Visualization and detection of early-stage gynecological malignancies represents a challenge for imaging due to limiting factors including tissue accessibility, device ease of use, and accuracy of imaging modalities. In this work, we introduce a miniaturized phased-array ultrasound and photoacoustic endoscopic probe which is capable of providing structural, functional, and molecular data for the characterization of gynecologic disease. The proposed probe consists of a 64-element ultrasound phased-array transducer coupled to a fiber-optic light delivery system for co-registered ultrasound and photoacoustic imaging. The fabricated US and PA imaging endoscope’s diameter is 7.5 mm, allowing for potential passage through the cervical canal and thus an intimate contact with gynecological tissues such as the cervical canal and uterus. The developed endoscopic probe was tested and characterized in a set of tissue-mimicking phantoms. US and PA resolutions were measured experimentally using 200 μm diameter wires, resulting in apparent axial and lateral diameters of 289 μm and 299 μm for US, and 308 μm and 378 μm for PA, respectively. The probe’s abilities to operate in both discrete and integrated illumination/acquisition were tested in gelatin phantoms with embedded optical absorbers with the results demonstrating the ability to acquire volumetric dual-modal US and PA images.

The uterine cervix plays a central role in the maintenance of pregnancy and in the process of parturition. Cervical remodeling involves dramatic changes in extracellular matrix composition and, in particular, of collagen and water content during cervical ripening (a term that describes the anatomical, biochemical, and physiologic changes in preparation for labor). Untimely cervical ripening in early gestation predisposes to preterm labor and delivery, the leading cause of infant death worldwide. Inadequate ripening of the cervix is associated with failure of induction or prolonged labor. The current approach to evaluate the state of the cervix relies on digital examination and sonographic examination. Herein, we present a novel imaging method that combines ultrasound (US) and photoacoustic (PA) techniques to evaluate cervical remodeling by assessing the relative collagen and water content of this organ. The method was tested in vitro in extracted collagen phantoms and ex vivo in murine cervical tissues that were collected in mid-pregnancy and at term. We report, for the first time, that our imaging approach provides information about the molecular changes in the cervix at different gestational ages. There was a strong correlation between the results of PA imaging and the histological assessment of the uterine cervix over the course of gestation. These findings suggest that PA imaging is a powerful method to assess the biochemical composition of the cervix and open avenues to non-invasively investigate the composition of this organ, which is essential for reproductive success.

In Photoacoustic imaging (PAI), the most prevalent beamforming algorithm is delay-and-sum (DAS) due to its simple implementation. However, it results in a low quality image affected by the high level of sidelobes. Coherence factor (CF) can be used to address the sidelobes in the reconstructed images by DAS, but the resolution improvement is not good enough compared to the high resolution beamformers such as minimum variance (MV). As a weighting algorithm in linear-array PAI, it was proposed to use high-resolution-CF (HRCF) weighting technique in which MV is used instead of the existing DAS in the formula of the conventional CF. The higher performance of HRCF was proved numerically and experimentally. The quantitative results obtained with the simulations show that at the depth of 40 mm, in comparison with DAS+CF and MV+CF, HRCF improves the full-width-half-maximum of about 91 % and 15 % and the signal-to-noise ratio about 40 % and 14 %, respectively. Moreover, the contrast ratio at the depth of 20 mm has been improved about 62 % and 21 % by HRCF, compared to DAS+CF and MV+CF, respectively.

Significance: Photoacoustic imaging (PAI) has been greatly developed in a broad range of diagnostic applications. The efficiency of light to sound conversion in PAI is limited by the ubiquitous noise arising from the tissue background, leading to a low signal-to-noise ratio (SNR), and thus a poor quality of images. Frame averaging has been widely used to reduce the noise; however, it compromises the temporal resolution of PAI. Aim: We propose an approach for photoacoustic (PA) signal denoising based on a combination of low-pass filtering and sparse coding (LPFSC). Approach: LPFSC method is based on the fact that PA signal can be modeled as the sum of low frequency and sparse components, which allows for the reduction of noise levels using a hybrid alternating direction method of multipliers in an optimization process. Results: LPFSC method was evaluated using in-silico and experimental phantoms. The results show a 26% improvement in the peak SNR of PA signal compared to the averaging method for in-silico data. On average, LPFSC method offers a 63% improvement in the image contrast-tonoise ratio and a 33% improvement in the structural similarity index compared to the averaging method for objects located at three different depths, ranging from 10 to 20 mm, in a porcine tissue phantom. Conclusions: The proposed method is an effective tool for PA signal denoising, whereas it ultimately improves the quality of reconstructed images, especially at higher depths, without limiting the image acquisition speed.

Early stage cancer detection technologies can provide functional information and potentially decrease the mortality rate caused by cervical cancer. In our previous work, a miniaturized ultrasound and photoacoustic endoscopic system has been developed to image the cervical tissue through the cervical canal to fulfills the need for a safe, low-cost, and high-resolution functional diagnostic system. However, the miniaturized size of endoscope and American National Standards Institute safety limits cause constraints of using high-intensity illumination during imaging. In addition, the strong light scattering of tissues limits the light penetration depth. Fortunately, the cervix anatomy allows for the delivery of additional light from the ectocervix by using an external illumination system. Here we propose a dual, co-planar illumination system, which can provide adequate illumination to the cervical tissue via combined internal and external light delivery strategies. Therefore, an increase in the area of light-tissue interaction allows us to raise the laser light energy while keeping fluence under safety limits. Thus, a reliable PA imaging can be obtained for the whole cervical tissue thickness. The system performance was tested using a Monte Carlo simulation, and laser-light fluence was calculated and compared at different depths within a simulated cervical-tissue model. The results indicated a higher and more uniform fluence in the Monte Carlo simulations. In addition, the photoacoustic imaging of the proposed system was evaluated by two cervical tissue-mimicking phantoms with human blood and graphite rods as inclusions inside it. In accordance with the simulations, the phantom study revealed a more reliable photoacoustic signal for the entire depth of the phantoms with an improved contrast to noise ratio and signal to noise ratio, and a higher coverage ratio of the imaging field of view. In summary, the dual-mode illumination system can provide more realistic information of inclusions within the tissue while considering safety limits, which can lead to more accuracy in biomarker detection for cervical cancer diagnostics.