Source: http://aoot.osa.org/boe/abstract.cfm?uri=boe-10-4-1942
Timestamp: 2019-04-21 00:15:36+00:00

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Stromal collagen organization has been identified as a potential prognostic indicator in a variety of cancers and other diseases accompanied by fibrosis. Changes in the connective tissue are increasingly considered for grading dysplasia and progress of oral squamous cell carcinoma, investigated mainly ex vivo by histopathology. In this study, polarization-sensitive optical coherence tomography (PS-OCT) with local phase retardation imaging is used for the first time to visualize depth-resolved (i.e., local) birefringence of healthy human oral mucosa in vivo. Depth-resolved birefringence is shown to reveal the expected local collagen organization. To demonstrate proof-of-principle, 3D image stacks were acquired at labial and lingual locations of the oral mucosa, chosen as those most commonly affected by cancerous alterations. To enable an intuitive evaluation of the birefringence images suitable for clinical application, color depth-encoded en-face projections were generated. Compared to en-face views of intensity or conventional cumulative phase retardation, we show that this novel approach offers improved visualization of the mucosal connective tissue layer in general, and reveals the collagen fiber architecture in particular. This study provides the basis for future prospective pathological and comparative in vivo studies non-invasively assessing stromal changes in conspicuous and cancerous oral lesions at different stages.
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Fig. 1 PS-OCT system with standard scanner head modified from  for imaging the oral mucosa of the anterior human oral cavity in vivo. The system contains a swept laser source, a fiber-based interferometer including a polarization delay unit, a scanning unit for 2D beam deflection, a reference arm and a polarization-diverse balanced receiver. FC, fiber coupler; OC, optical circulator; RM, reference mirror; BS, beamsplitter; PBS, polarizing beamsplitter; S,P, orthogonal input polarization states; BD, balanced detectors; H,V, horizontal and vertical polarization state channels; GS, galvanometer scanner.
Fig. 2 Measurement points within the anterior oral cavity for representative polarization-sensitive OCT imaging of the oral mucosa. (a) Position A: labial oral mucosa of inner lower lip; Positions B and C: vestibular (mucolabial fold) mucosa; (b) Positions D and E: tip of the dorsal tongue; (c) Positions F and G: lateral dorsal tongue, and Positions H and I: transition of dorsal to ventral lateral tongue; (d) Positions J and K: ventral tongue.
Fig. 3 (a,b,c) Cross-sectional (B-scan) images of the labial oral mucosa by PS-OCT. (a) Intensity image showing the epithelium (EP), papillary layer (PL) and the the dense, fibrous reticular layer (RL). The border between the EP and PL cannot be readily located on the basis of the intensity image. Minor salivary glands (SG) are below the RL. (b) Depth-resolved birefringence (Δn) revealing highly aligned collagen fibers within the RL immediately below and parallel to the EP; (c) Cumulative phase retardation (δ); Images are scaled in depth using refractive index of n = 1.4 . Scale bar: 300 µm. (d,e,f) En-face projections (single slices; imaged area: 2.1 mm × 2.1 mm) of the corresponding data set for (d) the intensity signal (dynamic range 30 dB); (e) the depth-resolved birefringence (Δn range 0.0 × 10−3 - 1.5 × 10−3); (f) the cumulative phase retardation (δ range 0 to π/2) at a depth of 265 µm below the surface (black arrows in (a) and (c)).
Fig. 4 (a,b) Averaged (AVG) intensity and maximum intensity projection of the depth-resolved birefringence (MIP Δn) of N = 30 en-face slices within the RL at measurement point A in Fig. 2(a). (c) Corresponding color depth-encoded tissue birefringence (∆n) for representative depths within the absolute range 214-367 µm below the surface. (d) Resulting color depth-encoded birefringence using isoluminant colormap; Scaling: intensity 20 dB; tissue birefringence Δn 0.3 × 10−3 - 1.5 × 10−3. Salivary glands marked by asterisk. The imaged area corresponds to 2.1 mm × 2.1 mm.
Fig. 5 En-face projections (single slices) of the labial oral mucosa detected at position A in Fig. 2(a) and displayed via B-scans in Fig. 3. (a) Intensity; (b) depth-resolved birefringence (Δn); and (c) cumulative retardation (δ). Depth position 117 µm: papillary layer with epithelial rete ridges and connective tissue papillae showing birefringence due to stretched connective tissue papillae (squares). Depth position 184 µm: transition from PL to RL of the lamina propria with visible gland duct orifice (asterisk). Depths 240 µm and 270 µm: aligned collagen fibers within RL (cross signs). The imaged area corresponds to 2.1 mm × 2.1 mm.
Fig. 6 (a,c) Intensity and birefringence (Δn) at different depths of the reticular layer (RL) within the lamina propria of the inner side of the lower lip at measurement points in Fig. 2(a) labelled B (a) and C (c) presenting the vestibular mucosa (mucolabial fold). The alignment of collagen fibers within the RL and around salivary glands (asterisk) are more visible by means of local tissue birefringence than by intensity. The imaged area corresponds to 2.1 mm × 2.1 mm. (b,d) Corresponding color depth-encoded depth-resolved birefringence. (b) Position B: N = 33 en-face slices; Δn: 0.5 × 10−3 – 1.5 × 10−3. (d) Position C: N = 17 en-face slices; Δn: 0.5 × 10−3 – 1.5 × 10−3.
Fig. 7 (a,c) Intensity and birefringence (Δn) at different depths of the dorsal tongue at measurement points in Fig. 2(b) labelled D (a) and E (c). The birefringence of the connective tissue core of the lingual papillae (filiform and fungiform papillae) is shown. The imaged area corresponds to 2.1 mm × 2.1 mm. (b,d) Corresponding color depth-encoded depth-resolved birefringence. (b) Position D: N = 20 en-face slices; Δn: 0.2 × 10−3 – 1.2 × 10−3. (d) Position E: N = 30 en-face slices; Δn: 0.1 × 10−3 – 1.5 × 10−3.
Fig. 8 (a,c) Intensity and birefringence (Δn) at different depths of the transition region from dorsal to lateral tongue at measurement points in Fig. 2(c) labelled F (a) and G (c). The higher birefringence of aligned collagen fibers surrounding small lingual papillae can be seen. The imaged area corresponds to 2.1 mm × 2.1 mm. (b,d) Corresponding color depth-coded depth-resolved birefringence. (b) Position F: N = 20 en-face slices; Δn: 0.2 × 10−3 – 1.5 × 10−3. (d) Position G: N = 12 en-face slices; Δn: 0.1 × 10−3 – 1.0 × 10−3.
Fig. 9 (a,c) Intensity and birefringence (Δn) at different depths of the transition from dorsal to ventral tongue at measurement points in Fig. 2(c) labelled H (a) and I (c). The imaged area corresponds to 2.1 mm × 2.1 mm. (b,d) Corresponding color depth-encoded depth-resolved birefringence. (b) Position H: N = 21 en-face slices; Δn: 0.3 × 10−3 – 1.5 × 10−3. (d) Position I: N = 31 en-face slices; Δn: 0.3 × 10−3 – 1.5 × 10−3.
Fig. 10 (a,c) Intensity and birefringence (Δn) at different depths of the ventral tongue at measurement points in Fig. 2(d) labelled J (a) and K (c). The imaged area corresponds to 2.1 mm × 2.1 mm. (b,d) Corresponding color depth-encoded depth-resolved birefringence. (b) Position J: N = 25 en-face slices; birefringence Δn: 0.3 × 10−3 – 2.5 × 10−3. (d) Position K: N = 16 en-face slices; Δn: 0.2 × 10−3 – 1.5 × 10−3.

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