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Brain temperature, a crucial yet under-researched neurophysiological parameter, is governed by the equilibrium between cerebral oxygen metabolism and hemodynamics. Therapeutic hypothermia has been demonstrated as an effective intervention for acute brain injuries, enhancing survival rates and prognosis. The success of this treatment hinges on the precise regulation of brain temperature. However, the absence of comprehensive brain temperature monitoring methods during therapy, combined with a limited understanding of human brain heat transmission mechanisms, significantly hampers the advancement of hypothermia-based neuroprotective therapies. Leveraging the principles of bioheat transfer and MRI technology, this study conducted quantitative analyses of brain heat transfer during mild hypothermia therapy. Utilizing MRI, we reconstructed brain structures, estimated cerebral blood flow and oxygen consumption parameters, and developed a brain temperature calculation model founded on bioheat transfer theory. Employing computational cerebral hemodynamic simulation analysis, we established an intracranial arterial fluid dynamics model to predict brain temperature variations across different therapeutic hypothermia modalities. We introduce a noninvasive, spatially resolved, and optimized mathematical bio-heat model that synergizes model-predicted and MRI-derived data for brain temperature prediction and imaging. Our findings reveal that the brain temperature images generated by our model reflect distinct spatial variations across individual participants, aligning with experimentally observed temperatures., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: It remains unclear how a single bout of exercise affects brain perfusion, oxygen metabolism, and blood-brain barrier (BBB) permeability. Addressing this unresolved issue is essential to understand the acute changes in cerebral physiology induced by aerobic exercise., Purpose: To dynamically monitor the acute changes in cerebral physiology subsequent to a single aerobic exercise training session using noninvasive MRI measurements., Study Type: Prospective., Population: Twenty-three healthy participants (18-35 years, 10 females/13 males) were enrolled and divided into 10-minute exercising (N = 10) and 20-minute exercising (N = 13) groups., Field Strength/sequence: 3.0 T/Phase Contrast (PC) MRI (gradient echo), T 2 -Relaxation-Under-Spin-Tagging (TRUST) MRI (gradient echo EPI), Water-Extraction-with-Phase-Contrast-Arterial-Spin-Tagging (WEPCAST) MRI (gradient echo EPI) and T 1 -weighted magnetization-prepared-rapid-acquisition-of-gradient-echo (MPRAGE) (gradient echo)., Assessment: A baseline MR measurement plus four repeated MR measurements immediately after 10 or 20 minutes moderate running exercise. MR measurements included cerebral blood flow (CBF) as measured by PC MRI, venous oxygenation (Y v ) and cerebral metabolic rate of oxygen (CMRO 2 ) as assessed by TRUST MRI, water extraction fraction (E), and BBB permeability-surface-area product (PS) as determined by WEPCAST MRI., Statistical Tests: The time dependence of the physiological parameters was studied with a linear mixed-effect model. Additionally, pairwise t-tests comparison of the physiological parameters at each time point was conducted. A P-value of <0.05 was considered statistically significant., Results: There was an initial drop (8.22 ± 2.60%) followed by a recovery in CBF after exercise, while Y v revealed a significant decrease (6.37 ± 0.92%), i.e., an increased oxygen extraction, and returned to baseline at later time points. CMRO 2 showed a trend of increase (5.68 ± 3.04%) and a significant interaction between time and group. In addition, E increased significantly (3.86% ± 0.89) and returned to baseline level at later time points, while PS remained elevated (13.33 ± 4.79%)., Data Conclusion: A single bout of moderate aerobic exercise can induce acute alterations in cerebral perfusion, metabolism, and BBB permeability., Evidence Level: 2 TECHNICAL EFFICACY: Stage 2., (© 2024 International Society for Magnetic Resonance in Medicine.)

Perinatal hypoxic-ischaemic encephalopathy (HIE) is the leading cause of irreversible brain damage resulting in serious neurological dysfunction among neonates. We evaluated the feasibility of positron emission tomography (PET) methodology with 15 O-labelled gases without intravenous or tracheal cannulation for assessing temporal changes in cerebral blood flow ( CBF ) and cerebral metabolic rate for oxygen ( CMRO 2 ) in a neonatal HIE rat model. Sequential PET scans with spontaneous inhalation of 15 O-gases mixed with isoflurane were performed over 14 days after the hypoxic-ischaemic insult in HIE pups and age-matched controls. CBF and CMRO 2 in the injured hemispheres of HIE pups remarkably decreased 2 days after the insult, gradually recovering over 14 days in line with their increase found in healthy controls according to their natural maturation process. The magnitude of hemispheric tissue loss histologically measured after the last PET scan was significantly correlated with the decreases in CBF and CMRO 2. This fully non-invasive imaging strategy may be useful for monitoring damage progression in neonatal HIE and for evaluating potential therapeutic outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: First implementation of dynamic oxygen-17 ( 17 O) MRI at 7 Tesla (T) during neuronal stimulation in the human brain., Methods: Five healthy volunteers underwent a three-phase 17 O gas ( 17 O 2 ) inhalation experiment. Combined right-side visual stimulus and right-hand finger tapping were used to achieve neuronal stimulation in the left cerebral hemisphere. Data analysis included the evaluation of the relative partial volume (PV)-corrected time evolution of absolute 17 O water (H 2 17 O) concentration and of the relative signal evolution without PV correction. Statistical analysis was performed using a one-tailed paired t test. Blood oxygen level-dependent (BOLD) experiments were performed to validate the stimulation paradigm., Results: The BOLD maps showed significant activity in the stimulated left visual and sensorimotor cortex compared to the non-stimulated right side. PV correction of 17 O MR data resulted in high signal fluctuations with a noise level of 10% due to small regions of interest (ROI), impeding further quantitative analysis. Statistical evaluation of the relative H 2 17 O signal with PV correction (p = 0.168) and without (p = 0.382) did not show significant difference between the stimulated left and non-stimulated right sensorimotor ROI., Discussion: The change of cerebral oxygen metabolism induced by sensorimotor and visual stimulation is not large enough to be reliably detected with the current setup and methodology of dynamic 17 O MRI at 7 T., (© 2023. The Author(s).)

Methylene Blue (MB) is a brain-penetrating drug with putative neuroprotective, antioxidant and metabolic enhancing effects. In vitro studies suggest that MB enhances mitochondrial complexes activity. However, no study has directly assessed the metabolic effects of MB in the human brain. We used in vivo neuroimaging to measure the effect of MB on cerebral blood flow (CBF) and brain metabolism in humans and in rats. Two doses of MB (0.5 and 1 mg/kg in humans; 2 and 4 mg/kg in rats; iv) induced reductions in global cerebral blood flow (CBF) in humans (F (1.74, 12.17) 5.82, p = 0.02) and rats (F (1,5) 26.04, p = 0.0038). Human cerebral metabolic rate of oxygen (CMRO 2 ) was also significantly reduced (F (1.26, 8.84) 8.01, p = 0.016), as was the rat cerebral metabolic rate of glucose (CMRglu) (t = 2.6 (16) p = 0.018). This was contrary to our hypothesis that MB will increase CBF and energy metrics. Nevertheless, our results were reproducible across species and dose dependent. One possible explanation is that the concentrations used, although clinically relevant, reflect MB's hormetic effects, i.e., higher concentrations produce inhibitory rather than augmentation effects on metabolism. Additionally, here we used healthy volunteers and healthy rats with normal cerebral metabolism where MB's ability to enhance cerebral metabolism might be limited., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Infants born at 29-36 weeks gestational age (GA) are at risk of experiencing neurodevelopmental challenges. We hypothesize that cerebral hemodynamics and oxygen metabolism measured by bedside optical brain monitoring are potential biomarkers of brain development and are associated with neurological examination at term-equivalent age (TEA)., Methods: Preterm infants ( N = 133) born 29-36 weeks GA and admitted in the neonatal intensive care unit were enrolled in this prospective cohort study. Combined frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) were used from birth to TEA to measure cerebral hemoglobin oxygen saturation and an index of microvascular cerebral blood flow (CBF i ) along with peripheral arterial oxygen saturation (SpO 2 ). In combination with hemoglobin concentration in the blood, these parameters were used to derive cerebral oxygen extraction fraction (OEF) and an index of cerebral oxygen metabolism (CMRO 2 i ). The Amiel-Tison and Gosselin Neurological Assessment was performed at TEA. Linear regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and GA at birth. Logistic regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and neurological examination at TEA., Results: Steeper increases in CBF i ( p < 0.0001) and CMRO 2 i ( p = 0.0003) were associated with higher GA at birth. Changes in OEF, CBF i , and CMRO 2 i from birth to TEA were not associated with neurological examination at TEA., Conclusion: In this population, cerebral FDNIRS-DCS parameters were not associated with neurological examination at TEA. Larger increases in CBF i and CMRO 2 i from birth to TEA were associated with higher GA. Non-invasive bedside FDNIRS-DCS monitoring provides cerebral hemodynamic and metabolic parameters that may complement neurological examination to assess brain development in preterm infants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Côté-Corriveau, Simard, Beaulieu, Chowdhury, Gagnon, Gagnon, Ledjiar, Bernard, Nuyt, Dehaes and Luu.)

Objectives: Hemodynamic abnormalities and brain development disorders have been reported previously in fetuses and infants with transposition of the great arteries and intact ventricular septum (TGA-IVS). A ventricular septal defect (VSD) is thought to be an additional risk factor for adverse neurodevelopment, but literature describing this population is sparse. The objectives of this study were to assess fetal cardiac hemodynamics throughout pregnancy, to monitor cerebral hemodynamics and oxygen metabolism in neonates, and to compare these data between patients with TGA-IVS, those with TGA-VSD and age-matched controls., Methods: Cardiac hemodynamics were assessed in TGA-IVS and TGA-VSD fetuses and compared with healthy controls matched for gestational age (GA) during three periods: ≤ 22 + 5 weeks (GA1), 27 + 0 to 32 + 5 weeks (GA2) and ≥ 34 + 5 weeks (GA3). Left (LVO), right (RVO) and combined (CVO) ventricular outputs, ductus arteriosus flow (DAF, sum of ante- and retrograde flow in systole and diastole), diastolic DAF, transpulmonary flow (TPF) and foramen ovale diameter were measured. Aortic (AoF) and main pulmonary artery (MPAF) flows were derived as a percentage of CVO. Fetal middle cerebral artery and umbilical artery (UA) pulsatility indices (PI) were measured and the cerebroplacental ratio (CPR) was derived. Bedside optical brain monitoring was used to measure cerebral hemoglobin oxygen saturation (SO 2 ) and an index of microvascular cerebral blood flow (CBF i ), along with peripheral arterial oxygen saturation (SpO 2 ), in TGA-IVS and TGA-VSD neonates. Using hemoglobin (Hb) concentration measurements, these parameters were used to derive cerebral oxygen delivery and extraction fraction (OEF), as well as an index of cerebral oxygen metabolism (CMRO 2i ). These data were acquired in the early preoperative period (within 3 days after birth and following balloon atrial septostomy) and compared with those of age-matched healthy controls, and repeat measurements were collected before discharge when vital signs were stable., Results: LVO was increased in both TGA groups compared with controls throughout pregnancy. Compared with controls, TPF was increased and diastolic DAF was decreased in TGA-IVS fetuses throughout pregnancy, but only during GA1 and GA2 in TGA-VSD fetuses. Compared with controls, DAF was decreased in TGA-IVS fetuses throughout pregnancy and in TGA-VSD fetuses at GA2 and GA3. At GA2, AoF was higher in TGA-IVS and TGA-VSD fetuses than in controls, while MPAF was lower. At GA3, RVO and CVO were higher in the TGA-IVS group than in the TGA-VSD group. In addition, UA-PI was lower at GA2 and CPR higher at GA3 in TGA-VSD fetuses compared with TGA-IVS fetuses. Within 3 days after birth, SpO 2 and SO 2 were lower in both TGA groups than in controls, while Hb, cerebral OEF and CMRO 2i were higher. Preoperative SpO 2 was also lower in TGA-VSD neonates than in those with TGA-IVS. From preoperative to predischarge periods, SpO 2 and OEF increased in both TGA groups, but CBF i and CMRO 2i increased only in the TGA-VSD group. During the predischarge period, SO 2 was higher in TGA-IVS than in TGA-VSD neonates, while CBF i was lower., Conclusions: Fetal cardiac and neonatal cerebral hemodynamic/metabolic differences were observed in both TGA groups compared with controls. Compared to those with TGA-IVS, fetuses with TGA-VSD had lower RVO and CVO in late gestation. A higher level of preoperative hypoxemia was observed in the TGA-VSD group. Postsurgical cerebral adaptive mechanisms probably differ between TGA groups. Patients with TGA-VSD have a specific physiology that warrants further study to improve neonatal care and neurodevelopmental outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 International Society of Ultrasound in Obstetrics and Gynecology.)

Neural-vascular coupling (NVC) is the process by which oxygen and nutrients are delivered to metabolically active neurons by blood vessels. Murine models of NVC disruption have revealed its critical role in healthy neural function. We hypothesized that, in humans, aging exerts detrimental effects upon the integrity of the neural-glial-vascular system that underlies NVC. To test this hypothesis, calibrated functional magnetic resonance imaging (cfMRI) was used to characterize age-related changes in cerebral blood flow (CBF) and oxygen metabolism during visual cortex stimulation. Thirty-three younger and 27 older participants underwent cfMRI scanning during both an attention-controlled visual stimulation task and a hypercapnia paradigm used to calibrate the blood-oxygen-level-dependent signal. Measurement of stimulus-evoked blood flow and oxygen metabolism permitted calculation of the NVC ratio to assess the integrity of neural-vascular communication. Consistent with our hypothesis, we observed monotonic NVC ratio increases with increasing visual stimulation frequency in younger adults but not in older adults. Age-related changes in stimulus-evoked cerebrovascular and neurometabolic signal could not fully explain this disruption; increases in stimulus-evoked neurometabolic activity elicited corresponding increases in stimulus-evoked CBF in younger but not in older adults. These results implicate age-related, demand-dependent failures of the neural-glial-vascular structures that comprise the NVC system., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Cardiac surgery utilizing circulatory arrest is most commonly performed under deep hypothermia (∼18°C) to suppress tissue oxygen demand and provide neuroprotection during operative circulatory arrest. Studies investigating the effects of deep hypothermic circulatory arrest (DHCA) on neurodevelopmental outcomes of patients with congenital heart disease give conflicting results. Here, we address these issues by quantifying changes in cerebral oxygen saturation, blood flow, and oxygen metabolism in neonates during DHCA and investigating the association of these changes with postoperative brain injury. Neonates with critical congenital heart disease undergoing DHCA were recruited for continuous intraoperative monitoring of cerebral oxygen saturation (ScO 2 ) and an index of cerebral blood flow (CBF i ) using 2 noninvasive optical techniques, diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS). Pre- and postoperative brain magnetic resonance imaging (MRI) was performed to detect white matter injury (WMI). Fifteen neonates were studied, and 11/15 underwent brain MRI. During DHCA, ScO 2 decreased exponentially in time with a median decay rate of -0.04 min -1 . This decay rate was highly variable between subjects. Subjects who had larger decreases in ScO 2 during DHCA were more likely to have postoperative WMI (P = 0.02). Cerebral oxygen extraction persists during DHCA and varies widely from patient-to-patient. Patients with a higher degree of oxygen extraction during DHCA were more likely to show new WMI in postoperative MRI. These findings suggest cerebral oxygen extraction should be monitored during DHCA to identify patients at risk for hypoxic-ischemic injury, and that current commercial cerebral oximeters may underestimate cerebral oxygen extraction., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Oral frailty associated with oral hypokinesia may cause dementia. Functional near-infrared spectroscopy (fNIRS) can be used while the participants are in seating position with few restrictions. Thus, it is useful for assessing brain function, particularly oral motor activity. However, methods for identifying oral motor cortex (OMC) activation via the scalp have not been established. The current study aimed to detect OMC activation, an indicator of activity phase ratio (APR), which reflects increased oxygen consumption (0 < [deoxyhemoglobin ( ΔDeoxyHb ) or 0 < {[ ΔDeoxyHb - oxyhemoglobin ( ΔOxyHb )/√2]}, via fNIRS to accurately identify local brain activity. The APR, calculated via zero-set vector analysis, is a novel index for quantifying brain function both temporally and spatially at rest and during tasks. In total, 14 healthy participants performed bite tasks for 3 s per side for 10 times while in the sitting position. Then, time-series data on concentration changes in ΔOxyHb and ΔDeoxyHb were obtained via fNIRS. The anatomical location of the OMC was determined using a pooled data set of three-dimensional magnetic resonance images collected in advance from 40 healthy adults. In the zero-set vector analysis, the average change in ΔOxyHb and ΔDeoxyHb concentrations was utilized to calculate the APR percentage in 140 trials. The significant regions (z-score of ≥2.0) of the APR and ΔOxyHb in the task were compared. During the bite task, the APR significantly increased within the estimated OMC region (56-84 mm lateral to Cz and 4-20 mm anterior to Cz) in both the right and left hemispheres. By contrast, the ΔOxyHb concentrations increased on the bite side alone beyond the OMC region. The mean APR at rest for 2 s before the task showed 59.5%-62.2% in the left and right OMCs. The average APR for 3 s during the task showed 75.3% for the left OMC and 75.7% for the right OMC during the left bite task, and 65.9% for the left OMC and 80.9% for the right OMC during the right bite task. Interestingly, the average increase in APR for the left and right OMCs for the left bite task and the right bite task was 13.9% and 13.7%, respectively, showing almost a close match. The time course of the APR was more limited to the bite task segment than that of ΔOxyHb or ΔDexyHb concentration, and it increased in the OMC. Hence, the APR can quantitatively monitor both the resting and active states of the OMC in the left and right hemispheres. Using the zero-set vector-based fNIRS, the APR can be a valid indicator of oral motor function and bite force., Competing Interests: MA was employed by the company Total Health Advisers Co. HK and TK were employed by the company KatoBrain Co., Ltd., (Copyright © 2022 Arai, Kato and Kato.)

Background and Purpose: Regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO 2 ) in whole brain, white matter, gray matter and lenticular nuclei were studied in people living with human immunodeficiency virus (PLHIV) as well as HIV-associated neurocognitive disorder (HAND)., Methods: Treatment-naïve PLHIV underwent neurocognitive assessment and magnetic resonance (MR) measurement of rCBF and rCMRO 2 with repeat after 12 months of antiretroviral therapy (ART). Age- and sex-matched controls underwent single MR measurements. Regional CBF and rCMRO 2 were compared amongst symptomatic, asymptomatic, normal HAND and controls using analysis of variance. Longitudinal analysis of HAND worsening (≥1 category) was assessed after 12 months of ART and correlated with rCBF and rCMRO 2 measured by MR imaging using the paired-sample t test., Results: Thirty PLHIV completed baseline and 12-month assessments (29 with rCMRO 2 measurement). At baseline HAND assessment, 13% had no cognitive impairment, 27% had asymptomatic neurocognitive impairment, 60% had mild neurocognitive disorder and none had HIV-associated dementia. At 12 months, 13% had no cognitive impairment, 20% had asymptomatic neurocognitive impairment, 50% had mild neurocognitive disorder and 17% had HIV-associated dementia. In those without HAND worsening (N = 21) rCMRO 2 remained stable and in those with HAND worsening (N = 8) rCMRO 2 measurement declined from baseline to 12 months in white matter (2.05 ± 0.40 to 1.73 ± 0.51, p = 0.03) and lenticular nuclei (4.32 ± 0.39 to 4.00 ± 0.51, p = 0.05)., Conclusions: In recently diagnosed PLHIV, no association was found between rCBF or rCMRO 2 and cognitive impairment at baseline. There was a reduction in rCMRO 2 in those with worsening of cognitive function at 12 months on ART. Reduction in rCMRO 2 may be a biomarker of cognitive decline in PLHIV., (© 2021 European Academy of Neurology.)

Objective: To observe the effect of dexmedetomidine-assisted intravenous inhalation combined anesthesia on cerebral oxygen metabolism and serum Th1/Th2 levels in elderly patients with colorectal cancer., Method: From April 2018 to May 2020,100 elderly patients undergoing elective laparoscopic radical resection of colorectal cancer were prospectively selected and randomly divided into observation group and control group. Before induction of anesthesia, the loading dose of dexmedetomidine was given at 0.5 μg/kg, and the infusion time was 15 min. After tracheal intubation, 0.4 μg/kg/h dexmedetomidine was continuously pumped, and the infusion was stopped 40 min before the end of the operation. In the control group, the same amount of 0.9% sodium chloride was injected intravenously in the same way. 30 min before induction of anesthesia (T 0 ), immediately before induction of anesthesia (T 1 ), immediately after tracheal intubation (T 2 ), 40 min before operation (T 3 ), and immediately after operation (T 4 ), record the blood oxygen content of the artery and internal jugular vein Difference (D(a-jv)O 2 ), brain oxygen uptake rate (COER%), brain oxygen saturation (rSO 2 ) mean. VAS scale, Ramsay scale, MoCA scale were taken at 6, 12, 24, and 48 h postoperatively to evaluate analgesia, sedation, and cognitive function. And monitor the levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), myelin basic protein (MBP), neuron-specific enolase (NSE) and S100β. The occurrence of restlessness and adverse reactions during the recovery period of the two groups were compared., Result: The levels of D(a-jv)O 2 , COER%, and rSO 2 in the control group and observation group were higher than the preoperative basic values at T2, T3, and T4 ( P < 0.05); The levels of D(a-jv)O 2 , COER%, and rSO 2 in the observation group were lower than those in the control group at T 2 , T 3 , and T 4 ( P < 0.05). The VAS score and Ramsay score of the observation group were lower than those of the control group at 6, 12, 24, and 48 h after surgery, while the MoCA score was higher than that of the control group ( P < 0.05). In addition, the serum IFN-γ, MBP, NSE and S100β levels of the observation group were lower than those of the control group ( P < 0.05), and the ratio of IFN-γ/IL-4 was higher than that of the control group ( P < 0.05). The overall incidence of adverse reactions in the observation group was lower than that in the control group [32.0% (16/50) vs. 12.0% (6/50), P < 0.05]., Conclusion: Dexmedetomidine-assisted combined intravenous and inhalation anesthesia is beneficial to reduce perioperative cerebral oxygen metabolism and improve postoperative immunosuppression in elderly patients with colorectal cancer. It has a certain protective effect on nerve injury after operation, thus improving the cognitive function of patients and reducing the occurrence of adverse reactions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tang, Liu, Huang, Ding, Tan and Zhu.)

Infant hydrocephalus poses a severe global health burden; 80% of cases occur in the developing world where patients have limited access to neurosurgical care. Surgical treatment combining endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC), first practiced at CURE Children's Hospital of Uganda (CCHU), is as effective as standard ventriculoperitoneal shunt (VPS) placement while requiring fewer resources and less post-operative care. Although treatment focuses on controlling ventricle size, this has little association with treatment failure or long-term outcome. This study aims to monitor the progression of hydrocephalus and treatment response, and investigate the association between cerebral physiology, brain growth, and neurodevelopmental outcomes following surgery. We will enroll 300 infants admitted to CCHU for treatment. All patients will receive pre/post-operative measurements of cerebral tissue oxygenation (SO 2 ), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO 2 ) using frequency-domain near-infrared combined with diffuse correlation spectroscopies (FDNIRS-DCS). Infants will also receive brain imaging, to monitor tissue/ventricle volume, and neurodevelopmental assessments until two years of age. This study will provide a foundation for implementing cerebral physiological monitoring to establish evidence-based guidelines for hydrocephalus treatment. This paper outlines the protocol, clinical workflow, data management, and analysis plan of this international, multi-center trial.

Objective: To study the effect of the combination treatment of ginkgo biloba extract and low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) on the oxidative stress and brain neurotransmitters of patients who had cerebral ischemic stroke (CIS)., Methods: A retrospective analysis was conducted, and 93 CIS patients admitted to the Sichuan Academy of Medical Sciences/Sichuan Provincial People's Hospital from January 2018 to January 2020 were included in the study. They were divided into three groups, the regular treatment group (31 cases), the LF-rTMS group (31 cases), and the combination treatment group (31 cases). Patients in the regular treatment group were given the conventional drug therapy and exercise regimen. The LF-rTMS group received LF-rTMS therapy (for 20-30 min each time, 1 time/d and 5 times/week) in addition to the treatment given to the regular treatment group. The combination treatment group was given ginkgo biloba extract (intravenous drips, once per day) in addition to the treatment given to the LF-rTMS group. The treatment was given continuously for 4 weeks and comparison was made at the end of the 4-week treatment regarding the clinical efficacy, oxidative stress response, cerebral oxygen metabolism, and brain neurotransmitter as shown by the three groups., Results: The treatment efficacy in the combination treatment group (96.77%) was higher than those of the LF-rTMS group (80.65%) and the regular treatment group (54.84%). The LF-rTMS group showed higher treatment efficacy than that of the regular group. The serum superoxide dismutase (SOD) of the combination treatment group was higher than that of the LF-rTMS group and that of the routine group, while the malondialdehyde (MDA) and endothelin-1 (ET-1) of the combination treatment group were lower than those of the LF-rTMS group and the regular treatment group ( P <0.05). The serum SOD of the LF-rTMS group was higher than that of the regular treatment group, while the MDA and ET-1 of the group was lower than those of the regular treatment group ( P <0.05). The arterial oxygen content (CaO 2 ), arterio-venous oxygen content difference (Ca-vO 2 ) and cerebral extraction rate of oxygen (CERO 2 ) in the combination treatment group were lower than those of the LF-rTMS group and the regular treatment group ( P <0.05). The levels of these three indicators of the LF-rTMS group were lower than those of the regular treatment group ( P <0.05). EEG frequencies of gamma-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT) and dopamine (DA) of the combination treatment group were higher than those of the LF-rTMS group and the regular treatment group, while the acetylcholine (Ach) EEG frequency of the combination treatment group was lower than that of the LF-rTMS group and regular treatment group ( P <0.05). The LF-rTMS group showed higher GABA, 5-HT and DA EEG frequencies than those of the regular treatment group, while the Ach EEG frequency of the group was lower than that of the regular treatment group ( P <0.05). All the patients were followed up for 6 months, and recurrence rate was lower in the combination treatment group (3.23%) than that of the LF-rTMS group (19.35%) and the regular treatment group (25.81%) ( P <0.05)., Conclusion: The combination treatment of ginkgo biloba extract and LF-rTMS helped to improve the clinical outcome of CIS patients, which may be related to the inhibition of oxidative stress, improvement in cerebral oxygen metabolism, and regulation of brain neurotransmitter., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Objective: To innvestigate the application of etomidate and propofol mixture in the evacuation of hematoma in patients with epidural hematoma., Methods: 98 patients with epidural hematoma were randomly divided into two groups: the joint group (n=49, anesthesia induction with etomidate and propofol) and the etomidate group (n=49, anesthesia induction with etomidate) using a random number table. Hemodynamics, stress response and cerebral oxygen metabolism were compared between the two groups at T0 (pre-anesthesia induction), T1 (after endotracheal intubation), T2 (10 min after the beginning of the operation) and T3 (the end of the operation). Adverse reactions were also analyzed., Results: Compared with T0, the mean arterial pressure (MAP) at T1, T2 and T3 in the joint group decreased first and then increased, and the MAP at T1 was significantly lower than that in the etomidate group (P<0.05). Compared with T0, blood oxygen saturation of internal jugular vein bulb (SjvO 2 ) increased in T1-T3 groups, and SjvO 2 in the joint group was higher than that in the etomidate group (all P<0.05). Compared with T0, cerebral oxygen uptake rate (CERO 2 ) in the T1-T3 groups decreased significantly, and CERO 2 at T3 in the joint group was higher than that in the etomidate group (all P<0.05). Compared with T0, the levels of cortisol and superoxide dismutase (SOD) at T3 in the two groups were significantly lower, but those in the etomidate group were higher than those in the combination group (all P<0.05). There was no significant difference in the incidence of postoperative anesthesia-related adverse reactions between the two groups (P>0.05)., Conclusion: Etomidate has less effect on hemodynamics and stress reaction during intravenous anesthesia, but its combination with propofol can improve cerebral oxygen metabolism to a certain extent with fewer adverse reactions., Competing Interests: None., (AJTR Copyright © 2021.)

Management of deep hypothermic (DH) cardiopulmonary bypass (CPB), a critical neuroprotective strategy, currently relies on non-invasive temperature to guide cerebral metabolic suppression during complex cardiac surgery in neonates. Considerable inter-subject variability in temperature response and residual metabolism may contribute to the persisting risk for postoperative neurological injury. To characterize and mitigate this variability, we assess the sufficiency of conventional nasopharyngeal temperature (NPT) guidance, and in the process, validate combined non-invasive frequency-domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS) for direct measurement of cerebral metabolic rate of oxygen ( CMRO 2 ). During CPB, n  = 8 neonatal swine underwent cooling from normothermia to 18℃, sustained DH perfusion for 40 min, and then rewarming to simulate cardiac surgery. Continuous non-invasive and invasive measurements of intracranial temperature (ICT) and CMRO 2 were acquired. Significant hysteresis ( p  < 0.001) between cooling and rewarming periods in the NPT versus ICT and NPT versus CMRO 2 relationships were found. Resolution of this hysteresis in the ICT versus CMRO 2 relationship identified a crucial insufficiency of conventional NPT guidance. Non-invasive CMRO 2 temperature coefficients with respect to NPT ( Q 10  = 2.0) and ICT ( Q 10  = 2.5) are consistent with previous reports and provide further validation of FD-DOS/DCS CMRO 2 monitoring during DH CPB to optimize management.

This study was aimed at evaluating the regional changes in the cerebral metabolic rate of oxygen (CMRO 2 ) in relation to the cerebral blood flow (CBF) in the bilateral common carotid artery occlusion (BCAO) rat model. Ligation of the bilateral common carotid arteries (or a sham operation in control animals) was performed in 10-week-old male Wistar rats. O-15 PET images were acquired in the subacute phase (1 week after the surgery) and chronic phase (6 weeks after the surgery) with the animals under anesthesia, using a small-animal PET system and the O-15 gas steady-state inhalation method with arterial blood sampling developed in our previous study. Histopathological staining by Klüver-Barrera method and immunocytochemistry staining by glial fibrillary acidic protein were performed. Cognitive function was tested by using the apparatus of Y-maze. Significantly lower CBF and higher oxygen extraction fraction were observed in broad areas of the cerebrum in the subacute phase in the BCAO rats, with recovery in the chronic phase. A stable decrease of the CMRO 2 in the subacute phase of arterial occlusion and later was observed in the BCAO rat model, mainly in the anterior cerebral artery territory. Atrophy and rarefaction of corpus callosum were found in the BCAO in the chronic phase. Activity of astrocytes in the BCAO was prominent in the both phases. Working memory was impaired in the BCAO in the chronic phase. Regional changes in cerebral perfusion and oxygen metabolism in the subacute and chronic phases of arterial occlusion were clarified in a rat model of BCAO by quantitative O-15 PET based on the steady-state method., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: We aimed to explore the effect of comprehensive cerebral protection on cerebral oxygen metabolism and vascular endothelial function in elderly patients with acute cerebral infarction., Methods: A total of 168 elderly patients with acute cerebral infarction treated in The First Affiliated Hospital of Nanchang University, China from January 2016 to January 2018 were selected. The patients were divided into a control group and an observation group using random number method, n=84. Patients in the observation group were given comprehensive cerebral protection treatment, and patients in the control group were treated with conventional standardized treatments. The changes of cerebral oxygen metabolism, hemorheology and vascular endothelial function before and after treatment were compared between the two groups., Results: After treatment, oxygen content in arteries and internal jugular veins (Da-vO 2 ), ofoxygen uptake fraction (OEF), Oxygen saturation (SpO 2 ), nitric oxide (NO) were increased in both groups in comparison to before treatment, jugular venous oxygen saturation (SjvO 2 ), brain oxygen uptake rate (ERO 2 ), endothelin (ET), intracranial pressure (ICP), whole blood viscosity, plasma viscosity, reduced viscosity of whole blood, and hematocrit were decreased. However, the changes in the observation group were larger than those in the control group, the difference was statistically significant ( P <0.05)., Conclusion: The treatment of cerebral infarction in elderly patients with acute cerebral infarction can effectively improve the cerebral oxygen metabolism and vascular endothelial function and improve the blood rheology, which has important clinical value., Competing Interests: Conflict of interests The authors declare that there is no conflict of interest.

Calibrated blood oxygenation level dependent (BOLD) imaging is a multimodal functional MRI technique designed to estimate changes in cerebral oxygen metabolism from measured changes in cerebral blood flow and the BOLD signal. This technique addresses fundamental ambiguities associated with quantitative BOLD signal analysis; however, its dependence on biophysical modeling creates uncertainty in the resulting oxygen metabolism estimates. In this work, we developed a Bayesian approach to estimating the oxygen metabolism response to a neural stimulus and used it to examine the uncertainty that arises in calibrated BOLD estimation due to the presence of unmeasured model parameters. We applied our approach to estimate the CMRO2 response to a visual task using the traditional hypercapnia calibration experiment as well as to estimate the metabolic response to both a visual task and hypercapnia using the measurement of baseline apparent R2' as a calibration technique. Further, in order to examine the effects of cerebral spinal fluid (CSF) signal contamination on the measurement of apparent R2', we examined the effects of measuring this parameter with and without CSF-nulling. We found that the two calibration techniques provided consistent estimates of the metabolic response on average, with a median R2'-based estimate of the metabolic response to CO2 of 1.4%, and R2'- and hypercapnia-calibrated estimates of the visual response of 27% and 24%, respectively. However, these estimates were sensitive to different sources of estimation uncertainty. The R2'-calibrated estimate was highly sensitive to CSF contamination and to uncertainty in unmeasured model parameters describing flow-volume coupling, capillary bed characteristics, and the iso-susceptibility saturation of blood. The hypercapnia-calibrated estimate was relatively insensitive to these parameters but highly sensitive to the assumed metabolic response to CO2., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Obstructive sleep apnea (OSA) is associated with extensive neurologic comorbidities. It is hypothesized that the repeated nocturnal apneas experienced in patients with OSA may inhibit the normal apneic response, resulting in hypoxic brain injury and subsequent neurologic dysfunction. In this study, we applied the recently developedOxFlowMRI method for rapid quantification of cerebral metabolic rate of oxygen (CMRO2) during a volitional apnea paradigm. MRI data were analyzed in 11 OSA subjects and 10 controls (mean ± SD apnea-hypopnea index (AHI): 43.9 ± 18.1 vs. 2.9 ± 1.6 events/hour,P < 0.0001; age: 53.8 ± 8.2 vs. 45.3 ± 8.5 years,P = 0.027; BMI: 36.6 ± 4.4 vs. 31.9 ± 2.2 kg/m(2),P = 0.0064). Although total cerebral blood flow and arteriovenous oxygen difference were not significantly different between apneics and controls (P > 0.05), apneics displayed reduced baseline CMRO2(117.4 ± 37.5 vs. 151.6 ± 29.4 µmol/100 g/min,P = 0.013). In response to apnea, CMRO2decreased more in apneics than controls (-10.9 ± 8.8 % vs. -4.0 ± 6.7 %,P = 0.036). In contrast, group differences in flow-based cerebrovascular reactivity were not significant. Results should be interpreted with caution given the small sample size, and future studies with larger independent samples should examine the observed associations, including potential independent effects of age or BMI. Overall, these data suggest that dysregulation of the apneic response may be a mechanism for OSA-associated neuropathology., (© The Author(s) 2015.)

Low doses of the carbonic anhydrase inhibitor acetazolamide provides accelerated acclimatization to high-altitude hypoxia and prevention of cerebral and other symptoms of acute mountain sickness. We previously observed increases in cerebral O2 metabolism (CMRO2 ) during hypoxia. In this study, we investigate whether low-dose oral acetazolamide (250 mg) reduces this elevated CMRO2 and in turn might improve cerebral tissue oxygenation (PtiO2 ) during acute hypoxia. Six normal human subjects were exposed to 6 h of normobaric hypoxia with and without acetazolamide prophylaxis. We determined CMRO2 and cerebral PtiO2 from MRI measurements of cerebral blood flow (CBF) and cerebral venous O2 saturation. During normoxia, low-dose acetazolamide resulted in no significant change in CBF, CMRO2 , or PtiO2 . During hypoxia, we observed increases in CBF [48.5 (SD 12.4) (normoxia) to 65.5 (20.4) ml·100 ml(-1)·min(-1) (hypoxia), P < 0.05] and CMRO2 [1.54 (0.19) to 1.79 (0.25) μmol·ml(-1)·min(-1), P < 0.05] and a dramatic decline in PtiO2 [25.0 to 11.4 (2.7) mmHg, P < 0.05]. Acetazolamide prophylaxis mitigated these rises in CBF [53.7 (20.7) ml·100 ml(-1)·min(-1) (hypoxia + acetazolamide)] and CMRO2 [1.41 (0.09) μmol·ml(-1)·min(-1) (hypoxia + acetazolamide)] associated with acute hypoxia but also reduced O2 delivery [6.92 (1.45) (hypoxia) to 5.60 (1.14) mmol/min (hypoxia + acetazolamide), P < 0.05]. The net effect was improved cerebral tissue PtiO2 during acute hypoxia [11.4 (2.7) (hypoxia) to 16.5 (3.0) mmHg (hypoxia + acetazolamide), P < 0.05]. In addition to its renal effect, low-dose acetazolamide is effective at the capillary endothelium, and we hypothesize that local interruption in cerebral CO2 excretion accounts for the improvements in CMRO2 and ultimately in cerebral tissue oxygenation during hypoxia. This study suggests a potentially pivotal role of cerebral CO2 and pH in modulating CMRO2 and PtiO2 during acute hypoxia., (Copyright © 2015 the American Physiological Society.)

Because oxidative metabolism is the primary form of energy production in the brain, the amount of oxygen consumed by the brain, denoted by a physiological parameter termed cerebral metabolic rate of oxygen (CMRO2), represents a key marker for tissue viability and brain function. Quantitative assessment of cerebral oxygen metabolism in the neonate may provide an important marker in better understanding normal brain development and in making diagnosis and treatment decisions in neonatal brain injuries. Measurement of CMRO2 in humans has been a challenging task, particularly in neonates. Recently, several promising techniques have been proposed to quantify neonatal CMRO2 and the purpose of this article is to provide a technical review of these techniques. Among these, we will focus the review on the NIRS optic based methods and MRI methods which are non-invasive, have been applied in normal and sick newborns and show great potentials. Potential clinical prospects of CMRO2 techniques are discussed in the context of their advantages, challenges and limitations., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The aim of the present study was to investigate the effects of ulinastatin on cerebral oxygen metabolism and C-reactive protein (CRP) levels in patients with severe traumatic brain injury (sTBI). A total of 92 patients with sTBI, admitted to the First Affiliated Hospital of Xinxiang Medical University (Xinxiang, China), were randomly divided into control and observation groups. The control group received conventional therapy plus a placebo (0.9% sodium chloride), while the observation group were administered conventional therapy plus 200,000 units ulinastatin via intravenous injection twice a day for seven days. Arterial and jugular venous blood was collected for blood gas analysis. The jugular venous blood lactate (JVBL), jugular venous bulb oxygen saturation (SjvO 2 ), arteriovenous oxygen content difference (AVDO 2 ) and cerebral extraction of oxygen (CEO 2 ) levels were measured on day 1, 3, 5 and 7, as well as the level of CRP in the peripheral blood. In the control group, the level of JVBL decreased as compared with the level at day 1, however, no statistically significant differences were observed (P>0.05). By contrast, the observation group exhibited a significant reduction in the level of JVBL (P<0.05), which was also significantly lower compared with the control group (P<0.05). Statistically significant differences were observed between the two groups with regard to SjvO 2 , AVDO 2 and CEO 2 on day 3, 5 and 7. The CRP levels in the two groups increased and peaked on day 3. However, the CRP level in the observation group significantly decreased on day 5 (35.27±15.18 mg/l) and day 7 (22.65±10.48 mg/l), which was lower compared with the control group (56.19±13.24 mg/l and 47.36±15.73 mg/l, respectively); statistically significant differences were observed (P<0.05). Therefore, ulinastatin effectively improved cerebral oxygen metabolism and reduced the CRP level in patients with sTBI.

We review PET- and MR studies on hepatic encephalopathy (HE) metabolism in human subjects from the point of views of methods, methodological assumptions and use in studies of cirrhotic patients with clinically overt HE, cirrhotic patients with minimal HE, cirrhotic patients with no history of HE and healthy subjects. Key results are: (1) Cerebral oxygen uptake and blood flow are reduced to 2/3 in cirrhotic patients with clinically overt HE but not in cirrhotic patients with minimal HE or no HE compared to healthy subjects. (2) Cerebral ammonia metabolism is enhanced due to increased blood ammonia in cirrhotic patients but the kinetics of cerebral ammonia uptake and metabolism is not affected by hyperammonemia. (3) Recent advantages in MR demonstrate low-grade cerebral oedema not only in astrocytes but also in the white matter in cirrhotic patients with HE., (Copyright © 2013 Elsevier Inc. All rights reserved.)