Baseline oxygen consumption decreases with cortical depth

The cerebral cortex is organized in cortical layers that differ in their cellular density, composition, and wiring. Cortical laminar architecture is also readily revealed by staining for cytochrome oxidase—the last enzyme in the respiratory electron transport chain located in the inner mitochondrial membrane. It has been hypothesized that a high-density band of cytochrome oxidase in cortical layer IV reflects higher oxygen consumption under baseline (unstimulated) conditions. Here, we tested the above hypothesis using direct measurements of the partial pressure of O2 (pO2) in cortical tissue by means of 2-photon phosphorescence lifetime microscopy (2PLM). We revisited our previously developed method for extraction of the cerebral metabolic rate of O2 (CMRO2) based on 2-photon pO2 measurements around diving arterioles and applied this method to estimate baseline CMRO2 in awake mice across cortical layers. To our surprise, our results revealed a decrease in baseline CMRO2 from layer I to layer IV. This decrease of CMRO2 with cortical depth was paralleled by an increase in tissue oxygenation. Higher baseline oxygenation and cytochrome density in layer IV may serve as an O2 reserve during surges of neuronal activity or certain metabolically active brain states rather than reflecting baseline energy needs. Our study provides to our knowledge the first quantification of microscopically resolved CMRO2 across cortical layers as a step towards better understanding of brain energy metabolism.publishedVersio

Reference values of physiological 18F-FET uptake: Implications for brain tumor discrimination

PURPOSE The aim of this study was to derive reference values of 18F-fluoro-ethyl-L-tyrosine positron emission tomography (18F-FET-PET) uptake in normal brain and head structures to allow for differentiation from tumor tissue. MATERIALS AND METHODS We examined the datasets of 70 patients (median age 53 years, range 15-79), whose dynamic 18F-FET-PET was acquired between January 2016 and October 2017. Maximum standardized uptake value (SUVmax), target-to-background standardized uptake value ratio (TBR), and time activity curve (TAC) of the 18F-FET-PET were assessed in tumor tissue and in eight normal anatomic structures and compared using the t-test and Mann-Whitney U-test. Correlation analyses were performed using Pearson or Spearman coefficients, and comparisons between several variables with Pearson's chi-squared tests and Kruskal-Wallis tests as well as the Benjamini-Hochberg correction. RESULTS All analyzed structures showed an 18F-FET uptake higher than background (threshold: TBR > 1.5). The venous sinuses and cranial muscles exhibited a TBR of 2.03±0.46 (confidence interval (CI) 1.92-2.14), higher than the uptake of caudate nucleus, pineal gland, putamen, and thalamus (TBR 1.42±0.17, CI 1.38-1.47). SUVmax, TBR, and TAC showed no difference in the analyzed structures between subjects with high-grade gliomas and subjects with low-grade gliomas, except the SUVmax of the pineal gland (t-tests of the pineal gland: SUVmax: p = 0.022; TBR: p = 0.411). No significant differences were found for gender and age. CONCLUSION Normal brain tissue demonstrates increased 18F-FET uptake compared to background tissue. Two distinct clusters have been identified, comprising venous structures and gray matter with a reference uptake of up to SUVmax of 2.99 and 2.33, respectively

High-precision laser spectrometer for multiple greenhouse gas analysis in 1 mL air from ice core samples

The record of past greenhouse gas composition from ice cores is crucial for our understanding of global climate change. Future ice core projects will aim to extend both the temporal coverage (extending the timescale to 1.5 Myr) and the temporal resolution of existing records. This implies a strongly limited sample availability, increasing demands on analytical accuracy and precision, and the need to reuse air samples extracted from ice cores for multiple gas analyses. To meet these requirements, we designed and developed a new analytical system that combines direct absorption laser spectroscopy in the mid-infrared (mid-IR) with a quantitative sublimation extraction method. Here, we focus on a high-precision dual-laser spectrometer for the simultaneous measurement of CH4, N2O, and CO2 concentrations, as well as d13C(CO2). Flow-through experiments at 5 mbar gas pressure demonstrate an analytical precision (1 sigma) of 0.006 ppm for CO2, 0.02‰ for d13C(CO2), 0.4 ppb for CH4, and 0.1 ppb for N2O, obtained after an integration time of 100 s. Sample–standard repeatabilities (1 sigma) of discrete samples of 1 mL STP (Standard Temperature and Pressure) amount to 0.03 ppm, 2.2 ppb, 1 ppb, and 0.04‰ for CO2, CH4, N2O, and d13C(CO2), respectively. The key elements to achieve this performance are a custom-developed multipass absorption cell, custom-made high-performance data acquisition and laser driving electronics, and a robust calibration approach involving multiple reference gases. The assessment of the spectrometer capabilities in repeated measurement cycles of discrete air samples – mimicking the procedure for external samples such as air samples from ice cores – was found to fully meet our performance criteria for future ice core analysis. Finally, this non-consumptive method allows the reuse of the precious gas samples for further analysis, which creates new opportunities in ice core science

Diurnal T2-changes of the intervertebral discs of the entire spine and the influence of weightlifting

The purpose was to study if (1) diurnal changes occur in the entire spine and if (2) intervertebral discs (IVDs) of weightlifters (WL) have decreased baseline T2-values in the morning as well as (3) increased diurnal changes throughout the day. This prospective cohort study investigated healthy volunteers between 2015 and 2017. WL were required to have participated in weightlifting ≥ 4×/week for ≥ 5 years, while non-weightlifters (NWL) were limited to < 2×/week for ≥ 5 years. Both groups underwent magnetic resonance imaging (MRI) of the entire spine in the morning and evening. WL were requested to perform weightlifting in-between imaging. IVD regions of interest (nucleus pulposus) were defined and T2-maps were measured. Analysis consisted of unpaired t-test, paired t-test, propensity-score matching (adjusting for age and sex), and Pearson correlation. Twenty-five individuals (15 [60.0%] males) with a mean age of 29.6 (standard deviation [SD 6.9]) years were analyzed. Both groups (WL: n = 12 versus [vs.] NWL: n = 13) did not differ demographic characteristics. Mean IVD T2-values of all participants significantly decreased throughout the day (95.7 [SD 15.7] vs. 86.4 [SD 13.9] milliseconds [ms]) in IVDs of the cervical (71.8 [SD 13.4] vs. 64.4 [SD 14.1] ms), thoracic (98.8 [SD 19.9] vs. 88.6 [SD 16.3] ms), and lumbar (117.0 [SD 23.7] vs. 107.5 [SD 21.6] ms) spine (P < 0.001 each). There were no differences between both groups in the morning (P = 0.635) and throughout the day (P = 0.681), even after adjusting for confounders. It can be concluded that diurnal changes of the IVDs occurred in the entire (including cervical and thoracic) spine. WL and NWL showed similar morning baseline T2-values and diurnal changes. Weightlifting may not negatively affect IVDs chronically or acutely

Reference values of physiological 18F-FET uptake: Implications for brain tumor discrimination.

PURPOSE:The aim of this study was to derive reference values of 18F-fluoro-ethyl-L-tyrosine positron emission tomography (18F-FET-PET) uptake in normal brain and head structures to allow for differentiation from tumor tissue. MATERIALS AND METHODS:We examined the datasets of 70 patients (median age 53 years, range 15-79), whose dynamic 18F-FET-PET was acquired between January 2016 and October 2017. Maximum standardized uptake value (SUVmax), target-to-background standardized uptake value ratio (TBR), and time activity curve (TAC) of the 18F-FET-PET were assessed in tumor tissue and in eight normal anatomic structures and compared using the t-test and Mann-Whitney U-test. Correlation analyses were performed using Pearson or Spearman coefficients, and comparisons between several variables with Pearson's chi-squared tests and Kruskal-Wallis tests as well as the Benjamini-Hochberg correction. RESULTS:All analyzed structures showed an 18F-FET uptake higher than background (threshold: TBR > 1.5). The venous sinuses and cranial muscles exhibited a TBR of 2.03±0.46 (confidence interval (CI) 1.92-2.14), higher than the uptake of caudate nucleus, pineal gland, putamen, and thalamus (TBR 1.42±0.17, CI 1.38-1.47). SUVmax, TBR, and TAC showed no difference in the analyzed structures between subjects with high-grade gliomas and subjects with low-grade gliomas, except the SUVmax of the pineal gland (t-tests of the pineal gland: SUVmax: p = 0.022; TBR: p = 0.411). No significant differences were found for gender and age. CONCLUSION:Normal brain tissue demonstrates increased 18F-FET uptake compared to background tissue. Two distinct clusters have been identified, comprising venous structures and gray matter with a reference uptake of up to SUVmax of 2.99 and 2.33, respectively

ELIMU-MDx: a web-based, open-source platform for storage, management and analysis of diagnostic qPCR data

The Electronic Laboratory Information and Management Utensil for Molecular Diagnostics (ELIMU-MDx) is a user-friendly platform designed and built to accelerate the turnaround time of diagnostic qPCR assays. ELIMU-MDx is compliant with Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines and has extensive data-import capabilities for all major qPCR instruments by using the RDML data standard. This platform was designed as an open-source software tool and can be accessed through the web browser on all major operating systems

Data_Sheet_1_Tissue Oxygen Depth Explorer: an interactive database for microscopic oxygen imaging data.docx

The full text of this article can be freely accessed on the publisher's website

NH4+ triggers the release of astrocytic lactate via mitochondrial pyruvate shunting

Neural activity is accompanied by a transient mismatch between local glucose and oxygen metabolism, a phenomenon of physiological and pathophysiological importance termed aerobic glycolysis. Previous studies have proposed glutamate and K(+) as the neuronal signals that trigger aerobic glycolysis in astrocytes. Here we used a panel of genetically encoded FRET sensors in vitro and in vivo to investigate the participation of NH4(+), a by-product of catabolism that is also released by active neurons. Astrocytes in mixed cortical cultures responded to physiological levels of NH4(+) with an acute rise in cytosolic lactate followed by lactate release into the extracellular space, as detected by a lactate-sniffer. An acute increase in astrocytic lactate was also observed in acute hippocampal slices exposed to NH4(+) and in the somatosensory cortex of anesthetized mice in response to i.v. NH4(+). Unexpectedly, NH4(+) had no effect on astrocytic glucose consumption. Parallel measurements showed simultaneous cytosolic pyruvate accumulation and NADH depletion, suggesting the involvement of mitochondria. An inhibitor-stop technique confirmed a strong inhibition of mitochondrial pyruvate uptake that can be explained by mitochondrial matrix acidification. These results show that physiological NH4(+) diverts the flux of pyruvate from mitochondria to lactate production and release. Considering that NH4(+) is produced stoichiometrically with glutamate during excitatory neurotransmission, we propose that NH4(+) behaves as an intercellular signal and that pyruvate shunting contributes to aerobic lactate production by astrocytes

sj-pdf-1-jcb-10.1177_0271678X231203023 - Supplemental material for A lone spike in blood glucose can enhance the thrombo-inflammatory response in cortical venules

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X231203023 for A lone spike in blood glucose can enhance the thrombo-inflammatory response in cortical venules by Iftach Shaked, Conrad Foo, Philipp Mächler, Rui Liu, Yingying Cui, Xiang Ji, Thomas Broggini, Tomasz Kaminski, Suchita Suryakant Jadhav, Prithu Sundd, Michael Firer, Anna Devor, Beth Friedman and David Kleinfeld in Journal of Cerebral Blood Flow & Metabolism</p