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Optical methods Parameter Feature PET MRI Confocal, multiphoton microscopy Reflectance and raster scan DOT Contrast Sensitivity to probes High fM–pM Low μM–mM High fM–pM High pM–nM High pM–nM Activating probes No No Yes Yes Yes Intrinsic No Yes Yes Nonionizing No Yes Yes Imaging Resolution 1–5 mm 40 μm–1 mm ∼0.3–10 μm 0.1–3 mm 0.1–10 mm Depth Not limited Not limited 0.01–0.5 0.1–2 mm 0.1–50 mm Tomography/sectioning Yes Yes Yes No Yes Optical methods have many flexible and powerful modes of molecular and functional contrast. Effect of depth on imaging performance is dramatic.