suitable method for inducing cerebral vasomotor reactivity (VMR). The assessment of VMR is of clinical importance for the early detection of risk conditions and for the follow-up of disabled patients. Transcranial Doppler ultrasonography (TCD) is used to measure cerebral blood flow velocity (CBFV) during BH, whereas near-infrared spectroscopy (NIRS) measures the concentrations of the oxygenated (O2Hb) and reduced (CO2Hb) hemoglobin. The two techniques provide circulatory and functional-related parameters. The aim of the study is the analysis of the relationship between oxygen supply and CBFV as detected by TCD and NIRS in healthy subjects performing BH.
20 healthy subjects (15 males and 5 females, age 33 ± 4.5 years) underwent TCD and NIRS examination during voluntary breath – holding. VMR was quantified by means of the breath-holding index (BHI). We evaluated the BHI based on mean CBFV, O2Hb and CO2Hb concentrations, relating the baseline to post-stimulus values. To quantify VMR we also computed the slope of the linear regression line of the concentration signals during BH. From the NIRS signals we also derived the bidimensional representation of VMR, plotting the instantaneous O2Hb concentration vs the CO2Hb concentration during the BH phase. Two subjects, a 30 years old current smoker female and a 63 years old male with a ischemic stroke event at the left middle cerebral artery, were tested as case studies.
The BHI for the CBFV was equal to 1.28 ± 0.71 %/s, the BHI for the O2Hb to 0.055 ± 0.037 μmol/l/s and the BHI for CO2Hb to 0.0006 ± 0.0019 μmol/l/s, the O2Hb slope was equal to 0.15 ± 0.09 μmol/l/s and the CO2Hb slope to 0.09 ± 0.04 μmol/l/s. There was a positive correlation between the CBFV and the O2Hb increments during BH (r = 0.865). The bidimensional VMR pattern shows common features among healthy subjects that are lost in the control studies.
We show that healthy subjects present a common VMR pattern when counteracting cerebral blood flow perturbations induced by voluntary BH. The proposed methodology allows for the monitoring of changes in the VMR pattern, hence it could be used for assessing the efficacy of neurorehabilitation protocols.
Brain-mapping techniques have proven to be vital in understanding the molecular, cellular, and functional mechanisms of recovery after stroke. This article briefly summarizes the current molecular and functional concepts of stroke recovery and addresses how various neuroimaging techniques can be used to observe these changes. The authors provide an overview of various techniques including diffusion-tensor imaging (DTI), magnetic resonance spectroscopy (MRS), ligand-based positron emission tomography (PET), single-photon emission computed tomography (SPECT), regional cerebral blood flow (rCBF) and regional metabolic rate of glucose (rCMRglc) PET and SPECT, functional magnetic resonance imaging (fMRI), near infrared spectroscopy (NIRS), electroencephalography (EEG), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS). Discussion in the context of poststroke recovery research informs about the applications and limitations of the techniques in the area of rehabilitation research. The authors also provide suggestions on using these techniques in tandem to more thoroughly address the outstanding questions in the field.
DTI; EEG; fMRI; MEG; NIRS; PET; poststroke recovery; rehabilitation; SPECT; stroke; TMS
Using transcranial near-infrared spectroscopy (NIRS) to measure changes in the redox state of
cerebral cytochrome c oxidase (Δ[oxCCO]) during functional activation
in healthy adults is hampered by instrumentation and algorithm issues. This study reports the
Δ[oxCCO] response measured in such a setting and investigates possible confounders of
this measurement. Continuous frontal lobe NIRS measurements were collected from 11 healthy
volunteers during a 6-minute anagram-solving task, using a hybrid optical spectrometer (pHOS)
that combines multi-distance frequency and broadband components. Only data sets showing a
hemodynamic response consistent with functional activation were interrogated for a
Δ[oxCCO] response. Simultaneous systemic monitoring data were also available. Possible
influences on the Δ[oxCCO] response were systematically investigated and there was no
effect of: 1) wavelength range chosen for fitting the measured attenuation spectra; 2) constant
or measured, with the pHOS in real-time, differential pathlength factor; 3) systemic
hemodynamic changes during functional activation; 4) changes in optical scattering during
functional activation. The Δ[oxCCO] response measured in the presence of functional
activation was heterogeneous, with the majority of subjects showing significant increase in
oxidation, but others having a decrease. We conclude that the heterogeneity in the
Δ[oxCCO] response is physiological and not induced by confounding factors in the
(170.0170) Medical optics and biotechnology; (170.6510) Spectroscopy, tissue diagnostics; (170.2655) Functional monitoring and imaging; (170.1610) Clinical applications; (170.5380) Physiology; (300.6190) Spectrometers