**1. Introduction**

One of the most common models used in pre-clinical studies is nude mice implanted with brain tumors. In fact, owing to a deficiency in their immune systems, nude mice allow many tumor models to be studied and a wide range of therapeutic treatments to be investigated.

The best way to evaluate the efficiency of a treatment is to compare the kinetics of the tumor volume between a control group and a treatment group [1-3]. Since brain tumors generally evolve very quickly (7 to 15 days) in mice, the tumor must be detected early and characterized daily.

The advantages of non-invasive imaging methods are evident compared with conventional methods such as histochemistry, where animal sacrifice, end-point analysis only, and 2D tumor-diameter measurement are mandatory.

However, obtaining images of high spatial resolution and high contrast for the same animal in a longitudinal study is not trivial.

As in clinical MR imaging, the tumor can be detected in two possible ways. The first consists of using a gadolinium-based contrast agent injected intravenously to visualize the breakdown of the blood–brain barrier. Using a T1-weighted 3D gradient-echo sequence, high-resolution images can be obtained in a reasonable acquisition time. Nevertheless, because of the injuries caused by repeated injection of contrast agent into the tail vein, experiments cannot be performed frequently [1]. The other way consists of using T2 weighted sequences. RARE imaging, with or without magnetization transfer preparation [3– 5], allows small tumors to be detected noninvasively. The sequence is usually acquired in multi-slice 2D imaging in order to limit the total acquisition time. However, high-resolution,

3D TrueFISP MRI Provides Accurate Longitudinal Measurements of Glioma Volumes in Mice 127

 (1) The actual resolution is inversely proportional to the relaxation time, T2\*, and to the

 (2) The advantages of using intense magnetic field gradients are thus obvious, particularly at

Commercial gradient systems have been developed with intensities of greater than 400 mT/m over 10 cm, up to 1 T/m over 3 cm. Because the target diameter of these gradient systems is spatially limited, they can only be used to study animals such as rats or mice.

Fig. 1. Photograph of a 1-T/m gradient system. The system can be inserted into a magnet equipped with a 12-cm-diameter tunnel and can contain an antenna up to 6 cm in diameter.

Image quality is also significantly affected by the choice of antenna. The S/N depends entirely on this component as it is proportional to the square root of the antenna's quality factor, Q. Thus, a well-designed antenna is recommended. In addition, the S/N is directly

 (3) Optimal image quality will therefore be obtained using an antenna with a size and shape perfectly adapted to the zone to be imaged. Several types of antennae have been developed and can be used to meet these criteria. Volumetric emission/reception antennae are the most common. They provide a very homogeneous radio-frequency field, often required when

proportional to the filling factor for the antenna, represented by η in Eq. [3].

The gradient is linear over a distance of approximately 3 cm.

**2.3 Coil** 

gradient intensity and application time (Eq. [2]).

strong magnetic fields, with very short T2\*.

accurate 3D information is very important in longitudinal studies such as, for instance, the evaluation of a therapeutic treatment.

An alternative to RARE T2 [6] or 3D contrast-enhanced T1 imaging is fully balanced SSFP imaging (also called bSSFP, TrueFISP or FIESTA) [7]. In fact, it has recently been shown that this sequence can be used at high field, in 3D, to detect tumors of very small size [8]. The advantage of this sequence is the ability to combine the speed of 3D gradient echo and T1/T2 contrast.

The purpose of this study is to demonstrate that a 3D TrueFISP MRI sequence is applicable, at high magnetic field, to glioma-bearing mouse models in longitudinal studies. Theoretical considerations of tumor contrast and signal-to-noise ratio as a function of sequence parameters (TE/TR/flip angle) were carried out and compared with experimental data.

The 3D TrueFISP MRI sequence was also compared with the sequence most widely used in clinical applications: 2D RARE. Finally, the sequence was used to perform accurate longitudinal measurements of glioma volumes in mice.
