Dosimetry modeling of focused kV x‐ray radiotherapy for wet age‐related macular degeneration

Abstract

Purpose: Wet (neovascular) age-related macular degeneration (AMD) is the leading cause of blindness in the United States. The mainstay treatment requires monthly intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs, associated with multiple visits, high cost, and the risk of procedural injury and infection. Anti-VEGF drugs inhibit the formation of neovasculature but do not directly attack it. Radiotherapy can destroy neovasculature and potentially also inhibit wet-AMD associated inflammation and fibrosis not addressed by VEGF inhibitors. However, the current collimation-based radiotherapy device uses fixed 4 mm beams, which are prone to overtreat or undertreat the choroidal neovascularization (CNV) lesions because of their various sizes and shapes. This simulation study evaluates personalized conformal treatment with focused kV radiation using cutting-edge polycapillary x-ray optics. Methods: Simulation of the polycapillary optics was achieved via Monte Carlo (MC)-based three-dimensional (3D) geometric ray tracing. Phase-space files modeling the focused photons were generated. The method was previously verified by phantom measurements. The ultrasmall~0.2 mm beam focal spot perpendicular to the beam direction enables spatially fractionated grid therapy, which has been shown to preferentially damage abnormal neovascular blood vessels vs normal ones. Geant4based MC simulations of scanning while rotating beam delivery were performed to conformally treat three clinical cases of large, medium, and small CNV lesions with regular and grid deliveries. Dose delivery uncertainties due to positioning errors were analyzed, including AE0.75 mm displacement in the three orthogonal directions and AE5°vertical/horizontal rotation of the eyeball. Results: The simulated CNV treatments by 60-kVp focused x-ray beams show highly conformal delivery of dose to the lesion plus margin (0.75 mm) with sharp dose fall-offs and controllable spatial modulation patterns. The 90%-10% isodose penumbra is <0.5 mm. With a prescription dose of 16 Gy to the lesions, the critical structure doses are well below the tolerance. The average CNV dose varies within 10% (mostly within 4%) due to 0.75-mm linear displacements and 5-degree gaze angle rotation of the eyeball. Conclusion: Focused kV technique allows personalized treatment of CNV lesions and reduces unwanted radiation to adjacent healthy tissue. The simulated dose distribution is superior to currently available techniques.

Robust treatment planning for small animal radio‐neuromodulation using focused kV x‐ray beams

“…The scanning‐while‐rotating pattern was used for its simplicity in robotic arm motion trajectory design and suitable for small collimation problems. The beam trajectories, described by Yan et al., 13 can be summarized as a combination of beam rotation and translation relative to the target center. The diagrammatic sketch of scanning‐while‐rotating pattern is shown in Figure 2a.…”

“…The target region covered by a margin was evenly separated into multiple narrow horizontal stripes in the x‐z plane, corresponding to the coronal plane Yan et al 13 . depicted.…”

“…A rat head model used in the Geant4 simulation and the Cartesian coordinate position are shown in Figure 2c. The target region covered by a margin was evenly separated into multiple narrow horizontal stripes in the x-z plane, corresponding to the coronal plane Yan et al 13 depicted. The width of horizontal stripes represented the displacement step along the y-axis.…”

“…Focused kV x‐ray technique based on modern x‐ray polycapillary focusing lens is a promising modality for small animal radio‐neuromodulation. Compared with conventional collimation from large field size, the x‐ray polycapillary focusing lens could produce a focal beam perpendicular to the beam direction after the lens output with full width at half maximum (FWHM) less than 0.3 mm 11–15 . Polychromatic kV x‐rays are collected with a wide collection angle and guided by multiple total reflections to travel through the focusing lens consisting of 10 5 −10 6 small hollow glass tubes.…”

“…Compared with conventional collimation from large field size, the xray polycapillary focusing lens could produce a focal beam perpendicular to the beam direction after the lens output with full width at half maximum (FWHM) less than 0.3 mm. [11][12][13][14][15] Polychromatic kV x-rays are collected with a wide collection angle and guided by multiple total reflections to travel through the focusing lens consisting of 10 5 −10 6 small hollow glass tubes. The power efficiency at the focal area is hundreds of times higher than a collimated aperture.…”