Quantitative photoacoustic computed tomography (qPACT) holds great promise to advance a variety of important clinical applications with its potential to estimate vital physiological properties such as oxygen saturation. However, the qPACT reconstruction problem is highly nonlinear and ill-posed. Conventional spectral unmixing methods often oversimplify the problem, resulting in suboptimal accuracy. Alternatively, more principled image reconstruction approaches that comprehensively model the imaging physics are computationally burdensome and require the design of effective regularization strategies. To overcome these limitations, learning-based methods have been proposed. To date, however, the effectiveness of such methods on full-scale problems in which clinically relevant variability in anatomy and physiological parameters is considered has not been established. To address this, we investigated the use of a convolutional neural network with spatial and channel attention modules to estimate the three-dimensional (3D) distribution of tissue oxygenation within vessels and lesions in the female breast. The network was provided with input data comprising noise-corrupted 3D initial pressure distributions corresponding to three wavelengths (757, 800, 850 nm). An additional novel aspect of our study was the use of realistic 3D numerical breast phantoms that described stochastic variations in breast anatomy and functional properties, which enabled a meaningful, quantitative, and systematic evaluation of the proposed method. This study represents an important contribution to the field of qPACT and will guide the exploration of learning-based methods to help translate this important technology by delineating potential prospects and limitations.
KEYWORDS: Image restoration, Photoacoustic tomography, Tunable filters, Data modeling, Education and training, Data acquisition, Signal filtering, Linear filtering, Image filtering, 3D modeling
Photoacoustic computed tomography (PACT) is being actively developed for breast cancer imaging. In 3D PACT imagers for breast imaging, a hemispherical measurement geometry that encloses the breast has been employed. Such measurement data are referred to as “half-scan” data. Existing closed-form reconstruction methods assume a closed measurement aperture; however, the direct application of these methods to half-scan data results in inaccurate images with artifacts. Previous studies have demonstrated that half-scan data are “complete” in the sense that they contain sufficient information for accurate and stable reconstruction of an object contained within a hemispherical measurement aperture. However, direct closed-form methods for use with half-scan data have not been reported. Although optimization-based iterative image reconstruction methods are applicable, they are computationally intensive. In this work, for the first time, a semi-analytic image reconstruction method of filtered backprojection (FBP) form was proposed for use with half-scan PACT data. To accomplish this, the unknown data filtering operation is learned in a data-driven way by use of a linear U-Net neural network. To investigate the method, stochastic 3D numerical breast phantoms (NBPs) were used for model training and testing. As a result of the completeness of the half-scan data, we demonstrate that the learned FBP method can be widely applied, even when the to-be-reconstructed object differs considerably from those that were used to learn the data filtering. This is a key feature of the method that will enable it to have an important practical impact on PACT.
Transcranial photoacoustic computed tomography (PACT) is an emerging human neuroimaging modality that holds significant potential for clinical and scientific applications. However, accurate image reconstruction remains challenging due to skull-induced aberration of the measurement data. Model-based image reconstruction methods have been proposed that are based on the elastic wave equation. To be effective, such methods require that the elastic and acoustic properties of the skull are known accurately, which can be difficult to achieve in practice. Additionally, such methods are computationally burdensome. To address these challenges, a novel learningbased image reconstruction was proposed. The method involves the use of a deep neural network to map a preliminary image that was computed by use of a computationally efficient but approximate reconstruction method to a high-quality, de-aberrated, estimate of the induced initial pressure distribution within the cortical region of the brain. The method was systematically evaluated via computer-simulations that involved realistic, full-scale, three-dimensional stochastic head phantoms. The phantoms contained physiologically relevant optical and acoustic properties and stochastically synthesized vasculature. The results demonstrated that the learning-based method could achieve comparable performance to a state-of-the-art model-based method when the assumed skull parameters were accurate, and significantly outperformed the model-based method when uncertainty in the skull parameters was present. Additionally, the method can reduce image reconstruction times from days to tens of minutes. This study represents an important contribution to the development of transcranial PACT and will motivate the exploration of learning-based methods to help advance this important technology.
SignificanceWhen developing a new quantitative optoacoustic computed tomography (OAT) system for diagnostic imaging of breast cancer, objective assessments of various system designs through human trials are infeasible due to cost and ethical concerns. In prototype stages, however, different system designs can be cost-efficiently assessed via virtual imaging trials (VITs) employing ensembles of digital breast phantoms, i.e., numerical breast phantoms (NBPs), that convey clinically relevant variability in anatomy and optoacoustic tissue properties.AimThe aim is to develop a framework for generating ensembles of realistic three-dimensional (3D) anatomical, functional, optical, and acoustic NBPs and numerical lesion phantoms (NLPs) for use in VITs of OAT applications in the diagnostic imaging of breast cancer.ApproachThe generation of the anatomical NBPs was accomplished by extending existing NBPs developed by the U.S. Food and Drug Administration. As these were designed for use in mammography applications, substantial modifications were made to improve blood vasculature modeling for use in OAT. The NLPs were modeled to include viable tumor cells only or a combination of viable tumor cells, necrotic core, and peripheral angiogenesis region. Realistic optoacoustic tissue properties were stochastically assigned in the NBPs and NLPs.ResultsTo advance optoacoustic and optical imaging research, 84 datasets have been released; these consist of anatomical, functional, optical, and acoustic NBPs and the corresponding simulated multi-wavelength optical fluence, initial pressure, and OAT measurements. The generated NBPs were compared with clinical data with respect to the volume of breast blood vessels and spatially averaged effective optical attenuation. The usefulness of the proposed framework was demonstrated through a case study to investigate the impact of acoustic heterogeneity on OAT images of the breast.ConclusionsThe proposed framework will enhance the authenticity of virtual OAT studies and can be widely employed for the investigation and development of advanced image reconstruction and machine learning-based methods, as well as the objective evaluation and optimization of the OAT system designs.
In OAT breast imaging, the optical fluence distribution in the breast under the skin layer is influenced by the melanin concentration in the epidermis. However, the extent to which skin color affects the ability to detect lesions and estimate physiological parameters in OAT breast imaging remains relatively unexplored. To address this, for the first time, realistic virtual imaging studies were conducted to assess the impact of skin color on 3D breast OAT. These studies quantitatively revealed the extent to which skin color diminishes the optical fluence within breast tissue and degrades the signal-to-noise ratio of lesions at various depths.
The ability to perform dynamic imaging of time-varying physiological processes in small animal models is critically needed to understand the progression of human diseases and develop new therapies. Photoacoustic computed tomography (PACT) has been recognized as a promising tool for small animal imaging because of its relatively low expense, high resolution, and good signal-to-noise ratio. By exploiting the optical absorption of hemoglobin or exogenous contrast agents, dynamic PACT holds excellent potential for measuring important time-varying biomarkers like tumor vascular perfusion. Nonetheless, current dynamic PACT technologies possess several limitations. Most three-dimensional (3D) PACT imagers employ a tomographic measurement process in which a gantry containing acoustic transducers is rotated about the animal. Such a rotating gantry is advantageous for limiting the cost of the system due to the decreased number of acoustic transducers and associated electronics and for enabling convenient delivery of the light to the object. However, this presents significant challenges for dynamic image reconstruction because only a few tomographic views are available to reconstruct each temporal frame. This work presents an efficient and accurate dynamic image reconstruction method that can be deployed with widely available 3D imagers using rotating gantries. In particular, a low-rank matrix estimation based spatiotemporal image reconstruction (LRME-STIR) algorithm is proposed. In a stylized virtual dynamic contrast-enhanced imaging study, the proposed LRME-STIR algorithm is shown to accurately recover a well characterized dynamic numerical murine phantom in which tumor vascular perfusion and breathing motion are modeled.
KEYWORDS: Breast, Tissue optics, 3D image processing, Signal attenuation, Optoacoustics, Blood, 3D image reconstruction, Blood vessels, Imaging systems, Breast imaging
Significance: In three-dimensional (3D) functional optoacoustic tomography (OAT), wavelength-dependent optical attenuation and nonuniform incident optical fluence limit imaging depth and field of view and can hinder accurate estimation of functional quantities, such as the vascular blood oxygenation. These limitations hinder OAT of large objects, such as a human female breast.
Aim: We aim to develop a measurement-data-driven method for normalization of the optical fluence distribution and to investigate blood vasculature detectability and accuracy for estimating vascular blood oxygenation.
Approach: The proposed method is based on reasonable assumptions regarding breast anatomy and optical properties. The nonuniform incident optical fluence is estimated based on the illumination geometry in the OAT system, and the depth-dependent optical attenuation is approximated using Beer–Lambert law.
Results: Numerical studies demonstrated that the proposed method significantly enhanced blood vessel detectability and improved estimation accuracy of the vascular blood oxygenation from multiwavelength OAT measurements, compared with direct application of spectral linear unmixing without optical fluence compensation. Experimental results showed that the proposed method revealed previously invisible structures in regions deeper than 15 mm and/or near the chest wall.
Conclusions: The proposed method provides a straightforward and computationally inexpensive approximation of wavelength-dependent effective optical attenuation and, thus, enables mitigation of the spectral coloring effect in functional 3D OAT imaging.
The goal of quantitative optoacoustic tomography (qOAT) is to reconstruct a distribution of absolute chromophore concentrations and/or functional properties from measurements of the optically induced pressure (ultrasound signals) acquired at multiple excitation wavelengths. Estimating the distribution of hemoglobin, an endogenous OAT chromophore, is important because the oxygen saturation distribution of the blood vessels is a well-known indicator of aggressive growth of a cancerous tumor. In a number of studies, a spectral linear unmixing method has been applied to two-dimensional slices of tissue acquired with OAT at multiple wavelengths, leading to promising results at moderate penetration depths of ≤ 2 cm. In the three-dimensional (3D) OAT of the breast, such functional images cannot be accurately reconstructed via the spectral linear unmixing method due to unknown spatial distribution of the optical fluence in a relatively large size of the volume of interest (≥ 4 cm). Optical attenuation in biological tissue depends on the optical wavelength, and the optical fluence is exponentially attenuated with increasing imaging depth. Thus, the accuracy of the estimated distribution decreases with depth. To overcome this challenge, we investigated a spectral linear unmixing method with a simplified optical fluence normalization based on measurements of background absorbed optical energy in the breast. We compare estimates of blood oxygen saturations from two-wavelength clinical OAT breast images and demonstrate acceptable accuracy of ~10% while lack of compensation for the optical fluence distribution can lead to values outside the physiological range. We also quantitatively compare the accuracy of oxygen saturation estimates using numerical simulation of photon transport in realistic 3D OAT breast phantoms at dual wavelengths of 757 and 850 nm with inverse ratio of the optical absorption by deoxy- (Hb) and oxy-hemoglobin (HbO2) and three wavelengths of 757, 800, and 850 nm with inclusion of isosbestic point of the optical absorption in Hb/HbO2.
Dynamic reconstruction of three-dimensional (3D) photoacoustic tomography (PAT) recovers a sequence of 3D optical contrast distributions and enables to monitor time-varying changes of the chromophore concentrations in biological tissues. To achieve a high frame rate, only a limited-angle few-view (even a single-view) acoustic measurements can be collected at each time frame. These sparse incomplete data represent a formidable challenge to obtain sequences of reconstructed images with both high spatial and temporal resolution. Furthermore, dynamic PAT reconstruction is extremely computationally and memory expensive. High-resolution spatiotemporal reconstruction of 3D objects is, in fact, computationally unfeasible using naïve extensions of classical PAT reconstruction methods for static images. In this study, we present a fast and accurate randomized algorithm for dynamic PAT reconstruction from few tomographic views. Our method is based on the fact that, for many applications of clinical interest, dynamic PAT images are semi-separable in space and time. That is the sequence of PAT images can be expanded using a relatively small number r of basis functions in space and time. Under this assumption, the dynamic PAT reconstruction problem is reformulated as a penalized least squares model, where the nuclear norm of the space-time image is used for the regularization term. By use of a randomized truncated singular value thresholding method, our approach can be implemented in a memory-efficient (only need to store the r spatial and temporal basis functions) and computationally-scalable (only r PAT reconstructions per iteration) manner. The effectiveness of the proposed method is demonstrated using numerical simulation and experimental data of a 3D phantom.
In silico studies for ultrasound computed tomography (USCT) can allow to explore imaging system parameters and reconstruction methods, without the economic burden and ethical concerns of clinical trials. A framework is proposed for virtual imaging trials of USCT. First, an ensemble of three-dimensional numerical breast phantoms consisting of anatomically realistic tissue structures and lesions is created. Next, acoustic properties are assigned to each tissue-type within physiological ranges. Finally, USCT measurement data are computed by simulating acoustic wave propagation. The proposed framework will establish a standard pipeline for USCT virtual imaging trials and provide publicly available large-scale datasets
Due to a demonstrated capability to assess tumor angiogenesis and hypoxia in mammalian systems, there is great interest in applying optoacoustic tomography (OAT) to the study and screening of breast cancer. In order to translate OAT to clinical applications, in silico studies are crucial for studying imaging system parameters that might be impossible to assess via direct experimentation. Previous numerical phantoms have proven to be too unrealistic for rigorous testing of modern image reconstruction methods and clinically relevant signal detection tasks. Recently, the U.S. Food and Drug Administration has released software to generate realistic three-dimensional numerical realizations of the human female breast as part of the Virtual Imaging Clinical Trials for Regulatory Evaluation (VICTRE) project. By careful selection of physical attributes and material coefficients, the VICTRE breast phantom can be customized for particular imaging tasks, but no such customization has been given for OAT. We propose a general framework of in silico studies for OAT breast imaging using the VICTRE breast phantom. We will create an ensemble of OAT breast phantoms, using appropriate optical and acoustic parameters, that have typical sizes and tissue densities. Various lesions will be created and embedded based on clinical scenarios. We will define and perform several signal detection tasks by which the system performance may be compared. Generation of such an ensemble requires substantial computation but once produced, it can be utilized in other numerical simulation studies of the configuration of OAT imaging systems customized for diverse tasks. We will make this ensemble of phantoms publicly available online. The proposed framework will permit standardization of the assessment of 3D OAT data-acquisition parameters and image reconstruction methods.
Optoacoustic tomography (OAT) is a promising modality for breast imaging that provides high resolution, detection sensitivity and diagnostic specificity for vascularized breast tumors. In OAT systems employing an arc- shaped illuminator, irregular overlaps of light beams can yield a non-uniform illumination throughout the entire volume of the breast. The imbalance in optical fluence leads to intensity loss in the reconstructed OAT images. Additionally, because optical fluence decreases with depth from breast skin surface, i.e., optical attenuation, deep breast tissues are diminished in the reconstructed images. For qualitative enhancement in 3D OAT imaging, we propose an image processing method to estimate, and compensate for, both the non-uniform incident optical fluence and the optical attenuation. We approximate the non-uniform illumination via maximum intensity extraction for polar angles in a spherical coordinate system. The location of the breast surface is estimated by detecting blood vessels nearest to the breast skin layer that appear with relatively high intensities in the reconstructed image. The breast depth is computed as the minimum distance between each voxel and the detected breast surface. The depth-dependent optical attenuation in the breast is estimated using the Beer– Lambert law down to the maximum penetration depth determined from an analysis of noise and artifacts in the reconstructed image. At each polar angle, the reciprocals of the estimated attenuation is used to compensate for the loss in intensity. The results are that previously invisible structures near the chest wall are revealed, and visible penetration depth was increased by 67% over the conventional, non-compensated volumes.
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