ReviewThe clinical value of proton magnetic resonance spectroscopy in adult brain tumours
Introduction
Proton magnetic resonance spectroscopy (1H MRS) of the human brain has been possible for at least 20 years and has been readily available in the clinical arena for over half that time. However, its clinical use as a routine part of the initial diagnostic examination for intracranial masses has been slow to develop, in part this is because a simple visual interpretation of 1H spectra is difficult and few radiologists are trained to use the technique. However, the manufacturer's automated single voxel spectroscopy (SVS) currently available on clinical machines has resulted in an increased interest in the clinical application of the technique.
There is a large body of work assessing the accuracy of 1H MRS in the diagnosis of adult brain tumours, although few have concentrated on assessing the additional benefit it has provided over conventional magnetic resonance imaging (MRI), or whether it obviates the need for biopsy. These issues are important to address, given that stereotactic biopsy is non-diagnostic in 8–12% of cases1, 2 and has a reported morbidity of 3–4%.1, 3
The aim of this paper is to review the clinical application of 1H MRS in adult brain tumours, and establish those areas where the authors believe the technique to be of proven clinical value.
Section snippets
Basic principles of 1H MRS
In contrast to the structural information provided by MRI, 1H MRS provides a qualitative analysis of a number of metabolites within the brain, and a quantitative analysis if a reference of known concentration is used. These metabolites reflect aspects of neuronal integrity, cell membrane proliferation or degradation, energy metabolism and necrotic transformation of brain or tumour tissue. Thus, 1H MRS provides information about a number of disease processes and adds another dimension to imaging
Technical difficulties of SVS and MVS
The quality of SVS is highly dependent on voxel positioning and avoidance of signal contamination that usually results if the lesion is close to bone, cerebrospinal fluid or fat. Voxel size less than 4 cm3 impairs spectral quality due to poor SNR, and the assessment of heterogeneous tumours with SVS is either limited to one voxel or time consuming if multiple single voxels are acquired. In contrast, MVS can sample the entire tumour volume but can result in spectra of poorer quality due to the
MRS metabolic profiles of brain tumours
Major metabolites detected with 1H MRS include N-acetyl aspartate (NAA), total cholines (tCho), total creatines (tCr), lactate (Lac), mobile lipids (Lip) and other macromolecules (MM), mI and glutamine and glutamate (Glx; Fig. 1). NAA (assigned at 2.05 ppm) is considered a neuronal marker and is the most dominant peak in normal adult spectra.9 As most brain tumours are of non-neuronal origin, NAA is absent or greatly reduced, as it is with other insults to the brain such as infarction or
Astrocytomas
Conventional MRI with gadolinium enhancement is an established and useful tool in the characterization of cerebral tumours, relying on features such as mass effect, necrosis and contrast enhancement to predict tumour grade. These characteristics are sometimes unreliable13, 14 and moreover, peritumoral T2 hyperintensity may represent tumour infiltration, vasogenic oedema or both.
In broad terms, typical MRS findings of astrocytomas include a reduction in NAA and tCr and an elevation in tCho. tCho
Neoplastic versus non-neoplastic lesions
Conventional MRI is poor at differentiating brain abscesses from cystic or necrotic tumours, although there are reports that diffusion-weighted imaging can reliably distinguish the pathologies.42, 43 However, their metabolic profiles have been shown to be distinguishable from each other. Chang et al.44 evaluated 39 cystic metastases and found that, although lactate was found in both tumours and abscesses, acetate (1.9 ppm) and succinate (2.38 ppm) were also present in abscesses, presumably
Response to therapy: necrosis versus tumour progression
The limitations of MRI are highlighted in its inability to differentiate between tumour recurrence and radiation necrosis, given that both lesions can show mass effect and enhancement. Small studies using MVS have shown a moderate reduction in tCho and an increase in lactate and/or lipids in tumours that respond to gamma knife radiosurgery, presumably reflecting transformation of viable tumour cells towards necrosis.56, 57 Conversely, an increase in tCho is associated with tumour progression.58
Guidance for biopsy and radiotherapy
MVS techniques have a potentially useful role in biopsy guidance and radiotherapy planning by virtue of their ability to assess the metabolic profile across a heterogeneous tumour (Fig. 3). A retrospective analysis of the metabolic profiles of biopsy locations of 29 tumours revealed that an elevation in tCho correlated with an elevation in tumour cell density. Furthermore, MRS findings correlated with histology which showed tumour cells in one biopsy specimen and astrogliosis in the other in
Added value of 1H MRS
A key question regarding new techniques is whether they add diagnostic value over and above that of conventional MRI. On review of the literature, only three studies were found that specifically addressed this issue.54, 62, 63 In all three studies, the MRS data were post-processed and interpreted off line using sophisticated data analysis packages by expert spectroscopists.
The largest study of 176 intracranial lesions (including non-neoplastic lesions) found that the additive information of
Conclusions
1H MRS undoubtedly yields information about intracranial lesions beyond that obtained from anatomical images. Although there is a paucity of data analysing the additional diagnostic value of MRS, it is of the authors' opinion that MRS can increase the level of diagnostic confidence in three situations in which conventional MRI may be unhelpful: (1) the distinction of high-grade gliomas and metastases from abscesses, (2) the assessment of tumour recurrence versus radiation necrosis, and (3) the
Future directions
Although brain tumour research has gone some way to establishing the clinical and radiological role of MRS in the diagnosis of brain tumours, to establish its’ diagnostic role we need to construct a study that truly reflects clinical practice. This would (1) exclude all brain tumours in which the radiology is characteristic and upon which management can be determined, (2) include only those patients in which the clinical/radiological diagnosis is uncertain or in which knowledge of the tumour
Acknowledgements
Informed consent has been provided by volunteers and patients for the use of their images and spectra for research. The data in Figure 1, Figure 4, Figure 5, Figure 6 are taken from the fully validated INTEPRET database (http://azizu.uab.es/INTERPRET/index.html), and these particular data were acquired at St George's in studies fully approved by the Local Ethics Committee and with consent of all subjects to the use of their data.
Dominick McIntyre, Physicist at St George's Hospital, supplied the
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