Review paperMicro-CT of rodents: State-of-the-art and future perspectives
Graphical abstract
The availability of micro-computed tomography (micro-CT) imaging has increased over the last decade and has shown its utility in many preclinical applications. The micro-CT instruments (Fig. 1) have evolved from custom-made to commercially available scanners designed for either ex vivo or in vivo imaging. We present fundamental principles, relevant technologies, and established applications before introducing new developments associated with spectral and phase contrast imaging. Micron-scale micro-CT is now an essential tool for phenotyping and for elucidating diseases and their therapies. These new technological advancements promise to further develop micro-CT into a commonplace, functional and even molecular imaging modality.
Introduction
The availability of micro-CT imaging has increased over the last decade and has shown its utility in many preclinical applications. The micro-CT instruments have evolved from custom-made to commercially available scanners designed for either ex vivo or in vivo imaging. Relative to other imaging methods, the strengths of micro-CT lie in its high resolution, relatively low cost, and scanning efficiency. In essence, a micro-CT scanner is based on the same physical principles as a clinical CT scanner, but it is designed for higher-resolution imaging.
A schematic of the complete micro-CT imaging process is shown in Fig. 1. Micro-CT typically produces three-dimensional (3D) tomographic data at microscopic resolution (voxel size ≤ 100 μm3) by taking several hundred, two-dimensional (2D) cone-beam projections from multiple angles around the animal [1]. The raw projection data are stored on a computer, where they are pre-processed prior to image reconstruction using dark current and flat-field images. The set of log-transformed projection images, also referred to as the cone-beam, X-ray transform of the linear attenuation coefficients, are the input to a tomographic reconstruction algorithm such as the Feldkamp algorithm [2]. The geometric parameters of the scanning are also incorporated into the reconstruction algorithm to produce tomographic images free from misalignment artifacts [3]. The intensity of each voxel within the reconstruction is proportional to the mean linear attenuation coefficient in the specimen at the same spatial location. Reconstructing isotropic voxels allows visualization in any orientation as 2D slices or a rendered 3D volume. This paper is a review of state-of-the-art micro-CT for rodent imaging. We present fundamental principles, relevant technologies, and established applications before introducing new developments associated with spectral and phase contrast imaging. These new developments promise to extend micro-CT imaging as functional and molecular imaging modality.
Section snippets
X-ray sources
The choice of the X-ray source strongly affects micro-CT system performance. Due to the tradeoff between focal spot size and thermal loading of the source's metallic anode, most X-ray tubes with mini-focus or micro-focus tubes (focal spot diameter: <∼50 μm) operate with very low photon output (on the order of 100-times lower) compared to the high-power tubes used in clinical scanners [4]. This fact leads to a dramatic increase in the average scan time required in micro-CT to get within an order
Bone imaging
Micro-CT has been used to investigate the structure and density of rodent bone since its very beginnings [15], [80], due to its high spatial resolution and high contrast in imaging mineralized tissues. In fact, the study of bone architecture and density drove the early developments of micro-CT systems [81]. When employed in ex vivo studies, the spatial resolution of dedicated bench-top systems approaches that provided by synchrotron sources [82]. Since the acquisition protocol is constrained by
Spectral micro-CT
As previously stated (Section Contrast agents), one of the major challenges for CT imaging is its poor contrast sensitivity. Increased contrast discrimination can be achieved using spectral CT combined with intrinsic (e.g. bone) and extrinsic (e.g. blood pool contrast agents) sources of contrast. Dual energy (DE) CT imaging using an X-ray energy integrating detector and a polychromatic X-ray source is the simplest form of spectral CT [158]. Additional metallic beam filters placed between the
Conclusions
Micro-CT provides a reliable platform for small animal imaging that is complementary to other small animal imaging methods, enabling numerous morphological and functional imaging applications. The radiation dose and low contrast associated with X-ray imaging are well-known; however, newly developed contrast agents and novel acquisition and reconstruction strategies show extraordinary promise in overcoming these limitations. Combined with exciting new opportunities in spectral and phase contrast
Acknowledgments
Some of the work presented here was performed at the Duke Center for In Vivo Microscopy, an NIH/NIBIB national Biomedical Technology Resource Center (P41 EB015897). Liposomal contrast agent was provided by Ketan Ghaghada and Ananth Annapragrada (Texas Children's Hospital, Houston, TX). We thank Sally Zimney for the editorial assistance, and Drs. G. Allan Johnson and Nicholas Befera for their contributions related to micro-SPECT.
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