In vivo hamster cheek pouch subepithelial ablation, biomaterial injection, and localization: pilot study.

SIGNIFICANCE: The creation of subepithelial voids within scarred vocal folds via ultrafast laser ablation may help in localization of injectable biomaterials toward a clinically viable therapy for vocal fold scarring. AIM: We aim to prove that subepithelial voids can be created in a live animal model and that the ablation process does not engender additional scar formation. We demonstrate localization and long-term retention of an injectable biomaterial within subepithelial voids. APPROACH: A benchtop nonlinear microscope was used to create subepithelial voids within healthy and scarred cheek pouches of four Syrian hamsters. A model biomaterial, polyethylene glycol tagged with rhodamine dye, was then injected into these voids using a custom injection setup. Follow-up imaging studies at 1- and 2-week time points were performed using the same benchtop nonlinear microscope. Subsequent histology assessed void morphology and biomaterial retention. RESULTS: Focused ultrashort pulses can be used to create large subepithelial voids in vivo. Our analysis suggests that the ablation process does not introduce any scar formation. Moreover, these studies indicate localization, and, more importantly, long-term retention of the model biomaterial injected into these voids. Both nonlinear microscopy and histological examination indicate the presence of biomaterial-filled voids in healthy and scarred cheek pouches 2 weeks postoperation. CONCLUSIONS: We successfully demonstrated subepithelial void formation, biomaterial injection, and biomaterial retention in a live animal model. This pilot study is an important step toward clinical acceptance of a new type of therapy for vocal fold scarring. Future long-term studies on large animals will utilize a miniaturized surgical probe to further assess the clinical viability of such a therapy.

Strong bonding of corneal incisions using a noncontact fiber-optic laser soldering method.

Suturing of corneal incisions requires significant skill. We demonstrate a noncontact method that will simplify the bonding process. 5-mm-long penetrating vertical and slanted incisions were made in corneas of eyes, extracted from dead piglets. A fiber-optic laser system was used for laser soldering of the incisions, under close temperature control, using albumin solder. The burst-pressure PB immediately after the soldering was found to be PB ≈ 92 and 875 mmHg, for vertical and slanted incisions, respectively. PB = 875 mmHg is an exceptionally high figure, ≈10 times the clinically acceptable value for sutured incisions. Laser soldering was then performed on penetrating incisions made in the corneas of live healthy piglets, of weight ≈10 Kg. After a healing period, the eyes were extracted, and the corneas were examined by histopathology and by optical coherence tomography. Our method immediately generated watertight and strong bonding without noticeable corneal shape distortion. These results would be beneficial for cataract surgery and for corneal transplantations. The fiber-optic system makes it much easier to bond corneal incisions. In the future, laser soldering could be automated and efficiently used by less experienced surgeons, thereby reducing the workload on the experienced ones.

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 fiber's 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 probe's 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.

High efficiency near diffraction-limited mid-infrared flat lenses based on metasurface reflectarrays.

We report the first demonstration of a mid-IR reflection-based flat lens with high efficiency and near diffraction-limited focusing. Focusing efficiency as high as 80%, in good agreement with simulations (83%), has been achieved at 45° incidence angle at λ = 4.6 µm. The off-axis geometry considerably simplifies the optical arrangement compared to the common geometry of normal incidence in reflection mode which requires beam splitters. Simulations show that the effects of incidence angle are small compared to parabolic mirrors with the same NA. The use of single-step photolithography allows large scale fabrication. Such a device is important in the development of compact telescopes, microscopes, and spectroscopic designs.

Design and fabrication of a miniature objective consisting of high refractive index zinc sulfide lenses for laser surgery.

A miniature laser ablation probe relying on an optical fiber to deliver light requires a high coupling efficiency objective with sufficient magnification in order to provide adequate power and field for surgery. A diffraction-limited optical design is presented that utilizes high refractive index zinc sulfide to meet specifications while reducing the miniature objective down to two lenses. The design has a hypercentric conjugate plane on the fiber side and is telecentric on the tissue end. Two versions of the objective were built on a diamond lathe-a traditional cylindrical design and a custom-tapered mount. Both received an antireflective coating. The objectives performed as designed in terms of observable resolution and field of view as measured by imaging a 1951 USAF resolution target. The slanted edge technique was used to find Strehl ratios of 0.75 and 0.78, respectively, indicating nearly diffraction-limited performance. Finally, preliminary ablation experiments indicated threshold fluence of gold film was comparable to similar reported probes.

Temperature-controlled laser-soldering system and its clinical application for bonding skin incisions.

Laser tissue soldering is a method of repairing incisions. It involves the application of a biological solder to the approximated edges of the incision and heating it with a laser beam. A pilot clinical study was carried out on 10 patients who underwent laparoscopic cholecystectomy. Of the four abdominal incisions in each patient, two were sutured and two were laser soldered. Cicatrization, esthetical appearance, degree of pain, and pruritus in the incisions were examined on postoperative days 1, 7, and 30. The soldered wounds were watertight and healed well, with no discharge from these wounds or infection. The total closure time was equal in both methods, but the net soldering time was much shorter than suturing. There was no difference between the two types of wound closure with respect to the pain and pruritus on a follow-up of one month. Esthetically, the soldered incisions were estimated as good as the sutured ones. The present study confirmed that temperature-controlled laser soldering of human skin incisions is clinically feasible, and the results obtained were at least equivalent to those of standard suturing.

Bonding surgical incisions using a temperature-controlled laser system based on a single infrared fiber.

ABSTRACT. Although there has been great interest in laser heating for bonding of surgical incisions in tissues, it has not gained wide acceptance by surgeons. We argue that the main obstacle has been the lack of temperature control, which may lead to a weak bonding. We previously developed a laser bonding system based on two infrared transmitting AgBrCl fibers, one for laser heating and one for temperature control. In view of the inherent limitations of such systems observed in many animal experiments, we developed an improved system based on a single infrared fiber. Besides the decreased dimensions, this system offers many advantages over the two-fiber system. It is less sensitive to accuracy of height and tilt of the fiber distal tip above the tissue, ensuring more accurate heating that can potentially lead to stronger bonding with minimal thermal damage. The system is successfully tested in the soldering of 15 corneal incisions, ex vivo. Histopathology shows little thermal damage and good wound apposition. The average burst pressure is 100±30 mm Hg. These findings indicate the usefulness of the system for ophthalmic surgery as well as other surgical procedures, including endoscopic and robotic surgery.

Temperature-controlled two-wavelength laser soldering of tissues.

BACKGROUND AND OBJECTIVE: Laser tissue soldering is a method for bonding of incisions in tissues. A biological solder is spread over the cut, laser radiation heats the solder and the underlying cut edges and the incision is bonded. This method offers many advantages over conventional techniques (e.g., sutures). Past researches have shown that laser soldering, using a single laser, does not provide sufficient strength for bonding of cuts in thick (>1 mm) tissues. This study introduces a novel method for laser soldering of thick tissues, under temperature control, using two lasers, emitting two different wavelengths. STUDY DESIGN/MATERIALS AND METHODS: An experimental system was built, using two lasers: (i) a CO(2) laser, whose radiation heated the upper surface of the tissue and (ii) a GaAs laser that heated an albumin layer under the tissue. An infrared fiber-optic radiometer monitored the temperature of the tissue. All three devices were connected to a computer that controlled the process. A computer simulation was written to optimize the system parameters. The system was tested on tissue phantoms, to validate the simulation and ensure that both the upper and lower sides of the cut were heated, and that the temperature could be controlled on both sides. The system was then used ex vivo to bond longitudinal cuts of lengths ∼12 mm in the esophagi of large farm pigs. RESULTS: The theoretical simulations showed a good stabilization of the temperatures at the upper and lower tissue surfaces at the target values. Experiments on tissue phantom showed a good agreement with these simulations. Incisions in esophagi, removed from large farm pigs, were then successfully bonded. The mean burst pressure was ∼3.6 m of water. CONCLUSIONS: This study demonstrated the capability of soldering cuts in thick tissues, paving the way for new types of surgical applications.

A multi-wavelength fiber-optic temperature-controlled laser soldering system for upper aerodigestive tract reconstruction: an animal model.

OBJECTIVE: Laser soldering of a thick multilayer organ using conventional CO(2) lasers is ineffective. The purpose of this work was to develop a method for bonding the multilayer tissue of the upper aerodigestive tracts (UADT) without the need of sutures or stapling. STUDY DESIGN: Animal model. SETTING: Academic research laboratory. SUBJECTS AND METHODS: The authors developed a multi-wavelength laser system, based on 2 fiber-optic lasers applied simultaneously. A highly absorbable CO(2) laser interacts with the muscular layer, and a nonabsorbable GaAs laser interacts with indocyanine-green solid albumin, placed between the mucosa and the muscular layer. The authors used an ex vivo porcine model to examine the capability of this system to effectively correct esophageal tears. RESULTS: The soldered esophagi burst pressure was >175 cm H(2)O (98% success rate) in 88 of the 90 experiments. A conventional CO(2) laser soldering resulted in insufficient bonding (mean burst pressure of 40 ± 7 cm H(2)O, n = 5), while the multi-wavelength laser system provided an ~9-fold tighter seal (359 ± 75.4 cm H(2)O, P < .0001, n = 15). Burst pressures after conventional suturing of the defect was significantly lower (106 ± 65.8 cm H(2)O, P < .001) than in the multi-wavelength laser system. CONCLUSIONS: Bonding of the UADT mucosa using a multi-wavelength, temperature-controlled laser soldering system can support significantly higher pressures then conventional CO(2) laser soldering and suture repair. The mean bonding pressure was 3.5-fold higher than the maximal swallowing pressure. Our findings provide a basis for implementation of new surgical tools for repair of esophageal perforations.