Toward finding the best machine learning classifier for LIBS-based tissue differentiation

Lasers have become generally accepted devices in surgical applications, especially as a cutting tool, for cutting both soft and hard tissues including bone (laserosteotomy). It has been shown that applying lasers in osteotomy have important advantages over mechanical tools, including faster healing, more precise cut and functional cutting geometries as well as less trauma [1, 2]. However, the ability of detecting the type of tissue that being cut during surgery can extend the application and safety of laserosteotomes in practice. As a result, the laser could be stopped automatically in case of cutting a tissue that should be preserved. Authors have previously demonstrated that laser-induced breakdown spectroscopy (LIBS) is a potential candidate to differentiate surrounding soft tissue from the bone in ex vivo condition [3]. In the current study, different machine learning classifiers were examined to find the best possible method to differentiate bone from soft tissues based on LIBS data. These methods include decision tree, K Nearest Neighbor (KNN), linear and quadratic Support Vector Machine (SVM) as well as linear and quadratic discriminant analysis. All classifiers were applied on LIBS data obtained from bone, muscle, and fat tissues using an Nd:YAG laser and an Echelle spectrometer. Confusion matrix and Receiver Operating Characteristic (ROC) curve were obtained for each classifier afterwards. Moreover, in order to estimate the model's performance on new data and also to protect the model against overfitting, cross-validation was applied. All mentioned examinations were performed with MATLAB (R2017b)

All fiber-based LIBS feedback system for endoscopic laser surgery

There has been a particular interest to use laser-induced breakdown spectroscopy (LIBS) as a feedback mechanism for laser surgeries in the past decade 1-6. However, none of the mentioned setups 1-6 is suitable for endoscopic applications due to their bulky free-space configurations. In minimally nvasive surgeries, the major challenge is to integrate ablating laser waveguides and also all sensors inside the narrow channel of the endoscope. In this paper, we present a LIBS setup, which uses a multimode silica fiber for both delivering the inducing laser pulse and collecting the plasma emission light through the endoscope. The fiber-based LIBS setup consists of a frequency-doubled Q-switched Nd:YAG laser (Q-smart 450, Quantel, 532 nm, 5 ns, 60 mJ, 1 Hz), a cleaved large-core silica fiber (1.5 m-long, 1500 um-core, 0.39-NA, 70 mm-bending radius), and an in-house Echelle spectrometer (See Fig. 1). A 75 cm plano-convex laser line lens (Thorlabs, LA1978-YAG) was used to couple the laser beam into a multimode step-index silica fiber. Such a long focal length convex lens was used to avoid breakdown process in air. Moreover, the input face of the fiber was placed at 1 cm behind the focal point to maintain the laser power density below the damage threshold of the fiber. Two tight focusing lenses were placed in front of the fiber end face to collimate the highly divergent laser beam and refocus it onto the sample surface. The light emitted from the microplasma generated at the surface of the sample (bone and its surrounding soft tissues) was collected by the same optics and directed to the spectrometer for characterization. The performance of the developed fiber-based LIBS setup for classification of different tissues has been investigated and compared with the free-space LIBS. The feedback provided by this fiber-based LIBS setup can be used in minimally invasive laserosteotomies in order to stop the laser before causing any collateral damage to surrounding tissues. References [1] F. Yueh, H. Zheng, J.P. Singh, S. Burgess, Preliminary evaluation of laser-induced breakdown spectroscopy for tissue classification, Spectrochim. Acta B 64 (2009) 1059-1067. [2] R. Kanawade, F. Mehari, C. Knipfer, M. Rohde, K. Tangermann-Gerk, et al., Pilot study of laser induced breakdown spectroscopy for tissue differentiation by monitoring the plume created during laser surgery-An approach on a feedback Laser control mechanism, Spectrochim. Acta B 87 (2013) 175-181. [3] K. Henn, G.G. Gubaidullin, J. Bongartz, J. Wahrburg, H. Roth, et al., A spectroscopic approach to monitor the cut processing in pulsed laser osteotomy, Lasers Med. Sci. 28 (2013) 87-92. [4] H. Huang, L.-M. Yang, S. Bai, J. Liu, Smart surgical tool, J. Biomed. Opt. 20 (2015) 028001. [5] R.K. Gill, Z.J. Smith, C. Lee, S. Wachsmann-Hogiu, The effects of laser repetition rate on femtosecond laser ablation of dry bone: a thermal and LIBS study, J. Biophotonics 9 (2016) 171-180. [6] H. Abbasi, G. Rauter, R. Guzman, P.C. Cattin, A. Zam, Laser-induced breakdown spectroscopy as a potential tool for auto carbonization detection in laserosteotomy, J. Biomed. Opt. 23 (2018) 071206

Design and implementation of a compact high-throughput echelle spectrometer using off-the-shelf off-axis parabolic mirrors for analysis of biological samples by LIBS (Conference Presentation)

This work presents the development of an Echelle spectrometer that is optimized for the characterization of laser-driven plasma emission of biological samples for application in smart laser surgery systems. Despite the compact (portable) and cost-efficient design of the developed spectrometer, it allows analyzing the spectrum of a plasma emitted from bone, and its surrounding soft tissues (bone marrow, muscle, and fat) in nearly the same way as a full-sized Echelle spectrometer as used in commercial laser-induced breakdown spectroscopy (LIBS) systems. Most of the commercially available Echelle spectrometers on the market use a long focal length on-axis mirror to have a reasonable F number (which defines the optical throughput of the system) and low aberration. While a long focal length requires less tilting of the mirror than a shorter focal length (the higher the tilt angle, the higher the aberration), a long focal length increases the system size and decreases sensitivity (i.e., less optical throughput). In this work, a parabolic 90o off-axis mirror with a focal length of 152.4 mm and a diameter of 50.8 mm, which leads to an F-number of 3, has been used. This low F-number provides a high optical throughput compared to other similar commercial Echelle spectrometers with F-numbers of 10 or more [1-5]. Since most of the important peaks in biological tissue are in the interval of 240 to 840 nm [6], the design was done by using off-the-shelf aluminum mirrors with a UV-enhanced coating for both collimating and focusing purposes to cover this range with sub-Angstrom resolution. Both collimating and focusing mirrors were chosen with the same radius of curvature and declination angle (opposite direction) to cancel the coma. In this antiparallel configuration, the second parabolic mirror largely eliminates the aberrations from the first one. Moreover, we positioned the Echelle grating under the condition of quasi-Littrow design to have high diffraction efficiency with an off-axis angle in the horizontal plane. A ruled reflection grating with dispersion perpendicular to that of the Echelle grating was utilized as a cross dispenser (order separator) after the Echelle grating to distinguish the overlapping diffraction harmonics. The spectrometer has been connected to a gated ICCD to measure time-resolved spectra. The developed spectrometer was installed on a 3-tier utility cart, the inducing laser (Q-switched Nd:YAG) for LIBS was placed on the middle tier, and the last tier was dedicated for calibration instruments (a NIST traceable balanced Deuterium-Halogen light source for intensity calibration, and some gas/vapor spectral lamps including Mercury-Argon, Argon, Neon, and Krypton for wavelength calibration). The portability feature of this LIBS setup provides a remarkable value for testing and characterizing different biological samples on-site. This is a great capability especially if the target sample has the potential of being contagious. This setup is meant to be used for so-called smart laser osteotomies, i.e., the osteotome will be able to identify the type of the tissue being cut through the feedback provided by LIBS [6-8]

Highly flexible fiber delivery of a high peak power nanosecond Nd:YAG laser beam for flexiscopic applications

Minimally invasive laser surgeries that require the use of a flexible endoscope (flexiscope) could benefit from high-energy nanosecond laser pulses delivered through fibers for real-time tissue characterization and phenotyping. The damage threshold of the fiber's glass material limits the maximum amount of deliverable peak power. To transmit high-energy pulses without damaging the fiber material, large-diameter fibers are typically used, leading to a limited bending radius. Moreover, in a large-core fiber, self-focusing can damage the fiber even if the tip remains intact. In this work, we tested a fused-end fiber bundle combined with a beam shaper capable of delivering more than 20 MW (>100 mJ/5 ns). The fiber bundle was tested over more than eight hours of operation, with different bending radiuses down to 15 mm. The results demonstrate, to the best of our knowledge, the highest peak power delivered through a flexible fiber, for a frequency-doubled Q-switched Nd:YAG laser

Prevention of mammary carcinogenesis by short-term estrogen and progestin treatments

INTRODUCTION: Women who have undergone a full-term pregnancy before the age of 20 have one-half the risk of developing breast cancer compared with women who have never gone through a full-term pregnancy. This protective effect is observed universally among women of all ethnic groups. Parity in rats and mice also protects them against chemically induced mammary carcinogenesis. METHODS: Seven-week-old virgin Lewis rats were given N-methyl-N-nitrosourea. Two weeks later the rats were treated with natural or synthetic estrogens and progestins for 7–21 days by subcutaneous implantation of silastic capsules. RESULTS: In our current experiment, we demonstrate that short-term sustained exposure to natural or synthetic estrogens along with progestins is effective in preventing mammary carcinogenesis in rats. Treatment with 30 mg estriol plus 30 mg progesterone for 3 weeks significantly reduced the incidence of mammary cancer. Short-term exposure to ethynyl estradiol plus megesterol acetate or norethindrone was effective in decreasing the incidence of mammary cancers. Tamoxifen plus progesterone treatment for 3 weeks was able to confer only a transient protection from mammary carcinogenesis, while 2-methoxy estradiol plus progesterone was effective in conferring protection against mammary cancers. CONCLUSIONS: The data obtained in the present study demonstrate that, in nulliparous rats, long-term protection against mammary carcinogenesis can be achieved by short-term treatments with natural or synthetic estrogen and progesterone combinations

Plasma plume expansion dynamics in nanosecond Nd:YAG laserosteotome

In minimal invasive laser osteotomy precise information about the ablation process can be obtained with LIBS in order to avoid carbonization, or cutting of wrong types of tissue. Therefore, the collecting fiber for LIBS needs to be optimally placed in narrow cavities in the endoscope. To determine this optimal placement, the plasma plume expansion dynamics in ablation of bone tissue by the second harmonic of a nanosecond Nd:YAG laser at 532 nm has been studied. The laserinduced plasma plume was monitored in different time delays, from one nanosecond up to one hundred microseconds. Measurements were performed using high-speed gated illumination imaging. The expansion features were studied using illumination of the overall visible emission by using a gated intensified charged coupled device (ICCD). The camera was capable of having a minimum gate width (Optical FWHM) of 3 ns and the timing resolution (minimum temporal shift of the gate) of 10 ps. The imaging data were used to generate position-time data of the luminous plasma-front. Moreover, the velocity of the plasma plume expansion was studied based on the time-resolved intensity data. By knowing the plasma plume profile over time, the optimum position (axial distance from the laser spot) of the collecting fiber and optimal time delay (to have the best signal to noise ratio) in spatial-resolved and time-resolved laser-induced breakdown spectroscopy (LIBS) can be determined. Additionally, the function of plasma plume expansion could be used to study the shock wave of the plasma plume

Differentiation of femur bone from surrounding soft tissue using laserinduced breakdown spectroscopy as a feedback system for Smart Laserosteotomy

Although laserosteotomes have become generally accepted devices in surgical applications, they still suffer from a lack of information about the type of tissue currently being ablated; as a result, critical structures of the body under or near the focal spot of the laser beam are prone to inadvertent ablation. The lack of information about the properties of the ablated tissue can be solved by connecting the laserosteotome to an optical detection setup which can differentiate various types of tissues, especially bone from connective soft tissues. This study examines the applicability of laser-induced breakdown spectroscopy (LIBS) as a potential technique to differentiate bone from surrounding soft tissue (fat and muscle). In this experiment, fresh porcine femur bone, muscle, and fat were used as hard and soft tissue samples. The beam of a nanosecond frequency-doubled Nd:YAG laser was used to ablate the tissue samples and generate the plasma. The plasma light emitted from the ablated spot, which corresponds to the recombination spectra of ionized atoms and molecules, was gathered with a collection optic (including a reflective light collector and a fiber optic) and sent to an Echelle spectrometer for resolving the atomic composition of the ablated sample. Afterwards, Discriminant Function Analysis (DFA) based on the ratio of the intensity of selected peak pairs was performed to classify three sample groups (bone, muscle, and fat). Lastly, the sensitivity, specificity, and accuracy of the proposed method were calculated. Sensitivity and specificity of 100 % and 99 % were achieved, respectively, to differentiate bone from surrounding soft tissue

Laser-induced breakdown spectroscopy as a potential tool for autocarbonization detection in laserosteotomy

In laserosteotomy, it is vital to avoid thermal damage of the surrounding tissue, such as carbonization, since carbonization does not only deteriorate the ablation efficiency but also prolongs the healing process. The state-of-the-art method to avoid carbonization is irrigation systems; however, it is difficult to determine the desired flow rate of the air and cooling water based on previous experiments without online monitoring of the bone surface. Lack of such feedback during the ablation process can cause carbonization in case of a possible error in the irrigation system or slow down the cutting process when irrigating with too much cooling water. The aim of this paper is to examine laser-induced breakdown spectroscopy as a potential tool for autocarbonization detection in laserosteotomy. By monitoring the laser-driven plasma generated during nanosecond pulse ablation of porcine bone samples, carbonization is hypothesized to be detectable. For this, the collected spectra were analyzed based on variation of a specific pair of emission line ratios in both groups of samples: normal and carbonized bone. The results confirmed a high accuracy of over 95% in classifying normal and carbonized bone

Combined Nd:YAG and Er:YAG lasers for real-time closed-loop tissue-specific laser osteotomy

A novel real-time and non-destructive method for differentiating soft from hard tissue in laser osteotomy has been introduced and tested in a closed-loop fashion. Two laser beams were combined: a low energy frequency-doubled nanosecond Nd:YAG for detecting the type of tissue, and a high energy microsecond Er:YAG for ablating bone. The working principle is based on adjusting the energy of the Nd:YAG laser until it is low enough to create a microplasma in the hard tissue only (different energies are required to create plasma in different tissue types). Analyzing the light emitted from the generated microplasma enables real-time feedback to a shutter that prevents the Er:YAG laser from ablating the soft tissue

Effect of Cooling Water on Ablation in Er:YAG Laserosteotome of Hard Bone

The aim of this paper is to examine the effect of pig bone immersion in different levels of cooling water during laser ablation with a Er:YAG laser. The laser worked at 2940 nm wavelength and 10 Hz repetition rate in microseconds pulse duration regime. The bone was immersed in different levels of cooling water in a sample container for preventing carbonization. The bone samples were ablated with fixed deposited energy to investigate at which water level Er:YAG lasers start ablating bone through a layer of water. Results showed that the maximum level of water that laser can pass through to start the ablation nonlinearly depends on pulse energy