Propagation of Light in Tissue and Imaging

我们的NICHD合作者继续发展光在组织中传播的理论模型，这些模型解释了光的散射、吸收和偏振状态，并预测了重新发射和传输的光的表面强度的空间分布。这些模型允许重新发射引入的光和由嵌入的生色团产生的荧光光的发射，这些荧光是组织固有的或引入组织中的。通过测量一系列表面强度分布，可以使用逆分析技术重建组织的三维结构。同样，基于偏振的模型允许用与组织相关的散射变化来解释偏振状态的变化。 偏振敏感成像提供了区分皮肤表面下形成的隐藏结构的可能性，例如胶原网，可用于跟踪从正常组织状态到疾病组织状态的转变。皮尔逊相关数据分析技术能够增强图像，并能够表征生物组织的亚表面结构。我们的NICHD合作者正在寻求的一种这样的临床应用是阴道镜检查，以评估可能由疾病或其他因素引起的宫颈变化。与我们的合作者合作，我们设计了该仪器的光学配置和机械布局，制造并测试了适用于商业镜的适配，允许捕获这些偏振敏感测量，同时允许临床医生同时对宫颈进行视觉和摄影或视频评估。该仪器目前正在临床上进行评估。今年，根据临床经验的反馈，我们对该仪器进行了几次修改，使其更易于使用。此外，机械调整增加了相机焦点位置的范围和精度，从而改善了捕获图像的质量和随后的图像分析。这一工具的关键方面是正在进行的专利申请的基础。 在一个正在进行的监测Karposi肉瘤血管系统的相关项目中，正在对一种多光谱成像方式进行评估，以评估由于散射引起的形态变化，同时使用光谱信息评估与临床上正在进行的不同治疗方式相关的血管功能变化--如血管生成和坏死。当前的仪器是基于过滤的顺序改变，这是耗时的，受顺序访问的影响，并且其提供可变照明强度的能力有限。快速随机访问近红外线照明系统减少了执行必要测量所需的时间，并允许患者显著改善。通过毫秒级的分辨率，随机访问不同波长的光(600 nm到1100 nm)，修改照明的带宽和强度，曝光时间从亚毫秒到“无限”，实时分析提供了更完整的临床数据，并允许对临床情况进行后续评估。这些工作的各个方面在以下出版物中涵盖：Kainerstorfer JM，Smith PD，Gandjbakhche AH(2012)用于组织表征的非接触式广域多光谱成像。IEEE Journal of Select Topics in Quantum Electronics 18：1343-1354。 与NICHD和CIT合作，设计了一种便携式仪器，可以评估颅脑损伤后硬膜下血肿的严重程度，从而能够廉价、便携、现场筛查可疑的创伤性脑损伤。在概念上，单个近红外光源和两个分离的探测器安装在手持设备中，可以使用运动作为信号扫描整个头骨，以检测头部硬脑膜区域血容量的变化，从而指示脑损伤的存在。在这一年里，开发了一个原理装置的原型验证和一个带有模拟硬膜下血肿的组织状头部体模并进行了评估。这证明了这种方法的可行性，并产生了出色的夹杂物定位和定量评估结果。这项工作在2011年12月的《生物医学光学快报》的《美国光学学会研究要点》中得到了强调。 在与NICHD小组的其他合作中，我们正在寻求建立一种小型、便携和可穿戴的系统，使用近红外光进行大脑成像。我们设想，用于处理、发送和接收数据的必要的源、探测器和相关电子电路可以安装在头盔内。光源将光耦合到大脑中，接收器收集通过扩散的脑组织传输后产生的光，处理后的数据将能够评估血液动力学响应。为了实现该项目的这一方面，我们最近订购了双波长(780 nm和850 nm)光学电极的原型，我们将把它们集成到患者佩戴的包装中。据估计，头盔内的最终单元将小于4厘米x 4厘米。 我们继续对这些研究中使用的近红外上变频器感兴趣(我们还在寻求将其用作发光标签-见“仪器”年度报告)。通过延伸到光谱的近红外区以及通过使用新的红外化合物作为定位在组织内所需位置的探针，可以识别组织内的更深层次的结构。

Our NICHD collaborators continue to develop theoretical models of light propagation in tissue, which account for scattering, absorption, and polarization state of light, and that predict the spatial profile of the surface intensity of re-emitted and transmitted light. These models allow for both re-emission of the introduced light and emission of fluorescent light generated by an embedded chromophore, either inherent to or introduced into the tissue. Measurement of a series of surface intensity profiles allows reconstruction of the three-dimensional structure of the tissue using inverse analytical techniques. Likewise, polarization-based models allow interpretation of the change of polarization state with scattering changes associated with tissue. Polarization sensitive imaging offers the potential of distinguishing hidden structures developed below the skin surface, such as the collagen network, that can be used to follow the transition from normal to diseased tissue state. Pearson correlation data analysis techniques enable enhancement of images and allow characterization of subsurface structures of biological tissue. One such clinical application being pursued by our NICHD collaborators is colposcopy to assess changes in the cervix that may result from disease or other factors. In partnership with our collaborators we designed both the optical configuration and mechanical layout of this instrument, fabricated, and tested an adaption to a commercial colposcope that permits these polarization sensitive measurements to be captured and at the same time allows the clinician simultaneous visual and photographic or video assessment of the cervix. This instrument is currently being evaluated in the clinic. In the current year, based on feedback form the clinical experience, we have made several modifications to the instrument to make it more user-friendly. Additionally, a mechanical adaptation has increased the range and precision of the cameras focal position that has improved the quality of the captured images and the subsequent image analysis. Key aspects of this instrumentation are the basis of an ongoing patent application. In a related on-going project to monitor the vasculature of Karposi's sarcoma, a multi-spectral imaging modality is being evaluated to assess changes in morphology due to scattering and simultaneously to use spectral information to assess changes in vasculature function - such as angiogenesis and necrosis - associated with the different treatment modalities being pursued in the clinic. The current instrumentation is based on sequential change of filtration that is time consuming, subject to sequential access, and limited in its ability to provide for variable intensity of illumination. A fast random-access near-infra-red illumination system reduces the time taken to perform the necessary measurements and allows for a significant improvement for the patient. Through millisecond resolution, random access to different wavelengths of light (600nm to 1100nm), modification of the bandwidth and intensity of illumination, exposure times from sub-millisecond to "infinite and real time analysis provides more complete clinical data and allows for follow-up assessment of clinical condition. Aspects of this work are covered in the following publication: Kainerstorfer JM, Smith PD, Gandjbakhche AH (2012) Noncontact wide-field multispectral imaging for tissue characterization. IEEE Journal of Selected Topics in Quantum Electronics 18:1343-1354. In collaboration with both NICHD and CIT, a portable instrument was designed that assesses the severity of sub-dural hematomas following head injury that should enable inexpensive, portable, on-site screening of suspected traumatic brain injury. In concept, a single near ir light source and dual separated detectors are mounted in a hand-held device that can be scanned across the skull using motion as a signal for detecting changes in blood volume in the dural regions of the head, thus indicating the presence of brain injury. In the current year, a prototype proof of principle device and a tissue-like head phantom with a simulated sub-dural hematoma were developed and evaluated. These demonstrated the viability of such an approach and produced results with excellent localization of inclusions and quantitative assessment. This work was highlighted in the Optical Society of America Research Highlights from Biomedical Optics Express for December 2011. In other collaborations with the NICHD group, we are pursuing building a small, portable, and wearable system that uses near infrared light for brain imaging. We envision that the necessary sources, detectors, and associated electronic circuits for processing, transmitting and receiving data can be mounted within a helmet. The optical source couples light into the brain and the resulting light after transmission through the diffusive brain tissue is collected by the receivers, and the processed data will enable an evaluation of the hemodynamic response. To enable this aspect of the project, we have recently ordered prototype dual-wavelength (780nm and 850nm) optrodes that we will integrate into the package worn by the patient. It is estimated that the final unit within the helmet will be less than 4cm x 4cm. We continue our interest in the use of near infrared upconverters for use in these studies (we are also pursuing the use of these as luminescent labels - see "Instrumentation" annual report). Identification of deeper structures within the tissue is possible by extending to the near infra-red region of the spectrum and by the use of novel infrared compounds to act as probes localized at desired sites within the tissue.