Correlation of diffusion tensor, dynamic susceptibility contrast MRI and 99mTc-Tetrofosmin brain SPECT with tumour grade and Ki-67 immunohistochemistry in glioma

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Abstract

Objective

Assessment of the grade and type of glioma is of paramount importance for prognosis. Tumour proliferative potentials may provide additional information on the behaviour of the tumour, its response to treatment and prognosis. The purpose of this study was to investigate the correlation between diffusion tensor imaging (DTI), dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) and 99mTc-Tetrofosmin brain single-photon emission computed tomography (SPECT), and the tumour grade and Ki-67 labelling index in newly diagnosed gliomas.

Methods

Study was made of patients with suspected glioma on brain MRI between December 2010 and January 2012, by DTI, DSC MRI and 99mTc-Tetrofosmin brain SPECT. The proliferative activity of each tumour was measured by deriving the Ki-67 proliferation index from immunohistochemical staining of tumour specimens.

Results

Glioma was newly diagnosed in 25 patients (17 men, 8 women, aged 19–79 years, median 55 years). The Ki-67 index ranged from 1% to 80% (mean 19.4%). On evaluation of the relationship between the 99mTc-Tetrofosmin tumour uptake by gliomas was found to be significantly correlated with cellular proliferation (rho = 0.924, p < 0.0001). Regarding DTI, significant negative correlation was demonstrated between the apparent diffusion coefficient (ADC) ratio and the Ki-67 index (rho = −0.545, p = 0.0087). Significant correlation was also observed between the fractional anisotropy (FA) ratio and the Ki-67 index (rho = 0.489, p = 0.02). Strong correlation was found between relative cerebral blood volume (rCBV) and Ki-67 index (rho = 0.853, p < 0.0001), and between the 99mTc-Tetrofosmin lesion-to-normal (L/N) uptake ratio and rCBV (rho = 0.808, p  0.0001). Significant negative correlation was demonstrated between the 99mTc-Tetrofosmin L/N ratio and ADC ratio (rho = −0.513, p = 0.014). These imaging techniques were able to distinguish between low-grade and high-grade gliomas.

Conclusions

Findings on DSC MRI and brain SPECT with 99mTc-Tetrofosmin metrics were more closely correlated with glioma cellular proliferation.

Introduction

Glioma is the most common type of malignant brain tumour. Glioma grading and typing are crucial for prognosis, but patients with tumours of the same histopathological characterization and receiving similar treatment may display diverse outcome because of differences in the proliferative potential of the disease [1]. Assessment of tumour proliferation has therefore been suggested as an important additional predictor of tumour behaviour [1]. In addition, identification of the tumour “hot spot” is important for biopsy guidance. Various methods have been proposed for the estimation of proliferation in tissue samples, but these require tissue sampling via stereotactic biopsy or craniotomy [2]. The validation of a non-invasive method of assessment of tumour proliferation potential would therefore be of obvious significance.

Various imaging modalities have been employed in the attempt at non-invasive assessment of glioma proliferation [1]. Although indispensable in the structural study of intracranial neoplasms, conventional magnetic resonance imaging (MRI) has limitations as regards evaluation of the tumour proliferation potential, but correlation has been reported of diffusion MRI, perfusion MRI and MR spectroscopy metrics with glioma proliferative indices [3], [4]. In nuclear medicine, molecular imaging has been employed in the non-invasive assessment of glioma proliferation by single-photon emission computed tomography (SPECT) and positron emission tomography (PET) [1]. Although PET may be credited with providing the impetus for the clinical interest in functional neuroimaging and constitutes an increasingly important imaging tool in the non-invasive assessment of brain tumours, SPECT offers an alternative technique with the advantages of lower cost and wide availability. Recently, 99mTc-Tetrofosmin, a SPECT tracer, has been reported to be a suitable radiotracer for the detection of recurrent tumours and its uptake has been found correlated with both the proliferation of glioma and meningioma and the prognosis of patients with glioma [5], [6], [7], [8], [9], but no comparative study with other imaging modalities has yet been reported. The purpose of this study was to investigate the possible correlation between diffusion tensor imaging (DTI), dynamic susceptibility contrast (DSC) MRI, 99mTc-Tetrofosmin brain SPECT and the tumour grade and Ki-67 labelling index in patients with newly diagnosed glioma.

Section snippets

Patients

Successive patients with suspected glioma on brain MRI between December 2010 and January 2012 were included in the study. The institutional review board for clinical investigation approved the study protocol, and informed consent was obtained from all patients studied. Their lesions were investigated using DTI, DSC MRI and 99mTc-Tetrofosmin brain SPECT. Histopathological diagnosis and grading of brain tumours was conducted according to the WHO 2007 classification for central nervous system

Results

During the study period a diagnosis of glioma was made in 25 patients (17 men, 8 women, aged 19–79 years; median 55 years). There were 18 cases of glioblastoma (GBM), 2 anaplastic astrocytomas, 1 gliosarcoma, 2 diffuse astrocytomas, 1 oligoastrocytoma and 1 oligodendroglioma. The Ki-67 index ranged from 1% to 80% (mean 19.4%).

Discussion

The present study compared the capability of DTI and DSC MRI metrics and 99mTc-Tetrofosmin brain SPECT in the assessment of glioma proliferation. The results showed that both imaging modalities metrics correlate with glioma proliferation, but that 99mTc-Tetrofosmin brain SPECT and rCBV ratio demonstrated better performance than ADC and FA ratio. Both imaging modalities were also able to differentiate between low-grade and high-grade gliomas.

The use of non-invasive quantitative imaging and

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