scholarly journals Heterogeneity of Ex Vivo and In Vivo Properties along the Length of the Abdominal Aortic Aneurysm

2021 ◽  
Vol 11 (8) ◽  
pp. 3485
Author(s):  
Arianna Forneris ◽  
Miriam Nightingale ◽  
Alina Ismaguilova ◽  
Taisiya Sigaeva ◽  
Louise Neave ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Three Dimensional ◽  
Strain Analysis ◽  
Tissue Level ◽  
Aortic Tissue ◽  
Biaxial Testing ◽  
Mechanical Heterogeneity ◽  
Abdominal Aortic ◽  
Central Regions

The current clinical guidelines for the management of aortic abdominal aneurysms (AAAs) overlook the structural and mechanical heterogeneity of the aortic tissue and its role in the regional weakening that drives disease progression. This study is a comprehensive investigation of the structural and biomechanical heterogeneity of AAA tissue along the length and circumference of the aorta, by means of regional ex vivo and in vivo properties. Biaxial testing and histological analysis were performed on ex vivo human aortic specimens systematically collected during open repair surgery. Wall-shear stress and three-dimensional principal strain analysis were performed to allow for in vivo regional characterization of individual aortas. A marked effect of position along the aortic length was observed in both ex vivo and in vivo properties, with the central regions corresponding to the aneurysmal sac being significantly different from the adjacent regions. The heterogeneity along the circumference of the aorta was reflected in the ex vivo biaxial response at low strains and histological properties. Present findings uniquely show the importance of regional characterization for aortic assessment and the need to correlate heterogeneity at the tissue level with non-invasive measurements aimed at improving clinical outcomes.

Method for Incorporating Three-Dimensional Residual Stresses Into Patient-Specific Simulations of Arteries

2013 ◽  
Author(s):  
David M. Pierce ◽  
Thomas E. Fastl ◽  
Hannah Weisbecker ◽  
Gerhard A. Holzapfel ◽  
Borja Rodriguez-Vila ◽  
...  
Keyword(s):  
Medical Imaging ◽  
Three Dimensional ◽  
Constitutive Models ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Patient Specific ◽  
Abdominal Aortic ◽  
Model Geometry ◽  
Reconstructed Model

Through progress in medical imaging, image analysis and finite element (FE) meshing tools it is now possible to extract patient-specific geometries from medical images of, e.g., abdominal aortic aneurysms (AAAs), and thus to study clinically relevant problems via FE simulations. Medical imaging is most often performed in vivo, and hence the reconstructed model geometry in the problem of interest will represent the in vivo state, e.g., the AAA at physiological blood pressure. However, classical continuum mechanics and FE methods assume that constitutive models and the corresponding simulations start from an unloaded, stress-free reference condition.

Wall Stresses Before and After Endovascular Repair of Abdominal Aortic Aneurysms

2004 ◽  
Author(s):  
Elena S. Di Martino ◽  
Ajay Bohra ◽  
Christine Scotti ◽  
Ender Finol ◽  
David A. Vorp
Keyword(s):  
Endovascular Aneurysm Repair ◽  
Three Dimensional ◽  
Invasive Procedure ◽  
Aortic Aneurysms ◽  
Aortic Tissue ◽  
Type I ◽  
Abdominal Aortic ◽  
Before And After ◽  
Anchoring System ◽  
Three Dimensional Finite Element

Endovascular aneurysm repair (EVAR) technique is a minimally invasive procedure approach to abdominal aortic aneurysm (AAA) repair. Following EVAR, isolated aortic tissue starts remodeling after the new blood path is established. The commercially available endovascular grafts (EVG) have been found to be prone to Type I endoleak, which is re-pressurization of the degenerated AAA sac following a breach in the seal mechanism of the EVG or migration due to failure of the mechanism holding the graft in place (Chuter, 2002) These inadequacies of EVGs might be attributed to the effect of non-optimal design of graft anchoring system. In the present study, we utilized pre-operative and post-operative computer tomography (CT) data with previously derived material properties to construct three-dimensional finite element (FE) models for AAA before and after the EVAR procedure. We studied the nature of stresses acting on the aorta before and after EVAR. In particular we investigated the physical forces acting on the EVG and how they are transferred to the aortic wall at graft anchoring sites.

scholarly journals Video-rate multimodal multiphoton imaging and three-dimensional characterization of cellular dynamics in wounded skin

2020 ◽  
Vol 13 (02) ◽  
pp. 2050007
Author(s):  
Joanne Li ◽  
Madison N. Wilson ◽  
Andrew J. Bower ◽  
Marina Marjanovic ◽  
Eric J. Chaney ◽  
...  
Keyword(s):  
Cell Tracking ◽  
Skin Diseases ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Biological Information ◽  
Cellular Dynamics ◽  
Multiphoton Imaging ◽  
Cellular Events ◽  
Analysis Platform

To date, numerous studies have been performed to elucidate the complex cellular dynamics in skin diseases, but few have attempted to characterize these cellular events under conditions similar to the native environment. To address this challenge, a three-dimensional (3D) multimodal analysis platform was developed for characterizing in vivo cellular dynamics in skin, which was then utilized to process in vivo wound healing data to demonstrate its applicability. Special attention is focused on in vivo biological parameters that are difficult to study with ex vivo analysis, including 3D cell tracking and techniques to connect biological information obtained from different imaging modalities. These results here open new possibilities for evaluating 3D cellular dynamics in vivo, and can potentially provide new tools for characterizing the skin microenvironment and pathologies in the future.

scholarly journals Morphological and Biomechanical Differences in the Elastase and AngIIapoE−/−Rodent Models of Abdominal Aortic Aneurysms

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Evan H. Phillips ◽  
Alexa A. Yrineo ◽  
Hilary D. Schroeder ◽  
Katherine E. Wilson ◽  
Ji-Xin Cheng ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Aortic Aneurysms ◽  
Circulating Biomarkers ◽  
Induction Method ◽  
Future Studies ◽  
Disease Characteristics ◽  
Abdominal Aortic ◽  
Extracellular Matrix Molecules ◽  
Biomechanical Parameters

An abdominal aortic aneurysm (AAA) is a potentially fatal cardiovascular disease with multifactorial development and progression. Two preclinical models of the disease (elastase perfusion and angiotensin II infusion in apolipoprotein-E-deficient animals) have been developed to study the disease during its initiation and progression. To date, most studies have usedex vivomethods to examine disease characteristics such as expanded aortic diameter or analytic methods to look at circulating biomarkers. Herein, we provide evidence fromin vivoultrasound studies of the temporal changes occurring in biomechanical parameters and macromolecules of the aortic wall in each model. We present findings from 28-day studies in elastase-perfused rats and AngIIapoE−/−mice. While each model develops AAAs specific to their induction method, they both share characteristics with human aneurysms, such as marked changes in vessel strain and blood flow velocity. Histology and nonlinear microscopy confirmed that both elastin and collagen, both important extracellular matrix molecules, are similarly affected in their levels and spatial distribution. Future studies could make use of the differences between these models in order to investigate mechanisms of disease progression or evaluate potential AAA treatments.

Newmouse models of melanoma metastasis and differences in brain tropism and metastatic growth pattern.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19015-e19015
Author(s):  
Amr M. Morsi ◽  
Avital Gazial-Sovran ◽  
Hana Baig ◽  
Robert S. Kerbel ◽  
John Golfinos ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Melanoma Cells ◽  
Melanoma Metastasis ◽  
Optimal Method ◽  
In Vivo Models ◽  
Dismal Prognosis ◽  
Intracardiac Injection

e19015 Background: 75% of patients with metastatic melanoma develop brain metastases (B-mets). Such patients show dismal prognosis with a median survival of < 6 months. Scarcity of clinically relevant in vivo models has hindered melanoma B-met studies. We compared the in vivo dissemination upon ultrasound (u/s) guided intracardiac injection of B16F10 cells to 131/4-5B1 (hereafter 5B1), a WM239A subclone with enhanced brain tropism. We also implemented an ex vivo MRI protocol as a high throughput three dimensional approach for characterizing B-mets penetrance and growth. Methods: B16-F10 or 5B1 melanoma cells were injected in C57BL/6J mice (n=40) or athymic/nude mice (n=40) respectively using u/s-guided intracardiac injection. Upon weight loss, mice were euthanized, and heads prepared for ex vivo imaging. All µMRI experiments were performed with a 7T Bruker Avance II console. The protocol consisted of (110-mm)3 isotropic T1-, T2- and T2*-weighted sequences. Results: Our ex vivo MRI recapitulates the clinical radiological T1 and T2 brightening as well as susceptibility-induced T2* darkening effect of melanoma. The B16F10 model revealed exclusive ventricular and leptomeningeal spread while the 5B1 model showed parenchymal lesions. In addition, 90% of the 5B1 mice with brain tumors showed multiple lesions (3-16) vs. 18% in the B16F10 model (1- 3). Finally, 3D volume studies revealed a higher B-met penetrance (68% vs. 18%), delayed onset of tumor detection (earliest-day 27 vs. day 15) post-injection and a slower growth rate of 5B1 brain metastases compared to B16F10 tumors. Conclusions: Our results suggest that u/s-guided intracardiac injection of melanoma cells is an optimal method to capture the cells’ spontaneous dissemination pattern (or site-specific tropism) and that the 5B1 model is a more clinically relevant model of melanoma B-met for preclinical studies.

scholarly journals Spatially Resolved Measurement of Dynamic Glucose Uptake in Live Ex Vivo Tissues

2020 ◽  
Author(s):  
Austin F. Dunn ◽  
Megan A. Catterton ◽  
Drake D. Dixon ◽  
Rebecca R. Pompano
Keyword(s):  
Lymph Node ◽  
T Cell ◽  
Glucose Uptake ◽  
Ex Vivo ◽  
Cell Types ◽  
Tissue Level ◽  
Slice Culture ◽  
Spatially Resolved ◽  
Glucose Analogue

ABSTRACTHighly proliferative cells depend heavily on glycolysis as a source of energy and biological precursor molecules, and glucose uptake is a useful readout of this aspect of metabolic activity. Glucose uptake is commonly quantified by using flow cytometry for cell cultures and positron emission tomography for organs in vivo. However, methods to detect spatiotemporally resolved glucose uptake in intact tissues are far more limited, particularly those that can quantify changes in uptake over time in specific tissue regions and cell types. Using lymph node metabolism as a case study, we developed a novel assay of dynamic and spatially resolved glucose uptake in living tissue by combining ex vivo tissue slice culture with a fluorescent glucose analogue. Live slices of murine lymph node were treated with the glucose analogue 2-[N-(7-nitrobenz-2-oxa-1,3-dia-xol-4-yl)amino]-2-deoxyglucose (2-NBDG). Incubation parameters were optimized to differentiate glucose uptake in activated versus naïve lymphocytes. Regional glucose uptake could be imaged at both the tissue level, by widefield microscopy, and at the cellular level, by confocal microscopy. Furthermore, the assay was readily multiplexed with live immunofluorescence labelling to generate maps of 2-NBDG uptake across tissue regions, revealing highest uptake in T cell-dense regions. The signal was predominantly intracellular and localized to lymphocytes rather than stromal cells. Finally, we demonstrated that the assay was repeatable in the same slices, and imaged the dynamic distribution of glucose uptake in response to ex vivo T cell stimulation for the first time. We anticipate that this assay will serve as a broadly applicable, user-friendly platform to quantify dynamic metabolic activities in complex tissue microenvironments.

scholarly journals Effect of Doxycycline on Survival in Abdominal Aortic Aneurysms in a Mouse Model

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Lisa C. Adams ◽  
Julia Brangsch ◽  
Jan O. Kaufmann ◽  
Dilyana B. Mangarova ◽  
Jana Moeckel ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ex Vivo ◽  
Endothelial Damage ◽  
Aortic Aneurysms ◽  
Clinical Dose ◽  
Doxycycline Treatment ◽  
Abdominal Aortic ◽  
Significant Difference ◽  
Aneurysm Growth

Background. Currently, there is no reliable nonsurgical treatment for abdominal aortic aneurysm (AAA). This study, therefore, investigates if doxycycline reduces AAA growth and the number of rupture-related deaths in a murine ApoE−/− model of AAA and whether gadofosveset trisodium-based MRI differs between animals with and without doxycycline treatment. Methods. Nine ApoE−/− mice were implanted with osmotic minipumps continuously releasing angiotensin II and treated with doxycycline (30 mg/kg/d) in parallel. After four weeks, MRI was performed at 3T with a clinical dose of the albumin-binding probe gadofosveset (0.03 mmol/kg). Results were compared with previously published wild-type control animals and with previously studied ApoE−/− animals without doxycycline treatment. Differences in mortality were also investigated between these groups. Results. In a previous study, we found that approximately 25% of angiotensin II-infused ApoE−/− mice died, whereas in the present study, only one out of 9 angiotensin II-infused and doxycycline-treated ApoE−/− mice (11.1%) died within 4 weeks. Furthermore, doxycycline-treated ApoE−/− mice showed significantly lower contrast-to-noise (CNR) values ( p = 0.017 ) in MRI compared to ApoE−/− mice without doxycycline treatment. In vivo measurements of relative signal enhancement (CNR) correlated significantly with ex vivo measurements of albumin staining (R2 = 0.58). In addition, a strong visual colocalization of albumin-positive areas in the fluorescence albumin staining with gadolinium distribution in LA-ICP-MS was shown. However, no significant difference in aneurysm size was observed after doxycycline treatment. Conclusion. The present experimental in vivo study suggests that doxycycline treatment may reduce rupture-related deaths in AAA by slowing endothelial damage without reversing aneurysm growth.

scholarly journals An Effective Multi-Stage Liposomal DNA Origami Nanosystem for In Vivo Cancer Therapy

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1997 ◽  
Author(s):  
Stefano Palazzolo ◽  
Mohamad Hadla ◽  
Concetta Russo Spena ◽  
Isabella Caligiuri ◽  
Rossella Rotondo ◽  
...  
Keyword(s):  
Immune System ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Dna Origami ◽  
Bone Marrow Toxicity ◽  
Ex Vivo Model ◽  
Innovative Drug ◽  
Multi Stage ◽  
Liver Organoids

DNA origami systems could be important candidates for clinical applications. Unfortunately, their intrinsic properties such as the activation of non-specific immune system responses leading to inflammation, instability in physiological solutions, and a short in vivo lifetime are the major challenges for real world applications. A compact short tube DNA origami (STDO) of 30 nm in length and 10 nm in width was designed to fit inside the core of a stealth liposome (LSTDO) of about 150 nm to remote load doxorubicin. Biocompatibility was tested in three-dimensional (3D) organoid cultures and in vivo. Efficacy was evaluated in different cell lines and in a xenograft breast cancer mouse model. As described in a previous work, LSTDO is highly stable and biocompatible, escaping the recognition of the immune system. Here we show that LSTDO have an increased toleration in mouse liver organoids used as an ex vivo model that recapitulate the tissue of origin. This innovative drug delivery system (DDS) improves the antitumoral efficacy and biodistribution of doxorubicin in tumor-bearing mice and decreases bone marrow toxicity. Our application is an attractive system for the remote loading of other drugs able to interact with DNA for the preparation of liposomal formulations.

scholarly journals 3D culture technologies of cancer stem cells: promising ex vivo tumor models

2020 ◽  
Vol 11 ◽  
pp. 204173142093340 ◽  
Author(s):  
Chengye Zhang ◽  
Zhaoting Yang ◽  
Da-Long Dong ◽  
Tae-Su Jang ◽  
Jonathan C. Knowles ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Ex Vivo ◽  
Three Dimensional ◽  
3D Culture ◽  
Cell Matrix ◽  
Culture Models ◽  
Three Dimensional Culture ◽  
Three Dimensional Models

Cancer stem cells have been shown to be important in tumorigenesis processes, such as tumor growth, metastasis, and recurrence. As such, many three-dimensional models have been developed to establish an ex vivo microenvironment that cancer stem cells experience under in vivo conditions. Cancer stem cells propagating in three-dimensional culture systems show physiologically related signaling pathway profiles, gene expression, cell–matrix and cell–cell interactions, and drug resistance that reflect at least some of the tumor properties seen in vivo. Herein, we discussed the presently available Cancer stem cell three-dimensional culture models that use biomaterials and engineering tools and the biological implications of these models compared to the conventional ones.

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