Equation (9) suggests that the CRS signal rapidly grows when the average excitation intensity is increased. Nonetheless, photodamaging of the sample prevents a continual increase of the signal with incident power as higher powers inevitably lead to damage of the specimen. Photodamage may result from a plethora of mechanisms, which are all highly dependent on the excitation conditions and the material properties of the specimen. General rules that predict photodamage are, therefore, difficult to synthesize. A useful categorization of photodamaging mechanisms takes into consideration the intensity dependence of the damaging process. As indicated above, both linear and nonlinear photodamage may occur to the sample. Linear photodamage is the result of linear absorption and subsequent heating of the sample. For instance, local increases in the temperature of a few degrees or more can negatively impact cell functions and may result in cell abnormalities or trigger apoptosis. Substantial rises in local temperature may occur when strong absorbers are present in the sample at relatively high concentrations. Examples include chromophores such as carotenoids and chlorophylls in plant tissues and melanin in human skin. When the tissue is devoid of strongly absorbing chromophores, linear heating in aqueous environments is generally small, much less than a degree in fast imaging applications, for near-infrared pulsed excitation and average powers .90,91 Nonlinear photodamage includes heating of UV chromophores after multiphoton absorption, Raman heating, and the excitation of high-energy molecular states that are reactive. The latter process can generate photoproducts that are toxic, such as highly reactive radicals.92 In the high intensity limit, nonlinear processes can also ionize the sample and generate local plasmas.93 Several experiments indicate that under typical CRS conditions, using high-repetition rate, near-infrared picosecond pulses at average powers of 10 mW or more, both linear and nonlinear effects contribute to photodamaging in live cells.50,94 Although the effects of laser illumination on biological samples can never be fully avoided, keeping average powers and pulse energies has been shown to minimize the impact of light-induced changes to cell cultures under fast CRS imaging conditions.