Optical investigations of physiology: a study of intrinsic and extrinsic biomedical contrast.

The utility and performance of optical studies of tissue depends upon the contrast and the changes of contrast in health and disease and in functional activity. The contrast is determined both by the optical properties of extrinsic chromophores and scatterers but especially upon the changes evoked by physiological activity and pathological states. Here, we have focused upon absorption changes of the intrinsic probe, blood absorbance changes due to cortical hypoxia and to haematomas, giving, for particular conditions, absorbance changes of 0.15 and over 0.4 delta OD, respectively. Functional activity may give changes of blood volume of over 0.05 delta OD with some variability due to individual responses that is best expressed as histogram displays of the distribution of response among a significant population. Responses have been observed in prefrontal parietal and occipital functions (242 tests). Extrinsic probes afford signals dependent upon the dose tolerance of the subject and can readily equal or exceed the blood volume and oxygenation signals, and currently afford vascular volume and flow indications. However, contrast agents for the functional activity of cellular function are ultimately to be expected. Finally, light-scattering changes afford osmolyte-related responses and are here shown to indicate a larger signal attributed to cortical depolarization and K+ release in hypoxia/ischaemia. Thus, the optical method affords imaging of manifold contrasts that greatly enhance its specificity and sensitivity for diagnostic procedures.