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Author

Martin Ahrens

Bio: Martin Ahrens is an academic researcher from University of Lübeck. The author has contributed to research in topics: Optical coherence tomography & Contrast (vision). The author has an hindex of 4, co-authored 8 publications receiving 58 citations.

Papers
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Journal ArticleDOI
TL;DR: In this article, the authors demonstrate dynamic contrast with a scanning frequency-domain OCT (FD-OCT), which is a promising tool for the histological analysis of unstained tissues.
Abstract: While optical coherence tomography (OCT) provides a resolution down to 1 µm, it has difficulties in visualizing cellular structures due to a lack of scattering contrast. By evaluating signal fluctuations, a significant contrast enhancement was demonstrated using time-domain full-field OCT (FF-OCT), which makes cellular and subcellular structures visible. The putative cause of the dynamic OCT signal is the site-dependent active motion of cellular structures in a sub-micrometer range, which provides histology-like contrast. Here we demonstrate dynamic contrast with a scanning frequency-domain OCT (FD-OCT), which we believe has crucial advantages. Given the inherent sectional imaging geometry, scanning FD-OCT provides depth-resolved images across tissue layers, a perspective known from histopathology, much faster and more efficiently than FF-OCT. Both shorter acquisition times and tomographic depth-sectioning reduce the sensitivity of dynamic contrast for bulk tissue motion artifacts and simplify their correction in post-processing. Dynamic contrast makes microscopic FD-OCT a promising tool for the histological analysis of unstained tissues.

30 citations

Journal ArticleDOI
TL;DR: Endo-microscopic OCT (emOCT) is presented, which may be used for in-vivo imaging of lung diseases like cystic fibrosis or primary ciliary dyskinesia, which manifest already at the nasal mucosa and may considerably improve clinical diagnosis.
Abstract: Intravital microscopy (IVM) offers the opportunity to visualize static and dynamic changes of tissue on a cellular level. It is a valuable tool in research and may considerably improve clinical diagnosis. In contrast to confocal and non-linear microscopy, optical coherence tomography (OCT) with microscopic resolution (mOCT) provides intrinsically cross-sectional imaging. Changing focus position is not needed, which simplifies especially endoscopic imaging. For in-vivo imaging, here we are presenting endo-microscopic OCT (emOCT). A graded-index-lens (GRIN) based 2.75 mm outer diameter rigid endoscope is providing 1.5 – 2 µm nearly isotropic resolution over an extended field of depth. Spherical and chromatic aberrations are used to elongate the focus length. Simulation of the OCT image formation, suggests a better overall image quality in this range compared to a focused Gaussian beam. Total imaging depth at a reduced sensitivity and lateral resolution is more than 200 µm. Using a frame rate of 80 Hz cross-sectional images of concha nasalis were demonstrated in humans, which could resolve cilial motion, cellular structures of the epithelium, vessels and blood cells. Mucus transport velocity was successfully determined. The endoscope may be used for diagnosis and treatment control of different lung diseases like cystic fibrosis or primary ciliary dyskinesia, which manifest already at the nasal mucosa.

29 citations

Journal ArticleDOI
TL;DR: A forward-viewing fiber scanning endoscope for high-speed volumetric optical coherence tomography (OCT) by substituting the focusing optics by an all-fiber-based imaging system which consists of a combination of scanning single-mode fibers, a glass spacer, made from a step-index multi-mode fiber, and a gradient-index fiber.
Abstract: We present a forward-viewing fiber scanning endoscope (FSE) for high-speed volumetric optical coherence tomography (OCT). The reduction in size of the probe was achieved by substituting the focusing optics by an all-fiber-based imaging system which consists of a combination of scanning single-mode fibers, a glass spacer, made from a step-index multi-mode fiber, and a gradient-index fiber. A lateral resolution of 11 μm was achieved at a working distance of 1.2 mm. The newly designed piezo-based FSE has an outer diameter of 1.6 mm and a rigid length of 13.5 mm. By moving the whole imaging optic in spirals for scanning the sample, the beam quality remains constant over the entire field of view with a diameter of 0.8 mm. The scanning frequency was adjusted to 1.22 kHz for use with a 3.28 MHz Fourier domain mode locked OCT system. Densely sampled volumes have been imaged at a rate of 6 volumes per second.

21 citations

Journal ArticleDOI
TL;DR: High-speed volumetric mOCT will enable the correction of global tissue motion and is a prerequisite for applying dynamic contrast mO CT in vivo, and may be used to complement or partly replace biopsies.
Abstract: Volumetric imaging of dynamic processes with microscopic resolution holds a huge potential in biomedical research and clinical diagnosis. Using supercontinuum light sources and high numerical aperture (NA) objectives, optical coherence tomography (OCT) achieves microscopic resolution and is well suited for imaging cellular and subcellular structures of biological tissues. Currently, the imaging speed of microscopic OCT (mOCT) is limited by the line-scan rate of the spectrometer camera and ranges from 30 to 250 kHz. This is not fast enough for volumetric imaging of dynamic processes in vivo and limits endoscopic application. Using a novel CMOS camera, we demonstrate fast 3-dimensional OCT imaging with 600,000 A-scans/s at 1.8 µm axial and 1.1 µm lateral resolution. The improved speed is used for imaging of ciliary motion and particle transport in ex vivo mouse trachea. Furthermore, we demonstrate dynamic contrast OCT by evaluating the recorded volumes rather than en face planes or B-scans. High-speed volumetric mOCT will enable the correction of global tissue motion and is a prerequisite for applying dynamic contrast mOCT in vivo. With further increase in imaging speed and integration in flexible endoscopes, volumetric mOCT may be used to complement or partly replace biopsies.

19 citations

Posted Content
TL;DR: Short acquisition times and tomographic depth-sectioning reduce the sensitivity of dynamic contrast for bulk tissue motion artifacts and simplify their correction in post-processing, which makes microscopic FD-OCT a promising tool for the histological analysis of unstained tissues.
Abstract: While optical coherence tomography (OCT) provides a resolution down to 1 micrometer it has difficulties to visualize cellular structures due to a lack of scattering contrast. By evaluating signal fluctuations, a significant contrast enhancement was demonstrated using time-domain full-field OCT (FF-OCT), which makes cellular and subcellular structures visible. The putative cause of the dynamic OCT signal is ATP-dependent motion of cellular structures in a sub-micrometer range, which provides histology-like contrast. Here we demonstrate dynamic contrast with a scanning frequency-domain OCT (FD-OCT). Given the inherent sectional imaging geometry, scanning FD-OCT provides depth-resolved images across tissue layers, a perspective known from histopathology, much faster and more efficiently than FF-OCT. Both, shorter acquisition times and tomographic depth-sectioning reduce the sensitivity of dynamic contrast for bulk tissue motion artifacts and simplify their correction in post-processing. The implementation of dynamic contrast makes microscopic FD-OCT a promising tool for histological analysis of unstained tissues.

16 citations


Cited by
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Journal Article
TL;DR: In this article, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter, which was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.
Abstract: Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as "optical biopsy," was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.

1,285 citations

Journal ArticleDOI
TL;DR: The new technique allowed in vivo monitoring and quantitative segmentation of (1) viable, (2) dystrophic, (3) necrotic tumor cells and (4) edema zones very similar to morphological segmentations of histological images, which can be foreseen.
Abstract: We present a non-invasive (albeit contact) method based on Optical Coherence Elastography (OCE) enabling the in vivo segmentation of morphological tissue constituents, in particular, monitoring of morphological alterations during both tumor development and its response to therapies. The method uses compressional OCE to reconstruct tissue stiffness map as the first step. Then the OCE-image is divided into regions, for which the Young’s modulus (stiffness) falls in specific ranges corresponding to the morphological constituents to be discriminated. These stiffness ranges (characteristic "stiffness spectra") are initially determined by careful comparison of the "gold-standard" histological data and the OCE-based stiffness map for the corresponding tissue regions. After such pre-calibration, the results of morphological segmentation of OCE-images demonstrate a striking similarity with the histological results in terms of percentage of the segmented zones. To validate the sensitivity of the OCE-method and demonstrate its high correlation with conventional histological segmentation we present results obtained in vivo on a murine model of breast cancer in comparative experimental study of the efficacy of two antitumor chemotherapeutic drugs with different mechanisms of action. The new technique allowed in vivo monitoring and quantitative segmentation of (1) viable, (2) dystrophic, (3) necrotic tumor cells and (4) edema zones very similar to morphological segmentation of histological images. Numerous applications in other experimental/clinical areas requiring rapid, nearly real-time, quantitative assessment of tissue structure can be foreseen.

39 citations

Journal ArticleDOI
TL;DR: The clinical translation of a 1-μm resolution micro-optical coherence tomography (μOCT) technology is reported to quantitatively characterize the functional microanatomy of human upper airways to demonstrate the utility of μOCT to determine epithelial function and monitor disease status of CF airways on a per-patient basis.
Abstract: Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Although impairment of mucociliary clearance contributes to severe morbidity and mortality in people with CF, a clear understanding of the pathophysiology is lacking. This is, in part, due to the absence of clinical imaging techniques capable of capturing CFTR-dependent functional metrics at the cellular level. Here, we report the clinical translation of a 1-μm resolution micro-optical coherence tomography (μOCT) technology to quantitatively characterize the functional microanatomy of human upper airways. Using a minimally invasive intranasal imaging approach, we performed a clinical study on age- and sex-matched CF and control groups. We observed delayed mucociliary transport rate at the cellular level, depletion of periciliary liquid layer, and prevalent loss of ciliation in subjects with CF. Distinctive morphological differences in mucus and various forms of epithelial injury were also revealed by μOCT imaging and had prominent effects on the mucociliary transport apparatus. Elevated mucus reflectance intensity in CF, a proxy for viscosity in situ, had a dominant effect. These results demonstrate the utility of μOCT to determine epithelial function and monitor disease status of CF airways on a per-patient basis, with applicability for other diseases of mucus clearance.

33 citations

Journal ArticleDOI
TL;DR: In this article , a systematic review of diagnostic accuracy studies that used deep learning models on dental imagery (including radiographs, photographs, optical coherence tomography images, near-infrared light transillumination images).

33 citations

Journal ArticleDOI
TL;DR: Depth-resolved d-µOCT images of intact tissue show that intracellular dynamics provides a new contrast mechanism for µOCT that highlights subcellular morphology and activity in epithelial surface maturation patterns.
Abstract: This paper describes a new technology that uses 1-µm-resolution optical coherence tomography (µOCT) to obtain cross-sectional images of intracellular dynamics with dramatically enhanced image contrast. This so-called dynamic µOCT (d-µOCT) is accomplished by acquiring a time series of µOCT images and conducting power frequency analysis of the temporal fluctuations that arise from intracellular motion on a pixel-per-pixel basis. Here, we demonstrate d-µOCT imaging of freshly excised human esophageal and cervical biopsy samples. Depth-resolved d-µOCT images of intact tissue show that intracellular dynamics provides a new contrast mechanism for µOCT that highlights subcellular morphology and activity in epithelial surface maturation patterns.

31 citations