Changes In Cerebral Metabolism Research Articles

Neurobiological mechanisms and therapeutic impact of electroconvulsive therapy (ECT).

Electroconvulsive therapy (ECT) is an efficient therapeutic resource for psycho-pharmacotherapeutic resistant forms of depression. ECT is a form of electrical brain stimulation involving the induction of a controlled seizure, clinically similar to an epileptic seizure, that is initiated in the prefrontal region of the brain and spreads to the cortex and subcortex, including the diencephalic structures. This is achieved by creating a transcranial electric field and synchronously depolarizing neuronal membranes. The mechanisms of action of ECT are not yet fully understood, but several hypotheses have been proposed to explain how it affects the brain: neurotransmitter changes, neuroplasticity, network connectivity, endocrine system regulation and changes in regional cerebral blood flow and regional metabolism.

Non-invasive assessment of stimulation-specific changes in cerebral glucose metabolism with functional PET.

Functional positron emission tomography (fPET) with [18F]FDG allows quantification of stimulation-induced changes in glucose metabolism independent of neurovascular coupling. However, the gold standard for quantification requires invasive arterial blood sampling, limiting its widespread use. Here, we introduce a novel fPET method without the need for an input function. We validated the approach using two datasets (DS). For DS1, 52 volunteers (23.2 ± 3.3years, 24 females) performed Tetris® during a [18F]FDG fPET scan (bolus + constant infusion). For DS2, 18 participants (24.2 ± 4.3years, 8 females) performed an eyes-open/finger tapping task (constant infusion). Task-specific changes in metabolism were assessed with the general linear model (GLM) and cerebral metabolic rate of glucose (CMRGlu) was quantified with the Patlak plot as reference. We then estimated simplified outcome parameters, including GLM beta values and percent signal change (%SC), and compared them, region and whole-brain-wise. We observed higher agreement with the reference for DS1 than DS2. Both DS resulted in strong correlations between regional task-specific beta estimates and CMRGlu (r = 0.763…0.912). %SC of beta values exhibited strong agreement with %SC of CMRGlu (r = 0.909…0.999). Average activation maps showed a high spatial similarity between CMRGlu and beta estimates (Dice = 0.870…0.979) as well as %SC (Dice = 0.932…0.997), respectively. The non-invasive method reliably estimates task-specific changes in glucose metabolism without blood sampling. This streamlines fPET, albeit with the trade-off of being unable to quantify baseline metabolism. The simplification enhances its applicability in research and clinical settings.

Assessment of a one-week ketogenic diet on brain glycolytic metabolism and on the status epilepticus stage of a lithium–pilocarpine rat model

The ketogenic diet (KD) has been shown to be effective in refractory epilepsy after long-term administration. However, its interference with short-term brain metabolism and its involvement in the early process leading to epilepsy remain poorly understood. This study aimed to assess the effect of a short-term ketogenic diet on cerebral glucose metabolic changes, before and after status epilepticus (SE) in rats, by using [18F]-FDG PET. Thirty-nine rats were subjected to a one-week KD (KD-rats, n = 24) or to a standard diet (SD-rats, n = 15) before the induction of a status epilepticus (SE) by lithium-pilocarpine administrations. Brain [18F]-FDG PET scans were performed before and 4 h after this induction. Morphological MRIs were acquired and used to spatially normalize the PET images which were then analyzed voxel-wisely using a statistical parametric-based method. Twenty-six rats were analyzed (KD-rats, n = 15; SD-rats, n = 11). The 7 days of the KD were associated with significant increases in the plasma β-hydroxybutyrate level, but with an unchanged glycemia. The PET images, recorded after the KD and before SE induction, showed an increased metabolism within sites involved in the appetitive behaviors: hypothalamic areas and periaqueductal gray, whereas no area of decreased metabolism was observed. At the 4th hour following the SE induction, large metabolism increases were observed in the KD- and SD-rats in areas known to be involved in the epileptogenesis process late—i.e., the hippocampus, parahippocampic, thalamic and hypothalamic areas, the periaqueductal gray, and the limbic structures (and in the motor cortex for the KD-rats only). However, no statistically significant difference was observed when comparing SD and KD groups at the 4th hour following the SE induction. A one-week ketogenic diet does not prevent the status epilepticus (SE) and associated metabolic brain abnormalities in the lithium-pilocarpine rat model. Further explorations are needed to determine whether a significant prevention could be achieved by more prolonged ketogenic diets and by testing this diet in less severe experimental models, and moreover, to analyze the diet effects on the later and chronic stages leading to epileptogenesis.

Hyperpolarized 13C magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy: First investigations in a large animal model.

Early biomarkers of cerebral damage are essential for accurate prognosis, timely intervention, and evaluation of new treatment modalities in newborn infants with hypoxia and ischemia at birth. Hyperpolarized 13C magnetic resonance imaging (MRI) is a novel method with which to quantify metabolism in vivo with unprecedented sensitivity. We aimed to investigate the applicability of hyperpolarized 13C MRI in a newborn piglet model and whether this method may identify early changes in cerebral metabolism after a standardized hypoxic-ischemic (HI) insult. Six piglets were anesthetized and subjected to a standardized HI insult. Imaging was performed prior to and 2 h after the insult on a 3-T MR scanner. For 13C studies, [1-13C]pyruvate was hyperpolarized in a commercial polarizer. Following intravenous injection, images were acquired using metabolic-specific imaging. HI resulted in a metabolic shift with a decrease in pyruvate to bicarbonate metabolism and an increase in pyruvate to lactate metabolism (lactate/bicarbonate ratio, mean [SD]; 2.28 [0.36] vs. 3.96 [0.91]). This is the first study to show that hyperpolarized 13C MRI can be used in newborn piglets and applied to evaluate early changes in cerebral metabolism after an HI insult.

Different effect of hypo- and hypermetabolism on cognition in dementia with Lewy bodies: are they coupled or independent?

Patients with dementia with Lewy bodies (DLB) show widespread brain metabolic changes. This study investigated whether brain hypo- and hypermetabolism in DLB have differential effects on cognition. We enrolled 55 patients with DLB (15 prodromal DLB [MCI-LB] and 40 probable DLB) and 13 healthy controls who underwent 18F-fluorodeoxyglucose positron emission tomography and detailed neuropsychological tests. Metabolic indices reflecting associated changes in regional cerebral glucose metabolism were calculated as follows: index(-) for hypometabolism [DLB-hypo] and index(+) for hypermetabolism [DLB-hyper]. The effects of DLB-hypo or DLB-hyper on cognitive function were assessed using a multivariate linear regression model. Additionally, a linear mixed model was used to investigate the association between each index and the longitudinal cognitive decline. There was no correlation between DLB-hypo and DLB-hyper in the disease group. The multivariate linear regression model showed that DLB-hypo was associated with language, visuospatial, visual memory, and frontal/executive functions; whereas DLB-hyper was responsible for attention and verbal memory. There was significant interaction between DLB-hypo and DLB-hyper for verbal and visual memory, which was substantially affected by DLB-hyper in relatively preserved DLB-hypo status. A linear mixed model showed that DLB-hypo was associated with longitudinal cognitive outcomes, regardless of cognitive status, and DLB-hyper contributed to cognitive decline only in the MCI-LB group. The present study suggests that DLB-hypo and DLB-hyper may be independent of each other and differentially affect the baseline and longitudinal cognitive function in patients with DLB.

Near-Infrared Spectroscopy and Continuous Glucose Monitoring During Therapeutic Hypothermia.

The relation between glucose homeostasis and cerebral blood flow (CBF) and their correlation to outcome in neonatal hypoxic-ischemic encephalopathy are unclear. In this short communication, we tried to determine whether changes in regional oxygen saturation (rSO2), as measured by near-infrared spectroscopy (NIRS), in asphyxiated neonates during therapeutic hypothermia correlate with the glycemic profile and whether NIRS and continuous glucose monitoring are useful in identifying cooled asphyxiated neonates at high risk of brain injury. Although there was no correlation between blood glucose and CBF in this small cohort of asphyxiated neonates (13 neonates admitted to the IRCCS Giannina Gaslini NICU in Genoa between March and September 2021), after 24 h of life, increased rSO2 and glucose variability with a tendency toward hyperglycemia distinguished neonates who subsequently acquired brain injury from those who did not. As a result of this, it may be possible to monitor cerebral perfusion and metabolic changes as soon as possible after delivery in order to prevent poorer outcomes.

Alterations in cerebral glucose metabolism measured by FDG PET in subjects performing a meditation practice based on clitoral stimulation

Background The relationship between sexuality, or the libido, and spirituality or religion has long been debated in psychiatry. Recent studies have explored the neurophysiology of both sexual experiences and spiritual practices such as meditation or prayer. In the present study, we report changes in cerebral glucose metabolism in a unique meditation practice augmented by clitoral stimulation called, Orgasmic Meditation, in which a spiritual state is described to be attained by both male and female participants engaged in the practice as a pair. Methods Male (N=20) and female (N=20) subjects had an intravenous catheter connected to a bag of normal saline inserted prior to the practice. During the practice, men stimulated their partner’s clitoris for exactly 15 minutes (he received no sexual stimulation). Midway through the practice, researchers injected 18F-fluorodeoxyglucose so the scan would reflect cerebral metabolism during the practice. Positron emission tomography (PET) imaging was performed approximately 30 minutes later. Results In the female participants, the meditation state showed significant decreases in the left inferior frontal, inferior parietal, insula, middle temporal, and orbitofrontal regions as well as in the right angular gyrus, anterior cingulate and parahippocampus compared to a neutral state (p<0.01). Male subjects had significant decreases in the left middle frontal, paracentral, precentral, and postcentral regions as well as the right middle frontal and paracentral regions during meditation (p<0.01). Men also had significantly increased metabolism in the cerebellum and right postcentral and superior temporal regions (p<0.01). Conclusions These findings represent a distinct pattern of brain activity, for both men and women, that is a hybrid between that of other meditation practices and sexual stimulation. Such findings have potential psychotherapeutic implications and may deepen our understanding of the relationship between spiritual and sexual experience.

The role of Kir6.2‐KATP channels in modulating sleep, brain metabolism, and neuronal excitability in AD

AbstractBackgroundATP sensitive potassium (KATP) channels act as metabolic sensors to regulate cellular excitability. We recently demonstrated that neuronal KATP channels are composed of Kir6.2 subunits, are highly expressed on excitatory and inhibitory neurons, and are differentially expressed in the Alzheimer’s brain (Grizzanti et al. 2022). Mechanistically, we demonstrated that KATP channels couple changes in cerebral metabolism with neuronal activity and amyloid‐beta (Aβ) release, suggesting a role for KATP channels in Alzheimer’s disease. Here, we extend these studies to explore how KATP channels contribute to excitatory/inhibitory (E/I) balance in the brain to impact sleep and Alzheimer’s pathology. How KATP channels coordinate sleep, metabolism, and neuronal activity was examined using the Kir6.2‐/‐ mice, a mouse model lacking neuronal KATP channel activity.MethodIntracranial biosensors measuring interstitial fluid (ISF) glucose and ISF lactate concurrent with EEG/EMGs were implanted into the hippocampus of wild type (WT) and Kir6.2‐/‐ mice. Diurnal rhythms of ISF glucose, ISF lactate, and EEG/EMG were recorded for 72 hours. Mice were injected with saline, glucose, or glibenclamide to determine effects of metabolic challenges on ISF glucose, ISF lactate, and sleep/wake cycles. Quantitative EEG analysis and sleep staging was performed and correlated with ISF glucose and lactate over the 24 hour light/dark period.ResultWildtype mice have diurnal fluctuations in ISF glucose and lactate, with increases during the dark cycle when mice are awake and decreases in the light cycle when mice are asleep. In Kir6.2‐/‐ mice lacking neuronal KATP channel activity, diurnal fluctuations in ISF glucose and lactate are lost. Kir6.2‐/‐ mice spent more time in NREM sleep and less time awake than WT mice. Furthermore, reductions in absolute EEG power suggest changes in the brain’s E/I balance. Lastly, Kir6.2‐/‐ mice were unresponsive to metabolic challenges, demonstrating that ISF lactate, a metabolic trigger for wakefulness, is controlled by KATP channels.ConclusionWe describe the role of neuronal KATP channels as metabolic sensors in coordinating sleep/wake architecture in mice. Ongoing studies are exploring the impact of KATP channels on sleep and brain excitability in AD.

53 Change in Cerebral Metabolite Concentrations Following Bariatric Surgery

Objective:Obesity is associated with adverse effects on brain health, including increased risk for neurodegenerative diseases. Changes in cerebral metabolism may underlie or precede structural and functional brain changes. While bariatric surgery is known to be effective in inducing weight loss and improving obesity-related medical comorbidities, few studies have examined whether it may be able to improve brain metabolism. In the present study, we examined change in cerebral metabolite concentrations in participants with obesity who underwent bariatric surgery.Participants and Methods:35 patients with obesity (BMI > 35 kg/m2) were recruited from a bariatric surgery candidate nutrition class. They completed single voxel 1H-proton magnetic resonance spectroscopy at baseline (pre-surgery) and within one year post-surgery. Spectra were obtained from a large medial frontal brain region. Tissue-corrected absolute concentrations for metabolites including choline-containing compounds (Cho), myo-inositol (mI), N-acetylaspartate (NAA), creatine (Cr), and glutamate and glutamine (Glx) were determined using Osprey. Paired t-tests were used to examine within-subject change in metabolite concentrations, and correlations were used to relate these changes to other health-related outcomes, including weight loss and glycemic control.Results:Bariatric surgery was associated with a reduction in cerebral Cho (f[34j = -3.79, p < 0.001, d = -0.64) and mI (f[34] = -2.81, p < 0.01, d = -0.47) concentrations. There were no significant changes in NAA, Glx, or Cr concentrations. Reductions in Cho were associated with greater weight loss (r = 0.40, p < 0.05), and reductions in mI were associated with greater reductions in HbA1c (r = 0.44, p < 0.05).Conclusions:Participants who underwent bariatric surgery exhibited reductions in cerebral Cho and mI concentrations, which were associated with improvements in weight loss and glycemic control. Given that elevated levels of Cho and mI have been implicated in neuroinflammation, reduction in these metabolites after bariatric surgery may reflect amelioration of obesity-related neuroinflammatory processes. As such, our results provide evidence that bariatric surgery may improve brain health and metabolism in individuals with obesity.

Abnormal Cerebral FDG Accumulation in Acute Intracerebral and Subarachnoid Hemorrhages Due to Different Mechanisms.

Changes in cerebral glucose metabolism after acute intracranial hemorrhage have been rarely described. We present a patient with abnormal cerebral FDG accumulation in acute intracerebral and subarachnoid hemorrhages due to different mechanisms on FDG PET/CT. The patient received conservative management and died 2 months later. This case demonstrated the different mechanisms of cerebral FDG accumulation in different types of intracranial hemorrhage, which may be helpful for future research to optimize patient care.

Effects of STN-DBS surgery on cerebral glucose metabolism and distribution of DAT in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder that affects millions of people worldwide. Subthalamic nucleus (STN) deep brain stimulation (DBS) has been shown to be an effective treatment for PD; however, the effects of this surgery on cerebral metabolism and presynaptic dopamine transporter (DAT) distribution are still being studied. In this study, we included 12 PD patients (6 male and 6 female) who underwent STN-DBS surgery and had both 18 F-FDG and 11 C-CFT PET/CT imaging before and 1 year after the surgery. We used paired t-tests to identify changes in cerebral metabolism and calculated PD-related metabolic covariance pattern (PDRP) scores. We also assessed the uptake of 11 C-CFT in the striatum using striatal-to-occipital ratios (SORs). One year after surgery, we observed significant reductions in tremor, rigidity, akinesia, postural instability/gait disturbance, and Unified Parkinson's Disease Rating Scale Part III scores (p<.01, p<.001, p<.001, p<.001, and p<.001, respectively). Hamilton Depression Rating Scale and quality of life (PDQ-39 SI) were also significantly reduced (p<.05 and p<.01, respectively). The mean PDRP score decreased by 37% from 13.0±6.6 to 8.2±7.9 after STN-DBS surgery (p<.05). We observed decreased 18 F-FDG uptake in several areas, including the temporal lobe (BA22), thalamus, putamen, and cingulate gyrus (BA24), whereas it was increased in the supplementary motor area, postcentral gyrus, lingual gyrus, and precuneus (p<.05). SORs of 11 C-CFT in the bilateral caudate nucleus and ipsilateral posterior putamen were significantly decreased compared to preoperative levels (p<.05). Our findings suggest that STN-DBS surgery modifies the metabolic network of PD patients and improves motor symptoms, depression, and quality of life. However, it does not prevent the decrease of DAT in striatal areas.

Hybrid PET/MRI with Flutemetamol and FDG in Alzheimer's Disease Clinical Continuum.

We aimed to investigate the interaction between β -amyloid (Aβ) accumulation and cerebral glucose metabolism, cerebral perfusion, and cerebral structural changes in the Alzheimer's disease (AD) clinical continuum. Utility of positron emission tomography (PET) / magnetic resonance imaging (MRI) hybrid imaging for diagnostic categorization of the AD clinical continuum including subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI) and Alzheimer's disease dementia (ADD) has not been fully crystallized. To evaluate the interaction between Aβ accumulation and cerebral glucose metabolism, cerebral perfusion, and cerebral structural changes such as cortex thickness or cerebral white matter disease burden and to detect the discriminative yields of these imaging modalities in the AD clinical continuum. Fifty patients (20 women and 30 men; median age: 64 years) with clinical SCD (n=11), aMCI (n=17) and ADD (n=22) underwent PET/MRI with [18F]-fluoro-D-glucose (FDG) and [18F]- Flutemetamol in addition to cerebral blood flow (CBF) and quantitative structural imaging along with detailed cognitive assessment. High Aβ deposition (increased temporal [18F]-Flutemetamol standardized uptake value ratio (SUVr) and centiloid score), low glucose metabolism (decreased temporal lobe and posterior cingulate [18F]-FDG SUVr), low parietal CBF and right hemispheric cortical thickness were independent predictors of low cognitive test performance. Integrated use of structural, metabolic, molecular (Aβ) and perfusion (CBF) parameters contribute to the discrimination of SCD, aMCI, and ADD.

Hyperbaric Oxygen Therapy versus placebo for post-concussion syndrome (HOT-POCS): A randomized, double-blinded controlled pilot study

Post-Concussion Syndrome (PCS) refers to the persistence of physical, cognitive, and emotional symptoms following mild traumatic brain injury (mTBI)/concussion, occurring in roughly 15–30% of individuals. Hyperbaric oxygen therapy (HBOT) has been suggested as a potential treatment for PCS; however, the evidence to date is mixed due to inconsistencies in the treatment protocol and focus on veterans with combat-related injuries, which may not be generalizable to the general population. The goal of Hyperbaric Oxygen Therapy for Post-Concussion Syndrome (HOT-POCS) is to assess the efficacy and safety of HBOT for the treatment of PCS in the civilian population. This randomized, controlled pilot study will be using a standardized HBOT protocol (20 sessions of 100% O2 at 2.0 atm absolute [ATA]) compared with a true placebo gas system that mimics the oxygen composition at room air (20 sessions of 10.5% O2 and 89.5% nitrogen at 2.0 ATA) in a cohort of 100 adults with persistent post-concussive symptoms 3–12 months following injury. Change in symptoms on the Rivermead Post-concussion Questionnaire (RPQ) will be the primary outcome of interest. Secondary outcomes include the rate of adverse events, change in the quality of life, and change in cognitive function. Exploratory outcome measures will include changes in physical function and changes in cerebral brain perfusion and oxygen metabolism on MRI brain imaging. Overall, the HOT-POCS study will compare the efficacy of a standardized HBOT treatment protocol against a true placebo gas for the treatment of PCS within 12 months after injury.

Effect of APOE e4 allele on age‐related brain FDG‐PET uptake in older individuals at risk of dementia

AbstractBackgroundIn Alzheimer’s Disease (AD) patients, accumulating evidence suggests that the APOE‐e4 allele drives amyloid and tau pathology and decreases brain glucose metabolism. Similarly, in older healthy subjects, APOE‐e4 has been linked to brain hypometabolism. However, there are scarce clinical studies concerning the effect of APOE e4 and the age‐related cerebral glucose metabolism patterns of older individuals at‐risk for dementia.ObjectiveThis exploratory analysis aims to study the impact of carriage of the APOE‐e4 allele on age‐related brain glucose metabolism patterns of older individuals at‐risk for dementia.Method54 community‐dwelling older adults aged 60‐80 years with increased risk for AD due to cardiometabolic disorders (CMD, n = 32) or mild cognitive impairment (MCI, n = 22) who participated in a clinical trial. APOE genotyping was performed to identify carriers of the APOE‐e4 allele. 18F‐Fluoro‐2‐deoxy‐D‐glucose‐positron emission tomography/computed tomography (18F‐FDG PET/CT) was conducted and mean 18F‐FDG uptakes in brain regions of interest (ROI) from the atlas of anatomical labeling were obtained.Group differences by diagnosis (CMD,MCI) and APOE‐e4 status were examined using independent samples T‐tests. Linear regression models were conducted to evaluate the effect of age over mean 18F‐FDG uptake in each ROI. Age*APOE‐e4 interactions were examined, and the models were adjusted for diagnosis subgroup and gender effects. Adjusted models were corrected for multiple testing using the False Discovery Ratio (FDR).ResultMean 18F‐FDG uptake at each ROI was comparable between diagnosis and APOE‐e4 allele status groups. After correcting adjusted models for multiple testing, significant Age*APOE‐e4 interactions were found at the right inferior occipital gyrus (β ‐0.13, 95% CI ‐0.25 – 0.02, p = 0.035, FDR = 0.039), right paracentral lobule (β ‐0.14, 95% CI ‐0.25 – ‐0.03, p = 0.016, FDR = 0.024), and left superior parietal gyrus (β ‐0.11, 95% CI ‐0.20 – ‐0.02, p = 0.014, FDR = 0.021).ConclusionIn older individuals at risk of dementia, carriage of the APOE‐e4 allele was associated with an increased age‐related reduction in mean 18F‐FDG uptake in the right inferior occipital gyrus, right paracentral lobule, and left superior parietal gyrus. Knowledge of age‐ and APOE‐e4 allele‐related cerebral metabolic changes is critical to correctly interpreting brain 18F‐FDG PET/CT findings.

Early changes in cerebral metabolism after perinatal hypoxia-ischemia: a study in normothermic and hypothermic piglets.

Hypoxic ischemic encephalopathy (HIE) after a perinatal insult is a dynamic process that evolves over time. Therapeutic hypothermia (TH) is standard treatment for severe to moderate HIE. There is a lack of evidence on the temporal change and interrelation of the underlying mechanisms that constitute HIE under normal and hypothermic conditions. We aimed to describe early changes in intracerebral metabolism after a hypoxic-ischemic insult in piglets treated with and without TH and in controls. Three devices were installed into the left hemisphere of 24 piglets: a probe measuring intracranial pressure, a probe measuring blood flow and oxygen tension, and a microdialysis catheter measuring lactate, glucose, glycerol, and pyruvate. After a standardized hypoxic ischemic insult, the piglets were randomized to either TH or normothermia. Glycerol, a marker of cell lysis, increased immediately after the insult in both groups. There was a secondary increase in glycerol in normothermic piglets but not in piglets treated with TH. Intracerebral pressure, blood flow, oxygen tension, and extracellular lactate remained stable during the secondary increase in glycerol. This exploratory study depicted the development of the pathophysiological mechanisms in the hours following a perinatal hypoxic-ischemic insult with and without TH and controls.

Photoacoustic Microscopic Imaging of Cerebral Vessels for Intensive Monitoring of Metabolic Acidosis.

Metabolic acidosis as one of the most common perioperative complications has been associated with increased risks for poor prognosis. Routine monitoring methods include blood gas analysis and electrocardiogram, which are limited by time delay effects. And the existing intravital imaging modalities are difficult to achieve in one step. Here, we present a dual-wavelength photoacoustic imaging approach to overcome this dilemma. The aim of this study was to develop a rapid approach for intensive monitoring of acid-base imbalance and cerebral oxygen metabolism. We characterized the cerebrovascular structure by label-free dual-wavelength (532 and 559nm) photoacoustic microscopy in healthy and diabetic mouse models with metabolic acidosis. Concurrently, we developed a single-vessel analysis method to accurately delineate the differential responses of small vessels and quantify the cerebral oxygenation following experimental alteration of pH. We demonstrated that there was an increasing trend in changes of vascular measurements (density, diameter, and relative hemoglobin concentration) and cerebral microvascular oxygen metabolism with the aggravation of acidosis. Furthermore, we established a clinical nomogram for the diagnosis of disease severity and yielded good discrimination ability with area under the curve of 0.920-0.967 and accuracy of 81.9-93.0%. The nomogram was also validated well in the diabetic mouse model with metabolic acidosis. Our photoacoustic imaging approach has great potential for rapid detection of metabolic acidosis and brain oxygen metabolism, which could potentially be applied as a bedside monitoring method for brain protection and timely treatment of acid-base abnormalities.

Change in medial frontal cerebral metabolite concentrations following bariatric surgery.

Obesity is associated with adverse effects on brain health, including an increased risk of neurodegenerative diseases. Changes in cerebral metabolism may underlie or precede structural and functional brain changes. While bariatric surgery is known to be effective in inducing weight loss and improving obesity-related medical comorbidities, few studies have examined whether it may be able to improve brain metabolism. In the present study, we examined changes in cerebral metabolite concentrations in participants with obesity who underwent bariatric surgery. Thirty-five patients with obesity (body mass index ≥ 35 kg/m2 ) were recruited from a bariatric surgery candidate nutrition class. They completed single voxel proton magnetic resonance spectroscopy at baseline (presurgery) and within 1 year postsurgery. Spectra were obtained from a large medial frontal brain region using a PRESS sequence on a 3-T Siemens Verio scanner. The acquisition parameters were TR = 3000 ms and TE = 37 ms. Tissue-corrected metabolite concentrations were determined using Osprey. Paired t-tests were used to examine within-subject change in metabolite concentrations, and correlations were used to relate these changes to other health-related outcomes, including weight loss and glycated hemoglobin (HbA1c ), a measure of blood sugar levels. Bariatric surgery was associated with a reduction in cerebral choline-containing compounds (Cho; t [34] = - 3.79, p < 0.001, d = -0.64) and myo-inositol (mI; t [34] = - 2.81, p < 0.01, d = -0.47) concentrations. There were no significant changes in N-acetyl-aspartate, creatine, or glutamate and glutamine concentrations. Reductions in Cho were associated with greater weight loss (r = 0.40, p < 0.05), and reductions in mI were associated with greater reductions in HbA1c (r = 0.44, p < 0.05). In conclusion, participants who underwent bariatric surgery exhibited reductions in cerebral Cho and mI concentrations, which were associated with improvements in weight loss and glycemic control. Given that elevated levels of Cho and mI have been implicated in neuroinflammation, reduction in these metabolites after bariatric surgery may reflect amelioration of obesity-related neuroinflammatory processes. As such, our results provide evidence that bariatric surgery may improve brain health and metabolism in individuals with obesity.

Beyond intracranial pressure: monitoring cerebral perfusion and autoregulation in severe traumatic brain injury.

Severe traumatic brain injury (TBI) remains the most prevalent neurological condition worldwide. Observational and interventional studies provide evidence to recommend monitoring of intracranial pressure (ICP) in all severe TBI patients. Existing guidelines focus on treating elevated ICP and optimizing cerebral perfusion pressure (CPP), according to fixed universal thresholds. However, both ICP and CPP, their target thresholds, and their interaction, need to be interpreted in a broader picture of cerebral autoregulation, the natural capacity to adjust cerebrovascular resistance to preserve cerebral blood flow in response to external stimuli. Cerebral autoregulation is often impaired in TBI patients, and monitoring cerebral autoregulation might be useful to develop personalized therapy rather than treatment of one size fits all thresholds and guidelines based on unidimensional static relationships. Today, there is no gold standard available to estimate cerebral autoregulation. Cerebral autoregulation can be triggered by performing a mean arterial pressure (MAP) challenge, in which MAP is increased by 10% for 20 min. The response of ICP (increase or decrease) will estimate the status of cerebral autoregulation and can steer therapy mainly concerning optimizing patient-specific CPP. The role of cerebral metabolic changes and its relationship to cerebral autoregulation is still unclear and awaits further investigation.

Abstract 63: Age-related Changes In Gray Matter Cerebral Metabolism And Vascular Reactivity In Children

Introduction: Metabolic demand changes throughout childhood as the brain develops, peaking in the 2 nd decade of life. Cerebral blood flow (CBF) is dynamic throughout childhood, likely in response to the increased metabolic demand of brain development. Cerebrovascular reactivity (CVR) reflects the ability to further increase CBF in response to a stimulus, such as carbon dioxide (CO 2 ). We hypothesized that gray matter oxygen metabolism (GM CMRO 2 ) is increased in younger children, corresponding to higher GM CBF and lower GM CVR. Methods: CVR was calculated as the proportional change of a subject’s MRI-measured blood oxygen level dependent signal in response to an increase in end-tidal CO 2 administered by the RespirAct® RA-MR™ device. GM CMRO 2 was calculated voxel-by-voxel as the product of GM CBF (arterial spin labeling), GM oxygen extraction fraction (asymmetric spin echo), and arterial oxygen content (= Hb х (oxygen saturation)х1.34). Univariate relationships were tested using Spearman’s correlation coefficient, and corrected for multiple comparisons. Results: GM CVR, CBF, and CMRO 2 were calculated for 15 healthy participants (ages 8-19, 7 male). GM CMRO 2 was highest in young children and decreased with age (ρ=-0.68, P=0.005), as did CBF (ρ =-0.67, P=0.006). CVR was lower in young children, increasing with age (ρ=0.58, P=0.02). However, while GM CVR correlated with CBF (ρ=-0.64, P=0.01) it did not significantly associate with CMRO 2 (ρ=-0.43, P=0.114). Conclusion: Although GM CMRO 2 and CVR both have age-related changes, CVR does not directly correlate with CMRO 2 . Rather, their relationship may be moderated through other influences on CBF, as further study will investigate. Figure: Linear fits and 95% confidence intervals of subject data, including age, GM CBF, and GM CMRO 2 , versus GM CVR. P-values are from Spearman’s test for monotonic correlation.

Multimodal Neuromonitoring in Pediatric Neurocritical Care: Current Perspectives.

Children with neurological illness in the critical care unit are always at higher risk of developing secondary brain injury (SBI). Brain insult can lead to changes in cerebral autoregulation, intracranial pressure (ICP), cerebral oxygenation, and metabolism. This can cause a raised ICP, cerebral ischemia, hypoxia, excitotoxicity, cellular energy failure, and nonconvulsive status epilepticus. Simultaneous and continuous assessment of these parameters will help to improve patient care and neurological outcomes. Even thoughclinical examination and neuroimaging can help in the initial diagnosis of the neurological illness, they may not be helpful in continuous monitoring of cerebralpathophysiological changes. The ideal single neuromonitoring device to detect these real-time changes is currently unavailable. However, a range of invasive and noninvasive monitors are available to monitor these cerebral functional parameters. Invasive monitoring techniques include invasive ICP monitoring, cerebral autoregulation monitoring, brain tissue partial oxygen pressure, and cerebral microdialysis. Noninvasive-monitoring techniques include pupillometry, brain and ocular ultrasonography, near-infraredspectroscopy, and electrophysiological monitoring. Multimodal (MM) neuromonitoring involves incorporating these techniques and tools for the early identification and treatment of primary and secondary brain insults. The utility and feasibility of most of these techniques are well described in adult neurocritical care. Even though the evidence on their usage in children is primarily available in pediatric traumatic brain injury, the emerging data help to further expand their utility in pediatric nontraumatic coma. MM neuromonitoring aims to provide clinical and pathophysiological information to the intensivists to improve their understanding of the child's neurological status and to formulate patient-specific treatment approaches.