Responses in the diffusivity and vascular function of the irradiated normal brain are seen up until 18 months following SRS of brain metastases

Line Brennhaug Nilsen; Ingrid Digernes; Endre Grøvik; Cathrine Saxhaug; Anna Latysheva; Oliver Geier; Birger Breivik; Dag Ottar Sætre; Kari Dolven Jacobsen; Åslaug Helland; Kyrre Eeg Emblem

doi:10.1093/noajnl/vdaa028

Responses in the diffusivity and vascular function of the irradiated normal brain are seen up until 18 months following SRS of brain metastases

Neurooncol Adv. 2020 Feb 28;2(1):vdaa028. doi: 10.1093/noajnl/vdaa028. eCollection 2020 Jan-Dec.

Authors

Affiliations

¹ Department of Diagnostic Physics, Oslo University Hospital, Oslo, Norway.
² University of Oslo, Oslo, Norway.
³ Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
⁴ Department of Radiology, Hospital of Southern Norway, Kristiansand, Norway.
⁵ Department of Radiology, Østfold Hospital Trust, Klanes, Norway.
⁶ Department of Oncology, Oslo University Hospital, Oslo, Norway.

Abstract

Background: MRI may provide insights into longitudinal responses in the diffusivity and vascular function of the irradiated normal-appearing brain following stereotactic radiosurgery (SRS) of brain metastases.

Methods: Forty patients with brain metastases from non-small cell lung cancer (N = 26) and malignant melanoma (N = 14) received SRS (15-25 Gy). Longitudinal MRI was performed pre-SRS and at 3, 6, 9, 12, and 18 months post-SRS. Measures of tissue diffusivity and vascularity were assessed by diffusion-weighted and perfusion MRI, respectively. All maps were normalized to white matter receiving less than 1 Gy. Longitudinal responses were assessed in normal-appearing brain, excluding tumor and edema, in the LowDose (1-10 Gy) and HighDose (>10 Gy) regions. The Eastern Cooperative Oncology Group (ECOG) performance status was recorded pre-SRS.

Results: Following SRS, the diffusivity in the LowDose region increased continuously for 1 year (105.1% ± 6.2%; P < .001), before reversing toward pre-SRS levels at 18 months. Transient reductions in microvascular cerebral blood volume (P < .05), blood flow (P < .05), and vessel densities (P < .05) were observed in LowDose at 6-9 months post-SRS. Correspondingly, vessel calibers in LowDose transiently increased at 3-9 months (P < .01). The responses in HighDose displayed similar trends as in LowDose, but with larger interpatient variations. Vascular responses followed pre-SRS ECOG status.

Conclusions: Our results imply that even low doses of radiation to normal-appearing brain following cerebral SRS induce increased diffusivity and reduced vascular function for up until 18 months. In particular, the vascular responses indicate the reduced ability of the normal-appearing brain tissue to form new capillaries. Assessing the potential long-term neurologic effects of SRS on the normal-appearing brain is warranted.

Keywords: brain metastases; diffusion-weighted MRI; normal-appearing brain tissue response; perfusion MRI; stereotactic radiosurgery.