**8. References**


daminobutyric acid (DAB) to perfusate (Ronquist et al. 1992). This was extended by Bergenheim et al who recruited 10 patients with GBM that underwent stereotactic biopsy with the insertion of two microdialysis catheters: one in the contrast enhancing tumour (T), and the second 10mm outside the contrast enhancing region in the peritumour region (PT) (Bergenheim et al. 2006). Catheters inserted into T were LWCO with 30mm membranes, and were perfused with 80 or 120mmol/l DAB at a rate of 2µl/m. Samples were analysed for metabolites using a CMA 600 analyser, and for amino acids using HPLC. During treatment with DAB a significant increase in a number of amino acids including glutamate was observed suggesting cellular toxicity. PT samples were unaffected suggesting treatment effects was localised to the tumour compartment. Although the sample size was too small to determine whether there was an effect on clinical outcome, the study nevertheless provides

In the last decade there has been a surge of interest in the application of clinical microdialysis to neuro-oncology. In this chapter we have reviewed the principles of microdialysis, and systematically appraised studies on the use of the technique to investigate gliomagenesis, the effect of treatment with chemotherapy and radiotherapy, and the potential for administration of drugs with retrograde microdialysis. The utility of the technique lies in its use alongside other methods such as in-vitro, animal and imaging

We thank Keri Carpenter, Stephen Price, and Peter Hutchinson for their continued advice on

Behrens, P. F., H. Langemann, R. Strohschein, J. Draeger & J. Hennig (2000) Extracellular

Bellander, B. M., E. Cantais, P. Enblad, P. Hutchinson, C. H. Nordstrom, C. Robertson, J.

Benjamin, R. K., F. H. Hochberg, E. Fox, P. M. Bungay, W. F. Elmquist, C. F. Stewart, J. M.

Bergenheim, A. T., J. Capala, M. Roslin & R. Henriksson (2005) Distribution of BPA and

glutamate and other metabolites in and around RG2 rat glioma: an intracerebral

Sahuquillo, M. Smith, N. Stocchetti, U. Ungerstedt, A. Unterberg & N. V. Olsen (2004) Consensus meeting on microdialysis in neurointensive care. *Intensive Care* 

Gallo, J. M. Collins, R. P. Pelletier, J. F. de Groot, R. C. Hickner, I. Cavus, S. A. Grossman & O. M. Colvin (2004) Review of microdialysis in brain tumors, from concept to application: first annual Carolyn Frye-Halloran symposium. *Neuro* 

metabolic assessment in glioblastoma patients during BNCT treatment: a

evidence to support the feasibility of the technique.

microdialysis study. *J Neurooncol,* 47, 11-22.

microdialysis study. *J Neurooncol,* 71, 287-93.

**6. Conclusion** 

**7. Acknowledgments** 

*Med,* 30, 2166-9.

*Oncol,* 6, 65-74.

clinical microdialysis.

**8. References** 

studies.


**9** 

*Durham, NC,* 

*USA* 

**PET Imaging of Gliomas** 

*Harvard Medical School, Boston, MA* 

Aditya Bansal1, Terence Z. Wong2 and Timothy R. DeGrado1

*1Division of Nuclear Medicine and Molecular Imaging, Brigham and Women's Hospital,* 

*2Department of Radiology, Nuclear Medicine Division, Duke University Medical Center,* 

Noninvasive imaging methods, including positron emission tomography (PET), have become essential for diagnosis and staging of gliomas, and monitoring of treatment response. The utility of these techniques have been found to be highly dependent on tumor grade. According to the World Health Organization (WHO) classification of tumors (Kleihues and Sobin 2000), gliomas are classified into 3 main histological types: astrocytoma, oligodendroglioma and glioblastoma. These histological types are further classified on the basis of anaplasia and degree of malignancy as: grade I, noninvasive glioma (pilocytic astrocytoma); grade II, less-invasive glioma (astrocytomas and oligodendrogliomas); grade III, invasive glioma (analplastic astrocytoma/oligodendrogliomas); and grade IV, highly

Low-grade gliomas (grade I and II) typically affect younger patients. Grade I glioma is the most common form of glioma in children and is less frequent in adults (Burkhard et al. 2003) while grade II gliomas are common in adults (mean age of onset is 40 years) (Hagerstrand et al. 2008). Median survival for low-grade glioma is varied but prognosis and treatment require regular follow ups. Low-grade gliomas grow slowly or stabilize spontaneously and with surgical resection, median survival can be 20 years or more (Burkhard et al. 2003). For high-grade gliomas, the mean age of onset is 40 years for grade III glioma and 61 years for GBM (Ohgaki and Kleihues 2005). GBM is the most malignant and most common glioma, accounting for 45% - 50% of all adult gliomas. Median survival for grade III glioma is 2-3 years and for GBM is 1 year (Chen 2007). For optimal disease prognosis, treatment and follow up, one should be able to delineate the tumor lesion and most importantly, differentiate benign lesions from neoplastic lesions, low-grade from high grade tumors, and tumor progression from therapy induced necrosis. As will be discussed later, efforts are also

being directed toward defining early imaging predictors of response to therapy.

Conventional imaging with magnetic resonance imaging (MRI) provides excellent anatomical definition of brain tumors. MRI is highly sensitive in identifying lesions, mass effect, edema, hemorrhage, necrosis and signs of increased intracranial pressure (Chen 2007). Pathologic changes are characterized on MRI by increased water content (edema) and blood-brain barrier (BBB) disruption, visualized as contrast enhancement (Grosu et al. 2002). Most tumors (low-grade or high-grade) have prolonged T1 and T2 relaxation times and thus

**1. Introduction** 

invasive glioma (glioblastoma, or GBM).

