A method of trajectory optimization for radiotherapy treatment of multiple targets, the method comprising: providing a patient model including a plurality of planning target volumes (PTVs); defining a delivery coordinate space having a plurality of vertices, each respective vertex defining a respective beam's eye view plane; for each respective PTV of the plurality of PTVs: for each respective BEV plane of a respective vertex: for each respective pixel of the respective BEV plane: evaluating a dose of the respective PTV from a respective beamlet originating from the respective vertex and passing through the respective pixel of the respective BEV plane; and evaluating a respective BEV score of the respective pixel of the respective BEV plane for the respective PTV based at least in part on the dose of the respective PTV from the respective beamlet; determining a PTV-specific threshold BEV score for the respective PTV based at least in part on the BEV scores of the pixels of the BEV planes for the respective PTV; for each respective BEV plane of the respective vertex: determining one or more respective BEV regions of the respective PTV by comparing each respective BEV score of the respective pixel for the respective PTV to the PTV-specific threshold BEV score, wherein pixels within the one or more respective BEV regions have BEV scores greater than or equal to the PTV-specific threshold BEV score; and determining a respective BEV region connectivity manifold for the respective PTV representing connections between BEV regions of adjacent vertices; and selecting one or more optimal treatment trajectories for irradiating the plurality of PTVs based on the BEV region connectivity manifolds for the plurality of PTVs. providing a patient model including a plurality of planning target volumes (PTVs); defining a delivery coordinate space having a plurality of vertices, each respective vertex defining a respective beam's eye view plane; for each respective PTV of the plurality of PTVs: for each respective BEV plane of a respective vertex: for each respective pixel of the respective BEV plane: evaluating a dose of the respective PTV from a respective beamlet originating from the respective vertex and passing through the respective pixel of the respective BEV plane; and evaluating a respective BEV score of the respective pixel of the respective BEV plane for the respective PTV based at least in part on the dose of the respective PTV from the respective beamlet; determining a PTV-specific threshold BEV score for the respective PTV based at least in part on the BEV scores of the pixels of the BEV planes for the respective PTV; for each respective BEV plane of the respective vertex: determining one or more respective BEV regions of the respective PTV by comparing each respective BEV score of the respective pixel for the respective PTV to the PTV-specific threshold BEV score, wherein pixels within the one or more respective BEV regions have BEV scores greater than or equal to the PTV-specific threshold BEV score; and determining a respective BEV region connectivity manifold for the respective PTV representing connections between BEV regions of adjacent vertices; and for each respective BEV plane of a respective vertex: for each respective pixel of the respective BEV plane: evaluating a dose of the respective PTV from a respective beamlet originating from the respective vertex and passing through the respective pixel of the respective BEV plane; and evaluating a respective BEV score of the respective pixel of the respective BEV plane for the respective PTV based at least in part on the dose of the respective PTV from the respective beamlet; evaluating a dose of the respective PTV from a respective beamlet originating from the respective vertex and passing through the respective pixel of the respective BEV plane; and evaluating a respective BEV score of the respective pixel of the respective BEV plane for the respective PTV based at least in part on the dose of the respective PTV from the respective beamlet; determining a PTV-specific threshold BEV score for the respective PTV based at least in part on the BEV scores of the pixels of the BEV planes for the respective PTV; for each respective BEV plane of the respective vertex: determining one or more respective BEV regions of the respective PTV by comparing each respective BEV score of the respective pixel for the respective PTV to the PTV-specific threshold BEV score, wherein pixels within the one or more respective BEV regions have BEV scores greater than or equal to the PTV-specific threshold BEV score; and determining a respective BEV region connectivity manifold for the respective PTV representing connections between BEV regions of adjacent vertices; and selecting one or more optimal treatment trajectories for irradiating the plurality of PTVs based on the BEV region connectivity manifolds for the plurality of PTVs.