Distinguishing recurrent high-grade gliomas from radiation injury: a pilot study using dynamic contrast-enhanced MR imaging.

RATIONALE AND OBJECTIVES The accurate delineation of tumor recurrence and its differentiation from radiation injury in the follow-up of adjuvantly treated high-grade gliomas presents a significant problem in neuro-oncology. The aim of this study was to investigate whether hemodynamic parameters derived from dynamic contrast-enhanced (DCE) T1-weighted magnetic resonance imaging (MRI) can be used to distinguish recurrent gliomas from radiation necrosis. MATERIALS AND METHODS Eighteen patients who were being treated for glial neoplasms underwent prospectively conventional and DCE-MRI using a 3T scanner. The pharmacokinetic modelling was based on a two-compartment model that allows for the calculation of K(trans) (transfer constant between intra- and extravascular, extracellular space), v(e) (extravascular, extracellular space), k(ep) (transfer constant from the extracellular, extravascular space into the plasma), and iAUC (initial area under the signal intensity-time curve). Regions of interest (ROIs) were drawn around the entire recurrence-suspected contrast-enhanced region. A definitive diagnosis was established at subsequent surgical resection or clinicoradiologic follow-up. The hemodynamic parameters in the contralateral normal white matter, the radiation injury sites, and the tumor recurrent lesions were compared using nonparametric tests. RESULTS The K(trans), v(e), k(ep), and iAUC values in the normal white matter were significantly different than those in the radiation necrosis and recurrent gliomas (0.01, <P < .0001). The only significantly different hemodynamic parameter between the recurrent tumor lesions and the radiation-induced necrotic sites were K(trans) and iAUC, which were significantly higher in the recurrent glioma group than in the radiation necrosis group (P ≤ .0184). A K(trans) cutoff value higher than 0.19 showed 100% sensitivity and 83% specificity for detecting the recurrent gliomas, whereas an iAUC cutoff value higher than 15.35 had 71% sensitivity and 71% specificity. The v(e) and k(ep) values in recurrent tumors were not significantly higher than those in radiation-induced necrotic lesions. CONCLUSIONS These findings suggest that DCE-MRI may be used to distinguish between recurrent gliomas and radiation injury and thus, assist in follow-up patient management strategy.

[1]  M. Apuzzo,et al.  STEREOTACTIC RADIOSURGERY: ADJACENT TISSUE INJURY AND RESPONSE AFTER HIGH‐DOSE SINGLE FRACTION RADIATION—PART II STRATEGIES FOR THERAPEUTIC ENHANCEMENT, BRAIN INJURY MITIGATION, AND BRAIN INJURY REPAIR , 2007, Neurosurgery.

[2]  A. Gregory Sorensen,et al.  Angiogenesis in brain tumours , 2007, Nature Reviews Neuroscience.

[3]  Susan M. Chang,et al.  Dynamic susceptibility-weighted perfusion imaging of high-grade gliomas: characterization of spatial heterogeneity. , 2005, AJNR. American journal of neuroradiology.

[4]  A. Jackson,et al.  Abnormalities of the contrast re‐circulation phase in cerebral tumors demonstrated using dynamic susceptibility contrast‐enhanced imaging: A possible marker of vascular tortuosity , 2000, Journal of magnetic resonance imaging : JMRI.

[5]  Dieta Brandsma,et al.  Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. , 2008, The Lancet. Oncology.

[6]  A. Jackson,et al.  Enhancing Fraction in Glioma and Its Relationship to the Tumoral Vascular Microenvironment: A Dynamic Contrast-Enhanced MR Imaging Study , 2010, American Journal of Neuroradiology.

[7]  Thomas E Yankeelov,et al.  Incorporating contrast agent diffusion into the analysis of DCE‐MRI data , 2007, Magnetic resonance in medicine.

[8]  J. Hazle,et al.  Dynamic imaging of intracranial lesions using fast spin‐echo imaging: Differentiation of brain tumors and treatment effects , 1997, Journal of magnetic resonance imaging : JMRI.

[9]  R K Jain,et al.  Transport of molecules in the tumor interstitium: a review. , 1987, Cancer research.

[10]  R. Lucht,et al.  Microcirculation and microvasculature in breast tumors: Pharmacokinetic analysis of dynamic MR image series , 2004, Magnetic resonance in medicine.

[11]  J R Griffiths,et al.  Clinical studies. , 2005, Advances in pharmacology.

[12]  J. Hopewell,et al.  Microvasculature and radiation damage. , 1993, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[13]  M. Berger,et al.  Differentiation of Glioblastoma Multiforme and Single Brain Metastasis by Peak Height and Percentage of Signal Intensity Recovery Derived from Dynamic Susceptibility-Weighted Contrast-Enhanced Perfusion MR Imaging , 2007, American Journal of Neuroradiology.

[14]  M R Segal,et al.  Distinguishing Recurrent Intra-Axial Metastatic Tumor from Radiation Necrosis Following Gamma Knife Radiosurgery Using Dynamic Susceptibility-Weighted Contrast-Enhanced Perfusion MR Imaging , 2008, American Journal of Neuroradiology.

[15]  J C Waterton,et al.  Quantification of endothelial permeability, leakage space, and blood volume in brain tumors using combined T1 and T2* contrast‐enhanced dynamic MR imaging , 2000, Journal of magnetic resonance imaging : JMRI.

[16]  D. Moody,et al.  MRI of radiation injury to the brain. , 1986, AJR. American journal of roentgenology.

[17]  B. Rosen,et al.  Microscopic susceptibility variation and transverse relaxation: Theory and experiment , 1994, Magnetic resonance in medicine.

[18]  G Johnson,et al.  Comparison of microvascular permeability measurements, K(trans), determined with conventional steady-state T1-weighted and first-pass T2*-weighted MR imaging methods in gliomas and meningiomas. , 2006, AJNR. American journal of neuroradiology.

[19]  P. Wesseling,et al.  Angiogenesis in brain tumors; pathobiological and clinical aspects , 1997, Journal of Neuro-Oncology.

[20]  A. Maia,et al.  MR cerebral blood volume maps correlated with vascular endothelial growth factor expression and tumor grade in nonenhancing gliomas. , 2005, AJNR. American journal of neuroradiology.

[21]  R. Wurm,et al.  Pharmacokinetic Modeling of Gd-DTPA Extravasation in Brain Tumors , 2002, Investigative radiology.

[22]  E. Rostrup,et al.  Measurement of brain perfusion, blood volume, and blood‐brain barrier permeability, using dynamic contrast‐enhanced T1‐weighted MRI at 3 tesla , 2009, Magnetic resonance in medicine.

[23]  G. Brix,et al.  Simulation-based comparison of two approaches frequently used for dynamic contrast-enhanced MRI , 2010, European Radiology.

[24]  D. Gadian,et al.  Delay and dispersion effects in dynamic susceptibility contrast MRI: Simulations using singular value decomposition , 2000, Magnetic resonance in medicine.

[25]  Cheng Yu,et al.  STEREOTACTIC RADIOSURGERY: ADJACENT TISSUE INJURY AND RESPONSE AFTER HIGH‐DOSE SINGLE FRACTION RADIATION PART I—HISTOLOGY, IMAGING, AND MOLECULAR EVENTS , 2007, Neurosurgery.

[26]  G Johnson,et al.  Dynamic contrast-enhanced T2-weighted MR imaging of recurrent malignant gliomas treated with thalidomide and carboplatin. , 2000, AJNR. American journal of neuroradiology.

[27]  M Takahashi,et al.  Posttherapeutic intraaxial brain tumor: the value of perfusion-sensitive contrast-enhanced MR imaging for differentiating tumor recurrence from nonneoplastic contrast-enhancing tissue. , 2000, AJNR. American journal of neuroradiology.

[28]  N. Thacker,et al.  Breath‐hold perfusion and permeability mapping of hepatic malignancies using magnetic resonance imaging and a first‐pass leakage profile model , 2002, NMR in biomedicine.

[29]  S. Rose,et al.  Distinguishing Recurrent Primary Brain Tumor from Radiation Injury: A Preliminary Study Using a Susceptibility-Weighted MR Imaging−Guided Apparent Diffusion Coefficient Analysis Strategy , 2010, American Journal of Neuroradiology.

[30]  M Takahashi,et al.  Correlation of MR imaging-determined cerebral blood volume maps with histologic and angiographic determination of vascularity of gliomas. , 1998, AJR. American journal of roentgenology.

[31]  P. Tofts,et al.  Measurement of the blood‐brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts , 1991, Magnetic resonance in medicine.

[32]  A. Jackson,et al.  Can dynamic susceptibility contrast magnetic resonance imaging perfusion data be analyzed using a model based on directional flow? , 2003, Journal of magnetic resonance imaging : JMRI.

[33]  M. Berger,et al.  Differentiation of recurrent glioblastoma multiforme from radiation necrosis after external beam radiation therapy with dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. , 2009, Radiology.

[34]  Koen Van Laere,et al.  Direct comparison of 18F-FDG and 11C-methionine PET in suspected recurrence of glioma: sensitivity, inter-observer variability and prognostic value , 2004, European Journal of Nuclear Medicine and Molecular Imaging.

[35]  C. Eskey,et al.  Diffusion-weighted imaging in the follow-up of treated high-grade gliomas: tumor recurrence versus radiation injury. , 2004, AJNR. American journal of neuroradiology.

[36]  Ying Lu,et al.  Analysis of the spatial characteristics of metabolic abnormalities in newly diagnosed glioma patients , 2002, Journal of magnetic resonance imaging : JMRI.