Onur Ferhanoglu

Clinical Ultrafast Laser Surgery: Recent Advances and Future Directions

Ultrafast pulsed lasers can be used to achieve remarkable precision during surgical ablation. Through nonlinear interactions with tissue, ultrafast lasers can provide a largely non-thermal mechanism of ablation and a unique ability to create targeted damage within bulk tissue. These advantages have made ultrafast lasers the ideal surgical tool for various novel applications in ophthalmology. Clinical adoption of ultrafast lasers in other surgical applications remains limited in part due to the lack of a means for fiber delivery of ultrafast laser pulses as a flexible, hand-held surgical endoscope. This review provides an overview of the recent advances in bringing this unique surgical tool into the clinic. We discuss fundamental mechanisms and limitations of ultrafast laser ablation, novel techniques for overcoming these limitations, the current state of clinical applications, and conclude with our recent efforts in developing fiber-coupled probes for flexible ultrafast laser surgery and imaging.

Optical design and imaging performance testing of a 9.6-mm diameter femtosecond laser microsurgery probe

We present a 9.6-mm fiber-coupled probe for femtosecond laser microsurgery and nonlinear imaging. Towards enabling clinical use, we successfully reduced the volume of our earlier 18-mm surgery probe by 5 times, while improving optical performance.

A 5-mm piezo-scanning fiber device for high speed ultrafast laser microsurgery.

Towards developing precise microsurgery tools for the clinic, we previously developed image-guided miniaturized devices using low repetition rate amplified ultrafast lasers for surgery. To improve the speed of tissue removal while reducing device diameter, here we present a new 5-mm diameter device that delivers high-repetition rate laser pulses for high speed ultrafast laser microsurgery. The device consists of an air-core photonic bandgap fiber (PBF) for the delivery of high energy pulses, a piezoelectric tube actuator for fiber scanning, and two aspheric lenses for focusing the light. Its inline optical architecture provides easy alignment and substantial size reduction to 5 mm diameter as compared to our previous MEMS-scanning devices while realizing improved intensity squared (two-photon) lateral and axial resolutions of 1.16 μm and 11.46 μm, respectively. Our study also sheds light on the maximum pulse energies that can be delivered through the air-core PBF and identifies cladding damage at the input facet of the fiber as the limiting factor. We have achieved a maximum energy delivery larger than 700 nJ at 92% coupling efficiency. An in depth analysis reveals how this value is greatly affected by possible slight misalignments of the beam during coupling and the measured small beam pointing fluctuations. In the absence of these imperfections, self-phase modulation becomes the limiting factor for the maximum energy delivery, setting the theoretical upper bound to near 2 μJ for a 1-m long, 7-μm, air-core PBF. Finally, the use of a 300 kHz repetition rate fiber laser enabled rapid ablation of 150 µm x 150 µm area within only 50 ms. Such ablation speeds can now allow the surgeons to translate the surgery device as fast as ~4 mm/s to continuously remove a thin layer of a 150 µm wide tissue. Thanks to a high optical transmission efficiency of the in-line optical architecture of the device and improved resolution, we could successfully perform ablation of scarred cheek pouch tissue, drilling through a thin slice. With further development, this device can serve as a precise and high speed ultrafast laser scalpel in the clinic.

Parameters affecting ultrafast laser microsurgery of subepithelial voids for scar treatment in vocal folds

Abstract. Toward developing a new method for restoring tissue viscoelasticity in scarred vocal folds, we previously proposed a method to localize biomaterials within subepithelial voids ablated using ultrafast laser pulses. The clinical implementation of this method necessitates the quantification of the laser parameters for ablating scarred tissue. Here, we present a comprehensive study of these parameters including ablation threshold and bubble lifetime in healthy and scarred tissues. We also present a new method for extracting tissue-specific ablation threshold and scattering lengths of different tissue layers. This method involves finding the ablation threshold at multiple depths and solving the equations based on Beer’s law of light attenuation for each depth to estimate the unknown parameters. Measured threshold fluences were 1.75  J/cm2 for vocal folds and 0.5  J/cm2 for cheek pouches for 3-ps, 776-nm laser pulses. Scarred pouches exhibited 30% lower threshold than healthy pouches, possibly due to the degraded mechanical properties of scarred collagen during wound healing. The analysis of tissue architecture indicated a direct correlation between the ablation threshold and tissue tensile strength and that the bubble lifetime is inversely related to tissue stiffness. Overall, this study sheds light on the required laser parameters for successful implementation of ultrafast laser ablation for phonosurgery.

Two-Wavelength Grating Interferometry for MEMS Sensors

Diffraction gratings integrated with micro-electro-mechanical-systems (MEMS) offer shot noise limited sub-nanometer displacement detection sensitivities but are limited in detection range for mechanical transducers. A two-wavelength readout method is developed that maintains high sensitivity while increasing the detection range, which is demonstrated using a MEMS spectrometer with integrated diffraction grating. The two-laser illumination extended the detection range from 105 nm to 1.7mum assuming the readout sensitivity is maintained at >50% of the maximum sensitivity.

Lamellar grating optimization for miniaturized fourier transform spectrometers

Microfabricated Lamellar grating interferometers (LGI) require fewer components compared to Michelson interferotemeters and offer compact and broadband Fourier transform spectrometers (FTS) with good spectral resolution, high speed and high efficiency. This study presents the fundamental equations that govern the performance and limitations of LGI based FTS systems. Simulations and experiments were conducted to demonstrate and explain the periodic nature of the interferogram envelope due to Talbot image formation. Simulations reveal that the grating period should be chosen large enough to avoid Talbot phase reversal at the expense of mixing of the diffraction orders at the detector. Optimal LGI grating period selection depends on a number of system parameters and requires compromises in spectral resolution and signal-to-bias ratio (SBR) of the interferogram within the spectral range of interest. New analytical equations are derived for spectral resolution and SBR of LGI based FTS systems.

Measuring Local RF Heating in MRI: Simulating Perfusion in a Perfusionless Phantom

To overcome conflicting methods of local RF heating measurements by proposing a simple technique for predicting in vivo temperature rise by using a gel phantom experiment.

Kagome fiber based ultrafast laser microsurgery probe delivering micro-Joule pulse energies

We present the development of a 5 mm, piezo-actuated, ultrafast laser scalpel for fast tissue microsurgery. Delivery of micro-Joules level energies to the tissue was made possible by a large, 31 μm, air-cored inhibited-coupling Kagome fiber. We overcome the fibers low NA by using lenses made of high refractive index ZnS, which produced an optimal focusing condition with 0.23 NA objective. The optical design achieved a focused laser spot size of 4.5 μm diameter covering a 75 × 75 μm2 scan area in a miniaturized setting. The probe could deliver the maximum available laser power, achieving an average fluence of 7.8 J/cm2 on the tissue surface at 62% transmission efficiency. Such fluences could produce uninterrupted, 40 μm deep cuts at translational speeds of up to 5 mm/s along the tissue. We predicted that the best combination of speed and coverage exists at 8 mm/s for our conditions. The onset of nonlinear absorption in ZnS, however, limited the probes energy delivery capabilities to 1.4 μJ for linear operation at 1.5 picosecond pulse-widths of our fiber laser. Alternatives like broadband CaF2 crystals should mitigate such nonlinear limiting behavior. Improved opto-mechanical design and appropriate material selection should allow substantially higher fluence delivery and propel such Kagome fiber-based scalpels towards clinical translation.

Sensitivity enhancement of grating interferometer based two-dimensional sensor arrays using two-wavelength readout

Diffraction gratings integrated with microelectromechanical systems (MEMS) sensors offer displacement measurements with subnanometer sensitivity. However, the sensitivity of the interferometric readout may drop significantly based on the gap between the grating and the reference surface. A two-wavelength (2-λ) readout method was previously tested using a single MEMS sensor for illustrating increased displacement measurement capability. This work demonstrates sensitivity enhancement on a sensor array with large scale parallelization (~20,000 sensors). The statistical representation, which is developed to model sensitivity enhancement within a grating based sensor array, is supported by experimental results using a thermal sensor array. In the experiments, two lasers at different wavelengths (633 and 650 nm) illuminate the thermal sensor array from the backside, time-sequentially. The diffracted first order light from the array is imaged onto a single CCD camera. The target scene is reconstructed by observing the change in the first diffracted order diffraction intensity for both wavelengths. Merging of the data from two measurements with two lasers was performed by taking the larger of the two CCD measurements with respect to the reference image for each sensor. ~30% increase in the average sensitivity was demonstrated for a 160×120 pixel IR sensor array. Proposed architecture is also applicable to a variety of sensing applications, such as parallel biosensing and atomic force microscopy, for improved displacement measurements and enhanced sensitivity.

Diffraction grating-based optical readout for thermal imaging

The thermal sensor system presented in this paper is based on the mechanical bending due to the incident IR radiation. A diffraction grating is embedded under each pixel to facilitate optical readout. Typically the first diffraction order is used to monitor the sub-micron mechanical displacement with sub-nanometer precision. In this work; two different optical readout systems based on diffraction gratings are analyzed. First setup employs a conventional 4f optical system. In this one-to-one imaging system, collimated light is propagated through a lens, filtered with an aperture and then imaged onto a CCD by a second lens. Second system is more compact to improve image quality and to reduce noise. This is achieved by using an off-axis converging laser beam illumination that forms the Fourier plane near the imaging lens. This approach has important advantages such as reducing number of optical components and minimizing the optical path. The system was optimized considering parameters such as laser converging angle, laser beam size at MEMS chip, and magnification of the imaging system.