Macroscopic Blood Vessels Research Articles

On the identification of the blood vessel confounding effect in intravoxel incoherent motion (IVIM) Diffusion-Weighted (DW)-MRI in liver: An efficient sparsity based algorithm.

IntraVoxel Incoherent Motion (IVIM) Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) is of great interest for evaluating tissue diffusion and perfusion and producing parametric maps in clinical applications for liver pathologies. However, the presence of macroscopic blood vessels (not capillaries) in a given Region of Interest (ROI) results in a confounding effect that bias the quantification of tissue perfusion. Therefore, it is necessary to identify those voxels affected by blood vessels. In this paper, an efficient algorithm for an automatic identification of blood vessels in a given ROI is proposed. It relies on the sparsity of the spatial distribution of blood vessels. This sparsity prior can be easily incorporated using the all-voxel IVIM-MRI model introduced in this paper. In addition to the identification of blood vessels, the proposed algorithm provides a quantification of blood vessels, tissue diffusion and tissue perfusion of all voxels in a given ROI, in one single step. Besides, two strategies are proposed in this paper to deal with the nonnegativity of the model parameters. The efficiency of the proposed algorithm compared to the Non-Negative Least Square (NNLS)-based method, recently introduced to deal with the confounding blood vessel effect in the IVIM-MRI model, is confirmed using both realistic and real DW-MR images.

Spatial-temporal perfusion patterns of the human liver assessed by pseudo-continuous arterial spin labeling MRI

PurposeTo investigate the capabilities of a modern pseudo-continuous arterial spin labeling (PCASL) technique for non-invasive assessment of the temporal and spatial distribution of the liver perfusion in healthy volunteers on a clinical MR system at 3T. Materials and methodsA 2D-PCASL multi-slice echo planar imaging sequence was adapted to the specific conditions in liver: a) labeling by PCASL was optimized to the flow characteristics in the portal vein, b) background suppression was applied for reduction of motion related artifacts, c) post labeling delays (PLDs) were varied over a large range (0.7–3.5s) in order to get better insight in the temporal and spatial distribution of tagged blood in the liver, and d) a special timed-breathing protocol was used allowing for recording of 16 to 18 label-control image pairs and a reference M0 image for each of 4 to 6 slices within approx. 5min for one PLD. ResultsMeasurements with multiple PLDs showed dominating perfusion signal in macroscopic blood vessels for PLDs up to 1.5 s, whereas pure liver parenchyma revealed maximum perfusion signal for a PLD of approx. 2 s, and detectable signal up to PLDs of 3.5 s. Data fitting to a perfusion model for liver provided a mean global perfusion of 153±15ml/100g/min and a mean transit time of 1938±332ms in liver parenchyma. Measurements with a single PLD of 2 s demonstrated that portal-venous and arterial perfusion components can be measured separately by two measurements with two different positions of the labeling plane (one for labeling of the global hepatopetal blood flow and one for selective labeling of the portal blood flow only). Relative contribution of blood from the hepatic artery to the global liver perfusion, the hepatic perfusion index (HPI), amounted to approx. 23%. ConclusionModern and adapted protocols for assessment of liver perfusion by PCASL have the potential to provide perfusion and blood transit time maps in reasonable acquisition time.

Spatial specificity of the functional MRI blood oxygenation response relative to neuronal activity

Previous attempts at characterizing the spatial specificity of the blood oxygenation level dependent functional MRI (BOLD fMRI) response by estimating its point-spread function (PSF) have conventionally relied on retinotopic spatial representations of visual stimuli in area V1. Consequently, their estimates were confounded by the width and scatter of receptive fields of V1 neurons. Here, we circumvent these limits by instead using the inherent cortical spatial organization of ocular dominance columns (ODCs) to determine the PSF for both Gradient Echo (GE) and Spin Echo (SE) BOLD imaging at 7 Tesla.By applying Markov chain Monte Carlo sampling on a probabilistic generative model of imaging ODCs, we quantified the PSFs that best predict the spatial structure and magnitude of differential ODCs' responses. Prior distributions for the ODC model parameters were determined by analyzing published data of cytochrome oxidase patterns from post-mortem histology of human V1 and of neurophysiological ocular dominance indices. The average PSF full-widths at half-maximum obtained from differential ODCs’ responses following the removal of voxels influenced by contributions from macroscopic blood vessels were 0.86 mm (SE) and 0.99 mm (GE). Our results provide a quantitative basis for the spatial specificity of BOLD fMRI at ultra-high fields, which can be used for planning and interpretation of high-resolution differential fMRI of fine-scale cortical organizations.

Silk-based anisotropical 3D biotextiles for bone regeneration.

Bone loss in the craniofacial complex can been treated using several conventional therapeutic strategies that face many obstacles and limitations. In this work, novel three-dimensional (3D) biotextile architectures were developed as a possible strategy for flat bone regeneration applications. As a fully automated processing route, this strategy as potential to be easily industrialized. Silk fibroin (SF) yarns were processed into weft-knitted fabrics spaced by a monofilament of polyethylene terephthalate (PET). A comparative study with a similar 3D structure made entirely of PET was established. Highly porous scaffolds with homogeneous pore distribution were observed using micro-computed tomography analysis. The wet state dynamic mechanical analysis revealed a storage modulus In the frequency range tested, the storage modulus values obtained for SF-PET scaffolds were higher than for the PET scaffolds. Human adipose-derived stem cells (hASCs) cultured on the SF-PET spacer structures showed the typical pattern for ALP activity under osteogenic culture conditions. Osteogenic differentiation of hASCs on SF-PET and PET constructs was also observed by extracellular matrix mineralization and expression of osteogenic-related markers (osteocalcin, osteopontin and collagen type I) after 28 days of osteogenic culture, in comparison to the control basal medium. The quantification of convergent macroscopic blood vessels toward the scaffolds by a chick chorioallantoic membrane assay, showed higher angiogenic response induced by the SF-PET textile scaffolds than PET structures and gelatin sponge controls. Subcutaneous implantation in CD-1 mice revealed tissue ingrowth's accompanied by blood vessels infiltration in both spacer constructs. The structural adaptability of textile structures combined to the structural similarities of the 3D knitted spacer fabrics to craniofacial bone tissue and achieved biological performance, make these scaffolds a possible solution for tissue engineering approaches in this area.

Arteriogenic expansion of extratumoral macrovessels - impact of vascular ageing.

The critical role of the vasculature in cancer progression is predominantly studied at the capillary level, and often equated with angiogenesis. However, the mechanisms that ensure the supply of increasing blood volume to the expanding tumor microcirculation remain presently unclear. Here we used established mouse tumor models to document the enlargement (arteriogenesis), of macroscopic feeding vessels at considerable distances upstream from the malignant lesion, but not contralaterally. These changes are not affected by the procoagulant host tissue factor (TF), but are modulated by vascular ageing and atherosclerosis in ApoE-/- mice. Moreover, arteriogenic growth involves infiltration of bone marrow derived (YFP-labeled) cells and changes the gene expression profiles in the vessel wall. Thus, our observations suggest that in addition to local angiogenesis tumors influence distant remodeling of regional macroscopic blood vessels in amanner that is modulated by certain vascular comorbidities.

Flufenamic acid promotes angiogenesis through AMPK activation

Angiogenesis plays critical roles in development, tumor growth and metastasis. Flufenamic acid (FFA) is an anti-inflammatory agent known to alter ion fluxes across the plasma membrane. Its role in angiogenesis has not been fully addressed to date. Here, we report that FFA treatment promotes angiogenesis both in vitro and in vivo. Applying FFA for 12 h promoted tube formation of human umbilical vein endothelial cells (HUVECs) without affecting cell proliferation. Three angiogenesis-related genes, VEGF, e-NOS and AAMP, were analyzed by RT-PCR. A significant difference was found between the FFA group and the control; the FFA group had significantly higher mRNA accumulation levels of all the three genes (p<0.05). Moreover, in the chick embryo chorioallantoic membrane (CAM) assay, FFA promoted the formation of macroscopic blood vessels. Finally, western blotting showed that the FFA-treated group had significantly higher phosphorylated AMPK levels, compared with the control (p<0.05). These results suggest that FFA promotes angiogenesis both in vitro and in vivo likely via promoting tube formation through AMPK activation.

Angiogenic Potential of Gellan-Gum-Based Hydrogels for Application in Nucleus Pulposus Regeneration:In VivoStudy

Hydrogels for nucleus pulposus (NP) regeneration should be able to comprise a nonangiogenic or even antiangiogenic feature. Gellan gum (GG)-based hydrogels have been reported to possess adequate properties for being used as NP substitutes in acellular and cellular strategies, due to its ability to support cell encapsulation, adequate mechanical properties, and noncytotoxicity. In this study, the angiogenic response of GG-based hydrogels was investigated by performing the chorioallantoic membrane assay. The convergence of macroscopic blood vessels toward the GG, ionic-crosslinked methacrylated GG (iGG-MA), and photo-crosslinked methacrylated GG (phGG-MA) hydrogel discs was quantified. Gelatin sponge (GSp) and filter paper (FP) alone and with vascular endothelial growth factor were used as controls of angiogenesis. The images obtained were digitally processed and analyzed by three independent observers. The macroscopic blood vessel quantification demonstrated that the GG-based hydrogels are not angiogenic as compared with FP controls. No statistical differences between the GG-based hydrogels tested in respect to its angiogenic ability were observed. Hematoxylin and eosin staining and SNA-lectin immunohistochemistry assay indicated that the iGG-MA and phGG-MA hydrogels do not allow the ingrowth of chick endothelial cells, following 4 days of implantation. On the contrary, GG, GSp, and FP controls allowed cell infiltration. The histological data also indicated that the GG-based hydrogels do not elicit any acute inflammatory response. The results showed that the GG, iGG-MA, and phGG-MA hydrogels present different permeability to cells but functioned as a physical barrier for vascular invasion. These hydrogels present promising and tunable properties for being used as NP substitutes in the treatment of degenerative intervertebral disc.

Mechanisms underlying decoding at 7 T: Ocular dominance columns, broad structures, and macroscopic blood vessels in V1 convey information on the stimulated eye

Recent studies have demonstrated that multivariate machine learning algorithms applied to human functional MRI data can decode information segregated in cortical columns, despite the voxel size being large relative to the width of columns. The mechanism by which low spatial resolution imaging decodes information represented in a fine-scale organization is not clear.To investigate mechanisms underlying decoding signals we employed high-resolution gradient-echo BOLD functional MRI of visual area V1. We show that in addition to the fine-scale ocular dominance columns, coarse-scale structures extending over several millimeters also convey discriminative power for decoding the stimulated eye. Discriminative power is conveyed by both macroscopic blood vessels and gray matter regions. We hypothesize that gray-matter regions which drain into specific vessels may preferentially contain ocular-dominance columns biased towards one eye; the bias of a specific region thereby causing a functionally selective ocular-dominance response in the associated vessel. Our findings indicate that coarse-scale structures and macroscopic blood vessels contribute to decoding of the stimulated eye based on low-resolution multivariate data.

Negative functional response to sensory stimulation and its origins.

Functional imaging studies typically give prominence to positive responses. However, negative changes that accompany activation-induced positive responses are not yet clearly understood. The authors investigated the origin of sustained negative CBF responses that accompanied positive CBF changes. Measurements were made in the rat somatosensory cortex in response to whisker stimulation using laser-Doppler imaging. Flux images indicative of CBF were obtained at rest and during whisker stimulation with a spatial resolution of 200 microm. Large and intermediate blood vessels in the cortical surface exhibiting high flux values were clearly resolved. This greatly reduced the contamination of the tissue pixel volume with macroscopic blood vessels. Regions that responded positively to whisker stimulation were from areas with intermediate to low baseline flux and distinctly away from high flux areas. Stimulation-induced change in signal intensity was the largest in pixels with low baseline flux, presumably from tissue and microvessels. Simultaneously, a sustained decrease in signal intensity was observed in regions with high baseline flux values. The temporal coherence, macrovascular origin, lesser trial-to trial variability, and complete absence of the negative CBF response in the microvascular regions suggest that it may be purely hemodynamic in nature.

Use of ultrasound for noninvasive study of blood vessel responsiveness.

To provide a noninvasive means for studying individual macroscopic blood vessels, an ultrasound scanner was modified to provide a recording of blood vessel diameter. The instrument has A- and B-modes of signal display. The B-mode is used to position the probe and the A-mode to measure vessel diameter. The A-mode has two electronic gates for tracking the echo from each of two structures, i.e., near and far wall of vessel. The front gate was modified to pick up the falling rather than rising edge of a peak generated by the vessel wall. An analog signal proportional to the distance between gates was derived for recording with a strip-chart recorder. Probe holders were constructed to optimize positioning and holding of probe. Stability was excellent (reading varied 0.05 mm over 1 h). Axial resolution was between 0.3 and 0.73 mm. Discrepancy of measurements of plastic tubing made by ocular and ultrasound varied from 1.1 to 4.6%. Discrepancy with lightly fixed vessels was 2.7-8.2%. Ex vivo measurements on vessels with viable smooth muscle were more variable, perhaps because of actual change during measurements. Changes in vessel diameter induced by change in hydrostatic pressure and exposure to histamine were recorded.

Microscopic studies of skin blood vessels in relation to sympathetic nerve stimulation.

Studies have been made of the diameters of microscopic and macroscopic blood vessels in the leg skin of 8 dogs and 13 cats, under pentobarbital anesthesia in parallel with observations on blood pressures in similar vessels, using two techniques, micro-cannulation and a recently described micro-chamber method. During stimulation of the homolateral sympathetic trunk, with or without curarization, there was a rise in venule and small vein pressure, associated with an initial decrease in venous vessel diameter. After cessation of stimulation the venous diameters returned to or exceeded control values while the arteriolar diameters were still markedly reduced. These observations provide direct evidence that even in the absence of mechanical obstruction to venous blood flow the pressures in venules, and therefore necessarily in capillaries when blood is flowing forward, may be elevated by sympathetic nerve stimulation which reduces the blood flow into the vascular bed in question. The possible importance of this mechanism in edema formation and in blood pooling is pointed out.