Magnetic resonance spectroscopic study of radiogenic changes after radiosurgery of cerebral arteriovenous malformations with implications for the differential diagnosis of radionecrosis

BackgroundThe incidence of radionecrosis after radiosurgery is 5–20%. That radionecrosis after radiosurgery may be confused with a malignant tumor is a known phenomenon and problem.MethodsThree similarly treated patients with cAVM, 1 patient with symptomatic radionecrosis and 2 patients with normal post-radiation MRI changes, were selected and studied in detail with magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and magnetic resonance spectroscopy (MRS). 2 cAVM were located in eloquent locations and were classified as Spetzler-Martin grade (SM) III such that interdisciplinary radiosurgery was recommended; a third patient with a left frontal SM II cAVM refused surgery. 1 patient was male, and 2 were female. The patient’s ages ranged from 38 to 62 years (median, 39 years). The nidus volume (= planning target volume = PTV) ranged from 2.75 to 6.89 ccm (median, 6.41 ccm). The single dose was 20 Gy at the isocenter of the PTV encompassing the 80 – 90% isodose. The median follow-up period was 20 months (range, 16 – 84 months). Toxicities were evaluated with the Common Terminology Criteria (CTC) for adverse events version 3.0.ResultsNo patient suffered a bleeding from cAVM during the study period. A complete nidus occlusion was shown in all patients with time-resolved MRA. All patients showed radiogenic MRI changes, 1 patient showed excessive radionecrosis. This patient was oligosymptomatic and under temporary corticoid therapy symptoms resolved completely.Following patterns associated with radionecrosis in the MRS studies were identified in our collective:• 2D spectroscopic imaging (2D-SI) revealed much lower concentrations of metabolites in the lesion as compared to contralateral healthy tissue in all patients.• Whereas regions with regular post-radiosurgery effects showed almost normal levels of Cho and a Cho/Cr ratio < 2.0, regions with radionecrosis were characterized by increased lipid levels and a Cho/Cr ratio > 2.0 in conjunction with decreased absolute levels of all metabolites, especially of Cr and NAA.ConclusionsMRS is an increasingly valuable tool for the differential diagnosis of radiation reactions. Specific patterns of MRS spectra in radionecrosis were identified; in synopsis with clinical parameters, these changes have to be taken into account to avoid misdiagnosis.

[1]  P Bachert,et al.  Proton MR spectroscopic evaluation of suspicious brain lesions after stereotactic radiotherapy. , 2001, AJNR. American journal of neuroradiology.

[2]  R. de Beer,et al.  Java-based graphical user interface for MRUI, a software package for quantitation of in vivo/medical magnetic resonance spectroscopy signals , 2001, Comput. Biol. Medicine.

[3]  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.

[4]  H. Schild,et al.  Axonal Damage But No Increased Glial Cell Activity in the Normal-Appearing White Matter of Patients with Clinically Isolated Syndromes Suggestive of Multiple Sclerosis Using High-Field Magnetic Resonance Spectroscopy , 2007, American Journal of Neuroradiology.

[5]  K. Herfarth,et al.  PET and SPECT for detection of tumor progression in irradiated low-grade astrocytoma: a receiver-operating-characteristic analysis. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[6]  H. Vinters,et al.  Vulnerable Plaque in a Swine Model of Carotid Atherosclerosis , 2009, American Journal of Neuroradiology.

[7]  P. Bottomley Spatial Localization in NMR Spectroscopy in Vivo , 1987, Annals of the New York Academy of Sciences.

[8]  M. Lehecka,et al.  Operative intervention for delayed symptomatic radionecrotic masses developing following stereotactic radiosurgery for cerebral arteriovenous malformations—case analysis and literature review , 2010, Acta Neurochirurgica.

[9]  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.

[10]  Harald Hampel,et al.  A multicenter reproducibility study of single-voxel 1H-MRS of the medial temporal lobe , 2006, European Radiology.

[11]  Horst Urbach,et al.  Cerebral arteriovenous malformation: Spetzler-Martin classification at subsecond-temporal-resolution four-dimensional MR angiography compared with that at DSA. , 2008, Radiology.

[12]  Horst Urbach,et al.  Cerebral Arteriovenous Malformations at 3.0 T: Intraindividual Comparative Study of 4D-MRA in Combination With Selective Arterial Spin Labeling and Digital Subtraction Angiography , 2010, Investigative radiology.

[13]  D. Graveron-Demilly,et al.  Java-based graphical user interface for the MRUI quantitation package , 2001, Magnetic Resonance Materials in Physics, Biology and Medicine.

[14]  R. Warnick,et al.  Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. , 2010, International journal of radiation oncology, biology, physics.

[15]  Vanhamme,et al.  Improved method for accurate and efficient quantification of MRS data with use of prior knowledge , 1997, Journal of magnetic resonance.

[16]  H. Kauczor,et al.  [Metabolic imaging to follow stereotactic radiation of gliomas -- the role of 1H MR spectroscopy in comparison to FDG-PET and IMT-SPECT]. , 2004, RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin.

[17]  K Herholz,et al.  Enhanced accuracy in differential diagnosis of radiation necrosis by positron emission tomography-magnetic resonance imaging coregistration: technical case report. , 2000, Neurosurgery.

[18]  P. Sundgren MR Spectroscopy in Radiation Injury , 2009, American Journal of Neuroradiology.

[19]  M. Morino,et al.  Methionine positron emission tomography for differentiation of recurrent brain tumor and radiation necrosis after stereotactic radiosurgery —In malignant glioma— , 2004, Annals of nuclear medicine.

[20]  Heinz-Peter Schlemmer,et al.  Follow-up gliomas after radiotherapy: 1H MR spectroscopic imaging for increasing diagnostic accuracy , 2005, Neuroradiology.

[21]  Jörg-Christian Tonn,et al.  Value of O-(2-[18F]fluoroethyl)-l-tyrosine PET for the diagnosis of recurrent glioma , 2004, European Journal of Nuclear Medicine and Molecular Imaging.

[22]  G. Barnett,et al.  The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery , 2001, International journal of cancer.

[23]  C. Plathow,et al.  Metabolische Bildgebung zur Verlaufskontrolle stereotaktisch bestrahlter Gliome: Wertigkeit der 1H-MR-Spektroskopie im Vergleich zur FDG-PET und IMT-SPECT , 2004 .

[24]  David Bonekamp,et al.  Regional apparent metabolite concentrations in young adult brain measured by 1H MR spectroscopy at 3 Tesla , 2008, Journal of magnetic resonance imaging : JMRI.

[25]  M. Gilbert,et al.  Erratum: Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system (International Journal of Radiation Oncology Biology Physics (2011) 79:5 (1487-95) DOI: 10.1016/j.ijrobp.2009.12.061) , 2012 .

[26]  Michael Wagner,et al.  N-acetylaspartylglutamate (NAAG) and N-acetylaspartate (NAA) in patients with schizophrenia. , 2013, Schizophrenia bulletin.

[27]  Bram Stieltjes,et al.  7 tesla imaging of cerebral radiation necrosis after arteriovenous malformations treatment using amide proton transfer (APT) imaging , 2012, Journal of magnetic resonance imaging : JMRI.

[28]  M. Gilbert,et al.  Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. , 2011, International journal of radiation oncology, biology, physics.

[29]  J. Fike,et al.  CNS complications of radiotherapy and chemotherapy , 2009, The Lancet.

[30]  Adam P Dicker,et al.  Radiation dose-volume effects in the brain. , 2010, International journal of radiation oncology, biology, physics.

[31]  B. Nan,et al.  Differentiation between brain tumor recurrence and radiation injury using MR spectroscopy. , 2005, AJR. American journal of roentgenology.