Diffusion Tensor Imaging of Brain Tumours at 3 T: A Potential Tool for Assessing White Matter Tract Invasion?
Introduction
Gliomas are the most common type of primary brain tumour in adults, glioblastoma (WHO grade IV) being the most common. Although accounting for only 2–3% of all cancers, the impact on average years of life lost is greater than with more common tumours [1]. Despite recent advances, survival remains poor, with median survival rates varying between 16 and 53 weeks [2]. Radiotherapy is the most important non-surgical treatment option for malignant gliomas and improves survival [3]. A radiotherapy dose–response relationship also exists; increasing dose providing a moderate improvement in survival 4, 5. Conventional doses are determined by the tolerance of surrounding normal brain, but an unfortunate consequence of sparing this tissue is that not all tumour cells are destroyed and therefore tumour recurs in virtually all patients.
Very high doses of radiotherapy, up to 90 Gy, have been shown to sterilize gliomas, but at the cost of normal brain necrosis [6], with tumour recurrence commonly occurring in the zone that received 60–70 Gy. One method of reducing radiation necrosis to normal brain, while delivering a higher dose, would be to target a smaller volume [7]. The difficulty lies with determining the margins of the brain that are infiltrated by glioma. Most tumours recur within 2 cm from the enhancing edge of the original tumour and only 4% are multicentric [8]. Gliomas have no capsule and spread diffusely through the brain [9], preferentially infiltrating along white matter tracts 9, 10, 11, 12. Such infiltration is very different to the margin of a cerebral metastasis, which typically has a well-defined margin and preferentially infiltrates along vascular planes [13].
Diffusion-weighted imaging (DWI) is a magnetic resonance (MR) technique that is sensitive to the movement of water. Diffusion tensor imaging (DTI) is a modification of DWI that is sensitive to the preferential diffusion of brain water along axonal fibres, a property called anisotropic diffusion; this technique can demonstrate white matter tract anatomy (Fig. 1) and can detect subtle changes in white matter tracts in disease [14]. We have used this method to investigate whether DTI can detect more extensive abnormalities compared with conventional imaging in patients with high-grade gliomas. Our aim, in this preliminary study, was to assess the possible use of DTI as a method of detecting occult white matter invasion in cerebral gliomas.
Section snippets
Patients
Twenty patients with radiological evidence of intrinsic brain tumours were recruited after referral to a multidisciplinary neuro-oncology group for consideration for biopsy. The mean age was 48 years (range 23–80); six patients were female (Table 1). Ten patients had a WHO grade IV glioblastoma, three had a WHO grade III glioma (one oligoastrocytoma, one oligodendroglioma and one anaplastic astrocytoma), three had WHO grade II low-grade gliomas, and four had solitary cerebral metastases (one
Comparing DTI with Conventional Imaging
In 10 out of 13 patients (77%) with high-grade gliomas (WHO grade III and IV) the abnormality in the DTI was larger than in the T2-weighted images. In four of these 13 patients (31%) abnormalities in the DTI were found in the contralateral hemisphere that was apparently normal on T2-weighted imaging. Fig. 4 demonstrates a patient with an occipital glioblastoma (WHO grade IV) that had marked white matter abnormalities on the contralateral hemisphere. In two patients where no difference was seen,
Discussion
Gliomas remain a difficult and challenging tumour type: they infiltrate widely making complete surgical excision impossible, and radiotherapy is limited by the normal tissue tolerance of surrounding brain. Despite considerable success in identifying the range of genetic changes that occur in malignant gliomas, especially those involved with disruption of cell cycle control [18], specific glioma-targeted treatments remain elusive [19]. Thus, there is every reason to develop existing treatment
Acknowledgements
We thank Dr Nikos Papadakis and Dr Kay Martin for their initial work developing the DTI sequences, Miss Vicky Liversedge for imaging the patients, and Dr Dominic O'Donovan for neuropathology advice. Mr Stephen Price was supported by the Sir Samuel Scott of Yews Clinical Research Fellowship from the Royal College of Surgeons of England. Dr Alonso Peña was supported by a Mathematical Biology Fellowship from the Wellcome Trust. These studies are funded, in part, by the Radiological Research Trust,
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