Towards disease diagnosis through spectrochemical imaging of tissue architecture.

该提案汇集了来自卡迪夫大学、兰开斯特大学、利物浦大学和曼彻斯特大学的大量科学家，以及来自克里斯蒂大学、兰开斯特大学和利物浦NHS医院信托基金的临床医生，他们具有互补的经验和专业知识，以促进对宫颈癌、食管癌和前列腺癌的理解、诊断和治疗。宫颈癌和前列腺癌非常常见，食管癌的发病率正在迅速上升。有细胞学、活组织检查和内窥镜检查技术可以从有发展这些疾病风险的个体中提取组织。然而，用标准技术分析组织是有问题的和主观的。显然，国家和国际上都需要为这些疾病制定更准确的诊断方法，这是本建议的一个主要目标。将使用四种不同的红外技术对所有三种疾病的标本进行实验，这些技术具有互补的优点和缺点：高光谱成像、拉曼光谱、将通过原子力显微镜与红外光谱相结合而开发的新仪器以及最近安装在达斯伯里ALICE加速器上的自由电子激光器上的扫描近场显微镜。后一种仪器最近被证明在食管癌的研究中具有相当大的潜力，产生的图像显示了前所未有的空间分辨率（0.1微米）的化学成分，而高光谱成像和拉曼光谱已经被团队成员证明可以提供高分辨率光谱，从而深入了解宫颈癌和前列腺癌的性质。新仪器将安装在达斯伯里的自由电子激光器上，并将产生纳米级的图像。这种技术的结合将使研究小组能够以前所未有的准确性探测这三种癌症的物理和化学结构，这将揭示有关它们的特征和恶性行为背后的化学过程的重要信息。这项研究的结果将对癌症研究产生广泛的兴趣，特别是如果它揭示了这三种癌症的共同特征。红外技术具有相当大的医学潜力，并在不同程度上即将找到实际应用。较新的太赫兹技术在这一领域也有很大的潜力，而且实施起来可能更便宜。不幸的是，廉价便携式太赫兹诊断仪器的发展受到现有太赫兹辐射源的弱点的阻碍。通过利用ALICE加速器的太赫兹辐射，该团队将推进两种不同太赫兹仪器的设计，并评估它们与更发达的红外技术在癌症诊断中的表现。然而，在医学专业人员使用这些技术之前，必须充分了解它们的优点和局限性。这是该提案的目标之一，它将通过比较每种技术在三种癌症样本研究中的结果来实现，这是研究的主要焦点。这将伴随着为光谱和成像数据的自动分析开发数据基础和算法，从而消除诊断过程中的主观性。最后，该团队将探索一种新的方法来监测病原体，药物和相关细胞或组织在细胞和亚细胞水平上的相互作用，使用部署在达斯伯里自由电子激光器上的仪器和拉曼显微镜。如果这项研究取得成功，从长远来看，它将对开发治疗癌症和其他疾病的新疗法具有重要意义。

This proposal brings together a critical mass of scientists from the Universities of Cardiff, Lancaster, Liverpool and Manchester and clinicians from the Christie, Lancaster and Liverpool NHS Hospital Trusts with the complementary experience and expertise to advance the understanding, diagnosis and treatment of cervical, oesophageal and prostate cancers. Cervical and prostate cancer are very common and the incidence of oesophageal is rising rapidly. There are cytology, biopsy and endoscopy techniques for extracting tissue from individuals who are at risk of developing these diseases. However the analysis of tissue by the standard techniques is problematic and subjective. There is clearly a national and international need to develop more accurate diagnostics for these diseases and that is a primary aim of this proposal. Experiments will be conducted on specimens from all three diseases using four different infrared based techniques which have complementary strengths and weaknesses: hyperspectral imaging, Raman spectroscopy, a new instrument to be developed by combining atomic force microscopy with infrared spectroscopy and a scanning near field microscope recently installed on the free electron laser on the ALICE accelerator at Daresbury. The latter instrument has recently been shown to have considerable potential for the study of oesophageal cancer yielding images which show the chemical composition with unprecedented spatial resolution (0.1 microns) while hyperspectral imaging and Raman spectroscopy have been shown by members of the team to provide high resolution spectra that provide insight into the nature of cervical and prostate cancers. The new instrument will be installed on the free electron laser at Daresbury and will yield images on the nanoscale. This combination of techniques will allow the team to probe the physical and chemical structure of these three cancers with unprecedented accuracy and this should reveal important information about their character and the chemical processes that underlie their malignant behavior. The results of the research will be of interest to the study of cancer generally particularly if it reveals feature common to all three cancers. The infrared techniques have considerable medical potential and to differing extents are on the verge of finding practical applications. Newer terahertz techniques also have significant potential in this field and may be cheaper to implement. Unfortunately the development of cheap portable terahertz diagnositic instruments is being impeded by the weakness of existing sources of terahertz radiation. By exploiting the terahertz radiation from the ALICE accelerator, which is seven orders of magnitude more intense that conventional sources, the team will advance the design of two different terahertz instruments and assess their performance against the more developed infrared techniques in cancer diagnosis. However before any of these techniques can be used by medical professionals it is essential that their strengths and limitations of are fully understood. This is one of the objectives of the proposal and it will be realised by comparing the results of each technique in studies of specimens from the three cancers that are the primary focus of the research. This will be accompanied by developing data basis and algorithms for the automated analysis of spectral and imaging data thus removing subjectivity from the diagnostic procedure. Finally the team will explore a new approach to monitoring the interactions between pathogens, pharmaceuticals and relevant cells or tissues at the cellular and subcellular level using the instruments deployed on the free electron laser at Daresbury together with Raman microscopy. If this is successful, it will be important in the longer term in developing new treatments for cancer and other diseases.