scholarly journals Functional Capillary Density for in Vivo Estimation of Intestinal Perfusion using Real-Time Confocal Endomicroscopy

2015 ◽  
Vol 06 (04) ◽  
Author(s):  
Luigi Schiraldi Francesco
Keyword(s):  
Real Time ◽  
Capillary Density ◽  
Functional Capillary Density ◽  
Intestinal Perfusion ◽  
Confocal Endomicroscopy

scholarly journals Reduction of Functional Capillary Density in Human Brain after Stroke

1990 ◽  
Vol 10 (3) ◽  
pp. 317-326 ◽  
Author(s):  
Albert Gjedde ◽  
Hiroto Kuwabara ◽  
Antoine M. Hakim
Keyword(s):  
Blood Flow ◽  
Brain Tissue ◽  
Capillary Density ◽  
Functional Capillary Density ◽  
Functional Density ◽  
Hemodynamic Variables ◽  
Cortical Gray Matter ◽  
Cerebral Ischemic ◽  
Reduced Density

The blood flow of brain tissue often returns to normal after an ischemic episode. As “luxury” rather than “reactive” reperfusion, this hyperemia is associated with low metabolism. It is not known to what extent the high blood flow accompanies a high, normal, or low density of capillaries. The resolution of this question may indicate whether the functional capillary density is variable and, if so, whether it is coupled to blood flow or metabolism. To answer these questions, we defined functional capillaries as capillaries that transport glucose. We then calculated the density of functional capillaries ( Dcap) and the mean time of transit of blood through the capillaries ( tcap) from hemodynamic variables obtained in vivo by positron tomography of five patients afflicted by cerebral ischemic stroke. Each patient was studied twice, within 36 h of the insult and 1 week later. We identified nominally “ischemic” regions in the first study as cortical gray matter regions, contiguous with the ischemic focus, in which the magnitude of blood flow did not exceed 20 ml 100 g−1 min−1. In these regions, values of metabolism and functional capillary density were proportionately low compared with normal values obtained in the contralateral hemisphere. The studies revealed a reduction of the functional density of exchange vessels in postischemic brain tissue as soon as 36 h after the insult. In “ischemic” regions, within 36 h of the insult, the net extraction of oxygen was inversely related to the capillary transit time and appeared to be limited mainly by the low functional density of the capillaries. Contrary to expectations, the reduced density persisted, even when more than adequate perfusion of the tissue returned. For these reasons, we concluded that changes of the capillary density were associated with changes of the metabolism of the tissue rather than with blood flow.

scholarly journals In Vivo Real Time Imaging of Hepatocyte Apoptosis With Confocal Endomicroscopy Identifies Early Cell Swelling and Barrier Defect

2011 ◽  
Vol 140 (5) ◽  
pp. S-926
Author(s):  
Martin Goetz ◽  
Jacqueline V. Ansems ◽  
Marcus Schuchmann ◽  
Peter R. Galle ◽  
Ralf Kiesslich
Keyword(s):  
Real Time ◽  
Cell Swelling ◽  
Hepatocyte Apoptosis ◽  
Real Time Imaging ◽  
Confocal Endomicroscopy ◽  
Barrier Defect

Evolution of a “falx lunatica” in demarcation of critically ischemic myocutaneous tissue

2005 ◽  
Vol 288 (3) ◽  
pp. H1224-H1232 ◽  
Author(s):  
Yves Harder ◽  
Michaela Amon ◽  
Mirko Georgi ◽  
Andrej Banic ◽  
Dominique Erni ◽  
...  
Keyword(s):  
Capillary Density ◽  
Functional Capillary Density ◽  
Tissue Necrosis ◽  
Capillary Perfusion ◽  
Edema Formation ◽  
Perfusion Failure ◽  
Ischemic Tissue ◽  
Flap Elevation ◽  
Observation Period

Using intravital microscopy in a chronic in vivo mouse model, we studied the demarcation of myocutaneous flaps and evaluated microvascular determinants for tissue survival and necrosis. Chronic ischemia resulted in a transition zone, characterized by a red fringe and a distally adjacent white falx, which defined the demarcation by dividing the proximally normal from the distally necrotic tissue. Tissue survival in the red zone was determined by hyperemia, as indicated by recovery of the transiently reduced functional capillary density, and capillary remodeling, including dilation, hyperperfusion, and increased tortuosity. Angiogenesis and neovascularization were not observed over the 10-day observation period. The white rim distal to the red zone, appearing as “falx lunatica,” showed a progressive decrease of functional capillary density similar to that of the necrotic distal area but without desiccation, and thus transparency, of the tissue. Development of the distinct zones of the critically ischemic tissue could be predicted by partial tissue oxygen tension (Pt[Formula: see text]) analysis by the time of flap elevation. The falx lunatica evolved at a Pt[Formula: see text] between 6.2 ± 1.3 and 3.8 ± 0.7 mmHg, whereas tissue necrosis developed at <3.8 ± 0.7 mmHg. Histological analysis within the falx lunatica revealed interstitial edema formation and muscle fiber nuclear rarefaction but an absence of necrosis. We have thus demonstrated that ischemia-induced necrosis does not demarcate sharply from normal tissue but develops beside a fringe of tissue with capillary remodeling an adjacent falx lunatica that survives despite nutritive capillary perfusion failure, probably by direct oxygen diffusion.

Diaphragmatic microcirculation during halothane and isoflurane exposure in pentobarbital-anesthetized rats

1992 ◽  
Vol 73 (4) ◽  
pp. 1614-1618 ◽  
Author(s):  
A. Leon ◽  
J. Boczkowski ◽  
B. Dureuil ◽  
E. Vicaut ◽  
M. Aubier ◽  
...  
Keyword(s):  
Capillary Density ◽  
Baseline Period ◽  
Functional Capillary Density ◽  
Dependent Manner ◽  
Minimal Alveolar Concentration ◽  
Arterial Blood ◽  
Anesthetized Rats ◽  
Isoflurane Group ◽  
Dose Dependent

We investigated the effects of halothane and isoflurane on diaphragmatic microcirculation in pentobarbital-anesthetized rats by in vivo video microscopy. After a baseline period, rats were randomly allocated into three groups according to administration of 0.5, 0.75, and 1 minimal alveolar concentration (MAC) of either halothane (group Hal, n = 16), isoflurane (group Iso, n = 14), or no halogenated agent (group C, n = 20) in three succeeding steps of 15 min. Mean arterial blood pressure (MAP), arteriolar diameters, and functional capillary density were analyzed in the last 3 min of each step. MAP remained unchanged in group C but decreased in a dose-dependent manner in both halogenated receiving groups. MAP was significantly lower in rats breathing Hal compared with those breathing Iso. Arterioles were classified in second (A2, n = 39), third (A3, n = 24), and fourth (A4, n = 30) order according to their relative location in the network. No changes in A2 and A3 diameters were noted in either group. A4 diameters remained unchanged in groups C and Iso, whereas a significant reduction was found in group Hal at 0.75 and 1 MAC exposure (P < 0.05 compared with baseline and with groups C and Iso, respectively). During Iso exposure, functional capillary density was not significantly different when compared with baseline and group C, whereas in group Hal it decreased significantly at 0.5, 0.75, and 1 MAC, amounting to 61.1 +/- 9, 30.7 +/- 10.3, and 22.8 +/- 6.3%, respectively, of baseline (P < 0.01 vs. baseline and P < 0.05 vs. groups Iso and C for 0.75 and 1 MAC).(ABSTRACT TRUNCATED AT 250 WORDS)

Voltammetric Detection of Tetrodotoxin Real-Time In Vivo of Mouse Organs using DNA-Immobilized Carbon Nanotube Sensors

2019 ◽  
Vol 15 (5) ◽  
pp. 567-574
Author(s):  
Huck Jun Hong ◽  
Suw Young Ly
Keyword(s):  
Carbon Nanotube ◽  
Real Time ◽  
Anticancer Agents ◽  
Cancer Metastasis ◽  
Anodic Stripping Voltammetry ◽  
Stripping Voltammetry ◽  
Takifugu Rubripes ◽  
In Vivo Detection ◽  
Voltammetric Detection

Background: Tetrodotoxin (TTX) is a biosynthesized neurotoxin that exhibits powerful anticancer and analgesic abilities by inhibiting voltage-gated sodium channels that are crucial for cancer metastasis and pain delivery. However, for the toxin’s future medical applications to come true, accurate, inexpensive, and real-time in vivo detection of TTX remains as a fundamental step. Methods: In this study, highly purified TTX extracted from organs of Takifugu rubripes was injected and detected in vivo of mouse organs (liver, heart, and intestines) using Cyclic Voltammetry (CV) and Square Wave Anodic Stripping Voltammetry (SWASV) for the first time. In vivo detection of TTX was performed with auxiliary, reference, and working herring sperm DNA-immobilized carbon nanotube sensor systems. Results: DNA-immobilization and optimization of amplitude (V), stripping time (sec), increment (mV), and frequency (Hz) parameters for utilized sensors amplified detected peak currents, while highly sensitive in vivo detection limits, 3.43 µg L-1 for CV and 1.21 µg L-1 for SWASV, were attained. Developed sensors herein were confirmed to be more sensitive and selective than conventional graphite rodelectrodes modified likewise. A linear relationship was observed between injected TTX concentration and anodic spike peak height. Microscopic examination displayed coagulation and abnormalities in mouse organs, confirming the powerful neurotoxicity of extracted TTX. Conclusion: These results established the diagnostic measures for TTX detection regarding in vivo application of neurotoxin-deviated anticancer agents and analgesics, as well as TTX from food poisoning and environmental contamination.

scholarly journals Real-time observation of tetrapyrrole binding to an engineered bacterial phytochrome

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yusaku Hontani ◽  
Mikhail Baloban ◽  
Francisco Velazquez Escobar ◽  
Swetta A. Jansen ◽  
Daria M. Shcherbakova ◽  
...  
Keyword(s):  
Real Time ◽  
Rational Design ◽  
Near Infrared ◽  
Fluorescent Proteins ◽  
Covalent Bond ◽  
Binding Pocket ◽  
Tissue Imaging ◽  
Covalent Attachment ◽  
Time Resolved

AbstractNear-infrared fluorescent proteins (NIR FPs) engineered from bacterial phytochromes are widely used for structural and functional deep-tissue imaging in vivo. To fluoresce, NIR FPs covalently bind a chromophore, such as biliverdin IXa tetrapyrrole. The efficiency of biliverdin binding directly affects the fluorescence properties, rendering understanding of its molecular mechanism of major importance. miRFP proteins constitute a family of bright monomeric NIR FPs that comprise a Per-ARNT-Sim (PAS) and cGMP-specific phosphodiesterases - Adenylyl cyclases - FhlA (GAF) domain. Here, we structurally analyze biliverdin binding to miRFPs in real time using time-resolved stimulated Raman spectroscopy and quantum mechanics/molecular mechanics (QM/MM) calculations. Biliverdin undergoes isomerization, localization to its binding pocket, and pyrrolenine nitrogen protonation in <1 min, followed by hydrogen bond rearrangement in ~2 min. The covalent attachment to a cysteine in the GAF domain was detected in 4.3 min and 19 min in miRFP670 and its C20A mutant, respectively. In miRFP670, a second C–S covalent bond formation to a cysteine in the PAS domain occurred in 14 min, providing a rigid tetrapyrrole structure with high brightness. Our findings provide insights for the rational design of NIR FPs and a novel method to assess cofactor binding to light-sensitive proteins.

scholarly journals Spatio-temporal biodistribution of 89Zr-oxine labeled huLym-1-A-BB3z-CAR T-cells by PET imaging in a preclinical tumor model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naomi S. Sta Maria ◽  
Leslie A. Khawli ◽  
Vyshnavi Pachipulusu ◽  
Sharon W. Lin ◽  
Long Zheng ◽  
...  
Keyword(s):  
T Cells ◽  
Real Time ◽  
Pet Imaging ◽  
Dose Group ◽  
Low Dose ◽  
High Dose ◽  
Car T Cells ◽  
Nsg Mice ◽  
Car T

AbstractQuantitative in vivo monitoring of cell biodistribution offers assessment of treatment efficacy in real-time and can provide guidance for further optimization of chimeric antigen receptor (CAR) modified cell therapy. We evaluated the utility of a non-invasive, serial 89Zr-oxine PET imaging to assess optimal dosing for huLym-1-A-BB3z-CAR T-cell directed to Lym-1-positive Raji lymphoma xenograft in NOD Scid-IL2Rgammanull (NSG) mice. In vitro experiments showed no detrimental effects in cell health and function following 89Zr-oxine labeling. In vivo experiments employed simultaneous PET/MRI of Raji-bearing NSG mice on day 0 (3 h), 1, 2, and 5 after intravenous administration of low (1.87 ± 0.04 × 106 cells), middle (7.14 ± 0.45 × 106 cells), or high (16.83 ± 0.41 × 106 cells) cell dose. Biodistribution (%ID/g) in regions of interests defined over T1-weighted MRI, such as blood, bone, brain, liver, lungs, spleen, and tumor, were analyzed from PET images. Escalating doses of CAR T-cells resulted in dose-dependent %ID/g biodistributions in all regions. Middle and High dose groups showed significantly higher tumor %ID/g compared to Low dose group on day 2. Tumor-to-blood ratios showed the enhanced extravascular tumor uptake by day 2 in the Low dose group, while the Middle dose showed significant tumor accumulation starting on day 1 up to day 5. From these data obtained over time, it is apparent that intravenously administered CAR T-cells become trapped in the lung for 3–5 h and then migrate to the liver and spleen for up to 2–3 days. This surprising biodistribution data may be responsible for the inactivation of these cells before targeting solid tumors. Ex vivo biodistributions confirmed in vivo PET-derived biodistributions. According to these studies, we conclude that in vivo serial PET imaging with 89Zr-oxine labeled CAR T-cells provides real-time monitoring of biodistributions crucial for interpreting efficacy and guiding treatment in patient care.

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