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

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.

A systematic review on the use of quantitative imaging to detect cancer therapy adverse effects in normal-appearing brain tissue

“… Metastasis SRS 16-24 Gy DSC CBV↑ 43%, CBF↑ 34% after 1 m in 5-10 Gy vs T0 Lee [ 41 ] 1.5T 22/9F (49 ± ?) HGG III–IV RTx 60 Gy DSC CBV↓ non-significant vs T0 Nilsen [ 44 ] 3T 40/24F (63 ± ?) Metastasis SRS 15-21 Gy DSC CBF, CBV↓ 5%, vessel caliber↑ 5% after 6–9 m vs T0 Price [ 38 ] 3T 3/1F (?…”

“…Transient reductions of 5% in microvascular CBV and CBF were observed in low-dose regions at 6–9 months normalized to < 1 Gy region. A corresponding 5% increase in the average vessel caliber was observed when using a combined gradient-echo spin-echo based readout scheme [ 44 ].…”

MR Image Changes of Normal-Appearing Brain Tissue after Radiotherapy

“…CBF decreased in normal-appearing GM with a more pronounced decrease of 16.8% in high-dose areas > 50 Gy and a weak decrease of 2.3% in low dose volumes < 10 Gy, even so suggesting damages to the capillary bed or supplying artery. The hypothesis of radiation affecting tissue even in low-dose regions is supported by the results of Nilsen and co-authors [84], who measured decreasing vascular function with DSC after stereotactic radiosurgery (SRS) of brain metastases from non-small cell lung cancer and malignant melanoma in 40 patients. They reported decreasing CBV, CBF, and vessel density even in low-dose areas < 10 Gy at three to nine months post-SRS.…”

“…Several studies focused on microstructural tissue changes in white matter structures after radiotherapy. The most prominent effects are decreasing FA [ 24 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 ], increasing MD [ 24 , 68 , 70 , 72 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ], and increasing RD [ 71 , 76 , 77 , 78 , 79 , 80 , 82 , 85 , 86 , 87 ]. AD was both measured as increasing [ 77 , 78 , 80 , 82 ] and decreasing [ 71 , 83 , 85 , 86 , 87 , 88 , 89 ] as a response to radiation.…”

“…Radiation-induced vascular changes can be detected with perfusion-weighted imaging (PWI) methods such as dynamic susceptibility contrast (DSC), dynamic contrast enhancement (DCE), and arterial spin labeling (ASL). Most PWI studies found a perfusion decrease after radiotherapy, characterized by decreasing cerebral blood volume (CBV) [ 84 , 97 , 98 , 99 , 100 ], decreasing cerebral blood flow (CBF) [ 36 , 84 , 95 , 98 , 101 ], and increased K trans (volume transfer constant between blood plasma and extravascular extracellular space (EES)), v e (volume of EES) and v p (fractional plasma volume) [ 102 , 103 ]. Table 3 summarizes the results of the studies focusing on vascular changes of normal-appearing brains after irradiation.…”