In vivo harmonic generation microscopy (HGM) has been applied successfully in healthy human skin and can achieve a submicron resolution, similar to histopathologic examination, even at a penetration depth up to 270 μm. This study aims to investigate the clinical applicability of HGM imaging for differential diagnosis of nonmelanoma pigmented skin lesions. A total of 42 pigmented skin tumors, including pigmented basal cell carcinoma, melanocytic nevus, and seborrheic keratosis were evaluated by HGM ex vivo or in vivo. Based on the standard histopathologic characteristics, we established the corresponding HGM imaging criteria for each pigmented tumor. Diagnostic performance of HGM for differentiating nonmelanoma pigmented skin tumors was evaluated through the observers’ direct general assessment (overall evaluation) or the presence of two imaging criteria with the highest sensitivity and specificity (major criteria evaluation). Our results show that, based on the direct general assessment, the sensitivity is 92% [95% confidence interval (CI): 67 to 97%] and the specificity is 96% (95% CI: 83 to 99%); by major criteria evaluation, 94% sensitivity (95% CI: 70 to 99%) and 100% specificity (95% CI: 87 to 100%) are achieved. Our study indicates that HGM serves as a promising histopathological examination tool for noninvasive differential diagnostics of nonmelanoma pigmented skin tumors.
Oral cancer is one of the most frequently diagnosed human cancers and leading causes of cancer death all over the world, but the prognosis and overall survival rate are still poor because of delay in diagnosis and lack of early intervention. The failure of early diagnosis is due to insufficiency of proper diagnostic and screening tools and most patients are reluctant to undergo biopsy. Optical virtual biopsy techniques, for imaging cells and tissues at microscopic details capable of differentiating benign from malignant lesions non-invasively, are thus highly desirable. A novel multi-harmonic generation microscope, excited by a 1260 nm Cr:forsterite laser, with second and third harmonic signals demonstrating collagen fiber distribution and cell morphology in a sub-micron resolution, was developed for clinical use. To achieve invivo observation inside the human oral cavity, a small objective probe with a suction capability was carefully designed for patients’ comfort and stability. By remotely changing its focus point, the same objective can image the mucosa surface with a low magnification, illuminated by side light-emitting diodes, with a charge-coupled device (CCD) for site location selection before the harmonic generation biopsy was applied. Furthermore, the slow galvanometer mirror and the fast resonant mirror provide a 30 fps frame rate for high-speed real-time observation and the z-motor of this system is triggered at the same rate to provide fast 3D scanning, again ensuring patients’ comfort. Focusing on the special cytological and morphological changes of the oral epithelial cells, our preliminary result disclosed excellent consistency with traditional histopathology studies.
In this work, we investigated the principle of the two-photon absorption (TPA) detection with a loss modulation technique, and first demonstrated the existence of two-photon photoacoustics ultrasound excited by a femtosecond high repetition rate laser. By using the AO modulation with different modulation frequencies, we successfully create the beating of the light signal when the two arms of the beams are both spatial and temporal overlapping. The pulse train of the femtosecond laser causes the narrow band excitation, providing the frequency selectivity and sensitivity. Moreover, the pulse energy is no more than 15nJ/pulse, which is at least 3 orders of magnitude smaller than that of the nanosecond laser, and therefore prevents the thermal damage of the sample. With the help of lock-in detection and a low noise amplifier, we can separate the signal of two-photon absorption from one-photon absorption. We used an ultrasonic transducer to detect the response of the sample, and verified the existence of the two-photon photoacoustics ultrasound generating by the femtosecond laser. Several contrast agents, such as the black carbon solution, the fluorescence dye and the nano-particles, were used in the experiment. In the end, we demonstrated the application, two photo-acoustic imaging, which provides the high spatial resolution (<10μm) and large penetration depth (~1mm), to the simulated biological tissue. This is a milestone to develop the two-photon photoacoustics microscopy, which, in principle, has the great potential to achieve the in vitro and in vivo high resolution deep tissue imaging.
In this paper, we demonstrated two types of novel displays: light waveguide display and arrayed waveguide display. In
the light waveguide display, light emitted from commercial LEDs propagates in a glass planar waveguide with a polymer
dispersed liquid crystal (PDLC) upper layer. When the voltage is off, light would be partially scattered via PDLC and
that pixel becomes bright and opaque. When the voltage is on, PDLC is properly aligned so that light would not be
scattered, showing a transparent pixel. By electrically controlling the PDLC, a counting seven-segment pattern is clearly
displayed. Arrayed waveguide display had been theoretically proposed to be a full color display with high light-use
efficiency. Light of three primary colors from an emitter array could be coupled into a waveguide array upon which is
the PDLC switches. In our design, the core of the waveguide is made of SU-8 photoresist while the side and under
cladding is polymethyl methacrylate (PMMA). The upper cladding PDLC is controlled pixel by pixel so that the light
can be selectively scattered. Both displays were carefully patterned and packaged with their driving circuits.
Furthermore, since most materials are transparent and low weight, the displays are applicable for see-through headmounted