CARS-imaging guidance for fs-laser ablation precision surgery.

Due to ageing populations the number of tumors is increasing worldwide. Successful surgical treatment requires complete resection of tumors to reduce recurrence rates. To reach this goal, novel methods combining in vivo tumor and tumor margin detection with low invasive precision surgical tools are needed. Coherent anti-Stokes Raman scattering (CARS) imaging is a highly promising optical tool for visualizing tumors based on characteristic changes in tissue morphology and molecular composition, while fs-laser ablation is to date the most precise surgical tool established in ophthalmology. In this contribution, CARS imaging has been combined with fs-laser ablation as a new approach for image-guided precision surgery for the first time. CARS guided fs-ablation has been applied to ablate brain, liver, skin, muscular and vascular tissues with µm-precision using sub-100 fs pulses of µJ level. We demonstrate superior imaging performance and contrast as well as detection of tissue margins by coherent Raman microscopy in comparison to laser reflectance imaging. The combination of CARS-image-guided tissue ablation is a promising tool for minimally invasive surgeries particularly in the vicinity of functional structures in the future.

Head-To-Head Assessment of Diagnostic Performance of Testosterone Immunoassays in Patients With Polycystic Ovary Syndrome.

BACKGROUND: Determination of plasma testosterone is critical for the proper diagnosis of polycystic ovary syndrome (PCOS), but the interpretation of biochemical tests is hampered by inadequate specificity and precision of available immunoassays. We here compared the diagnostic performance of three testosterone immunoassays (Advia Centaur, Immulite 2000 XPi, Cobas e411) in PCOS patients using receiver operator characteristics curve analysis. METHODS AND RESULTS: Plasma levels of testosterone, androstendione, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, estradiol, progesterone, steroid hormone binding globulin, luteinizing hormone, and follicular stimulating hormone were determined in 188 patients with PCOS and 202 controls. Free testosterone (fT) levels and free androgen index (FAI) were calculated. Testosterone levels measured on Advia Centaur, Immulite 2000 XPi, and Cobas e411 showed clear linear relationship to each other. Testosterone measured with Advia Centaur showed discriminatory performance superior to Immulite 2000 XPi and Cobas e411. Calculation of fT or FAI improved the performance of Advia Centaur and Immulite 2000 XPi, which nevertheless performed better than Cobas e411. The performance of other parameters was inferior to that of testosterone, fT, and FAI. CONCLUSION: Present study documents striking differences between testosterone immunoassays with respect to their capacity to identify PCOS patients and favors the use of calculated parameters reflecting active testosterone in plasma.

A feasibility study on femtosecond laser thrombolysis.

OBJECTIVE: In this feasibility study, we investigate possible femtosecond laser thrombolysis. BACKGROUND DATA: Because of low pulse energies, femtosecond laser surgery inherently minimizes side effects on the surrounding tissue. Moreover, current femtosecond laser sources as well as fiber technology allow consideration of catheter-based treatments. METHODS: Two femtosecond laser systems (λ=800 nm, λ=1030 nm) along with a three dimensional (3D) scanner system (NA ~0.1) were used in this study. In vitro experiments were performed on porcine thrombi and blood vessels. Ablation thresholds were determined in air, by determining the pulse energy at which single shot ablation was visible under the optical microscope. Ablation rates were determined in physiological saline. Additionally, ablation of thrombi and blood vessels was monitored by means of a fiber spectrometer. RESULTS: Depending upon the scan velocity, typical ablation rates for thrombi were ~0.04 mm(3)/sec. Ablation thresholds of thrombi and blood vessels differ by factors of 3 and 1.5 at laser wavelengths of 800 and 1030 nm, respectively. At a distance of 5 mm above the surface, second harmonic generation was observed in blood vessels, but not within thrombi. CONCLUSIONS: The results show that a typical thrombus volume can be destroyed within a reasonable time frame. Because of the higher threshold difference of thrombi and blood vessels, the use of a laser wavelength of 800 nm is preferable. Furthermore, the detection of the second harmonic could provide a feedback mechanism to protect the vascular wall from mechanical and laser damage.

An in vitro study on focusing fs-laser pulses into ocular media for ophthalmic surgery.

BACKGROUND AND OBJECTIVE: To investigate femtosecond (fs)-laser patterns within ocular media for ophthalmic surgery. METHODS: Vitreous and crystalline lens tissue from porcine eyes were treated with 2-dimensional fs-laser patterns and inspected under the optical microscope. Time resolved pump-probe experiments were conducted on vitreous tissue and gelatin, which should act as a model for crystalline lens tissue. RESULTS: Within crystalline lens tissue, pulse overlap leads to the formation of large bubbles, which is caused by subsequent energy input from the surrounding plasma channel. This effect can be used for bubble size control. Vitreous tissue behaves similar to water under fs-laser treatment, but it still allows fs-laser cutting. CONCLUSION: Bubble size control by laser bursts may reduce optical side-effects of fs-laser treatment. Furthermore, fs-laser treatment could be used for vitreoretinal applications.

Optical side-effects of fs-laser treatment in refractive surgery investigated by means of a model eye.

Optical side-effects of fs-laser treatment in refractive surgery are investigated by means of a model eye. We show that rainbow glare is the predominant perturbation, which can be avoided by randomly distributing laser spots within the lens. For corneal applications such as fs-LASIK, even a regular grid with spot-to-spot distances of ~3 µm is sufficient to minimize rainbow glare perception. Contrast sensitivity is affected, when the lens is treated with large 3D-patterns.

Analysis of optical side-effects of fs-laser therapy in human presbyopic lens simulated with modified contact lenses.

BACKGROUND: In a single-blinded study, optical side-effects of a potential femtosecond (fs)-laser therapy in presbyopic human lenses were tested. Simulation of this therapy was carried out by applying fs-laser patterns into standard contact lenses (CL). METHODS: In the first part of the study, the influence of the numerical aperture on optical side-effects was investigated by comparing a typical fs-LASIK configuration to a fs-presbyopia treatment (n = 11). The second part focused on a possible improvement of visual performance by comparing a regular grid pattern to a randomly chosen spacing of the laser spots (n = 16). Visual acuity was measured with ETDRS charts, contrast sensitivity with F.A.C.T. charts and mesopic vision with Mesotest II. Forward scattered light was measured with the C-Quant (both instruments: Oculus Optikgeräte GmbH, Germany). A questionnaire detected subjective quality of vision. Differences between laser-treated and untreated CL and among the modifications were analyzed. RESULTS: The laser-treated and standard CL indicated no significant difference in visual acuity, contrast sensitivity and mesopic vision without glare. While wearing modified lenses with a regular grid, quality of vision decreased significantly by means of mesopic vision with glare and subjective straylight. These modifications also caused an impairment of subjective quality of vision. In contrast, there was no significant difference between the random pattern and standard CL. CONCLUSION: The increase of optical side-effects was reproducibly dependent on the geometry of the laser-structure. A randomized grid induced the least limitation. The study results are useful for planning possible laser-patterns in fs-laser therapy of the presbyopic lens.

Femtosecond laser treatment of the crystalline lens: a 1-year study of possible cataractogenesis in minipigs.

BACKGROUND: To investigate the long-term stability and possible cataractogenesis after femtosecond laser treatment of the crystalline lens. METHODS: The crystalline lenses of ten Göttingen minipigs® underwent femtosecond laser treatment. During a subsequent 1-year follow-up, the pigs were monitored by means of slit-lamp examination of the anterior segment and Scheimpflug imaging of the lens. RESULTS: No laser-induced cataractogenesis was observed during the 1-year follow-up. The laser pattern showed a stable appearance under all examination devices. CONCLUSION: Femtosecond laser treatment seems to be no trigger for cataract formation. Moreover, the long-term stability of the laser pattern makes it suitable for applications such as presbyopia treatment.