scholarly journals Spatially Resolved Estimation of Metabolic Oxygen Consumption From Optical Measurements in Cortex

2019 ◽  
Author(s):  
Marte J. Sætra ◽  
Andreas V. Solbrå ◽  
Anna Devor ◽  
Anders M. Dale ◽  
Gaute T. Einevoll
Keyword(s):  
Ground Truth ◽  
Cylindrical Symmetry ◽  
Blood Oxygenation ◽  
Optical Measurements ◽  
Laplace Method ◽  
Important Indicator ◽  
Spatially Resolved ◽  
Key Steps ◽  
Erlang Formula

AbstractThe cerebral metabolic rate of oxygen (CMRO2) is an important indicator of brain function and pathology. Knowledge about its magnitude is also required for proper interpretation of the blood oxygenation level dependent (BOLD) signal measured with functional MRI (fMRI). The ability to measure CMRO2 with high spatial and temporal accuracy is thus highly desired. Traditionally the estimation of CMRO2 has been pursued with somewhat indirect approaches combining several different types of measurements with mathematical modeling of the underlying physiological processes. Given the numerous assumptions involved, questions have thus been raised about the accuracy of the resulting CMRO2 estimates. The recent ability to measure the level of oxygen (pO2) in cortex with high spatial resolution in in vivo conditions has provided a more direct way for estimating CMRO2. CMRO2 and pO2 are related via the Poisson partial differential equation. Assuming a constant CMRO2 and cylindrical symmetry around the blood vessel providing the oxygen, the so-called Krogh-Erlang formula relating the spatial pO2 profile to a constant CMRO2 value can be derived. This Krogh-Erlang formula has previously been used to estimate the average CMRO2 close to cortical blood vessels based on pO2 measurements in rats.Here we introduce a new method, the Laplace method, to provide spatial maps of CMRO2 based on the same measured pO2 profiles. The method has two key steps: First the measured pO2 profiles are spatially smoothed to reduce effects of spatial noise in the measurements. Next, the Laplace operator (a double spatial derivative) in two spatial dimensions is applied on the smoothed pO2 profiles to obtain spatially resolved CMRO2 estimates. The smoothing introduces a bias, and a balance must be found where the effects of the noise are sufficiently reduced without introducing too much bias. In this model-based study we explore this balance in situations where the ground truth, that is, spatial profile of CMRO2 is preset and thus known, and the corresponding pO2 profiles are found by solving the Poisson equation, either numerically or by taking advantage of the Krogh-Erlang formula. MATLAB code for using the Laplace method is provided.

scholarly journals Simulating a Ground Truth for Transit Time Analysis of Indicator Dilution Curves

2020 ◽  
Vol 6 (3) ◽  
pp. 268-271
Author(s):  
Michael Reiß ◽  
Ady Naber ◽  
Werner Nahm
Keyword(s):  
Transit Time ◽  
Sampling Rate ◽  
Ground Truth ◽  
Indicator Dilution ◽  
Cross Sectional ◽  
In Vivo Measurements ◽  
Multiple Indicator Dilution ◽  
Transit Times ◽  
Dilution Curves

AbstractTransit times of a bolus through an organ can provide valuable information for researchers, technicians and clinicians. Therefore, an indicator is injected and the temporal propagation is monitored at two distinct locations. The transit time extracted from two indicator dilution curves can be used to calculate for example blood flow and thus provide the surgeon with important diagnostic information. However, the performance of methods to determine the transit time Δt cannot be assessed quantitatively due to the lack of a sufficient and trustworthy ground truth derived from in vivo measurements. Therefore, we propose a method to obtain an in silico generated dataset of differently subsampled indicator dilution curves with a ground truth of the transit time. This method allows variations on shape, sampling rate and noise while being accurate and easily configurable. COMSOL Multiphysics is used to simulate a laminar flow through a pipe containing blood analogue. The indicator is modelled as a rectangular function of concentration in a segment of the pipe. Afterwards, a flow is applied and the rectangular function will be diluted. Shape varying dilution curves are obtained by discrete-time measurement of the average dye concentration over different cross-sectional areas of the pipe. One dataset is obtained by duplicating one curve followed by subsampling, delaying and applying noise. Multiple indicator dilution curves were simulated, which are qualitatively matching in vivo measurements. The curves temporal resolution, delay and noise level can be chosen according to the requirements of the field of research. Various datasets, each containing two corresponding dilution curves with an existing ground truth transit time, are now available. With additional knowledge or assumptions regarding the detection-specific transfer function, realistic signal characteristics can be simulated. The accuracy of methods for the assessment of Δt can now be quantitatively compared and their sensitivity to noise evaluated.

scholarly journals Automated analysis of filopodial length and spatially resolved protein concentration via adaptive shape tracking

2016 ◽  
Vol 27 (22) ◽  
pp. 3616-3626 ◽  
Author(s):  
Tanumoy Saha ◽  
Isabel Rathmann ◽  
Abhiyan Viplav ◽  
Sadhana Panzade ◽  
Isabell Begemann ◽  
...  
Keyword(s):  
Protein Concentration ◽  
Growth Dynamics ◽  
Automated Analysis ◽  
Cell Types ◽  
Control Mechanisms ◽  
Spatially Resolved ◽  
Novel Approach ◽  
Associated Proteins

Filopodia are dynamic, actin-rich structures that transiently form on a variety of cell types. To understand the underlying control mechanisms requires precise monitoring of localization and concentration of individual regulatory and structural proteins as filopodia elongate and subsequently retract. Although several methods exist that analyze changes in filopodial shape, a software solution to reliably correlate growth dynamics with spatially resolved protein concentration along the filopodium independent of bending, lateral shift, or tilting is missing. Here we introduce a novel approach based on the convex-hull algorithm for parallel analysis of growth dynamics and relative spatiotemporal protein concentration along flexible filopodial protrusions. Detailed in silico tests using various geometries confirm that our technique accurately tracks growth dynamics and relative protein concentration along the filopodial length for a broad range of signal distributions. To validate our technique in living cells, we measure filopodial dynamics and quantify spatiotemporal localization of filopodia-associated proteins during the filopodial extension–retraction cycle in a variety of cell types in vitro and in vivo. Together these results show that the technique is suitable for simultaneous analysis of growth dynamics and spatiotemporal protein enrichment along filopodia. To allow readily application by other laboratories, we share source code and instructions for software handling.

scholarly journals Spatially resolved measurements of hyperpolarized gas properties in the lung in vivo. Part I: Diffusion coefficient

1999 ◽  
Vol 42 (4) ◽  
pp. 721-728 ◽  
Author(s):  
X. Josette Chen ◽  
Harald E. M�ller ◽  
Mark S. Chawla ◽  
Gary P. Cofer ◽  
Bastiaan Driehuys ◽  
...  
Keyword(s):  
Diffusion Coefficient ◽  
Spatially Resolved ◽  
Hyperpolarized Gas ◽  
Gas Properties

scholarly journals Is the resting rate of oxygen consumption of locomotor muscles in crustaceans limited by the low blood oxygenation strategy?

2001 ◽  
Vol 204 (5) ◽  
pp. 933-940 ◽  
Author(s):  
J. Forgue ◽  
A. Legeay ◽  
J.C. Massabuau
Keyword(s):  
Blood Oxygenation ◽  
Whole Body ◽  
Blood Gas ◽  
Astacus Leptodactylus ◽  
Night Time ◽  
Arterial Blood ◽  
Rate Of Oxygen Consumption ◽  
Locomotor Muscles

Numerous water-breathers exhibit a gas-exchange regulation strategy that maintains O(2) partial pressure, P(O2), in the arterial blood within the range 1–3 kPa at rest during the daytime. In a night-active crustacean, we examined whether this could limit the rate of O(2)consumption (M(O2)) of locomotor muscles and/or the whole body as part of a coordinated response to energy conservation. In the crayfish Astacus leptodactylus, we compared the in vitro relationship between the M(O2) of locomotor muscles as a function of the extracellular P(O2) and P(CO2) and in vivo circadian changes in blood gas tensions at various values of water P(O2). In vitro, the M(O2) of locomotor muscle, either at rest or when stimulated with CCCP, was O(2)-dependent up to an extracellular P(O2) of 8–10 kPa. In vivo, the existence of a night-time increase in arterial P(O2) of up to 4 kPa at water P(O2) values of 20 and 40 kPa was demonstrated, but an experimental increase in arterial P(O2) during the day did not lead to any rise in whole-body M(O2). This suggested that the low blood P(O2) in normoxia has no global limiting effect on daytime whole-body M(O2). The participation of blood O(2) status in shaping the circadian behaviour of crayfish is discussed.

scholarly journals Spatiotemporal co-dependency between macrophages and exhausted CD8+ T cells in cancer

2021 ◽  
Author(s):  
Kelly Kersten ◽  
Kenneth H Hu ◽  
Alexis J Combes ◽  
Bushra Samad ◽  
Tory Harwin ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Light Sheet ◽  
Light Sheet Microscopy ◽  
Spatially Resolved ◽  
Hypoxic Conditions ◽  
Synaptic Interactions ◽  
Positive Feedback Circuit ◽  
Major Impediment

T cell exhaustion is a major impediment to anti-tumor immunity. However, it remains elusive how other immune cells in the tumor microenvironment (TME) contribute to this dysfunctional state. Here we show that the biology of tumor-associated macrophages (TAM) and exhausted T cells (Tex) in the TME is extensively linked. We demonstrate that in vivo depletion of TAM reduces exhaustion programs in tumor-infiltrating CD8+ T cells and reinvigorates their effector potential. Reciprocally, transcriptional and epigenetic profiling reveals that Tex express factors that actively recruit monocytes to the TME and shape their differentiation. Using lattice light sheet microscopy, we show that TAM and CD8+ T cells engage in unique long-lasting antigen-specific synaptic interactions that fail to activate T cells, but prime them for exhaustion, which is then accelerated in hypoxic conditions. Spatially resolved sequencing supports a spatiotemporal self-enforcing positive feedback circuit that is aligned to protect rather than destroy a tumor.

Evaluation of an infrared laser-Doppler blood flowmeter

1987 ◽  
Vol 252 (6) ◽  
pp. G832-G839 ◽  
Author(s):  
A. P. Shepherd ◽  
G. L. Riedel ◽  
J. W. Kiel ◽  
D. J. Haumschild ◽  
L. C. Maxwell
Keyword(s):  
Rotational Velocity ◽  
Rotating Disk ◽  
Tissue Perfusion ◽  
Infrared Laser ◽  
Blood Oxygenation ◽  
Laser Doppler ◽  
Laser Doppler Velocimeter ◽  
Flow Signal

Several laser-Doppler blood flowmeters are now commercially available; however, only one utilizes an infrared laser diode (Laserflo, TSI, St. Paul, MN). Because of this and other unique features such as its microprocessor-based signal analyzer, we evaluated this device's ability to measure tissue perfusion. Initially, we determined whether laser illumination directly affected the microvasculature. Intravital microscopic observations in the hamster cremaster muscle indicated that neither He-Ne nor infrared laser light affected the diameters of arterioles that were responsive to vasoactive agents. To test the flowmeter for linearity and repeatability, we used a rotating disk to simulate a light-scattering, flowing medium. The "flow" signal was highly correlated (r = 0.99) with the rotational velocity of the disk, was consistent among flow probes, and showed a high degree of reproducibility. The second model consisted of microsphere suspensions pumped through cuvettes. The laser-Doppler velocimeter (LDV) flow signal was linear with respect to pump output. With red blood cells in the perfusate, we examined the effects of blood oxygenation on the flowmeter's performance. The LDV flow signal was unaffected by changes in blood oxygenation. We evaluated linearity in vivo in isolated, perfused rat livers and in isolated canine gastric flaps. We observed linear relationships between total flow and laser-Doppler flow measured on the surface of the liver (r = 0.98) and in the gastric mucosa (r = 0.98), but the slopes of the relationships between total and local LDV flow showed considerable variability not noted in the in vitro studies.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Toward Development of a Vocal Fold Contact Pressure Probe: Sensor Characterization and Validation Using Synthetic Vocal Fold Models

2019 ◽  
Vol 9 (15) ◽  
pp. 3002 ◽  
Author(s):  
Mohsen Motie-Shirazi ◽  
Matías Zañartu ◽  
Sean D. Peterson ◽  
Daryush D. Mehta ◽  
James B. Kobler ◽  
...  
Keyword(s):  
Contact Pressure ◽  
Vocal Fold ◽  
Ground Truth ◽  
Pressure Probe ◽  
Primary Role ◽  
Novel Approach ◽  
Sensor Position ◽  
Probe Sensor ◽  
Contact Pressures

Excessive vocal fold collision pressures during phonation are considered to play a primary role in the formation of benign vocal fold lesions, such as nodules. The ability to accurately and reliably acquire intraglottal pressure has the potential to provide unique insights into the pathophysiology of phonotrauma. Difficulties arise, however, in directly measuring vocal fold contact pressures due to physical intrusion from the sensor that may disrupt the contact mechanics, as well as difficulty in determining probe/sensor position relative to the contact location. These issues are quantified and addressed through the implementation of a novel approach for identifying the timing and location of vocal fold contact, and measuring intraglottal and vocal fold contact pressures via a pressure probe embedded in the wall of a hemi-laryngeal flow facility. The accuracy and sensitivity of the pressure measurements are validated against ground truth values. Application to in vivo approaches are assessed by acquiring intraglottal and VF contact pressures using a synthetic, self-oscillating vocal fold model in a hemi-laryngeal configuration, where the sensitivity of the measured intraglottal and vocal fold contact pressure relative to the sensor position is explored.

scholarly journals Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

2020 ◽  
Vol 16 ◽  
pp. 738-755
Author(s):  
Valerian Dragutan ◽  
Ileana Dragutan ◽  
Albert Demonceau ◽  
Lionel Delaude
Keyword(s):  
Therapeutic Agents ◽  
Ruthenium Catalysts ◽  
Diels Alder ◽  
Bioactive Molecules ◽  
Enyne Metathesis ◽  
Organic Transformations ◽  
Chemically Modified ◽  
Key Steps ◽  
Powerful Strategy

This account surveys the current progress on the application of intra- and intermolecular enyne metathesis as main key steps in the synthesis of challenging structural motifs and stereochemistries found in bioactive compounds. Special emphasis is placed on ruthenium catalysts as promoters of enyne metathesis to build the desired 1,3-dienic units. The advantageous association of this approach with name reactions like Grignard, Wittig, Diels–Alder, Suzuki–Miyaura, Heck cross-coupling, etc. is illustrated. Examples unveil the generality of such tandem reactions in providing not only the intricate structures of known, in vivo effective substances but also for designing chemically modified analogs as valid alternatives for further therapeutic agents.

scholarly journals Brain Tissue Conductivity Measurements with MR-Electrical Properties Tomography: An In Vivo Study

2020 ◽  
Author(s):  
Stefano Mandija ◽  
Petar I. Petrov ◽  
Jord J. T. Vink ◽  
Sebastian F. W. Neggers ◽  
Cornelis A. T. van den Berg
Keyword(s):  
Electrical Properties ◽  
Healthy Subjects ◽  
Ex Vivo ◽  
Simulated Data ◽  
Ground Truth ◽  
In Vivo Study ◽  
Conductivity Measurements ◽  
Tissue Conductivity ◽  
Before And After

AbstractFirst in vivo brain conductivity reconstructions using Helmholtz MR-Electrical Properties Tomography (MR-EPT) have been published. However, a large variation in the reconstructed conductivity values is reported and these values differ from ex vivo conductivity measurements. Given this lack of agreement, we performed an in vivo study on eight healthy subjects to provide reference in vivo brain conductivity values. MR-EPT reconstructions were performed at 3 T for eight healthy subjects. Mean conductivity and standard deviation values in the white matter, gray matter and cerebrospinal fluid (σWM, σGM, and σCSF) were computed for each subject before and after erosion of regions at tissue boundaries, which are affected by typical MR-EPT reconstruction errors. The obtained values were compared to the reported ex vivo literature values. To benchmark the accuracy of in vivo conductivity reconstructions, the same pipeline was applied to simulated data, which allow knowledge of ground truth conductivity. Provided sufficient boundary erosion, the in vivo σWM and σGM values obtained in this study agree for the first time with literature values measured ex vivo. This could not be verified for the CSF due to its limited spatial extension. Conductivity reconstructions from simulated data verified conductivity reconstructions from in vivo data and demonstrated the importance of discarding voxels at tissue boundaries. The presented σWM and σGM values can therefore be used for comparison in future studies employing different MR-EPT techniques.

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