Differential Diagnosis Between Radiation Necrosis and Glioma Progression Using Sequential Proton Magnetic Resonance Spectroscopy and Methionine Positron Emission Tomography

Abstract

Differential diagnosis between radiation necrosis and tumor recurrence is important in the clinical management of glioma. Multi-modality imaging including proton magnetic resonance spectroscopy ( 1 H-MRS) and positron emission tomography (PET) with L-[methyl-11 C]methionine (MET) was evaluated. Eighteen patients underwent sequential 1 H-MRS and MET-PET. The expressions of metabolites including choline-containing compounds (Cho), creatine phosphate (Cre), and lactate (Lac) were calculated as the ratios of Cho to Cre (Cho/Cre) and Lac to Cho (Lac/Cho). The uptake of MET was determined as the ratio of the lesion to the contralateral reference region (L/R). The final diagnoses were determined by histological examination and/or follow-up MR imaging and clinical course. The Lac/Cho ratio was 0.63 ± 0.25 (mean ± standard deviation) in recurrence (7 cases) and 2.35 ± 1.81 in necrosis (11 cases). The Lac/Cho ratio was significantly different between the two groups (p º 0.01). Consecutive investigation of 1 H-MRS revealed temporary elevation of Cho in 4 of 9 cases of necrosis, which could be identified as false positive findings for recurrence. Including those cases, MET-PET demonstrated significant difference in the L/R ratio between the two groups (2.18 ± 0.42 vs. 1.49 ± 0.35, p º 0.01). According to a 2 × 2 factorial table analysis, the borderline values of Lac/Cho and L/R to differentiate recurrence from necrosis were 1.05 and 2.00, respectively. 1 H-MRS is reliable and accessible for the differentiation of recurrence and necrosis, although the temporary elevation of Cho in the course of necrosis should be recognized. Additional MET-PET imaging can establish the diagnosis.

Role of magnetic resonance spectroscopy for the differentiation of recurrent glioma from radiation necrosis: A systematic review and meta-analysis

“…1. Eighteen articles [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] comprising a total sample size of 455 patients (447 lesions) with suspected glioma recurrence after radiotherapy, met all inclusion and exclusion criteria, and were included in our metaanalysis. The characteristics of the included studies are presented in Table 1.…”

“…Overall, 262 MRS examinations were performed to detect glioma recurrence by calculating the ratio of Cho to Cr in the 12 included studies [13,14,[16][17][18][19]21,[23][24][25]28,30]. The diagnostic threshold of Cho/Cr ranged between 1.05 and 2.6.…”

Diagnostic Accuracy of PET for Recurrent Glioma Diagnosis: A Meta-Analysis

“…Similarly, studies reported widely ranging sensitivity and specificity estimates for 11 C-MET PET. When we considered both low-and high-grade gliomas, 20,25,29,30 sensitivity ranged between 0.55 and 0.80 and specificity ranged between 0.70 and 1.0 (Online Fig 1). For high-grade gliomas, 20,25,30,36,39 sensitivity ranged between 0.44 and 0.93 and specificity ranged between 0.50 and 1.0.…”

“…When we considered both low-and high-grade gliomas, 20,25,29,30 sensitivity ranged between 0.55 and 0.80 and specificity ranged between 0.70 and 1.0 (Online Fig 1). For high-grade gliomas, 20,25,30,36,39 sensitivity ranged between 0.44 and 0.93 and specificity ranged between 0.50 and 1.0. For high-grade gliomas, the summary sensitivity was 0.70 (95% CI, 0.50 -0.84) and summary specificity was 0.93 (95% CI, 0.44 -1.00), corresponding to a positive likelihood ratio of 10.31 (95% CI, 0.76 -139.39) and a negative likelihood ratio of 0.32 (95% CI, 0.18 -0.57), and the Q* statistic was 0.79 (Fig 2).…”

A Meta-Analysis on the Diagnostic Performance of 18F-FDG and 11C-Methionine PET for Differentiating Brain Tumors

“…Several reports confirmed that 11 C-MET PET differentiated brain tumors with high sensitivity and specificity. 29,30 A recent meta-analysis concluded that 18 F-FDG and 11 C-MET PET have moderately good overall accuracy for diagnosing recurrent glioma. 31 …”