Significance: We propose a customized animal-specific head cap and an near-infrared spectroscopy (NIRS) system to obtain NIRS signals in mobile small animals. NIRS studies in mobile small animals provide a feasible solution for comprehensive brain function studies.
Aim: We aim to develop and validate a multichannel NIRS system capable of performing functional brain imaging along with a closed-box stimulation kit for small animals in mobile conditions.
Approach: The customized NIRS system uses light-weight long optical fibers, along with a customized light-weight head cap to securely attach the optical fibers to the mouse. A customized stimulation box was designed to perform various stimuli in a controlled environment. The system performance was tested in a visual stimulation task on eight anesthetized mice and eight freely moving mice.
Results: Following the visual stimulation task, we observed a significant stimulation-related oxyhemoglobin (HbO) increase in the visual cortex of freely moving mice during the task. In contrast, HbO concentration did not change significantly in the visual cortex of anesthetized mice.
Conclusions: We demonstrate the feasibility of a wearable, multichannel NIRS system for small animals in a less confined experimental design.
Childhood Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder whose symptoms include the inability to focus, impulsivity, and extremely active behavior. Advanced Test of Attention (ATA) is used to diagnose ADHD by measuring the patient’s impulse rate, average response rate, standard deviation rate, and omission rate during visual and auditory stimulation. However, ATA metrics are often skewed due to long task times and level of difficulty. We recruited healthy and ADHD children to monitor their performance during ATA. This work highlights diffuse optical tomography’s capability in providing cerebral perfusion changes to supplement ATA results for monitoring the cognitive effects of ADHD.
KEYWORDS: Visualization, Optical coherence tomography, Volume rendering, Microsurgery, Data acquisition, Computing systems, Data processing, Surgery, Digital video recorders, Image processing
Mechanical interactions of living cells with the surrounding environment via focal adhesion (FA) in three dimensions (3-D) play a key role in dynamic biological events, such as tissue regeneration, wound healing, and cancer invasion. Recently, several methods for observing 3-D cell–extracellular matrix (ECM) interactions have been reported, lacking solid and quantitative analysis on the dynamics of the physical interaction between the cell and the ECM. We measured the submicron displacements of ECM deformation in 3-D due to protrusion-retraction dynamics during cell migration, using second-harmonic generation without labeling the matrix structures. We then quantitatively analyzed the mechanical deformation between the ECM and the cells based on spatiotemporal volumetric correlations. The greatest deformations within the collagen matrix were found to occur at sites of colocalization of the FA site-related proteins vinculin and actin, which confirms that FA sites play a critical role in living cells within the ECM as a point for adhesion, traction, and migration. We believe that this modality can be used in studies of cell–ECM interaction during angiogenesis, wound healing, and metastasis.
Research trends in endoscopy have been to reduce the dimension of the system for minimally invasive diagnostics and to improve spatial resolution to the microscopic level for the detailed investigation of specimens. In developing endoscopes that meet these needs, ultrathin imaging probes such as graded index lenses and fiber bundles have been widely used. And a single imaging probe is used for both illumination and detection to maintain the small diameter of the probe unit. However, this causes a fundamental problem, that is the back-reflection noise from the surface of the imaging probes. This back-reflection noise can overwhelm signals from target objects with weak contrast, which is the case for biological tissues, and degrade image contrast to such an extent that the objects remain unresolved.
Here, we present an endomicroscope free from back-reflection noise generated at an ultrathin imaging probe and yet guaranteeing microscopic spatial resolution. In our method, we send illumination through single individual core fibers in the image fiber bundle, and detect signal light by the other core fibers. By blocking the back-reflection occurring only at the core used for the illumination, we remove the back-reflection noise before it reaches the detector sensor. The transmission matrix of the fiber bundle is measured and used to reconstruct a pixelation-free and high-resolution image from the raw images captured by the other fibers, which are blurred and pixelated. We demonstrated that the proposed imaging method improved 3.2 times on the signal to noise ratio produced by the conventional illumination-detection scheme.
KEYWORDS: Real time imaging, Brain mapping, Neuroimaging, Hemodynamics, Monte Carlo methods, Near infrared spectroscopy, Photon transport, Brain, Oxygen, Tissues
Accurate and efficient reconstruction of hemodynamic changes is an important step towards the implementation of NIRS as an enhanced clinical tool for understanding oxygenation changes at various depths within the brain. Depth information could provide insight on how oxygen transported to the tissue. For this work, we ran Monte Carlo simulations to develop sensitivity profiles for various source-detector separations. The source-detector separations were based on our custom built 108 channel NIRS probe and consisted of separations of 15 mm, 30 mm, 36 mm, and 45 mm. We used the mesh-based Monte Carlo program MMCLAB (Fang et al. 2010) to acquire the sensitivity profiles. The sensitivity profiles consisted of a tetrahedral mesh which was converted to a regular grid in three-dimensional space. Then, the structural tensor was calculated for each voxel and the Hamilton-Jacobi equation was solved anisotropically for the tensor volume. As the result, the distance map was in same space as the calculated tensor volume. Using this distance map, we modeled the probabilistic path of photons. We then weighted the hemodynamic changes acquired by our NIRS probe according to the probabilistic path to reconstruct hemodynamic changes in the prefrontal area of the brain.
In this work, we analyzed the clinical applicability of NIRS for use during Quantitative Autonomic Testing (QAT). QAT is a protocol consisting of deep breathing, Valsalva maneuver, and tilt table examination. It is used to diagnose a patient with disorders of the autonomic nervous system (ANS). Disorders of ANS includes orthostatic hyper/hypotension, vasovagal syncope, and postural orthostatic tachycardia syndrome. The results of QAT are typically analyzed with the use of blood pressure and heart rate data, however these metrics may be influenced by factors such as arrhythmia, making the data interpretation and diagnosis difficult for clinicians. We tested our custom built 108-channel NIRS probe on 26 elderly patients during the QAT protocol with various ANS disorders. We found that prefrontal cerebral oxygenation correlated well with blood pressure and heart rate changes for all three tasks, making it a clinically feasible tool for observing ANS functionality. During the Valsalva maneuver, we observed a longer delayed and lower amplitude response of cerebral oxygenation to the prefrontal area in orthostatic intolerant patients. During the tilt table examination, we saw a larger response in cerebral oxygenation and less equal transient cerebral oxygenation during tilt up and tilt down in tilt table examinations that were positive (unhealthy), compared to tilt table examinations that were negative (healthy). Overall, our study showcases NIRS as an enhanced tool for understanding ANS disorders.
Graded-index (GRIN) lenses have been widely used for developing compact imaging devices due to the small dimensions and simple optics designs. GRIN lenses, however, have intrinsic aberration which causes a distortion of the image and thus are subject to limited resolution and blurred imaging quality. Here, we employ the high-precision wavefront measurement technique for compensation of the distortion of a GRIN lens to obtain a high-resolution and high-contrast image. In doing so, we demonstrate a high-resolution and ultra-thin endo-microscope using a GRIN. A reflection-type interferometric microscope through a GRIN lens was constructed using multiple lasers (473 nm, 532 nm, and 633 nm) as light sources. The characteristics of the aberration of the GRIN lens were measured using the digital holographic method. The distortion of the GRIN lens was removed by numerical image processing with the prior information from the pre-calibration. We apply this technique to a reflection image of biological tissues acquired by our custom-built GRIN lens probe. Consequently, a diffraction limited lateral resolution as well as improved axial resolution can be achieved. Our approach will facilitate the use of GRIN lenses for compact imaging devices without compromising optical resolution and image quality.
When waves travel through disordered media such as ground glass and skin tissues, they are scattered multiple times. Most of the incoming energy bounces back at the superficial layers and only a small fraction can penetrate deep inside. This has been a limiting factor for the working depth of various optical techniques. We present a systematic method to enhance wave penetration to the scattering media. Specifically, we measured the reflection matrix of a disordered medium with wide angular coverage for each orthogonal polarization states. From the reflection matrix, we identified reflection eigenchannels of the medium, and shaped the incident wave into the reflection eigenchannel with smallest eigenvalue, which we call anti-reflection mode. This makes reflectance reduced and wave penetration increased as a result of the energy conservation. We demonstrated transmission enhancement by more than a factor of 3 by the coupling of the incident waves to the anti-reflection modes. Based on the uneven distribution of eigenvalues of reflection eigenchannels, we further developed an iterative feedback control method for finding and coupling light to anti-reflection modes. Since this adaptive control method can keep up with sample perturbation, it promotes the applicability of exploiting reflection eigenchannels. Our approach of delivering light deep into the scattering media will contribute to enhancing the sensitivity of detecting objects hidden under scattering layers, which is universal problem ranging from geology to life science.
A graded-index (GRIN) lens is suitable for developing an ultra-thin endoscope due to its small diameter and simplicity for optics design. A GRIN lens, however, generates intrinsic optical aberration causing low resolution and poor imaging quality. Recently, wavefronts of light can be measured with very high precision and the optical aberration can be corrected in numerical ways even for the case of highly scattering media. In this study, based on the high precision wavefront sensing and numerical image processing techniques, we demonstrate a high-resolution and ultra-thin endo-microscope using a GRIN rod lens as a core imaging optics. We constructed a reflection-type interferometric microscope through a GRIN rod lens using a p-polarized Nd:YAG laser (532 nm) as a light source. By recording and processing blank transmission images as a function of various illumination states, the characteristics of the aberration generated by the GRIN lens were obtained. After this pre-calibration, we could numerically compensate the aberration induced onto a reflection image of an object. Consequently, a diffraction limited lateral resolution as well as improved axial resolution could be achieved. Our approach will fascinate the use of GRIN lenses for compact and high-resolution imaging devices including ultra-thin endo-microscopes.
We implement differential interference contrast (DIC) microscopy using high-speed synthetic aperture imaging that expands the passband of coherent imaging by a factor of 2.2. For an aperture synthesized coherent image, we apply for the numerical post-processing and obtain a high-contrast DIC image for arbitrary shearing direction and bias retardation. In addition, we obtain images at different depths without a scanning objective lens by numerically propagating the acquired coherent images. Our method achieves high-resolution and high-contrast 3-D DIC imaging of live biological cells. The proposed method will be useful for monitoring 3-D dynamics of intracellular particles.
We propose a method based on wavefront shaping for enhancing the backscattered light detected from any location in a
sample medium, using low-coherence interferometry. The lateral phase profile of the light incident upon the sample is
controlled using a spatial light modulator (SLM). In this manner, we apply an orthogonal set of phase masks to the
illumination (input) and measure the backscattered signal response (output). These measurements permit us to determine
the linear transformation between the input complex-amplitude modulation profile and the output time-resolved signal.
Thus, we can determine the appropriate SLM write pattern for maximizing the detected signal for a given optical time
delay (in the sample arm). In this manuscript, we are interested in the degree to which maximizing this signal also
permits us to localize the three-dimensional sample region from which the backscattered signal is derived.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.