Radiology and Oncology | Ljubljana | Slovenia | www.radioloncol.com 1 Perfusion f magnetic resonance imaging changes h in normall appearing brain tissue after radiotherapy in glioblastoma patients may confound longitudinal evaluation of treatment response Markus Fahlström, Erik Blomquist, Tufve Nyholm, Elna-Marie Larsson doi: 10.2478/raon-2018-0022 GM 0-5 Gy nCBVWM 2.2 nCBV (a.u) 0-5 Gy 2.0 1.8 p=0.078 p=0.438 p=0.027 34.4 103.3 N/A 1.6 1.4 N/A 1.2 1.0 0.8 9.0 RT 3.1 Days Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 GM 5-10 Gy nCBVWM nCBVWM WM 5-10 Gy p=0.078 p=0.313 p=0.203 1.8 1.6 1.4 1.2 34.4 103.3 34.4 103.3 34.4 103.3 p=0.039 p=0.813 0.6 9.0 RT 3.1 Days 103.3 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 nCBVGM GM 20-30 Gy p=0.301 p=0.461 p=0.625 p=0.910 34.4 103.3 nCBV (a.u) 1.0 9.0 RT 3.1 Days 34.4 103.3 0.8 0.6 p=0.461 p=0.313 9.0 RT 3.1 Days Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 nCBVWM WM 30-40 Gy 1.4 p=0.570 nCBVGM GM 30-40 Gy p=0.999 1.2 p=0.641 p=0.313 p=0.496 34.4 103.3 1.6 1.4 1.2 nCBV (a.u) 1.2 1.8 1.0 0.8 1.0 0.8 0.6 9.0 RT 3.1 Days 34.4 103.3 0.4 p=0.999 34.4 103.3 0.6 p=0.129 1.8 1.6 1.4 1.2 p=0.148 p=0.813 9.0 RT 3.1 Days Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 nCBVWM WM 40-50 Gy 1.4 p=0.078 9.0 RT 3.1 Days Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 nCBVGM GM 40-50 Gy 1.2 p=0.820 p=0.641 p=0.313 p=0.820 34.4 103.3 1.2 nCBV (a.u) nCBV (a.u) 34.4 0.8 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 GM 40-50 Gy nCBVWM 1.0 0.8 1.0 0.8 0.6 9.0 RT 3.1 Days 34.4 103.3 0.4 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 GM 50-60 Gy nCBVWM p=0.625 34.4 103.3 0.6 nCBV (a.u) 1.6 1.4 1.2 p=0.625 nCBVGM GM 50-60 Gy 1.2 p=0.164 p=0.547 1.2 p=0.074 1.8 p=0.039 9.0 RT 3.1 Days Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 nCBVWM WM 50-60 Gy 1.4 p=0.148 9.0 RT 3.1 Days Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 2.2 nCBV (a.u) p=0.438 0.8 0.4 nCBV (a.u) nCBV (a.u) 30-40 Gy p=0.910 0.6 9.0 RT 3.1 Days 2.2 40-50 Gy 103.3 1.0 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 50-60 Gy p=0.625 1.2 GM 30-40 Gy nCBVWM 0.8 34.4 1.2 p=0.313 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 1.0 9.0 RT 3.1 Days nCBVWM WM 20-30 Gy 1.2 2.0 p=0.109 1.0 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 p=0.203 1.4 0.8 103.3 nCBVGM GM 10-20 Gy p=0.129 0.8 0.4 nCBV (a.u) nCBV (a.u) 20-30 Gy p=0.625 1.6 1.0 9.0 RT 3.1 Days Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 1.4 p=0.039 1.8 2.0 p=0.999 1.0 GM 20-30 Gy nCBVWM 0.8 0.6 0.6 9.0 RT 3.1 Days 2.2 1.0 34.4 0.8 1.2 p=0.148 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 2.0 103.3 nCBV (a.u) 1.2 2.2 p=0.999 1.2 1.4 0.8 34.4 nCBVWM WM 10-20 Gy p=0.301 nCBV (a.u) nCBV (a.u) 10-20 Gy p=0.625 1.6 1.0 9.0 RT 3.1 Days 1.4 p=0.023 1.8 2.0 p=0.813 1.0 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 GM 10-20 Gy nCBVWM 0.8 p=0.844 p=0.652 0.8 0.4 2.2 1.0 p=0.813 0.6 9.0 RT 3.1 Days Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 2.0 p=0.313 1.0 nCBV (a.u) 0.8 1.2 nCBV (a.u) 1.0 1.2 nCBV (a.u) nCBV (a.u) 5-10 Gy 2.0 nCBVGM GM 5-10 Gy 1.4 nCBV (a.u) 2.2 1.0 0.8 p=0.813 p=0.820 34.4 103.3 1.0 0.8 0.6 9.0 RT 3.1 Days 34.4 103.3 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 0.4 9.0 RT 3.1 Days 34.4 103.3 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 0.6 9.0 RT 3.1 Days Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 S1 FIGURE. Longitudinal change in regional nCBV. Regional nCBV (mean and 95% CI) graphically displayed for the different examinations in consecutive order. Derived P-values are included, and emphasised in bold and italics if less than 0.05. Radiol Oncol 2018; 52(2) 2 nCBF (a.u) 0-5 Gy GM 0-5 Gy nCBFWM 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 p=0.195 9.0 RT 3.1 Days p=0.125 p=0.027 34.4 103.3 N/A N/A Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 WM 5-10 Gy nCBFWM p=0.125 1.2 p=0.027 34.4 103.3 0.4 p=0.125 1.2 p=0.055 0.6 9.0 RT 3.1 Days 103.3 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 nCBFGM GM 10-20 Gy p=0.195 p=0.313 p=0.129 p=0.945 0.8 p=0.313 p=0.734 34.4 103.3 1.0 0.8 0.6 34.4 103.3 0.4 p=0.125 34.4 103.3 0.6 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 p=0.945 p=0.188 nCBFGM GM 20-30 Gy 1.2 p=0.820 p=0.742 1.2 p=0.027 9.0 RT 3.1 Days Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 WM 20-30 Gy nCBFWM 1.4 p=0.461 9.0 RT 3.1 Days nCBF (a.u) 9.0 RT 3.1 Days nCBF (a.u) 1.0 0.8 p=0.438 p=0.652 34.4 103.3 1.0 0.8 0.6 34.4 103.3 0.4 103.3 0.6 p=0.020 p=0.641 p=0.313 9.0 RT 3.1 Days Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 WM 30-40 Gy nCBFWM nCBFGM GM 30-40 Gy p=0.910 1.2 p=0.742 p=0.438 p=0.820 34.4 103.3 1.2 nCBF (a.u) p=0.125 34.4 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 1.4 p=0.461 9.0 RT 3.1 Days nCBF (a.u) 9.0 RT 3.1 Days 1.0 0.8 1.0 0.8 0.6 34.4 103.3 0.4 103.3 0.6 p=0.110 p=0.188 9.0 RT 3.1 Days Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 WM 40-50 Gy nCBFWM nCBFGM GM 40-50 Gy 1.2 p=0.652 p=0.383 p=0.074 p=0.813 p=0.910 34.4 103.3 1.2 nCBF (a.u) p=0.125 34.4 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 1.4 p=0.461 9.0 RT 3.1 Days nCBF (a.u) 9.0 RT 3.1 Days 1.0 0.8 1.0 0.8 0.6 9.0 RT 3.1 Days 34.4 103.3 0.4 103.3 0.6 1.4 p=0.195 p=0.063 nCBFGM GM 50-60 Gy 1.2 p=0.426 1.2 nCBF (a.u) p=0.074 9.0 RT 3.1 Days Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 WM 50-60 Gy nCBFWM GM 50-60 Gy nCBFWM p=0.125 34.4 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 p=0.461 9.0 RT 3.1 Days p=0.945 nCBF (a.u) nCBF (a.u) nCBF (a.u) nCBF (a.u) 34.4 0.8 1.2 1.0 GM 40-50 Gy nCBFWM nCBF (a.u) 103.3 nCBF (a.u) p=0.461 nCBF (a.u) nCBF (a.u) 10-20 Gy 20-30 Gy 30-40 Gy 34.4 WM 10-20 Gy nCBFWM Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 40-50 Gy 9.0 RT 3.1 Days 1.4 GM 30-40 Gy nCBFWM 50-60 Gy p=0.426 1.0 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 p=0.188 p=0.359 0.6 9.0 RT 3.1 Days GM 20-30 Gy nCBFWM 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 p=0.625 0.8 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 p=0.641 p=0.641 1.0 GM 10-20 Gy nCBFWM 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 1.2 nCBF (a.u) p=0.383 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 GM 5-10 Gy nCBFGM 1.4 nCBF (a.u) nCBF (a.u) 5-10 Gy GM 5-10 Gy nCBFWM 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 1.0 0.8 p=0.063 p=0.999 34.4 103.3 1.0 0.8 0.6 9.0 RT 3.1 Days 34.4 103.3 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 0.4 9.0 RT 3.1 Days 34.4 103.3 Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 0.6 9.0 RT 3.1 Days Pre-RT RTPOST-1 RTPOST-2 RTPOST-3 S2 FIGURE. Longitudinal change in regional nCBF. Regional nCBF (mean and 95% CI) graphically displayed for the different examinations in consecutive order. Derived P-values are included, and emphasised in bold and italics if less than 0.05. Radiol Oncol 2018; 52(2) 3 WM nCBFWM (RTPOST-2) WM nCBFWM (RTPOST-1) 15 45 0 60 y = -0.09536X + 0.1917 10 0 -10 -20 -30 -40 45 60 0 y = -0.2006X - 0.4133 10 0 -10 -20 -30 -40 15 30 45 0 y = 0.01367X - 5.563 10 0 -10 -20 -30 -40 15 -50 Dose (Gy) 30 45 10 0 -10 -20 -30 -40 10 0 -10 -20 -30 -40 -50 45 -30 -40 0 0 60 y = 0.02107X - 0.675 15 Dose (Gy) 30 45 60 y = 0.0006925X - 7.482 20 20 10 0 -10 -20 -30 -40 -50 15 Dose (Gy) 10 0 -10 -20 -30 -40 30 45 GM nCBFGM (RTPOST-3) 60 0 y = -0.02457X - 1.907 20 Relative Change (%) 20 30 -20 GM nCBFGM (RTPOST-2) Relative Change (%) 15 0 -50 GM nCBFGM (RTPOST-1) 0 60 -10 60 -50 Dose (Gy) 45 GM nCBFWM (RTPOST-3) y = -0.04295X - 11.22 20 Relative Change (%) 20 30 10 GM nCBFWM (RTPOST-2) 60 Dose (Gy) y = -0.06381X - 1.119 20 Relative Change (%) 0 Dose (Gy) 15 -50 GM nCBFWM (RTPOST-1) Relative Change (%) 30 WM nCBFWM (RTPOST-3) -50 -50 Relative Change (%) 15 20 Relative Change (%) 20 Relative Change (%) 30 Dose (Gy) Relative Change (%) 0 Dose (Gy) 15 Dose (Gy) 30 45 60 y = 0.00127X - 0.08148 10 0 -10 -20 -30 -40 -50 S3 FIGURE. Dose-dependent relative change and linear regression model for nCBF. Shows regional relative change for nCBF and derived line regression (line and equation). S1 TABLE. Volumes for derived dose regions. Mean volume in cm3 with 95% confident interval for the derived dose regions. Dose Region 0-5 Gy 5-10 Gy 10-20 Gy 20-30 Gy 30-40 Gy 40-50 Gy 50-60 Gy Volume (cm3) Mean (95% CI) GM WM 84.5 (74.5-94.5) 56.0 (47.1-64.8) 36.4 (27.5-45.2) 33.4 (24.3-42.4) 62.7 (54.8-70.6) 51.5 (43.5-59.6) 91.0 (81.0-101.1) 73.7 (65.1-82.4) 35.0 (31.9-38.2) 32.3 (29.0-35.7) 28.2 (24.1-34.2) 19.7 (18.2-21.2) 117.3 (106.7-127.8) 90.2 (78.4-102.0) Radiol Oncol 2018; 52(2) 4 S2 TABLE. Mean and SEM for regional nCBV and nCBF. Regional nCBV and nCBF (mean and SEM), decrease in percentage relative Pre-FRT (mean and SD) and derived P-values. GM nCBVWM " " " " " ! " " WM nCBVWM GM nCBFWM " " " " " " " " " " " " " GM nCBVGM WM nCBFWM Radiol Oncol 2018; 52(2) " " " " " " " " " " " " GM nCBFWM " " " " " "