Confocal Endoscopic Microscopy and Its Applications

Xuefang Yang; Zhexi Liu; Wang Pu

doi:10.3788/CJL202249.1907002

Chinese Journal of Lasers, Volume. 49, Issue 19, 1907002(2022)

Confocal Endoscopic Microscopy and Its Applications

Xuefang Yang, Zhexi Liu, and Wang Pu^*

Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, China

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Abstract Get PDF(in Chinese)

Figures & Tables(9)

Fig. 1. Schematic of confocal microscopic technology

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Fig. 2. Principle of confocal endoscope with different modes and their scanning mechanisms^[25-26]. (a)(c) Probe-based confocal endoscope with scanning at proximal end of fiber bundle and its proximal scanning mechanism; (b)(d) integrated confocal endoscope with scanning at distal end of single fiber and its distal scanning mechanism

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Fig. 3. Schematic of fiber scanning in spiral scan pattern^[38](co-axial scanner consists of single-mode optical fiber and tubular piezoelectric actuator which are fixed coaxially, and the part of the fiber that sticks out of the tubular piezoelectric actuator acts as cantilever)

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Fig. 4. Schematic of fiber bundle scanning confocal endoscopy^[47]

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Fig. 5. Probe-based confocal laser endomicroscopy (pCLE) criteria for low-grade dysplasia (LGD) and high-grade dysplasia (HGD) in Barrett’s oesophagus^[73]. (a) Dark non-round glands; (b) variable degree of darkness with sharp cut-off; (c) cellular stratification; (d) poorly identifiable goblet cells; (e) glands unequal in size and shape; (f) non-equidistant and irregular cells; (g)“saw-toothed”epithelial surface; (h) non-equidistant glands; (i) enlarged cells

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Fig. 6. eCLE appearance of normal and pathological gastric mucosa^[73] (magnification: 1000×). (a) Normal gastric mucosa in the fundus, where gastric pits are round (solid arrow) and net-like subepithelial capillary network patterns surround the gastric pits (dash arrow); (b) normal gastric mucosa in the body, where gastric pits are round (solid arrow), and honeycomb-like subepithelial capillary network patterns surround gastric pits (dash arrows); (c) normal gastric mucosa in the antrum, where gastric pits are the line type (solid arrow) and coil-shaped subepithelial capillary network patterns surround gastric pits (dash arrow); (d) low grade gastric intraepithelial neoplasia, where gastric pits is different in sizes, capillary network is thickened and circuitous; (e) high grade gastric intraepithelial neoplasia, where gastric pits exhibit abnormal arrangement, and the thickened capillary network and increasing branch present a mass shape

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Fig. 7. Endomicroscopy images of high-grade squamous intraepithelial lesion (HSIL) surface and stained histology sections corresponding to the same imaging locations (scale bar: 50 μm)^[109]. (a)－(d) Endomicroscopy images; (e)－(h) stained histology sections

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Table 1. Different types of confocal endoscopes

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Table 1. Different types of confocal endoscopes

Type

Fiber type

Advantage

Disadvantage

Stage

eCLE

Single-core fiber^[29，38-42]

Point scanning to achieve high resolution

Distal scanning: scanning device is contained in the probe, the scanning device needs to be miniaturized

Commercial EC3870CILK, Pentax (no sale)

pCLE

Fiber bundle^[47-51]

1) Proximal scanning: no scanning device is included in the probe, no size limitation of the scanning device；

2) Easy to operate

1) The resolution is limited by the distance between the cores；

2) The pixelation of the fiber bundle affects the image quality;

3) The background reflection on the end face of the fiber bundle limits the image contrast

Commercial Cellvizio, Mauna Kea Technologies

Chromatic confocal endoscope

Fiber bundle & single-core fiber^[54-56]

1) Multi-wavelength excitation, three-dimensional imaging without mechanical scanning；

2) Simultaneous acquisition of multi-depth information to improve imaging speed

Hard to guarantee large chromatic aberration and small spherical aberration at the same time in the case of lens miniaturization, and the axial resolution is poor due to the spherical aberration of the lens

In research

Table 2. Application of confocal endomicroscopy techniques in biomedicine

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Table 2. Application of confocal endomicroscopy techniques in biomedicine

Position	Disease	Modality
Esophagus	1) Early esophageal squamous cell carcinoma^[78]	Fluorescence confocal
	2) High-grade dysplasia and intramucosal adenocarcinoma^[75]
	3) Barrett’s esophagus and related neoplasia^[74，77]
	4) Mild and moderate dysplasia^[76]
Stomach	1) Atrophic gastritis, intestinal metaplasia, gastric cancer^[79]	Fluorescence confocal
	2) Low- and high-grade intraepithelial neoplasia and differentiated/poorly differentiated adenocarcinoma^[80]
	3) Low- and high-grade intraepithelial neoplasia^[73]
Skin	1) Psoriasis^[87-88]	Reflectance confocal
	2) Malignant pigmented, hyperpigmented and non-pigmented macules on the face^[95]
	3) Melanoma^[96-99]
	4) Skin inflammation^{[89-90，106]}
Eye	1) Keratitis^[114-116]	Fluorescence confocal
	2) Eye toxicity of preservatives^[117-118]
	3) Glaucoma^[119，124]
	4) Cataract^[120-121]
	5) Corneal dystrophy^[116，123]
	6) Corneal intraepithelial neoplasia^[128]
	7) Corneal pathology in Crohn’s disease^[129]
Cervix	1) Epithelial precancerous lesions of the cervix^{[107-110，112-113，132-134]}	Fluorescence confocal & reflectance confocal
Cervix	2) Cellular metabolic changes in dysplastic progression^{[107，117，120]}	Fluorescence confocal & reflectance confocal