Jason R. Case

Fiber-optic manipulation of urinary stone phantoms using holmium:YAG and thulium fiber lasers

Abstract. Fiber-optic attraction of urinary stones during laser lithotripsy may be exploited to manipulate stone fragments inside the urinary tract without mechanical grasping tools, saving the urologist time and space in the ureteroscope working channel. We compare thulium fiber laser (TFL) high pulse rate/low pulse energy operation to conventional holmium:YAG low pulse rate/high pulse energy operation for fiber-optic suctioning of plaster-of-paris (PoP) stone phantoms. A TFL (wavelength of 1908 nm, pulse energy of 35 mJ, pulse duration of 500 μs, and pulse rate of 10 to 350 Hz) and a holmium laser (wavelength of 2120 nm, pulse energy of 35 to 360 mJ, pulse duration of 300 μs, and pulse rate of 20 Hz) were tested using 270-μm-core optical fibers. A peak drag speed of ∼2.5  mm/s was measured for both TFL (35 mJ and 150 to 250 Hz) and holmium laser (210 mJ and 20 Hz). Particle image velocimetry and thermal imaging were used to track water flow for all parameters. Fiber-optic suctioning of urinary stone phantoms is feasible. TFL operation at high pulse rates/low pulse energies is preferable to holmium operation at low pulse rates/high pulse energies for rapid and smooth stone pulling. With further development, this novel technique may be useful for manipulating stone fragments in the urinary tract.

Using LED sources to selectively heat blood for enhanced mid-IR imaging of vascular structures

We present experimental results that demonstrate the ability of mid-IR imaging to map blood vessels 0.75cm deep in muscle tissue. Selective heating of the blood with LED sources provides the contrast in these mid-IR images.

Noninvasive enhanced mid-IR imaging of breast cancer development in vivo

Abstract. Lumpectomy coupled with radiation therapy and/or chemotherapy is commonly used to treat breast cancer patients. We are developing an enhanced thermal IR imaging technique that has the potential to provide real-time imaging to guide tissue excision during a lumpectomy by delineating tumor margins. This enhanced thermal imaging method is a combination of IR imaging (8 to 10  μm) and selective heating of blood (∼0.5°C) relative to surrounding water-rich tissue using LED sources at low powers. Postacquisition processing of these images highlights temporal changes in temperature and the presence of vascular structures. In this study, fluorescent, standard thermal, and enhanced thermal imaging modalities, as well as physical caliper measurements, were used to monitor breast cancer tumor volumes over a 30-day study period in 19 mice implanted with 4T1-RFP tumor cells. Tumor volumes calculated from fluorescent imaging follow an exponential growth curve for the first 22 days of the study. Cell necrosis affected the tumor volume estimates based on the fluorescent images after day 22. The tumor volumes estimated from enhanced thermal imaging, standard thermal imaging, and caliper measurements all show exponential growth over the entire study period. A strong correlation was found between tumor volumes estimated using fluorescent imaging, standard IR imaging, and caliper measurements with enhanced thermal imaging, indicating that enhanced thermal imaging monitors tumor growth. Further, the enhanced IR images reveal a corona of bright emission along the edges of the tumor masses associated with the tumor margin. In the future, this IR technique might be used to estimate tumor margins in real time during surgical procedures.

Characterization of random anti-reflecting surface structures and their polarization response at off-normal angles of incidence

Random anti-reflecting surface structures (rARSS) are fabricated on fused silica substrates, for broadband and omnidirectional applications. These structures are fabricated using dry reactive ion etching. Etching parameters, such as RF power, flow ratio of etching gases, and etching time, determine the surface morphology of the random structures. The surface roughness of the random structures induces a gradient index transition over the boundary, yielding transmission enhancement compared to plain polished fused silica. We present variable angle-of-incidence (AOI) and polarization transmission measurements, through rARSS on fused silica at 633nm, and compare the results with conventional AR coating simulations. We tested a number of different samples, all with optimized transmission near 633nm, but different surface characteristics, and found that rARSS have structural characteristics which affect transmission at non-normal angles of incidence. We show that rARSS on fused silica substrates outperform conventional BBAR and SLAR thin film coatings in transmission enhancement, for incident light with AOI from 0° to 55°. We measured rARSS with zero degree of polarization in transmission, for AOI ranging from 0° to 60° in certain cases. A figure of merit that includes both the transmission degree of polarization and transmission enhancement is formulated in order to quantify rARSS performance for both effects. We found that rARSS measured performance is better than SLAR and BBAR, for transmission with AOI greater than 30° and up to 70°, especially for p-polarized incident light, which is the stricter criterion. Applications requiring polarization insensitivity and AR performance can be positively impacted by these surface structures.

Entry and exit facet laser damage of optical windows with random antireflective surface structures

Nanosecond duration, high intensity and high average power laser pulses induce damage on uncoated optics, due to localized field enhancement at the exit surface of the components. Anti-reflection (AR) coated optics, due to their (multiple) thin film boundaries, have similar field enhancement regions, which lead to laser damage on both entry and exit sides. Nano-scale structured optical interfaces with AR performance (ARSS) have been widely demonstrated, and found to have higher laser damage resistance than conventional AR coatings. Comprehensive tests of optical entry and exit structured-surface laser damage using nanosecond pulses for ARSS are not widely available. We measured the laser damage of random anti-reflective surface structures (rARSS), on planar, optical quality, fused silica substrates, using single 6-8ns duration pulses at 1064 nm wavelength. The single-sided rARSS substrates were optimized for Fresnel reflectance suppression at 1064 nm, and the measured transmittance at normal incidence was increased by 3.2%, with a possible theoretical maximum of 3.5%. The high energy laser beam was focused to increase the incident intensity, in order to probe values above and below the damage thresholds reported in the literature. The source laser Q-switch durations were used to directly control incident fluence. Multiple locations were tested for each Q-switch setting, to build a statistical relationship between the fluence and damaging events. Single-sided, AR random surface structured substrates were tested, using entry and exit side orientations, to determine any effects the random structures may have in the damage induced by the field enhancement on the exit side. We found that the AR randomly structured surfaces have a higher resistance, to the onset of laser damage, when they are located at the entry (structured) side of the substrates. In comparison, when the same AR random structures are in the beam exit side of the substrates, the onset of laser damage occurs at lower fluence values. All tests resulting in damage of the optical-quality polished fused silica substrates, and those with the structures on the exit side of the samples, are ballistic in nature, showing surface cracks and outward-directed debris craters, all occurring at the beam exit facet. Of interest are the results from tests completed with the rARSS located on the beam entry side; the damage caused by these tests was not typically ballistic in nature (inward directed craters) and occurred on the structured side of the samples.

Heat as a contrast agent to enhance thermal imaging of blood vessels

In this study we test the feasibility of using low-cost LEDs to selectivity heat blood for enhanced thermal imaging of vascular structures. Applications of this new imaging technique include mapping blood vessels during surgeries such as tumor removal and vascular repair. In addition, this technique could potentially be used to determine the location of increased vascular density, and thus breast cancer tumors. Porcine blood, skeletal muscle, skin and fat were illuminated with LEDs that emit at 405 nm and 530 nm (near the blood absorption peaks) and the increase in temperature as a function of time was recorded using a thermal camera. In the studies with the 530 nm LED, blood heated more than other tissue types and the heating rate for the blood was significantly faster than other tissues. Illumination of blood with the 530 nm LED at low powers (tissue irradiance <500 mW/cm2) will selectively heat blood with no damage to surrounding tissue. Illumination with the 405 nm LED produced large temperature changes (up to 15°C) at low LED powers (tissue irradiance <500 mW/cm2). The heating and heating rates measured with this LED were higher than those measured for the 530nm LED. However, blood, skin and fat showed comparable amounts of heating and heating rates. The amount of heating in muscle tissue was dependent on the skeletal muscle type, but most samples showed heating comparable to or larger than blood. This LED was not effective at selectively heating blood relative to the other tissue types. The results of the preliminary studies suggest that the best contrast can be achieved with pulsed 530 nm LED illumination and an image analysis method that highlights rapid changes in temperature.

Fiber optic suctioning of urinary stone phantoms during laser lithotripsy

Fiber optic attraction of urinary stones during laser lithotripsy has been previously observed, and this phenomenon may potentially be exploited to pull stones inside the urinary tract without mechanical grasping tools, thus saving the urologist valuable time and space in the ureteroscope’s single working channel. In this study, Thulium fiber laser (TFL) high-pulse-rate/low-pulse-energy operation and Holmium:YAG low-pulse-rate/high-pulse-energy operation are compared for fiber optic “suctioning” of Plaster-of-Paris stone phantoms. A TFL with wavelength of 1908 nm, pulse energy of 35 mJ, pulse duration of 500 μs, and pulse rate of 10-350 Hz, and Holmium laser with wavelength of 2120 nm, pulse energy of 35-360 mJ, pulse duration of 300 μs, and pulse rate of 20 Hz were tested using 270-μm-core fibers. A peak “pull” speed of ~ 2.5 mm/s was measured for both TFL (35 mJ and 150-250 Hz) and Holmium laser (210 mJ and 20 Hz). Particle image velocimetry and thermal imaging were used to track water flow for all parameters. Fiber optic suctioning of urinary stone phantoms is feasible for both lasers. However, TFL operation at high-pulse-rates/low-pulse-energies provides faster, smoother stone pulling than Holmium operation at low-pulserates/ high-pulse-energies. After further study, this method may be used to manipulate urinary stones in the clinic.

Single Molecule Chemical Reactions within Femtoliter Volume Containers

We create and observe controlled single molecule chemical reactions within femtoliter containers called hydrosomes. Hydrosomes are stable aqueous nanodroplets suspended in a low index-of-refraction fluorocarbon medium. The index of refraction mismatch between the nanodroplets and fluorocarbon is such that individual hydrosomes can be optically trapped. Using optical tweezers, the hydrosomes are held within a confocal observation volume, and we interrogate the encapsulated molecule by means of fluorescence excitation. Hydrosome encapsulation has an important advantage over liposome encapsulation techniques in that hydrosomes fuse on contact, thereby mixing the encapsulated components. Optical tweezers are used to manipulate the hydrosomes and to induce a fusion event. Custom fabricated microfluidic channels are used to sort the hydrosomes containing different molecule species. We demonstrate the use of hydrosomes as microreactors by fusing two hydrosomes, each containing a complementary single strand of DNA, and observing the subsequent hybridization via FRET (Fluorescence Resonance Energy Transfer).