Oxygen imaging of hypoxic pockets in the mouse cerebral cortex.

Consciousness is lost within seconds upon cessation of cerebral blood flow. The brain cannot store oxygen, and interruption of oxidative phosphorylation is fatal within minutes. Yet only rudimentary knowledge exists regarding cortical partial oxygen tension (Po2) dynamics under physiological conditions. Here we introduce Green enhanced Nano-lantern (GeNL), a genetically encoded bioluminescent oxygen indicator for Po2 imaging. In awake behaving mice, we uncover the existence of spontaneous, spatially defined "hypoxic pockets" and demonstrate their linkage to the abrogation of local capillary flow. Exercise reduced the burden of hypoxic pockets by 52% compared with rest. The study provides insight into cortical oxygen dynamics in awake behaving animals and concurrently establishes a tool to delineate the importance of oxygen tension in physiological processes and neurological diseases.

Multifunctional IrOx Neural Probe for In Situ Dynamic Brain Hypoxia Evaluation.

Perioperative cerebral hypoxia and neonatal hypoxia-ischemic encephalopathy are the main triggers that lead to temporary or permanent brain dysfunction. The pathogenesis is intimately correlated to neural activities and the pH of the microenvironment, which calls for a high demand for in situ multitype physiological signal acquisition in the brain. However, conventional pH sensing neural interfaces cannot obtain the characteristics of multimodes, multichannels, and high spatial resolution of physiological signals simultaneously. Here, we report a multifunctional implantable iridium oxide (IrOx) neural probe (MIIONP) combined with electrophysiology recording, in situ pH sensing, and neural stimulation for real-time dynamic brain hypoxia evaluation. The neural probe modified with IrOx films exhibits outstanding electrophysiology recording and neural stimulation performance and long-term stable high spatial pH sensing resolution of about 100 µm, and the cytotoxicity of IrOx microelectrodes was investigated as well. In addition, 4 weeks' tracking of the same neuron firing and instantaneous population spike captured during electrical stimulation was achieved by MIIONP. Finally, in a mouse brain hypoxia model, the MIIONP has demonstrated the capability of synchronous in situ recording of the pH and neural firing changes in the brain, which has a valuable application in dynamic brain disease evaluation through real-time acquisition of multiple physiological signals.

Brain hypoxia, neurocognitive impairment, and quality of life in people post-COVID-19.

OBJECTIVE: Systemic hypoxia occurs in COVID-19 infection; however, it is unknown if cerebral hypoxia occurs in convalescent individuals. We have evidence from other conditions associated with central nervous system inflammation that hypoxia may occur in the brain. If so, hypoxia could reduce the quality of life and brain function. This study was undertaken to assess if brain hypoxia occurs in individuals after recovery from acute COVID-19 infection and if this hypoxia is associated with neurocognitive impairment and reduced quality of life. METHODS: Using frequency-domain near-infrared spectroscopy (fdNIRS), we measured cerebral tissue oxygen saturation (StO2) (a measure of hypoxia) in participants who had contracted COVID-19 at least 8 weeks prior to the study visit and healthy controls. We also conducted neuropsychological assessments and health-related quality of life assessments, fatigue, and depression. RESULTS: Fifty-six percent of the post-COVID-19 participants self-reported having persistent symptoms (from a list of 18), with the most reported symptom being fatigue and brain fog. There was a gradation in the decrease of oxyhemoglobin between controls, and normoxic and hypoxic post-COVID-19 groups (31.7 ± 8.3 µM, 27.8 ± 7.0 µM and 21.1 ± 7.2 µM, respectively, p = 0.028, p = 0.005, and p = 0.081). We detected that 24% of convalescent individuals' post-COVID-19 infection had reduced StO2 in the brain and that this relates to reduced neurological function and quality of life. INTERPRETATION: We believe that the hypoxia reported here will have health consequences for these individuals, and this is reflected in the correlation of hypoxia with greater symptomology. With the fdNIRS technology, combined with neuropsychological assessment, we may be able to identify individuals at risk of hypoxia-related symptomology and target individuals that are likely to respond to treatments aimed at improving cerebral oxygenation.

Discrepancies in the late auditory potentials of post-anoxic patients: Watch out for focal brain lesions, a pilot retrospective study.

AIMS: Late auditory evoked potentials, and notably mismatch negativity (MMN) and P3 responses, can be used as part of the multimodal prognostic evaluation in post-anoxic disorders of consciousness (DOC). MMN response preferentially stems from the temporal cortex and the arcuate fasciculus. Situations with discrepant evaluations, for example MMN absent but P3 present, are frequent and difficult to interpret. We hypothesize that discrepant MMN-/P3+ results could reflect a higher prevalence of lesions in MMN generating regions. This study presents correlations between neurophysiological and neuroradiological results. METHODS: This retrospective study was conducted on 38 post-anoxic DOC patients. Brain lesions were analyzed on 3T MRI both anatomically and through computation of the local arcuate fasciculus fractional anisotropy values on Diffusion Tensor Imaging sequences. Neurophysiological data and outcome were also analyzed. RESULTS: Our cohort included 8 MMN-/P3+, 7 MMN+/P3+, 21 MMN-/P3- and 2 MMN-/P3+ patients, assessed at a median delay of 20.5 days since cardiac arrest. Our results show that MMN-/P3+ patients tended to have fewer temporal and basal ganglia lesions than MMN-/P3- patients, and more than MMN+/P3+ patients (p-values for trend: p = 0.02 for temporal and p = 0.02 for basal ganglia lesions). There was a statistical difference across groups for mean fractional anisotropy values in the arcuate fasciculus (p = 0.008). The percentage of patients regaining consciousness at three months in MMN-/P3+ patients was higher than in MMN-/P3- patients and lower than in MMN+/P3+ patients. CONCLUSION: This study suggests that discrepancies in late auditory evoked potentials may be linked to focal post-anoxic brain lesions, visible on brain MRI.

A phase-II clinical trial of targeted cerebral near infrared spectroscopy using standardized treatment guidelines to improve brain oxygenation in preterm infants (BOx-II): A study protocol.

BACKGROUND: Mortality and brain injury are common adverse outcomes in infants born <28 weeks. Conventional pulse oximetry may not detect subclinical changes prior to deterioration and fails to detect changes within the brain. Increasing evidence supports the use of cerebral near-infrared spectroscopy (NIRS) in the early care of preterm infants, yet the impact of specific interventions on cerebral oxygenation and the relationship between cerebral hypoxia and brain injury on MRI remain to be determined. METHODS/DESIGN: 100 infants <28 completed weeks of gestation will be recruited for a prospective, multicenter intervention trial. After informed consent, infants will undergo cerebral NIRS monitoring starting within 6 h of birth and continuing through 72 h. Infants with persistent cerebral desaturation will receive interventions following a standard treatment algorithm selected by the provider based on the patient's clinical condition. Providers will record the timing and choice of intervention(s) and term equivalent brain MRI will be performed for survivors. There are three objectives of this study: 1) to identify the relationship between cerebral hypoxia burden and brain injury on term-equivalent MRI. 2) to identify most common interventions after cerebral hypoxia, and 3) to quantify frequency of occult cerebral hypoxia events. DISCUSSION: There is increasing evidence for the role of early cerebral NIRS monitoring in the neuroprotective care of preterm infants. This phase-II trial will provide essential data to improve the intervention approach, model the effect size of interventions on a wider extent of brain injury, and quantify the discrepancy between measurements of systemic and cerebral hypoxia.

The role of F-18 FDG PET/CT in the prognosis of patients with hypoxic/anoxic brain injury after cardio-circulatory arrest.

BACKGROUND: Advances in resuscitation techniques have resulted in more patients surviving cardio-circulatory arrest (CA) and consequently developing hypoxic/anoxic brain damage. The aim of this study is to evaluate the role of PET/CT (Positron Emission Tomography/Computerized Tomography scan) with F-18 FDG (F-18 fluorodeoxyglucose) during the early rehabilitative hospitalization phase in determining the V/C (Vermis/Cerebellar) ratio as a prognostic index to predict patient outcome, as defined by clinical evaluation scales. METHODS: This is a single-center retrospective study of 37 consecutive adult patients admitted to the neurorehabilitation center between January 2011 and June 2019. Functional status was measured by the following clinical scales: FIM (Functional Indipendence Measure), LCFS (Levels of Cognitive Functioning Scale), GOS (Glasgow Outcome Scale) and CRS-R (Coma Recovery Scale-Revised). PET/CT with F-18 FDG as a functional imaging technique was used to calculate the V/C ratio as a ratio between the metabolism of the vermis and of the Cerebellar Hemisphere. RESULTS: A statistically significant correlation was observed between the V/C ratio and the delta values (difference between discharge and admission value) for each clinical evaluation scale (Delta FIM: P=0.0014; Delta LCFS P=0.0003). A statistically significant difference was observed between the V/C ratio of patients with LCFS ≥4 that showed an improved outcome (defined as an improvement of at least two points in LCFS), and that of patients with LCFS <4 that did not improve (P=0.0011). A V/C ratio cut-off of 1.5 corresponded with a positive predictive power of 80% and a negative predictive power of 82%; a value <1.5 predicted a better outcome. CONCLUSIONS: Clinical evaluation scales when associated with F-18 FDG PET/CT measurement of metabolism, provide a more reliable prognosis. This allows for more focused rehabilitation treatment and better management of family members' expectation.

Relationship between Brain Tissue Oxygen Tension and Transcranial Doppler Ultrasonography.

BACKGROUND: Multimodal monitoring of intracranial pressure and brain tissue oxygen tension (PbtO2) have been increasingly used to detect delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. At our center, patients who cannot be easily assessed clinically will undergo intracranial pressure and PbtO2 monitoring via a NEUROVENT-PTO bolt. We aimed to determine whether the Lindegaard ratios (LRs) computed from transcranial Doppler ultrasonography (TCDU) would correlate with, or can predict, the simultaneously recorded PbtO2 value. METHODS: Patients with aneurysmal subarachnoid hemorrhage, PbtO2 recordings from the middle cerebral artery territory, and simultaneous TCDU scans available from the ipsilateral middle cerebral artery and internal carotid artery from August 2018 to 2019 were included in the present study. The index test result was vasospasm (LR of ≥3) found on TCDU. The reference standard was the presence of regional hypoxia (PbtO2 <20 mm Hg). The PbtO2 results were compared with those from computed tomography angiography as a radiological standard. The predictive values were calculated using a contingency table and receiver operating characteristic curve. RESULTS: A total of 28 patients (6 men and 22 women; age, 59.04 ± 13.75 years) were identified with simultaneous brain tissue oxygen and TCDU recordings available. Of the 28 patients, 7 had cerebral hypoxia (PbtO2 <20 mm Hg). We found no correlation between the PbtO2 measurements and simultaneously recorded LRs (r2 = 0.048; P = 0.26). A LR of ≥3 had high specificity (95.24%) for hypoxia but relatively low sensitivity (42.86%; P = 0.037). CONCLUSION: We find TCDU to be specific for predicting cerebral hypoxia (measured via an intraparenchymal probe). Therefore, it could be a useful and noninvasive tool in the context of preventative DCI monitoring. However, given the low sensitivity, the lack of vasospasm on TCDU should not preclude the possibility of the presence of evolving DCI.

Reversal of neurovascular coupling in the default mode network: Evidence from hypoxia.

Local changes in cerebral blood flow are thought to match changes in neuronal activity, a phenomenon termed neurovascular coupling. Hypoxia increases global resting cerebral blood flow, but regional cerebral blood flow (rCBF) changes are non-uniform. Hypoxia decreases baseline rCBF to the default mode network (DMN), which could reflect either decreased neuronal activity or altered neurovascular coupling. To distinguish between these hypotheses, we characterized the effects of hypoxia on baseline rCBF, task performance, and the hemodynamic (BOLD) response to task activity. During hypoxia, baseline CBF increased across most of the brain, but decreased in DMN regions. Performance on memory recall and motion detection tasks was not diminished, suggesting task-relevant neuronal activity was unaffected. Hypoxia reversed both positive and negative task-evoked BOLD responses in the DMN, suggesting hypoxia reverses neurovascular coupling in the DMN of healthy adults. The reversal of the BOLD response was specific to the DMN. Hypoxia produced modest increases in activations in the visual attention network (VAN) during the motion detection task, and had no effect on activations in the visual cortex during visual stimulation. This regional specificity may be particularly pertinent to clinical populations characterized by hypoxemia and may enhance understanding of regional specificity in neurodegenerative disease pathology.

Influence of exertional hypoxemia on cerebral oxygenation in fibrotic interstitial lung disease.

It is unknown whether hypoxemia, a hallmark of fibrotic interstitial lung disease (f-ILD), may impair cerebral oxygenation during exercise in these patients. Twenty-seven patients [23 males, 72 ± 8 years, lung diffusing capacity for carbon monoxide (DLCO) = 44 ± 11 % predicted] and 12 controls performed an incremental bicycle test. Prefrontal oxygenation [tissue saturation index (TSI)] was assessed by near-infrared spectroscopy. Patients showed lower arterial O2 saturation (SpO2) and larger fall in cerebral TSI during exercise vs controls (p < 0.05). However, changes (Δ) from rest to peak-exercise in SpO2 (-2.2 % to -26.9 %) and TSI (1.4 % to -16.6 %) varied substantially among patients. In the 16 patients showing significant cerebral deoxygenation (Δ TSI ≥ 4% based on controls), SpO2 decreased more (-12.6 ± 6.7 % vs -5.7 ± 2.8 %, p = 0.001) and peak O2 uptake was lower (68.3 ± 19.2 % vs 87.8 ± 24.8 % predicted, p = 0.03) vs their 11 counterparts. In association with DLCO and forced vital capacity, Δ cerebral TSI independently predicted peak O2 uptake on multivariable regression analysis (R2 = 0.54). Exertional hypoxemia impairs cerebral oxygenation in a dose-dependent fashion in f-ILD. Future studies are warranted to investigate whether this potentially reversible abnormality play a contributory role in limiting exercise tolerance in these patients.

Occlusion of activity dependent synaptic plasticity by late hypoxic long term potentiation after neonatal intermittent hypoxia.

To elucidate the mechanisms of memory impairment after chronic neonatal intermittent hypoxia (IH), we employed a mice model of severe IH administered at postnatal days 3 to 7. Since prior studies in this model did not demonstrate increased cell death, our primary hypothesis was that IH causes a functional disruption of synaptic plasticity in hippocampal neurons. In vivo recordings of Schaffer collateral stimulation-induced synaptic responses during and after IH in the CA1 region of the hippocampus revealed pathological late phase hypoxic long term potentiation (hLTP) (154%) that lasted more than four hours and could be reversed by depotentiation with low frequency stimulation (LFS), or abolished by NMDA and PKA inhibitors (MK-801 and CMIQ). Furthermore, late phase hLTP partially occluded normal physiological LTP (pLTP) four hours after IH. Early and late hLTP phases were induced by neuronal depolarization and Ca2+ influx, determined with manganese enhanced fMRI, and had increased both AMPA and NMDA - mediated currents. This was consistent with mechanisms of pLTP in neonates and also consistent with mechanisms of ischemic LTP described in vitro with OGD in adults. A decrease of pLTP was also recorded on hippocampal slices obtained 2 days after IH. This decrease was ameliorated by MK-801 injections prior to each IH session and restored by LFS depotentiation. Occlusion of pLTP and the observed decreased proportion of NMDA-only silent synapses after neonatal hLTP may explain long term memory, behavioral deficits and abnormal synaptogenesis and pruning following neonatal IH.

Strain Longitudinal e Acidente Vascular Encefálico Isquêmico na Ausência de Cardiopatia Conhecida / Longitudinal Strain and Ischemic Stroke in the Absence of Known Heart Disease

Fundamento: O acidente vascular encefálico (AVE) é prevalente no mundo. Reconhecimento precoce da doença cardiovascular subclínica pode predizer um primeiro episódio de AVE isquêmico; o speckle tracking associado à ecocardiografia (STE) permite detecção precoce da disfunção miocárdica subclínica. Objetivo: Provar a associação entre deformação miocárdica avaliada pelo STE e primeiro episódio de AVE em indivíduos saudáveis. Método: Incluímos participantes entre 40-80 anos com primeiro episódio de AVE isquêmico sem cardiopatia conhecida, pareados por sexo, idade e hipertensão com grupo controle saudável na proporção 1:2. STE avaliou strain longitudinal (SL) do ventrículo esquerdo (VE), e ecocardiografia tradicional foi realizada. Análises univariada e multivariada avaliaram as relações do AVE com fatores de risco cardiovasculares e parâmetros derivados da ecocardiografia. Resultado: 29 casos e 62 controles foram incluídos. Média etária foi 60 ± 12 anos; 54% eram homens. Tabagismo foi mais prevalente em casos do que em controles (34% vs. 9%; p=0.001). Nenhum outro fator de risco evidenciou diferença estatística. Casos tiveram menor deformação miocárdica comparados aos controles (SL -16.7 ± 3.4% vs. -19.2 ± 2.8%; p < 0.001). Não houve diferença em relação aos parâmetros ecocardiográficos tradicionais. Após ajuste para tabagismo e hiperlipidemia, SL manteve-se independentemente associado com AVE (OR=1.3; 95% CI, 1.1 ­ 1.6; p=0.005). A área abaixo à curva ROC para AVE aumentou significativamente após adicionar SL ao tabagismo (0.65 para 0.78, respectivamente; p=0.009). Conclusão: SL tem independente associação com o primeiro episódio de AVE isquêmico em adultos de média idade com corações geralmente normais. SL pode ser potencial marcador de risco nesta população

Background: Stroke is prevalent worldwide, and early recognition of subclinical cardiovascular (CV) disease could predict a first ischemic stroke (IS) episode. Speckle-tracking echocardiography (STE) allows the detection of early subclinical myocardial dysfunction. Aim: To examine the association between myocardial deformation, evaluated by STE, and first episode of IS in a sample of otherwise healthy patients. Methods: We included individuals between 40­80 years old, with a first incidence of IS, with no known CV disease, matched to healthy controls by sex, age, and hypertension at a 1:2 ratio. STE was used to assess LV global longitudinal strain (GLS), and traditional echocardiography was performed. Univariate and multivariable analyses were performed to assess the relationship among stroke, CV risk factors, and echocardiographyderived parameters. Results: A total of 29 cases and 62 controls were included. The mean age of the patients was 60 ± 12 y/o, and 54% were males. Smoking was more prevalent in cases compared to controls (34% vs. 9%; p = 0.001), and there were no significant differences in the other examined risk factors. Cases had less myocardial deformation compared to controls (GLS: -16.7% ± 3.4% vs. -19.2 ± 2.8%; p < 0.001), and there was no

Acute Cerebellar Strokes with Anoxic Brain Injury After a Cardiopulmonary Arrest in SARS-CoV-2 Patient.

Neurological complications from novel coronavirus is becoming more common. These patients usually have primary pulmonary problem of acute lung injury. Presentation in the form of encephalitis, meningitis, Guillain-Barre syndrome and seizures are noted. It is also noted that SARS-CoV-2 has predilection for brain stem leading to patient not feeling extensive pulmonary injury. Here we share another neurological presentation.

Anoxic Brain Injury Detection with the Normalized Diffusion to ASL Perfusion Ratio: Implications for Blood-Brain Barrier Injury and Permeability.

BACKGROUND AND PURPOSE: Anoxic brain injury is a result of prolonged hypoxia. We sought to describe the nonquantitative arterial spin-labeling perfusion imaging patterns of anoxic brain injury, characterize the relationship of arterial spin-labeling and DWI, and evaluate the normalized diffusion-to-perfusion ratio to differentiate patients with anoxic brain injury from healthy controls. MATERIALS AND METHODS: We identified all patients diagnosed with anoxic brain injuries from 2002 to 2019. Twelve ROIs were drawn on arterial spin-labeling with coordinate-matched ROIs identified on DWI. Linear regression analysis was performed to examine the relationship between arterial spin-labeling perfusion and diffusion signal. Normalized diffusion-to-perfusion maps were generated using a custom-built algorithm. RESULTS: Thirty-five patients with anoxic brain injuries and 34 healthy controls were identified. Linear regression analysis demonstrated a significant positive correlation between arterial spin-labeling and DWI signal. By means of a combinatory cutoff of slope of >0 and R2 of > 0.78, linear regression using arterial spin-labeling and DWI showed a sensitivity of 0.86 (95% CI, 0.71-0.94) and specificity of 0.82 (95% CI, 0.66-0.92) for anoxic brain injuries. A normalized diffusion-to-perfusion color map demonstrated heterogeneous ratios throughout the brain in healthy controls and homogeneous ratios in patients with anoxic brain injuries. CONCLUSIONS: In anoxic brain injuries, a homogeneously positive correlation between qualitative perfusion and DWI signal was identified so that areas of increased diffusion signal showed increased ASL signal. By exploiting this relationship, the normalized diffusion-to-perfusion ratio color map may be a valuable imaging biomarker for diagnosing anoxic brain injury and potentially assessing BBB integrity.

Cerebral oxygen metabolism in adults with sickle cell disease.

In sickle cell disease (SCD), oxygen delivery is impaired due to anemia, especially during times of increased metabolic demand, and cerebral blood flow (CBF) must increase to meet changing physiologic needs. But hyperemia limits cerebrovascular reserve (CVR) and ischemic risk prevails despite elevated CBF. The cerebral metabolic rate of oxygen (CMRO2 ) directly reflects oxygen supply and consumption and may therefore be more insightful than flow-based CVR measures for ischemic risk in SCD. We hypothesized that adults with SCD have impaired CMRO2 at rest and that a vasodilatory challenge with acetazolamide would improve CMRO2 . CMRO2 was calculated from CBF and oxygen extraction fraction (OEF), measured with arterial spin labeling and T2 -prepared tissue relaxation with inversion recovery (T2 -TRIR) MRI. We studied 36 adults with SCD without a clinical history of overt stroke, and nine healthy controls. As expected, CBF was higher in patients with SCD versus controls (mean ± SD: 74 ± 16 versus 46 ± 5 mL/100 g/min, P < .001), resulting in similar oxygen delivery (SCD: 377 ± 67 versus controls: 368 ± 42 µmol O2 /100g/min, P = .69). OEF was lower in patients versus controls (27 ± 4 versus 35 ± 4%, P < .001), resulting in lower CMRO2 in patients versus controls (102 ± 24 versus 127 ± 20 µmol O2 /100g/min, P = .002). After acetazolamide, CMRO2 declined further in patients (P < .01) and did not decline significantly in controls (P = .78), indicating that forcing higher CBF worsened oxygen utilization in SCD patients. This lower CMRO2 could reflect variation between healthy and unhealthy vascular beds in terms of dilatory capacity and resistance whereby dysfunctional vessels become more oxygen-deprived, hence increasing the risk of localized ischemia.

Clinical Usefulness of Transcranial Doppler as a Screening Tool for Early Cerebral Hypoxic Episodes in Patients with Moderate and Severe Traumatic Brain Injury.

BACKGROUND: Brain tissue oxygenation (PbtO2) in traumatic brain injury (TBI) is known to be dependent on cerebral blood flow (CBF) which remains difficult to assess during the very early phase of TBI management. This study evaluates if blood flow velocity measurement with 2D color-coded transcranial Doppler (TCD) can predict cerebral hypoxic episodes in moderate-to-severe TBI measured with a PbtO2 probe. METHODS: This is a prospective observational study of serial TCD measurements to assess blood flow velocity and its association with PbtO2. Measurements were done bilaterally on the middle cerebral artery (MCA) early after the insertion of PbtO2 monitoring, daily for 5 days and during dynamic challenge tests. Physiological parameters affecting PbtO2 and Doppler velocities were collected simultaneously (PaO2, PaCO2, hemoglobin [Hb] level, intracranial pressure, and cerebral perfusion pressure [CPP]). RESULTS: We enrolled 17 consecutive patients with a total of 85 TCD studies. Using 2D color-coded TCD, signal acquisition was successful in 96% of the cases. Twenty-nine (34%) TCD measures were performed during an episode of cerebral hypoxia (PbtO2 ≤ 20 mmHg). For early episodes of cerebral hypoxia (occurring ≤ 24 h from trauma), all Vmean < 40 cm/s were associated with an ipsilateral PbtO2 ≤ 20 mmHg (positive predictive value 100%). However, when considering all readings over the course of the study, however, we found no correlation between PbtO2 and MCA's mean blood flow velocity (Vmean). Vmean is also positively correlated with PaCO2, whereas PbtO2 is also correlated with PaO2, CPP, and Hb level. CONCLUSIONS: Early TCD measurements compatible with low CBF (mean velocity < 40 cm/s) detect brain tissue hypoxia early after TBI (≤ 24 h) and could potentially be used as a screening tool before invasive monitoring insertion to help minimize time-sensitive secondary injury. Various factors influence the relationship between Vmean and PbtO2, affecting interpretation of their interaction after 24 h.

Near-Infrared Spectroscopy Reveals Brain Hypoxia and Cerebrovascular Dysregulation in Primary Biliary Cholangitis.

BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease linked to symptoms including fatigue and altered mood/cognition, indicating that chronic liver inflammation associated with PBC can impact brain function. We employed near-infrared spectroscopy (NIRS), a noninvasive neuroimaging technique, to determine whether patients with PBC exhibit reduced cerebral oxygen saturation (StO2 ) and altered patterns of microvascular cerebral blood perfusion and whether these alterations were associated with clinical phenotype. This observational case-control study was conducted at a tertiary hospital clinic (University of Calgary Liver Unit). APPROACH AND RESULTS: Thirteen female patients with noncirrhotic PBC, seven female patients with cirrhotic PBC, and 11 healthy female controls were recruited by physician referral and word of mouth, respectively. NIRS was used to measure cerebral hemoglobin and oxygen saturation. A wavelet phase coherence method was used to estimate the coherent frequency coupling of temporal changes in cerebral hemodynamics. The PBC group demonstrated significantly reduced cerebral StO2 (P = 0.01, d = 0.84), indicating cerebral hypoxia, significantly increased cerebral deoxygenated hemoglobin concentration (P < 0.01, d = 0.86), and significantly reduced hemodynamic coherence in the low-frequency band (0.08-0.15 Hz) for oxygenated hemoglobin concentration (P = 0.02, d = 0.99) and total hemoglobin (tHb) concentration (P = 0.02, d = 0.50), indicating alterations in cerebrovascular activity. Complete biochemical response to ursodeoxycholic acid (UDCA) therapy in early patients with PBC was associated with increased cerebral tHb concentration and decreased hemodynamic coherence. CONCLUSIONS: Using NIRS, patients with PBC were found to have hypoxia, increased cerebral hemoglobin concentration, and altered cerebrovascular activity, which were reversed in part in UDCA responders. In addition, symptoms and quality-of-life measures did not correlate with brain hypoxia or cerebrovascular dysregulation in patients with PBC.

Higher physiological vulnerability to hypoxic exposure with advancing age in the human brain.

The aging brain is associated with atrophy along with functional and metabolic changes. In this study, we examined age-related changes in resting brain functions and the vulnerability of brain physiology to hypoxic exposure in humans in vivo. Brain functions were examined in 81 healthy humans (aged 18-62 years) by acquisitions of gray and white matter volumes, cerebral blood flow, cerebral oxygen consumption, and concentrations of lactate, N-acetylaspartate, and glutamate+glutamine using magnetic resonance imaging and spectroscopy. We observed impaired cerebral blood flow reactivity in response to inhalation of hypoxic air (p = 0.029) with advancing age along with decreased cerebral oxygen consumption (p = 0.036), and increased lactate concentration (p = 0.009), indicating tissue hypoxia and impaired metabolism. Diminished resilience to hypoxia and consequently increased vulnerability to metabolic stress could be a key part of declining brain health with age. Furthermore, we observed increased resting cerebral lactate concentration with advancing age (p = 0.007), which might reflect inhibited brain clearance of waste products.