Technical considerations in the Verasonics research ultrasound platform for developing a photoacoustic imaging system

Photoacoustic imaging (PAI) is an emerging functional and molecular imaging technology that has attracted much attention in the past decade. Recently, many researchers have used the vantage system from Verasonics for simultaneous ultrasound (US) and photoacoustic (PA) imaging. This was the motivation to write on the details of US/PA imaging system implementation and characterization using Verasonics platform. We have discussed the experimental considerations for linear array based PAI due to its popularity, simple setup, and high potential for clinical translatability. Specifically, we describe the strategies of US/PA imaging system setup, signal generation, amplification, data processing and study the system performance.     

光声成像在关节炎性病变中的潜在临床应用价值

关节炎性疾病发病率逐年升高,给社会经济造成了巨大负担,其早期诊治具有重要意义.光声成像是一种新型光学影像技术,结合了光显像和超声波接收转换的优点,可对关节开展形态学、微血管及功能成像,并可通过外源性造影剂实现分子成像.近10年来,研究人员开发了一系列光声成像仪器,包括独立光声断层成像系统、多模态影像系统等,针对关节炎性...     

Combined Photoacoustic and Acoustic Imaging of Human Breast Specimens in the Mammographic Geometry

A photoacoustic volume imaging (PAVI) system was designed to study breast cancer detection and diagnosis in the mammographic geometry in combination with automated 3-D ultrasound (AUS). The goal of the work described here was to validate the design and evaluate its performance in human breast tissues for non-invasive imaging of deeply positioned structures covering such geometry. The good penetration of near-infrared light and high receiving sensitivity of a broad-bandwidth, 572-element, 2-D polyvinylidene fluoride (PVDF) array at a low center frequency of 1 MHz were used with 20 channel simultaneous acquisition. Pseudo-lesions filled with dilute blood were imaged in three human breast specimens at various depths up to 49 mm. With near-infrared light illumination and 256-sample averaging, the extrapolated maximum depth in imaging a 2.4-mm blood-rich lesion with a 3-dB contrast-to-noise ratio in a compressed breast was 54 mm. Three-dimensional photoacoustic volume image stacks of the breasts were co-registered with 3-D ultrasound image stacks, suggesting for the first time that PAVI, based on the intrinsic tissue contrast, can visualize tissue interfaces other than those with blood, including the inner skin surface and connective tissue sheets. With the designed system, PAVI revealed satisfactory imaging depth and sensitivity for coverage of the entire breast when imaged from both sides in the mammographic geometry with mild compression.     

High-Resolution Photoacoustic Imaging of Ocular Tissues

Optical coherence tomography (OCT) and ultrasound (US) are methods widely used for diagnostic imaging of the eye. These techniques detect discontinuities in optical refractive index and acoustic impedance, respectively. Because these both relate to variations in tissue density or composition, OCT and US images share a qualitatively similar appearance. In photoacoustic imaging (PAI), short light pulses are directed at tissues, pressure is generated due to a rapid energy deposition in the tissue volume and thermoelastic expansion results in generation of broadband US. PAI thus depicts optical absorption, which is independent of the tissue characteristics imaged by OCT or US. Our aim was to demonstrate the application of PAI in ocular tissues and to do so with lateral resolution comparable to OCT. We developed two PAI assemblies, both of which used single-element US transducers and lasers sharing a common focus. The first assembly had optical and 35-MHz US axes offset by a 30° angle. The second assembly consisted of a 20-MHz ring transducer with a coaxial optics. The laser emitted 5-ns pulses at either 532 nm or 1064 nm, with spot sizes at the focus of 35 μm for the angled probe and 20 μm for the coaxial probe. We compared lateral resolution by scanning 12.5 μm diameter wire targets with pulse/echo US and PAI at each wavelength. We then imaged the anterior segment in whole ex vivo pig eyes and the choroid and ciliary body region in sectioned eyes. PAI data obtained at 1064 nm in the near infrared had higher penetration but reduced signal amplitude compared to that obtained using the 532 nm green wavelength. Images were obtained of the iris, choroid and ciliary processes. The zonules and anterior cornea and lens surfaces were seen at 532 nm. Because the laser spot size was significantly smaller than the US beamwidth at the focus, PAI images had superior resolution than those obtained using conventional US. (E-mail: rsilverman@rri-usa.org)     

Frequency-domain analysis of photoacoustic imaging data from prostate adenocarcinoma tumors in a murine model

Photoacoustic imaging is an emerging technique for anatomical and functional sub-surface imaging but previous studies have predominantly focused on time-domain analysis. In this study, frequency-domain analysis of the radio-frequency signals from photoacoustic imaging was performed to generate quantitative parameters for tissue characterization. To account for the response of the imaging system, the photoacoustic spectra were calibrated by dividing the photoacoustic spectra (radio-frequency ultrasound spectra resulting from laser excitation) from tissue by the photoacoustic spectrum of a point absorber excited under the same conditions. The resulting quasi-linear photoacoustic spectra were fit by linear regression and midband fit, slope and intercept were computed from the best-fit line. These photoacoustic spectral parameters were compared between the region-of-interests (ROIs) representing prostate adenocarcinoma tumors and adjacent normal flank tissue in a murine model. The mean midband fit and intercept in the ROIs showed significant differences between cancerous and noncancerous regions. These initial results suggest that such frequency-domain analysis can provide a quantitative method for tumor tissue characterization using photoacoustic imaging in vivo. (E-mail: cxdeng@umich.edu and xdwang@umich.edu)     

光声成像技术及其在乳腺肿瘤诊断中的应用

光声成像作为一种新兴的生物医学成像技术,以光声效应为成像基础,兼备光学高对比度、超声高穿透度的优点,同时具有光谱信息获取能力,可进行功能成像,具有良好的临床应用前景。乳腺肿瘤是目前光声成像技术临床应用最广泛的领域,本文综述光声成像技术特点及其在乳腺肿瘤的临床应用现状,并对未来应用前景进行展望。     

Ultrafast photoacoustic imaging and its application to real-time 3D imaging with improved focusing

The restricted temporal resolution ofphotoacoustic imaging due to limited frame rates often prohibits its applications in areas such as real-time 3D imaging. This paper presents an ultrasound/photoacoustic multimodality imaging system that provides an ultrafast frame rate and consists of an ultrasound transducer array with plane wave excitation and a laser with pulse repetition frequency up to 2000 Hz. Its application to real-time 3D photoacoustic imaging is demonstrated and a synthetic-aperture focusing technique is applied to improve the elevational focusing quality of the mechanically-scanned 1D array. A 3D frame rate of 12 Hz in a volume covering a 19.2 mm x 19.2 mm scanning surface is demonstrated.     

Photoacoustic tomography: a potential new tool for prostate cancer

The feasibility of photoacoustic tomography (PAT) for noninvasive imaging of prostate cancer was explored through the study on a canine model in vivo. Imaging of blood-rich lesions mimicking prostate tumors was achieved using a commercial medical ultrasound (US) system without affecting its original imaging functions. Based on the optical contrast between hemoglobin and other tissues, PAT has demonstrated good sensitivity and high contrast-to-noise ratio in visualizing deep lesions; while US has presented the morphological features including the boundary and the urethral of the prostate. PAT of prostate cancer may facilitate improved tumor localization, staging of disease, and detection of recurrences.     

Photoacoustic imaging of salivary glands

In this work, we utilized photoacoustic imaging (PAI) with co-registered ultrasound (US) to non-invasively assess salivary gland function in vivo. A significant increase in salivary gland oxygen saturation was observed on PAI within minutes after gustatory stimulation of healthy mice reflective of the hyperemic response associated with secretion of saliva. Good correlation was seen between PAI and Doppler sonography. Salivary adenoid cystic carcinomas showed higher oxygen saturation compared to surrounding salivary gland tissue. Our results demonstrate the potential clinical utility of PAI for visualization of salivary gland physiology and pathology.OCIS codes: (170.5120) Photoacoustic imaging, (170.3880) Medical and biological imaging, (170.7170) Ultrasound, (170.4940) Otolaryngology, (170.4580) Optical diagnostics for medicine     

Quantitative photoacoustic image reconstruction improves accuracy in deep tissue structures

Photoacoustic imaging (PAI) is emerging as a potentially powerful imaging tool with multiple applications. Image reconstruction for PAI has been relatively limited because of limited or no modeling of light delivery to deep tissues. This work demonstrates a numerical approach to quantitative photoacoustic image reconstruction that minimizes depth and spectrally derived artifacts. We present the first time-domain quantitative photoacoustic image reconstruction algorithm that models optical sources through acoustic data to create quantitative images of absorption coefficients. We demonstrate quantitative accuracy of less than 5% error in large 3 cm diameter 2D geometries with multiple targets and within 22% error in the largest size quantitative photoacoustic studies to date (6cm diameter). We extend the algorithm to spectral data, reconstructing 6 varying chromophores to within 17% of the true values. This quantitiative PA tomography method was able to improve considerably on filtered-back projection from the standpoint of image quality, absolute, and relative quantification in all our simulation geometries. We characterize the effects of time step size, initial guess, and source configuration on final accuracy. This work could help to generate accurate quantitative images from both endogenous absorbers and exogenous photoacoustic dyes in both preclinical and clinical work, thereby increasing the information content obtained especially from deep-tissue photoacoustic imaging studies.OCIS codes: (110.5120) Photoacoustic imaging, (100.3010) Image reconstruction techniques     

光声成像技术及其临床应用

光声成像作为一种新兴的生物医学成像技术,以光声效应为成像基础,结合光学成像对比度高、光谱特异度好、声学成像空间分辨率高和穿透力强的特点,具有广泛的临床应用前景。本文从光声成像基本原理、成像模式、在临床医学领域的应用前景以及目前存在的技术局限等方面进行详细介绍。     

Handheld miniature probe integrating diffuse optical tomography with photoacoustic imaging through a MEMS scanning mirror

We describe a novel dual-modality imaging approach that integrates diffuse optical tomography (DOT) and photoacoustic imaging (PAI) through a miniaturized handheld probe based on microelectromechanical systems (MEMS) scanning mirror. We validate this dual-modal DOT/PAI approach using extensive phantom experiments, and demonstrate its application for tumor imaging using tumor-bearing mice systematically injected with targeted contrast agents.OCIS codes: (110.6960) Tomography, (170.0110) Imaging systems, (170.5120) Photoacoustic imaging     

Design of miniaturized illumination for transvaginal co-registered photoacoustic and ultrasound imaging

A novel lens-array based illumination design for a compact co-registered photoacoustic/ultrasound transvaginal probe has been demonstrated. The lens array consists of four cylindrical lenses that couple the laser beams into four 1-mm-core multi-mode optical fibers with optical coupling efficiency of ~87%. The feasibility of our lens array was investigated by simulating the lenses and laser beam profiles using Zemax. The laser fluence on the tissue surface was experimentally measured and was below the American National Standards Institute (ANSI) safety limit. Spatial distribution of hemoglobin oxygen saturation (sO₂) of a mouse tumor was obtained in vivo using photoacoustic measurements at multiple wavelengths. Furthermore, benign and malignant ovaries were imaged ex vivo and evaluated histologically. The co-registered images clearly showed different patterns of blood vasculature. These results highlight the clinical potential of our system for noninvasive photoacoustic and ultrasound imaging of ovarian tissue and cancer detection and diagnosis.OCIS codes: (110.0110) Imaging systems, (170.2945) Illumination design, (170.5120) Photoacoustic imaging, (170.6960) Tomography, (170.7170) Ultrasound     

Multimodal characterization of compositional, structural and functional features of human atherosclerotic plaques

Detection of atherosclerotic plaque vulnerability has critical clinical implications for avoiding sudden death in patients with high risk of plaque rupture. We report on multimodality imaging of ex-vivo human carotid plaque samples using a system that integrates fluorescence lifetime imaging (FLIM), ultrasonic backscatter microscopy (UBM), and photoacoustic imaging (PAI). Biochemical composition is differentiated with a high temporal resolution and sensitivity at the surface of the plaque by the FLIM subsystem. 3D microanatomy of the whole plaque is reconstructed by the UBM. Functional imaging associated with optical absorption contrast is evaluated from the PAI component. Simultaneous recordings of the optical, ultrasonic, and photoacoustic data present a wealth of complementary information concerning the plaque composition, structure, and function that are related to plaque vulnerability. This approach is expected to improve our ability to study atherosclerotic plaques. The multimodal system presented here can be translated into a catheter based intraluminal system for future clinical studies.     

Integrated optical coherence tomography, ultrasound and photoacoustic imaging for ovarian tissue characterization

Ovarian cancer has the lowest survival rate of the gynecologic cancers because it is predominantly diagnosed in Stages III or IV due to the lack of reliable symptoms, as well as the lack of efficacious screening techniques. Detection before the malignancy spreads or at the early stage would greatly improve the survival and benefit patient health. In this report, we present an integrated optical coherence tomography (OCT), ultrasound (US) and photoacoustic imaging (PAI) prototype endoscopy system for ovarian tissue characterization. The overall diameter of the prototype endoscope is 5 mm which is suitable for insertion through a standard 5-12.5mm endoscopic laparoscopic port during minimally invasive surgery. It consists of a ball-lensed OCT sample arm probe, a multimode fiber having the output end polished at 45 degree angle so as to deliver the light perpendicularly for PAI, and a high frequency ultrasound transducer with 35MHz center frequency. System characterizations of OCT, US and PAI are presented. In addition, results obtained from ex vivo porcine and human ovarian tissues are presented. The optical absorption contrast provided by PAI, the high resolution subsurface morphology provided by OCT, and the deeper tissue structure imaged by US demonstrate the synergy of the combined endoscopy and the superior performance of this hybrid device over each modality alone in ovarian tissue characterization.     

Simultaneous photoacoustic and optically mediated ultrasound microscopy: an in vivo study

We propose the use of thermoelastic (TE) excitation of an ultrasonic (US) detector by backscattered laser radiation as a means of upgrading a single-modality photoacoustic (PA) microscope to dual-modality PA/US imaging at minimal cost. The upgraded scanning head of our dual-modality microscope consists of a fiber bundle with 14 output arms and a 32MHz polyvinylidene difluoride (PVDF) detector with a 34 MHz bandwidth (−6 dB level), 12.7 mm focal length, and a 0.25 numerical aperture. A single optical pulse delivered through the fiber bundle to the biotissue being investigated, in combination with a metalized surface on the PVDF detector allows us to obtain both PA and US A-scans. To demonstrate the in vivo capabilities of the proposed method we present the results of bimodal imaging of the brain of a newborn rat, a mouse tail and a mouse tumor.OCIS codes: (170.5120) Photoacoustic imaging, (170.7180) Ultrasound diagnostics     

6种影像学技术在致密型乳腺诊断中的应用

乳腺癌居于我国女性恶性肿瘤发病的首位,严重危害女性健康。致密型乳腺是乳腺癌的风险因素之一。在致密型乳腺中早期发现、早期诊断乳腺癌非常重要。乳腺X线摄影因受组织重叠、致密腺体遮盖等影响,对致密型乳腺病变检出存在一定局限性。近年来不断发展的功能成像技术,如动态对比增强磁共振成像、弥散加权成像、正电子发射计算机断层显像、乳腺专用伽马成像,通过反映肿瘤血流动力和代谢的变化从而提高致密型乳腺病变的检出。同时,新兴的光声成像技术能提供生物组织结构信息与功能信息,在深层组织中空间分辨率高,其在乳腺疾病中的应用逐渐受到重视。本文对数字乳腺三维断层摄影、超声检查、MRI检查、PET/CT检查、BSGI检查及光声成像等几种影像学检查方法在致密型乳腺诊断中的应用进行综述,为临床医生对致密型乳腺疾病的早期诊断提供帮助。      

High frame rate photoacoustic imaging at 7000 frames per second using clinical ultrasound system

Photoacoustic tomography, a hybrid imaging modality combining optical and ultrasound imaging, is gaining attention in the field of medical imaging. Typically, a Q-switched Nd:YAG laser is used to excite the tissue and generate photoacoustic signals. But, such photoacoustic imaging systems are difficult to translate into clinical applications owing to their high cost, bulky size often requiring an optical table to house such lasers. Moreover, the low pulse repetition rate of few tens of hertz prevents them from being used in high frame rate photoacoustic imaging. In this work, we have demonstrated up to 7000 Hz photoacoustic imaging (B-mode) and measured the flow rate of a fast moving object. We used a ~140 nanosecond pulsed laser diode as an excitation source and a clinical ultrasound imaging system to capture and display the photoacoustic images. The excitation laser is ~803 nm in wavelength with ~1.4 mJ energy per pulse. So far, the reported 2-dimensional photoacoustic B-scan imaging is only a few tens of frames per second using a clinical ultrasound system. Therefore, this is the first report on 2-dimensional photoacoustic B-scan imaging with 7000 frames per second. We have demonstrated phantom imaging to view and measure the flow rate of ink solution inside a tube. This fast photoacoustic imaging can be useful for various clinical applications including cardiac related problems, where the blood flow rate is quite high, or other dynamic studies.OCIS codes: (110.5120) Photoacoustic imaging, (110.0110) Imaging systems, (140.2010) Diode laser arrays     

Second Harmonic and Subharmonic for Non-Linear Wideband Contrast Imaging Using a Capacitive Micromachined Ultrasonic Transducer Array

When insonified with suitable ultrasound excitation, contrast microbubbles generate various non-linear scattered components, such as the second harmonic (2H) and the subharmonic (SH). In this study, we exploit the wide frequency bandwidth of capacitive micromachined ultrasonic transducers (CMUTs) to enhance the response from ultrasound contrast agents by selective imaging of both the 2H and SH components simultaneously. To this end, contrast images using the pulse inversion method were recorded with a 64-element CMUT linear array connected to an open scanner. In comparison to imaging at 2H alone, the wideband imaging including both the 2H and SH contributions provided up to 130% and 180% increases in the signal-to-noise and contrast-to-tissue ratios, respectively. The wide-frequency band of CMUTs offers new opportunities for improved ultrasound contrast agent imaging.     

Remote temperature estimation in intravascular photoacoustic imaging

Intravascular photoacoustic (IVPA) imaging is based on the detection of laser-induced acoustic waves generated within the arterial tissue under pulsed laser irradiation. In general, laser radiant energy levels are kept low (20 mJ/cm(2)) during photoacoustic imaging to conform to general standards for safe use of lasers on biological tissues. However, safety standards in intravascular photoacoustic imaging are not yet fully established. Consequently, monitoring spatio-temporal temperature changes associated with laser-tissue interaction is important to address thermal safety of IVPA imaging. In this study we utilize the IVUS-based strain measurements to estimate the laser-induced temperature increase. Temporal changes in temperature were estimated in a phantom modeling a vessel with an inclusion. A cross-correlation-based time delay estimator was used to assess temperature-induced strains produced by different laser radiant energies. The IVUS-based remote measurements revealed temperature increases of 0.7+/-0.3 degrees C, 2.9+/-0.2 degrees C and 5.0+/-0.2 degrees C, for the laser radiant energies of 30 mJ/cm(2), 60 mJ/cm(2) and 85 mJ/cm(2), respectively. The technique was then used in imaging of ex vivo samples of a normal rabbit aorta. For arterial tissues, a temperature elevation of 1.1 degrees C was observed for a laser fluence of 60 mJ/cm(2) and lesser than 1 degrees C for lower energy levels normally associated with IVPA imaging. Therefore, the developed ultrasound technique can be used to monitor temperature during IVPA imaging. Furthermore, the analysis based on the Arrhenius thermal damage model indicates no thermal injury in the arterial tissue, suggesting the safety of IVPA imaging.