DEVELOPMENT AND APPLICATION OF PHOTOACOUSTIC IMAGING FOR THE CLINICAL AND LIFE SCIENCES

本研究的目的是开发一种有前途的新的生物医学成像技术，称为光声（PA）成像。这涉及向组织发射非常短（纳秒）的激光脉冲。光被血管等结构吸收，产生小的加热效应。这导致快速的热弹性膨胀，其产生高频（~数十MHz）声波，该声波穿过组织返回到表面。通过测量这些声波到达位于组织表面上的多个检测器的时间，并且知道声速，可以将声学信号反向投影以产生组织内的内部吸收结构的3D图像。该技术的主要优点是它结合了光学方法的强对比度和超声的高空间分辨率。这可能使该技术成为一种强大的诊断工具，用于识别异常，例如某些类型的癌症肿瘤，这些肿瘤使用常规医学成像技术（如X射线或超声成像）难以看到。该技术具有许多潜在的临床应用，包括检测乳腺肿瘤，评估皮肤异常，如恶性黑色素瘤或软组织损伤，如烧伤或伤口。它还可以用于对小动物进行成像，例如广泛用于模拟各种人类疾病的小鼠。光声成像技术最令人兴奋的特点之一是它能够探测特定的分子过程，即分子成像。这是通过使用探针分子来实现的，所述探针分子强烈吸收某些波长的光并且对特定的细胞或分子受体具有高亲和力，所述特定的细胞或分子受体是特定疾病（例如癌症）的特征。为了将该技术推向实际应用，将进行大量的研究计划。一种新型的高分辨率仪器，设计用于非侵入性成像到几毫米的深度，将开发用于临床使用，例如研究皮肤病理学和小动物模型中疾病过程的临床前研究。将开发能够插入体内并被引导深入体内以成像的内窥镜探针，例如，冠状动脉内部以评估可能积聚并导致心脏病发作的斑块。此外，还将设计一种专门的仪器，用于早期发现和诊断乳腺癌并监测其治疗情况。还将探索和临床测试恢复血氧和血流等生理信息的新方法。计划在人类和小动物体内进行成像，以应用和验证这些方法，特别强调证明该技术在诊断和治疗癌症、心血管疾病和神经系统疾病方面的实用性。总的来说，这项研究提供了开发一种强大的新诊断成像工具的前景，该工具可用于在解剖学，生理学和分子水平上促进我们对疾病机制的理解，并改善癌症和其他主要疾病的临床诊断和治疗。

The purpose of this research is to develop a promising new biomedical imaging technique called photoacoustic (PA) imaging. This involves firing very short (nanosecond) pulses of laser light into tissue. The light is absorbed by structures such as blood vessels producing a small heating effect. This leads to rapid thermoelastic expansion which generates high frequency (~tens of MHz) acoustic waves which travel though the tissue back to the surface. By measuring the time of arrival of these acoustic waves at a number of detectors positioned over the tissue surface, and with knowledge of the speed of sound, the acoustic signals can be backprojected to produce a 3D image of the internal absorbing structures within the tissue. The key advantage of the technique is that it combines the strong contrast of optical methods with the high spatial resolution available to ultrasound. This may make the technique a powerful diagnostic tool for identifying abnormalities such as certain types of cancer tumours that would be difficult to see using conventional medical imaging techniques such as X-ray or ultrasound imaging. This technique has many potential clinical applications, including detecting tumours in the breast, assessing skin abnormalities such as malignant melanomas or soft tissue damage such as burns or wounds. It can also be used to image small animals such as mice which are used extensively to model a wide range of human diseases. One of the most exciting features of photoacoustic imaging is its potential to characterise specific molecular processes, so called molecular imaging. This is achieved using probe molecules that strongly absorb certain wavelengths of light and have a high affinity for a specific cellular or molecular receptor that is characteristic of a particular disease such as cancer. In order to advance the technique to practical application, a substantial research program will be undertaken. A novel high resolution instrument, designed for non invasive imaging to depths of several mm, will be developed both for clinical use, for example to study skin pathologies and for the pre-clinical study of disease processes in small animal models. Endoscopic probes that are capable of being inserted into the body and guided deep within to image, for example, the inside of coronary arteries to assess the plaques that can build up and cause heart attacks will be developed. In addition, a dedicated instrument will be designed for the early detection and diagnosis of breast cancers and monitoring their treatment. Novel methods for recovering physiological information such as blood oxygenation and flow will also be explored and clinically tested. A programme of in vivo imaging both in humans and small animals to apply and validate these methods is planned, with specific emphasis on demonstrating the utility of the technique for the diagnosis and treatment of cancer, cardiovascular disease and neurological conditions. Overall this research offers the prospect of developing a powerful new diagnostic imaging tool that can be used to advance our understanding of disease mechanisms at an anatomical, physiological and molecular level and improving the clinical diagnosis and treatment of cancer and other major diseases.