Cancer prognosis and treatment efficacy are assessed by evaluating the hallmarks of a tumor which are volume change of the tumor and the vascular network reformation around a tumor. Non-invasive quantitative assessment of those indications, in-vivo, is still a challenge for traditional imaging modalities, owing to a large interrogation area and deep-seated molecular (fluorescence) signal in highly scattering, anatomically complex skin tissue. Currently available techniques either utilize surgically implanted imaging windows or conduct terminal experiments for each time point. The former is prone to inflammation at the implantation site thus interfering with the tumor microenvironment. The latter one is prone to sample variability thus results in a pseudo-longitudinal outcome for tumor development. Here, we combine Intravital Fluorescence Tomography (IFT) and Spectral Domain Optical Coherence Tomography (SD-OCT) for tumor imaging with a Non-invasive Intravital Imaging Window (NIIW) for tissue stabilization. This platform enabled us to follow tumor development non-invasively covering tumor initiation, development and regression on the same animal over months-long period. IFT-OCT multimodal imaging not only reveals tumor volume change but also skin anatomical features, and it is capable of revealing neo-vascularization around the tumor site. This platform thus serves as a useful non-invasive tool to explore future research questions pertaining to cancer biology in common fluorescence-based mouse models, such as tumor progression or treatment efficacy. In addition, our multi-modal platform alleviates the burden put on animals while imaging and reduce the experimental cost significantly.
Dental lesions located in the pulp are quite difficult to identify based on anatomical contrast, and, hence, to diagnose
using traditional imaging methods such as dental CT. However, such lesions could lead to functional and/or molecular
optical contrast. Herein, we report on the preliminary investigation of using Laminar Optical Tomography (LOT) to
image the pulp and root canals in teeth. LOT is a non-contact, high resolution, molecular and functional mesoscopic
optical imaging modality. To investigate the potential of LOT for dental imaging, we injected an optical dye into ex vivo
teeth samples and imaged them using LOT and micro-CT simultaneously. A rigid image registration between the LOT
and micro-CT reconstruction was obtained, validating the potential of LOT to image molecular optical contrast deep in
the teeth with accuracy, non-invasively. We demonstrate that LOT can retrieve the 3D bio-distribution of molecular
probes at depths up to 2mm with a resolution of several hundred microns in teeth.
Laminar optical tomography (LOT) combines the advantages of diffuse optical tomography image reconstruction and a
microscopy-based setup to allow non-contact imaging at depth up to a few millimeters. However, LOT image
reconstruction paradigm is inherently an ill-posed and computationally expensive inverse problem. Herein, we cast the
LOT inverse problem in the compressive sensing (CS) framework to exploit the sparsity of the fluorophore yield in the
image domain and to address the ill-posedness of the LOT inverse problem. We apply this new approach to thick tissue
engineering applications. We demonstrate the enhanced resolution of our method in 3-D numerical simulations of
anatomically accurate microvasculature and using real data obtained from phantom experiments. Furthermore, CS is
shown to be more robust against the reduction of measurements in comparison to the classic methods for such
application. Potential benefits and shortcomings of the CS approach in the context of LOT are discussed.
Three-dimensional imaging of thick tissue constructs is one of the main challenges in the field of tissue engineering and regenerative medicine. Optical methods are the most promising as they offer noninvasive, fast, and inexpensive solutions. Herein, we report the use of mesoscopic fluorescence molecular tomography (MFMT) to image function and structure of thick bioprinted tissue hosted in a 3-mm-thick bioreactor. Collagen-based tissue assembled in this study contains two vascular channels formed by green fluorescent protein- and mCherry-expressing cells. Transfected live cell imaging enables us to image function, whereas Flash Red fluorescent bead perfusion into the vascular channel allows us to image structure. The MFMT optical reconstructions are benchmarked with classical microscopy techniques. MFMT and wide-field fluorescence microscopy data match within 92% in area and 84% in location, validating the accuracy of MFMT reconstructions. Our results demonstrate that MFMT is a well-suited imaging modality for fast, longitudinal, functional imaging of thick, and turbid tissue engineering constructs.
We report an application of Mesoscopic Fluorescence Molecular Tomography to 3D tissue engineering construct. Engineered thick tissue was hosting two 3D printed vasculatures. The channels were formed by live cells, expressing GFP and mCherry reporter genes, embedded in 3mm turbid media. Tissue and cells kept in a 3mm thick perfusion chamber during the entire imaging process which took less than 5 minutes.
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