Does radiation therapy increase gadolinium accumulation in the brain?: Quantitative analysis of T1 shortening using R1 relaxometry in glioblastoma multiforme patients

PLOS ONE, Nov 2019

Objective This study evaluated the possibility of accelerated gadolinium accumulation in irradiated brain parenchyma where the blood-brain barrier was weakened. Methods From January 2010 to June 2015, 44 patients with supratentorial glioblastoma were retrospectively identified who underwent pre- and post-radiation brain MR imaging, including R1 mapping. The mean dose of administered gadobutrol (Gadovist, Bayer, Germany) was 5.1 vials. Regions of interest (ROIs) were drawn around tumors that were located within 50–100% iso-dose lines of maximum radiation dose. ROIs were also drawn at globus pallidus, thalamus, and cerebral white matter. Averages of R1 values (unit: s-1) before and after radiation and those of R1 ratio (post-radiation R1 / pre-radiation R1) were compared by t-test or rank sum test as appropriate. Multiple linear regression analysis was performed to evaluate independent association factors for R1 value increase at irradiated parenchyma. Results The mean R1 values in peri-tumoral areas were significantly increased after radiotherapy (0.7901±0.0977 [mean±SD] vs. 0.8146±0.1064; P <.01). The mean R1 ratio of high radiation dose areas was significantly higher than that of low dose areas (1.0055±0.0654 vs. 0.9882±0.0642; P <.01). The mean R1 ratio was lower in those who underwent hypofractionated radiotherapy (mean dose, 45.0 Gy) than those who underwent routine radiotherapy (mean dose, 61.1 Gy) (0.9913±0.0740 vs. 1.0463±0.0633; P = .08). Multiple linear regression analysis revealed that only radiotherapy type was significantly associated with increased R1 (P = .02) around tumors. Conclusions Radiotherapy can induce R1 value increase in the brain parenchyma, which might suggest accelerated gadolinium accumulation due to damage to the blood-brain barrier.

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Does radiation therapy increase gadolinium accumulation in the brain?: Quantitative analysis of T1 shortening using R1 relaxometry in glioblastoma multiforme patients

February Does radiation therapy increase gadolinium accumulation in the brain?: Quantitative analysis of T1 shortening using R1 relaxometry in glioblastoma multiforme patients Woo Hyeon Lim 0 1 Seung Hong Choi 0 1 Roh-Eul Yoo 0 1 Koung Mi Kang 0 1 Tae Jin Yun 0 1 Ji- Hoon Kim 0 1 Chul-Ho Sohn 0 1 0 Department of Radiology, Seoul National University College of Medicine , Seoul , Korea , 2 Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul National University , Seoul , Korea , 3 School of Chemical and Biological Engineering, Seoul National University , Seoul , Korea 1 Editor: Gabriele Multhoff, Technische Universitat Munchen , GERMANY - Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This study was supported by a grant from the Korea Healthcare Technology R&D Projects, Ministry for Health, Welfare & Family Affairs (HI16C1111 to SC), by the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning Objective Methods This study evaluated the possibility of accelerated gadolinium accumulation in irradiated brain parenchyma where the blood-brain barrier was weakened. From January 2010 to June 2015, 44 patients with supratentorial glioblastoma were retrospectively identified who underwent pre- and post-radiation brain MR imaging, including R1 mapping. The mean dose of administered gadobutrol (Gadovist, Bayer, Germany) was 5.1 vials. Regions of interest (ROIs) were drawn around tumors that were located within 50± 100% iso-dose lines of maximum radiation dose. ROIs were also drawn at globus pallidus, thalamus, and cerebral white matter. Averages of R1 values (unit: s-1) before and after radiation and those of R1 ratio (post-radiation R1 / pre-radiation R1) were compared by t-test or rank sum test as appropriate. Multiple linear regression analysis was performed to evaluate independent association factors for R1 value increase at irradiated parenchyma. Results The mean R1 values in peri-tumoral areas were significantly increased after radiotherapy (0.7901±0.0977 [mean±SD] vs. 0.8146±0.1064; P <.01). The mean R1 ratio of high radiation dose areas was significantly higher than that of low dose areas (1.0055±0.0654 vs. 0.9882 ±0.0642; P <.01). The mean R1 ratio was lower in those who underwent hypofractionated radiotherapy (mean dose, 45.0 Gy) than those who underwent routine radiotherapy (mean dose, 61.1 Gy) (0.9913±0.0740 vs. 1.0463±0.0633; P = .08). Multiple linear regression (2016M3C7A1914002), by the Creative-Pioneering Researchers Program through Seoul National University (SNU), and by Project Code (IBS-R006D1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. analysis revealed that only radiotherapy type was significantly associated with increased R1 (P = .02) around tumors. Conclusions Radiotherapy can induce R1 value increase in the brain parenchyma, which might suggest accelerated gadolinium accumulation due to damage to the blood-brain barrier. Introduction Gadolinium (Gd)-based contrast agents (GBCAs) are widely used contrast materials for magnetic resonance (MR) imaging in clinical setting. Recently, GBCAs are attracting attention to many radiologists after Kanda et al [ 1 ] and Errante et al [ 2 ] reported hyperintensity in the dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted image (T1WI) might be related with usage of GBCAs. Subsequent studies [3±8] revealed that hyperintensity in the DN on T1WI was associated with previous administration of linear GBCAs, whereas previous administration of macrocyclic GBCAs showed no such association. These studies [1±7] suggested that the mechanism of Gd deposition in the brain is the dissociation of the Gd from its chelate molecule. However, no study has examined why the DN and GP consistently show remarkable T1 hyperintensity, while other parts of the brain show less significant T1 hyperintensity. Meanwhile, the blood-brain barrier (BBB) functions as a barrier between blood and brain parenchyma that controls brain microenvironment by regulating transmembranous transportation [ 9 ]. Several conditions including irradiation [10±16] could result in disruption of BBB. We hypothesized that the integrity of the BBB might contribute to the selective deposition in the brain. No study has investigated the relationship between BBB damage and Gd deposition in the brain. Thus, the purpose of this study was to evaluate the absolute R1 (unit: s-1) changes after administration of macrocyclic GBCA in glioblastoma (GBM) patients who underwent radiotherapy, which can induce BBB weakness. Materials and methods Institutional Review Board at Seoul National University Hospital approved this study. The requirement of wr (...truncated)


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Woo Hyeon Lim, Seung Hong Choi, Roh-Eul Yoo, Koung Mi Kang, Tae Jin Yun, Ji-Hoon Kim, Chul-Ho Sohn. Does radiation therapy increase gadolinium accumulation in the brain?: Quantitative analysis of T1 shortening using R1 relaxometry in glioblastoma multiforme patients, PLOS ONE, 2018, Volume 13, Issue 2, DOI: 10.1371/journal.pone.0192838