Imaging the rat brain on a 1.5 T clinical MR-scanner

https://doi.org/10.1016/S0165-0270(00)00172-2Get rights and content

Abstract

Magnetic resonance imaging (MRI) offers a noninvasive technique for studying neurodegenerative events in the rat brain, however, most of the studies are performed on small bore purpose dedicated MR scanners of limited availability and at high cost. The present study explored the feasibility of using a clinical whole body MR-scanner to perform imaging in rat brain and specifically in models of Parkinson's (PD) and Huntington's disease (HD). For that purpose rats were placed into a specially designed PVC device equipped with a flexible surface coil-and T2-weighted spin echo sequences were acquired on a Siemens Magnetom Vision at 1.5 T. In the experimental protocols of PD and HD, animals underwent 6-hydroxydopamine (6-OHDA) and quinolinic acid (QA) injections, respectively and were subsequently grafted with fetal tissue. T2-weighted images showed a small hyperintense area at the 6-OHDA lesion site and a diffuse hyperintensity in the striata with QA lesions. Transplants were seen as a hypointense area surrounded by a hyperintense rim on T1-weighted images. Moreover, disturbances of the blood-brain-barrier and its time of restoration could be monitored. In conclusion, high-resolution in vivo imaging of small animals is feasible with clinical MR-scanners and hence allows the study of various experimental protocols.

Introduction

Rodent models are a widely used and accepted method for studying pathologies in the field of neuroscience. Most of the analyses, however, rely on the post-mortern examination of tissue. The application of imaging modalities has brought the advantage of in vivo monitoring of pathological changes for longitudinal studies, and leads therefore to a higher efficiency in animal experiments. Due to the small size of the rat brain, high-resolution imaging is required. 1H magnetic resonance imaging (MRI) has been found to meet these requirements providing a noninvasive, non-harmful technique. In most studies purpose-dedicated, small bore nuclear magnetic resonance systems have been used (Johnson et al., 1987, Peschanski et al., 1988, Wang et al., 1991, Detre et al., 1992, Sauer et al., 1992, Jackson et al., 1994, Mellin et al., 1994, Kamiryo et al., 1995, Mason et al., 1995, Silva et al., 1995, Ito et al., 1996, John et al., 1996, van Lookeren Campagne et al., 1996). This equipment is very expensive and not readily accessible to all research laboratories, moreover they have characteristics that differ strongly from clinical scanners. Even though clinical MR scanners are widely available, the spatial resolution routinely used to examine the human brain is not sufficient for the study of the rat brain. Therefore only few studies have been carried out on clinical MR scanners using specially developed radio frequency (RF)-coils (Martos and Petersen, 1993, Smith et al., 1993, Kennedy et al., 1995). We addressed this issue by studying the feasibility of imaging the rat brain using a clinical MR-scanner and clinically available RF-coils. Special considerations have to be directed towards the design of the sequences in term of resolution on the one hand, and signal to noise ratio (SNR) on the other hand. The spatial resolution in MRI is dependent of the sample volume that is acquired. This so called voxel size can be altered, either by reducing the field of view (xy plane) or the slice thickness (z plane). Reducing the field of view while keeping the same matrix and using thin slice thickness is required to avoid too much volume-averaging. This is done at the expense of the signal-to-noise ratio, which increases linearly with the voxel size. Reduction of the voxel size results in diminished signal and therefore reduces the signal-to-noise ratio (Smith et al., 1993). Signal averaging of multiple excitations provides an increase in signal-to-noise ratio proportional to the square root of the number of excitations which, however, leads to increased measurement time.

The goal of the present study was to obtain MR images with good resolution in a consistent and repetitive way using a clinical whole body MR scanner and a commercially available RF-coil. In order to image the rat brain in the clinical scanner we designed an installation that allows to put the rat in the MR-scanner and to fix the rat in order to avoid movement artifacts. The present study shows that accurate imaging in the rat brain can be performed on clinically available material. Moreover we describe the potential of a clinical MR-scanner to detect changes in the brain after excitotoxic lesions and neural transplantation.

Section snippets

MR-imaging and coil

MR-scannings were performed on a Siemens Magnetom Vision at 1.5 T (Siemens Erlangen, Germany) with a field gradient strength of 25 mT/M using a flexible surface coil. Rats were anesthetized (Nembutal, 40 mg/kg i.p.) and placed into the polyvinyl chloride (PVC) rat holder. The rat head was fixed with two ear bars screwed on the sliding head-rest (Fig. 1A). The fixation of the head avoids image artifacts due to bulk movement. The tail was accessible for intravenous contrast agent injections

Anatomy

T2-weighted images typically showed high contrast between gray matter and highly myelinated white matter which appeared black and structures such as the corpus callosum or the arbor vitae of the cerebellum could be differentiated. The cerebrospinal fluid filled spaces are seen as high intensity areas (Fig. 2). It was possible to discern anatomical structures within the rat brain. The transverse plane at the level of the eyes depicted the neocortex, the caudate putamen and the cerebellar

Discussion

The present study aimed at investigating the rat brain by means of a clinical MR-scanner. MRI reveals to be a powerful approach in the study of brain pathologies in small laboratory animals. In order to demonstrate the resolution capacity of a clinical MR-scanner in the study of the rat brain, the excitotoxic and neurotransplantation rat models for Parkinson's and Huntington's disease were used.

MR imaging of small animal brains is technically challenging. The quality of the resulting image is

Conclusions

In summary, high resolution rat brain imaging has been performed on a clinical magnetic resonance scanner and a clinical transmitter–receiver coil demonstrating that clinical whole body MR scanners are suitable for in vivo study of small animals. This technique was found applicable in the study of neural excitotoxicity and neural grafting and may well be expanded to other experimental models in the field of neuroscience research.

Acknowledgements

Tanja Bosnjak, Beatrice Bühler, Sandra Krebs and Benoı̂t Schaller are gratefully acknowledged. The study was supported by the Swiss National Science Foundation (Grant No. 31-52947.97).

References (38)

  • A.B. Norman et al.

    A magnetic resonance imaging contrast agent differentiates between the vascular properties of fetal striatal tissue transplants and gliomas in rat brain in vivo

    Brain Res.

    (1989)
  • M. Peschanski et al.

    Magnetic resonance imaging of intracerebral neural grafts

    Prog Brain Res.

    (1988)
  • J.M. Rosenstein et al.

    Blood–brain and blood–cerebrospinal fluid alterations following neural transplantation

    Prog. Brain Res.

    (1988)
  • D. Sauer et al.

    Evaluation of quinolinic acid induced excitotoxic neurodegeneration in rat striaturn by quantitative magnetic resonance imaging in vivo

    Neurosci. Methods

    (1992)
  • N.E. Simmons et al.

    Magnetic resonance imaging of neuronal grafts in the primate

    Exp. Neurol.

    (1994)
  • D.A. Smith et al.

    Use of a clinical MR scanner for imaging the rat brain

    Brain Res. Bull.

    (1993)
  • C. Spenger et al.

    Long-term survival of dopaminergic neurones in free-floating roller tube cultures of human fetal ventral mesencephalon

    J. Neurosci. Methods

    (1994)
  • P. Brundin et al.

    Intracerebral xenografts of dopamine neurons: the role of immunosuppression and the blood–brain barrier

    Exp. Brain Res.

    (1989)
  • J.A. Detre et al.

    Perfusion imaging

    Magn. Reson. Med

    (1992)
  • Cited by (40)

    • Establishment of novel technical methods for evaluating brain edema and lesion volume in stroked rats: A standardization of measurement procedures

      2019, Brain Research
      Citation Excerpt :

      Moreover, most previous studies used a small number of animals (about 10) in the experiment (Robertson et al., 2011). Until now, rare are the studies have used clinical MRI in the study of rodent brains (Attenberger et al., 2009; Chen et al., 2004; Guzman et al., 2000; Ulmer et al., 2008). In our study, we sought to establish a unitary MRI protocol for stroke assessment in rats, using a 3 T MRI clinical scanner, as well as another clinical equipment to render results reproducible.

    • 6-Hydroxydopamine leads to T2 hyperintensity, decreased claudin-3 immunoreactivity and altered aquaporin 4 expression in the striatum

      2012, Behavioural Brain Research
      Citation Excerpt :

      TH expression was investigated in the striatum of all animals used for experiments and animals with a decrease of less than 10% in TH immunoreactivity, TH protein or TH mRNA were excluded from the experiments (see also [14]). Hyperintensity in T2w MRI images is described following injection of neurotoxic agents like kainic acid [25], N-methyl-d-aspartate [26,27] and 6-OHDA [3–5]. The location of the hyperintensity in 6-OHDA lesions is shown to correlate with the site of injection and is shown so far following injection into the striatum [3], the MFB [4], the SN [3] and the medial preoptic area [5].

    • Delayed intervention in experimental stroke with TRC051384 - A small molecule HSP70 inducer

      2011, Neuropharmacology
      Citation Excerpt :

      Further in our study MRI was used as it offers advantage of non invasiveness in order to examine the progression of the core and penumbra over a period of time. The imaging modalities, which earlier have been used extensively, such as T2 weighted and ADC (Guzman et al., 2000; Li et al., 2000b; van der Weerd et al., 2005) helped in monitoring the development of brain edema and extent of penumbra being further recruited into the ischemic core. Hence, disease monitoring in individual rats was done in this study by serial magnetic imaging with a 1.5 T clinical MR machine at various time points post-initiation of MCAo.

    View all citing articles on Scopus
    View full text