Monitoring Of Brain Metabolism Research Articles

Technical notes on the placement of cerebral microdialysis: A single center experience.

Cerebral microdialysis enables monitoring of brain metabolism and can be an important part of multimodal monitoring strategies in a variety of brain injuries. Microdialysis catheters can be placed in brain parenchyma through a burr hole, a cranial bolt, or directly at the time of an open craniotomy or craniectomy. The location of catheters in relation to brain pathology is important to the interpretation of data and guidance of interventions. Here we retrospectively review the use of cerebral microdialysis at a US Regional Medical Center between March 2018 and February 2022 and provide detailed descriptions and technical nuances of the different methods to place microdialysis catheters. Eighty two unique microdialysis catheters were utilized in 52 patients. 35 (42.68%) were placed via a quad-lumen bolt and 47 (57.32%) were placed through craniotomies. 27 catheters (32.93%) were placed in a perilesional location, 50 (60.98%) were located in healthy tissue, and 6 (7.32%) were mispositioned. No significant difference was seen between placement by bolt or craniotomy in regard to perilesional location, mispositioning, or complications. With careful planning and thoughtful execution, cerebral microdialysis catheters can be successfully placed though a variety of strategies to optimize and individualize brain monitoring in different clinical settings. This paper provides a detailed guide for the various methods of catheter placement to help providers begin or expand their use of cerebral microdialysis.

Evaluation of Two Post-Processing Analysis Methods of Proton Magnetic Resonance Spectroscopy in Glioma Tumors.

Magnetic resonance spectroscopy (MRS) is a non-invasive diagnostic and the neuroimaging method of choice for the noninvasive monitoring of brain metabolism in patients with glioma tumors. 1H-MRS is a reliable and non-invasive tool used to study glioma. However, the metabolite spectra obtained by 1H-MRS requires a specific quantification procedure for post-processing. According to our knowledge, no comparisons have yet been made between spectrum analysis software for quantification of gliomas metabolites. Current study aims to evaluate the difference between this two common software in quantifying cerebral metabolites. In this analytical study, we evaluate two post-processing software packages, java-based graphical for MR user interface packages (jMRUI) and totally automatic robust quantitation in NMR (TARQUIN) software. 1H-MRS spectrum from the brain of patients with gliomas tumors was collected for post-processing. AMARES algorithms were conducted to metabolite qualification on jMRUI software, and TARQUIN software were implemented with automated quantification algorithms. The study included a total of 30 subjects. For quantification, subjects were divided into a normal group (n=15) and group of gliomas (n=15). When calculated by TARQUIN, the mean metabolites ratio was typically lower than by jMRUI. While, the mean ratio of metabolites varied when quantified by jMRUI vs. TARQUIN, both methods apparent clinical associations. TARQUIN and jMRUI are feasible choices for the post-processing of cerebral MRS data obtained from glioma tumors.

Vasoactive agents to improve brain perfusion: pathophysiology and clinical utilization.

This review highlights the aspects of pathophysiology that make it difficult to predict the effects of any attempt to improve brain perfusion and reviews the options to improve brain perfusion according to the needs of an individual patient, focusing on the choice of a suitable threshold for cerebral perfusion pressure. Typically, vasopressors or vasodilators that do not directly influence the cerebral vascular bed are used to improve cerebral perfusion. Positive inotropic substances are rarely used, as the relationship between cardiac output and cerebral blood flow is complex and difficult to measure. Combining perfusion pressure monitoring with monitoring of brain metabolism or oxygenation to adapt cerebral perfusion to the needs of an individual patient has been disappointing. Recently, attempts to individualize perfusion pressure based on measurements of cerebrovascular autoregulation have shown promising results in the management of traumatic brain injury and during cardiac surgery. Currently, only preliminary data are available linking optimized cerebral perfusion to improved outcome. Optimizing cerebral perfusion remains a difficult goal. All our attempts to manipulate brain perfusion are influenced in an unpredictable manner by underlying diseases. Autoregulation-based strategies to individualize cerebral perfusion management warrant further investigation.

Metabolomic Assays of Postmortem Brain Extracts: Pitfalls in Extrapolation of Concentrations of Glucose and Amino Acids to Metabolic Dysregulation In Vivo in Neurological Diseases.

Glucose utilization is reduced in vulnerable brain regions affected by neurological disorders, especially Alzheimer's disease (AD), but the basis for abnormal glucose homeostasis is unknown. Studies of brain-bank human tissue have made major contributions to understanding complex aspects of neurological, psychiatric, and neurodegenerative diseases, but they are not appropriate for metabolomic analysis of labile metabolites because postmortem intervals between death and tissue freezing are much too long. Recent reports of postmortem brain glucose levels led to suggestions that AD patients may be hyperglycemic and that elevated brain glucose levels along with reduced glycolytic activity reveal abnormal glucose homeostasis before clinical symptoms become manifest. These conclusions are, however, questioned because virtually all brain glucose is consumed within minutes after death, followed by progressive increases in glucose and amino acid levels, presumably due to autolytic changes. To illustrate pitfalls in use of autopsy material for metabolomic assays of labile metabolites, data from living human brain are compared with those from autopsy samples, and metabolism at the onset of postmortem ischemia is compared with calculated glycolytic enzyme activities. Postmortem glucose levels range from extremely low to unrealistically high, precluding their extrapolation to living brain. Indirect evaluation of glycolytic enzyme activities in postmortem AD brain is not valid because the glucose and amino acid concentrations used in the calculations are not stable after death, and reported values are unrealistically high. Specific recommendations are provided for non-invasive longitudinal monitoring of brain metabolism and metabolite levels in patients with neurological diseases.

Hemodynamic and metabolic parameters in brain injury

Introduction: Indirect monitoring of brain metabolism through parameters such as cerebral perfusion pressure (CPP), intracranial pressure (ICP), arterial CO2 partial pressure (PaCO2) and mean arterial blood pressure (MABP) is necessary to guide treatment and to prevent secondary cerebral ischemia. The aim of the present study was to analyze the association between cerebral hemodynamic and metabolic parameters and the occurrence of traumatic brain ischemia. Methods: Thirty-one patients were prospectively assessed in the pediatric or adult intensive care unit of Hospital de Pronto Socorro (HPS), in Porto Alegre, Brasil, from April to December, 2003. Patients were 23 adults (aged 17 to 66 years-old ) and eight children (aged 3 to 13 years-old) with severe traumatic brain injury( TBI ) . Mean age was 24 years. The inclusioncriteria were Glasgow coma scale (GCS) below 8 and abnormal cranial computed tomography (CT) results. Intracranial pressure, mean arterial blood pressure, arterial CO2 partial pressure and cerebral perfusion pressure were recorded. Results: Cerebral ischemia was identified in 13 adults (56.5%) and in seven children (87.5%). High MABP was associated with mortality (P<=0.005) in children. High ICP (P= 0.03) and low CPP (P=0.007) in adults were associated with cerebral ischemia. Fourteen patients (45.2%) died: 13 adults (56.5%) and one child (12.5%). Adult patients with low CPP had a worse outcome with higher mortality rate (P=0.045). Conclusions: High ICP, high MABP and low CPP were associated with traumatic brain ischemia and higher mortality rate in these patients.

Parallel Effect of Nicotine and MK-801 on Brain Metabolism: An In vivo Non Invasive Near-Infrared Spectroscopy Analysis in Rats

Oxygenated haemoglobin, deoxyhaemoglobin and total blood volume are measured with our recently developed Near-Infrared Spectroscopy [NIRS] apparatus allowing in vivo non invasive real time monitoring of brain metabolism in anaesthetized rats. These measurements are indicative of the state of vascular activity and the state of the oxygen saturation, thus of the level of metabolism in the living tissue. Nicotine is a natural alkaloid derived from tobacco that has been implicated in various effects ranging from addiction to toxic effects and neuro-protective actions. Here we analyse the influence of nicotine as well as that of the non competitive NMDA receptor antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate)] upon brain metabolism in anaesthetized rats. In the first 30min after treatment, nicotine decreases significantly although in a transient manner oxygenated haemoglobin and total blood volume while increasing significantly deoxyhaemoglobin. In addition, MK-801 performed in another group of rats was followed by changes in these three parameters that were similar to those monitored in nicotine treated rats. The NIRS methodology appears to be apt to analyzing non-invasively and in real time the influence of systemic pharmacological treatments upon brain metabolism. In particular the data gathered show similarity of action of the two chemicals studied on influencing metabolic brain “behaviour” proposing that their central protective action may pass via the observed similar changes in brain metabolism. These changes could be a common mechanism of adaptation and protection towards neurotoxicity: mechanism that should be also considered in the intent of developing new pharmaceutical approaches for neuro-protective treatments.

The diagnostic accuracy of brain microdialysis during surgery: a qualitative systematic review

Monitoring of brain function and metabolism during surgery may be of benefit for patient outcome. Microdialysis is the only sampling technique to date that allows continuous monitoring of drug or metabolite concentrations in the extracellular fluid of multiple tissues in the brain. This qualitative systematic review aimed to determine whether microdialysis is a valid tool for detecting changes in tissue composition as would be expected upon changes in (induced) tissue metabolic composition during brain surgery. A systematic review was conducted by performing a MEDLINE search using the terms "Intraoperative Period" (Medical Subject Heading [MeSH]) OR "Surgery" [Subheading] OR "Monitoring, Intraoperative" [MeSH] AND "Microdialysis" [MeSH] AND "Brain" [MeSH]. Two reviewers independently assessed the methodological quality of the studies. For each study the grades of recommendation were determined. The search strategy yielded 46 publications in Medline. Data extraction was performed on 16 studies. The methodological quality of studies was low, with overall scores of 4 or 5. A quantitative analysis could not be performed because of lack of sufficient data. A qualitative analysis was positive with regard to the detection of different states of tissue composition by microdialysis. However, the levels of recommendation on the outcome statements were low, resulting in a grade D level of recommendation on all statements. The available evidence for the validity of cerebral microdialysis as a diagnostic tool during brain surgery is of low scientific quality. In order to develop cerebral microdialysis as a valid instrument for monitoring of brain metabolism during surgery, standardised clinical prospective studies in homogeneous patient populations are required.

Elevated Intracranial Pressure, Low Cerebral Perfusion Pressure, and Impaired Brain Metabolism Correlate with Fatal Outcome After Severe Brain Injury

New brain tissue monitoring techniques (tissue oxymetry, microdialysis) provide direct information about the state of brain oxygenation and brain metabolism in patients with severe traumatic brain injury (TBI). Despite this information being limited to a small region of the brain surrounding the probes, it could be associated with such global parameters as the clinical outcome. To study the predictive value of monitoring brain oxygenation and metabolism on clinical outcome in patients in the acute phase of severe TBI. An observational study of 20 patients with a severe TBI was undertaken, utilizing intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygenation, and brain metabolism monitoring. We correlated the clinical outcome of the patients with the following parameters: ICP, CPP, brain tissue oxymetry (PbtO2), glucose and glycerol levels, and the lactate/pyruvate (LP) ratio. Further, we analyzed the relationship between ICP, CPP, PbtO2, and the metabolism parameters. We found a correlation of the mean ICP values (8.73 ± 1.18 in group A vs. 26.32 ± 5.01 mmHg in group B, p < 0.005), the mean CPP values (84.82 ± 2.02 in group A vs. 66.62 ± 4.64 mmHg, p < 0.005), the LP ratio (37.36 ± 3.44 vs. 199 ± 87.97, p < 0.05), and glycerol levels (62.07 ± 12.14 vs. 215 ± 46.52 μmol/l, p < 0.05) with the clinical outcome. High ICP correlated with both a high LP ratio (Spearman R = 0.61, p < 0.05), and elevated glycerol concentrations (Spearman R = 0.48, p < 0.05). A low CPP correlated with a high LP ratio (Spearman R = -0.57, p < 0.05), while a low PbtO2 correlated with a high LP ratio (Spearman R = -0.49, p < 0.05). High ICP, low CPP, an elevated mean LP ratio, and high glycerol concentrations in the acute phase predict fatal outcome 6 months after TBI. Further, high ICP, low CPP, and low PbtO2 correlate with impaired brain metabolism.

Elevated Intracranial Pressure, Low Cerebral Perfusion Pressure, and Impaired Brain Metabolism Correlate with Fatal Outcome After Severe Brain Injury

BACKGROUND New brain tissue monitoring techniques (tissue oxymetry, microdialysis) provide direct information about the state of brain oxygenation and brain metabolism in patients with severe traumatic brain injury (TBI). Despite this information being limited to a small region of the brain surrounding the probes, it could be associated with such global parameters as the clinical outcome. OBJECTIVE To study the predictive value of monitoring brain oxygenation and metabolism on clinical outcome in patients in the acute phase of severe TBI. METHODS An observational study of 20 patients with a severe TBI was undertaken, utilizing intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygenation, and brain metabolism monitoring. We correlated the clinical outcome of the patients with the following parameters: ICP, CPP, brain tissue oxymetry (PbtO2), glucose and glycerol levels, and the lactate/pyruvate (LP) ratio. Further, we analyzed the relationship between ICP, CPP, PbtO2, and the metabolism parameters. RESULTS We found a correlation of the mean ICP values (8.73 ± 1.18 in group A vs. 26.32 ± 5.01 mmHg in group B, p < 0.005), the mean CPP values (84.82 ± 2.02 in group A vs. 66.62 ± 4.64 mmHg, p < 0.005), the LP ratio (37.36 ± 3.44 vs. 199 ± 87.97, p < 0.05), and glycerol levels (62.07 ± 12.14 vs. 215 ± 46.52 μmol/l, p < 0.05) with the clinical outcome. High ICP correlated with both a high LP ratio (Spearman R = 0.61, p < 0.05), and elevated glycerol concentrations (Spearman R = 0.48, p < 0.05). A low CPP correlated with a high LP ratio (Spearman R = -0.57, p < 0.05), while a low PbtO2 correlated with a high LP ratio (Spearman R = -0.49, p < 0.05). CONCLUSIONS High ICP, low CPP, an elevated mean LP ratio, and high glycerol concentrations in the acute phase predict fatal outcome 6 months after TBI. Further, high ICP, low CPP, and low PbtO2 correlate with impaired brain metabolism.

Two-photon deep imaging through skin and skull of Zebra finch for in vivo brain metabolism monitoring.

Zebra Finches are songbirds which constitute a model for neuro-ethologists to study the neuro-mechanisms of vocal recognition. For this purpose, in vivo and non invasive monitoring of brain activity is required during acoustical stimulation. MRI (Magnetic Resonance Imaging) or NIRS (Near InfraRed Spectroscopy) are suitable methods for these measurements, even though MRI is difficult to link quantitatively with neural activity and NIRS suffers from a poor resolution. In the particular case of songbirds (whose skin is thin and quite transparent and whose skull structure is hollow), two-photon microscopy enables a quite deep penetration in tissues and could be an alternative. We present here preliminary studies on the feasability of two-photon microscopy in these conditions. To do so, we chose to image hollow fibers, filled with Rhodamine B, through the skin of Zebra finches in order to evaluate the spatial resolution we may expect in future in vivo experiments. Moreover, we used the reflectance-mode confocal configuration to evaluate the exponential decrease of backreflected light in skin and in skull samples. Following this procedure recently proposed by S.L. Jacques and co-workers, we planned to determine the scattering coefficient μ s and the anisotropy g of these tissues and make a comparison between fixed and fresh skin and skull samples for future Monte Carlo simulations of the scattering in our particular multi-layered structure.

The implications of cerebral ischemia and metabolic dysfunction for treatment strategies in neurointensive care

This review outlines recent observations made in a clinical setting that document the extent and degree of cerebral ischemia and metabolic dysfunction after acute brain injury. The intent is to guide clinicians in considering how best to monitor and treat brain metabolism in the intensive care unit. Recent findings have documented that following brain injury there is a heterogeneous distribution of disturbed metabolism with some areas of the brain rendered severely oligemic or ischemic while other areas are less affected. Areas that are not truly ischemic, however, still appear to be at risk of excitotoxic injury. Various methods of monitoring the brain are compared and discussed, including positron emission tomography, brain parenchymal oxygenation monitoring, brain microdialysis, and continuous electroencephalography; important caveats are also presented. These methods are complementary and provide information about oxygen utilization and other aspects of brain metabolism. Integration of these methods into a practical clinical protocol is discussed. The intensive care of acute brain injury has entered a new era in which monitoring of brain metabolism will permit targeted therapy and may possibly minimize iatrogenic adverse effects by making better use of our powerful therapies.

Monitoring of head injured patients

This article reviews recent advances in multimodality monitoring of patients following severe head injury during the period of 2004-2005. Whilst intracranial pressure measurement remains the cornerstone of neuromonitoring, analysis of the intracranial pressure waveform provides additional information, which may help guide treatment and predict outcome. Non-invasive detection of intracranial hypertension and assessment of cerebral perfusion pressure and autoregulation is the focus of ongoing research. Although jugular venous saturation monitoring remains a useful method for detecting global hypoperfusion its sensitivity to regional ischaemia is low. Brain tissue oxygen monitoring overcomes this deficiency and sheds new light on the pathophysiology of cerebral ischaemia following brain injury. Further studies are required to define ischaemic thresholds and their association with outcome. Extracellular brain pH has been recently linked to outcome and further studies are required to establish the role of pH regulation. Monitoring of brain metabolism using a cerebral microdialysis continues to develop its niche in clinical neuromonitoring, although it currently remains a research tool. Multimodality neuromonitoring plays an important role in managing patients with severe head injury. It helps guide treatment, provides prognostic information and explores the pathophysiology of evolving brain injury.

Resolving dynamic changes in brain metabolism using biosensors and on-line microdialysis

A tight coupling exists in the brain between the activity of neurons, the energetic consequences of this activity and the local blood flow. This makes the monitoring of the levels of energy metabolites, such as glucose and lactate, in the fluid surrounding the neurons a particularly effective means of studying brain function. This review outlines why rapid monitoring of brain metabolism in vivo is effective, and demonstrates how the in vivo techniques of implanted biosensors and on-line microdialysis can be used to study the brain in the laboratory and in brain-injury patients.

Monitoring of brain metabolism during aneurysm surgery using microdialysis and brain multiparameter sensors

The aim of the study was to monitor brain metabolism during aneurysm clipping using microdialysis and multiparameter sensors, particularly to investigate the effects of temporary clipping of vessels. Microdialysis catheters (n= 10) and Paratrend brain multiparameter (02, C02, pH and temperature) sensors (n = 15) were inserted into the cerebral cortex via a specially designed triple bolt prior to craniotomy. Baseline brain 02 levels ranging from 15-45 mmHg (2.0-6.0 kPa) and glucose levels from 0.5-3 mmol l~1 were stable during uneventful periods. The mean lactate/pyruvate (L/P) ratio ranged from 32 to 65 (normal < 30), indicating a tendency towards anerobic metabolism in all patients. Overall, short periods of temporary clipping (<3 min; n = 6) were well tolerated producing no significant reduction in brain 02 (pre-clip mean 23mmHg (3.0 kPa) vs. post-clip mean 20 mmHg (2.6 kPa)) or elevation of the L/P ratio (pre-clip mean 42 vs. post-clip mean 43). Two patients with prolonged temporary clipping showed derangements in the Paratrend parameters associated with increases in the L/P ratio. The results demonstrated that the monitored variables remained stable during uneventful procedures, including transient temporary clipping, but adverse events such as prolonged temporary clipping resulted in pronounced changes in brain metabolism. Monitoring of metabolism during aneurysm surgery may be of benefit in selected patients. [Neurol Res 1999; 21: 352-358]

Brain Metabolism Monitoring during Aneurysm Clipping

Brain Metabolism Monitoring during Aneurysm Clipping

Multiparametric continuous monitoring of brain metabolism and substrate delivery in neurosurgical patients

Brain function and tissue integrity are highly dependent on continuous oxygen supply and clearance of CO2. Aerobic metabolism is the major energy source to normal brain, however, during hypoxia and ischemia, lactate accumulation may sometimes be seen, indicating anaerobic glycolysis after severe head injury. Current monitoring techniques often fail to detect such events which can affect substrate delivery to the injured brain. We have recently adapted a method for continuous monitoring of brain tissue p02, pC02, pH and temperature, using a single sensor. The multiparameter sensor is inserted into brain tissue, via a new three lumen bolt, together with a standard ventriculostomy catheter and a microdialysis probe. The system has been left in place as long as needed, but never more than 7, days. All readings were compared to clinical parameters, and outcome. Stable measurements could be obtained in the first group of 20 patients, after calibration and rigid fixation, using the new bolt. Severely head injured patients had brain oxygen levels of less than 25-30 mmHg for the first hours, after injury. Thereafter two patterns could be seen. Patients with favorable outcome had a slow increase in brain oxygen, and braln CO2 decreased to normal values, as long as the cerebral perfusion pressure (CPP) was kept above 70 mmHg. However, in those patients with secondary isc;;hemic events, and bad outcome, a further decline in brain oxygen to anaerobic levels (< 20 mmHg) was seen. For these patients, both decreased and increased brain CO2 levels could be seen. Brain CO2 levels of 90–150 mmHg were consistently seen after brain death. Brain pH was inversely related to brain CO2 for all fatients. Brain glucose and lactate in patients with poor outcome were 639 pM 1- 1 ± 330, and 1642 μM 1- ± 788, whereas patIents wIth good outcome had brain glucose levels of 808 μM 1- 1 ± 321 and lactate levels of 1001 μM 1- 1 ± 417. Extended neuromonitoring using a combined sensor for brain oxygen, CO2, pH and temperature measurements, as well as a microdialysis probe for glucose and lactate analysis may optimize the management of comatose neurosurgical patients in the future, by allowing a fuller understanding of dynamic factors affecting brain metabolism. [Neural Res 1997; 19: 265–273]

Multisite measurements of NADH redox state from cerebral cortex of the awake animal.

There are few non-destructive non-invasive approaches to the study of cortical oxidative metabolism. Nevertheless, the great necessity for the development and application of such approaches arises from the inadequacy of cell and brain slice models on the one hand and the need for interpretive monitoring of brain metabolism in humans, or if possible, under non-operative conditions. Two techniques can be used to study metabolism of the brain without the necessity of an operation, 31P NMR which is totally non-invasive and positron emission tomography which requries injection and delivery of the radio isotope. Neither of these methods affords an adequately sharp localization to provide better than regional localization (lam) under current conditions of development and application, on the other hand, when the subject is sacrificed and autoradiography of tritium labelled deoxyglucose is employed, a high degree of metabolic resolution can be obtained albeit the method averages events over times as long as 45 minutes. The need for a non-destructive continuous read out method for brain metabolism providing a high degree of localization, both spacially and within appropriate metabolic compartments is obtained with the fluorescence of mitochondrial pigments, NADH or flavoprotein. Furthermore, this method is applicable as well to frozen tissue surfaces affording high resolution 3D spacial resolution. The discovery that mitochondrial NADH is fluorescent and that the fluorescence is enhanced 15 or more times over that of the pigment in solution afforded a unique “look” at metabolic events in the matrix base of mitochondria; the NADPH therein was found not to respond to variations of electron transport in the respiratory chain (1–3). Furthermore, comparisons of changes of NADH fluorescence could be well correlated with actual tissue assays of NADH in heart and liver (4,5).KeywordsLight GuideSpreading DepressionCarotid Artery OcclusionAwake AnimalGerbil BrainThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.