scholarly journals Ex VivoFluorescence Molecular Tomography of the Spine

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Monish Pimpalkhare ◽  
Jin Chen ◽  
Vivek Venugopal ◽  
Xavier Intes
Keyword(s):  
Ex Vivo ◽  
Imaging Study ◽  
Intervertebral Disk ◽  
Large Animal Model ◽  
Data Sets ◽  
Large Animal ◽  
Wide Field ◽  
Accurate Localization ◽  
Quantification Accuracy ◽  
The Impact

We investigated the potential of fluorescence molecular tomography to imageex vivosamples collected from a large animal model, in this case, a dog spine. Wide-field time-gated fluorescence tomography was employed to assess the impact of multiview acquisition, data type, and intrinsic optical properties on the localization and quantification accuracy in imaging a fluorescent inclusion in the intervertebral disk. As expected, the TG data sets, when combining early and late gates, provide significantly better performances than the CW data sets in terms of localization and quantification. Moreover, the use of multiview imaging protocols led to more accurate localization. Additionally, the incorporation of the heterogeneous nature of the tissue in the model to compute the Jacobians led to improved imaging performances. This preliminary imaging study provides a proof of concept of the feasibility of quantitatively imaging complexex vivosamples nondestructively and with short acquisition times. This work is the first step towards employing optical molecular imaging of the spine to detect and characterize disc degeneration based on targeted fluorescent probes.

scholarly journals Cellular and acellular ex vivo lung perfusion preserve functional lung ultrastructure in a large animal model: a stereological study

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Jasmin Steinmeyer ◽  
Simon Becker ◽  
Murat Avsar ◽  
Jawad Salman ◽  
Klaus Höffler ◽  
...  
Keyword(s):  
Animal Model ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
Large Animal Model ◽  
Large Animal ◽  
Ex Vivo Lung Perfusion ◽  
Lung Ultrastructure

scholarly journals Light-degradable hydrogels as dynamic triggers for gastrointestinal applications

2020 ◽  
Vol 6 (3) ◽  
pp. eaay0065 ◽  
Author(s):  
Ritu Raman ◽  
Tiffany Hua ◽  
Declan Gwynne ◽  
Joy Collins ◽  
Siddartha Tamang ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Implantable Devices ◽  
Large Animal Model ◽  
Large Animal ◽  
Gi Tract ◽  
Biomedical Device ◽  
Precise Tool ◽  
And Performance

Triggerable materials capable of being degraded by selective stimuli stand to transform our capacity to precisely control biomedical device activity and performance while reducing the need for invasive interventions. Here, we describe the development of a modular and tunable light-triggerable hydrogel system capable of interfacing with implantable devices. We apply these materials to two applications in the gastrointestinal (GI) tract: a bariatric balloon and an esophageal stent. We demonstrate biocompatibility and on-demand triggering of the material in vitro, ex vivo, and in vivo. Moreover, we characterize performance of the system in a porcine large animal model with an accompanying ingestible LED. Light-triggerable hydrogels have the potential to be applied broadly throughout the GI tract and other anatomic areas. By demonstrating the first use of light-degradable hydrogels in vivo, we provide biomedical engineers and clinicians with a previously unavailable, safe, dynamically deliverable, and precise tool to design dynamically actuated implantable devices.

scholarly journals Autoregulation assessment by direct visualisation of pial arterial blood flow in the piglet brain

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
S. P. Klein ◽  
V. De Sloovere ◽  
G. Meyfroidt ◽  
B. Depreitere
Keyword(s):  
Blood Flow ◽  
Brain Injury ◽  
Therapeutic Interventions ◽  
Arterial Blood Flow ◽  
Large Animal Model ◽  
Large Animal ◽  
Main Site ◽  
Cranial Window ◽  
Arterial Blood ◽  
The Impact

Abstract Impairment of cerebrovascular autoregulation (CAR) is common after brain injury, although the pathophysiology remains elusive. The mechanisms of vascular dysregulation, their impact on brain function, and potential therapeutic implications are still incompletely understood. Clinical assessment of CAR remains challenging. Observational studies suggest that CAR impairment is associated with worse outcomes, and that optimization of cerebral blood flow (CBF) by individual arterial blood pressure (ABP) targets could potentially improve outcome. We present a porcine closed cranial window model that measures the hemodynamic response of pial arterioles, the main site of CBF control, based on changes in their diameter and red blood cell velocity. This quantitative direct CAR assessment is compared to laser Doppler flow (LDF). CAR breakpoints are determined by segmented regression analysis and validated using LDF and brain tissue oxygen pressure. Using a standardized cortical impact, CAR impairment in traumatic brain injury can be studied using our method of combining pial arteriolar diameter and RBC velocity to quantify RBC flux in a large animal model. The model has numerous potential applications to investigate CAR physiology and pathophysiology of CAR impairment after brain injury, the impact of therapeutic interventions, drugs, and other confounders, or to develop personalized ABP management strategies.

Ex Vivo Expanded T Regulatory (Treg) Cells Block Conversion of Mixed Chimeras To Complete Donor Chimerism.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5168-5168
Author(s):  
Marina Lesnikova ◽  
Alla Nikitine ◽  
Nicola Mason ◽  
Richard A. Nash ◽  
George E. Georges
Keyword(s):  
T Cells ◽  
Ex Vivo ◽  
Treg Cells ◽  
Large Animal Model ◽  
Control Group ◽  
Large Animal ◽  
Not Given ◽  
Tolerance Mechanism ◽  
Donor Chimerism ◽  
Mixed Chimeras

Abstract A highly effective method to establish long-term, stable mixed hematopoietic chimerism was developed in the dog model. This involves nonmyeloablative allogeneic hematopoietic cell transplantation (HCT), consisting of 2 Gray (Gy) total body irradiation (TBI), dog leukocyte antigen (DLA)-identical marrow, and short-term post-grafting immunosuppression. We hypothesized that CD4+CD25+ Treg cells may be important regulators for the maintenance of cellular immune tolerance after allogeneic HCT. Previously, we showed in 8 mixed chimeras that naive donor lymphocyte infusion (DLI) did not change the level of donor chimerism. However, reconditioning mixed chimeras with 2 Gy TBI followed by DLI “breaks” tolerance and increases the level of donor chimerism. Seven mixed chimeras were reconditioned with 2 Gy TBI followed by DLI. Within 4 weeks after DLI, conversion to 100% donor chimerism was seen in 5 of 7 dogs and 2 dogs had a > 50% sustained increase in donor chimerism. Four recipients developed graft-versus host disease (GVHD). A control group of 3 mixed chimeras reconditioned with 2 Gy TBI without DLI had no change in donor chimerism. These results suggest that reconditioning with 2 Gy TBI followed by DLI can break the tolerance mechanism established in mixed chimeras. Next we asked if CD4+CD25+ Treg cells obtained from mixed chimeras before reconditioning could block the increase in donor chimerism following 2 Gy TBI and DLI. Peripheral blood mononuclear cells (PBMC) from 8 mixed chimeras were obtained by leukapheresis and cultured in bulk mixed leukocyte culture (MLC) with 3rd party DLA-mismatched, unrelated and irradiated CD34+ derived dendritic cells (10:1 responder: stimulator ratio) or PBMC (1:1). On day 4 of MLC, CD25+ cells were isolated by positive immunomagnetic selection. Next, artificial antigen presenting cells (aAPC, KT32) were added to expand the CD4+CD25+ Treg cells. The aAPC expressed Fcγ receptor CD32, canine CD86, and human IL-15, were loaded with the canine-specific mitogenic anti-CD3ε antibody 17.6F9 and irradiated prior to stimulation of CD4+CD25+ Treg. After 7 days, Treg were expanded a median of 23 (range, 8–36)-fold. Expanded CD4+CD25+ Treg were assessed for phenotype and in vitro function. The Treg cells were generated from 8 mixed chimeras and were infused back into the respective dogs (median dose 1× 107/kg) after reconditioning with 2 Gy TBI and immediately prior to DLI. In 6 of 8 dogs there was no change in the level of donor chimerism at 16–20 weeks follow-up; 2 dogs converted to complete donor chimerism within 6 weeks. Treatment with expanded Treg cells blocked conversion to complete donor chimerism after 2 Gy TBI +DLI in 6 of 8 dogs, compared with significant increases in donor chimerism for all 7 dogs after 2 Gy TBI +DLI not given Treg (p=.007). None of the 8 Treg recipient dogs developed GVHD, compared with 4 of 7 not given Treg, (p=0.02). A control group of 4 mixed chimeras were infused with expanded, non-Treg CD25− T cells. To this end, CD25+ T cells were immunomagneticaly depleted on day 4 of MLC. CD25− T cells were expanded with aAPC. Three of 4 dogs converted to the complete donor chimerism within 7 weeks after 2 Gy TBI, non-Treg and DLI. These results suggest that ex vivo expanded CD4+CD25+ Treg cells have in vivo function in a large animal model and can restore the tolerance mechanism in mixed chimeras that is broken by 2 Gy TBI and DLI.

scholarly journals Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine

BJS Open ◽  
2021 ◽  
Vol 5 (2) ◽  
Author(s):  
M O Hamed ◽  
A D Barlow ◽  
N Dolezalova ◽  
S Khosla ◽  
A Sagar ◽  
...  
Keyword(s):  
Small Intestine ◽  
Reperfusion Injury ◽  
Ex Vivo ◽  
Autologous Blood ◽  
Functional Model ◽  
Unmet Need ◽  
Large Animal ◽  
Normothermic Perfusion ◽  
The Impact ◽  
Venous Glucose

Abstract Background There is an unmet need for suitable ex vivo large animal models in experimental gastroenterology and intestinal transplantation. This study details a reliable and effective technique for ex vivo normothermic perfusion (EVNP) of segmental porcine small intestine. Methods Segments of small intestine, 1.5–3.0 m in length, were retrieved from terminally anaesthetized pigs. After a period of cold ischaemia, EVNP was performed for 2 h at 37°C with a mean pressure of 80 mmHg using oxygenated autologous blood diluted with Ringer’s solution. The duration of EVNP was extended to 4 h for a second set of experiments in which two segments of proximal to mid-ileum (1.5–3.0 m) were retrieved from each animal and reperfused with whole blood (control) or leucocyte-depleted blood to examine the impact of leucocyte depletion on reperfusion injury. Results After a mean cold ischaemia time of 5 h and 20 min, EVNP was performed in an initial group of four pigs. In the second set of experiments, five pigs were used in each group. In all experiments bowel segments were well perfused and exhibited peristalsis during EVNP. Venous glucose levels significantly increased following luminal glucose stimulation (mean(s.e.m.) basal level 1.8(0.6) mmol/l versus peak 15.5(5.8) mmol/l; P < 0.001) and glucagon-like peptide 1 (GLP-1) levels increased in all experiments, demonstrating intact absorptive and secretory intestinal functions. There were no significant differences between control and leucocyte-depleted animals regarding blood flow, venous glucose, GLP-1 levels or histopathology at the end of 4 h of EVNP. Conclusions This novel model is suitable for the investigation of gastrointestinal physiology, pathology and ischaemia reperfusion injury, along with evaluation of potential therapeutic interventions.

Abstract 2953: Myocardial Uptake of 7′(Z)-[ 123 I]Iodorotenone During Vasodilator Stress in Dogs with Coronary Stenoses

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Alexis Broisat ◽  
Mirta Ruiz ◽  
Henry F VanBrocklin ◽  
Norman C Goodman ◽  
Stephen M Hanrahan ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ex Vivo ◽  
Quantitative Estimation ◽  
Canine Model ◽  
Vasodilator Stress ◽  
Large Animal Model ◽  
Regional Myocardial Blood Flow ◽  
Large Animal ◽  
Myocardial Uptake ◽  
Wide Range

There is a well recognized need for a new generation of SPECT perfusion tracers with improved myocardial extraction over a wide flow range. 7′(Z)-[ 123 I]Iodorotenone (ZIROT) is a new myocardial perfusion imaging (MPI) agent with excellent myocardial uptake and favorable biodistribution. Our objective was to fully characterize the myocardial ZIROT extraction vs flow relationship during vasodilator stress in a large animal model. Accordingly, the adenosine A 2A receptor agonist ATL-146e was infused i.v. (0.3 μg/kg/min) in 5 anesthetized, open-chest dogs with critical LAD stenoses. When LCx flow was maximal, 111 MBq (3mCi) of ZIROT and microspheres were co-injected and the dogs were euthanized 5 min later. The LV was divided into 4 short axis slices for ex vivo imaging followed by gamma well counting of myocardial segments. At the time of ZIROT injection, transmural flow in the stenotic LAD zone was similar to baseline (0.90 ± 0.22 vs 0.87 ± 0.11 ml/min/g, respectively P = NS), whereas normal LCx zone flow increased significantly (3.25 ± 0.51 vs 1.00 ± 0.17 ml/min/g, P<0.05). As shown, myocardial ZIROT extraction tracked regional myocardial blood flow better than either 201 thallium or 99m Tc-sestamibi in our previous studies using a similar canine model. Furthermore, the ZIROT LAD/LCx activity ratios obtained by ex vivo imaging or gamma well counting (0.42 ± 0.08 and 0.45 ± 0.1 respectively) only slightly underestimated the LAD/LCx microsphere flow ratio (0.32 ± 0.09). The ability of ZIROT to more accurately track blood flow over a wide range makes it a very promising new MPI agent with potential for improved CAD detection and better quantitative estimation of the severity of flow impairment.

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