The Non-Invasive in vivo Molecular Imaging Platform for Long-Term Assessment of Structural and Functional Recoveries in Vascularized Composite Allotransplantation

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Vascularized composite allotransplantation (VCA; e.g., face transplantation, hand transplantation) is an emerging concept that is groundbreaking and beneficial to patients. Structural/functional recovery is one of the key issues of VCA. For both the research of structural/functional recovery and its improving therapies, a long-term assessment is indispensable. A non-invasive in vivo real time imaging platform for the long-term assessment of structural/functional recovery is urgently needed. In our two previous projects, our research team of the center for VCA has initially developed an in vivo assessment platform with various molecular imaging methods such as optical imaging, magnetic resonance imaging (MRI) and ultrasound imaging for the structural/functional recovery of the neuronal regeneration and blood vessel/flow in two simple animal models: denervation/reinnervation rat model and blood vessel-transplantation rat model. In terms of neuronal regeneration: Our research team has already overcome the technical difficulties in previous projects, in which the long-term longitudinal assessments continuing for over one year by fMRI of the denervation and reinnervation rat model had been successfully conducted. The functional reconstruction through neuronal regeneration displayed on the contralateral hemicerebrum of the denervation/reinnervation side and the functional compensation displayed on the other hemicerebrum were assessed with the age effect ruled out. This is an unprecedented achievement, which has never been achieved neither with electrophysiology nor in the past animal fMRI literature. In terms of blood vessel: The Vevo 2100 ultrasound imaging with high resolution and high penetration is the only method at present that allows the in vivo non-invasive mensuration for the thickness of blood vessel walls and the diameter of the blood vessel lumen. It will be an irreplaceable method in clinical VCA. For the large requirement of fluorescence imaging for blood/lymphatic flow, our research team has also developed a series of novel imaging agents. With higher contrast, higher resolution, a much more persistent time window allows to be imaged, and a much more economic price, this series is more superior than the popular commercial imaging agent, indocyanine green (ICG), possessing a great market value. From the initial assessing results, several targets have been identified for further assessments: 1. Structure creates function. The functional reconstruction and compensation of the brain are necessarily based on the structural basis. On this account, the diffusion tensor imaging-MRI (DTI-MRI) with its analysis, Apparent Diffusion Coefficient (ADC) and Fractional Anisotropy (FA), will be used to conduct the non-invasive structural imaging and analysis for the long-term brain plasticity. 2. Behavior recovery depends on both the nerves and muscles. Unsuccessful behavior recovery could be neurogenic, myogenic, or both. Therefore, the muscle assessment with ultrasound imaging, DTI-MRI and near-infrared spectroscopy imaging (NIRS imaging) will be added in this advanced project. The rehabilitation training is also necessary. 3. Until now, there has been no imaging technique that could tell the blood flow apart from the lymphatic flow. Unlike other blood flow imaging techniques that are based on “fluid”, laser speckle imaging is an imaging technique based on “blood cell”. With this characteristic, it can be used as a method to distinguish the blood flow from the lymphatic flow. Through the comparison of laser speckle imaging with fluorescence imaging, the blood flow and the lymphatic flow will be distinguished. Therefore, this advanced further in-depth project has been planned and prepared. Ensuring an effective assessment, the in vivo non-invasive long-term follow-up imaging platform will be even more complete and comprehensive. This advanced platform with its tissomic validation will be formally applied to assess the VCA rat model, and the efficacy of potential therapies will be also evaluated.

Project IDs

Project ID:PC10308-1891
External Project ID:MOST103-2314-B182-031-MY3
StatusFinished
Effective start/end date01/08/1431/07/15

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