Application of Imaging Technology to Humans
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Recent development of imaging technology has been remarkable and has given great impact to life science research. Moreover, attempts to apply this novel technique to humans and practice it in clinical medicine have also started. Especially, some articles report the utility of imaging living tissues that do not require any labeling in recent years. This “non-labeling imaging” technique has a great potential in human application and clinical medicine practice. In this review, we describe the application of imaging technology to humans, mainly focusing on the diagnosis of cancer by non-labeling imaging with multiphoton excitation microscopy.
KeywordsMultiphoton excitation microscopy Non-labeling imaging Second harmonic generation Auto-fluorescence Carcinoma diagnosis
Through the history of clinical medicine, detailed observation of patient symptoms has been most important for both diagnosis and treatment, and several attempts to observe the human body more precisely have been conducted for a long time. Of the numerous brilliant inventions, histopathology established by Rudolf Ludwig Karl Virchow continues to occupy the central position of definite diagnosis. However, there still exist some problems with typical histopathological diagnostic procedures. First, histological analysis with biopsy procedure inevitably needs some tissue damage. Second, it takes much time to make a diagnosis after biopsy because of the various steps necessary to make pathological specimens, such as fixation, dehydration, embedding, and staining. Therefore, it is desirable to develop a new histological diagnostic system for use in real time, with a less invasive way. On the other hands, the development of imaging technology has greatly influenced life science research in recent years. Especially, intravital imaging technique has a strong impact because it enables to observe life phenomena visually while keeping animals alive. Multiphoton excitation microscopy (MPM) is one of the major tools used to observe deep regions of the living body using fluorescence and multiphoton absorption process. In the field of life science research, MPM is now widely used for intravital imaging of deep tissues such as brain (Meyer-Luehmann et al. 2008) and bone marrow (Ishii et al. 2009). Now life science and clinical medicine are inseparably connected, and the development of new imaging techniques such as MPM recalls the application to humans in the field of clinical medicine. Especially, malignant neoplasms are extremely important diseases that continue to be a major cause of death all over the world, and have a large number of patients. So detailed diagnosis of cancer at the cellular level through the application of imaging technology is thought to be of great interest all over the world and have much potential demand. However, there are many obstacles before application of MPM to the clinic. One of the most serious hurdles is that it is difficult to label fluorescently cells in human body, because fluorescent dyes are often toxic. It is obviously impossible as well to perform genetic fluorescent labeling unlike laboratory animals such as mice. In recent years, several articles have been reported the methods of imaging living tissues that do not require any labeling. For example, Raman spectroscopy obtains images by detecting Raman scattered light generated when a sample is irradiated with laser light. Depending on the vibrational properties and component distribution such as proteins, lipids, DNA and so on, image contrast generates without any labeling (Freudiger et al. 2008). Photoacoustic microscopy is also known as an efficient tool for non-labeling imaging. It images tissue by photoacoustic effect, a phenomenon in which molecules absorbing light energy emit heat and acoustic waves are generated by volume expansion due to the heat (Yao et al. 2015). There are some reports indicating the usefulness of imaging for human using these techniques described above (Ji et al. 2013; Hsu et al. 2016), and these facts recall the possible utility of non-labeling MPM (NL-MPM) imaging for human. Moreover, fluorescent imaging including MPM is considered superior to these techniques in spatiotemporal resolution. Here, we introduce our attempt of colorectal carcinoma diagnosis by non-labeling imaging for human colorectal tissues using MPM (Matsui et al. 2017).
21.2 MPM Technique Enables to Visualize the Histological Features of Fresh, Unstained Human Colorectal Mucosa and Can Be Used for Histopathological Diagnoses
21.3 Classification by Numerical Parameters Enables to Distinguish NL-MPM Images to Normal and Cancerous Tissues Quantitatively
We have described the diagnostic approach of cancer tissue using NL-MPM imaging as an example of imaging technology application to humans. Although we described the analysis of colon tissue, similar analysis is possible in other organs, depending on the distribution of auto-fluorescent substances as well as the degree of nonlinear optical phenomena (Ulrich et al. 2013; Miyamoto and Kudoh 2013). The usefulness of observing and diagnosing human tissues with imaging system lies in its rapidity and quantitativeness. Deep observation capability is also another useful advantage for MPM imaging, although the observation range is limited now (up to typical depth of 120 μm in colorectal mucosa). In life science research, imaging technologies have made it possible to perform quantitative assessment of life phenomena in real time, and have contributed greatly to elucidation of life phenomena. The usefulness of imaging procedures is also considered high in experiments targeting humans and clinical medicine. We hope that further development of imaging technology will introduce the breakthrough into clinical medicine as well and contribute to the happiness of humans.
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