1. Differentiation between Primary Central Nervous System Lymphoma and Glioblastoma on 3T-MR Imaging: Multivariate Analysis M. Kitajima 1, T. Hirai 1, Y. Shigematsu 1, A. Sasao 1, S. Nishimura 1, K. Iwashita 1, K. Makino 2, H. Nakamura 2, Y. Yamashita 1 Department of Diagnostic Radiology 1 and Neurosurgery 2, Kumamoto University Kumamoto, Japan

2. Introducti on The incidence of PCNSL has increased in the last few decades, while GB is by far the most common primary glial tumor in adults. Management for PCNSL and GB –PCNSL: a brain biopsy and CTx with MTX and/or RT –GB: combination of maximal surgical resection, RT, and concomitant and adjuvant CTx with temozolomide Various MR imaging features of PCNSL and GB have been reported; however, the most useful MR imaging finding for differentiation between PCNSL and GB has not been evaluated.

3. Purpos e The purpose of this study was to determine the useful MR imaging findings to differentiate between PCNSL and GB based on selected features on 3T-MR imaging.

4. Materials and Methods Patients –16 PCNSLs 9 men and 7 women mean 69.9-years, range 37–83 years no history of HIV infection –35 GBs 21 men and 14 women mean 67-years, range 40–85 years –The contrast enhancement of the lesion was observed in all cases.

5. 3T-MRI Conventional imaging: T1-, T2WI, FLAIR, Gd-T1WI DWI –spin-echo EPI, b=0, 1000 s/mm 2 –ADC maps were obtained on a pixel-by-pixel basis from the diffusion imaging data sets DSC –gradient-echo EPI –Gd-DTPA (0.1 mmol/kg) 3 ml/sec + 20 ml saline flush –rCBV maps were obtained on a pixel-by-pixel basis from DSC imaging data sets MR spectroscopy –PRESS (long TE: 270 or 288ms) –Spectral maps were obtained.

6. Evaluation Qualitative assessment – Two neuroradiologists assessed 3 MR imaging features by consensus. Table 1. Visual Scores System for PCNLS and GB MR Characteristic Score 012 HomogeneityHomogeneous Inhomogeneou s Markedly Inhomogeneou s Distribution1 site2 sites More than 3 sites Enhancement Pattern Homogeneous Inhomogeneou s Ring

7. Quantitative assessment –minimum ADC (minADC) The lowest ADC value selected among 4 ROIs within the lesion –normalized max rCVB ratio (n-rCVB ratio) Ratio between highest rCBV selected among 4 ROIs within the lesion and the contralateral normal region –Cho/NAA at the enhanced lesion(l-Cho/NAA) Ratio of the peak height between Cho and NAA at the enhanced lesion –Cho/NAA at the peritumoral lesion (p-Cho/NAA) Ratio of the peak height between Cho and NAA at the non-enhanced region adjacent to the enhanced lesion

8. Statistical analysis –All numeric data were reported as the mean ± SD. –Univariate and multivariate logistic regression analyses were performed to determine which MR findings were useful to differentiate between PCNSL and GB. –For numeric data which showed statistically significant difference, ROC curve analysis was performed to identify the optimal cutoff value for prediction purposes of PCNSL and GB.

9. Result s PCNSL (n=16) GB (n=35) Homogeneit y Homogeneous 4 (25.0)2 (5.7) Inhomogeneous 9 (56.3)14 (40.0) Markedly inhomogeneous 3 (18.8)19 (54.3) Distribution 1 site 6 (37.5)22 (62.9) 2 sites 7 (43.8)12 (34.3) More than 3 sites 3 (18.8)1 (2.9) Enhancemen t pattern Homogeneous 4 (25.0) 0 (0) Inhomogeneous 11 (38.8) 8 (22.9) Ring 1 (6.3) 27 (77.1) Note- Data are numbers (%) of patients Table 2. Qualitative MR findings in PCNSL and GB

10. Table 3. Quantitative MR findings in PCNSL and GB PCNSL (n=16) Mean (SD) GB (n=35) Mean (SD) minADC0.83 (0.18)0.93 (0.19) n-rCBV ratio 1.72 (1.22)6.86 (2.84) MR Spectroscopy l-Cho/NAA l-Cho/NAA2.72 (2.78)3.93 (2.95) p-Cho/NAA p-Cho/NAA0.89 (0.35)1.26 (0.77)

11. Variable Regression Coefficient (β) POdds ratio95 % CI Homogeneity -1.2970.0120.2730.100-0.751 Distribution 1.0110.0402.7501.045-7.233 Enhancement pattern -3.7160.00060.0240.003-0.206 min ADC -3.3680.0770.0340.001-1.435 n-rCBV ratio -0.9560.00030.3850.230-0.644 l-Cho/NAA -0.1760.1830.8390. 647-1.086 p-Cho/NAA -1.0830.0890.3390.097-1.180 Table 4. Results of Univariate Logistic Analysis for Differentiation between PCNSL and GB * Computed using GB group as the reference group.

12. Table 5. Results of Multivariate Logistic Analysis for Differentiation between PCNSL and GB Variable Regression Coefficient (β) POdds ratio95 % CI Homogeneity-0.2510.8430.7780.061-9.956 Enhancement pattern -4.2930.0190.0140.0004-0.487 Distribution-0.9740.4350.3770.033-4.349 n-rCBV ratio -0.8500.0110.4280.222-0.823 *Computed using GB group as the reference group.

13. ROC analysis demonstrated a cutoff value of 1.86 for n-rCBV ratio to provide for discrimination between PCNSL and GB Az value 0.9321 Sensitivity100% Specificity92.1% PPV 81.3 % NPV 100% at cutoff value of 1.86

14. Fig. 1. a 53-y.o. male with PCNSL Homogeneity: markedly inhomonegeneous, Distribution: 1 site, Enhancement pattern: ring minADC 0.56, n-rCBV ratio 0.09, l-Cho/NAA 2.1, p-Cho/NAA 0.54 T2WIGd-T1WIADC maprCBV map MRS at enhanced lesionMRS at peritumoral region

15. Fig. 2. a 85-y.o. female with GB Homogeneity: inhomogeneous, Distribution: >3 sites （ extends to contralateral hemisphere and the posterior fossa ） Enhancement pattern: inhomogeneous minADC 0.87, n-rCBV ratio 9.5, l-Cho/NAA 6.0, p-Cho/NAA 1.8 T2WIGd-T1WIADC maprCBV map MRS at enhanced lesion MRS at peritumoral region

16. Discussion Conventional MR imaging findings –Intratumoral hemorrhage or necrosis 2 cases (12.5%) in PCNSL (reported incidence 2- 8%) –Lesion distribution >60% of PCNSL cases distributed in >2 sties (reported incidence 19-45%) >60% of GB distributed in 1 site. –Ring enhancement 1 case (6.3%) in PCNSL (reported incidence 4– 13%) min ADC –Low ADC value of PCNSL due to higher cellularity –Histological heterogeneity in the tumor

17. n-rCBV ratio –PCNSL < GB –The max rCBV ratio correlated well with tumor neo- vascularization PCNSL<<GB Laio W. et al. Acta radiol 2009:50:217-25. MRS –tumor core NAA ↓↓, Cho↑↑, Lip↑in PCNSL NAA ↓↓, Cho ↑, Lip ↑(depends on necrosis) in GB Harting I et al. Neurosci Lett. 2003:342:163-6. –peritumoral lesion a combination of vasogenic edema and neoplastic cell infiltration may be seen in both PCNSL and GB.

18. Conclusion Contrast enhancement pattern and n- rCBV ratio were useful at MR imaging performed to differentiate between PCNSL and GB. The ring enhancement and high n- rCBV ratio suggest glioblastoma, and homogenous enhancement and low n- rCBV ratio (<1.86) suggest PCNSL.