Technical Aspects for Performing Small Animal MRI
Jiangyang Zhang1

1New York University

Synopsis

Among the imaging modalities commonly encountered in small animal imaging, MRI is arguably the most versatile imaging modality because of the rich tissue contrasts it provides. In designing and implementing small animal MRI studies, there are several technical aspects, mainly related to the unique anatomy and physiology of small animals, that need to be considered, including but not limited to: pros and cons of in vivo and ex vivo MRI; imaging resolution and speed; and image contrasts. Instead of providing a one-size-fit-all solution, this course tries to provide a general guide for people interested in this topic.

Highlights

Pros and cons of in vivo MRI and ex vivo MRI

Spatial resolution

Image contrasts

Target audience

MR physicists interested in testing new techniques in small animal models and biologists interested in using MRI to study small animal models.

Objective

Demonstrate key technical considerations of small animal MRI

Introduction

The laboratory mouse and rat have been widely used in biomedical research to study disease mechanisms and potential treatments. While histology has been the method of choice for capturing the cellular and molecular processes in small animal models, there is an increasing need for complementary imaging tools, ideally non-invasive methods, to monitor disease progression and define treatment efficacy, even at lower resolution and reduced sensitivity and specificity. In the past decade, rapid developments in several imaging modalities have greatly increased our capability to study more aspects of small animals physiology and pathology (1). Some of these imaging modalities, such as CT, MRI, and PET, have been used to image both human and animals, and for them, findings in small animal studies may be readily translated to human studies. Among the imaging modalities commonly encountered in small animal imaging, MRI is arguably the most versatile imaging modality because of the rich tissue contrasts it provides (both endogenous and with contrast agents, both structural and functional). With the increasing availability of high field (> 7 Tesla) preclinical MR systems and high sensitivity coils, small animal MRI has been increasingly adopted in biomedical research. In designing and implementing small animal MRI studies, it is often assumed, initially, that clinical MRI protocols can be transferred to preclinical MR systems with minimal modifications. In practice, there are several technical aspects, mainly related to the unique anatomy and physiology of small animals, that need to be considered, followed by careful fine-tuning and validation of the imaging protocols.

In vivo or ex vivo MRI

When designing an MRI study of the small animal, one of the first considerations is whether it should be carried out in post-mortem tissue specimens or in live animals. Ex vivo MRI offers higher resolution than in vivo MRI because the structures of interest can often be dissected out and fitted into a high-sensitivity coil (2, 3) and imaged for a prolonged time (4). The resolution advantage of ex vivo MRI may benefit certain applications, e.g., morphological studies of the mouse brain. It has been suggested that ex vivo MRI is more sensitive to detect changes in hippocampal volumes than in vivo MRI (5). In vivo MRI, on one hand, is limited by the time that anesthesia can maintain animals in a stable condition (often less than 3 hours for normal adult mice and less for young and injured animals), and the sensitivity of the coils due to the need to accommodate the animal as well as the anesthesia and monitoring systems. On the other hand, in vivo MRI offers some unique advantages. In vivo MRI allows longitudinal imaging, which decrease the number of animals required due to its higher statistical powers. In vivo MRI also allows measurements under normal physiological conditions. It has been shown that death and chemical fixation can significantly alter tissue properties, such as T1, T2, cell size, and membrane permeability (6, 7). Furthermore, key pathological processes, e.g. inflammation and cytotoxic edema after acute stroke, can only be more easily detected using in vivo MRI than ex vivo MRI (8, 9).

Imaging resolution

Currently, there is no consensus on the optimal imaging resolution for small animal MRI. It depends on several factors, e.g., the structures of interest and instrument stability and cost. In this section, we will focus on MRI of the mouse brain to show the highest resolution achieved for in vivo and ex vivo MRI in order to provide a guide on what is available. We only include studies with conventional T1/T2-weighted and diffusion MRI because they have been commonly used to study the mouse brain and body (4, 10-13), for which high resolution is often desirable. Table 1 lists several high-resolution ex vivo MRI studies of the mouse brain, including the sequences and scan times. In these studies, Gadolinium (Gd)-based contrast agents were used as these agents can penetrate post-mortem tissue specimens and significantly shorten the T1 and T2 relaxation times of brain tissue to enhance signals and tissue contrasts (14-16). With optimized imaging protocols, we can now acquire conventional T1/T2-weighted images at spatial resolutions that approach the size of large cells in the brain (12).

In vivo MRI is often performed using 2D multi-slice imaging sequences because it is relatively high speed compared to 3D imaging. A typical multi-slice T2-weighted MRI of the mouse brain can be acquired with an in-plane resolution of 0.1 mm x 0.1 mm, a 0.5 – 1 mm slice thickness, and within 10-15 minutes. In order to achieve higher resolution, especially in the slice direction, it is necessary to use 3D imaging. Table 2 lists several in vivo high-resolution MRI studies of the mouse brain. Because of the blood-brain-barrier, most Gd-based contrast agents cannot penetrate the brain.

Image Contrast

In this section, we focus on recent technical developments in several commonly used MRI techniques based on endogenous tissue contrasts. MRI techniques based on contrast agent, for example, dynamic-contrast MRI and Manganese-enhanced MRI, are not discussed in this section. T1/T2 MRI: T1/T2-weighted MRI has been the most widely used techniques in small animal MRI studies. They provide basic anatomical information, and quantitative mapping of tissue T1 and T2 values can provide important information, e.g., tissue water content and degree of myelination. It is necessary to note that T1 and T2 values of tissue are field dependent, as shown in a recent report (24). Diffusion MRI: While conventional T1/T2-weighted MRI provides satisfactory contrasts for delineation of internal organs and major brain compartments, such as the ventricles and cerebellum, it often lacks good contrasts to further distinguish internal structures within major brain compartments (25), e.g., early white matter tracts. In comparison, diffusion MRI techniques, e.g., diffusion tensor imaging (DTI) (26, 27), provide superior contrasts for delineation of the premature gray and white matter structures. In the recent years, high-resolution diffusion MRI of the mouse brain using sophisticated diffusion MRI techniques has been implemented to enhance our ability to resolve microstructural organizations of the developing mouse brain (17, 22, 28). Perfusion MRI: Arterial spin labelling (ASL) is an important MRI technique to image tissue perfusion. Both pulsed and continuous ASL techniques have been used in small animal studies, as demonstrated by several groups (29-31). Recently, Xu et al. developed a modified labeling scheme that can speed up the acquisition of multi-slice perfusion images from the mouse brain (32). Resting-state functional MRI (rs-fMRI): While rs-fMRI has become a routine procedure in human studies, its application in the mouse and rat brain remains challenging mainly due to the need to fine-tune the level of anesthesia and to maintain the physiology at a stable level (33, 34). Rs-fMRI of the rat brain has been reported before (35, 36) but only recently has rs-fMRI of the mouse brain been reported with interesting applications in mouse models of disease (37-39).

Summary

Unlike clinical MRI, small animal MRI faces unique technical challenges, and it is difficult to find a one-size-fit-all solution to fit a variety of small animal models. As a result, this course only tries to provide a general guide on designing and implementing small animal MRI.

Acknowledgements

No acknowledgement found.

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Figures

Table 1: Imaging parameters of selected reports on ex vivo MRI of the mouse brain. Abbreviations are: dw: diffusion-weighted; FSE: fast spin echo; GRASE: gradient and spin echo; SE: spin echo; T: Tesla; TE: echo time; TR: repetition time.

Table 2: Imaging parameters of selected reports on in vivo MRI of the mouse brain. Abbreviations are: dw: diffusion-weighted; FSE: fast spin echo; GRASE: gradient and spin echo; SE: spin echo; T: Tesla; TE: echo time; TR: repetition time.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)