**6. References**

142 Advances in the Biology, Imaging and Therapies for Glioblastoma

total acquisition time: good T2 weighting is required for tumor detection, and can only be obtained with TRs greater than 3,500 ms. This leads to a total acquisition time on the order of 1 hour, whereas around 10 minutes is adequate with the 2D sequence or the 3D TrueFISP

The TrueFISP sequence provides adequate contrast, allowing even very small tumors to be detected clearly, and semi-automatically segmented using generic image-analysis tools. However, as shown in both simulations and images, the contrast between the healthy brain and the tumor remains lower than that provided by the spin-echo sequence. This is due to TrueFISP-sequence weighting, which relies on the T1/T2 ratio, while the RARE sequence only uses T2 weighting. This has several consequences. In some cases, e.g. when the tumor becomes very large and heterogeneous, semi-automatic segmentation becomes difficult due to inadequate contrast with the healthy brain. Manual segmentation therefore becomes necessary, which may be both tedious and subjective. Nevertheless, the error rate when

Another consequence is that it is almost impossible to detect a glioma in the brain at fields higher than 4.7 T based on natural contrast. This is because the T1 and T2 values for the brain and tumor become almost identical, which limits the contrast at very high magnetic

Thus, for this type of application, the TrueFISP sequence at 9.4 T or greater provides little advantage over other, more commonly used sequences. However, at low fields, the S/N and contrast provided by the TrueFISP sequence make it particularly interesting. It has already been shown with specific instruments that it allows tumors to be easily detected in mice based on natural contrast, and that it provides an excellent signal-to-noise ratio at clinical

In terms of spatial resolution, the advantages of 3D compared with 2D imaging are obvious. Three-dimensional imaging results in much smaller voxel sizes with comparable acquisition times, while maintaining a high S/N. This requires the addition of a phase-encoding table in the slice direction, i.e. a much greater number of lines read in the Fourier volume. The advantages of sequences with short TRs thus become obvious. As shown, the TrueFISP sequence also provides a much greater precision when measuring tumor volume, in particular for small tumors. With the 2D RARE sequence, it is impossible to precisely measure volume changes in the first days following tumor implantation. With the 3D

In addition, as the sequence is relatively rapid in terms of total acquisition time, it can be repeated at very short intervals to follow tumor progression, even in relatively fragile mice. The total examination, between preparation of the animal and imaging, lasts less than 20 minutes. This makes it possible to study animals on a daily basis. This is much more difficult when contrast agents must be injected, or with acquisition times of around 1 hour,

To conclude, the 3D TrueFISP sequence can be easily used to follow tumor progression in a small animal model imaged at 4.7 T. Thanks to a particularly high S/N, artifact-free images can be acquired, with excellent spatial resolution and good tumor/healthy brain contrast. The total acquisition time remains under 15 minutes, thus offering precise longitudinal follow-up of tumor volume. Thus, this sequence could be used to noninvasively validate the

At lower magnetic fields, the sequence has also demonstrated its efficacy. In contrast, it is

currently not applicable at 9.4 T or higher to precisely measure tumor volumes.

fields. The T2-weighted RARE sequence still works perfectly at these higher fields.

sequence.

estimating even large volumes remains low.

magnetic fields (1.5 T and 3 T) [16,17].

as with 3D RARE sequences [15].

TrueFISP sequence, this information is readily available.

efficacy of new genetic or pharmacological treatments for glioma.


**8** 

**Clinical Microdialysis in Glioma** 

Microdialysis is a technique that may be used to directly investigate brain chemistry in-vivo. Although initially developed over 35 years ago (Ungerstedt and Pycock 1974), it is only relatively recently that studies have begun to utilise microdialysis in patients with glioma and other brain tumours. In this chapter we will review the general principles of microdialysis, the use of the technique to investigate glioma pathogenesis and evaluate chemo- and radiotherapy, and the potential utilisation of retrograde microdialysis to

Present-day microdialysis is the result of several decades of technological advancement. An understanding of the principles underlying the technique is an essential prerequisite to

Microdialysis enables sampling of the extracellular fluid (ECF). A microdialysis catheter or probe with a semi-permeable membrane at its tip is placed into the tissue of interest. Perfusate with a similar composition to the ECF is then slowly and continuously infused through the catheter. Substances of interest diffuse across the semi-permeable membrane into the catheter, and the resulting dialysate is collected in microvials, which are changed at

Diffusion of substances from the ECF, across the membrane, and into the flowing perfusate, is often incomplete. Thus, the concentration of a substance within the dialysate represents a fraction of that in the ECF. The *extraction fraction* or *relative recovery* is defined as the ratio of a substance's concentration in the dialysate (*Cdialysate*) compared to the actual concentration

Relative Recovery = Cdialysate / CECF x 100% A number of variables may influence the relative recovery including the flow rate, the semipermeable membranes length and pore size, and the properties of the substance of interest itself (see Table 1) (de Lange et al. 1997, de Lange, de Boer and Breimer 1999, Hutchinson et al. 2000, Benjamin et al. 2004, Helmy et al. 2009, Chefer et al. 2009, Blakeley et al. 2009).

administer chemotherapeutic agents directly to the tumour bed.

regular intervals and subsequently analysed (see Figure 1).

appreciating its potential uses and limitations.

**2.1 Principles, uses and limitations** 

**1. Introduction** 

**2. Microdialysis** 

**2.1.1 Principles** 

in the ECF (*CECF*).

Hani Marcus and Dipankar Nandi

*Imperial College London* 

*United Kingdom* 

