In vivo co-registered hybrid-contrast imaging by successive photoacoustic tomography and magnetic resonance imaging.

Magnetic resonance imaging (MRI) and photoacoustic tomography (PAT) offer two distinct image contrasts. To integrate these two modalities, we present a comprehensive hardware-software solution for the successive acquisition and co-registration of PAT and MRI images in in vivo animal studies. Based on commercial PAT and MRI scanners, our solution includes a 3D-printed dual-modality imaging bed, a 3-D spatial image co-registration algorithm with dual-modality markers, and a robust modality switching protocol for in vivo imaging studies. Using the proposed solution, we successfully demonstrated co-registered hybrid-contrast PAT-MRI imaging that simultaneously displays multi-scale anatomical, functional and molecular characteristics on healthy and cancerous living mice. Week-long longitudinal dual-modality imaging of tumor development reveals information on size, border, vascular pattern, blood oxygenation, and molecular probe metabolism of the tumor micro-environment at the same time. The proposed methodology holds promise for a wide range of pre-clinical research applications that benefit from the PAT-MRI dual-modality image contrast.

MRI Information-Based Correction and Restoration of Photoacoustic Tomography.

As an emerging molecular imaging modality, Photoacoustic Tomography (PAT) is capable of mapping tissue physiological metabolism and exogenous contrast agent information with high specificity. Due to its ultrasonic detection mechanism, the precise localization of targeted lesions has long been a challenge for PAT imaging. The poor soft-tissue contrast of the PAT image makes this process difficult and inaccurate. To meet this challenge, in this study, we first make use of the rich and clear structural information brought about by another advanced imaging modality, Magnetic Resonance Imaging (MRI), to assist organ segmentation and correct for the light fluence attenuation of PAT. We demonstrate improved feature visibility and enhanced localization of endogenous and exogenous agents in the fluence corrected PAT images. Compared with PAT-based methods, the contrast-to-noise ratio (CNR) of our MRI-assisted method increases by 29.1% in live animal experiments. Furthermore, we show that the co-registered MRI image can also be incorporated into PAT image restoration, and achieves improved anatomical landscape and soft-tissue contrast (CNR increased by 25.36%) while preserving similar spatial resolution. This PAT-MRI combination provides excellent structural, functional and molecular images of the subject, and may enable more comprehensive analysis of various preclinical research applications.

Automatic 3-D segmentation and volumetric light fluence correction for photoacoustic tomography based on optimal 3-D graph search.

Preclinical imaging with photoacoustic tomography (PAT) has attracted wide attention in recent years since it is capable of providing molecular contrast with deep imaging depth. The automatic extraction and segmentation of the animal in PAT images is crucial for improving image analysis efficiency and enabling advanced image post-processing, such as light fluence (LF) correction for quantitative PAT imaging. Previous automatic segmentation methods are mostly two-dimensional approaches, which failed to conserve the 3-D surface continuity because the image slices were processed separately. This discontinuity problem further hampers LF correction, which, ideally, should be carried out in 3-D due to spatially diffused illumination. Here, to solve these problems, we propose a volumetric auto-segmentation method for small animal PAT imaging based on the 3-D optimal graph search (3-D GS) algorithm. The 3-D GS algorithm takes into account the relation among image slices by constructing a 3-D node-weighted directed graph, and thus ensures surface continuity. In view of the characteristics of PAT images, we improve the original 3-D GS algorithm on graph construction, solution guidance and cost assignment, such that the accuracy and smoothness of the segmented animal surface were guaranteed. We tested the performance of the proposed method by conducting in vivo nude mice imaging experiments with a commercial preclinical cross-sectional PAT system. The results showed that our method successfully retained the continuous global surface structure of the whole 3-D animal body, as well as smooth local subcutaneous tumor boundaries at different development stages. Moreover, based on the 3-D segmentation result, we were able to simulate volumetric LF distribution of the entire animal body and obtained LF corrected PAT images with enhanced structural visibility and uniform image intensity.

Multispectral interlaced sparse sampling photoacoustic tomography based on directional total variation.

BACKGROUND AND OBJECTIVE: Photoacoustic tomography (PAT) is capable of obtaining cross-sectional images of small animals that represent the optical absorption of biological tissues. The multispectral Interlaced Sparse Sampling PAT, or ISS-PAT, is a previously proposed PAT imaging method that offered high quality images with much sparser transducer angular coverage. Although it provides superior imaging performance, the original ISS-PAT method suffered from a heavy computation burden, which hinders its practical application. METHODS: Here, we propose a new regularization scheme based on the directional total variation (dTV) for ISS-PAT. This method efficiently imposes the structural information by considering both the edge position and direction information of the anatomical prior image in ISS-PAT. It does not require image segmentation, and can be conveniently solved by a modified alternating direction of multipliers (ADMM) algorithm. RESULTS: We perform simulation, tissue mimicking phantom and in vivo small animal experiments to evaluate the proposed scheme. The reconstructed PAT images showed image quality and spectral un-mixing accuracy close to those obtained by non-local means based ISS-PAT, but with much shorter image reconstruction time. For a 1/6 sparse sampling rate, the average efficiency improvement is nearly 16-folds. CONCLUSIONS: The experimental results demonstrate the feasibility of the dTV regularization scheme for ISS-PAT. Its efficient image reconstruction performance facilitates the potential of the hardware realization and practical applications of the ISS-PAT.

Photoacoustic Tomography Image Restoration With Measured Spatially Variant Point Spread Functions.

The spatial resolution of photoacoustic tomography (PAT) can be characterized by the point spread function (PSF) of the imaging system. Due to the tomographic detection geometry, the PAT image degradation model could be generally described by using spatially variant PSFs. Deconvolution of the PAT image with these PSFs could restore image resolution and recover object details. Previous PAT image restoration algorithms assume that the degraded images can be restored by either a single uniform PSF, or some blind estimation of the spatially variant PSFs. In this work, we propose a PAT image restoration method to improve image quality and resolution based on experimentally measured spatially variant PSFs. Using photoacoustic absorbing microspheres, we design a rigorous PSF measurement procedure, and successfully acquire a dense set of spatially variant PSFs for a commercial cross-sectional PAT system. A pixel-wise PSF map is further obtained by employing a multi-Gaussian-based fitting and interpolation algorithm. To perform image restoration, an optimization-based iterative restoration model with two kinds of regularizations is proposed. We perform phantom and in vivo mice imaging experiments to verify the proposed method, and the results show significant image quality and resolution improvement.

Cross-sectional photoacoustic tomography image reconstruction with a multi-curve integration model.

BACKGROUND AND OBJECTIVE: In acoustic inversion of photoacoustic tomography (PAT), an imaging model that precisely describes both the ultrasonic wave propagation and the detector properties is of crucial importance. Inspired by the multi-stripe integration model in clinical X-ray computed tomography systems, in this work, we introduce the Multi-Curve-Integration-based acoustic inversion for cross-sectional Photoacoustic Tomography (MCI-PAT). METHODS: We assumed that in cross-sectional PAT system, the three-dimensional (3-D) wave propagation problem could be reduced to a two-dimensional (2-D) problem in a limited, yet sufficient field of view. Under such condition, the MCI-PAT imaging model is generated by integrating several circular acoustic curves, the centers of which are points evenly distributed on the finite-size ultrasonic transducer surface. In this way, the spatial detector response is taken into account, while its computational burden does not largely increase because the integration process is performed only on a 2-D plane. RESULTS: As proven by simulation, phantom and in vivo small animal experiments, the MCI-PAT method leads to promising improvement in PAT image quality. Comparing to traditional imaging models that considered only a single acoustic curve, our proposed method successfully improved the visibility of small structures and achieved evident enhancement on signal-to-noise ratio. CONCLUSIONS: The performance of the MCI-PAT method demonstrates that for cross-sectional PAT, a 2-D simplification of the propagation of multiple photoacoustic waves is feasible. Due to its simplicity, our method can be used as an add-on to current system models considering only a single acoustic curve.

Multispectral Interlaced Sparse Sampling Photoacoustic Tomography.

Multispectral photoacoustic tomography (PAT) is capable of resolving tissue chromophore distribution based on spectral un-mixing. It works by identifying the absorption spectrum variations from a sequence of photoacoustic images acquired at multiple illumination wavelengths. Due to multispectral acquisition, this inevitably creates a large dataset. To cut down the data volume, sparse sampling methods that reduce the number of detectors have been developed. However, image reconstruction of sparse sampling PAT is challenging because of insufficient angular coverage. During spectral un-mixing, these inaccurate reconstructions will further amplify imaging artefacts and contaminate the results. To solve this problem, we present the interlaced sparse sampling (ISS) PAT, a method that involved: 1) a novel scanning-based image acquisition scheme in which the sparse detector array rotates while switching illumination wavelength, such that a dense angular coverage could be achieved by using only a few detectors; and 2) a corresponding image reconstruction algorithm that makes use of an anatomical prior image created from the ISS strategy to guide PAT image computation. Reconstructed from the signals acquired at different wavelengths (angles), this self-generated prior image fuses multispectral and angular information, and thus has rich anatomical features and minimum artefacts. A specialized iterative imaging model that effectively incorporates this anatomical prior image into the reconstruction process is also developed. Simulation, phantom, and in vivo animal experiments showed that even under 1/6 or 1/8 sparse sampling rate, our method achieved comparable image reconstruction and spectral un-mixing results to those obtained by conventional dense sampling method.

Photoacoustic imaging of living mice enhanced with a low-cost contrast agent.

One of the advantages of photoacoustic imaging (PAI) is that its image contrast may come from exogenous agents. Such advantage leads to the development of a great number of exogenous probes. However, the biosafety of most of these contrast agents has not yet been confirmed, thus hindering their clinical translation. In this work, we report on the utilization of a clinically commonly used nutritional medicine, the Intralipid, as a new contrast agent for photoacoustic imaging. Intralipid consists of soybean oil, lecithin and glycerin and has long been adapted in clinical practices, mainly as a parenteral nutrition. In our study, we found that with Intralipid, the imaging sensitivity of PAI can be effectively enhanced, as demonstrated in in vivo imaging of different organs of nude mice. Further imaging studies on cancerous mice showed not only a twofold PA signal enhancement, but also a strong and long-lasting signal aggregation in the tumor region. Our result revealed the potential of Intralipid to be used in clinical PAI applications, since it is clinically safe, and can be easily prepared at very low cost.

Automatic three-dimensional segmentation of endoscopic airway OCT images.

Automatic delineation and segmentation of airway structures from endoscopic optical coherence tomography (OCT) images improve image analysis efficiency and thus has been of particular interest. Conventional two-dimensional automatic segmentation methods, such as the dynamic programming approach, ensures the edge-continuity in the xz-direction (intra-B-scan), but fails to preserve the surface-continuity when concerning the y-direction (inter-B-scan). To solve this, we present a novel automatic three-dimensional (3D) airway segmentation strategy. Our segmentation scheme includes an artifact-oriented pre-processing pipeline and a modified 3D optimal graph search algorithm incorporating adaptive tissue-curvature adjustment. The proposed algorithm is tested on endoscopic airway OCT image data sets acquired by different swept-source OCT platforms, and on different animal and human models. With our method, the results show continuous surface segmentation performance, which is both robust and accurate.