Elsevier

The Lancet Neurology

Volume 6, Issue 8, August 2007, Pages 711-724
The Lancet Neurology

Review
Metabolic and molecular imaging in neuro-oncology

https://doi.org/10.1016/S1474-4422(07)70192-8Get rights and content

Summary

Techniques for human brain imaging have undergone rapid developments in recent years. Technological progress has enabled the assessment of many physiological parameters in vivo that are highly relevant for tumour grading, tissue characterisation, definition of the extent and infiltration of tumours, and planning and monitoring of therapy. In this review, we provide a brief overview of advanced MRI and molecular-tracer techniques that have many potential clinical uses. A broad range of techniques, including dynamic MRI, PET, and single photon emission computed tomography, provide measurements of various features of tumour blood flow and microvasculature. Using PET to measure glucose consumption enables visualisation of tumour metabolism, and magnetic resonance spectroscopy techniques provide complementary information on energy metabolism. Changes in protein and DNA synthesis can be assessed through uptake of labelled amino acids and nucleosides. Advanced imaging techniques can be used to assess tumour malignancy, extent, and infiltration, and might provide diagnostic clues to distinguish between lesion types and between recurrent tumour and necrosis. Stereotactic biopsies should be taken from the most malignant part of tumours, which can be identified by changes in microvascular structure and metabolic activity. Functional and metabolic imaging can improve the planning and monitoring of radiation and chemotherapy and contribute to the development of new therapies.

Introduction

Introduced in 1977, 18F-labelled 2-fluoro-2-deoxy-D-glucose (FDG) is now in wide clinical use in human beings,1 and more positron-labelled tracers are being used for quantitative in vivo metabolic imaging with PET. These techniques have been complemented by magnetic resonance spectroscopy (MRS), which has given insight into the main endogenous substrates of energy and intermediary metabolism,2 and newer experimental techniques have provided methods for the imaging of gene expression and other specific molecular processes.3 Experimental MRI and optical imaging methods can also be used to image molecular processes, although their application to human metabolic and molecular imaging is restricted, and PET is still predominant.4 New MRI methods for the imaging of brain perfusion and water diffusion provide insights into the metabolic and molecular changes seen in brain tumours.5 The translation of these advances in diagnostic imaging into improvements in therapy and outcome for patients with glioma is a challenge. In this review, we summarise the available metabolic and molecular tracer techniques in this context.

Section snippets

Tomographic imaging methods

Tomographic methods can be used to image diverse physiological and structural targets (figure 1). Modern, multislice CT systems can image the brain in 1–2 seconds, and enhancement with conventional iodinated contrast media can generate dynamic data for functional images, particularly for the measurement of blood flow. MRI also enables the use of dynamic contrast-enhanced techniques for blood flow measurement and provides opportunities to study other contrast mechanisms, such as fluid flow, free

Tumour grading

The WHO scheme for grading tumours is widely accepted,10 and four histological grades have prognostic relevance in brain tumours. Grade I tumours, such as most meningiomas and neurinomas or schwannomas, are the most likely to be cured after macroscopic removal. Grade II tumours, such as astrocytomas and oligodendrogliomas, are classified as low grade because of their low proliferation rates and lack of histological features of malignancy. However, these tumours infiltrate healthy brain tissue

Identification of lesion type

Definitive diagnosis of lesion type usually requires histopathological examination of the tissue. Although metabolic and molecular imaging methods are macroscopic techniques and cannot replace microscopic examination of the tissues, the indicators of tumour vascularity, metabolism, invasiveness, and malignancy provided by these techniques can improve the likelihood of making a correct diagnosis.

All imaging modalities help to distinguish between tumours and non-tumorous lesions.

Tumour extent and infiltration

The extent of solid malignant tumours and benign tumours, such as meningiomas, which lack an intact blood–brain barrier, is usually assessed by the extent of contrast enhancement on CT or MRI. The accurate definition of tumour boundries is more difficult for low-grade gliomas, and many high-grade gliomas are heterogeneous and include regions that do not show contrast enhancement. Another problem is infiltration of normal brain tissue by gliomas, which causes their recurrence and commonly

Response to therapy

Oncological therapy typically aims to change the perfusion or molecular processes of tumours to achieve regression. Metabolic and molecular imaging can be used to monitor many of these targets directly and thus guide therapy and provide direct measures of therapeutic success.

Experimental molecular imaging

Directly imaging tumour components, such as cell surface markers or tumour products, might help to identify potential therapeutic targets that can be used to select individualised treatments. Endothelial growth factors are of particular interest because they mediate the interaction between tumours and their environments, to promote endothelial proliferation and angiogenesis. Vascular endothelial growth factor and endothelial growth factor are potential targets for antiangiogenic treatments.

Summary and perspectives

Many metabolic and molecular imaging techniques are now available for clinical use but their influence on clinical research and diagnostic practice is limited. Most studies cited in this review, although having the potential to improve our understanding of the pathophysiology of disease and to contribute to therapeutic progress, are based on selected clinical case series, which are commonly collected retrospectively. The choice of method depends on locally available technology, technical

Search strategy and selection criteria

References for this review were selected through searches of PubMed with the terms “glioma” or “brain tumour”, in combination with “positron” or “magnetic resonance”. We selected the most original, relevant, and recent papers. Articles identified through searches of the references of articles and the authors' own files were also included. Only papers in English were included. The final list reflects papers relevant to the topics covered in the review.

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