Fluorescence detection of flat transitional cell carcinoma after intravesical instillation of aminolevulinic acid.

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.

Fluorescence imaging of bladder cancer.

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.

In vivo fluorescence detection of human bladder carcinoma without sensitizing agents.

The diagnosis of transitional cell bladder carcinoma and especially carcinoma in situ of the bladder in spinal cord disordered persons is often made difficult by catheters, infections or stone-induced chronic inflammation. Fluorescence tagging of tumors by sensitizing agents such as hematoporphyrin derivatives enhances visualization but presents a number of drawbacks for the patients, even at low doses. We have developed a cystoscopic fiber optic instrument, based on a mercury arc lamp, for in vivo detection of human bladder carcinoma without sensitizing agents. The tissue autofluorescence upon UV excitation (365 nm) is detected and a demarcation contrast ratio for carcinoma in situ and transitional cell carcinoma of 2.6 and 3.2 respectively is obtained. This demarcation ratio is 60 percent higher than the contrast ratio obtained after photosensitizer injection. The integration of a reliable diagnostic method with a known efficient therapeutic technique (Nd YAG laser irridiation) opens the way for cost-effective preventive care of high-risk patients.

Self-focusing and self-defocusing by cascaded second-order effects in KTP.

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.

Picosecond laser system continuously tunable in the 0.6-4-microm range.

A continuously tunable picosecond laser system has been developed that operates in two modes: cw (100 MHz) and pulsed (10 Hz). In either mode the tuning range is approximately the same: from 0.6-4 microm. The pulse duration can also be selected: either short (typically 5 ps) or long (typically 50 ps) pulses are available. The average output power is in the milliwatt range for both repetition rates. In addition, both modes of operation are simultaneously available, and they are mutually synchronized. The system is based on a mode locked high power Nd:YLF laser which synchronously pumps a dye laser and seeds a Nd:YLF regenerative amplifier. Frequency mixing and parametric generation/amplification in KTiOPO(4) are used to obtain the large tunability.

Generation of tunable infrared picosecond pulses at 100 MHz by difference-frequency mixing in KTiOPO(4).

Picosecond pulses, tunable in the wavelength range of 1.2-4.5 microm, are generated at a 100-MHz repetition rate in KTiOPO(4) by difference-frequency mixing the output of a synchronously mode-locked dye laser and a Nd:YLF laser that pumps the dye laser. The typical average infrared output power is in the milliwatt range, which represents an improvement of several orders of magnitude over previously reported results using other nonlinear materials in a similar setup with Nd:YAG as the driving source. The high average power of this infrared source and its broad tunability make it an attractive alternative for mode-locked color-center lasers.

Thermal lensing measurement and compensation in a continuous-wave mode-locked Nd:YLF laser.

Thermal lensing effects in a cw-pumped Nd:YLF rod have been characterized, permitting the optimization of the laser resonator. In the mode-locking regime, a well-designed system generates an average output power similar to that of a typical Nd:YAG laser with, however, an increased stability and pulse durations that are significantly shorter.

Optimization of a cw mode-locked frequency-doubled Nd:LiYF(4) laser.

Several drawbacks of a cw-pumped mode-locked Nd:LiYF(4) laser are outlined, and it is shown how to overcome them. For the first time, attention is paid to thermally induced astigmatism and its compensation in a Nd:LiYF(4) rod. An optimized system generates an average output power similar to that of a typical Nd:YAG laser, however, with an increased stability and with pulse durations that are significantly shorter. The higher peak power in Nd:LiYF(4) can result in a higher conversion efficiency in a frequency-doubling process, provided the doubling crystal can handle the high average power. It will be demonstrated that a well-engineered Nd:LiYF(4) system may become the preferred choice for many applications, including seeding regenerative amplifiers and pumping synchronously mode-locked dye laser oscillators and amplifiers.

Energy band-gap dependence of two-photon absorption.

We present measurements of the two-photon absorption coefficients beta(2) of 10 different semiconductors having band-gap energies between 1.4 and 3.7 eV. We find that beta(2) varies as E(g)(-3), as predicted by theory. In addition, the absolute values of beta(2) agree with theory, which includes the effect of nonparabolic bands, the average difference being less than 26%. This agreement permits confident predictions of two-photon absorption coefficients of other materials at other wavelengths.

Tunable passive colliding-pulse mode locking in a linear dye laser.

We demonstrate the versatile operation of a linear femtosecond dye laser that terminates in an antiresonant ring for passive colliding-pulse mode locking. The system combines several advantages of a conventional ring laser with those of a linear laser and in addition offers the unique possibility of continuously tuning the pulse-repetition rate over a 1-GHz band. Moreover, the geometry allows a commercial linear laser to be mode locked easily without significant cavity changes.

Mode-locked laser oscillation using self-pumped phase-conjugate reflection.

Efficient phase conjugation of 40-psec Nd:YAG laser pulses in Eastman Kodak mode-locking dyes A 9740 and A 9860 has been obtained. Variation of the phase-conjugate reflectivity with pump intensity is quadratic, without saturation effects, and variation with dye concentration agrees with a simple analytical model. We have used this reflectivity to obtain self-sustained oscillation and mode locking of a novel self-pumped phase-conjugate laser resonator.