Magne Kleppestø1, Christopher Larsson1, and Atle Bjornerud1,2
1The Intervention Centre, Oslo University Hospital, Oslo, Norway, 2Department of Physics, University of Oslo, Oslo, Norway
Synopsis
Brain tumors are usually subjected to radiation therapy upon diagnosis. In this work, it is made an attempt at investigating if this therapy might cause injury to the non-cancerous parts of the brain. To this end dynamic contrast-enhanced MRI was used to estimate leakage across the blood-brain barrier.22 patients were imaged before and after undergoing a treatment schedule, and findings from the two examinations were compared to uncover any change. The data shows no significant variation in either permeability or blood plasma volume.Purpose
Patients suffering from malignant brain tumors are routinely treated with radiotherapy (RT) as well as chemotherapy. This will in most cases lead to a significant part of apparently healthy brain tissue receiving high radiation doses. In this work we attempt to assess blood-brain barrier (BBB) damage in normal appearing brain tissue in high grade glioma (HGG) patients after receiving RT treatment by estimating contrast agent extravasation from dynamic contrast-enhanced (DCE) MRI.
Methods
Structural and dynamic MRI images was acquired in 22 HGG patients before and after receiving combined radio- and chemotherapy for 8 weeks, as part of a prospective study. Patients received RT in daily fractions, with a total of 64 Gy being administered to the target volume. The imaging protocol included structural FLAIR and pre-/post-contrast T1 series in addition to DCE acquisition immediately following a Look-Locker based T1-mapping sequence. The DCE sequence used a saturation recovery gradient echo sequence with TR/TE/flip angle = 8.2 ms/2.1 ms/28 degrees. Trigger delay of 80 ms was used, giving a time resolution of 3.4 s. A total of 100 timepoints were acquired (5.5 min). Tumor and edema ROIs were produced by a radiologist, and radiation dose maps was obtained and co-registered to the DCE volumes of each patient. Tissue concentration curves were estimated from the DCE images in combination with the pre-contrast T1-map. The In order to assess damage to the BBB from RT, a ROI was defined as tissue having received more than 50 Gy, excluding tumor and edema. Pixel-wise tissue concentration curves in this ROI was averaged together in order to maximize SNR. For each examination an AIF was measured in the most accessible feeding artery. Using the Patlak model
1, estimates of
Ktrans and
vp were obtained for the selected ROI. These estimates were used for each patient to compare pre- and post-RT kinetic parameters, and the Wilcoxon rank sum test was applied to test for changes between them. A similar approach have been utilized previously to investigate BBB disruptances in normal appearing brain in multiple sclerosis patients
2.
Results
No significant correlations was found for either
Ktrans (p>0.86) or
vp (p>0,78). Figure 1 (
Ktrans) and figure 2 (
vp) show corresponding pre- and post-RT estimations of ROI parameter values.
Discussion
The present study presents no evidence for radiation induced BBB damage from a conventional HGG treatment regimen. However, the grouping together of all voxels with a certain radiation dose across the whole brain might obfuscate regional variations. While the results presented herein do not imply that the BBB is significantly compromised by treatment-grade radiation for the duration of the treatment, it can not be ruled out that damages are made that does not manifest themselves as increased permeability across the BBB before at a later time.
Acknowledgements
No acknowledgement found.References
1. Patlak C, Blasberg R, Fenstermacher J. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 1983 (3)
2. Cramer SP, Simonsen H, Frederiksen JL, Rostrup E, Larsson HBW. Abnormal blood-brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI. Neuroimage Clin 2014 (4)