Cerebral Blood Flow Index Research Articles

Cerebral Hemodynamics at Altitude: Effects of Hyperventilation and Acclimatization on Cerebral Blood Flow and Oxygenation

Alterations in cerebral blood flow (CBF) and cerebral oxygenation are implicated in altitude-associated diseases. We assessed the dynamic changes in CBF and peripheral and cerebral oxygenation engendered by ascent to altitude with partial acclimatization and hyperventilation using a combination of near-infrared spectroscopy, transcranial Doppler ultrasound, and diffuse correlation spectroscopy. Peripheral (Spo2) and cerebral (Scto2) oxygenation, end-tidal carbon dioxide (ETCO2), and cerebral hemodynamics were studied in 12 subjects using transcranial Doppler and diffuse correlation spectroscopy (DCS) at 75 m and then 2 days and 7 days after ascending to 4559 m above sea level. After obtaining baseline measurements, subjects hyperventilated to reduce baseline ETCO2 by 50%, and a further set of measurements were obtained. Cerebral oxygenation and peripheral oxygenation showed a divergent response, with cerebral oxygenation decreasing at day 2 and decreasing further at day 7 at altitude, whereas peripheral oxygenation decreased on day 2 before partially rebounding on day 7. Cerebral oxygenation decreased after hyperventilation at sea level (Scto2 from 68.8% to 63.5%; P<.001), increased after hyperventilation after 2 days at altitude (Scto2 from 65.6% to 69.9%; P=.001), and did not change after hyperventilation after 7 days at altitude (Scto2 from 62.2% to 63.3%; P=.35). An intensification of the normal cerebral hypocapnic vasoconstrictive response occurred after partial acclimatization in the setting of divergent peripheral and cerebral oxygenation. This may help explain why hyperventilation fails to improve cerebral oxygenation after partial acclimatization as it does after initial ascent. The use of DCS is feasible at altitude and provides a direct measure of CBF indices with high temporal resolution.

Impact of kangaroo mother care on cerebral blood flow of preterm infants.

BackgroundKangaroo mother care (KMC) has been widely used to improve the care of preterms and low birth weight infants. However, very little is known about cerebral hemodynamics responses in preterm infants during KMC intervention. The aim of this study is to evaluate the changes of cerebral blood flow (CBF) in middle cerebral artery, before and after a 30 minute application of KMC in stable preterm infants.MethodsIt is a prospective, pre-post test without a control group study. CBF flow paremeters were measured with Doppler ultrasonography in one middle cerebral artery. Sixty preterm stable infants were assessed before and after 30 min KMC. CBF indices were assessed in different positions before KMC, forty neonates in supine position and 20 in vertical suspension (baby is held vertically away from the skin of his mother). Other dependent variables heart rate and mean arterial blood pressure and Spo2 were also studied before and after KMC.ResultsThe mean gestational age of the infants was (32 ± 2 weeks), and mean birth weight was (2080 ± 270 gm). Comparing CBF indices (Pulsatility index and Resistive index) before and after KMC has shown a significant decrease in both Pulsatility index (PI) and Resistive index (RI) after 30 min. KMC, the mean values were (2.0 ± 0.43 vs 1.68 ± 0.33 & 0.81 ± 0.05 vs 0.76 ± 0.06 respectively P < 0.05*) with mean difference (0.32 & 95% CI 0.042-0.41 & 0.05 & 95% CI 0.04 to 0.06 respectively P < 0.05*) and increase in end diastolic velocity & mean velocity 30 min of KMC (10.97 ± 4.63 vs. 15.39 ± 5.66 P < 0.05*& 25.66 ± 10.74 vs. 32.86 ± 11.47 P < 0.05* ) with mean difference (− 4.42 & 95% CI −5.67 to −3.18 and −7.21 & 95% CI - 9.41 to 5.00 respectively). These changes indicate improvement in CBF. No correlation has been found between CBF parameters and studied vital signs or SpO2.ConclusionKangaroo mother care improves cerebral blood flow, thus it might influence the structure and promote development of the premature infant's brain.

PO-0439 Evaluation Of The Cerebral Blood Flow In Children With Perinatal Cns Damage Born By Women With Diabetes Mellitus According To Data Of Transcranial Doppler Scanning

Background The leading position in the structure of high perinatal morbidity of children born by women with diabetes mellitus (DM) is taken by the perinatal damage of CNS. It is known that in pathogenesis of hypoxic-ischaemic damages of CNS in newborns the dominant role is assigned to vascular disorders. Aim To study of indices of the cerebral hemodynamics in such children. Methods 105 full-term children born by women with DM were examined: mothers of 55 children had DM of type 1, mothers of 50 children had gestational DM (GDM). The control group was comprised of 17 healthy children born by women with physiological pregnancy and delivery. The cerebral blood flow was evaluated by means of Doppler scanning of medial cerebral and anterior cerebral arteries, deep veins of Rozenthal circle (vein of Galen and basal veins of brain) using ultrasonographs. The children were examined and observed in dynamics during one year (in the early neonatal period in 1, 3, 6, 9 and 12 months of life). Results The perinatal CNS damage was diagnosed in all children both born by women with DM of type 1 and with GDM. In the majority of children neurological symptoms remained by the end of the first year of life despite of the provided treatment. The analysis of dynamics of the cerebral blood flow indices in medial cerebral and anterior cerebral arteries circulation showed the stable increase of resistance index during the whole period of observation as compared with the control values in the observed children (p Conclusions All children both born by women with diabetes mellitus of type 1 and with gestational diabetes mellitus have prolonged retained symptoms of the cerebral arteriovenous dysfunction, and it shall be considered with the purpose of optimisation of the pathogenetic therapy in such children.

INTEGRATION OF COGNITIVE TESTS AND RESTING STATE FMRI INDICES FOR THE IDENTIFICATION OF AMNESTIC MILD COGNITIVE IMPAIRMENT

WARM among the subjects of two sets of PET data from, respectively, 31 patients with dementia of Alzheimer’s type, and 28 healthy volunteers, compared to a conventional Standard Uptake Value Ratio (SUVR) index. Results: The discriminatory powers of binding potential (BP) and sCBF measures determined withWARM exceeded the power of SUVR. Estimated as the area under the curves (AUC) of the ROC of ten brain regions, the sCBFmeasure had the AUC closest to unity (Table). The discriminatory power of a measure ranges from AUC 0.5 (no discrimination) to AUC 1 (complete discrimination). The differences between the two groups, both of PIB retention and surrogate CBF index, were highly significant (P< 0.001), with the CBF index providing the greatest degree of discrimination between patients and healthy volunteers (Table). Conclusions: We conclude that WARM yields two important variables that independently discriminate among patients with Alzheimer’s disease and healthy volunteers with operating characteristics that are superior to conventional methods of analysis. Gjedde A, Aanerud J, Braendgaard H, Rodell A (2013) Front Aging Neurosci. http://dx.doi.org/10.3389/fnagi.2013.00070 Rodell A, Aanerud J, Braendgaard H, Gjedde A (2013) Front Aging Neurosci. http://dx.doi. org/10.3389/fnagi.2013.00045.

Transcranial Doppler to assess sepsis-associated encephalopathy in critically ill patients

BackgroundTranscranial Doppler can detect cerebral perfusion alteration in septic patients. We correlate static Transcranial Doppler findings with clinical signs of sepsis-associated encephalopathy.MethodsForty septic patients were examined with Transcranial Doppler on the first and third day of sepsis diagnosis. The pulsatility index (PI) and cerebral blood flow index (CBFi) were calculated by blood velocity in the middle cerebral artery (cm/sec). Patients underwent a daily cognitive assessment with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) test.ResultsTwenty-one patients (55%) were found to present confusion. The majority of the patients presented a PI > 1.1 (76%). PI on the first day (but not the third day) could predict a positive CAM-ICU test in septic patients (PI cut-off: 1.3, AUC: 0.905, p < 0.01, sensitivity: 95%, specificity: 88%, AUC: 0.618, p = 0.24). Multivariable analysis showed that PI on the first day is related to a positive CAM-ICU test independent of age and APACHE II score (OR: 5.6, 95% CI: 1.1-29, p = 0.03). A decrease of the PI on the third day was observed in the group that presented initially high PI (>1.3) (2.2 ± 0.71 vs. 1.81 ± 0.64; p = 0.02). On the other hand, an increase in PI was observed in the other patients (1.01 ± 0.15 vs. 1.58 ± 0.57; p < 0.01). On only the first day, the mean blood velocity in the middle cerebral artery and CBFi were found to be lower in those patients with a high initial PI (36 ± 21 vs. 62 ± 28 cm/sec; p < 0.01, 328 ± 101 vs. 581 ± 108; p < 0.01, respectively).ConclusionsCerebral perfusion disturbance observed with Transcranial Doppler could explain clinical symptoms of sepsis-associated encephalopathy.

Improvement of image quality and radiation dose of CT perfusion of the brain by means of low-tube voltage (70 KV).

To investigate the feasibility of 70 kV cerebral CT perfusion by comparing image quality and radiation exposure to 80 kV. Thirty patients with suspected cerebral ischemia who underwent dual-source CT perfusion were divided into group A (80 kV, 150 mAs) and group B (70 kV, 150 mAs). Quantitative comparisons were used for maximum enhancement, signal-to-noise index (SNI), and values of cerebral blood flow (CBF), cerebral blood flow (CBV), mean transit time (MTT) on CBF, CBV, and MTT images, and radiation dose from these two groups. Qualitative perfusion images were assessed by two readers. Maximum enhancement for group B was higher than group A (P < 0.05). There were no significant differences between the two groups for SNI on CBF and CBV maps (P = 0.06 - 0.576), but significant differences for MTT when SNI was measured on frontal white matter and temporo-occipital white matter (P < 0.05). There were no differences among values of CBF, CBV, and MTT for both groups (P = 0.251-0.917). Mean image quality score in group B was higher than group A for CBF (P < 0.05), but no differences for CBV (P = 0.542) and MTT (P = 0.962). Radiation dose for group B decreased compared with group A. 70 kV cerebral CT perfusion reduces radiation dose without compromising image quality. • Radiation dose is a key concern with the increased using cerebral CT perfusion. Cerebral CT perfusion of 70 kV reduces radiation dose without compromising image quality. • A 70-kV protocol could be used for cerebral CT perfusion.

AltitudeOmics: effect of ascent and acclimatization to 5260 m on regional cerebral oxygen delivery

Cerebral hypoxaemia associated with rapid ascent to high altitude can be life threatening; yet, with proper acclimatization, cerebral function can be maintained well enough for humans to thrive. We investigated adjustments in global and regional cerebral oxygen delivery (DO2) as 21 healthy volunteers rapidly ascended and acclimatized to 5260m. Ultrasound indices of cerebral blood flow in internal carotid and vertebral arteries were measured at sea level, upon arrival at 5260m (ALT1; atmospheric pressure 409mmHg) and after 16days of acclimatization (ALT16). Cerebral DO2 was calculated as the product of arterial oxygen content and flow in each respective artery and summed to estimate global cerebral blood flow. Vascular resistances were calculated as the quotient of mean arterial pressure and respective flows. Global cerebral blood flow increased by ∼70% upon arrival at ALT1 (P<0.001) and returned to sea-level values at ALT16 as a result of changes in cerebral vascular resistance. A reciprocal pattern in arterial oxygen content maintained global cerebral DO2 throughout acclimatization, although DO2 to the posterior cerebral circulation was increased by ∼25% at ALT1 (P=0.032). We conclude that cerebral DO2 is well maintained upon acute exposure and acclimatization to hypoxia, particularly in the posterior and inferior regions of the brain associated with vital homeostatic functions. This tight regulation of cerebral DO2 was achieved through integrated adjustments in local vascular resistances to alter cerebral perfusion during both acute and chronic exposure to hypoxia.

Cerebral oxygenation during the Richalet hypoxia sensitivity test and cycling time-trial performance in severe hypoxia

The Richalet hypoxia sensitivity test (RT), which quantifies the cardiorespiratory response to acute hypoxia during exercise at an intensity corresponding to a heart rate of ~130 bpm in normoxia, can predict susceptibility of altitude sickness. Its ability to predict exercise performance in hypoxia is unknown. Investigate: (1) whether cerebral blood flow (CBF) and cerebral tissue oxygenation (O2Hb; oxygenated hemoglobin, HHb; deoxygenated hemoglobin) responses during RT predict time-trial cycling (TT) performance in severe hypoxia; (2) if subjects with blunted cardiorespiratory responses during RT show greater impairment of TT performance in severe hypoxia. Thirteen men [27 ± 7 years (mean ± SD), Wmax: 385 ± 30 W] were evaluated with RT and the results related to two 15 km TT, in normoxia and severe hypoxia (FIO2 = 0.11). During RT, mean middle cerebral artery blood velocity (MCAv: index of CBF) was unaltered with hypoxia at rest (p > 0.05), while it was increased during normoxic (+22 ± 12 %, p < 0.05) and hypoxic exercise (+33 ± 17 %, p < 0.05). Resting hypoxia lowered cerebral O2Hb by 2.2 ± 1.2 μmol (p < 0.05 vs. resting normoxia); hypoxic exercise further lowered it to -7.6 ± 3.1 μmol below baseline (p < 0.05). Cerebral HHb, increased by 3.5 ± 1.8 μmol in resting hypoxia (p < 0.05), and further to 8.5 ± 2.9 μmol in hypoxic exercise (p < 0.05). Changes in CBF and cerebral tissue oxygenation during RT did not correlate with TT performance loss (R = 0.4, p > 0.05 and R = 0.5, p > 0.05, respectively), while tissue oxygenation and SaO2 changes during TT did (R = -0.76, p < 0.05). Significant correlations were observed between SaO2, MCAv and HHb during RT (R = -0.77, -0.76 and 0.84 respectively, p < 0.05 in all cases). CBF and cerebral tissue oxygenation changes during RT do not predict performance impairment in hypoxia. Since the changes in SaO2 and brain HHb during the TT correlated with performance impairment, the hypothesis that brain oxygenation plays a limiting role for global exercise in conditions of severe hypoxia remains to be tested further.

The effect of maternal supine position on umbilical and cerebral blood flow indices

ObjectiveThe brain sparing phenomenon in the fetus is a protective mechanism aimed at maintaining sufficient blood flow towards the brain during chronic or acute fetal stress, such as that caused by hypoxemia or utero-placental insufficiency. In this study we investigated whether the brain sparing effect can also be elicited by a physiological stress associated with maternal posture.Study design Twenty-three low-risk pregnant women participated in the study. Between 36 and 40 weeks’ gestation, Doppler flow velocity waveforms were obtained from the fetal middle cerebral and the umbilical artery in the supine and the left lateral decubitus positions. Pulsatility index, systolic/diastolic index, and peak systolic velocities were measured and comparison was made between the left lateral and supine positions. ResultsThe pulsatility index in the middle cerebral artery decreased from 1.78±0.27 in the left lateral decubitus position to 1.29±0.16 in supine position (p<0.0001). Peak systolic velocity decreased from 46.05±7.85cm/s to 39.43±7.95cm/s, respectively (p=0.001). The pulsatility index in the umbilical artery decreased from 0.89±0.13 in the left lateral position to 0.74±0.11 in the supine position (p<0.0001). ConclusionsThis study demonstrates that the supine position in late pregnancy, causing aortic and venacaval compression, leads to brain auto-regulation that activates the brain sparing effect in the fetus. This protective mechanism, shown here for the first time to be linked to a physiological stress, may provide the basis for a novel approach in the assessment of fetal wellbeing.

Quantitative cerebral perfusion assessment using microscope-integrated analysis of intraoperative indocyanine green fluorescence angiography versus positron emission tomography in superficial temporal artery to middle cerebral artery anastomosis.

Background:Intraoperative qualitative indocyanine green (ICG) angiography has been used in cerebrovascular surgery. Hyperperfusion may lead to neurological complications after superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis. The purpose of this study is to quantitatively evaluate intraoperative cerebral perfusion using microscope-integrated dynamic ICG fluorescence analysis, and to assess whether this value predicts hyperperfusion syndrome (HPS) after STA-MCA anastomosis.Methods:Ten patients undergoing STA-MCA anastomosis due to unilateral major cerebral artery occlusive disease were included. Ten patients with normal cerebral perfusion served as controls. The ICG transit curve from six regions of interest (ROIs) on the cortex, corresponding to ROIs on positron emission tomography (PET) study, was recorded. Maximum intensity (IMAX), cerebral blood flow index (CBFi), rise time (RT), and time to peak (TTP) were evaluated.Results:RT/TTP, but not IMAX or CBFi, could differentiate between control and study subjects. RT/TTP correlated (|r| = 0.534-0.807; P < 0.01) with mean transit time (MTT)/MTT ratio in the ipsilateral to contralateral hemisphere by PET study. Bland–Altman analysis showed a wide limit of agreement between RT and MTT and between TTP and MTT. The ratio of RT before and after bypass procedures was significantly lower in patients with postoperative HPS than in patients without postoperative HPS (0.60 ± 0.032 and 0.80 ± 0.056, respectively; P = 0.017). The ratio of TTP was also significantly lower in patients with postoperative HPS than in patients without postoperative HPS (0.64 ± 0.081 and 0.85 ± 0.095, respectively; P = 0.017).Conclusions:Time-dependent intraoperative parameters from the ICG transit curve provide quantitative information regarding cerebral circulation time with quality and utility comparable to information obtained by PET. These parameters may help predict the occurrence of postoperative HPS.

FLOW 800 Allows Visualization of Hemodynamic Changes After Extracranial-to-Intracranial Bypass Surgery but Not Assessment of Quantitative Perfusion or Flow

FLOW 800 delivers a color-coded map for snapshot visualization of the temporal distribution dynamics after indocyanine green angiography with post hoc calculation of FLOW 800-specific hemodynamic parameters. However, the value of these parameters regarding quantitative flow assessment remains unclear. To determine the value of FLOW 800-specific hemodynamic parameters in neurosurgical patients that permit assessment of hemodynamic changes within the microcirculation and macrocirculation. FLOW 800 was performed in 25 patients undergoing superficial temporal artery to middle cerebral artery bypass grafting and in 5 patients undergoing high- or intermediate-flow bypass grafting. The time to half-maximum fluorescence (t1/2max) and the cerebral blood flow index were calculated in the recipient vessel (macrocirculation) and the cortical territory (microcirculation) surrounding the anastomosis. For further evaluation, FLOW 800-specific hemodynamic parameters were compared with cortical laser speckle imaging and quantitative Doppler flow within the graft. FLOW 800 provided color-coded information on the temporospatial distribution dynamics of the dye with excellent assessment of bypass patency. In the recipient vessel and in the cortical territory surrounding the anastomosis, FLOW 800 detected hemodynamic changes after superficial temporal artery to middle cerebral artery bypass grafting in terms of a significant decrease in t1/2max and increase in cerebral blood flow index. Interestingly, comparison of t1/2max with semiquantitative laser speckle imaging-specific cortical perfusion within the microcirculation demonstrated poor agreement, and neither t1/2max nor the cerebral blood flow index within the graft correlated with quantitative graft flow assessed by Doppler. FLOW 800 may detect procedure-related hemodynamic changes within the microcirculation and macrocirculation but should not be used as a stand-alone tool for quantitative flow assessment.

Cerebral Oxygen Metabolism in Neonates with Congenital Heart Disease Quantified by MRI and Optics

Neonatal congenital heart disease (CHD) is associated with altered cerebral hemodynamics and increased risk of brain injury. Two novel noninvasive techniques, magnetic resonance imaging (MRI) and diffuse optical and correlation spectroscopies (diffuse optical spectroscopy (DOS), diffuse correlation spectroscopy (DCS)), were employed to quantify cerebral blood flow (CBF) and oxygen metabolism (CMRO(2)) of 32 anesthetized CHD neonates at rest and during hypercapnia. Cerebral venous oxygen saturation (S(v)O(2)) and CBF were measured simultaneously with MRI in the superior sagittal sinus, yielding global oxygen extraction fraction (OEF) and global CMRO(2) in physiologic units. In addition, microvascular tissue oxygenation (StO(2)) and indices of microvascular CBF (BFI) and CMRO(2) (CMRO(2)(i)) in the frontal cortex were determined by DOS/DCS. Median resting-state MRI-measured OEF, CBF, and CMRO(2) were 0.38, 9.7 mL/minute per 100 g and 0.52 mL O(2)/minute per 100 g, respectively. These CBF and CMRO(2) values are lower than literature reports for healthy term neonates (which are sparse and quantified using different methods) and resemble values reported for premature infants. Comparison of MRI measurements of global S(v)O(2), CBF, and CMRO(2) with corresponding local DOS/DCS measurements demonstrated strong linear correlations (R(2)=0.69, 0.67, 0.67; P<0.001), permitting calibration of DOS/DCS indices. The results suggest that MRI and optics offer new tools to evaluate cerebral hemodynamics and metabolism in CHD neonates.

Relationship between cardiac function and resting cerebral blood flow: MRI measurements in healthy elderly subjects

Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43.6 ml per 100 g min(-1), 5.5 l min(-1) and 2.7 l min(-1) m(-2), respectively, in males, and 53.4 ml per 100 g min(-1), 4.3 l min(-1) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender-related inverse association of increased low-to-high-frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender-related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease.

Depressive symptoms, atherosclerotic burden and cerebral blood flow disturbances in a cohort of octogenarian men from a general population

BackgroundThe aim of this study was to examine in elderly men a relationship between depressive symptoms, peripheral vascular disease and cerebral blood flow (CBF).MethodsPopulation-based cohort study started with an examination of 809 men at age 55, followed by the first (age 68ys) and second follow up (age 82ys). 128 survivors were examined at age 82 with 99mTc-HMPAO-SPECT to estimate CBF, Zung-Self-Rating-Depression Scale (ZSDS), and Ankle-Brachial Index (ABI). Analysis was performed on men free from stroke and dementia which defined the final study population to 120 subjects.ResultsZSDS in the whole cohort ranged from 0.26 to 0.71 (reference 0.25-1.0). As the frequency of depressive symptoms was low, the case group (n = 31) was defined by ZSDS index above 75th percentile (≥0.48), comprising 9 subjects with mild depression (ZSDS 0.55-0.71) and 22 subjects at 88th percentile and above of the normal range (ZSDS index 0.48-0.54). Cases were more often current smokers at age 68 (44% vs. 24%; p = .02) and had lower systolic blood presure (SBP), lower social and physical activity, and suffered from fatigue, nausea, freezing and leg edema at age 82. Within the case group, ZSDS-index correlated negatively with CBF in subcortical area (r = -.42*), left and right thalamus (r = -.40*, r = -.46**), and right basal nuclei (r = -.35*). ZSDS-index correlated also with ABI at age 82 (right leg r = -.40*; left leg r = -.37*), and with Δ between ABI at age 82 and 68 (right r = -.36*; left r = -.46**). Despite decreasing SBP from age 68 to 82, adjusted multiple regression analysis showed in the case group that higher SBP determined CBF changes in the frontal and parietal areas, independently of ZSDS index, Δ ABI, and smoking.ConclusionIn this population-based cohort of octogenarian men free from stroke or dementia, a proportion of subjects with depressive symptoms was low. Still, men with borderline or mild depression scores had lower social and physical activity, persistent smoking habit, worse peripheral circulation in legs, and cerebral perfusion changes in basal nuclei, thalamus and subcortical white matter. Regional CBF decline could be partly mediated by higher SBP.

The Effect of Adding CO2 to Hypoxic Inspired Gas on Cerebral Blood Flow Velocity and Breathing during Incremental Exercise

Hypoxia increases the ventilatory response to exercise, which leads to hyperventilation-induced hypocapnia and subsequent reduction in cerebral blood flow (CBF). We studied the effects of adding CO2 to a hypoxic inspired gas on CBF during heavy exercise in an altitude naïve population. We hypothesized that augmented inspired CO2 and hypoxia would exert synergistic effects on increasing CBF during exercise, which would improve exercise capacity compared to hypocapnic hypoxia. We also examined the responsiveness of CO2 and O2 chemoreception on the regulation ventilation (E) during incremental exercise. We measured middle cerebral artery velocity (MCAv; index of CBF), E, end-tidal PCO2, respiratory compensation threshold (RC) and ventilatory response to exercise (E slope) in ten healthy men during incremental cycling to exhaustion in normoxia and hypoxia (FIO2 = 0.10) with and without augmenting the fraction of inspired CO2 (FICO2). During exercise in normoxia, augmenting FICO2 elevated MCAv throughout exercise and lowered both RC onset andE slope below RC (P<0.05). In hypoxia, MCAv and E slope below RC during exercise were elevated, while the onset of RC occurred at lower exercise intensity (P<0.05). Augmenting FICO2 in hypoxia increased E at RC (P<0.05) but no difference was observed in RC onset, MCAv, or E slope below RC (P>0.05). The E slope above RC was unchanged with either hypoxia or augmented FICO2 (P>0.05). We found augmenting FICO2 increased CBF during sub-maximal exercise in normoxia, but not in hypoxia, indicating that the ‘normal’ cerebrovascular response to hypercapnia is blunted during exercise in hypoxia, possibly due to an exhaustion of cerebral vasodilatory reserve. This finding may explain the lack of improvement of exercise capacity in hypoxia with augmented CO2. Our data further indicate that, during exercise below RC, chemoreception is responsive, while above RC the ventilatory response to CO2 is blunted.

Cerebral Oxygen Metabolism in Neonatal Hypoxic Ischemic Encephalopathy during and after Therapeutic Hypothermia

Pathophysiologic mechanisms involved in neonatal hypoxic ischemic encephalopathy (HIE) are associated with complex changes of blood flow and metabolism. Therapeutic hypothermia (TH) is effective in reducing the extent of brain injury, but it remains uncertain how TH affects cerebral blood flow (CBF) and metabolism. Ten neonates undergoing TH for HIE and seventeen healthy controls were recruited from the NICU and the well baby nursery, respectively. A combination of frequency domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) systems was used to non-invasively measure cerebral hemodynamic and metabolic variables at the bedside. Results showed that cerebral oxygen metabolism (CMRO2i) and CBF indices (CBFi) in neonates with HIE during TH were significantly lower than post-TH and age-matched control values. Also, cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) were significantly higher in neonates with HIE during TH compared with age-matched control neonates. Post-TH CBV was significantly decreased compared with values during TH whereas SO2 remained unchanged after the therapy. Thus, FDNIRS-DCS can provide information complimentary to SO2 and can assess individual cerebral metabolic responses to TH. Combined FDNIRS-DCS parameters improve the understanding of the underlying physiology and have the potential to serve as bedside biomarkers of treatment response and optimization.

Cerebral Autoregulation of Blood Velocity and Volumetric Flow During Steady-State Changes in Arterial Pressure

The validity of using transcranial Doppler measurement of cerebral blood flow velocity (CBFV) to assess cerebral autoregulation (CA) still is a concern. This study measured CBFV in the middle cerebral artery using transcranial Doppler and volumetric cerebral blood flow (CBF) in the internal carotid artery (ICA) using color-coded duplex ultrasonography to assess CA during steady-state changes in mean arterial pressure (MAP). Twenty-one healthy adults participated. MAP was changed stepwise by intravenous infusion of sodium nitroprusside and phenylephrine. Changes in CBFV, CBF, cerebrovascular resistance (CVR=MAP/CBF), or cerebrovascular resistance index (CVRi=MAP/CBFV) were measured to assess CA by linear regression analysis. The relationship between changes in ICA diameter and MAP was assessed. All values were normalized as percentage changes from baseline. Drug-induced changes in MAP were from -26% to 31%. Changes in CBFV and CVRi in response to MAP were linear, and the regression slopes were similar between middle cerebral artery and ICA. However, CBF in ICA remained unchanged despite large changes in MAP. Consistently, a steeper slope of changes in CVR relative to CVRi was observed (0.991 versus 0.804; P<0.05). The ICA diameter changed inversely in response to MAP (r=-0.418; P<0.05). These findings indicate that CA can be assessed with transcranial Doppler measurements of CBFV and CVRi in middle cerebral artery. However, it is likely to be underestimated when compared with the measurements of CBF and CVR in ICA. The inverse relationship between changes in ICA diameter and MAP suggests that large cerebral arteries are involved in CA.

Transcranial doppler assessment of cerebral perfusion in critically ill septic patients: a pilot study

BackgroundThe aim of this study is to evaluate the feasibility and efficacy of Transcranial Doppler (TCD) in assessing cerebral perfusion changes in septic patients.MethodsUsing TCD, we measured the mean velocity in the middle cerebral artery (VmMCA, cm/sec) and calculated the pulsatility index (PI), resistance index (RI) and cerebral blood flow index (CBFi = 10*MAP/1.47PI) on the first day of patients’ admission or on the first day of sepsis development; measurements were repeated on the second day. Sepsis was defined according to standard criteria.ResultsForty-one patients without any known neurologic deficit treated in our 24-bed Critical Care Unit were assessed (Sepsis Group = 20, Control Group = 21). Examination was feasible in 91% of septic and 85% of non-septic patients (p = 0.89). No difference was found between the two groups in mean age, mean arterial pressure (MAP) or APACHE II score. The pCO2 values were higher in septic patients (46 ± 12 vs. 39 ± 4 mmHg p < 0.01). No statistically significant higher values of VmMCA were found in septic patients (110 ± 34 cm/sec vs. 99 ± 28 cm/sec p = 0.17). Higher values of PI and RI were found in septic patients (1.15 ± 0.25 vs. 0.98 ± 0.16 p < 0.01, 0.64 ± 0.08 vs. 0.59 ± 0.06 p < 0.01, respectively). No statistically significant lower values of CBFi were found in septic patients (497 ± 116 vs. 548 ± 110 p = 0.06).ConclusionsOur results suggest cerebral vasoconstriction in septic compared to non-septic patients. TCD is an efficient and feasible exam to evaluate changes in cerebral perfusion during sepsis.

Effect of end-tidal CO2 clamping on cerebrovascular function, oxygenation, and performance during 15-km time trial cycling in severe normobaric hypoxia: the role of cerebral O2 delivery

During heavy exercise, hyperventilation-induced hypocapnia leads to cerebral vasoconstriction, resulting in a reduction in cerebral blood flow (CBF). A reduction in CBF would impair cerebral O2 delivery and potentially account for reduced exercise performance in hypoxia. We tested the hypothesis that end-tidal Pco2 (PETCO2) clamping in hypoxic exercise would prevent the hypocapnia-induced reduction in CBF during heavy exercise, thus improving exercise performance. We measured PETCO2, middle cerebral artery velocity (MCAv; index of CBF), prefrontal cerebral cortex oxygenation (cerebral O2Hb; index of cerebral oxygenation), cerebral O2 delivery (DO2), and leg muscle oxygenation (muscle O2Hb) in 10 healthy men (age 27 ± 7 years; VO2max 63.3 ± 6.6 mL/kg/min; mean ± SD) during simulated 15-km time trial cycling (TT) in normoxia and hypoxia (FIO2 = 0.10) with and without CO2 clamping. During exercise, hypoxia elevated MCAv and lowered cerebral O2Hb, cerebral DO2, and muscle O2Hb (P < 0.001). CO2 clamping elevated PETCO2 and MCAv during exercise in both normoxic and hypoxic conditions (P < 0.001 and P = 0.024), but had no effect on either cerebral and muscle O2Hb (P = 0.118 and P = 0.124). Nevertheless, CO2 clamping elevated cerebral DO2 during TT in both normoxic and hypoxic conditions (P < 0.001). CO2 clamping restored cerebral DO2 to normoxic values during TT in hypoxia and tended to have a greater effect on TT performance in hypoxia compared to normoxia (P = 0.097). However, post hoc analysis revealed no effect of CO2 clamping on TT performance either in normoxia (P = 0.588) or in hypoxia (P = 0.108). Our findings confirm that the hyperventilation-induced hypocapnia and the subsequent drop in cerebral oxygenation are unlikely to be the cause of the reduced endurance exercise performance in hypoxia.

Interleaved imaging of cerebral hemodynamics and blood flow index to monitor ischemic stroke and treatment in rat by volumetric diffuse optical tomography

Diffuse optical tomography (DOT) has been used by several groups to assess cerebral hemodynamics of cerebral ischemia in humans and animals. In this study, we combined DOT with an indocyanine green (ICG)-tracking method to achieve interleaved images of cerebral hemodynamics and blood flow index (BFI) using two middle cerebral artery occlusion (MCAO) rat models. To achieve volumetric images with high-spatial resolution, we first integrated a depth compensation algorithm (DCA) with a volumetric mesh-based rat head model to generate three-dimensional (3D) DOT on a rat brain atlas. Then, the experimental DOT data from two rat models were collected using interleaved strategy for cerebral hemodynamics and BFI during and after ischemic stroke, with and without a thrombolytic therapy for the embolic MCAO model. The acquired animal data were further analyzed using the integrated rat-atlas-guided DOT method to form time-evolving 3D images of both cerebral hemodynamics and BFI. In particular, we were able to show and identify therapeutic outcomes of a thrombolytic treatment applied to the embolism-induced ischemic model. This paper demonstrates that volumetric DOT is capable of providing high-quality, interleaved images of cerebral hemodynamics and blood perfusion in small animals during and after ischemic stroke, with excellent 3D visualization and quantifications.