Modeling and Reducing the Effect of Geometric Uncertainties in Intracranial Aneurysms with Polynomial Chaos Expansion, Data Decomposition, and 4D-Flow MRI.

PURPOSE: Variations in the vessel radius of segmented surfaces of intracranial aneurysms significantly influence the fluid velocities given by computer simulations. It is important to generate models that capture the effect of these variations in order to have a better interpretation of the numerically predicted hemodynamics. Also, it is highly relevant to develop methods that combine experimental observations with uncertainty modeling to get a closer approximation to the blood flow behavior. METHODS: This work applies polynomial chaos expansion to model the effect of geometric uncertainties on the simulated fluid velocities of intracranial aneurysms. The radius of the vessel is defined as the uncertainty variable. Proper orthogonal decomposition is applied to characterize the solution space of fluid velocities. Next, a process of projecting the 4D-Flow MRI velocities on the basis vectors followed by coefficient mapping using generalized dynamic mode decomposition enables the merging of 4D-Flow MRI with the uncertainty propagated fluid velocities. RESULTS: Polynomial chaos expansion propagates the fluid velocities with an error of 2% in velocity magnitude relative to computer simulations. Also, the bifurcation region (or impingement location) shows a standard deviation of 0.17 m/s (since an available reported variance in the vessel radius is adopted to model the uncertainty, the expected standard deviation may be different). Numerical phantom experiments indicate that the proposed approach reconstructs the fluid velocities with 0.3% relative error in presence of geometric uncertainties. CONCLUSION: Polynomial chaos expansion is an effective approach to propagate the effect of the uncertainty variable in the blood flow velocities of intracranial aneurysms. Merging 4D-Flow MRI and uncertainty propagated fluid velocities leads to more realistic flow trends relative to ignoring the uncertainty in the vessel radius.

Super-resolution and denoising of 4D-Flow MRI using physics-Informed deep neural nets.

BACKGROUND AND OBJECTIVE: Time resolved three-dimensional phase contrast magnetic resonance imaging (4D-Flow MRI) has been used to non-invasively measure blood velocities in the human vascular system. However, issues such as low spatio-temporal resolution, acquisition noise, velocity aliasing, and phase-offset artifacts have hampered its clinical application. In this research, we developed a purely data-driven method for super-resolution and denoising of 4D-Flow MRI. METHODS: The flow velocities, pressure, and the MRI image magnitude are modeled as a patient-specific deep neural net (DNN). For training, 4D-Flow MRI images in the complex Cartesian space are used to impose data-fidelity. Physics of fluid flow is imposed through regularization. Creative loss function terms have been introduced to handle noise and super-resolution. The trained patient-specific DNN can be sampled to generate noise-free high-resolution flow images. The proposed method has been implemented using the TensorFlow DNN library and tested on numerical phantoms and validated in-vitro using high-resolution particle image velocitmetry (PIV) and 4D-Flow MRI experiments on transparent models subjected to pulsatile flow conditions. RESULTS: In case of numerical phantoms, we were able to increase spatial resolution by a factor of 100 and temporal resolution by a factor of 5 compared to the simulated 4D-Flow MRI. There is an order of magnitude reduction of velocity normalized root mean square error (vNRMSE). In case of the in-vitro validation tests with PIV as reference, there is similar improvement in spatio-temporal resolution. Although the vNRMSE is reduced by 50%, the method is unable to negate a systematic bias with respect to the reference PIV that is introduced by the 4D-Flow MRI measurement. CONCLUSIONS: This work has demonstrated the feasibility of using the readily available machinery of deep learning to enhance 4D-Flow MRI using a purely data-driven method. Unlike current state-of-the-art methods, the proposed method is agnostic to geometry and boundary conditions and therefore eliminates the need for tedious tasks such as accurate image segmentation for geometry, image registration, and estimation of boundary flow conditions. Arbitrary regions of interest can be selected for processing. This work will lead to user-friendly analysis tools that will enable quantitative hemodynamic analysis of vascular diseases in a clinical setting.

Towards multi-modal data fusion for super-resolution and denoising of 4D-Flow MRI.

4D-Flow magnetic resonance imaging (MRI) has enabled in vivo time-resolved measurement of three-dimensional blood flow velocities in the human vascular system. However, its clinical use has been hampered by two main issues, namely, low spatio-temporal resolution and acquisition noise. While patient-specific computational fluid dynamics (CFD) simulations can address the resolution and noise issues, its fidelity is impacted by accuracy of estimation of boundary conditions, model parameters, vascular geometry, and flow model assumptions. In this paper a scheme to address limitations of both modalities through data-fusion is presented. The solutions of the patient-specific CFD simulation are characterized using proper orthogonal decomposition (POD). Next, a process of projecting the 4D-Flow MRI data onto the POD basis and projection coefficient mapping using generalized dynamic mode decomposition (DMD) enables simultaneous super-resolution and denoising of 4D-Flow MRI. The method has been tested using numerical phantoms derived from patient-specific aneurysmal geometries and applied to in vivo 4D-Flow MRI data.

Denoising and spatial resolution enhancement of 4D flow MRI using proper orthogonal decomposition and lasso regularization.

4D-Flow MRI has emerged as a powerful tool to non-invasively image blood velocity profiles in the human cardio-vascular system. However, it is plagued by issues such as velocity aliasing, phase offsets, acquisition noise, and low spatial and temporal resolution. In imaging small blood vessel malformations such as intra-cranial aneurysms, the spatial resolution of 4D-Flow is often inadequate to resolve fine flow features. In this paper, we address the problem of low spatial resolution and noise by combining 4D-Flow MRI and patient specific computational fluid dynamics using Least Absolute Shrinkage and Selection Operator. Extensive experiments using numerical phantoms of two actual intra-cranial aneurysms geometries show the applicability of the proposed method in recovering the flow profile. Comparisons with the state-of-the-art denoising methods for 4D-Flow show lower error metrics. This method can enable more accurate computation of flow derived patho-physiological parameters such as wall shear stresses, pressure gradients, and viscous dissipation.

Curvelet Transform-based volume fusion for correcting signal loss artifacts in Time-of-Flight Magnetic Resonance Angiography data.

Flow fields in cerebral aneurysms can be measured in vivo with phase-contrast MRI (4D Flow MRI), providing 3D anatomical magnitude images as well as 3-directional velocities through the cardiac cycle. The low spatial resolution of the 4D Flow MRI data, however, requires the images to be co-registered with higher resolution angiographic data for better segmentation of the blood vessel geometries to adequately quantify relevant flow descriptors such as wall shear stress or flow residence time. Time-of-Flight Magnetic Resonance Angiography (TOF MRA) is a non-invasive technique for visualizing blood vessels without the need to administer contrast agent. Instead TOF uses the blood flow-related enhancement of unsaturated spins entering into an imaging slice as means to generate contrast between the stationary tissue and the moving blood. Because of the higher resolutions, TOF data are often used to assist with the segmentation process needed for the flow analysis and Computational Fluid Dynamics (CFD) modeling. However, presence of slow moving and recirculating blood flow such as in brain aneurysms, especially regions where the blood flow is not perpendicular to the image plane, causes signal loss in these regions. In this work a 3D Curvelet Transform-based image fusion approach is proposed for signal loss artifact reduction of TOF volume data. Experiments show the superiority of the proposed approach in comparison to other multi-resolution 3D Wavelet-based image fusion methodologies. The proposed approach can further facilitate model-based fluid analysis and pre/post-operative treatment of patients with brain aneurysms.

Multi-Modal Medical Image Registration with Full or Partial Data: A Manifold Learning Approach.

Multi-modal image registration is the primary step in integrating information stored in two or more images, which are captured using multiple imaging modalities. In addition to intensity variations and structural differences between images, they may have partial or full overlap, which adds an extra hurdle to the success of registration process. In this contribution, we propose a multi-modal to mono-modal transformation method that facilitates direct application of well-founded mono-modal registration methods in order to obtain accurate alignment of multi-modal images in both cases, with complete (full) and incomplete (partial) overlap. The proposed transformation facilitates recovering strong scales, rotations, and translations. We explain the method thoroughly and discuss the choice of parameters. For evaluation purposes, the effectiveness of the proposed method is examined and compared with widely used information theory-based techniques using simulated and clinical human brain images with full data. Using RIRE dataset, mean absolute error of 1.37, 1.00, and 1.41 mm are obtained for registering CT images with PD-, T1-, and T2-MRIs, respectively. In the end, we empirically investigate the efficacy of the proposed transformation in registering multi-modal partially overlapped images.

Slanted support window-based stereo matching for surface reconstruction of microscopic samples.

This work is to address the limitations of 2D Scanning Electron Microscopy (SEM) micrographs in providing 3D topographical information necessary for various types of analysis in biological and biomedical sciences as well as mechanical and material engineering by investigating modern stereo vision methodologies for 3D surface reconstruction of microscopic samples. To achieve this, micrograph pairs of the microscopic samples are acquired by utilizing an SEM equipped with motor controlled specimen stage capable of precise translational, rotational movements and tilting of the specimen stage. After pre-processing of the micrographs by SIFT feature detection/description followed by RANSAC for matching outlier removal and stereo rectification, a dense stereo matching methodology is utilized which takes advantage of slanted support window formulation for sub-pixel accuracy stereo matching of the input images. This results in a dense disparity map which is used to determine the true depth/elevation of individual surface points. This is a major improvement in comparison to previous matching methodologies which require additional post-processing refinement steps to reduce the negative effects of discrete disparity assignment or the blurring artifacts in near the edge regions. The provided results are great representatives of the superior performance of the slanted support window assumption employed here for surface reconstruction of microscopic samples.

Merging computational fluid dynamics and 4D Flow MRI using proper orthogonal decomposition and ridge regression.

Time resolved phase-contrast magnetic resonance imaging 4D-PCMR (also called 4D Flow MRI) data while capable of non-invasively measuring blood velocities, can be affected by acquisition noise, flow artifacts, and resolution limits. In this paper, we present a novel method for merging 4D Flow MRI with computational fluid dynamics (CFD) to address these limitations and to reconstruct de-noised, divergence-free high-resolution flow-fields. Proper orthogonal decomposition (POD) is used to construct the orthonormal basis of the local sampling of the space of all possible solutions to the flow equations both at the low-resolution level of the 4D Flow MRI grid and the high-level resolution of the CFD mesh. Low-resolution, de-noised flow is obtained by projecting in vivo 4D Flow MRI data onto the low-resolution basis vectors. Ridge regression is then used to reconstruct high-resolution de-noised divergence-free solution. The effects of 4D Flow MRI grid resolution, and noise levels on the resulting velocity fields are further investigated. A numerical phantom of the flow through a cerebral aneurysm was used to compare the results obtained using the POD method with those obtained with the state-of-the-art de-noising methods. At the 4D Flow MRI grid resolution, the POD method was shown to preserve the small flow structures better than the other methods, while eliminating noise. Furthermore, the method was shown to successfully reconstruct details at the CFD mesh resolution not discernible at the 4D Flow MRI grid resolution. This method will improve the accuracy of the clinically relevant flow-derived parameters, such as pressure gradients and wall shear stresses, computed from in vivo 4D Flow MRI data.

Three-dimensional reconstruction of highly complex microscopic samples using scanning electron microscopy and optical flow estimation.

Scanning Electron Microscope (SEM) as one of the major research and industrial equipment for imaging of micro-scale samples and surfaces has gained extensive attention from its emerge. However, the acquired micrographs still remain two-dimensional (2D). In the current work a novel and highly accurate approach is proposed to recover the hidden third-dimension by use of multi-view image acquisition of the microscopic samples combined with pre/post-processing steps including sparse feature-based stereo rectification, nonlocal-based optical flow estimation for dense matching and finally depth estimation. Employing the proposed approach, three-dimensional (3D) reconstructions of highly complex microscopic samples were achieved to facilitate the interpretation of topology and geometry of surface/shape attributes of the samples. As a byproduct of the proposed approach, high-definition 3D printed models of the samples can be generated as a tangible means of physical understanding. Extensive comparisons with the state-of-the-art reveal the strength and superiority of the proposed method in uncovering the details of the highly complex microscopic samples.

An Automated Reference Frame Selection (ARFS) Algorithm for Cone Imaging with Adaptive Optics Scanning Light Ophthalmoscopy.

PURPOSE: To develop an automated reference frame selection (ARFS) algorithm to replace the subjective approach of manually selecting reference frames for processing adaptive optics scanning light ophthalmoscope (AOSLO) videos of cone photoreceptors. METHODS: Relative distortion was measured within individual frames before conducting image-based motion tracking and sorting of frames into distinct spatial clusters. AOSLO images from nine healthy subjects were processed using ARFS and human-derived reference frames, then aligned to undistorted AO-flood images by nonlinear registration and the registration transformations were compared. The frequency at which humans selected reference frames that were rejected by ARFS was calculated in 35 datasets from healthy subjects, and subjects with achromatopsia, albinism, or retinitis pigmentosa. The level of distortion in this set of human-derived reference frames was assessed. RESULTS: The average transformation vector magnitude required for registration of AOSLO images to AO-flood images was significantly reduced from 3.33 ± 1.61 pixels when using manual reference frame selection to 2.75 ± 1.60 pixels (mean ± SD) when using ARFS (P = 0.0016). Between 5.16% and 39.22% of human-derived frames were rejected by ARFS. Only 2.71% to 7.73% of human-derived frames were ranked in the top 5% of least distorted frames. CONCLUSION: ARFS outperforms expert observers in selecting minimally distorted reference frames in AOSLO image sequences. The low success rate in human frame choice illustrates the difficulty in subjectively assessing image distortion. TRANSLATIONAL RELEVANCE: Manual reference frame selection represented a significant barrier to a fully automated image-processing pipeline (including montaging, cone identification, and metric extraction). The approach presented here will aid in the clinical translation of AOSLO imaging.

SD-SEM: sparse-dense correspondence for 3D reconstruction of microscopic samples.

Scanning electron microscopy (SEM) imaging has been a principal component of many studies in biomedical, mechanical, and materials sciences since its emergence. Despite the high resolution of captured images, they remain two-dimensional (2D). In this work, a novel framework using sparse-dense correspondence is introduced and investigated for 3D reconstruction of stereo SEM images. SEM micrographs from microscopic samples are captured by tilting the specimen stage by a known angle. The pair of SEM micrographs is then rectified using sparse scale invariant feature transform (SIFT) features/descriptors and a contrario RANSAC for matching outlier removal to ensure a gross horizontal displacement between corresponding points. This is followed by dense correspondence estimation using dense SIFT descriptors and employing a factor graph representation of the energy minimization functional and loopy belief propagation (LBP) as means of optimization. Given the pixel-by-pixel correspondence and the tilt angle of the specimen stage during the acquisition of micrographs, depth can be recovered. Extensive tests reveal the strength of the proposed method for high-quality reconstruction of microscopic samples.

Involuntary eye motion correction in retinal optical coherence tomography: Hardware or software solution?

In this paper, we review state-of-the-art techniques to correct eye motion artifacts in Optical Coherence Tomography (OCT) imaging. The methods for eye motion artifact reduction can be categorized into two major classes: (1) hardware-based techniques and (2) software-based techniques. In the first class, additional hardware is mounted onto the OCT scanner to gather information about the eye motion patterns during OCT data acquisition. This information is later processed and applied to the OCT data for creating an anatomically correct representation of the retina, either in an offline or online manner. In software based techniques, the motion patterns are approximated either by comparing the acquired data to a reference image, or by considering some prior assumptions about the nature of the eye motion. Careful investigations done on the most common methods in the field provides invaluable insight regarding future directions of the research in this area. The challenge in hardware-based techniques lies in the implementation aspects of particular devices. However, the results of these techniques are superior to those obtained from software-based techniques because they are capable of capturing secondary data related to eye motion during OCT acquisition. Software-based techniques on the other hand, achieve moderate success and their performance is highly dependent on the quality of the OCT data in terms of the amount of motion artifacts contained in them. However, they are still relevant to the field since they are the sole class of techniques with the ability to be applied to legacy data acquired using systems that do not have extra hardware to track eye motion.

Application of Independent Component Analysis Techniques in Speckle Noise Reduction of Retinal OCT Images.

Optical Coherence Tomography (OCT) is an emerging technique in the field of biomedical imaging, with applications in ophthalmology, dermatology, coronary imaging etc. OCT images usually suffer from a granular pattern, called speckle noise, which restricts the process of interpretation. Therefore the need for speckle noise reduction techniques is of high importance. To the best of our knowledge, use of Independent Component Analysis (ICA) techniques has never been explored for speckle reduction of OCT images. Here, a comparative study of several ICA techniques (InfoMax, JADE, FastICA and SOBI) is provided for noise reduction of retinal OCT images. Having multiple B-scans of the same location, the eye movements are compensated using a rigid registration technique. Then, different ICA techniques are applied to the aggregated set of B-scans for extracting the noise-free image. Signal-to-Noise-Ratio (SNR), Contrast-to-Noise-Ratio (CNR) and Equivalent-Number-of-Looks (ENL), as well as analysis on the computational complexity of the methods, are considered as metrics for comparison. The results show that use of ICA can be beneficial, especially in case of having fewer number of B-scans.

3DSEM++: Adaptive and intelligent 3D SEM surface reconstruction.

Structural analysis of microscopic objects is a longstanding topic in several scientific disciplines, such as biological, mechanical, and materials sciences. The scanning electron microscope (SEM), as a promising imaging equipment has been around for decades to determine the surface properties (e.g., compositions or geometries) of specimens by achieving increased magnification, contrast, and resolution greater than one nanometer. Whereas SEM micrographs still remain two-dimensional (2D), many research and educational questions truly require knowledge and facts about their three-dimensional (3D) structures. 3D surface reconstruction from SEM images leads to remarkable understanding of microscopic surfaces, allowing informative and qualitative visualization of the samples being investigated. In this contribution, we integrate several computational technologies including machine learning, contrario methodology, and epipolar geometry to design and develop a novel and efficient method called 3DSEM++ for multi-view 3D SEM surface reconstruction in an adaptive and intelligent fashion. The experiments which have been performed on real and synthetic data assert the approach is able to reach a significant precision to both SEM extrinsic calibration and its 3D surface modeling.

State-of-the-art in retinal optical coherence tomography image analysis.

Optical coherence tomography (OCT) is an emerging imaging modality that has been widely used in the field of biomedical imaging. In the recent past, it has found uses as a diagnostic tool in dermatology, cardiology, and ophthalmology. In this paper we focus on its applications in the field of ophthalmology and retinal imaging. OCT is able to non-invasively produce cross-sectional volumetric images of the tissues which can be used for analysis of tissue structure and properties. Due to the underlying physics, OCT images suffer from a granular pattern, called speckle noise, which restricts the process of interpretation. This requires specialized noise reduction techniques to eliminate the noise while preserving image details. Another major step in OCT image analysis involves the use of segmentation techniques for distinguishing between different structures, especially in retinal OCT volumes. The outcome of this step is usually thickness maps of different retinal layers which are very useful in study of normal/diseased subjects. Lastly, movements of the tissue under imaging as well as the progression of disease in the tissue affect the quality and the proper interpretation of the acquired images which require the use of different image registration techniques. This paper reviews various techniques that are currently used to process raw image data into a form that can be clearly interpreted by clinicians.