Utility of FET-PET in detecting high-grade gliomas presenting with equivocal MR imaging features

Abstract

High-grade gliomas, metastases, and primary central nervous system lymphoma (PCNSL) are common high-grade brain lesions, which may have overlapping features on magnetic resonance (MR) imaging. Our objective was to assess the utility of 18-fluoride-fluoro-ethyl-tyrosine positron emission tomography (FET-PET) in reliably differentiating between these lesions, by studying their metabolic characteristics. Patients with high-grade brain lesions suspicious for glioma, with overlapping features for metastases and PCNSL were referred for FET-PET by Neuroradiologists from Multidisciplinary Neuro-Oncology Joint Clinic. Tumor-to-contralateral white mater ratio (T/Wm) at 5 and 20 min was derived and compared to histopathology. Receiver operating characteristic curve analysis was used to find the optimal T/Wm cutoff to differentiate between the tumor types. T/Wm was higher for glial tumors compared to nonglial tumors (metastases, PCNSL, tuberculoma, and anaplastic meningioma). A cutoff of 1.9 was derived to reliably diagnose a tumor of glial origin with a sensitivity and specificity of 93.8% and 91%, respectively. FET-PET can be used to diagnose glial tumors presenting as high-grade brain lesions when MR findings show overlapping features for other common high-grade lesions.

Keywords: Brain lesions; fluoroethyl-tyrosine-positron-emission tomography; high-grage glioma; magnetic resonance imaging.

Figure 1

Region of interest generated over coronal (a), sagittal (b), and axial (c) FET-PET images. Background region of interest drawn over contralateral white mater (d) on axial PET image

Figure 2

Patient 3 was a 55-year-old female, presented with headache for 1 month, axial MR sequences (arrows) show well-circumscribed mass along the occipital horn of left lateral ventricle, (a) iso-to-hypointense on T2-weighted image (b) enhancing on postcontrast T1-weighted image, with (d) restricted diffusion and (e) low apparent diffusion coefficient, hyperperfusion on MR perfusion sequence; MR spectroscopy was noncontributory. Although features were favoring PCNSL, age and rapid clinical deterioration raised the suspicion of glial tumor. Axial FET-PET (c and f) fused PET/CT images (arrows) showed increased tracer uptake in the mass, with a tumor-to-contralateral white mater ratio of 2.6 and 2.2 at 5 and 20 min. Biopsy was suggestive of the WHO Grade IV glioma – glioblastoma

Figure 3

An 86-year-old male (patient 8), known case of chronic kidney disease, presenting with headache and limb weakness, underwent a MRI at a regional center; axial images (a) showed an ill-defined T1 hypointense, T2 iso-to-hypointense corpus callosal lesion infiltrating the ventricles and right thalamus, no contrast could be administered, there was facilitated diffusion on diffusion-weighted imaging and ADC map; hyperperfusion on MR perfusion images differentials of PCNSL and high-grade glioma were given. FET-PET showed tumor-to-contralateral white mater (T/Wm) ratio of 2.6 on both 5 (c) and 20 (d) minute images. 5-min image is an index of vascularity, however, since maximum uptake occurs till 20 min, increased 20-min uptake in the hyperperfused lesions seen at 5 min is suggestive of high-grade glioma. Histopathology revealed Grade IV gliomas

Figure 4

Patient 7 is a 54-year-old male, presented with progressive bilateral diminution of vision and right hemiparesis for 2 months, MRI showed (a) T2-hypointense lesion in the left occipital region, with perilesional edema. (b) Axial postcontrast T1-weighted image showed homogeneous enhancement. MR spectroscopy and perfusion were noncontributory. Differentials were high-grade glioma, PCNSL with rare possibility of metastases. FET-PET was done (c), which showed low-grade uptake in the lesion with a tumor-to-contralateral white mater (T/Wm) ratio of 1.6 at 5 and 20 min. Patient was not willing for biopsy; hence, whole-body FDG PET was done which showed rim of increased uptake in the brain lesion ([d] equal to gray matter), and primary site in the anal canal, seen on maximum intensity projection (MIP) image ([e] – arrow), biopsy showed anal melanoma, thus brain lesion was most likely metastatic. FET-PET (T/Wm) ratio was useful in ruling out high-grade glioma

Figure 5

Patient 12 was a 78-year-old male presented with memory loss, MRI showed well-defined lesion in the left parietal region (arrows), periventricular location, (a) hyperintense on T2 with edema, (b) T1-postcontrast showed minimal enhancement, (c and d) rim of restricted diffusion and low apparent diffusion coefficient, (e) MR spectroscopy showed choline peak with raised Cho/Cr ratio, and MR perfusion imaging showed relative cerebral blood volume of 158.3 suggestive of mild hyperperfusion. Considering the age and overlapping imaging features, differentials of PCNSL, metastases, and high-grade glioma were given. FET-PET showed intense uptake in lesion on axial PET (f) and fused PET/CT (g) images with tumor-to-contralateral white mater (T/Wm) ratio of 2.4 and 2.5 at 5 and 20 min, favoring high-grade glioma. Histopathology was WHO Grade IV glioma – glioblastoma

Figure 6

(a) Box plot and (b) dot plot depicting the tumor-to-white matter (T/Wm) ratio across PCNSL, metastases, glioblastoma, and other lesions

Figure 7

Area under the curve showing a 1.9 tumor-to-white matter (T/Wm) ratio cutoff to differentiate high-grade glial and nonglial high-grade lesions with a sensitivity of 93.8% and specificity of 91%, at 5 min (a) and 20 min (b). ROC: Receiver operating characteristic