Disclosed are systems and methods for characterizing interactions or proton beams in tissues. In certain embodiments, charged particles emitted during passage of protons, such as those used for therapeutic and/or imaging purposes, can be detected at relatively large angles. In situations where beam intensity is relatively low, such as in certain imaging applications, characterization of the proton beam with charged particles can provide sufficient statistics for meaningful results while avoiding the beam itself. In situations where beam intensity is relatively high, such as in certain therapeutic applications, characterization of the proton beam with scattered primary protons and secondary protons can provide information such as differences in densities encountered by the beam as it traverses the tissue and dose deposited along the beam path. In certain situations, such beam characterizations can facilitate more accurate planning and monitoring of proton-based therapy.