The First Bioluminescence Tomography System for Simultaneous Acquisition of Multiview and Multispectral Data

We describe the system design of the first bioluminescence tomography (BLT) system for parallel acquisition of multiple bioluminescent views around a mouse in a number of spectral channels simultaneously. The primary component of this BLT system is a novel mirror module and a unique mouse holder. The mirror module consists of a mounting plate and four mirrors with stages. These mirror stages are right triangular blocks symmetrically arranged and attached to the mounting plate such that the hypotenuse surfaces of the triangular blocks all make 45∘ to the plate surface. The cylindrical/polygonal mouse holder has semitransparent rainbow bands on its side surface for the acquisition of spectrally resolved data. Numerical studies and experiments are performed to demonstrate the feasibility of this system. It is shown that bioluminescent signals collected using our system can produce a similar BLT reconstruction quality while reducing the data acquisition time, as compared to the sequential data acquisition mode

A Fast full-body fluorescence/bioluminescence imaging system for small animals

ABSTRACT Whole body in vivo optical imaging of small animals has widened its applications and increased the capabilities for preclinical researches. However, most commercial and prototype optical imaging systems are camera-based systems using epi-or trans-illumination mode, with limited views of small animals. And for more accurate tomographic image reconstruction, additional data and information of a target animal is necessary. To overcome these issues, researchers have suggested several approaches such as maximizing the detection area or using the information of other highresolution modalities such as CT, MRI or Ultrasound, or using multi-spectral signals. As one of ways to maximizing the detection area of a target animal, we present a new fluorescence and bioluminescence imaging system for small animals, which can image entire surface of a target animal simultaneously. This system uses double mirror reflection scheme and it consists of input unit, imaging unit with two conical mirrors, the source illumination part and the surface scanner, and the detection unit with an intensified CCD camera system. Two conical mirrors are configured that a larger size mirror captures a target animal surface, and a smaller size mirror projects this captured image onto a CCD camera with one acquisition. With this scheme, we could capture entire surface of a target animal simultaneously and improve back reflection issue between a mirror and an animal surface of a single conical mirror scheme. Additionally, we could increase accessibility to an animal for multi-modality integration by providing unobstructed space around a target animal

Multi-modal molecular diffuse optical tomography system for small animal imaging

A multi-modal optical imaging system for quantitative 3D bioluminescence and functional diffuse imaging is presented, which has no moving parts and uses mirrors to provide multi-view tomographic data for image reconstruction. It is demonstrated that through the use of trans-illuminated spectral near infrared measurements and spectrally constrained tomographic reconstruction, recovered concentrations of absorbing agents can be used as prior knowledge for bioluminescence imaging within the visible spectrum. Additionally, the first use of a recently developed multi-view optical surface capture technique is shown and its application to model-based image reconstruction and free-space light modelling is demonstrated. The benefits of model-based tomographic image recovery as compared to 2D planar imaging are highlighted in a number of scenarios where the internal luminescence source is not visible or is confounding in 2D images. The results presented show that the luminescence tomographic imaging method produces 3D reconstructions of individual light sources within a mouse-sized solid phantom that are accurately localised to within 1.5mm for a range of target locations and depths indicating sensitivity and accurate imaging throughout the phantom volume. Additionally the total reconstructed luminescence source intensity is consistent to within 15% which is a dramatic improvement upon standard bioluminescence imaging. Finally, results from a heterogeneous phantom with an absorbing anomaly are presented demonstrating the use and benefits of a multi-view, spectrally constrained coupled imaging system that provides accurate 3D luminescence images

A Small Animal Optical Tomographic Imaging System with Omni-Directional, Non-Contact, Angular-Resolved Fluorescence Measurement Capabilities

The overall goal of this thesis is to develop a new non-contact, whole-body, fluorescence molecular tomography system for small animal imaging. Over the past decade, small animal in vivo imaging has led to a better understanding of many human diseases and improved our ability to develop and test new drugs and medical compounds. Among various imaging modalities, optical imaging techniques have emerged as important tools. In particular, fluorescence and bioluminescence imaging systems have opened new ways for visualizing many molecular pathways inside living animals including gene expression and protein functions. While substantial progress has been made in available prototype and commercial optical imaging systems, there still exist areas for further improvement in the outcome of existing instrumentations. Currently, most small animal optical imaging systems rely on 2D planar imaging that provides limited ability to accurately locate lesions deep inside an animal. Furthermore, most existing tomographic imaging systems use a diffusion model of light propagation, which is of limited accuracy. While more accurate models using the equation of radiative transfer have become available, they have not been widely applied to small animal imaging yet. To overcome the limitations of existing optical small animal imaging systems, a novel imaging system that makes use of the latest hardware and software advances in the field was developed. At the heart of the system is a new double-conical-mirror-based imaging head that enables a single fixed position camera to capture multi-directional views simultaneously. Therefore, the imaging head provides 360-degree measurement data from an entire animal surface in one step. Another benefit provided by this design is the substantial reduction of multiple back-reflections between the animal and mirror surfaces. These back reflections are common in existing mirror-based imaging heads and tend to degrade the quality of raw measurement data. Furthermore, the conical-mirror design offers the capability to measure angular-resolved data from the animal surface. To make full use of this capability, a novel equation of radiative transfer-based ray-transfer operator was introduced to map the spatial and angular information of emitted light on the animal surface to the captured image data. As a result, more data points are involved into the image reconstructions, which leads to a higher image resolution. The performance of the imaging system was evaluated through numerical simulations, experiments using a well-defined tissue phantom, and live-animal studies. Finally, the double reflection mirror scheme presented in this dissertation can be cost-effectively employed with all camera-based imaging systems. The shapes and sizes of mirrors can be varied to accommodate imaging of other objects such as larger animals or human body parts, such as the breast, head, or feet