Carcinoma in situ (CIS) of the bladder is a confounding disease that is difficult to recognize endoscopically because it is a flat cancer. Many studies have suggested its relationship with subsequent invasive disease. Early recognition of CIS therefore is essential in offering the patient the most appropriate treatment and the highest cure rate. Because white light cystoscopic examination is not sufficient to reveal areas of dysplasia or CIS, random biopsies are recommended. The authors evaluate whether amino levulinic acid (ALA) fluorescence detection could be helpful in diagnosing CIS and if the specificity could be enhanced by reducing the ALA dose. Sixteen patients with papillary bladder cancer, and CIS and dysplasia were given low-dose ALA. Fluorescence detection of the metabolized ALA was performed 3 hours later, with the naked eye, after blue light illumination. Carcinoma in situ or dysplasia was found in 50 biopsies. The sensitivity for detecting CIS was 94% with a specificity of 54%. Carcinoma in situ can be diagnosed with a very high accuracy through fluorescence detection after ALA instillation. Fluorescence detection can be achieved with the naked eye and does not necessitate either complex equipment or specially trained personnel.

Bladder tissue autofluorescence spectra are obtained in vivo at two excitation wavelengths (334 nm and 365 nm) with a cystoscopic fiber- optic device based on a small mercury arc lamp. Upon 365 nm excitation, both normal and cancerous bladder tissue have nearly identical fluorescence spectra, characterized by a broad peak at 455 nm. However, the fluorescence yield from malignant tissue is approximately a factor 3 lower compared to normal tissue. A similar decrease in fluorescence yield is observed upon 334 nm excitation. More importantly, at this excitation wavelength, the spectra from normal and malignant tissue have different lineshape. Normal tissue shows two distinct fluorescence peaks (at 385 nm and 455 nm), while malignant tissue only shows the 455 nm peak. Based on these insights, we have developed a simple spectroscopic algorithm, to differentiate normal from malignant bladder tissue with our device. The main underlying biophysics will be addressed. The integration of the diagnostic method with a reliable therapeutic technique for tumor cell destruction, may open the way for cost- effective preventive care of high-risk patients.

An investigation of the refractive index and third-order nonlinear optical susceptibility chi(3) of two polypernigraniline derivatives, poly (4,4'-diphenylimine methine) (PDPIM) and poly(4,4'-diphenylimine p-heptyloxybenzylidene) (PDPIHB) reveals effects of molecular structure on the linear optical and nonlinear optical properties of conjugated polymers. The chi(3) (-3omega; omega, omega, omega) of PDPIM was found to decrease relative to polypemigraniline, reflecting the observed decrease of the oscillator strength of the 2.2 eV absorption band when a methine carbon replaces one of the nitrogen atoms of pernigraniline repeat unit. The alkoxyphenylene side group substitution at the methine carbon in PDPIHB, however, significantly enhances the nonlinear optical response of PDPIHB while reducing the refractive index compared to PDPIM and polypemigraniline. The present results suggest that structural changes in conjugated polymers can be made in such a way as to enhance the nonlinear optical properties while modulating the linear optical properties. (C) 1994 John Wiley & Sons, Inc.

Fluorescence tagging of tumors by sensitizing agents such as hematoporphyrin derivatives is an efficient method for diagnosing tumors but presents, even at low doses, a number of serious drawbacks for the patients. We demonstrate a fiberoptic instrument for the diagnosis of bladder cancer, based on a tripled frequency Nd YAG laser, without need for sensitizing agents, based on the autofluorescence of tissues. The contrast demarcation obtained for CIS and TCC respectively is 2.2 and 2.7, which is about 30% higher than what can be obtained after photosensitizing. The integration of the diagnostic method with a reliable therapeutic technique for tumor cell destruction, opens the way for cost-effective preventive care of high risk patients.

We demonstrate that bladder tissue autofluorescence provides more adequate information for tumor demarcation, thus eliminating the need for sensitizing agents. During initial experiments, autofluorescence spectra were recorded with an optical multichannel analyzer for both normal and tumor bladder tissue upon excitation with the third harmonic of a pulsed Nd:YAG laser (355 nm). In both cases, the spectra show a relatively broad peak centered at 470 nm accompanied by a long tail extending into the red. However, malignant tumors show a decrease of the 470 nm peak by approximately a factor of 2.5 with respect to normal tissue, while the red tail (/spl lambda/>600 nm) of the spectrum remains unaffected. As a result, the ratio F of the autofluorescence signals at 470 nm and 630 nm can be used as a demarcation function, independent of both the excitation energy and the collection efficiency of the optical system. From the insights gained in these experiments, we have developed and extensively tested in vivo a cystoscopic fiber optic diagnostic system.<>

We monitor the induced phase change produced by a cascaded chi((2)):chi((2)) process in KTP near the phase-matching angle on a picosecond 1.06-microm-wavelength beam using the Z-scan technique. This nonlinear refraction is observed to change sign as the crystal is rotated through the phase-match angle in accordance with theory. This theory predicts the maximum small-signal effective nonlinear refractive index of n(eff)(2) congruent with +/-2 x 10(-14) cm(2)/W (+/-1 x 10(-11) esu) for an angle detuning of +/-5 degrees from phase match for this 1-mm-thick crystal with a measured d(eff) of 3.1 pm/V. For a fixed phase mismatch, this n(eff)(2) scales linearly with length and as d(eff)(2) however, for the maximum n(eff)(2) the nonlinear phase distortion becomes sublinear with irradiance for phase shifts near pi/4.

The third-order optical susceptibility chi(3)(-3-omega;omega,omega,omega) of polyanilines and derivatives has been systematically investigated by picosecond third harmonic generation spectroscopy on spin-coated thin films of the polymers in the wavelength range 0.9-2.4-mu-m (1.4-0.5 eV). It is shown that the magnitude of chi(3)(-3-omega;omega,omega,omega) of this class of polymers is as large as that of other conjugated polymers and that the optical nonlinearity depends on the oxidation level and the derivatization of the p-phenylene rings. The dispersion of the optical nonlinearity is dominated by the three-photon resonance to the dipole allowed transition occuring at approximately 1.8 eV, so that the excitonic transition is the major contributor to the optical nonlinearity of polyanilines. Polyemeraldine base, with an oxidation level of about 50%, has a larger optical nonlinearity than the fully oxidized form pernigraniline or poly(phenylaniline) which we use aa a model compound for the fully reduced form. The effects of derivatization are more complex. Methoxy substitution of the phenyl ring increases the transition moment, which would increase the microscopic nonlinearity. However, these substituents also reduce the number density of the polymer repeat units, which in turn reduces the macroscopic nonlinearity.

The magnitude of the nonlinear-optical coefficients of KTiOPO4 are measured relative to those of quartz at 0.88 μm. When we use for quartz d11 = 0.308 pm/V at 0.88 μm (which corresponds to 0.30 pm/V at 1.06 μm), the following results (in pm/V) are obtained for KTiOPO4 (at 0.88 μm): d15 = 2.04, d24 = 3.92, d31 = 2.76, d32 = 4.74, and d33 = 18.5. The accuracy of the measurements is estimated to be ±10%. These results, if corrected for dispersion, predict an effective d coefficient for type II phase matching at 1.064 μm of 3.35 pm/V.

The third-order nonlinear optical susceptibility chi(3)(-3-omega;omega,omega,omega) of the conjugated rigid-rod polymer poly(p-phenylenebenzo[1,2-d:5,4-d']bisoxazole) (PBO) has been investigated by third-harmonic generation spectroscopy and theoretical modeling in the wavelength range 0.9-2.4-mu-m (1.4-0.5 eV). The chi(3) spectrum of PBO exhibits a strong three-photon resonance with a three-photon resonance enhanced chi(3)(-3-omega;omega,omega,omega) value of 7.0 X 10(-11) esu at 1.2-mu-m. The nonresonant-chi(3) value at 2.4-mu-m was 8.1 X 10(-12) esu, which is large and comparable to some of the best conjugated polymers. The chi(3) dispersion data were found to be well described by a theoretical two-level essential states model. These results for the oxygen-containing heterocyclic rigid-rod polymer (PBO) were compared and contrasted with those previously reported for the structurally analogous sulfur-containing poly(p-phenylenebenzobisthiazole) (PBZT). The results indicate that the magnitude of chi(3) is essentially identical in PBO and PBZT, suggesting the absence of an effect of the heteroatom on the nonlinear optical response of this class of heterocyclic rigid-rod polymers in contrast to prior oligomer model compound studies which had shown a factor of 3 enhancement by the sulfur heteroatom.

We describe the cascading of two second-order nonlinearities [χ (2) :χ (2) ] to produce an effective third-order nonlinearity in KTP. 1 This nonlinearity appears as either an irradiance dependent loss or phase distortion on the incident fundamental beam. The loss mechanism is simply the depletion of the fundamental due to second-harmonic generation. For low conversion efficiencies the loss of the fundamental is proportional to irradiance and appears as an effective Im[χ (3) ] (i.e., as two-photon absorption). The refractive part of the nonlinearity [i.e., Reχ (3) ] is less well known and usually ignored since it occurs off phase matching where Δ kL ≠ 0. This effect gives rise to either a phase advance or phase delay depending on the sign of Δ kL. In the experiment, we use a hydrothermally grown KTP sample of length L = 1 mm cut for type II SHG of 1064 nm and monitor the induced phase change of the incident fundamental beam using the Z-scan technique. 2 The sign of the nonlinear refractive index changes sign as the angle tuned KTP sample is rotated through phase matching in accordance with theory. The experiment gives a maximum effective nonlinear refractive index n 2 ≃±1 × 10 -11 esu (±2 × 10 -14 cm 2 /W) for an angle detuning of ±5°. This index scales with L and ( d eff ) 2 where we measure d eff (KTP) = 3.1 pm/V.

We report on an experimental study of a hydrothermally grown KTiOPO4 (KTP) Pockels cell, utilizing the effective electro-optic coefficient, rc1=28 pm/V. Compensation of the static birefringence of KTP, when it is used as amplitude modulator, has been achieved by temperature tuning. Our study revealed that a KTP Pockels cell does not suffer from piezoelectric-induced parasitics (acoustic ringing). Stable high-repetition rate pulse slicing has been obtained at 30 kHz. Intracavity use of a KTP Pockels cell also has been successfully demonstrated in a Q-switched Nd:YLF laser system.

Third harmonic generation (THG) experiments have been performed on a variety of conjugated organic materials over the energy range 0.5 - 1.5 eV. The measured dispersion of (chi) (3)(-3(omega) ;(omega) ,(omega) ,(omega) ) is presented and comparisons between structurally related materials are made to elucidate structure-property relationships. In the benzimidazobenzophenanthroline material series consisting of the fully fused ladder polymer BBL, the semiladder polymer BBB, and the model molecule cis-BB, the effects of polymerization and ring fusion are observed. The cis-BB displays an interference in the THG spectrum, while this feature is absent in the BBB and BBL. The difference in the nonlinearity of the BBB and BBL is attributed to the difference in the number density of the two materials. The effect of the ladder structure on the nonlinearity is demonstrated by comparing the nonlinearity of BBL with PPI, a polyazomethine possessing a similar backbone. The ladder structure increases the nonlinearity by a minimum factor of 5 throughout the energy range examined. The effect of donors on the polyazomethine backbone is examined using the hydroxy and methoxy donors. The methoxy donor increases the nonlinearity, while the hydroxy donor reduces the nonlinearity. The physical implications of these observations are discussed.

The nonresonant third-order nonlinear optical properties of thin films of poly(p-phenylene benzobisthiazole) (PBZT) and PBZT/nylon 66 and PBZT/poly(trimethylhexamethylene terephthalmide) (PTMHT) molecular composites have been investigated using picosecond third-harmonic generation at 1.9 μm. The measured χ(3)(−3ω,ω,ω,ω) for the pure PBZT was (1.37±0.27)×10−11 esu. The χ(3) of PBZT/nylon composites showed a linear dependence on composition. In contrast, the χ(3) of PBZT/PTMHT molecular composites significantly deviated from this linear dependence, showing enhanced values. No in-plane anisotropy in any of the films was detected. The optical damage threshold of PBZT was measured to be ≳50 GW/cm2 for 30 ps pulses at 1.9 μm.

In addition to having attractive nonlinear-optic characteristics, KTP has promising electro-optic and dielectric properties that make it useful for various electro-optical applications, such as modulators and Q switches.1 We report an experimental study of a 4 × 8 × 4 mm hydrothermally grown KTP Pockels cell that uses the effective electro-optic coefficient rcl = r33 − (ni.n3)3r13 = 28 pm/v. Compensation of the static birefringence of KTP, when it is used as an amplitude modulator has been realized. Our investigations revealed that, unlike other electro-optic materials, KTP Pockels cells do not suffer from piezoelectrically induced parasitics (acoustic ringing). Because of this, we have been able to demonstrate stable high-repetition rate pulse slicing. The dynamic half-wave voltage is close to the static one (2.9 kV) and it is significantly lower than that of the commonly used LiNbO3 Pockels cell. An additional advantage of KTP over other Pockels-cell materials, such as KD*P and LiNbO3, is its high damage threshold. Therefore, KTP is an ideal material for intracavity electro-optic applications, in particular for high-peak power regenerative amplifiers operating at high-repetition rate.2 We have successfully studied this mode of operation, and our results will be discussed.