RESUMO
In cochlear implant surgery, insertion of perimodiolar electrode arrays into the scala tympani can be complicated by trauma or even accidental translocation of the electrode array within the cochlea. In patients with partial hearing loss, cochlear trauma can not only negatively affect implant performance, but also reduce residual hearing function. These events have been related to suboptimal positioning of the cochlear implant electrode array with respect to critical cochlear walls of the scala tympani (modiolar wall, osseous spiral lamina and basilar membrane). Currently, the position of the electrode array in relation to these walls cannot be assessed during the insertion and the surgeon depends on tactile feedback, which is unreliable and often comes too late. This study presents an image-guided cochlear implant device with an integrated, fiber-optic imaging probe that provides real-time feedback using optical coherence tomography during insertion into the human cochlea. This novel device enables the surgeon to accurately detect and identify the cochlear walls ahead and to adjust the insertion trajectory, avoiding collision and trauma. The functionality of this prototype has been demonstrated in a series of insertion experiments, conducted by experienced cochlear implant surgeons on fresh-frozen human cadaveric cochleae.
Assuntos
Implante Coclear , Implantes Cocleares , Humanos , Implante Coclear/métodos , Cóclea/diagnóstico por imagem , Cóclea/cirurgia , Cóclea/lesões , Membrana Basilar , Rampa do Tímpano/diagnóstico por imagem , Rampa do Tímpano/cirurgia , Eletrodos ImplantadosRESUMO
SIGNIFICANCE: Imaging needles consist of highly miniaturized focusing optics encased within a hypodermic needle. The needles may be inserted tens of millimeters into tissue and have the potential to visualize diseased cells well beyond the penetration depth of optical techniques applied externally. Multimodal imaging needles acquire multiple types of optical signals to differentiate cell types. However, their use has not previously been demonstrated with live cells. AIM: We demonstrate the ability of a multimodal imaging needle to differentiate cell types through simultaneous optical coherence tomography (OCT) and fluorescence imaging. APPROACH: We characterize the performance of a multimodal imaging needle. This is paired with a fluorescent analog of the therapeutic drug, tamoxifen, which enables cell-specific fluorescent labeling of estrogen receptor-positive (ER+) breast cancer cells. We perform simultaneous OCT and fluorescence in situ imaging on MCF-7 ER+ breast cancer cells and MDA-MB-231 ER- cells. Images are compared against unlabeled control samples and correlated with standard confocal microscopy images. RESULTS: We establish the feasibility of imaging live cells with these miniaturized imaging probes by showing clear differentiation between cancerous cells. CONCLUSIONS: Imaging needles have the potential to aid in the detection of specific cancer cells within solid tissue.
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Neoplasias da Mama , Tomografia de Coerência Óptica , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Imagem Multimodal , Agulhas , Tamoxifeno/farmacologia , Tomografia de Coerência Óptica/métodosRESUMO
Multimodal microendoscopes enable co-located structural and molecular measurements in vivo, thus providing useful insights into the pathological changes associated with disease. However, different optical imaging modalities often have conflicting optical requirements for optimal lens design. For example, a high numerical aperture (NA) lens is needed to realize high-sensitivity fluorescence measurements. In contrast, optical coherence tomography (OCT) demands a low NA to achieve a large depth of focus. These competing requirements present a significant challenge in the design and fabrication of miniaturized imaging probes that are capable of supporting high-quality multiple modalities simultaneously. An optical design is demonstrated which uses two-photon 3D printing to create a miniaturized lens that is simultaneously optimized for these conflicting imaging modalities. The lens-in-lens design contains distinct but connected optical surfaces that separately address the needs of both fluorescence and OCT imaging within a lens of 330 µm diameter. This design shows an improvement in fluorescence sensitivity of >10x in contrast to more conventional fiber-optic design approaches. This lens-in-lens is then integrated into an intravascular catheter probe with a diameter of 520 µm. The first simultaneous intravascular OCT and fluorescence imaging of a mouse artery in vivo is reported.
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Fótons , Tomografia de Coerência Óptica , Animais , Tecnologia de Fibra Óptica , Camundongos , Imagem Óptica , Impressão Tridimensional , Tomografia de Coerência Óptica/métodosRESUMO
This study presents a highly miniaturized, handheld probe developed for rapid assessment of soft tissue using optical coherencetomography (OCT). OCT is a non-invasive optical technology capable of visualizing the sub-surface structural changes that occur in soft tissue disease such as oral lichen planus. However, usage of OCT in the oral cavity has been limited, as the requirements for high-quality optical scanning have often resulted in probes that are heavy, unwieldy and clinically impractical. In this paper, we present a novel probe that combines an all-fiber optical design with a light-weight magnetic scanning mechanism to provide easy access to the oral cavity. The resulting probe is approximately the size of a pen (10 mm × 140 mm) and weighs only 10 grams. To demonstrate the feasibility and high image quality achieved with the probe, imaging was performed on the buccal mucosa and alveolar mucosa during routine clinical assessment of six patients diagnosed with oral lichen planus. Results show the loss of normal tissue structure within the lesion, and contrast this with the clear delineation of tissue layers in adjacent inconspicuous regions. The results also demonstrate the ability of the probe to acquire a three-dimensional data volume by manually sweeping across the surface of the mucosa. The findings of this study show the feasibility of using a small, lightweight probe to identify pathological features in oral soft tissue.
Assuntos
Líquen Plano Bucal , Tomografia de Coerência Óptica , Desenho de Equipamento , Tecnologia de Fibra Óptica , Humanos , Tomografia de Coerência Óptica/métodosRESUMO
Local activation of an anti-cancer drug when and where needed can improve selectivity and reduce undesirable side effects. Photoswitchable drugs can be selectively switched between active and inactive states by illumination with light; however, the clinical development of these drugs has been restricted by the difficulty in delivering light deep into tissue where needed. Optical fibres have great potential for light delivery in vivo, but their use in facilitating photoswitching in anti-cancer compounds has not yet been explored. In this paper, a photoswitchable chemotherapeutic is switched using an optical fibre, and the cytotoxicity of each state is measured against HCT-116 colorectal cancer cells. The performance of optical-fibre-enabled photoswitching is characterised through its dose response. The UV-Vis spectra confirm light delivered by an optical fibre effectively enables photoswitching. The activated drug is shown to be twice as effective as the inactive drug in causing cancer cell death, characterised using an MTT assay and fluorescent microscopy. This is the first study in which a photoswitchable anti-cancer compound is switched using an optical fibre and demonstrates the feasibility of using optical fibres to activate photoswitchable drugs for potential future clinical applications.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Dimetil Sulfóxido/química , Fibras Ópticas/estatística & dados numéricos , Antineoplásicos/química , Sobrevivência Celular , Humanos , Células Tumorais CultivadasRESUMO
Preclinical and clinical diagnostics increasingly rely on techniques to visualize internal organs at high resolution via endoscopes. Miniaturized endoscopic probes are necessary for imaging small luminal or delicate organs without causing trauma to tissue. However, current fabrication methods limit the imaging performance of highly miniaturized probes, restricting their widespread application. To overcome this limitation, we developed a novel ultrathin probe fabrication technique that utilizes 3D microprinting to reliably create side-facing freeform micro-optics (<130 µm diameter) on single-mode fibers. Using this technique, we built a fully functional ultrathin aberration-corrected optical coherence tomography probe. This is the smallest freeform 3D imaging probe yet reported, with a diameter of 0.457 mm, including the catheter sheath. We demonstrated image quality and mechanical flexibility by imaging atherosclerotic human and mouse arteries. The ability to provide microstructural information with the smallest optical coherence tomography catheter opens a gateway for novel minimally invasive applications in disease.
RESUMO
INTRODUCTION: Optical coherence tomography (OCT) is a novel high-resolution imaging technique capable of visualizing in vivo structures at a resolution of ~10 µm. We have developed specialized OCT-based approaches that quantify diameter, speed, and flow rate in human cutaneous microvessels. In this study, we hypothesized that OCT-based microvascular assessments would possess comparable levels of reliability when compared with those derived using conventional laser Doppler flowmetry (LDF). METHODS: Speckle decorrelation images (OCT) and red blood cell flux (LDF) measures were collected from adjacent forearm skin locations on 2 d (48 h apart), at baseline, and after a 30-min rapid local heating protocol (30°C-44°C) in eight healthy young individuals. OCT postprocessing quantified cutaneous microvascular diameter, speed, flow rate, and density (vessel recruitment) within a region of interest, and data were compared between days. RESULTS: Forearm skin LDF (13 ± 4 to 182 ± 31 AU, P < 0.05) and OCT-derived diameter (41.8 ± 6.6 vs 64.5 ± 6.9 µm), speed (68.4 ± 9.5 vs 89.0 ± 7.3 µm·s), flow rate (145.0 ± 60.6 vs 485 ± 132 pL·s), and density (9.9% ± 4.9% vs 45.4% ± 5.9%) increased in response to local heating. The average OCT-derived microvascular flow response (pL·s) to heating (234% increase) was lower (P < 0.05) than the LDF-derived change (AU) (1360% increase). Pearson correlation was significant for between-day local heating responses in terms of OCT flow (r = 0.93, P < 0.01), but not LDF (P = 0.49). Bland-Altman analysis revealed that between-day baseline OCT-derived flow rates were less variable than LDF-derived flux. CONCLUSIONS: Our findings indicate that OCT, which directly visualizes human microvessels, not only allows microvascular quantification of diameter, speed, flow rate, and vessel recruitment but also provides outputs that are highly reproducible. OCT is a promising novel approach that enables a comprehensive assessment of cutaneous microvascular structure and function in humans.
Assuntos
Microcirculação/fisiologia , Pele/irrigação sanguínea , Tomografia de Coerência Óptica/métodos , Arteríolas/anatomia & histologia , Arteríolas/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Eritrócitos/fisiologia , Antebraço , Humanos , Reprodutibilidade dos TestesRESUMO
Intracranial hemorrhage can be a devastating complication associated with needle biopsies of the brain. Hemorrhage can occur to vessels located adjacent to the biopsy needle as tissue is aspirated into the needle and removed. No intraoperative technology exists to reliably identify blood vessels that are at risk of damage. To address this problem, we developed an "imaging needle" that can visualize nearby blood vessels in real time. The imaging needle contains a miniaturized optical coherence tomography probe that allows differentiation of blood flow and tissue. In 11 patients, we were able to intraoperatively detect blood vessels (diameter, >500 µm) with a sensitivity of 91.2% and a specificity of 97.7%. This is the first reported use of an optical coherence tomography needle probe in human brain in vivo. These results suggest that imaging needles may serve as a valuable tool in a range of neurosurgical needle interventions.
Assuntos
Vasos Sanguíneos/diagnóstico por imagem , Período Intraoperatório , Neurocirurgia , Imagem Óptica/instrumentação , Imagem Óptica/métodos , Idoso , Biópsia por Agulha , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Feminino , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Curva ROC , Tomografia de Coerência ÓpticaRESUMO
Miniaturised optical coherence tomography (OCT) fibre-optic probes have enabled high-resolution cross-sectional imaging deep within the body. However, existing OCT fibre-optic probe fabrication methods cannot generate miniaturised freeform optics, which limits our ability to fabricate probes with both complex optical function and dimensions comparable to the optical fibre diameter. Recently, major advances in two-photon direct laser writing have enabled 3D printing of arbitrary three-dimensional micro/nanostructures with a surface roughness acceptable for optical applications. Here, we demonstrate the feasibility of 3D printing of OCT probes. We evaluate the capability of this method based on a series of characterisation experiments. We report fabrication of a micro-optic containing an off-axis paraboloidal total internal reflecting surface, its integration as part of a common-path OCT probe, and demonstrate proof-of-principle imaging of biological samples.
Assuntos
Miniaturização , Fibras Ópticas , Fótons , Polimerização , Impressão Tridimensional , Tomografia de Coerência Óptica/métodos , Cucumis sativus/anatomia & histologia , Humanos , Imagens de FantasmasRESUMO
The ability to visualize structure while simultaneously measuring chemical or physical properties of a biological tissue has the potential to improve our understanding of complex biological processes. We report the first miniaturized single-fiber-based imaging+sensing probe capable of simultaneous optical coherence tomography (OCT) imaging and temperature sensing. An OCT lens is fabricated at the distal end of a double-clad fiber, including a thin layer of rare-earth-doped tellurite glass to enable temperature measurements. The high refractive index of the tellurite glass enables a common-path interferometer configuration for OCT, allowing easy exchange of probes for biomedical applications. The simultaneous imaging+sensing capability is demonstrated on rat brains.
Assuntos
Temperatura Corporal/fisiologia , Encéfalo/diagnóstico por imagem , Diagnóstico por Imagem/métodos , Tecnologia de Fibra Óptica/instrumentação , Fibras Ópticas , Tomografia de Coerência Óptica/instrumentação , Animais , Desenho de Equipamento , RatosRESUMO
Transbronchial needle aspiration (TBNA) of small lesions or lymph nodes in the lung may result in nondiagnostic tissue samples. We demonstrate the integration of an optical coherence tomography (OCT) probe into a 19-gauge flexible needle for lung tissue aspiration. This probe allows simultaneous visualization and aspiration of the tissue. By eliminating the need for insertion and withdrawal of a separate imaging probe, this integrated design minimizes the risk of dislodging the needle from the lesion prior to aspiration and may facilitate more accurate placement of the needle. Results from in situ imaging in a sheep lung show clear distinction between solid tissue and two typical constituents of nondiagnostic samples (adipose and lung parenchyma). Clinical translation of this OCT-guided aspiration needle holds promise for improving the diagnostic yield of TBNA.
Assuntos
Biópsia por Agulha , Neoplasias Pulmonares/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Linfonodos/patologia , Tomografia de Coerência Óptica , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Animais , Simulação por Computador , Desenho de Equipamento , Tecnologia de Fibra Óptica , Modelos Animais , Agulhas , Ovinos , Pesquisa Translacional BiomédicaRESUMO
Identifying tumour margins during breast-conserving surgeries is a persistent challenge. We have previously developed miniature needle probes that could enable intraoperative volume imaging with optical coherence tomography. In many situations, however, scattering contrast alone is insufficient to clearly identify and delineate malignant regions. Additional polarization-sensitive measurements provide the means to assess birefringence, which is elevated in oriented collagen fibres and may offer an intrinsic biomarker to differentiate tumour from benign tissue. Here, we performed polarization-sensitive optical coherence tomography through miniature imaging needles and developed an algorithm to efficiently reconstruct images of the depth-resolved tissue birefringence free of artefacts. First ex vivo imaging of breast tumour samples revealed excellent contrast between lowly birefringent malignant regions, and stromal tissue, which is rich in oriented collagen and exhibits higher birefringence, as confirmed with co-located histology. The ability to clearly differentiate between tumour and uninvolved stroma based on intrinsic contrast could prove decisive for the intraoperative assessment of tumour margins.
Assuntos
Birrefringência , Neoplasias da Mama/diagnóstico por imagem , Mama/diagnóstico por imagem , Tecnologia de Fibra Óptica/métodos , Algoritmos , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/cirurgia , Feminino , Tecnologia de Fibra Óptica/instrumentação , Humanos , Período Intraoperatório , Microscopia de Polarização/métodos , Agulhas , Reprodutibilidade dos Testes , Tomografia de Coerência Óptica/instrumentação , Tomografia de Coerência Óptica/métodosRESUMO
We present an optofluidic optical coherence tomography (OCT) needle probe capable of modifying the local optical properties of tissue to improve needle-probe imaging performance. The side-viewing probe comprises an all-fiber-optic design encased in a hypodermic needle (outer diameter 720 µm) and integrates a coaxial fluid-filled channel, terminated by an outlet adjacent to the imaging window, allowing focal injection of fluid to a target tissue. This is the first fully integrated OCT needle probe design to incorporate fluid injection into the imaging mechanism. The utility of this probe is demonstrated in air-filled sheep lungs, where injection of small quantities of saline is shown, by local refractive index matching, to greatly improve image penetration through multiple layers of alveoli. 3D OCT images are correlated against histology, showing improvement in the capability to image lung structures such as bronchioles and blood vessels.
Assuntos
Pulmão/citologia , Sistemas Microeletromecânicos/instrumentação , Microfluídica/instrumentação , Agulhas , Dispositivos Ópticos , Processamento de Sinais Assistido por Computador/instrumentação , Tomografia de Coerência Óptica/instrumentação , Animais , Meios de Contraste/administração & dosagem , Desenho de Equipamento , Análise de Falha de Equipamento , Técnicas In Vitro , Ovinos , Cloreto de Sódio/administração & dosagem , Integração de SistemasRESUMO
To the best of our knowledge, we present the first needle probe for combined optical coherence tomography (OCT), and fluorescence imaging. The probe uses double-clad fiber (DCF) that guides the OCT signal and fluorescence excitation light in the core and collects and guides the returning fluorescence in the large-diameter multimode inner cladding. It is interfaced to a 1310 nm swept-source OCT system that has been modified to enable simultaneous 488 nm fluorescence excitation and >500 nm emission detection by using a DCF coupler to extract the returning fluorescence signal in the inner cladding with high efficiency. We present imaging results from an excised sheep lung with fluorescein solution infused through the vasculature. We were able to identify alveoli, bronchioles, and blood vessels. The results demonstrate that the combined OCT plus fluorescence needle images provide improved tissue differentiation over OCT alone.
Assuntos
Espectrometria de Fluorescência/métodos , Tomografia de Coerência Óptica/métodos , Animais , Artérias/patologia , Vasos Sanguíneos/patologia , Bronquíolos/patologia , Meios de Contraste/farmacologia , Endoscopia/métodos , Desenho de Equipamento , Fluorescência , Imageamento Tridimensional , Pulmão/irrigação sanguínea , Pulmão/patologia , Agulhas , Imagem Óptica/métodos , Alvéolos Pulmonares/patologia , OvinosRESUMO
We present a high-optical-quality imaging needle for optical coherence tomography (OCT) that achieves sensitivity and resolution comparable to conventional free-space OCT sample arms. The side-viewing needle design utilizes total internal reflection from an angle-polished fiber tip, encased in a glass microcapillary. Fusion of the capillary to the fiber provides a robust, optical-quality output window. The needle's focusing optics are based on an astigmatism-free design, which exploits the "focal shift" phenomenon for focused Gaussian beams to achieve equal working distances (WDs) for both axes. We present a fabricated needle with a WD ratio of 0.98 for imaging in an aqueous environment. Our needle achieves the highest sensitivity of currently reported OCT imaging needles (112 dB), and we demonstrate its performance by superficial imaging of human skin and 3D volumetric imaging within a biological sample.
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Artefatos , Aumento da Imagem/instrumentação , Lentes , Agulhas , Tomografia de Coerência Óptica/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: The purpose of this study was to evaluate a new imaging technique for the assessment of breast cancer tumor margins. The technique entails deployment of a high-resolution optical imaging needle under ultrasound guidance. Assessment was performed on fresh ex vivo tissue samples. CONCLUSION: Use of the ultrasound-guided optical needle probe allowed in situ assessment of fresh tissue margins. The imaging findings corresponded to the histologic findings.
Assuntos
Neoplasias da Mama/patologia , Tomografia de Coerência Óptica , Ultrassonografia de Intervenção , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Técnicas In Vitro , Pessoa de Meia-IdadeRESUMO
Imaging of alveoli in situ has for the most part been infeasible due to the high resolution required to discern individual alveoli and limited access to alveoli beneath the lung surface. In this study, we present a novel technique to image alveoli using optical coherence tomography (OCT). We propose the use of OCT needle probes, where the distal imaging probe has been miniaturized and encased within a hypodermic needle (as small as 30-gauge, outer diameter 310 µm), allowing insertion deep within the lung tissue with minimal tissue distortion. Such probes enable imaging at a resolution of â¼12 µm within a three-dimensional cylindrical field of view with diameter â¼1.5 mm centered on the needle tip. The imaging technique is demonstrated on excised lungs from three different species: adult rats, fetal sheep, and adult pigs. OCT needle probes were used to image alveoli, small bronchioles, and blood vessels, and results were matched to histological sections. We also present the first dynamic OCT images acquired with an OCT needle probe, allowing tracking of individual alveoli during simulated cyclical lung inflation and deflation.
Assuntos
Agulhas , Alvéolos Pulmonares/anatomia & histologia , Tomografia de Coerência Óptica/instrumentação , Animais , Vasos Sanguíneos/anatomia & histologia , Bronquíolos/anatomia & histologia , Desenho de Equipamento , Técnicas Histológicas , Interpretação de Imagem Assistida por Computador , Imageamento Tridimensional , Miniaturização , Alvéolos Pulmonares/irrigação sanguínea , Alvéolos Pulmonares/embriologia , Ratos , Ratos Wistar , Ovinos , SuínosRESUMO
We present the first three-dimensional (3D) data sets recorded using optical coherence elastography (OCE). Uni-axial strain rate was measured on human skin in vivo using a spectral-domain optical coherence tomography (OCT) system providing >450 times higher line rate than previously reported for in vivo OCE imaging. Mechanical excitation was applied at a frequency of 125 Hz using a ring actuator sample arm with, for the first time in OCE measurements, a controlled static preload. We performed 3D-OCE, processed in 2D and displayed in 3D, on normal and hydrated skin and observed a more elastic response of the stratum corneum in the hydrated case.
Assuntos
Dermoscopia/instrumentação , Técnicas de Imagem por Elasticidade/instrumentação , Aumento da Imagem/instrumentação , Fenômenos Fisiológicos da Pele , Pele/diagnóstico por imagem , Tomografia de Coerência Óptica/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
In situ imaging of alveoli and the smaller airways with optical coherence tomography (OCT) has significant potential in the assessment of lung disease. We present a minimally invasive imaging technique utilizing an OCT needle probe. The side-facing needle probe comprises miniaturized focusing optics consisting of no-core and GRIN fiber encased within a 23-gauge needle. 3D-OCT volumetric data sets were acquired by rotating and retracting the probe during imaging. The probe was used to image an intact, fresh (not fixed) sheep lung filled with normal saline, and the results validated against a histological gold standard. We present the first published images of alveoli acquired with an OCT needle probe and demonstrate the potential of this technique to visualize other anatomical features such as bifurcations of the bronchioles.
Assuntos
Alvéolos Pulmonares/anatomia & histologia , Tomografia de Coerência Óptica/instrumentação , Animais , Bronquíolos/anatomia & histologia , Técnicas Histológicas , Imageamento Tridimensional , Modelos Animais , Dispositivos Ópticos , Fenômenos Ópticos , Alvéolos Pulmonares/irrigação sanguínea , Ovinos , Tomografia de Coerência Óptica/métodosRESUMO
We present a novel sample arm arrangement for dynamic optical coherence elastography based on excitation by a ring actuator. The actuator enables coincident excitation and imaging to be performed on a sample, facilitating in vivo operation. Sub-micrometer vibrations in the audio frequency range were coupled to samples that were imaged using optical coherence tomography. The resulting vibration amplitude and microstrain maps are presented for bilayer silicone phantoms and multiple skin sites on a human subject. Contrast based on the differing elastic properties is shown, notably between the epidermis and dermis. The results constitute the first demonstration of a practical means of performing in vivo dynamic optical coherence elastography on a human subject.