Electric field as a function of distance from center of electrode, calculated from a close form solution.

<p>The curved lines represent electric field for electrode voltages from 100 V (lower one) in increments of 100 V.</p

Enhancing lesion volume.

<p>Contrast-enhanced T1-weighted MRI without (A) and with (B) a mask selecting the enhancing portion of a GBM tumor (patient #4) are shown. The enhancing lesion volume was calculated from the pixels marked pink in (B). Enhancement subtraction maps calculated at 15 min (C) and 75 min (D) demonstrate the contributions of the red/non-tumor and blue/tumor contributions to the enhancing lesion volume.</p

Correlation with time to progression.

<p>The correlation between the late enhancement subtraction maps and time to progression was studied in a small cohort of 13 GBM patients post chemoradiation. Kaplan-Meier curves of time to progression in patients above and below the median of four predictors are shown: Initial fast volume (A), initial enhanced volume (B), initial fast growth rate (C) and initial enhanced growth rate (D). The curves are plotted for each predictor for patients above (black) and below (gray) the median. It can be seen that the initial fast growth rate predictor provides a near-significant difference between the two groups of patients, suggesting this predictor may be a candidate for prediction of time to progression.</p

Examples of progression and pseudoprogression in GBM patients post chemoradiation.

<p>Late enhancement subtraction maps of a patient (#6) with significant increase in the enhancing lesion due to increase in the red volume (A–C) and a patient (#3) with significant increase in the blue component (D–F) with minor changes in the enhancing volume are shown. In the first example, the total enhancing volume has increased by 34% from 3 weeks (A) to 4.2 months (B) post chemoradiation, and then decreased to 33% below the initial volume (C) 9 months post treatment. The blue volume slightly increased by 6% in the first 4 months (A, B) and then significantly decreased to 47% below the initial volume at 9 months (C) while the red volume increased by 51% in the first 4.2 months (A, B) and decreased to 13% above the initial volume by 9 months (C). This patient progressed 11.6 months post treatment. In the second example, the total enhancing volume has increased by 16% from 3 weeks (D) to 2.5 months (E) and then remained 17% above the initial volume (F) 6.5 months post treatment. The blue volume slightly increased by 2% in the first 2.5 months (D,E) and then significantly increased to 57% above the initial volume at 6.5 months (F) while the red volume increased by 39% in the first 2.5 months (D, E) and decreased to 61% below the initial volume by 6.5 months (F). This patient progressed 6.5 months post treatment when he was referred to surgery.</p

Additional file 2 of BBB opening by low pulsed electric fields, depicted by delayed-contrast MRI, enables efficient delivery of therapeutic doxorubicin doses into mice brains

Supplementary Material 2: Video 1a. Growth of GL261 cells without treatment

Additional file 6 of BBB opening by low pulsed electric fields, depicted by delayed-contrast MRI, enables efficient delivery of therapeutic doxorubicin doses into mice brains

Supplementary Material 6: Video 2b. Growth of U87 cells treated with 200nM Doxo

Enhancement subtraction maps.

<p>Examples of axial high resolution T1-weighted MR images acquired 2 min (A), 15 min (B) and 75 min (C) after contrast administration in a patient (#3) with newly diagnosed GBM undergoing standard chemoradiation are shown. Subtraction maps were calculated from the data acquired at 2 and 15 min (D) and 2 and 75 min (E) post contrast administration. Blue regions represent fast clearance of the contrast agent from the tumor while red regions represent slow accumulation of the contrast in the tissue. It can be seen that abnormal enhancement patterns in the 75 min map are depicted more clearly and over larger regions than in the 15 min map. The signal intensity of regions with different enhancement patterns as a function of time post contrast administration is shown in the plot. It can be seen that the red and blue components of the tumor enhance and decay at different rates.</p

Histological determination of tumor and non-tumoral components – GBM.

<p>Examples of contrast-enhanced T1-weighted MRI (A–C), enhancement subtraction maps calculated from the 2 and 75 min data (D–F) and H&E stained histological samples of a rapidly growing lesion in patient #1 with newly diagnosed GBM undergoing standard chemoradiation are shown. Data was acquired prior to surgery, 6 months after initiation of treatment. Samples were taken from a mixed blue and red region (A, D, arrows), a blue region (B, E, arrows) and a red region (C, F, arrows). Histological analysis reveals mixed regions of tumor and necrosis (G, magnification×200), hypercellular tumor (H, magnification×400) and radiation necrosis (J, magnification×400), respectively.</p