Propagation of Light in Tissue and Imaging

我们的NICHD合作者继续开发光在组织中传播的理论模型，该模型考虑了光的散射，吸收和偏振状态，并预测了重新发射和透射光的表面强度的空间分布。 这些模型允许引入的光的再发射和由嵌入的发色团产生的荧光的发射，所述发色团是组织固有的或引入到组织中。 一系列的表面强度分布的测量允许使用逆分析技术的组织的三维结构的重建。同样，基于偏振的模型允许解释偏振状态的变化以及与组织相关联的散射变化。 偏振敏感成像提供了区分皮肤表面下形成的隐藏结构的潜力，例如胶原蛋白网络，其可用于跟踪从正常组织状态到患病组织状态的转变。 皮尔逊相关数据分析技术能够增强图像，并允许表征生物组织的亚表面结构。我们的NICHD合作者正在追求的一个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子宫颈变化。 在与我们的合作者的合作中，我们设计了该仪器的光学配置和机械布局，制造并测试了对商业阴道镜的适应，该阴道镜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。 目前，该仪器正在临床上进行评估。 于本年度，根据临床经验的反馈，我们已对仪器作出若干修改，使其更易于使用。 此外，机械适配增加了相机焦点位置的范围和精度，这提高了捕获图像的质量和随后的图像分析。 该仪器的关键方面是正在进行的专利申请的基础。 在一个相关的正在进行的项目，以监测卡波西肉瘤的血管，多光谱成像模式正在进行评估，以评估由于散射的形态变化，同时使用光谱信息，以评估血管功能的变化-如血管生成和坏死-与临床上追求的不同治疗模式。 目前的仪器是基于过滤的顺序变化，这是耗时的，受到顺序访问，并在其能力有限，以提供可变的照明强度。 快速随机访问近红外照明系统减少了执行必要测量所需的时间，并为患者提供了显著的改善。 通过毫秒级分辨率、随机访问不同波长的光（600 nm至1100 nm）、修改照明的带宽和强度、曝光时间从亚毫秒到“无限”和真实的时间分析，提供了更完整的临床数据，并允许对临床状况进行后续评估。 这项工作的各个方面涵盖在以下出版物中：Kainerstorfer JM，Smith PD，Gandjbakhche AH（2012）非接触式宽场多光谱成像用于组织表征。IEEE Journal of Selected Topics in Quantum Electronics 18：1343-1354. 与NICHD和CIT合作，设计了一种便携式仪器，用于评估头部损伤后硬膜下血肿的严重程度，可以对疑似创伤性脑损伤进行廉价，便携式，现场筛查。 在概念上，单个近红外光源和两个分离的检测器安装在手持设备中，该手持设备可以使用运动作为检测头部硬脑膜区域中血容量变化的信号来扫描整个颅骨，从而指示脑损伤的存在。 在本年度，开发并评价了原理装置的原型证明和具有模拟硬膜下血肿的组织样头部体模。 这证明了这种方法的可行性，并产生了良好的夹杂物和定量评估的本地化的结果。 这项工作在2011年12月的美国光学学会生物医学光学快报的研究亮点中得到了强调。 在与NICHD小组的其他合作中，我们正在寻求建立一个小型，便携式和可穿戴的系统，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源、检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，并且在传输通过漫射脑组织之后所产生的光由接收器收集，并且经处理的数据将使得能够评估血液动力学响应。 为了实现该项目的这一方面，我们最近订购了原型双波长（780 nm和850 nm）光极，我们将集成到患者佩戴的包装中。 据估计，头盔内的最终单位将小于4cm x 4cm。 我们继续对近红外上转换器在这些研究中的使用感兴趣（我们也在寻求将其用作发光标签-参见“仪器”年度报告）。 通过扩展到光谱的近红外区域，并通过使用新型红外化合物作为定位在组织内所需部位的探针，可以识别组织内的更深结构。

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.