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Role of MR Spectroscopy in Differentiating Radiation Necrosis from Tumor Recurrence. Effects of radiation Injury. Elias A 1 , Carlos RC 1 , Smith EA 1 , Maly P 2 , Sundgren PC 1 2 1 Department of Radiology, University of Michigan Health

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## Role of MR Spectroscopy in Differentiating Radiation Necrosis from Tumor Recurrence. Effects of radiation Injury.

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**Role of MR Spectroscopy in Differentiating Radiation**Necrosis from Tumor Recurrence. Effects of radiation Injury. Elias A1, Carlos RC1, Smith EA1, Maly P2, Sundgren PC1 2 1Department of Radiology, University of Michigan Health Systems, Ann Arbor, MI 48109, USA 2Department of Radiology, Skåne University hospital , Lund University, Lund, Sweden**Learning Objectives**• Magnetic resonance spectroscopy (MRS) to detect early radiation changes. • Describe the most current data in differentiating tumor recurrence from radiation necrosis. • Metabolic ratio with highest statistical yield. • Application to clinical practice - Prediction models.**Disclosures**The authors do not currently have and have not within the past 12 months had a financial interest or other relationship with a commercial organization that may have an interest in the content of this presentation.**Introduction**• Present management of new enhancing lesion at the vicinity of treated brain neoplasm • invasive brain biopsy • clinical course • imaging follow-up • Differentiation on conventional MR imaging • Diagnostic dilemma - no specific imaging characteristics • post therapeutic changes • non specific enhancement to gadolinium • Radiation oncology protocols • improved outcome with high radiation dose • dose limiting radiation injury**Tumor recurrence versus radiation injury**• Radiation necrosis 5 - 24 % after conventional therapy • Early radiation changes are evident as early as 2- 6 months after therapy • Overlapping imaging features/findings between radiation injury and tumor recurrence Marks JE, Baglan RJ, Prassad SC, Blank WF. Cerebral radionecrosis: incidence and risk in relation to dose, time, fractionation and volume.Int J Radiation Oncology Biol Phys 1981;7(2): 243-52.**Background**Early radiation white matter changes • Radiation oncology protocols • improved outcome with high radiation dose • dose limiting radiation injury • Clinical status deterioration**Early radiation white matter changes**A B post Gd-DTPA T1-weighted images before RT (A) and 6 months after the completion of RT (B) Sundgren PC, et al. Metabolic alterations; a biomarker for radiation-induced injury of normal brain. An Spectroscopy study. JMRI 2009 Feb;29(2):291-7**Pre treatment 3 weeks in RT**6 months after RT**Differences of ratios of NAA/Cr (square) and Cho/Cr**(triangle) compared to the values prior to RT. Significant interval changes were observed in NAA/Cr and Cho/Cr during and after RT**Early radiation white matter changes**Conclusion • Occult injury to the normal brain begins during RT • and remains evident for at least 6 months. • Supports the hypothesis that MRS is sensitive for • early detection of metabolic changes in normal • brain tissue undergoing radiation Sundgren PC, Nagesh V, Elias A, Tsien C, Junck L, Gomez Hassan D, Lawrence T, Chenevert TL, Rogers L, McKeever P, Cao Y. Metabolic alterations; a biomarker for radiation-induced injury of normal brain. An Spectroscopy study. JMRI 2009 Feb;29(2):291-7**Controversy in the diagnosis of radiation necrosis**vs tumor recurrence with MRS • lesions often mixed • which type of MRS sequences to use • ratio calculations • - normalized ratios • - in lesion measurements • role of MRS in clinical decision making**Controversy regarding measurements and calculations**• MRS findings have been shown to correlate well with pathologic specimens obtained at biopsy and/or resection • No consensus in the spectroscopy community regarding measurements, ratios and methods to use when performing ratio calculations Background Rock JP et al. Neurosurgery 2002; 51:912-20.**Controversy regarding measurements and calculations**In a recent study of 25 patients we compared the ability of standard metabolic and normalized ratios to discriminate between recurrent tumor and radiation changes. • Inclusion criteria: • - primary intracranial neoplasm • - radiation therapy treatment • - new contrast enhanced lesion**Controversy regarding measurements and calculations**• Data and statistical analysis • Wilcoxon and rank-sum test • Nonparametric alternative to the two-sample t-test • Statistical significance was set at a p-value ≤ 0.05 • Receiver operating characteristic (ROC) curve • Statistical significance was set at a p-value ≤ 0.05 Methods**Controversy regarding measurements and calculations**Spectral analysis in a 35 y.o. woman with a left posterior parietal contrast enhancing lesion on follow-up MRI at 27 months**Controversy regarding measurements and calculations**Non-normalized Cho/NAA ratio AzROC= 0.92 Normalized Cho/NAA ratio AzROC= 0.77**Conclusion**Controversy regarding measurements and calculations • Non-normalized ratios have the best discriminatory ability compared to normalized ratios • Cho/NAA ratio had the highest sensitivity and specificity to differentiate and correctly classify new contrast enhancing lesions in patients with radiation-treated primary brain tumors**Background**Prediction models for clinical decision making Currently patients are subjected to invasive biopsy to determine diagnosis of new contrast enhancing lesions to differentiate between recurrent tumor and radiation changes.**Prediction models for clinical decision**making Materials • 33 patients • Inclusion criteria: • Primary intracranial neoplasm • Previous treatment with XRT • New contrast enhancing lesion Smith E et al Developing an prediction model . AJR Am J Roentgenol. 2009 Feb;192(2):W45-52**Prediction models for clinical decision**making • Wilcoxon rank sum analysis • non-parametric data • small sample size • Logistic regression model Statistical analysis**Prediction models for clinical decision**making • Lesions classified into two groups • - recurrent neoplasm • - post radiation changes • Lesion classification methods • - histopathologic diagnosis • - imaging and clinical follow up**Prediction models for clinical decision**making Results**1.00**0.75 Sensitivity 0.50 0.25 0.00 0.00 0.25 0.50 0.75 1.00 1 - Specificity Prediction models for clinical decision making • Cho/NAA • Sensitivity = 85% • Specificity = 69.2% • Area under the ROC curve = 0.92**Prediction models for clinical decision**making • Post test probability was estimated • Linear regression model • Range of Cho/NAA values**Results: Prediction Model**80% 15%**Results: Prediction Model**Probability of recurrent tumor using Cho /NAA ratio New contrast Pr ≤ 15% Routine follow - up enhancing lesion on (0/5) conventional MRI 15< Pr <80% Biopsy (33) (6/13) MR Spectroscopy Pr ≥ 80% Immediate Treatment (14/15) stratified Clinical Decision Making Risk - Smith E et al Developing an prediction model ..AJR Am J Roentgenol. 2009 Feb;192(2):W45-52**MR spectroscopy**Proton (1H) MRSmost used technique in clinical routine SVS (single voxel spectroscopy) STEAM / PRESS TE 20-35ms / 135-270 ms, TR 2000-3000ms VOI ( 2x2x2 cm ) placements basal ganglia, normal / abnormal white matter gray matter 2D-CSI (chemical shift imaging) PRESS TE 35 ms / 144 ms / 280 ms, TR 2000ms larger VOI - cover larger regions of normal and abnormal brain, basal ganglia, centrum semiovale**MR spectroscopy Protocol**• 2D-CSI (chemical shift imaging) • PRESS • TE 35 ms / 144 ms / 280 ms • TR 1000 - 2000 ms • FOV 16 cm • Matrix 16 x 16 • Slice thickness 10 - 20 mm • Scan time 4.2 minutes • Functool 2000 (GE Healthcare)**Important brain metabolites**• NAA 2.0ppm neuron marker, adult peak at age 15 • Cr1 3.03ppm fairly stable marker for energy dependent systems in brain cells • Cr2 3.9ppm ratio Cr2/Cr1=2/3 • Cho 3.25ppm tumor fraction/demyelination • Lac 1.32ppm hypoxia (anaerobic) Lac peak is inverted at TE 144 ms**Metabolic ratios**normal abnormal NAA/Cr 2.0 <1.6 NAA/Cho 1.6 <1.2 Cho/Cr 1.2 >1.5 Cho/NAA 0.7 > 1.0

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