Forsøksdyr: Magnetic resonance imaging enhanced with extracellular based contrast agents in a pig model


Godkjenningsdato 20.04.2018

Magnetic resonance imaging enhanced with extracellular based contrast agents in a pig model
1. The purpose of the experiment/project:
This study is the first experimental feasibility trial to assess the efficacy of a novel class of manganese (Mn) based magnetic resonance imaging (MRI) contrast agents (CA) as general-purpose MRI CA. The primary objective is to compare the performance of these new CAs to the performance of standard Gadolinium Based (GB)CA and to optimize clinical work flow for formulated MnCA using a set of standardized and pre-defined MRI scans.
2. The expected adverse effects on the animals:
The experiment will be performed as acute terminal experiments in general anesthesia, and the animals will be euthanized immediately after the experimental protocol has been completed. The animals will not experience pain or sensory impressions from the moment they are anesthetized. Continued stress from too low anesthesia depth, hypothermia/hyperthermia or signs of continued circulatory or ventilator instability will be corrected during all phases of the experiment.
3. The expected scientific benefits or benefits for society:
Traditionally GBCAs are used extensively in MRI in order to improve visualization and characterization of tissue structures and pathology. Recently there has been a growing concern that small amounts of gadolinium may detach from the ligand, leading to long term tissue retention of gadolinium metals in vivo. Mn is a metal naturally occurring in the body, and replacing the exogenous Gd with Mn, would to a large extent alleviate the raised concerns. As a proactive reaction GE Healthcare (HC) LS (Norway) has developed endogenous Mn-based CAs and the overall goal of the project is to evaluate the performance of these as a new platform of MRI CA.
4. The number of animals and species:
The experiment will require up to 20 pigs, where all pigs will serve as own controls in order to keep the number of animals to an absolute minimum. The number of animals in the study will be reduced if possible based on study outcome.
5. How will the requirements for 3R be accomplished by the experiment/project:
MnCA is not yet approved for clinical use but has so far been widely tested in both phantom and rodent models. It is not possible to continue the study without the use of an experimental in-vivo model more similar to human anatomy. The domestic farm pig has been chosen as the model in the study because of its cardiac anatomy, physiology and size similar to humans. The research group working on this study has extensive experience with acute pig models, including surgical and anesthesiological competence which minimizes the risk of losing animals due to adverse events from anesthesia or surgery.