Scaling down the dimensions of a Fabry-Perot polymer film acoustic sensor for photoacoustic endoscopy.

Significance: A Fabry-Perot (FP) polymer film sensor can be used to detect acoustic waves in a photoacoustic endoscope (PAE) if the dimensions can be adequately scaled down in size. Current FP sensors have limitations in size, sensitivity, and array configurability. Aim: We aim to characterize and demonstrate the imaging performance of a miniature FP sensor to evaluate the effects of reduced size and finite dimensions. Approach: A transfer matrix model was developed to characterize the frequency response of a multilayer miniature FP sensor. An analytical model was derived to describe the effects of a substrate with finite thickness. Finite-element analysis was performed to characterize the temporal response of a sensor with finite dimensions. Miniature 2×2 mm2 FP sensors were designed and fabricated using gold films as reflective mirrors on either side of a parylene C film deposited on a glass wafer. A single-wavelength laser was used to interrogate the sensor using illumination delivered by fiber subprobes. Imaging phantoms were used to verify FP sensor performance, and in vivo images of blood vessels were collected from a live mouse. Results: The finite thickness substrate of the FP sensor resulted in echoes in the time domain signal that could be removed by back filtering. The substrate acted as a filter in the frequency domain. The finite lateral sensor dimensions produced side waves that could be eliminated by surface averaging using an interrogation beam with adequate diameter. The fabricated FP sensor produced a noise-equivalent pressure = 0.76 kPa, bandwidth of 16.6 MHz, a spectral full-width at-half-maximum = 0.2886 nm, and quality factor Q=2694. Photoacoustic images were collected from phantoms and blood vessels in a live mouse. Conclusions: A miniature wafer-based FP sensor design has been demonstrated with scaled down form factor for future use in PAE.

Fabrication of a translational photoacoustic needle sensing probe for interstitial photoacoustic spectral analysis.

In our previous study, we demonstrated the feasibility of using an all-optical interstitial photoacoustic (PA) needle sensing probe for quantitative study of tissue architectures with PA spectral analysis (PASA). In this work, we integrated the optical components into an 18 G steel needle sheath for clinical translation. The dimensions of the needle probe are identical to those of a core biopsy probe and are fully compatible with standard procedures such as prostate biopsy. To our knowledge, this is the first interstitial PA probe that can acquire signals with sufficient temporal length for statistics-based PASA. We treated the inner surface of the steel needle sheath and successfully suppressed the vibrational PA signals generated at the surface. Purposed at boosting the measurement sensitivity and extending sensing volume, we upgraded the Fabry-Pérot hydrophone with a plano-concave structure. The performance of the translational needle PA sensing probe was examined with phantoms containing microspheres. The trend of the linear spectral slopes shows negatively correlated to the microsphere dimensions while the midband-fits are positively correlated to microsphere diameters and concentrations. The PASA quantifications show the ability to differentiate microspheres with varied dimensions.

Assessment of prostate cancer progression using a translational needle photoacoustic sensing probe: Preliminary study with intact human prostates ex-vivo.

In our previous studies, we demonstrated the ability of an interstitial all-optical needle photoacoustic (PA) sensing probe and PA spectral analysis (PASA) to assess the aggressiveness of prostate cancer. In this clinical translation investigation, we integrated the optical components of the needle PA sensing probe into a 18G steel needle. The translational needle PA sensing probe was evaluated using intact human prostates in a simulated ultrasound-guided transperineal prostate biopsy. PA signals were acquired at 1220 nm, 1370 nm, 800 nm and 266 nm at each interstitial measurement location and quantified by PASA within the frequency range of 8-28 MHz. The measurement locations were stained for establishing spatial correlations between the quantitative measurements and the histological diagnosing. Most of the quantitative PA assessments reveal statistically significant differences between the benign and cancerous regions. Multivariate analysis combining the PASA quantifications shows an accuracy close to 90% in differentiating the benign and cancerous regions in the prostates.

Penetration of Carbon Nanotubes into the Retinoblastoma Tumor after Intravitreal Injection in LH BETA T AG Transgenic Mice Reti-noblastoma Model.

PURPOSE: To evaluate the penetration of carbon nanotubes (CNTs) throughout retinoblastoma in a transgenic mice model. METHODS: CNTs functionalized with fluorescein isothiocyanate and targeting ligands biotin (CTN-FITC-Bio, 0.5mg/ml), or folic acid (CNT-FITC-FA, 0.5mg/ml) were injected into the vitreous of one eye of LH BETA T AG transgenic mice. Other eye did not receive any injection and was used as control. Three mice were sacrificed at days 1, 2, and 3. Eyes were enucleated and stained with 4,6-diamidino-2-phenylindole. The sections were imaged by fluorescent microscope. The images were transformed into grey-scale in MATLAB for intensity analysis. Background intensity was normalized by marking squares outside the eyeball and using the mean intensity of these squares. Fluorescent intensity (FI) for each image was measured by calculating the intensity of a same-sized square within retinoblastoma. RESULTS: Nine eyes of nine mice were included in each CNT-FITC-Bio and CNT-FITC-FA groups. The mean FI in CNT-FITC-Bio was 52.08 ± 6.33, 53.62 ± 9.00, and 65.54 ± 5.14 in days 1, 2, and 3, respectively. The mean FI in CNT-FITC-FA was 50.28 ± 7.37, 59.21 ± 6.43, and 58.38 ± 2.32 on days 1, 2, and 3, respectively. FI was significantly higher in eyes injected with CNT-FITC-Bio and CNT-FITC-FA compared to the control eyes (P = 0.02). There was no difference in FI between eyes with CNT-FITC-Bio and CNT-FITC-FA, and FI remained stable on days 1-3 in CNT-FITC-Bio, CNT-FITC-FA, and control eyes (P > 0.05). CONCLUSION: We observed higher FI in eyes with CNT-FITC-Bio and CNT-FITC-FA compared to control eyes, showing penetration of CNTs throughout retinoblastoma. CNTs can be a carrier candidate for imaging or therapeutic purposes in retinoblastoma.