SignificanceEsophageal cancer is becoming increasingly prevalent in Western countries. Early detection is crucial for effective treatment. Multimodal imaging combining optical coherence tomography (OCT) with complementary optical imaging techniques may provide enhanced diagnostic capabilities by simultaneously assessing tissue morphology and biochemical content.AimWe aim to develop a tethered capsule endoscope (TCE) that can accommodate a variety of point-scanning techniques in addition to OCT without requiring design iterations on the optical or mechanical design.ApproachWe propose a TCE utilizing exclusively reflective optics to focus and steer light from and to a double-clad fiber. Specifically, we use an ellipsoidal mirror to achieve finite conjugation between the fiber tip and the imaging plane.ResultsWe demonstrate a functional all-reflective TCE. We first detail the design, fabrication, and assembly steps required to obtain such a device. We then characterize its performance and demonstrate combined OCT at 1300 nm and visible spectroscopic imaging in the 500- to 700-nm range. Finally, we discuss the advantages and limitations of the proposed design.ConclusionsAn all-reflective TCE is feasible and allows for achromatic high-quality imaging. Such a device could be utilized as a platform for testing various combinations of modalities to identify the optimal candidates without requiring design iterations.
We demonstrate an all-reflective tethered capsule endoscope (RTCE) utilizing double-clad fiber and reflective optics for achromatic multimodal imaging of the esophagus. This device uses a custom ellipsoidal mirror to focus the light from the fiber tip onto the sample. In this work, we first describe key design parameters and highlight important assembly steps. We then demonstrate several data processing/analysis methods for signal multiplexing, rotation stabilization, and image analysis. Finally, we demonstrate the implementation of the capsule by performing combined OCT and spectral imaging in ex-vivo biological samples.
Bladder cancer was the 10th most prevalent cancer worldwide in 2020. Currently, the gold standard for diagnosing bladder cancer is a cystoscopy followed by a transurethral resection of the bladder tumour. The tumour invasion and grade are needed to determine the treatment plan. However, a transurethral resection is an invasive procedure, needs planning and has complication risks. Therefore, finding an alternative option to determine tumour invasion and grade is necessary. That would also enable other treatment options for bladder cancer such as laser fulguration, chemo-resection and active surveillance. Optical Coherence Tomography (OCT) has the potential to aid in the diagnosis of bladder cancer
We demonstrate a tethered capsule endoscope (TCE), which uses double-clad fiber and reflective optics for multimodal imaging in the esophagus without undesirable chromatic effects, such as focal shifts or back-reflections. We use a single, custom ellipsoidal mirror to focus the light from the fiber tip onto the sample. We describe the mechanical and optical designs and the fabrication and assembly protocols necessary for optimal performance. We demonstrate the implementation of the capsule by performing combined optical coherence tomography and spectral imaging in ex-vivo esophagus.
We present a bi-modal bench-top system combining OCT with broadband, single-fiber reflectance spectroscopy. This combination aims to address the limited molecular sensitivity of standard OCT imaging in order to obtain co-registered morphological and molecular information. We present various technical innovations for this work, including an all-reflective scanner head with adaptive optic components for focus scanning and reduction of field curvature. Furthermore, we demonstrate the use of specialty fiber components to obtain multiple illumination schemes for the spectroscopic channel and enhance the spatially resolved reconstruction of optical properties.
Extracellular vesicles (EVs) are nanoparticles secreted from cells into bodily fluids. EVs are potential biomarkers for diseases such as thrombosis or cancer. However, the small size and low refractive index of EVs complicates their detection. A flow cytometer is suited for EV characterisation, but typically lacks scatter sensitivity on one or both scatter detectors for derivation of both particle size and refractive index. Here, we aim to improve the FACSCanto (Becton Dickinson) forward scatter detector for the detection of 100 nm EVs, which requires an improvement in SNR of 107-fold based on Mie theory. This was achieved through replacement of the 20 mW laser by an 200 mW laser, replacement of the photodiode detector with a photomultiplier tube and a confocalized optical geometry. Using a prototype optical setup, we obtained an improvement in SNR which was 1,11·104 – fold better than the standard design. However, the optics was suboptimal and far from diffraction-limited. Zemax simulations led to a nearly diffraction limited optical design which is expected to yield another 200-fold improvement. Taken together these changes will improve the SNR 2.2·106-fold and thus improve the detection limit of the FACSCanto to 130 nm EVs.
Optical imaging of whole animals or animal organs is a rapidly growing field in translational research revealing the molecular events underlying disease and disease treatment mechanisms in cardiovascular, cancer and neurological research. Here we present a custom-built imaging system for visualisation of 3D distribution of fluorescent markers with high-resolution tissue structure and vasculature network images of small animals or whole organs.
The 3D Fluorescence Imaging Cryomicrotome System (3D-FICS) yields comprehensive structural and functional biological information by combining fluorescence remittance imaging. Moreover, the 3D-FICS is adapted to record large series of high-resolution images (2048 x 2048 pixels, with a selectable resolution of 27, 16 and 8μm, corresponding to a FOV of 53, 31 and 16mm) of the bulk tissue remaining in the cryomicrotome in a fully automated manner. All components are controlled through custom software (Labview) to enable fully automated serial cutting and imaging sessions. To ensure 3D reconstructions with isotropic voxels, the slice thickness of the cryomicrotome is set to match the imaging resolution of the camera.
Wavelength-selective illumination of the tissue is carried out using a Supercontinuum laser in conjunction with a tunable bandpass filter (400nm - 830nm) with a tunable bandwidth (5nm - 100nm) Similarly, a tunable emission filter (440nm - 800nm) with a bandwidth ranging from 11nm to 15nm is used for spectrally-resolved imaging of the fluorescent tracers injected in the specimen.
The 3D-FICS will be used in experimental studies on small animal organs from which we will present the first obtained images.
The scattering phase function (the probability distribution of the scattering angle) is intimately associated with the cellular organization and ultrastructure of tissue. Since these physical parameters change during e.g. carcinogenesis; quantification of the phase function and related parameters may allow for improved non-invasive, in vivo discrimination between healthy and diseased tissue. Furthermore, for the derivation of models to interpret measured optical signals, assumptions about the phase function of tissue are often made – regularly assuming a Modified Henyey Greenstein. However, in contrast to other optical properties, the phase function has not yet been extensively measured for different tissue types.
With conventional goniometers, the exact backscatter direction of 180 degrees cannot be measured. Especially for techniques that detect backscattered light – such as Optical Coherence Tomography and Elastic Scattering spectroscopy – the details of the backward part of the phase function will have a considerable impact on the measured signal.
We have therefore developed a setup that can measure the backward part of the phase function: 134 to 180 degrees. Our design is based on full field Optical Coherence Tomography. We detect all angles simultaneously with a camera, while scanning the reference mirror. The phase function scales with the amplitude of the OCT signal for each angle. We will show our results for validation measurements on two silica bead samples of 200 nm and 400 nm beads.
Despite the improvements in early cancer diagnosis, adequate diagnostic tools for early staging of bladder cancer tumors are lacking [1]. MEMS-probes based on optical coherence tomography (OCT) provide cross-sectional imaging with a high-spatial resolution at a high-imaging speed, improving visualization of cancerous tissue [2-3]. Additionally, studies show that the measurement of localized attenuation coefficient allows discrimination between healthy and cancerous tissue [4]. We have designed a new miniaturized MEMS-probe based on OCT that will optimize early diagnosis by improving functional visualization of suspicious lesions in bladder. During the optical design phase of the probe, we have studied the effect of the numerical aperture (NA) on the OCT signal attenuation. For this study, we have employed an InnerVision Santec OCT system with several numerical apertures (25mm, 40mm, 60mm, 100mm, 150mm and 200mm using achromatic lenses). The change in attenuation coefficient was studied using 15 dilutions of intralipid ranging between 6*10-5 volume% and 20 volume%. We obtained the attenuation coefficient from the OCT images at several fixed positions of the focuses using established OCT models (e.g. single scattering with known confocal point spread function (PSF) [5] and multiple scattering using the Extended Huygens Fresnel model [6]). As a result, a non-linear increase of the scattering coefficient as a function of intralipid concentration (due to dependent scattering) was obtained for all numerical apertures. For all intralipid samples, the measured attenuation coefficient decreased with a decrease in NA. Our results suggest a non-negligible influence of the NA on the measured attenuation coefficient.
[1] Khochikar MV. Rationale for an early detection program for bladder cancer. Indian J Urol 2011 Apr-Jun; 27(2): 218–225.
[2] Sun J and Xie H. Review Article MEMS-Based Endoscopic Optical Coherence Tomography. IJO 2011, Article ID 825629, 12 pages. doi:10.1155/2011/825629.
[3] Jung W and Boppart S. Optical coherence tomography for rapid tissue screening and directed histological sectioning. Anal Cell Pathol (Amst). 2012; 35(3): 129–143.
[4] R. Wessels et al. Optical coherence tomography in vulvar intraepithelial neoplasia. J Biomed Opt 2012 Nov; 17(11): 116022.
[5] Faber D, van der Meer F, Aalders M, van Leeuwen T. Quantitative measurement of attenuation coefficients of weakly scattering media using optical coherence tomography. OPT EXPRESS 2004; 12 (19): 4353-43.
[6] Thrane L, Yura HT, and Andersen PE. Analysis of optical coherence tomography systems based on the extended Huygens–Fresnel principle. JOSA 2000; 17(3): 484-490.
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