超声调制生物介质中光子自相关性质研究

本文首次用Monte Carlo方法研究了超声调制生物介质中散射光子的时间自相关性质,讨论了超声参数、介质的散射系数和吸收系数对自相关函数的影响。正常生物组织和病变生物组织的自相关函数有明显的判别,超声调制自相关函数为光学医学诊断提供了一种新参考。     

用去卷积法提高超声调制光学成像的空间分辨率

超声调制光学成像的空间分辨率取决于光在组织中的散射程度和扫描超声束的聚焦大小。由于组织是强散射介质,实际应用中的超声束都有一定的聚焦宽度(通常是毫米数量级),所以该技术成像空间分辨率一直无法提高。针对这个问题,首次将去卷积图像处理法运用在超声调制光学成像技术中,有效地解决了扫描超声束带来的信号展开,分辨率下降的影响。理论和防真结果表明,处理后的成像分辨率大大提高,图像质量明显改善。该方法无须对系统装置做任何改动,只利用适当的数据处理,就实现了成像超分辨,具有应用价值。     

生物组织的超声调制光学成像技术

具有超声定位的高空间分辨率和光学检测的高灵敏度的超声调制光学成像技术是一种有前途的无损的生物组织成像技术。文章阐述了该技术的成像原理,评述了前人在散射介质中声光作用机制的理论研究;介绍了该领域在技术路线上的最新研究进展;最后总结了超声调制光学成像技术的优点并展望了其在生物医学领域的应用前景。     

生物光学成像专题征文通知

本专刊主要由有关生物组织光学成像方面的邀稿和投稿组成。近年来 ,在高散射介质中 (尤其在生物组织中 )光输运问题被越来越广泛和深入的研究。这些研究可以开发一些新的无损而又廉价的医学光学成像技术。光学成像因其可以提供生理学功能型的医学影像 ,而引起学术界广泛的关注。光学成像主要包括漫射光断层成像、相干光断层成像 ( OCT)、早到光子技术、超声调制技术、磁光调制技术、偏振调制技术等等方面。在这些技术中 ,相干光断层成像具有较高的空间分辨率 ,技术相对比较成熟 ,但其检测深度有限。漫射光断层成像的空间分辨率是比较低的 …     

生物光学成像专刊征文通知

本专刊主要由有关生物组织光学成像方面的邀稿和投稿组成。近年来 ,在高散射介质中 (尤其在生物组织中 )光输运问题被越来越广泛和深入的研究。这些研究可以开发一些新的无损而又廉价的医学光学成像技术。光学成像因其可以提供生理学功能型的医学影像 ,而引起学术界广泛的关注。光学成像主要包括漫射光断层成像、相干光断层成像 ( OCT)、早到光子技术、超声调制技术、磁光调制技术、偏振调制技术等等方面。在这些技术中 ,相干光断层成像具有较高的空间分辨率 ,技术相对比较成熟 ,但其检测深度有限。漫射光断层成像的空间分辨率是比较低的 …     

生物光子成像专题序言

本专题刊由八篇有关生物组织光学成像方面的邀稿 (Invited papers)及一些常规文章组成。近年来 ,在高散射介质中 (尤其在生物组织中 )光输运问题被越来越广泛和深入的研究。这些研究可以开发一些新的无损而又廉价的医学光学成像技术。光学成像因其可以提供生理学功能型的医学影像 ,而引起学术界广泛的关注。光学成像主要包括漫射光断层成像、相干光断层成像 (OCT)、早到光子技术、超声调制技术、磁光调制技术、偏振调制技术、漫射光断层成像等等方面。另一方面 ,荧光标记成像、单分子探测等等手段 ,拓展了研究范围 ,提供了更多的处理方法…     

调制点光源在散射介质中的传输规律

首次揭示了调制点光源在均匀散射介质中的传输规律.只要调制光信号的中心角频率大大于其带宽且小小于光速与介质吸收系数的乘积,那么调制点光源在均匀散射介质中的峰值能流率分布与稳定的点光源分布相同.     

光声成像及其在生物医学中的应用

光声成像是一种新近迅速发展起来、基于生物组织内部光学吸收差异、以超声作媒介的无损生物光子成像方法,它结合了纯光学成像的高对比度特性和纯超声成像的高穿透深度特性的优点,以超声探测器探测光声波代替光学成像中的光子检测,从原理上避开了光学散射的影响,可以提供高对比度和高分辨率的组织影像,为研究生物组织的结构形态、生理特征、代谢功能、病理特征等提供了重要手段,在生物医学临床诊断以及在体组织结构和功能成像领域具有广泛的应用前景.对光声成像技术的机理、光声成像技术和方法、光声图像重建算法以及光声成像在生物医学上的应用情况作一个简单介绍,希望有助于推动我国在该领域的科研和开发应用工作的迅速发展.     

基于光谱编码的血管内光声组分成像

光声成像突破了传统的光学成像和超声成像在生物组织成像领域的困境,该技术基于光声(Photoacoustic,PA)效应,脉冲激光激励下的生物组织产生超声信号,超声信号被接收后,通过反投影算法将其携带的时间信息和强度信息转化为能够反映生物组织吸收结构和分布的可视化图像。基于不同生物组织的光吸收差异,当激发光强度均匀且稳定时,光声成像反映的就是该物质对于该波长光的吸收特性。本文中,我们基于导管式的血管内光声断层扫描平台结合多波长激发的光声成像算法开发了基于光谱编码的血管内光声组分成像系统,实现了在离体血管斑块中脂质组分的定量成像,高分辨获得了脂质核心的大小形态和边界信息,表征了斑块内的脂质相对含量。     

生物组织的折射和折射率

光在生物组织中的传播与组织的光学性质有关。光通过组织时,光强和光的偏振状态会发生变化。而折射率是组织光学用来评价组织改变光线行进方向的基本参量。本文以菲涅耳公式为理论依据,用空气一组织界面的反射率、生物组织薄膜的反射率和生物组织反射光的倔振分量,推算生物组织的折射率。     

生物组织中有限束宽光吸收的蒙特卡罗模拟

用蒙特卡罗法模拟了有限束宽均匀分布和高斯分布光在生物组织中的传播,分析了生物组织的光学参数及光源特性对光吸收分子的影响,结果表明：只要有效光吸收系数增加,最大光吸收率就会增加,光的侧向传输能力主要依赖于光的有效散射,光束宽度增加,辐照范围加宽,高斯光束的吸收分布的梯度更大。     

High-definition mapping of neural activity using voltage-sensitive dyes

The distribution of patterns of activity in different brain structures has been related to the encoding and processing of sensory information. Consequently, it is important to be able to image the distribution of these patterns to understand basic brain functions. The spatial resolution of voltage-sensitive dye (VSD) methods has recently been enhanced considerably by the use of video imaging techniques. The main factor that now hampers the resolution of VSD patterns is the inherent limitation of the optical systems. Unfortunately, the intrinsic characteristics of VSD images impose important limitations that restrict the use of general deconvolution techniques. To overcomes this problem, in this study an image restoration procedure has been implemented that takes into consideration the limiting characteristics of VSD signals. This technique is based on applying a set of imaging processing steps. First, the signal-to-noise (S/N) ratio of the images was improved to avoid an increase in the noise levels during the deconvolution procedures. For this purpose, a new filter technique was implemented that yielded better results than other methods currently used in optical imaging. Second, focal plane images were deconvolved using a modification of the well-known nearest-neighbor deconvolution algorithm. But to reduce the light exposure of the preparation and simplify image acquisition procedures, adjacent image planes were modeled according to the in-focus image planes and the empirical point spread function (PSF) profiles. Third, resulting focal plane responses were processed to reduce the contribution of optical responses that originate in distant image planes. This method was found to be satisfactory under simulated and real experimental conditions. By comparing the restored and unprocessed images, it was clearly demonstrated that this method can effectively remove the out-of-focus artifacts and produce focal plane images of better quality. Evaluations of the tissue optical properties allowed assessment of the maximum practical optical section thickness using this deconvolution technique in the optical system tested. Determination of the three-dimensional PSF permitted the correct application of deconvolution algorithms and the removal of the contaminating light arising from adjacent as well as distant optical planes. The implementation of this deconvolution approach in salamander olfactory bulb allowed the detailed study of the laminar distribution of voltage-sensitive changes across the bulb layer. It is concluded that (1) this deconvolution procedure is well suited to deconvolved low-contrast images and offers important advantages over other alternatives; (2) this method can be properly used only when the tissue optical properties are first determined; (3) high levels of light scattering in the tissue reduce the optical section capabilities of this technique as well as other deconvolution procedures; and (4) use of the highest numerical aperture in the objectives is advisable because this improves not only the light-collecting efficiency to detect poor-contrast images, but also the spatial frequency differences between adjacent image planes. Under this condition it is possible to overcome some of the limitations imposed by the light scattering/birefringence of the tissue.     

Computational optical biopsy

Optical molecular imaging is based on fluorescence or bioluminescence, and hindered by photon scattering in the tissue, especially in patient studies. Here we propose a computational optical biopsy (COB) approach to localize and quantify a light source deep inside a subject. In contrast to existing optical biopsy techniques, our scheme is to collect optical signals directly from a region of interest along one or multiple biopsy paths in a subject, and then compute features of an underlying light source distribution. In this paper, we formulate this inverse problem in the framework of diffusion approximation, demonstrate the solution uniqueness properties in two representative configurations, and obtain analytic solutions for reconstruction of both optical properties and source parameters.     

Detection of a Novel Mechanism of Acousto-Optic Modulation of Incoherent Light

A novel form of acoustic modulation of light from an incoherent source has been detected in water as well as in turbid media. We demonstrate that patterns of modulated light intensity appear to propagate as the optical shadow of the density variations caused by ultrasound within an illuminated ultrasonic focal zone. This pattern differs from previous reports of acousto-optical interactions that produce diffraction effects that rely on phase shifts and changes in light directions caused by the acoustic modulation. Moreover, previous studies of acousto-optic interactions have mainly reported the effects of sound on coherent light sources via photon tagging, and/or the production of diffraction phenomena from phase effects that give rise to discrete sidebands. We aimed to assess whether the effects of ultrasound modulation of the intensity of light from an incoherent light source could be detected directly, and how the acoustically modulated (AOM) light signal depended on experimental parameters. Our observations suggest that ultrasound at moderate intensities can induce sufficiently large density variations within a uniform medium to cause measurable modulation of the intensity of an incoherent light source by absorption. Light passing through a region of high intensity ultrasound then produces a pattern that is the projection of the density variations within the region of their interaction. The patterns exhibit distinct maxima and minima that are observed at locations much different from those predicted by Raman-Nath, Bragg, or other diffraction theory. The observed patterns scaled appropriately with the geometrical magnification and sound wavelength. We conclude that these observed patterns are simple projections of the ultrasound induced density changes which cause spatial and temporal variations of the optical absorption within the illuminated sound field. These effects potentially provide a novel method for visualizing sound fields and may assist the interpretation of other hybrid imaging methods.     

Ultrasound-biophysics mechanisms

Ultrasonic biophysics is the study of mechanisms responsible for how ultrasound and biological materials interact. Ultrasound-induced bioeffect or risk studies focus on issues related to the effects of ultrasound on biological materials. On the other hand, when biological materials affect the ultrasonic wave, this can be viewed as the basis for diagnostic ultrasound. Thus, an understanding of the interaction of ultrasound with tissue provides the scientific basis for image production and risk assessment. Relative to the bioeffect or risk studies, that is, the biophysical mechanisms by which ultrasound affects biological materials, ultrasound-induced bioeffects are generally separated into thermal and non-thermal mechanisms. Ultrasonic dosimetry is concerned with the quantitative determination of ultrasonic energy interaction with biological materials.

Whenever ultrasonic energy is propagated into an attenuating material such as tissue, the amplitude of the wave decreases with distance. This attenuation is due to either absorption or scattering. Absorption is a mechanism that represents that portion of ultrasonic wave that is converted into heat, and scattering can be thought of as that portion of the wave, which changes direction. Because the medium can absorb energy to produce heat, a temperature rise may occur as long as the rate of heat production is greater than the rate of heat removal. Current interest with thermally mediated ultrasound-induced bioeffects has focused on the thermal isoeffect concept. The non-thermal mechanism that has received the most attention is acoustically generated cavitation wherein ultrasonic energy by cavitation bubbles is concentrated. Acoustic cavitation, in a broad sense, refers to ultrasonically induced bubble activity occurring in a biological material that contains pre-existing gaseous inclusions. Cavitation-related mechanisms include radiation force, microstreaming, shock waves, free radicals, microjets and strain. It is more challenging to deduce the causes of mechanical effects in tissues that do not contain gas bodies. These ultrasonic biophysics mechanisms will be discussed in the context of diagnostic ultrasound exposure risk concerns.     

Fluorescence-enhanced,near infrared diagnostic imaging with contrast agents

The deep tissue propagation of near-infrared (NIR) light between 700-900 nm offers new opportunities for diagnostic imaging when employing sensitive detection techniques and NIR excitable fluorescent agents that target and report disease and metabolism. Herein, we highlight approaches for illuminating tissues and monitoring the re-emitted fluorescence for tomographic reconstruction, strategies for developing fluorescent dye constructs, and clinical opportunities for fluorescence-enhanced NIR optical imaging.     

Uniform light delivery in volumetric optoacoustic tomography

Accurate image reconstruction in volumetric optoacoustic tomography implies the efficient generation and collection of ultrasound signals around the imaged object. Non‐uniform delivery of the excitation light is a common problem in optoacoustic imaging often leading to a diminished field of view, limited dynamic range and penetration, as well as impaired quantification abilities. Presented here is an optimized illumination concept for volumetric tomography that utilizes additive manufacturing via 3D printing in combination with custom‐made optical fiber illumination. The custom‐designed sample chamber ensures convenient access to the imaged object along with accurate positioning of the sample and a matrix array ultrasound transducer used for collection of the volumetric image data. Ray tracing is employed to optimize the positioning of the individual fibers in the chamber. Homogeneity of the generated light excitation field was confirmed in tissue‐mimicking agar spheres. Applicability of the system to image entire mouse organs ex vivo has been showcased. The new approach showed a clear advantage over conventional, single‐sided illumination strategies by eliminating the need to correct for illumination variances and resulting in enhancement of the effective field of view, greater penetration depth and significant improvements in the overall image quality.      

Optical clearing for multiscale biological tissues

Three‐dimensional reconstruction of tissue structures is essential for biomedical research. The development of light microscopes and various fluorescent labeling techniques provides powerful tools for this motivation. However, optical imaging depth suffers from strong light scattering due to inherent heterogeneity of biological tissues. Tissue optical clearing technology provides a distinct solution and permits us to image large volumes with high resolution. Until now, various clearing methods have been developed. In this study, from the perspective of the end users, we review in vitro tissue optical clearing techniques based on the sample features in terms of size and age, enumerate the methods suitable for immunostaining and lipophilic dyes and summarize the combinations with various imaging techniques. We hope this review will be helpful for researchers to choose the most suitable clearing method from a variety of protocols to meet their specific needs.      

Quantitative subsurface spatial frequency‐domain fluorescence imaging for enhanced glioma resection

The rate of complete resection of glioma has improved with the introduction of 5‐aminolevulinic acid‐induced protoporphyrin IX (PpIX) fluorescence image guidance. Surgical outcomes are further enhanced when the fluorescence signal is decoupled from the intrinsic tissue optical absorption and scattering obtained from diffuse reflectance measurements, yielding the absolute PpIX concentration, [PpIX]. Spatial frequency domain imaging was used previously to measure [PpIX] in near‐surface tumors under blue fluorescence excitation. Here, we extend this to subsurface [PpIX] fluorescence under red‐light excitation. The decay rate of the modulation amplitude of the fluorescence signal was used to calculate the PpIX depth, which was then applied in a forward diffusion model to estimate [PpIX] at depth. For brain‐like optical properties in phantoms with PpIX fluorescent inclusions, the depth can be recovered up to depths of 9.5 mm ± 0.4 mm, with [PpIX] ranging from 5 to 15 μg/mL within an average deviation of 15% from the true [PpIX] value.