Abstract: Systems are shown that utilize differential measurement of radiation that has migrated through migration paths between two source-detector pairs placed on the head in a manner that each path is localized in a portion of one hemisphere of the brain. Various spectrophotometer systems are also shown for in vivo examination of tissue of a human by measuring changes in electromagnetic radiation scattered and absorbed in a migration path in the tissue. Generally, the spectrophotometer systems comprise a light source for introducing the radiation into the tissue, a detector for detecting radiation that has migrated in the tissue, a processor for processing signals of the detected radiation to create processed data, and a system for determining physiological or pathophysiological changes in the tissue of interest such as bleeding or tumor.