Centrally Reduced Diffusion Sign for Differentiation between Treatment-Related Lesions and Glioma Progression: A Validation Study

Abstract

BACKGROUND AND PURPOSE: Differentiating between treatment-related lesions and tumor progression remains one of the greatest dilemmas in neuro-oncology. Diffusion MR imaging characteristics may provide useful information to help make this distinction. The aim of the study was to assess the diagnostic accuracy of the centrally reduced diffusion sign for differentiation of treatment-related lesions and true tumor progression in patients with suspected glioma recurrence. MATERIALS AND METHODS: The images of 231 patients who underwent an operation for suspected glioma recurrence were reviewed. Patients with susceptibility artifacts or without central necrosis were excluded. The final diagnosis was established according to histopathology reports. Two neuroradiologists classified the diffusion patterns on preoperative MR imaging as the following: 1) reduced diffusion in the solid component only, 2) reduced diffusion mainly in the solid component, 3) no reduced diffusion, 4) reduced diffusion mainly in the central necrosis, and 5) reduced diffusion in the central necrosis only. Diagnostic accuracy metrics and the area under the receiver operating characteristic curve were estimated for the diffusion patterns. RESULTS: One hundred three patients were included (22 with treatment-related lesions and 81 with tumor progression). The diagnostic accuracy results for the centrally reduced diffusion pattern as a predictor of treatment-related lesions ("mainly central" and "exclusively central" patterns versus all other patterns) were as follows: 64% sensitivity (95% CI, 41%-83%), 84% specificity (95% CI, 74%-91%), 52% positive predictive value (95% CI, 37%-66%), and 89% negative predictive value (95% CI, 83%-94%). CONCLUSIONS: The centrally reduced diffusion sign is associated with the presence of treatment effect. The probability of a histologic diagnosis of a treatment-related lesion is low (11%) in the absence of centrally reduced diffusion.

The centrally restricted diffusion sign on MRI for assessment of radiation necrosis in metastases treated with stereotactic radiosurgery

“…This methodology is similar to our study in that radiation necrosis was assessed for using visual analysis of imaging patterns alone without quantification or lesion segmentation. One main difference is that we did not differentiate layers within the contrast-enhancing rim, in line with previous glioma studies assessing for radiation necrosis using the centrally restricted diffusion sign [ 30 , 31 ]. The association between diffusion restriction and radiation necrosis has been shown in prior studies [ 20 , 30 ] and rat models [ 41 ] and appears to be due to coagulative necrosis with fibroblastic proliferation, hemosiderin laden macrophages, and inflammatory cells [ 34 ].…”

“…For tumor progression, opposing findings have been described in the literature with regards to central diffusivity. While some previous studies associate absent diffusion restriction within the necrosis with tumor progression [ 30 , 31 , 41 ], Cha et al found all 5 cases of centrally restricted diffusion to represent tumor progression in their 16 subject cohort. Clearly, there is a discrepancy with regards to the diffusivity of the central necrosis in tumor progression cases which was also seen in our study, with central restriction seen in 13/36 (35%) tumor progression cases and absent central restriction seen in the remaining 23/36 (65%) tumor progression cases.…”

“…Previous studies on brain metastases after SRS using ADC are based on quantitative differences on serial follow up imaging or require time-consuming lesion component segmentation [ 14 , 25 , 28 , 29 ]. In a recent study on high-grade gliomas, Zakhari et al [ 30 ] describe central diffusion restriction within a ring enhancing lesion to be indicative of radiation necrosis on visual analysis alone, with a study by Alcaide et al validating this finding [ 31 ].…”

Assessment of the hypervascularized fraction of glioblastomas using a volume analysis of dynamic susceptibility contrast-enhanced MRI may help to identify pseudoprogression

“…Sadly, automatic segmentation tools are not always available in clinical practice and segmentation of the enhancing part of glioblastomas can be tricky and time-consuming as necrosis is often ill-defined [ 27 ]. Besides, MRI analysis of the necrotic component may help in better characterisation of lesions as diffusion restriction in the non-enhancing necrotic centre of treated glioblastomas has been associated with radiation-induced coagulative necrosis [ 12 , 28 ]. In another study, Dijkstra et al .…”

Diagnostic Accuracy of Centrally Restricted Diffusion Sign in Cerebral Metastatic Disease: Differentiating Radiation Necrosis from Tumor Recurrence

“…A similar diagnostic performance was obtained in a validation study. 10 To date, the data in cerebral metastatic disease has been sparse, with only one small population study demonstrating the utility of DWI in necrotic enhancing lesions following SRS. 11 Therefore, additional studies are required to confirm the clinical utility of this sequence in treated metastases.…”