A sonographic short cervix is a major risk factor for spontaneous preterm birth (PTB). However, the cervical length is a suboptimal means to assess cervical status due to the lack of functional and molecular information. Spectroscopic photoacoustic (sPA) imaging is a non-invasive ultrasound-based technology for assessing cervical tissue compositions, such as collagen-to-water ratio (CWR), which are the major molecular changes during cervical ripening. A longitudinal CWR measurement by sPA was performed in murine cervices (n=3 per group) through the gestational ages from nonpregnant, 13.5 to 19.5 dpc, 6 to 12 hours, and 69 to 94 hours postpartum. The sPA data acquisition was performed in a range of wavelengths covering the peak absorption of collagen and water (1070to 1650 nm) with an amplified sPA wavelength unmixing method (sPA-CWR). The results indicated that the sPA-CWR method is capable of accurately quantifying cervical tissue composition changes during cervical remodeling. The non-pregnant murine cervical samples have significantly higher sPA-CWR than any other tissue group. A decrement in CWR at larger gestational ages was detected, which follows the cervical ripening process. In addition, the repair process was detected through increased CWR in tissue samples collected 6 to12 hours postpartum and completing their recovering process at about 69 to 94 hours postpartum. Finally, the imaging results were validated by quantitative histological analysis. These histological results confirm that the sPA-CWR measurements have a high correlation to the process of collagen reorganizing. Therefore, the sPA-CWR method can be a more accurate biomarker for estimating PTB risk.
Purpose: Transvaginal ultrasound (TVUS) is a widely used real-time and non-invasive imaging technique for fetal and maternal care. It can provide structural and functional measurements about the fetal brain, such as blood vessel diameter and blood flow. However, it lacks certain biochemical estimations, such as hemoglobin oxygen saturation (SO2), which limits its ability to indicate a fetus at risk of birth asphyxia. Photoacoustic (PA) imaging has been steadily growing in recognition as a complement to ultrasound (US). Studies have shown PA imaging is capable of providing such biochemical estimations as SO2 at relatively high penetration depth (up to 30 mm).
Approach: In this study, we have designed and developed a multi-modal (US, PA, and Doppler) endocavity imaging system (ECUSPA) around a commercialized TVUS probe (Philips ATL C9-5).
Results: The integrated system was evaluated through a set of in-vitro, ex-vivo, and in-vivo studies. Imaging of excised sheep brain tissue demonstrated the system’s utility and penetration depth in transfontanelle imaging conditions. The accuracy of using the spectroscopic PA imaging (sPA) method to estimate SO2 was validated by comparing sPA oximetry results with the gold standard measurements indicated by a blood gas analyzer. The ability of US and Doppler to measure moving blood volume was evaluated in-vivo. Spectral unmixing capabilities were tested using fluorophores within sheep brains.
Conclusion: The developed system is a high resolution (about 200 μm at 30 mm depth), real-time (at 30 Hz), and quantitative (SO2 estimation error <10 % ) imaging tool with a total diameter less than 30 mm, making it suitable for intrapartum applications such as fetal and maternal diagnostics.
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-to-noise 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.
Given that breast cancer is the second leading cause of cancer-related deaths among women in the United States, it is necessary to continue improving the sensitivity and specificity of breast imaging systems that diagnose breast lesions. Photoacoustic (PA) imaging can provide functional information during in vivo studies and can augment the structural information provided by ultrasound (US) imaging. A full-ring, all-reflective, illumination system for photoacoustic tomography (PAT) coupled to a full-ring US receiver is developed and tested. The US/PA tomography system utilizes a cone mirror and conical reflectors to optimize light delivery for PAT imaging and has the potential to image objects that are placed within the ring US transducer. The conical reflector used in this system distributes the laser energy over a circular cross-sectional area, thereby reducing the overall fluence. This, in turn, allows the operator to increase the laser energy achieving better cross-sectional penetration depth. A proof-of-concept design utilizing a single cone mirror and a parabolic reflector is used for imaging cylindrical phantoms with light-absorbing objects. For the given phantoms, it has been shown that there was no restriction in imaging a given targeted cross-sectional area irrespective of vertical depth, demonstrating the potential of mirror-based, ring-illuminated PAT system. In addition, the all-reflective ring illumination method shows a uniform PA signal across the scanned cross-sectional area.
Due to the high rate of gynecologic cancers among females, obtaining structural, functional, and molecular information from reproductive organs can potentially reveal diseases at their early stages of development . In this study, we aimed to develop a miniaturized phased-array ultrasound (US) and photoacoustic (PA) endoscope for potential imaging gynecologic cancer. The developed endoscope is built around a phased-array US transducer coupled to a fiber optic light delivery system. In particular, the proposed endoscope consists of a 64-element phased array US transducer, coupled to a light delivery system that includes six fiber optics. The probe dimensions allow for utilizing this device for imaging various types of gynecologic cancers in which the probe can become close to the pathologic tissue. Given the small imaging aperture, adaptive beamforming was developed to reconstruct co-registered US and PA images in 90-degrees sector scan format. The developed endoscope was tested in a set of tissue-mimicking phantom studies to determine its characteristics and its ability to form form co-registered volumetric US and PA images. In addition, spectroscopic PA (sPA) imaging of biocompatible, folate conjugated dye was tested to demonstrate the possibility of using the developed endoscope in imaging PA molecular contrast agents.
KEYWORDS: Acoustics, Acquisition tracking and pointing, Tissue optics, Photoacoustic tomography, Monte Carlo methods, Tissues, Diffusion, Pathology, Cancer, Signal attenuation
Photoacoustic tomography (PAT) is a noninvasive, high-resolution imaging modality, capable of providing functional and molecular information of various pathologies such as cancer. In most PAT systems, the effect of tissue heterogeneity (i.e. variations in acoustic properties such as speed of sound and acoustic attenuation) is neglected. This is due to the lack of information about acoustic properties of tissue and complexity of a model to compensate for these variations. We have been developing a full-ring PAT system consists of an omni-directional illumination and a ring-based acoustic detection. In this study, we investigate using a model-based method that employs light diffusion (Monte-carlo) and acoustic wave propagation (K-wave) to compensate for both optical and acoustic heterogeneity of the tissue and provide fully compensated (i.e. quantitative) PAT images for our full-ring PAT system. To demonstrate the feasibility of providing fully compensated PAT images, in silico studies were performed in which a heterogeneous breast-tissue-mimicking phantoms were computationally generated. The map includes optical (µa, µs, g) and acoustic properties (ρ, Cs) of the fatty, fibroglandular and breast lesions. The monte-carlo light diffusion model was first utilized to generate the fluence map and thus the initial photoacoustic pressure fields (P0) within the tissue. Following to the generation of P0, the propagation of acoustic waves through a heterogeneous medium was simulated using K-wave. Using a ring-geometry ultrasound transducers (N=256), the pressure waves were received and were utilized to reconstruct PAT images. Our results indicate the PAT improvement using acoustic and optical compensation and more importantly the feasibility of achieving “quantitative” PAT images upon compensating for tissue heterogeneity.
100 Word Abstract:
Spontaneous preterm birth (sPTB) occurs in about one in ten infants born in the United States and is leading to almost 1 million neonatal deaths worldwide [1]. Diagnostic imaging of cervix is mostly limited to using ultrasound (US) to measure cervical length and has shown a low specificity to determine the risk of sPTB [2-7]. Quantitative functional imaging modalities such as elastography (EL) and photoacoustic (PA) imaging, are commonly used in conjunction with US imaging to provide additional information on tissue compositions and function. We propose using an endocavity probe to acquire US, PA, and EL information of the cervical tissue. Specifically, spectroscopic PA (sPA) is proposed to provide information on cervical tissue such as total hemoglobin (blood perfusion), tissue oxygenation level, and more importantly the collagen-to-water ratio in tissue. Shear wave elastography (SWE) measurements of cervical tissue indicates the correlation between cervical ripening and lower tissue elasticity. Our custom-designed imaging system consists of an endovaginal US transducer (ATL C9-5) capable of performing high frame rate US and acoustic radiation force shear wave imaging, and an optimized fiber-optic light delivery system’s for PA imaging. Our experimental results indicate the system’s ability to measure the presence of different concentrations of hemoglobin in tissue-mimicking phantoms as well as accurate measurement of hemoglobin oxygen saturation (SO2). In another set of experiments, we demonstrated the feasibility of monitoring collagen-to-water ratio in tissues through monitoring changes in sPA signature between 1100 and 1650 nm. Monitoring the variations of collagen in cervical tissue can help to predict sPTB.
Among various types of cancer, breast cancer is considered to be the most common that affects thousands of women all over the world. Several imaging tools are being used for breast cancer detection and diagnosis. Mammography and B-mode ultrasound (US) are the primary screening tools for breast lesions. However, mammography is limited with low sensitivity especially in women with dense breasts, who appear to be at higher risk of breast cancer. Additionally, the B-mode US suffers from low specificity in the differential diagnosis of breast lesions. Therefore, it is clinically significant to develop screening techniques that could eliminate previous limitations. Photoacoustic (PA) has been showing potential for early stage detection and staging breast cancer due to its unique abilities to acquire functional and molecular information of the breast lesions. We have developed an optimized US and PA tomography system, which uses custom designed all reflective based optics to create an omnidirectional ring-shaped beam to illuminate a cross-section of the breast tissue and acquire thegenerated acoustic waves by using a full-ring US transducer. The developed PA tomography (PAT) system can potentially make a more uniform illumination of the breast tissue and more importantly enhance the imaging depth. In this study, development of the full-ring illumination and the results of our initial feasibility US/PA tests are presented.
Nearly 20% of the United States’ population is affected by varicose veins at some point in their lives. Currently, ultrasound (US) imaging is used as clinical imaging modality to help surgeons visualize and place the ablation catheter within the diseased vein accurately. However, US imaging of catheters has limitations such as angular dependency, especially for treating perforating veins. In addition, the laser ablation procedure is often performed without any real-time temperature monitoring, which could lead to non-sufficient thermal dose or heat induced thrombosis. We propose using combined US and Photoacoustic (PA) imaging for accurate localization of the laser ablation fibers within the veins. More specifically, we proposed coupling both ablation CW laser and pulsed laser into a single ablation catheter to perform both ablation and PA localization and of the catheter and thermometry. Our studies clearly indicated that while US imaging visualizes the body of the catheter, PA signal is only generated at the interface between the fiber tip and the tissue. As a result, PA images of the catheter indicate the location of the tip of the catheter only, without any possibility of error and mislocation. We initially investigated and compared the utility of US and PA in tracking fiber tip in a set of vessel-mimicking phantoms. Our results indicated artifact-free and accurate detection of the fiber tip using PA in contrast to US. Using the PA signal temperature dependency, we also demonstrated the utility of PA for real-time monitoring of temperature increase during laser ablation procedures.
Photoacoustic imaging (PAI) is a promising medical imaging modality providing the spatial resolution of ultrasound imaging and the contrast of optical imaging. For linear-array PAI, a beamformer can be used as the reconstruction algorithm. Delay-and-sum (DAS) is the most prevalent beamforming algorithm in PAI. However, using DAS beamformer leads to low-resolution images as well as high sidelobes due to nondesired contribution of off-axis signals. Coherence factor (CF) is a weighting method in which each pixel of the reconstructed image is weighted, based on the spatial spectrum of the aperture, to mainly improve the contrast. We demonstrate that the numerator of the formula of CF contains a DAS algebra and propose the use of a delay-multiply-and-sum beamformer instead of the available DAS on the numerator. The proposed weighting technique, modified CF (MCF), has been evaluated numerically and experimentally compared to CF. It was shown that MCF leads to lower sidelobes and better detectable targets. The quantitative results of the experiment (using wire targets) show that MCF leads to for about 45% and 40% improvement, in comparison with CF, in the terms of signal-to-noise ratio and full-width-half-maximum, respectively.
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