Near-infrared spectroscopy--a new method for non-invasive monitoring of cerebral hemodynamics

Non-invasive techniques allow monitoring in prematures and newborns with the maxime of "minimal handling". Cerebral changes in oxi- and deoxihemoglobin and in total hemoglobin, which reflects the intracranial blood volume, can be monitored continuously by near infrared spectroscopy (NIRS) for the first time. As derived parameter the cerebral blood flow can be determined. With reservations the method allows to get a view of the cellular level by recorded changes of the cytochromeoxidase. This article gives a survey of the physics, the technique and shows the clinical application of the method.     

Near-infrared spectroscopy: theory and applications

In conclusion, NIRS appears to offer both a new monitoring modality and new information about cerebral oxygenation. Technical problems in the application of this technology persist, most notably determination of pathlength and the volume of tissue interrogated. Those familiar with the history of pulse oximetry will recall that although Millikan developed an ear oximeter in 1947, it was not until Aoyagi combined recognition of the pulse signal with spectroscopy in the 1970s that oximetry was transformed into a clinically applicable monitor. In much the same way, NIRS may find the same tremendous usefulness as a noninvasive monitor of cerebral oxygen utilization, pending resolution of the remaining technical problems.     

Measurement of regional blood oxygenation and cerebral hemodynamics

An echo planar linewidth mapping technique, Shufflebutt, has allowed temporal measurements of changes in linewidth caused by static inhomogeneities (delta LWSI) and transverse relaxation rate (delta R2) in models of hypoxia and hypercapnia. We demonstrate these changes are due to intravascular susceptibility differences/(delta chi) between the blood and tissue. Contrast agent injections at a delta chi equivalent to that of deoxygenated blood showed a twofold difference between the contrast agent and physiological anoxia values. Hypercapnia decreased both delta LWSI and delta R2 consistent with an increase in blood oxygenation. We attribute these findings to constant oxygen extraction during an increase in blood flow, resulting in less deoxygenated venous blood and thus reduced delta chi. For in vivo perturbations we found that delta R2/delta R2' approximately 0.33, a ratio much different from that measured in whole blood phantoms (delta R2/delta R2' approximately 2). This demonstrates that signal changes in these studies are produced predominantly by dephasing of extravascular protons due to field inhomogeneities produced by intravascular deoxygenated hemoglobin (deoxyHb).     

The extra- and intracranial correlations of cerebral hemodynamics

The transcranial Doppler method, at the present, allow us to study, in non-invasive way, the cerebral haemodynamics and its changes in case of extra- and intracranial vascular disease. The correlations between the intracranial data, obtained by means the transcranial doppler, and the informations, received by the duplex Doppler ultrasound and the color doppler ultrasonography, permit us to effect a complete and correct assessment of the cerebral circulation and to indicate an efficient medical or surgical therapy. The valuation of the compensatory intracranial circulation and the cerebral vasodilatator capacity is very important to establish the degree of cerebrovascular damage. Finally the transcranial Doppler allow us an indirect valuation of the intracranial lesion of the circle of Willis.     

Critical closing pressure explains cerebral hemodynamics during the Valsalva maneuver

Immunization with a particulate fraction of blood-stage antigens was shown previously to protect mice against Plasmodium yoelii malaria. To identify antigens inducing the protective response, sera from immunized mice were used to screen a P. yoelii cDNA expression library. Sequence analysis of one 2.6-kb cDNA clone indicated that the identified gene, pypag-1, encoded a novel plasmodial antigen. Two nonoverlapping regions of pypag-1 were expressed in Escherichia coli. The first recombinant antigen, pAg-1N, contained the N-terminal 337 residues, which included a putative transmembrane domain and a region relatively rich in tryptophan residues. The second recombinant antigen, pAg-1C, contained the remaining C-terminal 211 residues, which included 31 copies of a 5-amino-acid degenerative repeat. Immunoblot studies using rabbit antiserum raised against recombinant pAg-1N showed that the native pypAg-1 protein migrated at approximately 98 kDa, considerably slower than its predicted molecular mass of 66 kDa. Immunofluorescence studies localized the expression of the native pypAg-1 protein both to the cytoplasm and at the surface of P. yoelii-infected erythrocytes. Immunization with either pAg-1N or pAg-1C induced a four- to sevenfold reduction in P. yoelii blood-stage parasitemia. As such, pypAg-1 appears to contain at least two distinct protective epitopes. To our knowledge, this is the first characterization of a protective antigen of P. yoelii that is associated with the erythrocyte membrane.     

Age and sex differences in cerebral hemodynamics: a transcranial Doppler study

BACKGROUND AND PURPOSE: Hemodynamic factors seem to play an important role in the pathogenesis of cerebral ischemic events. The aim of this study was to evaluate whether changes in cerebrovascular reactivity occur in women after menopause. METHODS: Using transcranial Doppler ultrasonography, we studied the changes of flow velocity after hypercapnia in the middle cerebral arteries of 45 healthy premenopausal women (mean age, 32.3 years; range, 20 to 47 years) and 40 postmenopausal women (mean age, 54.4 years; range, 48 to 64 years). The same measurements were recorded in two groups of healthy male subjects age matched with premenopausal (45 subjects) and postmenopausal women (40 subjects). Moreover, a subgroup of postmenopausal women aged 48 to 53 years (15 subjects) were compared with a group of 15 premenopausal women of the same age. We obtained hypercapnia with breath holding and evaluated cerebrovascular reactivity with the breath-holding index (BHI). RESULTS: BHI was significantly lower in postmenopausal women (0.89+/-0.3) than in premenopausal women (1.59+/-0.3; P<0.0001) and in young (1.34+/-0.5; P<0.001) and old men (1.20+/-0.4; P<0.04). In the latter group, BHI was significantly lower than in premenopausal women (P<.0001). BHI values were also significantly lower in postmenopausal than in premenopausal women of the same age (0.81+/-0.1 versus 1.34+/-0.1; P<0.0001). CONCLUSIONS: These findings suggest that the large reduction of cerebrovascular reactivity in postmenopausal women cannot be considered a simple factor related to aging but is probably influenced by hormonal changes. The alteration in cerebrovascular regulation could be involved in the increase of cerebrovascular disease in postmenopausal women.     

Near-infrared measurement of cerebral oxygenation. Correlation with electroencephalographic ischemia during ventricular fibrillation

BACKGROUND: The application of phase-modulated near-infrared techniques for measurement of the oxygen saturation of cerebral tissue requires both validation by conventional measures of cerebral oxygenation and determination of normal and abnormal values. This study was undertaken to validate phase-modulated near-infrared measurements of cerebral oxygen saturation by comparing them with electroencephalographic evidence of cerebral ischemia during implantation of cardioverting defibrillators. This comparison also yields an estimate of the ischemic threshold as measured with near-infrared techniques. METHODS: Electroencephalograms and near-infrared measurements were performed during 85 episodes of ventricular fibrillation in ten patients. Light at 754, 785, and 816 nm was modulated at 200 MHz, transmitted through the skull, and the path lengths of the reflected light were determined by measuring the phase shifts. The electroencephalogram was inspected for changes during the hypotension associated with the arrhythmia and the oxygen saturation was calculated from the near-infrared path lengths. Changes in oxygen saturation were then compared with electroencephalographic evidence of cerebral ischemia. RESULTS: The mean saturation before fibrillation was 56.5% +/- 1.2 (SEM). In 40 (47%) of the events, electroencephalographic evidence of ischemia was observed. Such changes were related to the minimum saturation observed during ventricular fibrillation (44% +/- 2.5 vs. 56% +/- 1.9 in the absence of electroencephalographic changes; P < 0.001). The ischemic threshold was estimated to be 47% saturation. The sensitivity of this technique was estimated to be 0.6, the specificity 0.84, and the predictive accuracy 0.73. CONCLUSIONS: Near-infrared measurements reflect changes in cerebral oxygenation as indicated by electroencephalographic evidence of cerebral ischemia.     

Cerebral hemodynamics and oxygenation in the fetus. The role of intrapartum near-infrared spectroscopy

Current methods of intrapartum surveillance have made little impact on fetal mortality and morbidity while leading to increased caesarean section rates. Near-infrared spectroscopy is a powerful new technique that can continuously measure changes in fetal cerebral oxygenation and hemodynamics during labor. Data are presented suggest that near-infrared spectroscopy has potential as a new form of fetal monitoring. However, further technical developments and testing in clinical trials are necessary before its introduction into clinical practice.     

Collateral hemodynamics after middle cerebral artery occlusion in Wistar and Fischer-344 rats

We investigated whether the difference in infarction volume after occlusion of a long proximal segment of the middle cerebral artery between Wistar and Fischer-344 rats, is caused by differences in collateral blood flow rate through leptomeningeal anastomoses. In view of the retrograde direction of collateral blood flow into the middle cerebral artery territory, we developed parasagittal laser-Doppler flowmetry. Using this method two laser-Doppler probes are placed on the cerebral cortex: probe 1 is placed near the anastomoses between the middle- and anterior cerebral artery, probe 2 is placed 2 mm further away from these anastomoses than probe 1. We found in both rat strains a comparable relation between the areas under the curve of the signal measured by both laser-Doppler probes for 2 h after middle cerebral artery occlusion. This relation is considered to be a measurement of the collateral blood flow rate into the middle cerebral artery territory through leptomeningeal anastomoses after middle cerebral artery occlusion. We conclude that collateral blood flow for the two strains were essentially similar for the initial 2 h after MCA occlusion. Although these collateral blood flows could have been different at a later time, it is unlikely that the interstrain difference in cerebral infarction volume between Wistar and Fischer-344 rats after proximal middle cerebral artery occlusion is caused by an apparent interstrain difference in the magnitude of collateral blood flow rate through leptomeningeal anastomoses. The parasagittal laser-Doppler flowmetry technique we developed for these experiments is currently successfully used in our laboratory to evaluate the efficacy of hemodynamically active pharmacotherapeutical agents in raising the collateral blood flow rate into the middle cerebral artery territory after middle cerebral artery occlusion.     

Low cerebral blood flow and perfusion reserve induce hyperperfusion after surgical revascularization: case reports and analysis of cerebral hemodynamics

BACKGROUND: Hyperperfusion syndrome after surgical revascularization is a rare complication and there has not been any systematic study on factors that induce hyperperfusion after surgery. In this paper, we retrospectively analyzed the factors related to this syndrome. PATIENTS AND METHODS: We performed 46 cases of surgical revascularization including 33 cases of carotid endarterectomy (CEA) and 13 cases of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis during the past 5 years. Among these, we encountered three cases of hyperperfusion syndrome despite well-controlled blood pressure postoperatively. To evaluate factors related to the occurrence of hyperperfusion syndrome, we examined four parameters: (1) regional cerebral blood flow (rCBF), (2) the increase in the ratio of the postoperative rCBF compared to the preoperative rCBF (increase ratio), (3) cerebral perfusion reserve presented by the increase of rCBF after acetazolamide administration (delta rCBF), and (4) the difference in mean blood pressure between the preoperative and postoperative state (delta BP). RESULTS: Preoperative rCBF was significantly lower in cases of hyperperfusion syndrome than the control cases (p < 0.01 Mann-Whitney U-test). Moreover delta rCBF was evidently lower in the hyperperfusion cases than the control (p < 0.05 Fisher's exact method). However, there was no significant difference in the delta BP between the hyperperfusion cases and the control cases. CONCLUSION: In cases of marked low perfusion (low rCBF) with poor perfusion reserve (low delta rCBF), hyperperfusion after surgical revascularization can occur even if blood pressure is adequately controlled.     

Magnetic resonance imaging assessment of cerebral hemodynamics during spreading depression in rats

Cost-benefit and cost-effectiveness analyses (CEAs) are only now beginning to be used by business, government, and policymakers to evaluate various medical treatments. The evolution of why CEAs are being demanded is reviewed. To date, a formal CEA of obesity treatments has not been published. This article outlines how a CEA is performed, reviews data relevant to setting up a formal CEA of medical and surgical obesity treatments, and lists published reports that demonstrate the effectiveness of surgical obesity treatments. The general level of discrimination that society allows the obese to suffer also allows medical insurance companies, businesses, and government to not provide many obese Americans with obesity treatments that have established a level of effectiveness far surpassing many other forms of medical therapy. CEAs of obesity treatments, by themselves, cannot be expected to reverse this discrimination. This type of data, however, provides individual obese patients and their physicians with evidence to challenge policymakers' decisions, especially when cost-effective obesity treatments are excluded or placed at a lower priority than treatments with less proven effectiveness.     

Effects of cisatracurium on cerebral and cardiovascular hemodynamics in patients with severe brain injury

BACKGROUND: For neuroanesthesia and neurocritical care the use of drugs that do not increase or preferentially decrease intracranial pressure (ICP) or change cerebral perfusion pressure (CPP) and cerebral blood flow (CBF) are preferred. The current study investigates the effects of a single rapid bolus dose of cisatracurium on cerebral blood flow velocity, ICP, CPP, mean arterial pressure (MAP) and heart rate (HR) in 24 mechanically ventilated patients with intracranial hypertension after severe brain trauma (Glasgow coma scale <6) under continuous sedation with sufentanil and midazolam. METHODS: Patients were randomly assigned to receive either 2xED95 (n=12) or 4xED95 (n=12) of cisatracurium as a rapid i.v. bolus injection. Before and after bolus administration mean cerebral blood flow velocity (BFV, cm/s) was measured in the middle cerebral artery using a 2-MHz transcranial Doppler sonography system, ICP (mm Hg) was measured using an extradural probe, and MAP (mm Hg) and HR (b/min) were measured during a study period of 20 min. Cerebral perfusion pressure (CPP=MAP-ICP) was also calculated. RESULTS: Our data show that a single bolus dose of up to 4xED95 cisatracurium caused no significant (P<0.05) changes in BFV, ICP, CPP, MAP and HR. Possible histamine-related events were not observed during the study. CONCLUSIONS: The results from this study suggest that cisatracurium is a safe neuromuscular blocking agent for use in adult severe brain-injured patients with increased ICP under mild hyperventilation and continuous sedation.     

Effects of sufentanil on cerebral hemodynamics and intracranial pressure in patients with brain injury

BACKGROUND: The current study investigates the effects of sufentanil on cerebral blood flow velocity and intracranial pressure (ICP) in 30 patients with intracranial hypertension after severe brain trauma (Glasgow coma scale < 6). METHODS: Mechanical ventilation (FIO2 0.25-0.4) was adjusted to maintain arterial carbon dioxide tensions of 28-30 mmHg. Continuous infusion of midazolam (200 micrograms/kg/h intravenous) and fentanyl (2 micrograms/kg/h intravenous) was used for sedation. Mean arterial blood pressure (MAP, mmHg) was adjusted using norepinephrine infusion (1-5 micrograms/min). Mean blood flow velocity (Vmean, cm/s) was measured in the middle cerebral artery using a 2-MHz transcranial Doppler sonography system. ICP (mmHg) was measured using an epidural probe. After baseline measurements, a bolus of 3 micrograms/kg sufentanil was injected, and all parameters were continuously recorded for 30 min. The patients were assigned retrospectively to the following groups according to their blood pressure responses to sufentanil: group 1, MAP decrease of less than 10 mmHg, and group 2, MAP decrease of more than 10 mmHg. RESULTS: Heart rate, arterial blood gases, and esophageal temperature did not change over time in all patients. In 18 patients, MAP did not decrease after sufentanil (group 1). In 12 patients, sufentanil decreased MAP > 10 mmHg from baseline despite norepinephrine infusion (group 2). ICP was constant in patients with maintained MAP (group 1) but was significantly increased in patients with decreased MAP. Vmean did not change with sufentanil injection regardless of changes in MAP. CONCLUSIONS: The current data show that sufentanil (3 micrograms/kg intravenous) has no significant effect on middle cerebral artery blood flow velocity and ICP in patients with brain injury, intracranial hypertension, and controlled MAP. However, transient increases in ICP without changes in middle cerebral artery blood flow velocity may occur concomitant with decreases in MAP. This suggests that increases in ICP seen with sufentanil may be due to autoregulatory decreases in cerebral vascular resistance secondary to systemic hypotension.     

Near-infrared spectroscopy for monitoring of tissue oxygenation of exercising skeletal muscle in a chronic compartment syndrome model

Variations in the levels of muscle hemoglobin and of myoglobin oxygen saturation can be detected non-invasively with near-infrared spectroscopy. This technique could be applied to the diagnosis of chronic compartment syndrome, in which invasive testing has shown increased intramuscular pressure associated with ischemia and pain during exercise. We simulated chronic compartment syndrome in ten healthy subjects (seven men and three women) by applying external compression, through a wide inflatable cuff, to increase the intramuscular pressure in the anterior compartment of the leg. The tissue oxygenation of the tibialis anterior muscle was measured with near-infrared spectroscopy during gradual inflation of the cuff to a pressure of forty millimeters of mercury (5.33 kilopascals) during fourteen minutes of cyclic isokinetic dorsiflexion and plantar flexion of the ankle. The subjects exercised with and without external compression. The data on tissue oxygenation for each subject then were normalized to a scale of 100 per cent (the baseline value, or the value at rest) to 0 per cent (the physiological minimum, or the level of oxygenation achieved by exercise to exhaustion during arterial occlusion of the lower extremity). With external compression, tissue oxygenation declined at a rate of 1.4 +/- 0.3 per cent per minute (mean and standard error) during exercise. After an initial decrease at the onset, tissue oxygenation did not decline during exercise without compression. The recovery of tissue oxygenation after exercise was twice as slow with compression (2.5 +/- 0.6 minutes) than it was without the use of compression (1.3 +/- 0.2 minutes).     

The effects of hemodilution on cerebral hemodynamics and oxygen consumption during nonpulsatile hypothermic cardiopulmonary bypass

The effects of hemodilution on cerebral hemodynamics and oxygen consumption during nonpulsatile hypothermic cardiopulmonary bypass (CPB) were investigated in 16 patients undergoing elective open heart surgery under CPB. They were divided into 2 groups; high (25%) (H) and low hematocrit (15%) (L) groups according to the hematocrit values during CPB. Simultaneous measurements of blood flow velocity in the middle cerebral artery (VMCA) and oxygen tension in the jugular venous bulb (PjvbO2) were performed at prebypass, bypass, and post bypass periods. There were no significant differences in nasopharyngeal temperature (NPT), cerebral perfusion pressure, pump flow rate, and PaCO2 between the two groups at any period. VMCA changed in correlation with NPT in both groups, and VMCA in the L group was faster than that in the H group at any period. PjvbO2 increased during aortic cross clamp, and decreased on rewarming in both groups. However, there were no significant differences in VMCA and PjvbO2 between the two groups at any period. These findings suggest that increased cerebral blood flow may compensate the decreased oxygen content due to the hemodilution during CPB. Therefore, the profound hemodilution up to 15% of hematocrit is considered to be a safe technique during CPB.