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。     

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     

Axial accuracy and signal enhancement in acoustic-resolution photoacoustic microscopy by laser jitter effect correction and pulse energy compensation

In recent years, photoacoustic imaging has found vast applications in biomedical imaging. Photoacoustic imaging has high optical contrast and high ultrasound resolution allowing deep tissue non-invasive imaging beyond the optical diffusion limit. Q-switched lasers are extensively used in photoacoustic imaging due to the availability of high energy and short laser pulses, which are essential for high-resolution photoacoustic imaging. In most cases, this type of light source suffers from pulse peak-power energy variations and timing jitter noise, resulting in uncertainty in the output power and arrival time of the laser pulses. These problems cause intensity degradation and temporal displacement of generated photoacoustic signals which in turn deteriorate the quality of the acquired photoacoustic images. In this study, we used a high-speed data acquisition system in combination with a fast photodetector and a software-based approach to capture laser pulses precisely in order to reduce the effect of timing jitter and normalization of the photoacoustic signals based on pulse peak-powers simultaneously. In the experiments, maximum axial accuracy enhancement of 14 µm was achieved in maximum-amplitude projected images on XZ and YZ planes with ±13.5 ns laser timing jitter. Furthermore, photoacoustic signal enhancement of 77% was obtained for 75% laser pulses peak-power stability.     

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.     

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     

Considering sources and detectors distributions for quantitative photoacoustic tomography

Photoacoustic tomography (PAT) is a hybrid imaging modality that takes advantage of high optical contrast brought by optical imaging and high spatial resolution brought by ultrasound imaging. However, the quantification in photoacoustic imaging is challenging. Multiple optical illumination approach has proven to achieve uncoupling of diffusion and absorption effects. In this paper, this protocol is adopted and synthetic photoacoustic data, blurred with some noise, were generated. The influence of the distribution of optical sources and transducers on the reconstruction of the absorption and diffusion coefficients maps is studied. Specific situations with limited view angles were examined. The results show multiple illuminations with a wide field improve the reconstructions.OCIS codes: (170.0170) Medical optics and biotechnology, (170.5120) Photoacoustic imaging     

In vivo photoacoustic micro-imaging of microvascular changes for Achilles tendon injury on a mouse model

Since neovascularization has been reported that it is associated with tendinopathy, assessments of vascularity are important for both diagnosis and treatment estimation. Photoacoustic imaging, taking the advantages of good ultrasonic resolution and high optical absorption contrast, has been shown a promising tool for vascular imaging. In this study, we explore the feasibility of photoacoustic micro-imaging in noninvasive monitoring of microvascular changes in Achilles tendon injuries on a mouse model in vivo. During collagenase-induced tendinitis, a 25-MHz photoacoustic microscope was used to image microvascular changes in Achilles tendons of mice longitudinally up to 23 days. In addition, complementary tissue structural information was revealed by collateral 25-MHz ultrasound microscopy. Morphological changes and proliferation of new blood vessels in Achilles tendons were observed during and after the acute inflammation. Observed microvascular changes during tendinitis were similar to the findings in the literatures. This study demonstrates that photoacoustic imaging can potentially be a complementary tool for high sensitive diagnosis and assessment of treatment performance in tendinopathy.     

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。     

Development of a new pulsed source for photoacoustic imaging based on aperiodically poled lithium niobate

We present the development of a source of deep-red radiation for photoacoustic imaging. This source, which is based on two cascaded wavelength conversion processes in aperiodically poled lithium niobate, emits 10 nanosecond pulses of over 500 µJ at 710 nm. Photoacoustic images were obtained from phantoms designed to mimic the optical and acoustic properties of oral tissue. Results indicate this device is a viable source of optical pulses for photoacoustic applications.OCIS codes: (170.1065) Acousto-optics, (170.3880) Medical and biological imaging, (160.3730) Lithium niobate, (190.4223) Nonlinear wave mixing     

Correlation of transabdominal sonographic and cystoscopic findings in the diagnosis of focal abnormalities of the urinary bladder wall: a prospective study.

OBJECTIVE: The aim of this study was to prospectively assess the diagnostic capabilities of transabdominal sonography performed with newer sonography machines for showing focal bladder wall abnormalities (FBWAs) detected on cystoscopy. METHODS: One hundred twelve consecutive patients (97 male and 15 female; mean age, 68 years) underwent cystoscopy. Reasons for referral were macroscopic hematuria (44 cases [39%]), surveillance after transurethral resection (56 cases [49.5%]), and incidental sonographic findings (12 cases [11.5%]). One to 2 days before cystoscopy, sonography was carried out by a single operator who was blinded to clinical and recent sonographic findings. The presence, size, number, and location of FBWAs (eg, polypoid vegetations and asymmetric bladder wall thickening) were recorded and compared with cystoscopic and histologic findings. RESULTS: One hundred ten patients with a histologic diagnosis were available for the study. Benign conditions, nontransitional tumors, and transitional tumors were found in 26.3%, 3.7% and 70% of the patients, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of sonography of cystoscopic lesions were 91.4%, 79.3%, 91.4%, 79.3%, and 88.2%. Cancers of 15 mm or smaller and flat tumors were often missed by sonography, whereas chronic cystitis accounted for most of the false-positive sonographic findings; however, sonography had poor capability of characterizing FBWAs, with specificity of 62%. In this respect, color Doppler findings proved of little aid as well. CONCLUSIONS: In patients selected for cystoscopy, transabdominal sonography with newer sonography machines showed good diagnostic accuracy for focal alterations of the bladder wall found on cystoscopy.     

Iterative algorithm for multiple illumination photoacoustic tomography (MIPAT) using ultrasound channel data

Photoacoustic tomography is a promising imaging modality offering high ultrasonic resolution with intrinsic optical contrast. However, quantification in photoacoustic imaging is challenging. We present an algorithm for quantitative photoacoustic estimation of optical absorption and diffusion coefficients based on minimizing an error function between measured photoacoustic channel data and a calculated forward model with a multiple-illumination pattern. Unlike many other algorithms, the proposed method does not require the erroneous assumption of ideal tomographic reconstruction of initial pressures and to our knowledge is the first demonstration of the efficacy of multiple-illumination photoacoustic tomography requiring only transducer channel data. Simulations show promise for numerically robust optical property estimation as illustrated by well-conditioned Hessian singular values in 2D examples.OCIS codes: (100.0100) Image processing, (100.3010) Image reconstruction techniques     

Photoacoustic and ultrasound imaging using dual contrast perfluorocarbon nanodroplets triggered by laser pulses at 1064 nm

Recently, a dual photoacoustic and ultrasound contrast agent—named photoacoustic nanodroplet—has been introduced. Photoacoustic nanodroplets consist of a perfluorocarbon core, surfactant shell, and encapsulated photoabsorber. Upon pulsed laser irradiation the perfluorocarbon converts to gas, inducing a photoacoustic signal from vaporization and subsequent ultrasound contrast from the resulting gas microbubbles. In this work we synthesize nanodroplets which encapsulate gold nanorods with a peak absorption near 1064 nm. Such nanodroplets are optimal for extended photoacoustic imaging depth and contrast, safety and system cost. We characterized the nanodroplets for optical absorption, image contrast and vaporization threshold. We then imaged the particles in an ex vivo porcine tissue sample, reporting contrast enhancement in a biological environment. These 1064 nm triggerable photoacoustic nanodroplets are a robust biomedical tool to enhance image contrast at clinically relevant depths.OCIS codes: (110.5120) Photoacoustic imaging, (170.7170) Ultrasound, (160.4236) Nanomaterials, (170.3880) Medical and biological imaging, (170.7180) Ultrasound diagnostics     

Photoacoustic Oxygenation Quantification in Patients with Raynaud's: First-in-Human Results

The purpose of this study was to investigate the use of photoacoustic imaging for quantifying fingertip oxygenation as an approach to diagnosing and monitoring Raynaud's phenomenon. After 30?min of acclimation to room temperature, 22 patients (7 patients with secondary Raynaud's associated to Scleroderma and 15 healthy controls) provided informed consent to undergo fingertip Doppler imaging and high-frequency photoacoustic imaging before and 5, 15 and 30?min after cold stimulus (submerged hand in a 15?°C water bath for 1?min). High-frequency ultrasound and photoacoustic imaging was performed on the nail bed of each patient's second through fifth finger on their dominant hand, using a Vevo 2100 LAZR system with an LZ-250 probe (Fujifilm VisualSonics, Toronto, ON, Canada) in oxy-hemoglobin quantification mode. During each exam, volumetric data across a 3-mm span of data was acquired to produce a volumetric image of percent oxygenation and hemoglobin concentration. Changes in fingertip oxygenation between Raynaud's patients and healthy volunteers were compared, using receiver operator characteristic (ROC) analysis. Photoacoustic signal was detected in both the nail bed and nailfold in all study participants. Doppler ultrasound resulted in poor differentiation of Raynaud's patients from healthy volunteers, with an area under the ROC curve (A_z) of 0.51. Photoacoustic imaging demonstrated improved accuracy at baseline (A_z?=?0.72), which improved when quantifying normalized changes after cold stimulus (A_z?=?0.89 5-min post stimulus, A_z?=?0.91 15-min post stimulus, and A_z?=?0.85 after stimulus). Oxygenation levels derived using photoacoustic imaging are able to identify patients with Raynaud's and safely evaluate their response to a cold stimulus over time.     

High resolution three-dimensional photoacoutic tomography with CCD-camera based ultrasound detection

A photoacoustic tomograph based on optical ultrasound detection is demonstrated, which is capable of high resolution real-time projection imaging and fast three-dimensional (3D) imaging. Snapshots of the pressure field outside the imaged object are taken at defined delay times after photoacoustic excitation by use of a charge coupled device (CCD) camera in combination with an optical phase contrast method. From the obtained wave patterns photoacoustic projection images are reconstructed using a back propagation Fourier domain reconstruction algorithm. Applying the inverse Radon transform to a set of projections recorded over a half rotation of the sample provides 3D photoacoustic tomography images in less than one minute with a resolution below 100 µm. The sensitivity of the device was experimentally determined to be 5.1 kPa over a projection length of 1 mm. In vivo images of the vasculature of a mouse demonstrate the potential of the developed method for biomedical applications.OCIS codes: (110.0110) Imaging systems, (170.5120) Photoacoustic imaging, (170.3880) Medical and biological imaging, (170.6960) Tomography     

In vitro and in vivo mapping of drug release after laser ablation thermal therapy with doxorubicin-loaded hollow gold nanoshells using fluorescence and photoacoustic imaging

Doxorubicin-loaded hollow gold nanoshells (Dox@PEG-HAuNS) increase the efficacy of photothermal ablation (PTA) not only by mediating efficient PTA but also through chemotherapy, and therefore have potential utility for local anticancer therapy. However, in vivo real-time monitoring of Dox release and temperature achieved during the laser ablation technique has not been previously demonstrated before. In this study, we used fluorescence optical imaging to map the release of Dox from Dox@PEG-HAuNS and photoacoustic imaging to monitor the tumor temperature achieved during near-infrared laser-induced photothermal heating in vitro and in vivo. In vitro, treatment with a 3-W laser was sufficient to initiate the release of Dox from Dox@PEG-HAuNS (1:3:1 wt/wt, 1.32 × 10¹² particles/mL). Laser powers of 3 and 6 W achieved ablative temperatures of more than 50 °C. In 4T1 tumor-bearing nude mice that received intratumoral or intravenous injections of Dox@PEG-HAuNS, fluorescence optical imaging (emission wavelength = 600 nm, excitation wavelength = 500 nm) revealed that the fluorescence intensity in surface laser-treated tumors 24 h after treatment was significantly higher than that in untreated tumors (p = 0.015 for intratumoral, p = 0.008 for intravenous). Similar results were obtained using an interstitial laser to irradiate tumors following the intravenous injection of Dox@PEG-HAuNS (p = 0.002 at t = 24 h). Photoacoustic imaging (acquisition wavelength = 800 nm) revealed that laser treatment caused a substantial increase in tumor temperature, from 37 °C to ablative temperatures of more than 50 °C. Ex vivo analysis revealed that the fluorescence intensity of laser-treated tumors was twice as high as that of untreated tumors (p = 0.009). Histological analysis confirmed that intratumoral injection of Dox@PEG-HAuNS and laser treatment caused significantly more tumor necrosis compared to tumors that were not treated with laser (p < 0.001). On the basis of these findings, we conclude that fluorescence optical imaging and photoacoustic imaging are promising approaches to assessing Dox release and monitoring temperature, respectively, after Dox@PEG-HAuNS-mediated thermal ablation therapy.     

光声成像分子造影剂

光声成像是利用光声效应成像的新型影像技术, 具有光学成像高对比度和超声成像高穿透力的优势。光声成像分子包括内源性生色团和外源性造影剂, 其中外源性分子造影剂的应用, 使分子光声成像成为可能, 因而具有广阔的生物医学应用前景及重要的研究意义。本文对光声成像外源性分子造影剂的物理化学性质及合成方式进行综述, 重点介绍小分子有机染料、贵金属纳米颗粒、碳纳米材料、有机纳米多聚物、基因编码的生色团、铜铁化合物、半导体多聚物纳米颗粒等光声信号复合物及常见的配体分子, 如小分子、肽类、亲和小体、适体和抗体等, 并对未来本领域的相关研究进行展望。     

Non-contact photoacoustic imaging using a fiber based interferometer with optical amplification

In photoacoustic imaging the ultrasonic signals are usually detected by contacting transducers. For some applications contact with the tissue should be avoided. As alternatives to contacting transducers interferometric means can be used to acquire photoacoustic signals remotely. In this paper we report on non-contact three and two dimensional photoacoustic imaging using an optical fiber-based Mach-Zehnder interferometer. A detection beam is transmitted through an optical fiber network onto the surface of the specimen. Back reflected light is collected and coupled into the same optical fiber. To achieve a high signal/noise ratio the reflected light is amplified by means of optical amplification with an erbium doped fiber amplifier before demodulation. After data acquisition the initial pressure distribution is reconstructed by a Fourier domain reconstruction algorithm. We present remote photoacoustic imaging of a tissue mimicking phantom and on chicken skin.OCIS codes: (170.5120) Photoacoustic imaging, (120.0280) Remote sensing and sensors, (110.2350) Fiber optics imaging, (140.4480) Optical amplifiers, (110.7170) Ultrasound, (170.1470) Blood or tissue constituent monitoring, (120.3180) Interferometry     

经尿道膀胱腔内超声诊断膀胱癌分期的价值

从1996年7月至1998年3月,对30例膀胱肿瘤患者术前经尿道膀胱腔内超声判断分期,与术后病理分期结果对比,符合率为:T1期100％,T2期100％,T3期80％,T4期为0。经尿道腔内超声能清楚显示肿瘤浸润膀胱壁的深度,所以它被推荐为术前膀胱肿瘤分期的重要方法。     

载印度墨水相变型光声/超声双模态造影剂的制备及体外显影

目的 制备一种新型的光声/超声双模态造影剂,观察其体外光致相变作用以及光声/超声显影效果。方法 采用多步乳化法 合成载印度墨水及全氟己烷(PFH)的高分子微球(i-PFH-PLGA),检测其基本理化性质、光致相变作用及体外增强光声及超声成像的显像效果。结果 制备的i-PFH-PLGA呈球型,平均粒径为(542.1±68.91)nm。经激光辐照后,显微镜下可观察到较多的i-PFH-PLGA纳米粒发生液气相转变产生微泡;体外光声成像实验显示,i-PFH-PLGA纳米粒可检测到明显的光声信号,且光声信号的强度随纳米粒浓度的增加而增强;体外超声成像实验显示,经激光照射后,i-PFH-PLGA纳米粒组回声强度较辐照前明显增强(P<0.05),而单纯的液态氟碳和印度墨水辐照前后回声强度未见明显改变。结论 成功制备出的载印度墨水和液态氟碳的双模态造影剂可用于体外光声/超声成像研究。