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**10**

**13**

**Chapter 2**

**Abstract**

**1. Introduction**

Microendoscope

optical imaging modalities will be introduced in detail.

**Keywords:** optical imaging, microendoscope, micromachining,

micro-opto-electromechanical systems (MOEMS), confocal, multiphoton, wide-field, photoacoustic, Raman, surface-enhanced Raman scattering (SERS)

Optical imaging is a key part of molecular imaging which allows the in vivo characterization and measurement of biological process at the cellular and molecular level [1–3]. It uses the interaction between light and tissue to probe tissue morphology and functions. Compared to other molecular imaging techniques, such as magnetic resonance imaging (MRI) [4], computed tomography (CT) [5], ultrasound (US) [6], single-photon emission computed tomography (SPECT) [7], and positron-emission tomography (PET) [8], optical imaging builds an interdisciplinary approach to noninvasively probe disease-specific morphology and functions with high resolution. Biochemically specific contrast from light absorption, scattering, and fluorescence are widely used in optical imaging approaches, providing precise information from the tissue morphology, anatomy, and physiology. Optical imaging has been applied in a variety of biological research and is very useful in the early-stage diagnosis of diseases and monitoring the treatment outcomes [9, 10]. Optical imaging has been undergoing explosive growth over the past few decades since it is not limited to specific image-capture methods but includes various modalities, such as confocal fluorescence [11], wide-field fluorescence [12], multiphoton fluorescence and SHG imaging [13–15], photoacoustic tomography (PAT) [16], and SERS nanoparticle-based Raman spectroscopy [17–19] which are the major techniques optimized for different target visualization. The summary and comparisons are listed in **Table 1**. Wide-field, confocal, SERS-based Raman

*Lin Huang and Zhen Qiu*

Multimodal Optical Imaging by

In the past decades, optical imaging field has been developing rapidly. Noninvasive imaging enabled by microendoscopes has become a promising tool for early cancer detection and imaging-guided surgery. In this chapter, we will mainly introduce most advances in the miniaturized microendoscope development, including photoacoustic, confocal fluorescence, multiphoton fluorescence, second-harmonic generation (SHG) label-free imaging, wide-field fluorescence, surface-enhanced Raman scattering (SERS) nanoparticle-based Raman spectroscopy. Enabled by the frontier micromachining techniques, micro-opto-electromechanical system (MOEMS)-based novel microendoscopes with various imaging modalities have been prototyped and further translated into clinics. The working principle of representative microendoscopes and

#### **Chapter 2**
