Finger-mounted quantitative micro-elastography

We present a finger-mounted quantitative micro-elastography (QME) probe, capable of measuring the elasticity of biological tissue in a format that avails of the dexterity of the human finger. Finger-mounted QME represents the first demonstration of a wearable elastography probe. The approach realizes optical coherence tomography-based elastography by focusing the optical beam into the sample via a single-mode fiber that is fused to a length of graded-index fiber. The fiber is rigidly affixed to a 3D-printed thimble that is mounted on the finger. Analogous to manual palpation, the probe compresses the tissue through the force exerted by the finger. The resulting deformation is measured using optical coherence tomography. Elasticity is estimated as the ratio of local stress at the sample surface, measured using a compliant layer, to the local strain in the sample. We describe the probe fabrication method and the signal processing developed to achieve accurate elasticity measurements in the presence of motion artifact. We demonstrate the probe’s performance in motion-mode scans performed on homogeneous, bi-layer and inclusion phantoms and its ability to measure a thermally-induced increase in elasticity in ex vivo muscle tissue. In addition, we demonstrate the ability to acquire 2D images with the finger-mounted probe where lateral scanning is achieved by swiping the probe across the sample surface. © 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement


Introduction
For centuries, physicians have relied on the sense of touch to qualitatively assess disease based on changes in the mechanical properties of tissue, i.e., manual palpation [1].The sustained and widespread clinical use of manual palpation is largely attributed to the dexterity of hand motion and its ease of use [2,3].However, the inherent subjectivity, lack of quantification and relatively low spatial resolution, limit the efficacy of manual palpation in correctly identifying diseased tissue [4].One proposed solution is elastography, a family of imaging techniques developed over the past 30 years that map tissue elasticity by combining medical imaging with mechanical deformation [5].Elastography was initially developed using ultrasound [6,7] and magnetic resonance imaging [8], and has been proposed for a range of clinical applications, particularly in hepatology [9,10] and oncology [11].More recently, optical coherence tomography (OCT)-based elastography, optical coherence elastography (OCE), has been developed to improve both the spatial resolution (to 10s-100s µm) and sensitivity (to nanometer-scale deformations) in comparison to other approaches, albeit to a relatively shallow imaging depth of ~1 mm in turbid tissue [12][13][14][15][16][17][18].OCE is undergoing development in a range of fields, most prominently in ophthalmology [19], cardiology [20], and oncology [21,22].As a photonics-based technique, OCE is amenable to miniaturization into small form factor probes, such as needles and endoscopes [23][24][25].Such probes have the potential to enhance the clinical applicability of OCE.Initially, OCE probes, such as needle OCE, were limited to measurements of strain, yielding qualitative assessments and providing low contrast in some instances [26].For clinical applications, quantitative imaging can aid in the identification of diseased tissue, facilitate rapid interpretation of results and also enable more ready comparison of results obtained from different patients.More recently, to address this, there have been several demonstrations of quantitative OCE probes [25,27], however, in these demonstrations mechanical loading was applied using bulky mounted set-ups or by motorized stages that are impractical for routine use by clinicians.
Here, we propose a novel OCE probe, in which the sample arm of an OCE system is encased in a 3D-printed thimble and worn on the finger.This technique represents the first finger-mounted, and indeed wearable, version of OCE.In addition, more broadly, there have been few demonstrations of a free-hand OCE probe without the need for supporting apparatus [28].Our methodology is based on quantitative micro-elastography (QME) [29,30], a compression-based OCE technique that utilizes phase-sensitive detection to estimate the elasticity of a sample by combining the surface stress, measured using a compliant layer, with the local axial strain measured throughout the OCT field-of-view.To realize finger-mounted QME, we extend on QME signal processing to generate accurate elasticity measurements in the presence of motion artifact induced by the finger.
Finger-mounted QME has the potential to preserve much of the dexterity and ease of use of manual palpation, whilst also providing the quantification, relatively high spatial resolution and depth-sectioning capability of OCE.This technique may increase the clinical applicability of OCE, particularly in scenarios where the use of a relatively bulky handheld probe is not convenient, e.g., in assessing if residual tumor is present in small cavities following excision of the main tumor mass in breast-conserving surgery.In this paper, we provide experimental validation of finger-mounted QME on homogeneous, bi-layer and inclusion phantoms and ex vivo muscle tissue.We demonstrate that finger-mounted QME is capable of measuring the elasticity of silicone phantoms to within 21% of the expected value (compared to 8% for a bench-top implementation of QME [29]), and that it can distinguish the change in mechanical properties between raw and cooked kangaroo muscle tissue.Furthermore, we demonstrate a method to perform 2D scanning in finger-mounted QME by swiping the probe across the sample surface with a gentle, yet increasing, compression.The results presented in this paper highlight the potential of finger-mounted QME for development towards clinical applications that currently rely on manual palpation.

Probe design
Finger-mounted QME comprises a fiber probe (illustrated in Figs.1(a) and 1(b)) connected to a spectral-domain OCT system (TEL320, Thorlabs, USA) with a central wavelength of 1300 nm, a 3 dB-bandwidth of 170 nm, and a measured full-width-at-half-maximum (FWHM) axial resolution of 5.2 µm.The probe is configured as a common-path interferometer to maximize displacement sensitivity [10], which was measured to be 1.44 nm for an OCT signal-to-noise (SNR) of 40 dB [30].The probe consists of a single mode fiber (SMF) spliced to a 270 µm length of graded-index (GRIN) fiber (Miniprobes, Australia) that focuses the beam into the sample.The fiber probe is embedded within a thin channel along the underside of a 3D-printed thimble, as illustrated in Fig. 1(b), using an ultra-violet-curable optical adhesive (NOA68, Norland Products, USA).The adhesive also seals the fiber in place at the tip of the thimble (adhesive thickness, 70 µm) and provides the reference reflection in the common-path interferometer.In finger-mounted QME, A-scans are acquired at 10 kHz.
Two fiber probes were used in this study, manufactured to the same specifications; Probe 1 was used to generate the results presented in Figs.2-4, and Probe 2 was used for Figs.

Finger-m
Finger-mount imaging syste stress at the quantified as on the surface elastic modul measuring the sample interfa axial displace The probe orthogonally sample surfac compliant lay (M-mode) im (estimated fr to, u z = Δφλ material's refr Fig. 2 time.compl phanto n the OCT field aries within sa d 0.5 mg.ml − phantom was ed within a soft on was 160 kP mg.ml −1 to the ength × height ress in QME w t layer material yers had an ela thick and conta mounted QME ted QME is b em [29].In thi sample surface the ratio of the e of the sample lus with strain e strain in the l ace [32].The s ement using a f e is worn on to the tissue su ce.To deform yer and the sam mage, as show rom the phas λ/4πn, where λ fractive index [      confirmed qualitatively during the experiment by manual palpation and is consistent with prior studies on muscle tissue from other species [36].We can see in Fig. 6(e) that the measurements for the cooked sample in the stress range 0-3 kPa, show a lower elasticity than the raw sample.This discrepancy is likely due to the probe not being positioned exactly perpendicular to the surface, decoupling the direction of the applied force and the axis which is scanned, resulting in a lower measured elasticity.This phenomenon is noticeable in tissue scans due to the heterogeneous structure, however, it reduces with higher stresses.This is most likely because of the operator's finger naturally tending towards perpendicular in order to apply higher forces to the sample [37].

2D scanning on a silicone inclusion phantom
In addition to M-mode scanning, as shown in Fig. 7, we also acquired preliminary 2D scans with finger-mounted QME by swiping the finger across a silicone inclusion phantom whilst acquiring A-scans.A compliant layer was placed on the inclusion phantom and the probe was brought into contact the layer.During scanning, the finger applied both a lateral and axial motion, resulting in a ramp compression to the compliant layer and phantom.The increasing axial compression is a function of lateral position and ensured sufficient incremental strain was applied between consecutive A-scans.The speed at which the finger was swept across the sample was determined empirically by observing the real-time OCT image.The scans presented in Fig. 7 were taken on the inclusion phantom described in Section 2.2.The contrast between the surrounding bulk and the embedded inclusion is visible in the OCT image shown in Fig. 7(a).It is worth noting that the total length of the scan was ~5 mm and the inclusion was 1 mm wide.Considering this, it is apparent from Fig. 7 that the scanning performed by the finger is non-uniform, highlighting the effect of varying speeds of lateral hand motion.This results in a difference between the perceived and true dimensions of the imaged features, suggesting that a mechanism to compensate for this non-uniform scanning is required.This issue is described in more detail in the Discussion.
In finger-mounted QME, we consider compressive strain to be negative, and tensile strain to be positive [38].Furthermore, we assume that compression is uniform and uniaxial.This, however, does not always hold true as mechanical heterogeneity and complex surface topologies can introduce tensile strain as well as compressive strain [38].This is evident in 2D finger-mounted QME as the probe sweeps over the boundary between the bulk and inclusion, where regions of tensile strain were measured.To account for the presence of both compressive and tensile strain, Fig. 7(b) displays the magnitude of the elasticity, taken from both the positive (tensile) and negative (compressive) strains.The mean measured elasticity and standard deviation of this scan was 51 ± 4 kPa and 318 ± 67 kPa over 10-15% preload strain in the bulk and inclusion, respectively.These values are approximately twice the expected elasticity.While the contrast between the inclusion and bulk is apparent, there are regions of high elasticity that appear as orange lines in Fig. 7(b).The local boundary between tensile and compressive strain crosses zero, resulting in an asymptote in elasticity, corresponding to the orange lines.Due to the large smoothing kernels used in the processing code, this artifact also effects the surrounding regions of the bulk and inclusion, contributing to the overestimation of elasticity in these regions.This can be observed in the thin region of bulk above the inclusion.The mean measured elasticity in this region is 125 ± 12 kPa, ~2.5 times the measured elasticity in the rest of the bulk.Furthermore, the use of a logarithmic scale reduces the contrast of this particular region relative to the inclusion, however, there is still sufficient contrast in the elasticity measurements to delineate the inclusion from the bulk.

Discussio
In this paper, measurements probe.While palpation, fin palpation wit because the n probe, we hav delineate the compact impl surgical cavit [29].This rep and diseased carcinoma in cirrhotic liver The error force between compliant lay deformation o from the com elasticity of t like tissue, ex rain, this relati ain in the sam y linear regio the bulk will bulk, allows 2 g. applied to both sides of the compliant layer to mitigate this friction on both the imaging window and the sample [29].In finger-mounted QME, however, PDMS oil is only applied to the probe-compliant layer interface as PDMS oil between the sample and compliant layer, coupled with the indenter-like profile of the probe tip, will cause the compliant layer to slip during scanning.At higher stresses, the compliant layer will slip completely off the sample, therefore preventing the estimation of elasticity.Applying oil to only the probe-compliant layer interface, results in an increased error due to friction compared to the bench-top counterpart.This error is also seen in the measurement of Layer 2 for the bi-layer scans presented in Fig. 5, however, in the same scan Layer 1 was slightly overestimated.This overestimation may be due to a similar effect, where Layer 2 restricts the lateral expansion of the thinner top layer, resulting in a lower axial strain and a higher measured elasticity, which was prominent enough to dominate the effects of friction at the compliant layer-Layer 1 interface.Finger-mounted QME demonstrated a MAPE of 22% and 8% for the upper and lower layers respectively, which is similar to the 15% reported by benchtop QME [29].This shows that despite the simplified optical design and hand-motion associated with the fingermounted probe, this technique is still capable of reproducing elasticity measurements with high accuracy and providing high contrast between different materials.One of the key challenges facing finger-mounted QME is the implementation of accurate 2D and, eventually, 3D scanning.In this paper, we have presented preliminary 2D scans that serve as an example for the extension of the technique to 2D.These results were acquired by swiping the finger along the tissue surface and using the finger motion as both the scanning and mechanical loading mechanism.A main issue with this approach is that the reconstruction of OCT images and elastograms does not account for non-uniform velocities of the scanning finger.Without implementing a method to accurately track the motion of the probe, it is challenging to determine the location of A-scans within a 2D scan, resulting in distortion of the apparent dimensions of sample features as seen in Fig. 7.This could be overcome by using a lateral scanning mechanism, such as compact microelectromechanical system (MEMS) scanning mirrors, already deployed in other OCT probes [42][43][44][45].This, however, would add considerable bulk to the design, increasing the probe footprint and reducing dexterity.Alternatively, an external tracking system, such as a magnetic position sensor, could be used to determine the probe location during the scan [46].However, the spatial and temporal resolution of magnetic tracking systems is low compared to OCT, and such a system would likely need to be complemented by additional sensors, such as accelerometers, or some form of image registration to infer the motion of the probe from the changes in the acquired images.Another option would be to exploit the decorrelation time of the speckle pattern to estimate velocity [47].This approach has been employed to account for non-uniform rotation distortion (NURD) in endoscopic OCT applications [47], and could be modified to account for linear motion across the sample surface in finger-mounted QME.
Finger-mounted QME aims to improve diagnostic outcomes by complementing manual palpation with a quantitative assessment of disease.One area of potential application, is in breast-conserving surgery, which relies heavily on manual palpation to detect traces of tumor during surgery [4].During this procedure, the surgeon strives to excise the tumor, in addition to a thin surrounding layer of healthy tissue [48,49].Surgeons then often manually palpate the surgical cavity to determine if there is residual tumor in the patient [4].However, in 20-30% of breast-conserving surgery patients, additional surgery is required as not all of the residual tumor was excised [50].Finger-mounted QME scanning of the cavity walls could improve the detection of residual tumor.By looking for changes in the mechanical properties of cancerous tissue, our technique could potentially identify tumor that was not picked up by manual palpation.Finger-mounted QME also holds potential in applications relating to the intraoperative detection of hepatic metastases [51] and pancreatic insulinomas [52], both of which typically present as stiff lesions.As with BCS, surgeons performing these procedures rely on manual palpation to detect changes in the mechanical properties of tissue to guide them in locating the malignancies and finger-mounted QME has the potential to improve on this existing approach [51,52].Finger-mounted QME is particularly well-suited to these applications as the compact design is ideal for confined spaces such as a surgical cavity and the acquisition rate used (10 kHz) enables finger-mounted QME to be performed within several seconds, comparable to the time scale of some manual palpation techniques.Furthermore, OCT systems with acquisition times orders of magnitude faster than 10 kHz are readily available [53].In this first demonstration of finger-mounted QME, we chose to use conservative acquisition times and to focus on the proof-of-principle.In future development, using faster acquisition times, combined with more rapid compression of the tissue with the finger, would allow measurements to be acquired in milliseconds.
The clinical suitability of finger-mounted QME could be enhanced by replacing the plastic thimble case with a surgical glove to ensure the probe can be used in sterile scenarios.Embedding the optical components in a glove would better preserve tactile sensation and could provide surgeons with improved dexterity over the rigid plastic case currently used.However, even the addition of a second set of gloves has shown reductions in hand sensitivity during surgery [54] and the addition of the optical fiber and associated components would more than likely incur a similar or greater reduction in sensitivity.As manual palpation is predominantly performed using the fingertips [3], positioning any components that would hinder sensitivity away from the fingertip would better preserve tactile sensitivity whilst still providing the surgeon with the benefits of QME.

Conclusions
This paper presented the first finger-mounted OCE probe.The probe features a forwardfacing fiber probe in a compact implementation of QME.Demonstrations in 1D on silicone samples have shown that finger-mounted QME is capable of estimating the elasticity of materials within 21% of the expected value.Finger-mounted QME was also capable of measuring the thermally-induced changes in kangaroo muscle tissue.In addition, a preliminary 2D scan over an inclusion phantom showed the capability to detect features based on the mechanical contrast, albeit, at a reduced accuracy compared to the 1D measurements.With further enhancement of 2D scanning, we believe that finger-mounted QME has potential to augment existing clinical practices that rely on manual palpation.

2 .
(a) OCT M-mod In (b) and (c), the liant layer materia om, evaluated from d of view, allow amples.The to −1 /3 mg.ml −1 o also fabricated ter bulk materi Pa, both measu bulk and 3 mg t) of ~1 mm an were also fabric l matched that astic modulus o ained no scatte E measureme based on a te s approach, ph e and the dep ese parameters e.The layer is n [29].Using t layer using OC strain in the sa finite difference the finger and urface, assumin the sample, ax mple.A-scans a wn in Fig. 2(a se difference, λ is the centra 34].de, (b) axial displ e compliant layer ( al and (e) tangent m tangent modulus wing us to con op/bottom laye of TiO 2 , and w d for the 2D sc ial.The elastic ured at 10% str g.ml −1 of TiO 2 nd ~0.5 mm, re cated from this of the sample of 24 kPa at 10 erers to ensure nts echnique prev hase-sensitive d th-dependent s [29].To meas nonlinear-elas the known str CT allows us to ample was mea e approach [33 d is forward-fa ng that the fin xial compressio are acquired an a).Figure 2(b , Δφ) betwee al wavelength o acement, and (c) (CL) is masked in t modulus plot m s map shown in ( Fig. 3 artifacThe absol from the layer over strain, e estimated from which is repr

Figure 4
Figure 4 show probe for fiv elasticity (blu the ideal outc error bars repr sample.As th strain varies i and 16 kPa r corresponden error (MAPE) of the expect using the fing in friction, wh Fig. 4 (blue error b3.2 Bi-layer sIn order to va in finger-mou mode OCT im averaged over distinguished between the Fig. 6 being ROIs for the It can be samples beco elasticity of t 117 kPa and Fig. 7 and (b black) Silicone, changes in str limit the stra approximately measured in surrounding b shown in Fig however, as th finger-mounte high contrast elastogram, d 7. (a) 2D-OCT sca b) the correspondi ).
1, 5-7.The working distance of Probe 1 was 1.9 mm from the tip of the probe and the FWHM