Development of computational small animal models and their applications in preclinical imaging and therapy research

Abstract

The development of multimodality preclinical imaging techniques and the rapid growth of realistic computer simulation tools have promoted the construction and application of computational laboratory animal models in preclinical research. Since the early 1990s, over 120 realistic computational animal models have been reported in the literature and used as surrogates to characterize the anatomy of actual animals for the simulation of preclinical studies involving the use of bioluminescence tomography, fluorescence molecular tomography, positron emission tomography, single-photon emission computed tomography, microcomputed tomography, magnetic resonance imaging, and optical imaging. Other applications include electromagnetic field simulation, ionizing and nonionizing radiation dosimetry, and the development and evaluation of new methodologies for multimodality image coregistration, segmentation, and reconstruction of small animal images. This paper provides a comprehensive review of the history and fundamental technologies used for the development of computational small animal models with a particular focus on their application in preclinical imaging as well as nonionizing and ionizing radiation dosimetry calculations. An overview of the overall process involved in the design of these models, including the fundamental elements used for the construction of different types of computational models, the identification of original anatomical data, the simulation tools used for solving various computational problems, and the applications of computational animal models in preclinical research. The authors also analyze the characteristics of categories of computational models (stylized, voxel-based, and boundary representation) and discuss the technical challenges faced at the present time as well as research needs in the future. C 2016 American Association of Physicists in Medicine. [http://dx

Preclinical dosimetry models and the prediction of clinical doses of novel positron emission tomography radiotracers

“…Normalization of rodent:human 17 , 18 , non-human primate:human 19 – 21 and pig:human 17 organ sizes has been previously used to estimate PET dosimetry of new radiotracers. Many studies focus on developing preclinical models of animal dosimetry (see review 22 ) and well-established human PET dosimetry models 23 , 24 . Unfortunately, dichotomous dosimetry findings are prevalent when translating a novel radiotracer from preclinical research to clinical use, which is likely a result of an important knowledge gap of the bias between preclinical dose estimates and human doses.…”

Development of a nonhuman primate computational phantom for radiation dosimetry

“…At present, there is a lack of realistic computational models and radiation dose estimates for NHPs to enable the calculation of absorbed doses in preclinical research studies. 7,8 As such, human models were commonly used to perform dosimetry calculations. [9][10][11][12] Therefore, there is a need for such models and detailed dose estimates to fill a gap in the radiation dosimetry literature.…”

“…To reach the full potential of ARS studies, multimodality imaging, radiation therapy, and radiotracer development research using NHPs, suitable computational models, and radiation dosimetry data must be made available to the research community. At present, there is a lack of realistic computational models and radiation dose estimates for NHPs to enable the calculation of absorbed doses in preclinical research studies . As such, human models were commonly used to perform dosimetry calculations .…”

The specific absorption rate in different brain regions of rats exposed to electromagnetic plane waves

“…Studies on small animals, especially rats, are usually conducted to determine the EMF dose-effect relationship in the brain, which can then be translated to humans 6 . Accurate evaluation of power deposited in the brains of rats is essential for establishing the dose-effect relationship.…”

“…Therefore, the numerical methods based on voxel rat models had been widely used to evaluate the SAR distribution. Realistic numerical voxel models can be constructed based on magnetic resonance imaging (MRI) or computer tomography (CT) data 6,18 . Based on voxel models, numerical methods such as finite difference time domain (FDTD) scheme can be performed to provide high resolution SAR distribution 7 .…”