Deuterium labeling enables non-invasive 3D proton MR imaging of glucose and neurotransmitter metabolism in the human brain

2021 ◽  
Author(s):  
Petr Bednarik ◽  
Dario Goranovic ◽  
Alena Svátková ◽  
Fabian Niess ◽  
Lukas Hingerl ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Brain Diseases ◽  
Gamma Aminobutyric Acid ◽  
Deuterium Labeling ◽  
Non Invasive ◽  
Positron Emission ◽  
Novel Method ◽  
Specialized Hardware ◽  
First Time ◽  
Higher Sensitivity

Abstract Impaired brain glucose metabolism characterizes most severe brain diseases. Recent studies have proposed deuterium (2H)-Magnetic Resonance Spectroscopic Imaging (MRSI) as a reliable, non-invasive, and safe method to quantify the human metabolism of 2H-labeled substrates such as glucose and their downstream metabolism (e.g., aerobic/anaerobic glucose utilization and neurotransmitter synthesis) and address the major drawbacks of positron emission tomography (PET) or carbon (13C)-MRS. Here, for the first time, we show an indirect dynamic proton (1H)-MRSI technique in humans, which overcomes four critical 2H-MRSI limitations. Our innovative approach provides higher sensitivity with improved spatial/temporal resolution and higher chemical specificity to differentiate glutamate (Glu4), glutamine (Gln4), and gamma-aminobutyric acid (GABA2) deuterated at specific molecular positions while allowing simultaneous mapping of both labeled and unlabeled metabolites without the need for specialized hardware. Our novel method demonstrated significant Glu4, Gln4, and GABA2 decreases, with 18% faster Glu4 reduction in the gray matter than white matter after ingestion of deuterated glucose. Thus, robustly detected downstream glucose metabolism utilizing clinically available MR hardware without the need for radioactive tracers and PET.

scholarly journals Kinetic modeling and parameter estimation of TSPO PET imaging in the human brain

2021 ◽  
Author(s):  
Catriona Wimberley ◽  
Sonia Lavisse ◽  
Ansel Hillmer ◽  
Rainer Hinz ◽  
Federico Turkheimer ◽  
...  
Keyword(s):  
Human Brain ◽  
Input Function ◽  
Translocator Protein ◽  
Alternative Methods ◽  
Brain Diseases ◽  
Brain Vessels ◽  
Non Invasive ◽  
Positron Emission ◽  
The Brain ◽  
Tspo Imaging

Abstract Purpose Translocator protein 18-kDa (TSPO) imaging with positron emission tomography (PET) is widely used in research studies of brain diseases that have a neuro-immune component. Quantification of TSPO PET images, however, is associated with several challenges, such as the lack of a reference region, a genetic polymorphism affecting the affinity of the ligand for TSPO, and a strong TSPO signal in the endothelium of the brain vessels. These challenges have created an ongoing debate in the field about which type of quantification is most useful and whether there is an appropriate simplified model. Methods This review focuses on the quantification of TSPO radioligands in the human brain. The various methods of quantification are summarized, including the gold standard of compartmental modeling with metabolite-corrected input function as well as various alternative models and non-invasive approaches. Their advantages and drawbacks are critically assessed. Results and conclusions Researchers employing quantification methods for TSPO should understand the advantages and limitations associated with each method. Suggestions are given to help researchers choose between these viable alternative methods.

scholarly journals Advanced Fusion and Empirical Mode Decomposition-Based Filtering Methods for Breathing Rate Estimation from Seismocardiogram Signals

Information ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 368
Author(s):  
Christina Kozia ◽  
Randa Herzallah
Keyword(s):  
Empirical Mode Decomposition ◽  
Absolute Error ◽  
Invasive Technique ◽  
Breathing Rate ◽  
Non Invasive ◽  
Use Of Data ◽  
Mode Decomposition ◽  
Novel Method ◽  
The Individual ◽  
First Time

Breathing Rate (BR), an important deterioration indicator, has been widely neglected in hospitals due to the requirement of invasive procedures and the need for skilled nurses to be measured. On the other hand, biomedical signals such as Seismocardiography (SCG), which measures heart vibrations transmitted to the chest-wall, can be used as a non-invasive technique to estimate the BR. This makes SCG signals a highly appealing way for estimating the BR. As such, this work proposes three novel methods for extracting the BR from SCG signals. The first method is based on extracting respiration-dependent features such as the fundamental heart sound components, S1 and S2 from the SCG signal. The second novel method investigates for the first time the use of data driven methods such as the Empirical Mode Decomposition (EMD) method to identify the respiratory component from an SCG signal. Finally, the third advanced method is based on fusing frequency information from the respiration signals that result from the aforementioned proposed methods and other standard methods. The developed methods in this paper are then evaluated on adult recordings from the combined measurement of ECG, the Breathing and Seismocardiograms database. Both fusion and EMD filter-based methods outperformed the individual methods, giving a mean absolute error of 1.5 breaths per minute, using a one-minute window of data.

Bee Markers: A Novel Method for Non-Invasive Short Term Marking of Bats

2020 ◽  
Vol 21 (2) ◽  
pp. 465 ◽  
Author(s):  
Lucinda Kirkpatrick ◽  
Grzegorz Apoznański ◽  
Luc De Bruyn ◽  
Ralf Gyselings ◽  
Tomasz Kokurewicz
Keyword(s):  
Short Term ◽  
Non Invasive ◽  
Novel Method

Organic Reactivity Control by Means of Neighboring Groups and Organometallics. A Personal Account

1994 ◽  
Vol 59 (1) ◽  
pp. 1-74 ◽  
Author(s):  
Pavel Kočovský
Keyword(s):  
Transition Metals ◽  
Cyclopropane Ring ◽  
Allylic Substitutions ◽  
Recent Developments ◽  
Cardioactive Drug ◽  
Novel Method ◽  
Metal Catalyzed ◽  
Electrophilic Additions ◽  
Near Future ◽  
First Time

This review summarizes the main topics of our research and covers the period of the last 15 years. The prime interest is focused on various ways of controlling the regio- and stereoselectivity of selected organic reactions, in particular electrophilic additions, cleavage of cyclopropane rings, and allylic substitutions by means of neighboring groups and/or transition and non-transition metals. In the first part, the factors governing the course of electrophilic additions are assessed, culminating in the formulation of selection rules for the reactivity of cyclohexene systems, and in a concise synthesis of the natural cardioactive drug, strophanthidin. These studies also contribute to a better understanding of the mechanisms of electrophilic additions. The second part describes recent developments in the stereo- and regiocontrolled cleavage of cyclopropane rings by non-transition metals (Tl and Hg), and the reactivity and transmetalation (with Pd) of the primary products. This methodology has resulted in novel routes to unique polycyclic structures, and will have synthetic applications in the near future. Evidence for the stereospecific "corner" cleavage of the cyclopropane ring has been provided for the first time for Tl and later for Hg. The third part deals with transition metal-catalyzed allylic substitution. Evidence for a new "syn" mechanism for the formation of the intermediate (π-allyl)palladium complex has been provided, which runs counter to the generally accepted "anti" mechanism. A novel method for a Pd-catalyzed allylic oxidation has been developed and employed in the synthesis of natural sesquiterpenes. The increasing importance of transition and non-transition metals for synthetic organic chemistry is demonstrated by their unique reactivity in a number of the papers included in this review.

[11C]Flumazenil Positron Emission Tomography Analyses of Brain Gamma-Aminobutyric Acid Type A Receptors in Angelman Syndrome

2008 ◽  
Vol 152 (4) ◽  
pp. 546-549.e3 ◽  
Author(s):  
Naoko Asahina ◽  
Tohru Shiga ◽  
Kiyoshi Egawa ◽  
Hideaki Shiraishi ◽  
Shinobu Kohsaka ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Angelman Syndrome ◽  
Type A ◽  
Emission Tomography ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Positron Emission ◽  
Acid Type

scholarly journals Raman spectroscopic detection of interleukin-10 and angiotensin converting enzyme

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Shuo Zhang ◽  
Frederieke A. M. van der Mee ◽  
Roel J. Erckens ◽  
Carroll A. B. Webers ◽  
Tos T. J. M. Berendschot
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Biomedical Applications ◽  
Interleukin 10 ◽  
Spectral Features ◽  
Converting Enzyme ◽  
Raman Spectroscopic ◽  
Non Invasive ◽  
Confocal Raman ◽  
First Time ◽  
Enzyme Characteristic

AbstractIn this report we present a confocal Raman system to identify the unique spectral features of two proteins, Interleukin-10 and Angiotensin Converting Enzyme. Characteristic Raman spectra were successfully acquired and identified for the first time to our knowledge, showing the potential of Raman spectroscopy as a non-invasive investigation tool for biomedical applications.

Evaluation and Diagnosis of Brain Diseases based on Non-invasive BCI

2021 ◽  
Author(s):  
Zuoting Song ◽  
Tao Fang ◽  
Jing Ma ◽  
Yuan Zhang ◽  
Song Le ◽  
...  
Keyword(s):  
Brain Diseases ◽  
Non Invasive

Ionized AGN outflows are less powerful than assumed: A multi-wavelength census of outflows in type II AGN

2019 ◽  
Vol 15 (S356) ◽  
pp. 225-225
Author(s):  
Dalya Baron
Keyword(s):  
Optical Emission ◽  
Infrared Emission ◽  
Type Ii ◽  
Ionized Gas ◽  
Kinetic Coupling ◽  
Mass Outflow ◽  
Multi Wavelength ◽  
Novel Method ◽  
First Time ◽  
Ionization Parameter

AbstractIn this talk I will show that multi-wavelength observations can provide novel constraints on the properties of ionized gas outflows in AGN. I will present evidence that the infrared emission in active galaxies includes a contribution from dust which is mixed with the outflow and is heated by the AGN. We detect this infrared component in thousands of AGN for the first time, and use it to constrain the outflow location. By combining this with optical emission lines, we constrain the mass outflow rates and energetics in a sample of 234 type II AGN, the largest such sample to date. The key ingredient of our new outflow measurements is a novel method to estimate the electron density using the ionization parameter and location of the flow. The inferred electron densities, ∼104.5 cm−3, are two orders of magnitude larger than found in most other cases of ionized outflows. We argue that the discrepancy is due to the fact that the commonly-used [SII]-based method underestimates the true density by a large factor. As a result, the inferred mass outflow rates and kinetic coupling efficiencies are 1–2 orders of magnitude lower than previous estimates, and 3–4 orders of magnitude lower than the typical requirement in hydrodynamic cosmological simulations. These results have significant implications for the relative importance of ionized outflows feedback in this population.

scholarly journals FSMP-06. IN VIVO MONITORING OF LDHA EXPRESSION IN GLIOBLASTOMA USING QUANTITATIVE EXCHANGED-LABEL TURNOVER 1H MRS TECHNIQUE

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. i17-i17
Author(s):  
Puneet Bagga ◽  
Laurie Rich ◽  
Mohammad Haris ◽  
Neil Wilson ◽  
Mitch Schnall ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Lactate Production ◽  
Deuterium Labeling ◽  
1H Mrs ◽  
In Vivo Monitoring ◽  
Lactate Turnover ◽  
Crucial Information ◽  
Specialized Hardware

Abstract Most cancers, including glioblastomas (GBMs), rely extensively on glycolysis to support growth, proliferation, and survival. A hallmark of this elevated glycolysis is overexpression of Lactate dehydrogenase-A (LDHA) protein leading to increased uptake of glucose and overproduction of lactate. Various clinical trials using LDHA as a target for diagnosis and treatment have yielded encouraging results. However, in vivo monitoring of LDHA expression has been challenging due to either requirement of administration of radioactive substrates or specialized hardware. In this presentation, we will demonstrate a new method-quantitative exchanged-label turnover MRS (QELT, or simply qMRS)-that increases the sensitivity of magnetic resonance-based metabolic mapping without the requirement for specialized hardware. qMRS relies on the administration of deuterated (2H-labeled) substrates to track the production of downstream metabolites. Since 2H is invisible on 1H MRS, replacement of 1H with 2H due to metabolic turnover leads to an overall reduction in 1H MRS signal for the corresponding metabolites. We applied our qMRS technique to monitor the rate of lactate production in a preclinical GBM model. Infusion of [6,6’-2H2]glucose led to downstream deuterium labeling of lactate, thereby resulting in a reduction in the 1.33 ppm lactate-CH3 peak on 1H MRS over time. The subtraction of post-administration 1H MR spectra from the pre-infusion spectra aided in the determination of the kinetics of the lactate turnover. We believe that the detection and quantification of lactate production kinetics may provide crucial information regarding tumor LDHA expression non-invasively in GBMs without requiring biopsies. Hence, qMRS is expected to open up new opportunities to probe LDHA expression differences in a variety of gliomas, including GBMs and astrocytomas. This method takes advantage of the universal availability and ease of implementation of 1H MRS on all clinical and preclinical magnetic resonance scanners.

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