Clinical translation of handheld optical coherence tomography: practical considerations and recent advancements

Abstract

Since the inception of optical coherence tomography (OCT), advancements in imaging system design and handheld probes have allowed for numerous advancements in disease diagnostics and characterization of the structural and optical properties of tissue. OCT system developers continue to reduce form factor and cost, while improving imaging performance (speed, resolution, etc.) and flexibility for applicability in a broad range of fields, and nearly every clinical specialty. An extensive array of components to construct customized systems has also become available, with a range of commercial entities that produce high-quality products, from single components to full systems, for clinical and research use. Many advancements in the development of these miniaturized and portable systems can be linked back to a specific challenge in academic research, or a clinical need in medicine or surgery. Handheld OCT systems are discussed and explored for various applications. Handheld systems are discussed in terms of their relative level of portability and form factor, with mention of the supporting technologies and surrounding ecosystem that bolstered their development. Additional insight from our efforts to implement systems in several clinical environments is provided. The trend toward well-designed, efficient, and compact handheld systems paves the way for more widespread adoption of OCT into point-of-care or point-of-procedure applications in both clinical and commercial settings.

Keywords: diagnostics; handheld; multimodal; optical coherence tomography; point-of-care; system development.

Fig. 1

Visual representation of stages 1 to 4 OCT systems. As system form factor is reduced, tradeoffs between image quality (SNR, phase stability, resolution, weight, and scan speed) and portability must be managed. For later-stage systems, reducing cost becomes more of a concern as well. Eventually, image quality and system capabilities become more focused on meeting the needs of a clinical application or a commercial product at a specific price point.

Fig. 2

First-generation intraoperative portable spectral-domain OCT clinical system—“The Beast.” OCT images of ex vivo resected tumor masses provide rapid and label-free discrimination of surgical tumor margins. Intraoperative OCT images were correlated and verified with postoperative histology.

Fig. 3

Second-generation intraoperative portable spectral-domain OCT clinical system. (a) OCT system schematic and (b) photo of the OCT system. Physical dimensions were greatly reduced over the previous version. (c, e) Representative intraoperative OCT and (d, f) corresponding histopathology images of a normal, nonmetastatic (left) and cancerous metastatic (right) ex vivo human LNs. All scale bars represent 0.5 mm. Modified and reprinted with permission.

Fig. 4

Third-generation intraoperative portable OCT system and handheld probe. (a) System schematic and (b) handheld probe, when used with surgical sheath, can be used intraoperatively and in situ. (c) Handheld probe and OCT system in portable cart. (d) In vivo images from a partial mastectomy margin. (e) Ex vivo confirmation of conjugate side. OCT images were correlated and confirmed with corresponding histology. Reprinted with permission.

Fig. 5

(a) Portable LCI-otoscopy system. (b) Schematic and photograph of the integration of the LCI fiber-based micro-optic probe into an ear speculum tip that would attach to the otoscope head. (c) Schematic and beam profile of the long-working-distance LCI probe, which used a gradient-index (GRIN) lens. Modified and reprinted with permission.

Fig. 6

Schematic diagram and photograph of the first-generation primary care portable OCT system and handheld scanner. The cart included a broadband source, spectrometer, and additional optical hardware. The handheld scanner contained the sample optical path with galvanometer-based scanning mirrors. With interchangeable tip attachments, the physicians could easily access multiple tissue sites on a patient. Users were able to monitor both video and OCT images of the tissue and save images with a button mounted on the probe handle. Abbreviations: DG, diffraction grating; PC, polarization controller; DC, dispersion compensation materials; NDF, neutral density filter. Modified and reprinted with permission.

Fig. 7

Redesigned first-generation primary care handheld OCT probe with representative data from pediatric human subjects with normal and infected ears. Left: Handheld unit was upgraded to include a MEMS-based scanning unit, new optics layout, and a small 5-in. LCD screen to display both surface video and cross-sectional OCT images during acquisition. (a–c) Representative cross-sectional OCT images of a normal ear, and ones with acute and chronic ear infections, respectively. (d–f) Representative corresponding digital otoscopy images. Modified and reprinted with permission.

Fig. 8

Second-generation primary care system and handheld probe. (a, b) Portable system and handheld probe in the primary care clinic. (c) System in use within our clinical imaging suite. (d) Automated segmentation and thickness analysis of an in vivo human TM. (e) Real-time thickness measurement tracking over time. Modified and reprinted with permission.^,

Fig. 9

Second-generation primary care imaging handheld probe modified to accommodate pneumatic functionality. (a) A rubber ear-bud tip was added to the ear speculum to ensure a pressure seal within the ear canal, along with a pressure sealed probe tip. (b) System schematic showing an input port for the computer-controlled air pressure stimulus (dotted box). This fast axial-scanning LCI system replaced the two-dimensional (2-D) scanning MEMS-driven mirror to lower costs and capture fast dynamic transients of the TM following the pressure stimulus. Abbreviations: M, gold mirror; C, collimator; DM, dichroic mirror; OBJ, objective.

Fig. 10

Third-generation primary care imaging portable system and handheld probe. (a) CAD schematic of cart layout and interior organization. (b) Portable systems testing different material choices (left: powder-coated metal frame and side panels; right: aluminum frame and plastic panels). (c) Schematic of handheld probe layout and final 3-D-printed enclosure. FM, fold mirror; CO, collimation optics; OBJ, objective lens; DM, dichroic mirror.

Fig. 11

(a) Photos representing different handling techniques of an otoscope during use by an experienced ENT otolaryngologist and (b) different grip shapes, materials, and textures in various commercial products.

Fig. 12

(a) Nature-inspired designs for handheld probes. Many future designs were considered for an ergonomic handheld probe. (b) A “doctor’s office of the future.” This lab space was redesigned for human subject imaging, with special attention given to color, layout, and function. The room not only included standard clinical equipment: otoscope, ophthalmoscope, blood pressure and pulse oximetry measurement systems, and sterile healthcare supplies, but also portable primary care imaging systems and teaching tools.

Fig. 13

Ultracompact SLO/OCT high-resolution handheld probe with widefield images assembled through mosaicking. (a) Optical design, schematic, and 3-D rendering of ultracompact handheld probe. SLD, superluminescent diode; APD, avalanche photodiode; Sp, spectrometer; BD, beam dump; RA, reference arm; OAP, reflective collimator (off-axes parabolic mirror); L1–L4, lenses. Blue and red text in the schematic corresponds to components used for imaging in the SLO or OCT modes, respectively. (b) Probe in use in a pediatric human subject. (c) SLO image near fovea. (d) Zoom of (c) (dotted red) to parafoveal receptors. (e) Zoom of (d) (dotted teal), with density calculations in several regions across (d). Modified and reprinted with permission.

Fig. 14

Handheld MEMS-based OCT probe. Demonstration of different grip styles including (a) “power grip” and (b) “camcorder” styles. (c–e) Optical layouts of (c) OCT 1060 nm optical path, (d) iris camera visible optical path, and (e) fixation target visible optical path. (f–j) Motion-corrected widefield volume; (f) en face OCT fundus image. (g–j) Color-indicated OCT scans from various regions in the retina. Modified and reprinted with permission.

Fig. 15

Handheld OCT angiography probe with automated tunable lens focus adjustment. (a) Schematic of the handheld OCTA probe. (b) 3-D perspective view of the probe including all the optical components and the designed plastic case for mounting and holding. (c) Photograph of the handheld OCTA probe with 3-D-printed enclosure. Reprinted with permission.

Fig. 16

Surgical removal of cataract from C’sar, an African elephant at the North Carolina Zoo. The handheld Envisu R2300 OCT scanner from Bioptigen was used to guide surgeons on this delicate surgery, dramatically improving the quality of life for this patient. Image courtesy of Eric Swanson, OCT News, and Eric Buckland, Leica (Bioptigen).

Fig. 17

Tethered capsule OCT endomicroscopy. (a) Overview of the device. The tether allows retrieval of the capsule, which also contains the drive shaft and optical fiber, after being swallowed through the esophagus and passing briefly into the stomach of the subject. Inset: schematic of the capsule. (b) Close-up of capsule with scanning mechanism active and positioned adjacent to a US penny for scale. (c) In vivo tethered capsule endomicroscopy image obtained from a patient with histopathologically confirmed Barrett’s esophagus. (d) Threefold ($3\times$) expanded view showing an irregular luminal surface, heterogeneous backscattering, and glands within the mucosa (arrowheads). Tick marks in (c) represent 1 mm. Scale bars represent 0.5 mm. Reprinted with permission from Macmillan Publishers Ltd.

Fig. 18

Schematic of a handheld rigid laryngoscope-based probe and OCT system. The working distance of the OCT-laryngoscope optical focus can be adjusted by the automated focusing lens, indicated in green, and by the OCT reference arm path-length, indicated in blue. (a) Handheld probe and interrogation area near vocal folds. (b) Photo of handheld probe. Reprinted with permission.

Fig. 19

Schematic of a handheld OCT needle probe system with a 30-gauge needle. Display shows the 3-D visualization of a fetile lamb lung showing alveoli and bronchiole bifurcations. Length of cylindrical scan is 2 mm. Reprinted with permission.

Fig. 20

Tissue boundary detection using OCT-elastography in a handheld needle probe. (a) Schematic of forward facing needle probe and OCT system. Abbreviations: SLD, superluminescent diode; PC, polarization controller; MTS, motorized translation stage; SMF, single-mode fiber; GRIN, gradient-index fiber. (b) Boundary detection in ex vivo porcine tracheal wall with comparative histology. Scale bar represents $100\mu \mathrm{m}$. Reprinted with permission.

Fig. 21

Handheld OCT scanner with a one-dimensional galvanometer-based scanner, suitable for small-scale production. (a, b) Exploded view (itemized) and transparent CAD design of the assembly. 1–17: optical components (see citation). (c) Completed handheld probe. Reprinted with permission.

Fig. 22

SMART handheld. (a) CAD design cross section. Abbreviations: FH, front holder; BH, back holder; J, joint; T, tail; ON, outer needle; IN, inner needle; PM, piezoelectric motor; LL, luer-lock combination; OF, optical fiber. (b) Completed probe, compared to a quarter (US currency). Reprinted with permission.

Fig. 23

Intraoperative MEMS-based handheld Doppler OCT probe to observe microvascular anastomosis. (a) CAD design of handheld probe compared to US currency (quarter). (b) Interior optical design within probe. (c) Handheld probe in hand. Reprinted with permission.

Fig. 24

Multimodal handheld probe for sampling ear infections. (a) Schematic setup of the multimodal RS-LCI probe. (b) Schematic of the LCI (top) and RS (bottom) components. (c) Photograph of the fiber-based RS-LCI probe encapsulated into an ear speculum. The inset shows magnified view of both the RS and LCI beam. Abbreviations: SP, spectrometer; LD, laser diode; SLD, superluminescent diode; and MM, multimode. Reprinted with permission.

Fig. 25

Combined OCT and FI probe schematic and results. (a) Schematic of distal end of the dual-mode endoscope design. A precision-cut metal enclosure (outer diam.: 2.4 mm) shows struts for minimal beam blockage ($<5\%$). A photograph of the constructed endoscope including the transparent sheath is shown below (outer diam.: 2.9 mm). (b) Representative 2-D cross-sectional OCT image and (c) 3-D volume of ex vivo rabbit esophagus (gray) with the overlaid inner annulus (red) of the fluorescence intensity. The normal layered structures of the esophagus can be clearly visualized, including the epithelium (E), lamina propria (LP), muscularis mucosa (MM), and glands (G). Reprinted with permission.

Fig. 26

Handheld OCT-RCM probe. (Top) CAD design and schematic. (Bottom) (a) Clinical image of an erythematous macule. (b) Dermoscopy image of shiny white lines and serpentine vessels in the imaging region. (c) En face and (d) cross-sectional OCT images of hypoechoic areas (arrows), suggestive of BCC. (e) RCM showing cord-like structures with peripheral palisading (arrows) admixed with a fibrotic stroma, suggestive of BCC. (f) Histology of the lesion confirms superficial BCC, with multiple small tumor nests originating from the epidermis (H&E, $4\times$). Modified and reprinted with permission.

Fig. 27

Integrated multimodal (OCT, US, and PAI) probe. (a) Schematic of distal end of probe and optical path. (b) CAD rendering of the probe. (Bottom) Cross-sectional images of human artery with atherosclerotic plaque. (c) PAI image, (d) US image, (e) OCT image, (f) color-coded RGB image, and (g) H & E histology. Reprinted (adapted) with permission from Ref. . Copyright (2016) American Chemical Society.

Fig. 28

Backpack OCT system for crop QC. (a) Schematic of the portable, compact, and battery-powered backpack-OCT system. (b) (1) wearable system, (2) user wearing pack, (3) user scanning plant leaves, and (4) handheld LCD screen. Reprinted with permission.

Fig. 29

Reduced cost linear-OCT handheld probe for ear imaging. (a) Optical layout of handheld probe. (b) An averaged A-line from a TM recorded from an in vivo human subject. (c) Completed (cover removed) handheld LCI imaging probe. Abbreviations: SLD, superluminescent diode; COL, collimation optics; ${\mathrm{BS}}_1/{\mathrm{BS}}_2$, 50:50 beam splitter; OBJ, objective lens; DM, dichroic mirror; DC, dispersion compensation; TS, translation stage; ${\mathrm{C}}_1/{\mathrm{C}}_2$, 2-D CCD camera for recording interference and surface images. Reprinted with permission.