Jinze Qiu

Optimal Power Settings for Holmium:YAG Lithotripsy

PURPOSE We determined the optimal Ho:YAG lithotripsy power settings to achieve maximal fragmentation, minimal fragment size and minimal retropulsion. MATERIALS AND METHODS Stone phantoms were irradiated in water with a Ho:YAG laser using a 365 μm optical fiber. Six distinct power settings were tested, including 0.2 to 2.0 J and 10 to 40 Hz. For all cohorts 500 J total radiant energy were delivered. A seventh cohort (0.2 J 40 Hz) was tested post hoc to a total energy of 1,250 J. Two experimental conditions were tested, including with and without phantom stabilization. Total fragmentation, fragment size and retropulsion were characterized. In mechanism experiments using human calculi we measured crater volume by optical coherence tomography and pressure transients by needle hydrophone across similar power settings. RESULTS Without stabilization increased pulse energy settings produced increased total fragmentation and increased retropulsion (each p <0.0001). Fragment size was smallest for the 0.2 J cohorts (p <0.02). With stabilization increased pulse energy settings produced increased total fragmentation and increased retropulsion but also increased fragment size (each p <0.0001). Craters remained symmetrical and volume increased as pulse energy increased. Pressure transients remained modest at less than 30 bars even at 2.0 J pulse energy. CONCLUSIONS Holmium:YAG lithotripsy varies as pulse energy settings vary. At low pulse energy (0.2 J) less fragmentation and retropulsion occur and small fragments are produced. At high pulse energy (2.0 J) more fragmentation and retropulsion occur with larger fragments. Anti-retropulsion devices produce more efficient lithotripsy, particularly at high pulse energy. Optimal lithotripsy laser dosimetry depends on the desired outcome.

Depth-resolved blood oxygen saturation measurement by dual-wavelength photothermal (DWP) optical coherence tomography

Non-invasive depth-resolved measurement of hemoglobin oxygen saturation (SaO2) levels in discrete blood vessels may have implications for diagnosis and treatment of various pathologies. We introduce a novel Dual-Wavelength Photothermal (DWP) Optical Coherence Tomography (OCT) for non-invasive depth-resolved measurement of SaO2 levels in a blood vessel phantom. DWP OCT SaO2 is linearly correlated with blood-gas SaO2 measurements. We demonstrate 6.3% precision in SaO2 levels measured a phantom blood vessel using DWP-OCT with 800 and 765 nm excitation wavelengths. Sources of uncertainty in SaO2 levels measured with DWP-OCT are identified and characterized.

Comparison of pulsed photothermal radiometry, optical coherence tomography and ultrasound for melanoma thickness measurement in PDMS tissue phantoms

Melanoma accounts for 75% of all skin cancer deaths. Pulsed photothermal radiometry (PPTR), optical coherence tomography (OCT) and ultrasound (US) are non-invasive imaging techniques that may be used to measure melanoma thickness, thus, determining surgical margins. We constructed a series of PDMS tissue phantoms simulating melanomas of different thicknesses. PPTR, OCT and US measurements were recorded from PDMS tissue phantoms and results were compared in terms of axial imaging range, axial resolution and imaging time. A Monte Carlo simulation and three-dimensional heat transfer model was constructed to simulate PPTR measurement. Experimental results show that PPTR and US can provide a wide axial imaging range (75 μm-1.7 mm and 120-910 μm respectively) but poor axial resolution (75 and 120 μm respectively) in PDMS tissue phantoms, while OCT has the most superficial axial imaging range (14-450 μm) but highest axial resolution (14 μm). The Monte Carlo simulation and three-dimensional heat transfer model give good agreement with PPTR measurement. PPTR and US are suited to measure thicker melanoma lesions (>400 μm), while OCT is better to measure thin melanoma lesions (<400 μm).

Femtosecond laser lithotripsy: feasibility and ablation mechanism

Light emitted from a femtosecond laser is capable of plasma-induced ablation of various materials. We tested the feasibility of utilizing femtosecond-pulsed laser radiation (lambda=800 nm, 140 fs, 0.9 mJ/pulse) for ablation of urinary calculi. Ablation craters were observed in human calculi of greater than 90% calcium oxalate monohydrate (COM), cystine (CYST), or magnesium ammonium phosphate hexahydrate (MAPH). Largest crater volumes were achieved on CYST stones, among the most difficult stones to fragment using Holmium:YAG (Ho:YAG) lithotripsy. Diameter of debris was characterized using optical microscopy and found to be less than 20 microm, substantially smaller than that produced by long-pulsed Ho:YAG ablation. Stone retropulsion, monitored by a high-speed camera system with a spatial resolution of 15 microm, was negligible for stones with mass as small as 0.06 g. Peak shock wave pressures were less than 2 bars, measured by a polyvinylidene fluoride (PVDF) needle hydrophone. Ablation dynamics were visualized and characterized with pump-probe imaging and fast flash photography and correlated to shock wave pressures. Because femtosecond-pulsed laser ablates urinary calculi of soft and hard compositions, with micron-sized debris, negligible stone retropulsion, and small shock wave pressures, we conclude that the approach is a promising candidate technique for lithotripsy.

Combined two-photon luminescence microscopy and OCT for macrophage detection in the hypercholesterolemic rabbit aorta using plasmonic gold nanorose

The macrophage is an important early cellular marker related to risk of future rupture of atherosclerotic plaques. Two‐channel two‐photon luminescence (TPL) microscopy combined with optical coherence tomography (OCT) was used to detect, and further characterize the distribution of aorta‐based macrophages using plasmonic gold nanorose as an imaging contrast agent.

Dual-wavelength multifrequency photothermal wave imaging combined with optical coherence tomography for macrophage and lipid detection in atherosclerotic plaques using gold nanoparticles

The objective of this study was to assess the ability of combined photothermal wave (PTW) imaging and optical coherence tomography (OCT) to detect, and further characterize the distribution of macrophages (having taken up plasmonic gold nanorose as a contrast agent) and lipid deposits in atherosclerotic plaques. Aortas with atherosclerotic plaques were harvested from nine male New Zealand white rabbits divided into nanorose- and saline-injected groups and were imaged by dual-wavelength (800 and 1210 nm) multifrequency (0.1, 1 and 4 Hz) PTW imaging in combination with OCT. Amplitude PTW images suggest that lateral and depth distribution of nanorose-loaded macrophages (confirmed by two-photon luminescence microscopy and RAM-11 macrophage stain) and lipid deposits can be identified at selected modulation frequencies. Radiometric temperature increase and modulation amplitude of superficial nanoroses in response to 4 Hz laser irradiation (800 nm) were significantly higher than native plaque (P<0.001). Amplitude PTW images (4 Hz) were merged into a coregistered OCT image, suggesting that superficial nanorose-loaded macrophages are distributed at shoulders on the upstream side of atherosclerotic plaques (P<0.001) at edges of lipid deposits. Results suggest that combined PTW-OCT imaging can simultaneously reveal plaque structure and composition, permitting characterization of nanorose-loaded macrophages and lipid deposits in atherosclerotic plaques.

Comparison of fluoride and sapphire optical fibers for Er: YAG laser lithotripsy

The long-pulse (200-350 micros) Holmium: YAG (Ho: YAG) laser (lambda = 2.12 microm) is used extensively in urology for laser lithotripsy. The long-pulse Erbium: YAG (Er: YAG) laser (lambda = 2.94 microm) fragments urinary calculi up to 5 times more efficiently than the Ho: YAG laser, however, no optical fibers are available to transmit efficiently 2.94 microm laser light for laser lithotripsy. We report results of a study evaluating a fluoride glass fiber to transmit Er: YAG laser light for laser lithotripsy and compare to a sapphire fiber that provides good transmission of Er: YAG light at low irradiance. The fluoride fiber provides superior light transmission efficiency over the sapphire fiber at an Er: YAG wavelength (2.94 microm). The sapphire fiber provides a more durable and robust delivery waveguide than the fluoride fiber when ablating urinary calculi in contact mode. Results of our study suggest that further development to improve performance of fluoride fibers for laser lithotripsy is warranted.

Deep subsurface cavities in skin utilizing mechanical optical clearing and femtosecond laser ablation

High precision subsurface ablation can be produced in transparent materials using femtosecond laser pulses and multiphoton absorption. Light scattering limits application of the same technique to most biological tissues. Previously, subsurface ablation was demonstrated at superficial depths (50–250 µm) in highly scattering tissues including murine skin and human sclera. We report application of mechanical optical clearing to produce deeper subsurface femtosecond ablation in rodent skin. Ability to target deeper structures in skin using subsurface ablation may allow novel clinical applications for dermatological laser surgery.

Nanorose and lipid detection in atherosclerotic plaque using dual-wavelength photothermal wave imaging

Atherosclerosis and specifically rupture of vulnerable plaques account for 23% of all deaths worldwide, far surpassing both infectious diseases and cancer. In atherosclerosis, macrophages can infiltrate plaques which are often associated with lipid deposits. Photothermal wave imaging is based on the periodic thermal modulation of a sample using intensity modulated light. Intensity modulated light enters the sample and is absorbed by targeted chromophores and generates a periodic thermal modulation. We report use of photothermal wave imaging to visualize nanoroses (taken up by macrophages via endocytosis) and lipids in atherosclerotic plaques. Two excitation wavelengths were selected to image nanoroses (800 nm) and lipids (1210 nm). Atherosclerotic plaque in a rabbit abdominal artery was irradiated (800 nm and 1210 nm separately) at a frequency of 4 Hz to generate photothermal waves. The radiometric temperature at the tissue surface was recorded by an infrared (IR) camera over a 10 second time period at the frame rate of 25.6 Hz. Extraction of images (256 × 256 pixels) at various frequencies was performed by Fourier transform at each pixel. Frequency amplitude images were obtained corresponding to 800 nm and 1210 nm laser irradiation. Computed images suggest that the distributions of both nanorose and lipid can be identified in amplitude images at a frequency of 4 Hz. Nanoroses taken up by macrophages are distributed at the edges of lipid deposits. Observation of high concentration of nanoroses in atherosclerotic plaque confirms that nanoroses are present at locations associated with lipid deposits.

Near infrared femtosecond laser ablation of urinary calculi in water

Pulsed light emitted from a near infrared (λ=800nm) femtosecond laser is capable of plasma induced photodisruption of various materials. We used femtosecond laser pulses to ablate human urinary calculi. Femtosecond pulsed laser interaction with urinary calculi was investigated with various stone compositions, different incident fluences and number of applied pulses. Spectral-domain optical coherence tomography was used to image cross sections of ablation craters on the surface of urinary calculi. Our results indicate that femtosecond laser pulses can ablate various calculi compositions. Crater diameter and depth varies from tens of microns to several hundred microns when up to 1000 pulses were applied. Future studies are required to determine if pulsed near infrared femtosecond laser pulses can be applied clinically for lithotripsy of urinary calculi.