血管内光声图像的建模与仿真

为了给血管内光声(intravascular photoacoustic,IVPA)成像的图像重建算法和图像后处理算法提供数据源,为培训医师提供图像库,提出一种二维IVPA图像的建模与仿真方法。建立包含斑块的血管横截面模型,并对成像导管发射激光脉冲照射血管壁组织、血管壁组织产生光声信号、利用得到的一组光声信号重建IVPA图像整个过程进行仿真,得到血管横截面模型的二维IVPA灰阶图像,同时根据冠状动脉血管随心脏搏动的规律,实现序列图像的仿真。利用仿真模型得到的IVPA图像与原电磁吸收分布图接近程度较高。仿真模型的物理意义清晰,可得到质量稳定的IVPA图像。      

Noninvasive detection of intimal xanthoma using combined ultrasound, strain rate and photoacoustic imaging

Background and motivation

The structure, composition and mechanics of carotid artery are good indicators of early progressive atherosclerotic lesions. The combination of three imaging modalities (ultrasound, strain rate and photoacoustic imaging) which could provide corroborative information about the named arterial properties could enhance the characterization of intimal xanthoma.

Methods

The experiments were performed using a New Zealand white rabbit model of atherosclerosis. The aorta excised from an atherosclerotic rabbit was scanned ex vivo using the three imaging techniques: (1) ultrasound imaging of the longitudinal section: standard ultrasound B-mode (74 Hz frame rate); (2) strain rate imaging: the artery was flushed with blood and a 1.5 Hz physiologic pulsation was induced, while the ultrasound data were recorded at higher frame rate (296 Hz); (3) photoacoustic imaging: the artery was irradiated with nanosecond pulsed laser light of low fluence in the 1210-1230 nm wavelength range and the photoacoustic data was recorded at 10 Hz frame rate. Post processing algorithms based on cross-correlation and optical absorption variation were implemented to derive strain rate and spectroscopic photoacoustic images, respectively.

Results

Based on the spatio-temporal variation in displacement of different regions within the arterial wall, strain rate imaging reveals differences in tissue mechanical properties. Additionally, spectroscopic photoacoustic imaging can spatially resolve the optical absorption properties of arterial tissue and identify the location of lipid pools.

Conclusions

The study demonstrates that ultrasound, strain rate and photoacoustic imaging can be used to simultaneously evaluate the structure, the mechanics and the composition of atherosclerotic lesions to improve the assessment of plaque vulnerability.     

In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure

We developed dual-modality microscope integrating photoacoustic microscopy (PAM) and fluorescence confocal microscopy (FCM) to noninvasively image hemoglobin oxygen saturation (sO?) and oxygen partial pressure (pO?) in vivo in single blood vessels with high spatial resolution. While PAM measures sO? by imaging hemoglobin optical absorption at two wavelengths, FCM quantifies pO? using phosphorescence quenching. The variations of sO? and pO? values in multiple orders of vessel branches under hyperoxic (100% oxygen) and normoxic (21% oxygen) conditions correlate well with the oxygen-hemoglobin dissociation curve. In addition, the total concentration of hemoglobin is imaged by PAM at an isosbestic wavelength.     

Deeply penetrating photoacoustic tomography in biological tissues enhanced with an optical contrast agent

Photoacoustic tomography (PAT) in a circular scanning configuration was developed to image deeply embedded optical heterogeneity in biological tissues. While the optical penetration was maximized with near-infrared laser pulses of 800-nm wavelength, the optical contrast was enhanced by Indocyanine Green (ICG) dye whose absorption peak matched the laser wavelength. This optimized PAT was able to image objects embedded at depths of as much as 5.2 cm, 6.2 times the 1/e optical penetration depth, in chicken breast muscle at a resolution of <780 microm and a sensitivity of <7 pmol of ICG in blood. The resolution was found to deteriorate slowly with increasing imaging depth. The effects of detection bandwidth on the quality of images acquired simultaneously by four different ultrasonic transducers are described.     

变量影响值与集群分析相结合的中红外波长选择方法

烷烃类气体的傅里叶变换红外光谱在中红外区域吸收峰重叠严重,为此,提出了一种基于变量影响值与集群分析相结合（IVPA）的波长选择方法对甲烷、乙烷、丙烷、异丁烷、正丁烷五种烷烃类气体红外光谱进行变量选择。该方法以迭代的方式逐步实现对变量的筛选,在每次迭代过程中,将变量划分为样本空间与变量空间。在样本空间中计算变量的影响值,根据变量影响值采用加权自举采样技术将变量划分为精英变量与普通变量;同时在变量空间中,统计每个变量在最优模型中出现的频率;最后利用指数衰减函数剔除普通变量中频率较低的变量,记录每次迭代过程中获取的均方根误差（RMSE）值。选择最小RMSE所对应的子集作为最终选择的变量。利用实测烷烃类光谱数据集来检验该方法的性能,并将该方法与近年来提出的稳定性竞争自适应重加权采样法（SCARS）、变量子集迭代优化（IVSO）变量选择方法所测结果进行了对比。以异丁烷分析结果为例,SCARS,IVSO与IVPA对其它四种气体的最小交叉灵敏度分别为0.67%,0.56%和0.11%;最大交叉灵敏度分别为1.69%,1.49%和1.02%;对异丁烷预测的相对误差分别为1.94%,1.65%和0.51%;上述3种方法选择的特征变量个数分别为52,17和13。结果表明,提出的IVPA方法选择的变量最少,仅为原始光谱数据的0.36%,对其他四种气体的交叉灵敏度最低,对异丁烷的预测最准确。该方法可以应用在吸收重叠的光谱中,能够提高分析模型的预测精度与运行效率。     

Full range complex ultrahigh sensitive optical microangiography

This Letter presents a useful method that combines the full range complex Fourier domain optical coherence tomography (OCT) with the ultrahigh sensitive optical microangiography (OMAG) to achieve full range complex imaging of blood flow within microcirculatory tissue beds in vivo. We propose to use the fast scanning axis to realize the full range complex imaging, while using the slow axis to achieve OMAG imaging of blood flow. We demonstrate the proposed method by using a high speed 1310?nm OCT/OMAG system running at 92?kHz line scan rate to image the flow phantoms in vitro, and the blood flows in tissue beds in vivo.     

Gold nanoshell bioconjugates for molecular imaging in living cells

Advances in scattering-based optical imaging technologies offer a new approach to noninvasive point-of-care detection, diagnosis, and monitoring of cancer. Emerging photonics technologies provide a cost-effective means to image tissue in vivo with high resolution in real time. Advancing the clinical potential of these imaging strategies requires the development of optical contrast agents targeted to specific molecular signatures of disease. We describe the use of a novel class of contrast agents based on nanoshell bioconjugates for molecular imaging in living cells. Nanoshells offer significant advantages over conventional imaging probes including continuous and broad wavelength tunability, far greater scattering and absorption coefficients, increased chemical stability, and improved biocompatibility. We show that nanoshell bioconjugates can be used to effectively target and image human epidermal growth factor receptor 2 (HER2), a clinically relevant biomarker, in live human breast carcinoma cells.     

吲哚菁绿对大鼠脑皮层血管近红外光学特性及光学相干层析成像的影响

研究观察了吲哚菁绿(ICG)对大鼠脑皮层血管近红外光谱学特性及光学相干层析成像(OCT)的影响。实验中,将SD大鼠颞部开颅,暴露并标记大脑中动脉,给予动物尾静脉注射ICG溶液,应用可见-近红外反射光谱仪和OCT系统检测脑皮层血管反射光谱的动态变化和衰减系数的特征性变化。结果显示,ICG注射后,大脑中动脉的反射光谱在ICG的吸收峰(800nm)左右出现一个特异性的低反射峰并随时间而逐渐变化;在注射ICG 3min时,本特异性低反射峰值达到最强,反射光谱的特征性变化可以为实现最佳OCT图像效果提供时间点。此外,ICG注射后的脑动脉OCT信号衰减系数为24.692±1.471,明显高于未注射ICG时15.088±1.602(p<0.01)。实验结果说明ICG可以增加血管对近红外光的吸收,为增强血管的检测能力提供理论参考,也为无损监测血管病变、肿瘤血管新生及血液动力学变化提供一种可行性检测手段。     

Intravascular photoacoustic imaging of human coronary atherosclerosis

We demonstrate intravascular photoacoustic imaging of human coronary atherosclerotic plaque. The data was obtained from two fresh human coronary arteries ex vivo, showing different stages of disease. A 1.25?mm diameter intravascular imaging catheter was built, comprising an angle-polished optical fiber adjacent to a 30?MHz ultrasound transducer. Specific photoacoustic imaging of lipid content, a key factor in vulnerable plaques that may lead to myocardial infarction, is achieved by spectroscopic imaging at different wavelengths between 1180 and 1230?nm. Simultaneous imaging with intravascular ultrasound was performed.     

Visualization and Characterization of Atherosclerotic Plaques by Micro-MRI at 4.7 T In Vivo and 11.7 T Ex Vivo

The aim of this study was to evaluate the capability of using micro-magnetic resonance imaging (MRI) to visualize and characterize atherosclerotic plaques of mouse models. Twenty five apolipoprotein E-knockout mice were fed atherogenic diet, which enabled creation of aortic atherosclerotic plaques. Aortic plaques were examined in vivo by 4.7 T MRI and then characterized ex vivo by 11.7 T three-dimensional MRI. MR images were correlated with subsequent histological confirmation. In vivo 4.7-T MRI demonstrated unevenly thickened aortic walls due to formation of atherosclerotic plaques. Ex vivo 11.7-T MRI enabled not only to acquire full volume-rendered images of the entire vessels but also to characterize plaque components (such as lipid cores and fibrous caps) at any level and any projection, which were confirmed by histological correlation. Micro-MRI provides an excellent imaging tool for basic science to investigate atherosclerosis in small animal models, which may become a supplement to histopathology of atherosclerotic cardiovascular disease.     

Neurosensory tissue morphology with intraoperative optical fiber probe in aqueous medium

In this work, the author has demonstrated cross-sectional imaging of a retina of an ex vivo fish sample using a common path frequency domain optical coherence tomography at 0.8 μm range. It has been introduced that an integrated surgical hypodermic needle fiber probe can stabilize the flexible glass optical fiber and provides a close proximity to the specimen for intraoperative image guiding. In addition, the light source characteristics were matched to the common path interferometer while operating in the aqueous medium (saline solution), in order to mimic the in vivo condition, in that it shows greater bandwidth and shorter center wavelength for larger input current or output power to sustain the appropriate level of coherence reference peak by the partial reflection at the glass fiber probe interface.     

Tissue velocity imaging of coronary artery by rotating-type intravascular ultrasound

Intravascular ultrasound (IVUS) provides not only the dimensions of coronary artery but the information of tissue components. In catheterization laboratory, soft and hard plaques are classified by visual inspection of echo intensity. So-called soft plaque contains lipid core or thrombus and it is believed to be more vulnerable than a hard plaque. However, it is not simple to analyze the echo signals quantitatively. When we look at a reflection signal, the intensity is affected by the distance of the object, the medium between transducer and objects and the fluctuation caused by rotation of IVUS probe. The time of flight is also affected by the sound speed of the medium and Doppler shift caused by tissue motion but usually those can be neglected. Thus, the analysis of RF signal in time domain can be more quantitative than intensity of RF signal. In the present study, a novel imaging technique called "intravascular tissue velocity imaging" was developed for searching a vulnerable plaque. Radio-frequency (RF) signal from a clinically used IVUS apparatus was digitized at 500 MSa/s and stored in a workstation. First, non-uniform rotation was corrected by maximizing the correlation coefficient of circumferential RF signal distribution in two consecutive frames. Then, the correlation and displacement were calculated by analyzing the radial difference of RF signal. Tissue velocity was determined by the displacement and the frame rate. The correlation image of normal and atherosclerotic coronary arteries clearly showed the internal and external borders of arterial wall. Soft plaque with low echo area in the intima showed high velocity while the calcified lesion showed the very low tissue velocity. This technique provides important information on tissue character of coronary artery.     

Ultrahigh-resolution optical coherence tomography using continuum generation in an air-silica microstructure optical fiber

We demonstrate ultrahigh-resolution optical coherence tomography (OCT) using continuum generation in an air-silica microstructure fiber as a low-coherence light source. A broadband OCT system was developed and imaging was performed with a bandwidth of 370 nm at a 1.3-mu;m center wavelength. Longitudinal resolutions of 2.5 microm in air and ~2 microm in tissue were achieved. Ultrahigh-resolution imaging in biological tissue in vivo was demonstrated.     

Interstitial Doppler optical coherence tomography

Doppler optical coherence tomography (OCT) can image tissue structure and blood flow at micrometer-scale resolution but has limited imaging depth. We report a novel, linear-scanning, needle-based Doppler OCT system using angle-polished gradient-index or ball-lensed fibers. A prototype system with a 19-guage (diameter of approximately 0.9 mm) echogenic needle is constructed and demonstrates in vivo imaging of bidirectional blood flow in rat leg and abdominal cavity. To our knowledge, this is the first demonstration of Doppler OCT through a needle probe in interstitial applications to visualize deeply situated microcirculation.     

Noninvasive imaging of in vivo blood flow velocity using optical Doppler tomography

We report the development of an optical technique for noninvasive imaging of in vivo blood flow dynamics and tissue structures with high spatial resolution (2-10 microm) in biological systems. The technique is based on optical Doppler tomography (ODT), which combines Doppler velocimetry with optical coherence tomography to measure blood flow velocity at discrete spatial locations. The exceptionally high resolution of ODT permits noninvasive in vivo imaging of both blood microcirculation and tissue structures surrounding the vessel, which has significance for biomedical research and clinical applications. Tomographic imaging of in vivo blood flow velocity in the chick chorioallantoic membrane and in rodent skin is demonstrated.     

In vivo label-free photoacoustic microscopy of cell nuclei by excitation of DNA and RNA

Imaging of cell nuclei plays a critical role in cancer diagnosis and prognosis. To image noninvasively cell nuclei in vivo without staining, we developed UV photoacoustic microscopy (UV-PAM), in which 266 nm wavelength UV light excites unlabeled DNA and RNA in cell nuclei to produce photoacoustic waves. We applied UV-PAM to ex vivo imaging of cell nuclei in a mouse lip and a mouse small intestine and to in vivo imaging of the cell nuclei in the mouse skin. The UV-PAM images of unstained cell nuclei match the optical micrographs of the histologically stained cell nuclei. Given intrinsic optical contrast and high spatial resolution, in vivo label-free UV-PAM has potential for unique biological and clinical application.     

Imager that combines near-infrared diffusive light and ultrasound

We introduce an imaging technique that combines complementary features of ultrasound and near-infrared diffusive light imaging. We achieve the combined technology experimentally by mounting an ultrasound array together with multiple laser source and optical detector fibers upon a hand-held probe. The technique is demonstrated with tissue phantoms wherein both acoustic and optical sensors image the volume underneath the probe. Coregistration of acoustic and optical images is achieved with an accuracy of 0.27+/-0.20cm, approximately half of the image pixel size of our prototype. Accurate determination of target optical absorption is also achieved by use of image segmentation on the ultrasound reconstruction. The combined technique may provide improved breast-cancer detection sensitivity and specificity.     

Fast voice-coil scanning optical-resolution photoacoustic microscopy

We developed a photoacoustic imaging system that has real-time imaging capability with optical resolution. The imaging system is capable of scanning at 20 Hz over a 9 mm range and up to 40 Hz over a 1 mm scanning range. A focused laser beam provides a lateral resolution of 3.4 μm as measured in an optically nonscattering medium. Flows of micrometer-sized carbon particles or whole blood in a silicone tube and individual red blood cells (RBCs) in mouse ear capillaries were also imaged in real time, demonstrating the capability to image highly dynamic processes in vivo at a micrometer-scale resolution.     

Selective ablation of atherosclerotic lesions with less thermal damage by controlling the pulse structure of a quantum cascade laser in the 5.7-µm wavelength range

Cholesteryl esters are the main components of atherosclerotic plaques, and they have an absorption peak at the wavelength of 5.75 µm. To realize less-invasive ablation of the atherosclerotic plaques using a quasi-continuous wave (quasi-CW) quantum cascade laser (QCL), the thermal effects on normal vessels must be reduced. In this study, we attempted to reduce the thermal effects by controlling the pulse structure. The irradiation effects on rabbit atherosclerotic aortas using macro pulse irradiation (irradiation of pulses at intervals) and conventional quasi-CW irradiation were compared. The macro pulse width and the macro pulse interval were determined based on the thermal relaxation time of atherosclerotic and normal aortas in the oscillation wavelength of the QCL. The ablation depth increased and the coagulation width decreased using macro pulse irradiation. Moreover, difference in ablation depth between the atherosclerotic and normal rabbit aortas using macro pulse irradiation was confirmed. Therefore, the QCL in the 5.7-µm wavelength range with controlling the pulse structure was effective for less-invasive laser angioplasty.     

A simulation study on tissue harmonic imaging with a single-element intravascular ultrasound catheter

Recently, in vivo feasibility of tissue harmonic imaging with a mechanically rotated intravascular ultrasound (IVUS) catheter was experimentally demonstrated. To isolate the second harmonic signal content, a combination of pulse inversion and analog filtering was used. In this paper the development of a simulation tool to investigate nonlinear IVUS beams is reported, and the influence of transducer rotation and axial catheter-to-tissue motion on the efficiency of PI signal processing is evaluated. Nonlinear beams were simulated in homogeneous tissue-mimicking media at a transmit frequency of 20 MHz, which resulted in second harmonic pressure fields at 40 MHz. The competing effects of averaging and decorrelation between neighboring rf lines on the signal-to-noise ratio (SNR) were studied for a single point scatterer. An optimal SNR was achieved when lines were combined over 3 degrees - 3.75 degrees. When the transducer was rotated with respect to point scatterers, simulating the acoustic response of tissue, the fundamental frequency suppression using PI degraded rapidly with increasing interpulse angles. The effect of axial catheter-to-tissue motion on the efficiency of pulse inversion seemed to be of less influence for realistic motion values. The results of this study will aid in the optimization of harmonic IVUS imaging systems.