自适应多光谱光声成像技术研究

光声成像技术是利用激光照射组织产生超声波成像的新型医学影像技术.在传统光声成像中,由于组织体内复杂的成分与环境会对入射光波产生较大的扰动而导致波前畸变、图像分辨率下降,从而降低诊断的准确性.为了克服这一影响,本文提出了一种自适应多光谱光声成像技术.该技术利用自适应光学技术可有效地降低组织对光波扰动的影响,提高系统成像分辨率与图像对比度.此外,该系统还融合了多光谱成像技术,可在多种波长下对目标成像,从而更好地进行组织结构识别、组分分析等.实验结果表明,该系统十分适用于复杂的生物组织光声成像,可极大地增强光声成像性能,在生物医学领域具有广阔的应用前景.     

多参量光声成像及其在生物医学领域的应用

光声成像兼具声学成像和光学成像两者的优点, 因而成为近十年来发展最迅速的生物医学成像技术之一. 本文介绍了光声成像的特点及其相对于广泛应用的光学成像技术和声学成像技术的优点; 其次, 解释了光声成像的成像原理, 在此基础上介绍了光声断层成像和光声显微镜这两种典型的光声成像方案, 并介绍了它们的技术特点; 然后, 介绍了光声成像对生物组织的生化特性、组织力学特性、血液流速分布、温度分布参数、微结构特性等多信息参量的提取能力, 及其在生物系统的结构成像、功能成像、代谢成像、分子成像、基因成像等多领域的应用; 最后, 展望了光声成像在生物医学领域的应用潜力并讨论了其局限性.     

生物医学光声成像的研究进展

光声成像是21世纪初发展起来的新兴的生物医学成像技术,它同时具备光学成像和声学成像两者的优点,因而备受关注。本文对生物医学光声成像的发展进行了综述。首先,介绍了光声成像的特点以及相对于广泛应用的光学成像技术和声学成像技术的优点;其次,在成像原理上解释了光声成像优点的成因,并介绍了光声断层成像和光声显微镜这两种典型的光声成像技术;再次,详细介绍了多尺度的光声图像分辨率和成像深度,以及多信息维度的光声成像参数;最后,展望了光声成像在生物医学领域的应用潜力并讨论了其局限性。     

光声成像研究进展

本文阐述了光声成像的工作原理,光声信号的产生,传播和探测过程,并总结了光声成像的研究进展,包括时域光声成像和频率域光声成像的研究进展、以及各自的特点,为光声成像领域的研究起到一定的借鉴作用。分析认为光声成像技术有着其他医学成像技术没有的诸多优点,如高分辨率、高对比度、成像深度深等具有广阔的应用前景和较高应用价值,是未来生物医学领域最重要的实时医学成像技术之一,因此得到了国际上的广泛关注。     

基于多元相控技术的一体化光声快速成像系统

利用多元相控技术发展了一体化光声快速成像系统,该成像系统集成了激光传输、光声激发和光声信号探测.多元线性阵列探测器以反射模式接收光声信号,并通过相控聚焦技术快速成像,得到了不同深度的猪油模拟样品的光声像和活体动物不同直径血管的光声像,系统的横向分辨率为0.5 mm,光声采集成像时间为5 s.该一体化光声快速成像系统与现有的光声成像系统相比,具有快速方便等特点.     

改进的同步迭代算法在光声血管成像中的应用

光声成像结合了光学成像和声学成像的优点，是一种高分辨率，高对比度的无损伤医学成像技术.一种改进的同步迭代算法应用于光声图像重建.仿真和模拟结果表明，与传统的代数迭代算法相比，在90°，135°，180°的有限场光声成像中，此算法对测量误差的校正和迭代次数的收敛上具有较大的优势，图像重建的速度和成像质量都有了明显的提高.实验中，一种圆形扫描结构的光声成像装置，用于180°的有限场扫描，利用改进的同步迭代算法，重建出了高对比度和高分辨率（60μm）的鸡胚胎光声血管图像.实验证明，这种算法的应用，大幅度减少了数据采集时间，为光声成像技术运用于实时监测血流灌注和肿瘤光动力治疗的血管损伤效应提供了潜在的应用价值. 关键词： 光声成像 有限角度 代数迭代算法 光声血管成像     

利用维纳滤波改善声透镜光声成像系统的分辨率

为了克服衍射效应对光声成像系统分辨率的限制,需要采用逆卷积方法进行图像反演.从理论上分析了声透镜成像原理,模拟仿真了声透镜的点扩展函数对声透镜成像系统分辨率的影响和维纳滤波解卷积方法复原光声成像的过程,并利用自搭建的声透镜光声成像系统进行了深入的实验研究,得到了物平面上相距4 mm和3 mm的两个黑胶带点的直接成像光声...     

对光声成像系统中声透镜的二元声学研究

基于二元声学的方法提出了一种折射／衍射混合声透镜设计方案,该声透镜在对光声信号进行二维成像时体现出了极大的优越性,与单声透镜相比,除了有实时成像、成像焦深较大且可以利用时间分辨技术实现层析成像的优点外,还可以利用二元声学透镜独特的色散特性校正单声透镜的轴向色差,可以极大提高成像的分辨力。通过计算机模拟了有一定带宽的点声源通过该声透镜像面上的点扩展函数,与经单声透镜的结果比较,可以看出点扩展函数弥散斑得到明显改善,极大地消除色差对成像质量的影响。     

超声分子成像进展

超声分子成像在超声医学成像的基础上,利用靶向超声造影剂为分子探针,以可视化和定量获取活体组织细胞的分子信息为目标的影像术。它不用进行手术活检,不仅可以给出病灶的空间信息,而且能确定它的性质,进行针对性的治疗和对疗效进行评估。本文对现有的核医学分子成像,磁共振分子成像,光学分子成像和光声分子成像技术作了简单介绍,着重讨论了超声分子成像技术和应用的进展。     

二维蜂窝结构声子晶体的负折射成像研究*

为了得到分辨率更好的平板透镜,对此进行了研究。利用有限元的方法研究了由水/水银材料组合的二维蜂窝结构声子晶体平板透镜的负折射成像特性,通过数值仿真计算了声子晶体的能带结构、等频色散曲线,模拟了点源成像,并且利用高斯波束验证了声子晶体平板透镜的负折射现象,得到了有效折射率neff =-1的成像。对比相同材料的正方晶格和三角晶格而言,该模型的成像效果更佳。为了改善成像分辨率,还在原来的模型上进行了改进,得到了分辨率约为0.37λ的亚波长像。     

利用FCLA特征荧光实现单态氧和超氧的高灵敏检测

活性氧(ROS)的检测对生物学和医学研究很多领域方面具有重要意义,如光动力治疗肿瘤的治疗检测、植物应激反应检测、种子活力检测等。实现活性氧中的单态氧、超氧阴离子高灵敏度的检测,是人们追求的目标。研究发现单态氧、超氧的选择性化学发光探针FCLA(fluoresceinyl cypridina luciferin analog)氧化后,在515 nm处荧光会大大增强。利用这个性质并结合非常成熟的荧光检测方法,可以实现活性氧的高灵敏度检测。尤其在微观检测方面,如单细胞, FCLA的化学发光很微弱而难以检测到,但是却可以灵敏地检测到其荧光变化。FCLA荧光检测不仅灵敏度高而且选择性好,其无毒和易于透膜的性质更适于在细胞和生物体上应用。另外如果同时结合FCLA的化学发光,对单态氧和超氧阴离子的检测将更准确、更具实时性。     

光谱法研究FCLA与人血清白蛋白的相互作用

在生物学和医学中活性氧的检测非常重要。海萤荧光素类似物FCLA是检测单态氧(1O₂)和超氧阴离子(O-₂)的一种高灵敏的化学发光探针。文章用光谱法研究了FCLA与人血清白蛋白(HSA)的结合反应,发现FCLA对HSA的荧光有很强的猝灭作用。从荧光猝灭结果求得了FCLA与HSA的结合位点数。根据Frster非辐射能量转移机理探讨了二者相互结合时其给体-受体间的距离和能量转移效率, 从而证实了它们的结合作用为静态猝灭过程。阐明了由于能量转移所导致的HSA荧光的猝灭及FCLA荧光的产生机理。通过光谱法对FCLA与HSA的相互作用的研究,阐明FCLA的运输过程及其在体内的作用机制,对实现利用探针在体检测活性氧具有一定的意义,同时也为药物动力分析、体内药物转运的研究提供了基础。     

In vivo ultrahigh-resolution optical coherence tomography

Ultrahigh-resolution optical coherence tomography (OCT) by use of state of the art broad-bandwidth femtosecond laser technology is demonstrated and applied to in vivo subcellular imaging. Imaging is performed with a Kerr-lens mode-locked Ti:sapphire laser with double-chirped mirrors that emits sub-two-cycle pulses with bandwidths of up to 350 nm, centered at 800 nm. Longitudinal resolutions of ~1mum and transverse resolution of 3mum, with a 110-dB dynamic range, are achieved in biological tissue. To overcome depth-of-field limitations we perform zone focusing and image fusion to construct a tomogram with high transverse resolution throughout the image depth. To our knowledge this is the highest longitudinal resolution demonstrated to date for in vivo OCT imaging.     

In vivo whole-body imaging of optical agent dynamics using full angle fluorescence diffuse optical tomography

Dynamic fluorescence diffuse optical tomography （FDOT） is important in drug deliver research. In this letter, we first image the metabolic processes of micelles indocyanine green throughout the whole body of a nude mouse using the full-angle FDOT system with line illumination （L-FDOT）. The resolution of L-FDOT is evaluated using phantom experiment. Next, in vivo dynamic tomographic images （100 frames; approximately 170 min） of mouse liver and abdomen are shown and cross-validated by planar fluorescence reflectance imaging in vitro. Results provide evidence on applicability of the tomographic image wholebody biological activities in vivo on minute timescale （approximately 1.7 min） using L-FDOT.     

Simultaneous acquisition of multiple orders of intermolecular multiple-quantum coherence images in vivo

Until recently, NMR imaging with intermolecular multiple-quantum coherences (iMQCs) has been based on the acquisition of a single echo. In vivo studies of iMQC image contrast would greatly benefit from a method that could acquire several orders of quantum coherence during the same acquisition. This would enable comparison of the image contrast for various orders and eliminate image coregistration problems between scans. It has previously been demonstrated that multiple orders of iMQC images can be simultaneously acquired of a simple phantom. Here, we examine the technique and its effect on biological tissue, both in vivo and in vitro. First, we establish the effectiveness of the iMQC sequence in vivo using earthworms as specimens. We then further show that the multi-CRAZED sequence enhances detection of next generation (nanoparticle) contrast agents on excised tumor tissue.     

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.     

3D spin-lock imaging of human gliomas

We investigated whether the simultaneous use of paramagnetic contrast medium and 3D on-resonance spin lock (SL) imaging could improve the contrast of enhancing brain tumors at 0.1 T. A phantom containing serial concentrations of gadopentetate dimeglumine (Gd-DTPA) in cross-linked bovine serum albumin (BSA) was imaged. Eleven patients with histologically verified glioma were also studied. T₁-weighted 3D gradient echo images with and without SL pulse were acquired before and after a Gd-DTPA injection. SL effect, contrast, and contrast-to-noise ratio (CNR) were calculated for each patient. In the glioma patients, the SL effect was significantly smaller in the tumor than in the white and gray matter both before (p = 0.001, p = 0.025, respectively), and after contrast medium injection (p < 0.001, p < 0.001, respectively). On post-contrast images, SL imaging significantly improved tumor contrast (p = 0.001) whereas tumor CNR decreased slightly (p = 0.024). The combined use of SL imaging and paramagnetic Gd-DTPA contrast agent offers a modality for improving tumor contrast in magnetic resonance imaging (MRI) of enhancing brain tumors. 3D gradient echo SL imaging has also shown potential to increase tissue characterization properties of MR imaging of human gliomas.     

Accelerated metallic artifact reduction imaging using spectral bin modulation of multiacquisition variable-resonance image combination selective imaging

ObjectivesTo assess the clinical utility of a prototype sequence for metal artifact reduction, the multiacquisition variable–resonance image combination selective (MAVRIC-SL) at 3 T. This sequence allows a surgical prosthesis-dependent reduction in the number of spectral bins. We compared the prototype MAVRIC SL to the conventional two-dimensional fast spin-echo (FSE) sequences and MAVRIC SL images acquired with all spectral bins to those acquired with the optimized number of spectral bins.MethodsMAVRIC SL images were acquired in 25 image sets from August 2017 to April 2018. For each subject, the optimized number of spectral bins was determined using a short spectral calibration scan. The image sets obtained with magnetic resonance imaging that were used for the analysis consisted of MAVRIC-SL proton density (PD)-weighted or short inversion time inversion recovery (STIR) images acquired with all 24 spectral bins, the corresponding images with the optimized number of spectral bins, and the conventional two-dimensional FSE or STIR PD-weighted images. A musculoskeletal radiologist reviewed and scored the images using a five-point scale for artifact reduction around the prosthesis and visualization of the prosthesis and peri-prosthetic tissues. Quantitative evaluation of the peri-prosthetic tissues was also performed. The Wilcoxon rank-sum test was used to test for significance.ResultsThe MAVRIC SL images enabled a significantly improved reduction in metallic artifacts compared to the conventional two-dimensional FSE sequences. The optimized number of spectral bins ranged from 6 to 20, depending on the prosthesis susceptibility difference, size, and orientation to the B₀ field. The scan times significantly decreased with a reduced number of spectral bins (354.0 ± 139.1 versus 283.0 ± 89.6 s; 20% reduced scan time; p < .05). Compared to the MAVRIC SL images acquired with all 24 bins, the artifact reduction and visualization of the prosthesis and peri-prosthetic tissues on the MAVRIC SL images acquired with calibrated bins were not significantly different.ConclusionsCompared to the MAVRIC SL images acquired with all 24 spectral bins, those acquired with an optimized number of spectral bins can reduce metallic artifacts with no significant image quality degradation while providing reduced scan time.     

Microimaging at 14 tesla using GESEPI for removal of magnetic susceptibility artifacts in T(2)(*)-weighted image contrast.

In magnetic resonance imaging (MRI), T(2)(*)-weighted contrast is significantly enhanced by extremely high magnetic field strength, offering broad potential applications. However, the T(2)(*)-weighted image contrast distortion and signal loss artifact arising from discontinuities of magnetic susceptibility within and around the sample are also increased, limiting utilization of high field systems for T(2)(*)-weighted contrast applications. Due to the B(0) dependence of the contrast distortions and signal losses, and the heterogeneity of magnetic susceptibility in biological samples, magnetic susceptibility artifacts worsen dramatically for in vivo microimaging at higher fields. Practical applications of T(2)(*)-sensitive techniques enhanced by higher magnetic fields are therefore challenged. This report shows that magnetic susceptibility artifacts dominate T(2)(*)-weighted image contrast at 14 T, and demonstrates that the GESEPI (gradient echo slice excitation profile imaging) technique effectively reduces or eliminates these artifacts at long TE in the highest field (14 T) currently available for (1)H imaging.     

Spin lock and magnetization transfer MR imaging of focal liver lesions

The present study was designed to evaluate tissue contrast characteristics obtained with the spin-lock (SL) technique by comparing the results with those generated with a magnetization transfer(MT)-weighted gradient echo [GRE, echo-time (TE) = 40 ms] sequence. Twenty-eight patients with hepatic hemangiomas (n = 14), or metastatic liver lesions (n = 14) were imaged at 0.1 T by using identical imaging parameters. Gradient echo, single–slice off-resonance MT, and multiple-slice SL sequences were obtained. SL and MT-effects were measured from the focal liver lesions and from normal liver parenchyma. In addition, tissue contrast values for the liver lesions were determined. Statistically significant difference between the SL-effects of the hemangiomas and metastases, and also between the MT-effects of the lesions was observed (p < 0.02). Tissue contrast values for the lesions proved to be quite similar between the SL and MT techniques. Our results indicate that at 0.1 T multiple-slice SL imaging provides MT based tissue contrast characteristics in tissues rich in protein with good imaging efficiency and wide anatomical coverage, and with reduced motion and susceptibility artifacts.