Browsing by Author "Clark, DP"

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    Advances in micro-CT imaging of small animals.
    (Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB), 2021-08) Clark, DP; Badea, CT

    Purpose

    Micron-scale computed tomography (micro-CT) imaging is a ubiquitous, cost-effective, and non-invasive three-dimensional imaging modality. We review recent developments and applications of micro-CT for preclinical research.

    Methods

    Based on a comprehensive review of recent micro-CT literature, we summarize features of state-of-the-art hardware and ongoing challenges and promising research directions in the field.

    Results

    Representative features of commercially available micro-CT scanners and some new applications for both in vivo and ex vivo imaging are described. New advancements include spectral scanning using dual-energy micro-CT based on energy-integrating detectors or a new generation of photon-counting x-ray detectors (PCDs). Beyond two-material discrimination, PCDs enable quantitative differentiation of intrinsic tissues from one or more extrinsic contrast agents. When these extrinsic contrast agents are incorporated into a nanoparticle platform (e.g. liposomes), novel micro-CT imaging applications are possible such as combined therapy and diagnostic imaging in the field of cancer theranostics. Another major area of research in micro-CT is in x-ray phase contrast (XPC) imaging. XPC imaging opens CT to many new imaging applications because phase changes are more sensitive to density variations in soft tissues than standard absorption imaging. We further review the impact of deep learning on micro-CT. We feature several recent works which have successfully applied deep learning to micro-CT data, and we outline several challenges specific to micro-CT.

    Conclusions

    All of these advancements establish micro-CT imaging at the forefront of preclinical research, able to provide anatomical, functional, and even molecular information while serving as a testbench for translational research.
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    Dual source hybrid spectral micro-CT using an energy-integrating and a photon-counting detector.
    (Physics in medicine and biology, 2020-10-21) Holbrook, MD; Clark, DP; Badea, CT
    Preclinical micro-CT provides a hotbed in which to develop new imaging technologies, including spectral CT using photon counting detector (PCD) technology. Spectral imaging using PCDs promises to expand x-ray CT as a functional imaging modality, capable of molecular imaging, while maintaining CT's role as a powerful anatomical imaging modality. However, the utility of PCDs suffers due to distorted spectral measurements, affecting the accuracy of material decomposition. We attempt to improve material decomposition accuracy using our novel hybrid dual-source micro-CT system which combines a PCD and an energy integrating detector. Comparisons are made between PCD-only and hybrid CT results, both reconstructed with our iterative, multi-channel algorithm based on the split Bregman method and regularized with rank-sparse kernel regression. Multi-material decomposition is performed post-reconstruction for separation of iodine (I), gold (Au), gadolinium (Gd), and calcium (Ca). System performance is evaluated first in simulations, then in micro-CT phantoms, and finally in an in vivo experiment with a genetically modified p53fl/fl mouse cancer model with Au, Gd, and I nanoparticle (NP)-based contrasts agents. Our results show that the PCD-only and hybrid CT reconstructions offered very similar spatial resolution at 10% MTF (PCD: 3.50 lp mm-1; hybrid: 3.47 lp mm-1) and noise characteristics given by the noise power spectrum. For material decomposition we note successful separation of the four basis materials. We found that hybrid reconstruction reduces RMSE by an average of 37% across all material maps when compared to PCD-only of similar dose but does not provide much difference in terms of concentration accuracy. The in vivo results show separation of targeted Au and accumulated Gd NPs in the tumor from intravascular iodine NPs and bone. Hybrid spectral micro-CT can benefit nanotechnology and cancer research by providing quantitative imaging to test and optimize various NPs for diagnostic and therapeutic applications.
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    Low-dose 4D cardiac imaging in small animals using dual source micro-CT.
    (Phys Med Biol, 2018-01-09) Holbrook, M; Clark, DP; Badea, CT
    Micro-CT is widely used in preclinical studies, generating substantial interest in extending its capabilities in functional imaging applications such as blood perfusion and cardiac function. However, imaging cardiac structure and function in mice is challenging due to their small size and rapid heart rate. To overcome these challenges, we propose and compare improvements on two strategies for cardiac gating in dual-source, preclinical micro-CT: fast prospective gating (PG) and uncorrelated retrospective gating (RG). These sampling strategies combined with a sophisticated iterative image reconstruction algorithm provide faster acquisitions and high image quality in low-dose 4D (i.e. 3D  +  Time) cardiac micro-CT. Fast PG is performed under continuous subject rotation which results in interleaved projection angles between cardiac phases. Thus, fast PG provides a well-sampled temporal average image for use as a prior in iterative reconstruction. Uncorrelated RG incorporates random delays during sampling to prevent correlations between heart rate and sampling rate. We have performed both simulations and animal studies to validate these new sampling protocols. Sampling times for 1000 projections using fast PG and RG were 2 and 3 min, respectively, and the total dose was 170 mGy each. Reconstructions were performed using a 4D iterative reconstruction technique based on the split Bregman method. To examine undersampling robustness, subsets of 500 and 250 projections were also used for reconstruction. Both sampling strategies in conjunction with our iterative reconstruction method are capable of resolving cardiac phases and provide high image quality. In general, for equal numbers of projections, fast PG shows fewer errors than RG and is more robust to undersampling. Our results indicate that only 1000-projection based reconstruction with fast PG satisfies a 5% error criterion in left ventricular volume estimation. These methods promise low-dose imaging with a wide range of preclinical applications in cardiac imaging.
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    Micro-CT imaging of multiple K-edge elements using GaAs and CdTe photon counting detectors.
    (Physics in medicine and biology, 2023-04) Allphin, AJ; Clark, DP; Thuering, T; Bhandari, P; Ghaghada, KB; Badea, CT
    Objective.To evaluate the performance of two photon-counting (PC) detectors based on different detector materials, gallium arsenide (GaAs) and cadmium telluride (CdTe), for PC micro-CT imaging of phantoms with multiple contrast materials. Another objective is to determine if combining these two detectors in the same micro-CT system can offer higher spectral performance and significant artifact reduction compared to a single detector system.Approach. We have constructed a dual-detector, micro-CT system equipped with two PCDs based on different detector materials: gallium arsenide (GaAs) and cadmium telluride (CdTe). We demonstrate the performance of these detectors for PC micro-CT imaging of phantoms with up to 5 contrast materials with K-edges spread across the x-ray spectrum ranging from iodine with a K-edge at 33.2 keV to bismuth with a K-edge at 90.5 keV. We also demonstrate the use of our system to image a mouse prepared with both iodine and bismuth contrast agents to target different biological systems.Main results.When using the same dose and scan parameters, GaAs shows increased low energy (<50 keV) spectral sensitivity and specificity compared to CdTe. However, GaAs performance at high energies suffers from spectral artifacts and has comparatively low photon counts indicating wasted radiation dose. We demonstrate that combining a GaAs-based and a CdTe-based PC detector in the same micro-CT system offers higher spectral performance and significant artifact reduction compared to a single detector system.Significance.More accurate PC micro-CT using a GaAs PCD alone or in combination with a CdTe PCD could serve for developing new contrast agents such as nanoparticles that show promise in the developing field of theranostics (therapy and diagnostics).
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    Micro-CT of rodents: state-of-the-art and future perspectives.
    (Phys Med, 2014-09) Clark, DP; Badea, CT
    Micron-scale computed tomography (micro-CT) is an essential tool for phenotyping and for elucidating diseases and their therapies. This work is focused on preclinical micro-CT imaging, reviewing relevant principles, technologies, and applications. Commonly, micro-CT provides high-resolution anatomic information, either on its own or in conjunction with lower-resolution functional imaging modalities such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). More recently, however, advanced applications of micro-CT produce functional information by translating clinical applications to model systems (e.g., measuring cardiac functional metrics) and by pioneering new ones (e.g. measuring tumor vascular permeability with nanoparticle contrast agents). The primary limitations of micro-CT imaging are the associated radiation dose and relatively poor soft tissue contrast. We review several image reconstruction strategies based on iterative, statistical, and gradient sparsity regularization, demonstrating that high image quality is achievable with low radiation dose given ever more powerful computational resources. We also review two contrast mechanisms under intense development. The first is spectral contrast for quantitative material discrimination in combination with passive or actively targeted nanoparticle contrast agents. The second is phase contrast which measures refraction in biological tissues for improved contrast and potentially reduced radiation dose relative to standard absorption imaging. These technological advancements promise to develop micro-CT into a commonplace, functional and even molecular imaging modality.