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Register a new userTreatment of carcinomas using atmospheric pressure plasma jets: from targets to in vivo models to investigate innocuity and therapeutic efficiency
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Atmospheric pressure plasma jets (APPJ) are investigated as an efficient approach to induce antitumor effects of cancerous tissues without inducing any damage (e.g. dessication, burnings). For this, a two-steps methodology has been developed where first APPJ are calibrated and characterized on targets mimicking electrical properties of living organisms (mice, human body) and second where they are applied on murine models to demonstrate their innocuity and therapeutic efficiency.
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Two atmospheric pressure plasma jet devices - a plasma gun and a plasma Tesla jet - are compared in terms of safety and therapeutic efficiency to reduce the tumor volume progression of cholangiocarcinoma, i.e. a rare and very aggressive cancer emerging in biliary tree. For this, a three steps methodology is carried out. First, the two APPJ have been benchmarked in regard to their electrical and physico-chemical properties while interacting with material targets: dielectric plate, liquid sample, metal plate and an equivalent electrical circuit of human body. The propagation properties of the ionization wave interacting with these targets are discussed, in particular the profile of the related pulsed atmospheric plasma streams. In a second step, a dermal toxicity survey is performed so as to define an experimental operating window where plasma parameters can be changed without damaging healthy skin of mice during their exposure to plasma and without inducing any electrical hazards (burnings, ventricular fibrillation). Optimal conditions are identified discarding the conditions where slight alterations may be evidenced by histology (e.g. prenecrotic aspect of keratinocytes, alterations in the collagen structure). Hence, for the two APPJ plasma parameters these conditions are as follow: duty cycle=14 %, repetition frequency=30 kHz, magnitude=7 kV, gap=10 mm and exposure time=1 min. In a third step, the two plasma jets are utilized on cholangiocarcinoma xenograft tumor model developed in immunodeficient mice. The two devices are safe and a significant therapeutic efficiency is demonstrated with the plasma Tesla. In conclusion, we have developed a safe cold atmospheric plasma device with antitumoral properties in preclinical model of cholangiocarcinoma, opening the path for new anticancer treatment opportunities.
A large number of mathematical models have been proposed to describe the measured signal in diffusion-weighted (DW) magnetic resonance imaging (MRI) and infer properties about the white matter microstructure. However, a head-to-head comparison of DW-MRI models is critically missing in the field. To address this deficiency, we organized the White Matter Modeling Challenge during the International Symposium on Biomedical Imaging (ISBI) 2015 conference. This competition aimed at identifying the DW-MRI models that best predict unseen DW data. in vivo DW-MRI data was acquired on the Connectom scanner at the A.A.Martinos Center (Massachusetts General Hospital) using gradients strength of up to 300 mT/m and a broad set of diffusion times. We focused on assessing the DW signal prediction in two regions: the genu in the corpus callosum, where the fibres are relatively straight and parallel, and the fornix, where the configuration of fibres is more complex. The challenge participants had access to three-quarters of the whole dataset, and their models were ranked on their ability to predict the remaining unseen quarter of data. In this paper we provide both an overview and a more in-depth description of each evaluated model, report the challenge results, and infer trends about the model characteristics that were associated with high model ranking. This work provides a much needed benchmark for DW-MRI models. The acquired data and model details for signal prediction evaluation are provided online to encourage a larger scale assessment of diffusion models in the future.
Currently, gold nanorods can be synthesized in a wide range of sizes. However, for intended biological applications gold nanorods with approximate dimensions 50 nm x 15 nm are used. We investigate by computer simulation the effect of particle dimensions on the optical and thermal properties in the context of the specific applications of photoacoustic imaging. In addition we discuss the influence of particle size in overcoming the following biophysical barriers when administrated in vivo: extravasation, avoidance of uptake by organs of the reticuloendothelial system, penetration through the interstitium, binding capability and uptake by the target cells. Although more complex biological influences can be introduced in future analysis, the present work illustrates that larger gold nanorods, designated by us as nanobig rods, may perform relatively better at meeting the requirements for successful in vivo applications compared to their smaller counterparts which are conventionally used.
We derive a full 3-dimensional (3-D) model of inhomogeneous -- anisotropic diffusion in a tumor region coupled to a binary population model. The diffusion tensors are acquired using Diffusion Tensor Magnetic Resonance Imaging (DTI) from a patient diagnosed with glioblastoma multiform (GBM). Then we numerically simulate the full model with Finite Element Method (FEM) and produce drug concentration heat maps, apoptosis regions, and dose-response curves. Finally, predictions are made about optimal injection locations and volumes, which are presented in a form that can be employed by doctors and oncologists.
Healing of soft biological tissue is the process of self-recovering or self-repairing the injured or damaged extracellular matrix (ECM). Healing is assumed to be stress-driven, with the objective of returning to a homeostatic stress metrics in the tissue after replacing the damaged ECM with new undamaged one. However, based on the existence of intrinsic length-scales in soft tissues, it is thought that computational models of healing should be non-local. In the present study, we introduce for the first time two gradient-enhanced con-stitutive healing models for soft tissues including non-local variables. The first model combines a continuum damage model with a temporally homogenized growth model, where the growth direction is determined according to local principal stress directions. The second one is based on a gradient-enhanced healing model with continuously recoverable damage variable. Both models are implemented in the finite-element package Abaqus by means of a user sub-routine UEL. Three two-dimensional situations simulating the healing process of soft tissues are modeled numerically with both models, and their application for simulation of balloon angioplasty is provided by illustrating the change of damage field and geometry in the media layer throughout the healing process.
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