Volume Fraction Of Blood Vessels Research Articles

Quantitative CT Metrics Associated with Variability in the Diffusion Capacity of the Lung of Post-COVID-19 Patients with Minimal Residual Lung Lesions.

(1) Background: A reduction in the diffusion capacity of the lung for carbon monoxide is a prevalent longer-term consequence of COVID-19 infection. In patients who have zero or minimal residual radiological abnormalities in the lungs, it has been debated whether the cause was mainly due to a reduced alveolar volume or involved diffuse interstitial or vascular abnormalities. (2) Methods: We performed a cross-sectional study of 45 patients with either zero or minimal residual lesions in the lungs (total volume < 7 cc) at two months to one year post COVID-19 infection. There was considerable variability in the diffusion capacity of the lung for carbon monoxide, with 27% of the patients at less than 80% of the predicted reference. We investigated a set of independent variables that may affect the diffusion capacity of the lung, including demographic, pulmonary physiology and CT (computed tomography)-derived variables of vascular volume, parenchymal density and residual lesion volume. (3) Results: The leading three variables that contributed to the variability in the diffusion capacity of the lung for carbon monoxide were the alveolar volume, determined via pulmonary function tests, the blood vessel volume fraction, determined via CT, and the parenchymal radiodensity, also determined via CT. These factors explained 49% of the variance of the diffusion capacity, with p values of 0.031, 0.005 and 0.018, respectively, after adjusting for confounders. A multiple-regression model combining these three variables fit the measured values of the diffusion capacity, with R = 0.70 and p < 0.001. (4) Conclusions: The results are consistent with the notion that in some post-COVID-19 patients, after their pulmonary lesions resolve, diffuse changes in the vascular and parenchymal structures, in addition to a low alveolar volume, could be contributors to a lingering low diffusion capacity.

A transmural gradient of myocardial remodeling in early-stage heart failure with preserved ejection fraction in the pig.

Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction. This study aimed to analyze whether early HFpEF is already associated with ultrastructural alterations and whether they differ quantitatively among the layers of the left ventricular wall. HFpEF was induced in pigs by deoxy‐corticosterone acetate (DOCA) treatment along with a high‐salt/high lipid diet over 3 months and compared with weight‐matched normal pigs (n = 5 each). Samples of the left ventricle were taken and processed for light and electron microscopy. Interstitial fibrosis, subcellular composition of cardiomyocytes and mean cardiomyocyte diameter were evaluated by stereology in subendocardial, midmyocardial and subepicardial regions. DOCA enhanced the mean cardiomyocyte diameter in all locations of the ventricle wall to the same degree. The subcellular composition did not differ between the locations and was not altered by DOCA. The volume fraction of interstitium was smaller in the subendocardium of DOCA group than of control group. Within the interstitium, the volume fraction of collagen fibrils (between cardiomyocytes) was increased in the subendocardial and midmyocardial wall layers of the DOCA group but not in the subepicardial layer. Although the capillary length density and average supply area were not altered in response to DOCA in any of the wall layers, the volume fraction of blood vessels related to the interstitial space was enhanced in the subendocardium of the DOCA group but not in the other wall layers. In conclusion, cardiomyocyte changes due to DOCA were similar in subepicardial, midmyocardial and subendocardial regions but DOCA‐induced changes in the interstitium appeared to be more pronounced in the subendocardial ventricular wall layers. This suggests a pivotal role of the subendocardial interstitium in the pathogenesis of HFpEF.

Diffusion lung imaging with hyperpolarized gas MRI.

Lung imaging using conventional 1 H MRI presents great challenges because of the low density of lung tissue, lung motion and very fast lung tissue transverse relaxation (typical T2 * is about 1-2 ms). MRI with hyperpolarized gases (3 He and 129 Xe) provides a valuable alternative because of the very strong signal originating from inhaled gas residing in the lung airspaces and relatively slow gas T2 * relaxation (typical T2 * is about 20-30 ms). However, in vivo human experiments should be performed very rapidly - usually during a single breath-hold. In this review, we describe the recent developments in diffusion lung MRI with hyperpolarized gases. We show that a combination of the results of modeling of gas diffusion in lung airspaces and diffusion measurements with variable diffusion-sensitizing gradients allows the extraction of quantitative information on the lung microstructure at the alveolar level. From an MRI scan of less than 15 s, this approach, called in vivo lung morphometry, allows the provision of quantitative values and spatial distributions of the same physiological parameters as measured by means of 'standard' invasive stereology (mean linear intercept, surface-to-volume ratio, density of alveoli, etc.). In addition, the approach makes it possible to evaluate some advanced Weibel parameters characterizing lung microstructure: average radii of alveolar sacs and ducts, as well as the depth of their alveolar sleeves. Such measurements, providing in vivo information on the integrity of pulmonary acinar airways and their changes in different diseases, are of great importance and interest to a broad range of physiologists and clinicians. We also discuss a new type of experiment based on the in vivo lung morphometry technique combined with quantitative computed tomography measurements, as well as with gradient echo MRI measurements of hyperpolarized gas transverse relaxation in the lung airspaces. Such experiments provide additional information on the blood vessel volume fraction, specific gas volume and length of the acinar airways, and allow the evaluation of lung parenchymal and non-parenchymal tissue. Copyright © 2015 John Wiley & Sons, Ltd.

Pharmacokinetic Model and Arterial Input Function Selection in Dynamic Contrast Enhanced-MRI in Head and Neck Cancers

Introduction: Head and Neck cancers constitute 6% of all cancers. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has the potential to measure the physiological properties of the tissue, like vascularization, vascular leakage, blood vessel volume fraction and blood flow, all of which play important roles in oncology. DCE-MRI is an effective MR imaging technique suitable for characterizing tumor angiogenesis, which is a critical process in tumor growth and metastasis. DCE-MRI technique is performed by acquiring MR images during the passage of an exogenous contrast agent (CA) in the tissue of interest. When the acquisition time is short, it allows to get valuable information about perfusion, tracer uptake and wash-out rate (WOR). Quantitative measures of tumor vascularity could be computed by investigating the signal intensity change during CA passage with respect to the signal intensity before CA injection in the tissue of interest and a reference artery, representing the arterial input function (AIF). Accurate definition of the behavior of the tissue during CA passage highly depends on selected tracer kinetic parameters, which can be modeled using pharmacokinetic (PK) modeling approach, and the AIF selection strategy. Here, we aim to introduce the proper PK model, describing hemodynamic characteristics of head and neck cancer, and AIF selection approach. Materials and Methods: Various PK models have been introduced in literature to be used in combination with DCE-MR imaging, each exploiting different subsets of kinetic parameters. In most tissues, CA leaks rapidly into intracellular intravascular space (EES) at a rate determined by the permeability of the micro vessels (KTrans), their surface area (PS), and blood flow (F).Two other parameters include Ve , which shows the EES volume per unit volume of tissue and Vp , that indicates the blood plasma volume per unit volume of tissue. In order to achieve the optimal tissue-specific model, it is essential to select suitable descriptive parameters of the tissue of interest. Accurate quantification of kinetic parameters highly rely on accurate characterization of AIF, which could itself be affected by many technical factors such as spatial and temporal resolution accuracy of the T1 measurements, in-flow effects, B1-inhomogenity and also many patient-related factors such as heart output rate, vascular tone, hematocrit and tracer distribution in the body and kidney. Recently, it has been proposed that measuring the contrast agent concentration in veins could be preferable in brain perfusion studies, as it could reduce the in-flow effects. Conclusion: Results show that there are two models, namely Tofts and Brix, which can be used in head and neck cancers. One of the problems of PK modeling would be AIF selection. In order to increase the validation of AIF selection it is possible to use the vein CTCs for Tofts model to measure the reliable pharmacokinetic parameters.

Depth distributions of light action spectra for skin chromophores

Light action spectra over wavelengths of 300–1000 nm are calculated for components of the human cutaneous covering: melanin, basal (bloodless) tissue, and blood oxy- and deoxyhemoglobin. The transformation of the spectra with depth in biological tissue results from two factors. The first is the wavelength dependence of the absorption coefficient corresponding to a particular skin chromophore and the second is the spectral selectivity of the radiation flux in biological tissue. This factor is related to the optical properties of all chromophores. A significant change is found to take place in the spectral distribution of absorbed radiant power with increasing depth. The action spectrum of light for the molecular oxygen contained in all components of biological tissue is also studied in the 625–645 nm range. The spectra are found to change with both the volume fraction of blood vessels and the degree of oxygenation of the blood. These results are useful for analyzing processes associated with optical absorption that are possible mechanisms for the interaction of light with biological tissues: photodissociation of oxyhemoglobin and the light-oxygen effect.

Calcaneal Tendon Regions Exhibit Different MMP‐2 Activation After Vertical Jumping and Treadmill Running

Increased activity of matrix metalloproteinases (MMPs) -2 and -9 was found in calcaneal tendon after physical training. However, little attention has been given to the distinct biomechanical and tissue structure of the calcaneal tendon's proximal and distal regions. Herein, we evaluated the effect of two types of physical activities on tendon morphology and matrix metalloproteinase activities in the proximal and distal regions of rat calcaneal tendon, separately. Adult male Wistar rats from control, water-adapted, vertical-jumping, and treadmill-running groups were sacrificed after 1 or 4 days of physical exercise, 6 hr after the end of that day's exercise session. Tendons were processed for histology, morphometry, and gelatin zymography. Tendons from adapted and trained animals showed active secretory cells and increased thickness, cellularity, and blood vessel volume fraction of peritendinous sheath, but without inflammatory process. In the proximal region, both pro- and active MMP-2 were increased after vertical jumping, but only pro-MMP-2 was increased after treadmill running. In contrast, in the distal region, both exercise types increased the activity of pro- and active MMP-2, especially treadmill running, which increased the active MMP-2 by about 11- and eightfold, respectively, after 1 and 4 days of training. No activity of MMP-9 was observed in either tendon region in this study. In conclusion, distal and proximal regions of calcaneal tendon exhibit differential intensities of tissue remodeling after treadmill running or vertical jumping and MMP-2, in the absence of inflammation, plays a major role in this adaptive response.

Assessment of Axonal Growth into Collagen Nerve Guides Containing VEGF‐Transfected Stem Cells in Matrigel

The early events associated with axonal growth into 10-mm nerve gaps were studied histologically in the rat sciatic nerve model to determine if the outgrowth of blood vessels, Schwann cells, and axons could be enhanced. In the first two experimental groups, collagen nerve guides were filled with either saline or Matrigel. Marrow-derived mesenchymal stem cells (MSCs) were added to Matrigel in two other groups, one of which contained cells transfected with VEGF (MSC/VEGF). After 21 days, the injury site was exposed, fixed, sectioned, and volume fractions of the conduit contents were determined by point counting. The bioresorbable collagen conduits appropriately guided the axons and vessels in a longitudinal direction. The volume fraction of axons was significantly greater in the group with saline when compared with all three groups with Matrigel. This measure had a significant positive correlation with actual counts of myelinated axons. The blood vessel volume fraction in the Matrigel group decreased compared with the saline group, but was restored in the MSC/VEGF group. All Matrigel groups had comparable cellularity and showed a distribution of residual Matrigel in acellular zones. The saline group, by contrast, sustained a network of delicate fibroblastic processes that compartmentalized the nerve and its natural matrix as it became infiltrated by axons as minifascicles. In conclusion, the reduction of axonal outgrowth in the Matrigel groups, when compared with the saline group, suggests that Matrigel may impede the early regenerative process even when enriched by the addition of MSCs or VEGF-transfected cells.

Efficacy of Platelet‐Rich Plasma on Wound Healing in Rabbits

The purpose of this study was to evaluate if the healing of full-thickness skin wounds was accelerated by platelet-rich plasma (PRP). Four 2.5 x 2.5-cm full-thickness skin wounds were created on the backs of 15 New Zealand white rabbits. One wound on each animal received 0.3, 0.6, or 0.9 ml PRP, and the fourth wound served as a control. Seven and eight animals were sacrificed after 1 or 2 weeks, respectively, to determine histomorphometrically the epithelialization rate, contraction rate, healing rate, tissue fill, and volume fractions of fibroblasts, neutrophils, macrophages, and blood vessels. Only the 0.6- and 0.9-ml groups had significantly lower contraction rates than the controls after 2 weeks (P <0.05). Although no statistically significant differences were found in other parameters between the PRP-treated wounds and the controls, the PRP treatment led to increases in average epithelialization rates and volume fraction of blood vessels at both time periods. The PRP also seemed to have the most positive effect on healing rate, tissue fill, and volume fraction of fibroblasts during week 1 compared to week 2. The PRP treatment enhanced healing in full-thickness wounds by reducing the contraction rate with a trend toward acceleration of the epithelial migration and the angiogenic response. Further studies with larger sample sizes should be conducted to improve statistical sensitivity. Longer time intervals and modifications of PRP volume should also be explored to evaluate the long-term efficacy of PRP on wound healing.

Single‐shot 3D imaging techniques improve arterial spin labeling perfusion measurements

Arterial spin labeling (ASL) can be used to measure perfusion without the use of contrast agents. Due to the small volume fraction of blood vessels compared to tissue in the human brain (typ. 3-5%) ASL techniques have an intrinsically low signal-to-noise ratio (SNR). In this publication, evidence is presented that the SNR can be improved by using arterial spin labeling in combination with single-shot 3D readout techniques. Specifically, a single-shot 3D-GRASE sequence is presented, which yields a 2.8-fold increase in SNR compared to 2D EPI at the same nominal resolution. Up to 18 slices can be acquired in 2 min with an SNR of 10 or more for gray matter perfusion. A method is proposed to increase the reliability of perfusion quantification using QUIPSS II derivates by acquiring low-resolution maps of the bolus arrival time, which allows differentiation between lack of perfusion and delayed arrival of the labeled blood. For arterial spin labeling, single-shot 3D imaging techniques are optimal in terms of efficiency and might prove beneficial to improve reliability of perfusion quantitation in a clinical setup.

Tissue compartments in laminae II-V of rabbit visual cortex--three-dimensional arrangement, size and developmental changes.

The neuropil in laminae II/III and IV of the mature rabbit visual cortex is subdivided into (a) dendrite bundles consisting of apical dendrites of pyramidal cells and associated axons and glial processes, (b) bundles of myelinated axons ascending vertically from the white matter up to lamina IV and (c) neuropil between bundles comprising mainly thin unmyelinated axons, small dendrites and associated glial processes. In this investigation the three-dimensional structure of these compartments was analysed. In addition, the volume fractions of the three neuropil compartments, perikarya and blood vessels in the different laminae and their quantitative changes from the late fetal period up to young adulthood and in a group of aged animals were determined. Serial 1-micron epoxy sections were analysed. Dendrite bundles are more numerous and more intensively intertwined in lamina II/III than in lamina IV. At 28 days after conception the tissue in laminae II-V consists of approximately equal amounts, i.e. between 40 and 50%, of perikarya and neuropil. The volume fraction of blood vessels is about 4% and does not change much during development. During the first 16 days after birth the volume fraction of the neuropil increases to more than 70%, and conversely the volume fraction of nerve cells decreases to about 20%. Later, significant changes are seen only when the volume fractions of the three neuropil compartments are considered separately. The volume fraction of the neuropil between bundles increases throughout all laminae investigated, whereas the volume fraction of dendrite bundles is found to decrease. After 1 month, in lamina IV further increase of the neuropil between bundles is less marked, because here the bundles of myelinated axons become visible as an additional compartment. In young adult animals, the volume fractions of dendrite bundles are about 28% in the upper half, 16% in the lower half of lamina II/III and 7% in lamina IV. The neuropil between bundles comprises about 52% in the upper half, 65% in the lower half of lamina II/III and 62% in lamina IV. In lamina IV 14% is occupied by bundles of myelinated axons. In aged animals, the volume fraction of the neuropil between bundles decreases significantly in all laminae investigated. From previous ultrastructural studies, the extracellular space is known to be about 30% larger in the neuropil between bundles than in the dendrite bundles. Moreover, due to the prevalence of thin cell processes, the degree of tortuosity is larger in the neuropil between bundles than in the dendrite bundles. The present results together with these previous data are an indication of lamina-specific differences in the structure of the extracellular space. This may help to explain the electrical conductivity in the respective laminae of the cerebral cortex. The time course of postnatal changes of the neuropil compartments coincides with fundamental steps of structural and functional maturation of the rabbit visual cortex that are documented in the literature, and thus may be a valid parameter to investigate the degree of maturation or aging by morphological means.