In Vivo Imaging With Confirmation by Histopathology for Increased Rigor and Reproducibility in Translational Research: A Review of Examples, Options, and Resources

Abstract

Preclinical noninvasive imaging can be an indispensable tool for studying animal models of disease. In vivo imaging to assess anatomical, functional, and molecular features requires verification by a comparison to the macroscopic and microscopic morphological features, since all noninvasive in vivo imaging methods have much lower resolution than standard histopathology. Comprehensive pathological evaluation of the animal model is underutilized; yet, many institutions have veterinary or human pathologists with necessary comparative pathology expertise. By performing a rigorous comparison to gross or histopathology for image interpretation, these trained individuals can assist scientists with the development of the animal model, experimental design, and evaluation of the in vivo imaging data. These imaging and pathology corroboration studies undoubtedly increase scientific rigor and reproducibility in descriptive and hypothesis-driven research. A review of case examples including ultrasound, nuclear, optical, and MRI is provided to illustrate how a wide range of imaging modalities data can be confirmed by gross or microscopic pathology. This image confirmation and authentication will improve characterization of the model and may contribute to decreasing costs and number of animals used and to more rapid translation from preclinical animal model to the clinic.

Magnetic Resonance Imaging for Translational Research in Oncology

“…However, the employment of clinically-used contrast agents limits the repeated imaging in the same animal, in particular, due to the iodinated contrast, which is rapidly cleared from the blood, and therefore, should be administered repeatedly. Moreover, high dosages of this agent may result in nephrotoxicity, and its use may produce an ionization effect, resulting in radiation damage through reactive oxygen species [8,17,81,82,83,84].…”

“…As for clinical scanning, preclinical PET devices provide excellent sensitivity (from 2% to 7%, depending on the energy window) and spatial resolution (1.2 mm, on average), but the main disadvantages are the lack of an anatomical parameter, usually overcome by associating a CT scan or MR scans. Moreover, the short half-life of most radioisotopes requires strict coordination between radiotracer production, delivery, and use in small animal models [83,84].…”

“…In this setting, over the last few years, the sensitivities and specificities of ultrasound devices to detect microbubbles have progressively improved. Indeed, beyond the frequent use of color or power dopplers, non-targeted microbubbles are used as intravascular contrast agents improving the detection and characterization of cancerous lesions, inflammatory processes, and cardiovascular pathologies [83,84,88]. In preclinical investigations, HFUS can be applied to monitor tumor growth and vasculature development, and in combination with contrast-enhanced microbubbles agents (CEMAs), is used to assess tumor angiogenesis, inflammation, and therapeutic effects.…”

“…The MRI is one technique with multiple possible outcomes; indeed, depending on the sequences, it allows studying, other than the merely displaying the anatomy, of various aspects of the same lesion. In particular, diffusion of water molecules can be studied with diffusion-weighted sequences (DWI); spectroscopy allows detecting and quantifying small amounts of known molecules; angiographic sequences (like time-of-flight or phase contrast angiography) allow evaluating large blood vessels, even without the need of contrast agents, and so on [17,82,83,84]. The MRI has also proven to be useful in preclinical research, allowing the evaluation of biological processes at the molecular level in in vivo rodent models of diseases.…”

Noninvasive in vivo cell tracking using molecular imaging: A useful tool for developing mesenchymal stem cell-based cancer treatment

“…With the use of in vivo three-dimensional (3D) imaging, different biological processes including gene expression, protein trafficking, and cell migration/ homing/tumor infiltration can be visualized using high resolution[ 11 ]. For studies involving animal models, readouts can be acquired with the use of the same animal over time, thereby reducing the sample size and discrepancies in measurements[ 12 ]. Implementing in vivo imaging at the preclinical level can save a lot of time, money, and resources, which can then be invested in clinical studies.…”