Molecular Contrast Optical Coherence Tomography: A Review

This article reviews the current state of research on the use of molecular contrast agents in optical coherence tomography (OCT) imaging techniques. After a brief discussion of the basic principle of OCT and the importance of incorporating molecular contrast agent usage into this imaging modality, we shall present an overview of the different molecular contrast OCT (MCOCT) methods that have been developed thus far. We will then discuss several important practical issues that define the possible range of contrast agent choice, the design criteria for engineered molecular contrast agent and the implementability of a given MCOCT method for clinical or biological applications. We will conclude by outlining a few areas of pursuit that deserve a greater degree of research and development

OCT methods for capillary velocimetry

To date, two main categories of OCT techniques have been described for imaging hemodynamics: Doppler OCT and OCT angiography. Doppler OCT can measure axial velocity profiles and flow in arteries and veins, while OCT angiography can determine vascular morphology, tone, and presence or absence of red blood cell (RBC) perfusion. However, neither method can quantify RBC velocity in capillaries, where RBC flow is typically transverse to the probe beam and single-file. Here, we describe new methods that potentially address these limitations. Firstly, we describe a complex-valued OCT signal in terms of a static scattering component, dynamic scattering component, and noise. Secondly, we propose that the time scale of random fluctuations in the dynamic scattering component are related to red blood cell velocity. Analysis was performed along the slow axis of repeated B-scans to parallelize measurements. We correlate our purported velocity measurements against two-photon microscopy measurements of RBC velocity, and investigate changes during hypercapnia. Finally, we image the ischemic stroke penumbra during distal middle cerebral artery occlusion (dMCAO), where OCT velocimetry methods provide additional insight that is not afforded by either Doppler OCT or OCT angiography

Dual modality optical coherence tomography : Technology development and biomedical applications

Optical coherence tomography (OCT) is a cross-sectional imaging modality that is widely used in clinical ophthalmology and interventional cardiology. It is highly promising for in situ characterization of tumor tissues. OCT has high spatial resolution and high imaging speed to assist clinical decision making in real-time. OCT can be used in both structural imaging and mechanical characterization. Malignant tumor tissue alters morphology. Additionally, structural OCT imaging has limited tissue differentiation capability because of the complex and noisy nature of the OCT signal. Moreover, the contrast of structural OCT signal derived from tissue’s light scattering properties has little chemical specificity. Hence, interrogating additional tissue properties using OCT would improve the outcome of OCT’s clinical applications. In addition to morphological difference, pathological tissue such as cancer breast tissue usually possesses higher stiffness compared to the normal healthy tissue, which indicates a compelling reason for the specific combination of structural OCT imaging with stiffness assessment in the development of dual-modality OCT system for the characterization of the breast cancer diagnosis. This dissertation seeks to integrate the structural OCT imaging and the optical coherence elastography (OCE) for breast cancer tissue characterization. OCE is a functional extension of OCT. OCE measures the mechanical response (deformation, resonant frequency, elastic wave propagation) of biological tissues under external or internal mechanical stimulation and extracts the mechanical properties of tissue related to its pathological and physiological processes. Conventional OCE techniques (i.e., compression, surface acoustic wave, magnetomotive OCE) measure the strain field and the results of OCE measurement are different under different loading conditions. Inconsistency is observed between OCE characterization results from different measurement sessions. Therefore, a robust mechanical characterization is required for force/stress quantification. A quantitative optical coherence elastography (qOCE) that tracks both force and displacement is proposed and developed at NJIT. qOCE instrument is based on a fiber optic probe integrated with a Fabry-Perot force sensor and the miniature probe can be delivered to arbitrary locations within animal or human body. In this dissertation, the principle of qOCE technology is described. Experimental results are acquired to demonstrate the capability of qOCE in characterizing the elasticity of biological tissue. Moreover, a handheld optical instrument is developed to allow in vivo real-time OCE characterization based on an adaptive Doppler analysis algorithm to accurately track the motion of sample under compression. For the development of the dual modality OCT system, the structural OCT images exhibit additive and multiplicative noises that degrade the image quality. To suppress noise in OCT imaging, a noise adaptive wavelet thresholding (NAWT) algorithm is developed to remove the speckle noise in OCT images. NAWT algorithm characterizes the speckle noise in the wavelet domain adaptively and removes the speckle noise while preserving the sample structure. Furthermore, a novel denoising algorithm is also developed that adaptively eliminates the additive noise from the complex OCT using Doppler variation analysis

Quantum metrology and its application in biology

Quantum metrology provides a route to overcome practical limits in sensing devices. It holds particular relevance to biology, where sensitivity and resolution constraints restrict applications both in fundamental biophysics and in medicine. Here, we review quantum metrology from this biological context, focusing on optical techniques due to their particular relevance for biological imaging, sensing, and stimulation. Our understanding of quantum mechanics has already enabled important applications in biology, including positron emission tomography (PET) with entangled photons, magnetic resonance imaging (MRI) using nuclear magnetic resonance, and bio-magnetic imaging with superconducting quantum interference devices (SQUIDs). In quantum metrology an even greater range of applications arise from the ability to not just understand, but to engineer, coherence and correlations at the quantum level. In the past few years, quite dramatic progress has been seen in applying these ideas into biological systems. Capabilities that have been demonstrated include enhanced sensitivity and resolution, immunity to imaging artifacts and technical noise, and characterization of the biological response to light at the single-photon level. New quantum measurement techniques offer even greater promise, raising the prospect for improved multi-photon microscopy and magnetic imaging, among many other possible applications. Realization of this potential will require cross-disciplinary input from researchers in both biology and quantum physics. In this review we seek to communicate the developments of quantum metrology in a way that is accessible to biologists and biophysicists, while providing sufficient detail to allow the interested reader to obtain a solid understanding of the field. We further seek to introduce quantum physicists to some of the central challenges of optical measurements in biological science.Comment: Submitted review article, comments and suggestions welcom

Computational aberration correction in optical coherence tomography with phase-unstable systems

La tomografía de coherence óptica (OCT) es una técnica usada ampliamente en medicina, pero al tratarse de una técnica óptica es susceptible la aberraciones ópticas que degradan la calidad de la imagen, lo que dificulta la visualización de estructuras finas con alta resolución. Este trabajo presenta una técnica computacional para corregir aberraciones en OCT, cuya operación es compatible con muchos tipos de sistemas estandarés, y se muestran resultados en imagen del ojo, la via area y la piel.Optical coherence tomography (OCT) is an imaging technique widely use in medicine. OCT is an optical technique, therefore it is prone to optical aberrations that degrade image quality, making it difficult to visualize fine structures with high resolution.This work presents SHARP, a computational technique for correction of aberrations in OCT, that is compatible with most standard systems, and we present results in eye, airway and skin imagin

Image Restoration Methods for Retinal Images: Denoising and Interpolation

Retinal imaging provides an opportunity to detect pathological and natural age-related physiological changes in the interior of the eye. Diagnosis of retinal abnormality requires an image that is sharp, clear and free of noise and artifacts. However, to prevent tissue damage, retinal imaging instruments use low illumination radiation, hence, the signal-to-noise ratio (SNR) is reduced which means the total noise power is increased. Furthermore, noise is inherent in some imaging techniques. For example, in Optical Coherence Tomography (OCT) speckle noise is produced due to the coherence between the unwanted backscattered light. Improving OCT image quality by reducing speckle noise increases the accuracy of analyses and hence the diagnostic sensitivity. However, the challenge is to preserve image features while reducing speckle noise. There is a clear trade-off between image feature preservation and speckle noise reduction in OCT. Averaging multiple OCT images taken from a unique position provides a high SNR image, but it drastically increases the scanning time. In this thesis, we develop a multi-frame image denoising method for Spectral Domain OCT (SD-OCT) images extracted from a very close locations of a SD-OCT volume. The proposed denoising method was tested using two dictionaries: nonlinear (NL) and KSVD-based adaptive dictionary. The NL dictionary was constructed by adding phases, polynomial, exponential and boxcar functions to the conventional Discrete Cosine Transform (DCT) dictionary. The proposed denoising method denoises nearby frames of SD-OCT volume using a sparse representation method and combines them by selecting median intensity pixels from the denoised nearby frames. The result showed that both dictionaries reduced the speckle noise from the OCT images; however, the adaptive dictionary showed slightly better results at the cost of a higher computational complexity. The NL dictionary was also used for fundus and OCT image reconstruction. The performance of the NL dictionary was always better than that of other analytical-based dictionaries, such as DCT and Haar. The adaptive dictionary involves a lengthy dictionary learning process, and therefore cannot be used in real situations. We dealt this problem by utilizing a low-rank approximation. In this approach SD-OCT frames were divided into a group of noisy matrices that consist of non-local similar patches. A noise-free patch matrix was obtained from a noisy patch matrix utilizing a low-rank approximation. The noise-free patches from nearby frames were averaged to enhance the denoising. The denoised image obtained from the proposed approach was better than those obtained by several state-of-the-art methods. The proposed approach was extended to jointly denoise and interpolate SD-OCT image. The results show that joint denoising and interpolation method outperforms several existing state-of-the-art denoising methods plus bicubic interpolation.4 month

Roadmap on digital holography [Invited]

This Roadmap article on digital holography provides an overview of a vast array of research activities in the field of digital holography. The paper consists of a series of 25 sections from the prominent experts in digital holography presenting various aspects of the field on sensing, 3D imaging and displays, virtual and augmented reality, microscopy, cell identification, tomography, label-free live cell imaging, and other applications. Each section represents the vision of its author to describe the significant progress, potential impact, important developments, and challenging issues in the field of digital holography