Low　signal-to-noise　ratios　and　limited　imaging　depths　restrict　the　ability　of　optical-imaging　modalities　to　detect　and　accurately　quantify　molecular　emissions　from　tissue.　Here,　by　using　a　scanning　external　X-ray　beam　from　a　clinical　linear　accelerator　to　induce　Cherenkov　excitation　of　luminescence　in　tissue,　we　demonstrate　in　vivo　mapping　of　the　oxygenation　of　tumours　at　depths　of　several　millimetres,　with　submillimetre　resolution　and　nanomolar　sensitivity.　This　was　achieved　by　scanning　thin　sheets　of　the　X-ray　beam　orthogonally　to　the　emission-detection　plane,　and　by　detecting　the　signal　via　a　time-gated　CCD　camera　synchronized　to　the　radiation　pulse.　We　also　show　with　experiments　using　phantoms　and　with　simulations　that　the　performance　of　Cherenkov-excited　luminescence　scanned　imaging　(CELSI)　is　limited　by　beam　size,　scan　geometry,　probe　concentration,　radiation　dose　and　tissue　depth.　CELSI　might　provide　the　highest　sensitivity　and　resolution　in　the　optical　imaging　of　molecular　tracers　in　vivo.