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

<div><p>Objective</p><p>This study evaluated the possibility of accelerated gadolinium accumulation in irradiated brain parenchyma where the blood-brain barrier was weakened.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>Radiotherapy can induce R1 value increase in the brain parenchyma, which might suggest accelerated gadolinium accumulation due to damage to the blood-brain barrier.</p></div

Timeline of patient treatment and the imaging study.

<p>The standard treatment for newly diagnosed GBM includes gross total removal of the tumor and concurrent chemoradiotherapy with temozolomide, followed by adjuvant temozolomide. In this study, we enrolled patients who underwent pre- and post-radiation brain MRI including R1 map source images. Pre-radiation MRI included MRI performed either before or after tumor removal. The mean time interval between pre- and post-radiation MRI session was 4.2 ± 2.1 months. Further follow-up brain MRI with R1 mapping was available for 10 patients.</p

Definition of Area_H and Area_L.

<p>A 58-year-old female patient underwent radiotherapy for the treatment of GBM located in the right frontal lobe. The radiotherapy plan map was obtained from the electronic medical records system (EMR) and was composed of representative <b>(a)</b> axial, <b>(b)</b> coronal, and sagittal (not presented) CT images (note; arrows represent the iso-dose line of 3600 cGy). In this patient, <b>(c)</b> the right thalamus (dashed circle) was designated as a Area_H, whereas <b>(d)</b> the left frontal white matter (dashed circle) was considered a Area_L (presented images: pre-contrast T1WI).</p

ROI around primary tumors.

<p>A 28-year-old male patient with severe headache for 1 month underwent brain MR imaging. <b>(a)</b> Contrast-enhanced axial T1WI revealed a heterogeneous enhancing mass located at the right frontal lobe. He underwent gross total removal of the brain tumor, and final pathology confirmed GBM. He also completed radiotherapy (total dose = 61.2 Gy). <b>(b)</b> The black line (arrows) in the radiotherapy plan map showed the iso-dose line of 3600 cGy, which was the 56.7% iso-dose line of the maximum dose (6343.8 cGy). For R1 measurement, the ROI was drawn at the peri-tumoral area located within the 50–100% iso-dose line of the maximum dose and both <b>(c)</b> overt enhancing area and <b>(d)</b> abnormal T2 hypersignal intensity area were avoided.</p

Flow chart of the study population.

<p>Note: MRI = magnetic resonance imaging, CCRT = concurrent chemoradiotherapy, TMZ = temozolomide, GBM = glioblastoma multiforme.</p

Basic information regarding patients, target lesions, treatment, and imaging work-up in 44 patients with supratentorial GBM.

<p>Basic information regarding patients, target lesions, treatment, and imaging work-up in 44 patients with supratentorial GBM.</p

Clinical characteristics and MRI findings between CCD-positive and CCD-negative groups.

<p>Clinical characteristics and MRI findings between CCD-positive and CCD-negative groups.</p

A 71-year-old man with a history of sudden onset left-sided weakness.

<p>(A) Diffusion-weighted image demonstrating hyperacute infarction in the right basal ganglia without (B) signal change on the fluid-attenuated inversion recovery image. (C) Arterial occlusion is noted in MR angiography at the right M1 (arrow). (D) ASL image of the cerebellum showing hypoperfusion in the contralateral cerebellar hemisphere (grade III and AI of 44.48).</p

Detection of crossed cerebellar diaschisis in hyperacute ischemic stroke using arterial spin-labeled MR imaging

<div><p>Background and purpose</p><p>Arterial spin-labeling (ASL) was recently introduced as a noninvasive method to evaluate cerebral hemodynamics. The purposes of this study were to assess the ability of ASL imaging to detect crossed cerebellar diaschisis (CCD) in patients with their first unilateral supratentorial hyperacute stroke and to identify imaging or clinical factors significantly associated with CCD.</p><p>Materials and methods</p><p>We reviewed 204 consecutive patients who underwent MRI less than 8 hours after the onset of stroke symptoms. The inclusion criteria were supratentorial abnormality in diffusion-weighted images in the absence of a cerebellar or brain stem lesion, bilateral supratentorial infarction, subacute or chronic infarction, and MR angiography showing vertebrobasilar system disease. For qualitative analysis, asymmetric cerebellar hypoperfusion in ASL images was categorized into 3 grades. Quantitative analysis was performed to calculate the asymmetric index (AI). The patients’ demographic and clinical features and outcomes were recorded. Univariate and multivariate analyses were also performed.</p><p>Results</p><p>A total of 32 patients met the inclusion criteria, and 24 (75%) presented CCD. Univariate analyses revealed more frequent arterial occlusions, higher diffusion-weighted imaging (DWI) lesion volumes and higher initial NIHSS and mRS scores in the CCD-positive group compared with the CCD-negative group (all p < .05). The presence of arterial occlusion and the initial mRS scores were related with the AI (all p < .05). Multivariate analyses revealed that arterial occlusion and the initial mRS scores were significantly associated with CCD and AI.</p><p>Conclusion</p><p>ASL imaging could detect CCD in 75% of patients with hyperacute infarction. We found that CCD was more prevalent in patients with arterial occlusion, larger ischemic brain volumes, and higher initial NIHSS and mRS scores. In particular, vessel occlusion and initial mRS score appeared to be significantly related with CCD pathophysiology in the hyperacute stage.</p></div

Representative ASL images for each visual grade (upper row) and diffusion-weighted images showing supratentorial infarction for each case (lower row).

<p>(A) Grade I, no demonstrable asymmetric perfusion in the cerebellum. Diffusion-weighted image in the lower row shows hyperacute infarction in the left temporal lobe (arrow). (B) Grade II, the affected right cerebellum is slightly hypointense to the unaffected left cerebellum. Hyperacute infarction is seen in the posterior limb of the left internal capsule (arrow). (C) Grade III, the affected right cerebellum is markedly hypointense to the unaffected left cerebellum. Diffusion-weighted image in the lower row demonstrates hyperacute infarction in the left frontotemporal lobe (arrow). (D) An example of circular region of interests in the cerebellum. The calculated asymmetry index was 3.7 in <i>A</i>, 9.5 in <i>B</i>, and 34.2 in <i>C</i>.</p