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Journal of the Optical Society of America B

Photon-echo spectroscopy on biological systems I Application to tissues

Akira Furusawa, Takayuki Suga, Kiyoshi Uchikawa

Published Aug 1, 1994• 6 citations
Publisher

Abstract

The fluorescence detection technique of incoherent accumulated photon echo is applied to the investigation of animal and human tissues. The correlation between the kind of animal tissue and the dephasing time is determined. The dephasing times of normal and cancerous human tissues are measured by this technique. The cancer tissues exhibit shorter dephasing times than the normal tissues, and this is interpreted as being caused by the large number of conformational substates of cancer tissues. The dephasing time of a benign-tumor tissue is also measured and shows a value similar to that of the normal tissue. The dephasing time of a metastasizing cancer region is also measured. The applicability of photon-echo spectroscopy to diagnosis is noted.

DOI
10.1364/josab.11.001456

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The fluorescence detection technique of incoherent accumulated photon echo is applied to the investigation of animal and human tissues. The correlation between the kind of animal tissue and the dephasing time is determined. The dephasing times of normal and cancerous human tissues are measured by this technique. The cancer tissues exhibit shorter dephasing times than the normal tissues, and this is interpreted as being caused by the large number of conformational substates of cancer tissues. The dephasing time of a benign-tumor tissue is also measured and shows a value similar to that of the normal tissue. The dephasing time of a metastasizing cancer region is also measured. The applicability of photon-echo spectroscopy to diagnosis is noted.
We performed phase relaxation-time measurements of the accumulated photon echo for normal and cancerous tissue samples of human liver, that were stained with several kinds of dye. Each dye interacted selectively with a specific kind of biomolecule in the tissues, for example, DNA, proteins, or lipids. The cancerous tissues showed a tendency to have shorter relaxation times than the normal tissues had. The difference of relaxation time observed between the normal and the cancerous tissues depended on the dyes that were used for staining, and the difference became most clear when the tissues were stained with a cyanine dye derivative, i.e., YO-PRO3 Iodide, which has a high selectivity for DNA. We performed the relaxation-time mapping of the accumulated photon echo (photon-echo imaging) for a liver tissue sample stained by YO-PRO3 Iodide. The photon-echo imaging was successful in showing a region of a highly differentiated hepatocellular carcinoma in the tissue sample, while fluorescence-intensity mapping could not identify the cancerous region in the same tissue sample. These results indicated a possibility that the reduction of accumulated photon-echo relaxation time observed in the cancerous tissues was caused by a change of microscopic dynamics of DNA.
Generally, the photon echo measurement in opaque and scattering materials is difficult since the scattered pump beam overloads the detector. In this sense, a different modulation technique which does not induce the intensity modulation of the pump beam, is desirable for the scattering materials. We previously reported [1] that phase modulation method is also applicable to the measurement of accumulated photon echo. This technique has been much improved, and we have succeeded the fluorescence detection of the femtosecond accumulated photon echo.
Abstract The unique properties of single quantum photons have more potential for many applications in quantum metrology. Here, by using state-of-the-art techniques, the precision of the attenuation measurement of light by propagating in the tissue is enhanced and a method to diagnose cancer in the tissue is proposed. The measurement of light with precision beyond the shot-noise limit and near the ultimate quantum limit can be attained using the heralded single photons (HSPs) generated by the spontaneous parametric down-conversion process. The interaction of HSP with normal and malignant breast tissues announces the presence of its partner. Theoretically and experimentally, a quantum approach to diagnosing cancer by comparing the measured attenuation coefficient of the normal and malignant tissues is demonstrated using the HSPs. We experimentally show that it is possible to improve the attenuation uncertainty due to the scattering of HSPs from the bio-sample to distinguish the malignant tissue from the normal tissue. Here, we use a narrow-band filter to remove the Raman scattering effect and consequently increase the attenuation uncertainty. This method is one of the applications of quantum metrology for precision enhancement which can be used in the histology of unstained tissues and tumor margin detection.
Until now all reported studies of transient spectroscopy with incoherent light, including photon echo and pump-probe spectroscopy, were concerned with two-level systems where quasi-monochromatic light of only one frequency couples the two levels.[1-4] However, there exist various coherent transient phenomena where light of two or more frequencies are concerned, and time resolution of the transient spectroscopies using these phenomena are also expected to be limited not by the duration of used light pulses but by the correlation time of the radiation fields.[5]
A theory of optical echo spectroscopies of large polyatomic molecules in condensed phases is developed. Using phase space correlation functions, we examine the interrelationships among the following optical measurements: ordinary photon echo, stimulated photon echo, accumulated photon echo, incoherent accumulated photon echo, and pump–probe absorption. Conditions for the elimination of inhomogeneous broadening in these experiments are specified. A multimode Brownian oscillator model is used to account for high frequency molecular vibrations, as well as solvent modes, and electronic dephasing processes. The effects of quantum beats, spectral diffusion, and homogeneous dephasing on the echo signals are studied and compared in detail with pump–probe and hole burning spectroscopy.
Accumulated photon echoes (APE) were used to measure the dephasing rates of Nd3+ in various inorganic glasses as a function of excitation wavelength, sample temperature, and laser power. Although dephasing processes of optical transitions in solids are of considerable interest, they are poorly understood, largely due to the lack of experimental data on femtosecond and picosecond time scales. The APE technique using sub-picosecond laser sources has made it possible to measure in the time domain dephasing rates of inhomogeneously broadened transitions in amorphous systems.1,2