Significance: 2D fully convolutional neural networks have been shown capable of producing maps of sO$_2$ from 2D simulated images of simple tissue models. However, their potential to produce accurate estimates in vivo is uncertain as they are limited by the 2D nature of the training data when the problem is inherently 3D, and they have not been tested with realistic images.
Aim: To demonstrate the capability of deep neural networks to process whole 3D images and output 3D maps of vascular sO$_2$ from realistic tissue models/images.
Approach: Two separate fully convolutional neural networks were trained to produce 3D maps of vascular blood oxygen saturation and vessel positions from multiwavelength simulated images of tissue models.
Results: The mean of the absolute difference between the true mean vessel sO$_2$ and the network output for 40 examples was 4.4% and the standard deviation was 4.5%.
Conclusions: 3D fully convolutional networks were shown capable of producing accurate sO$_2$ maps using the full extent of spatial information contained within 3D images generated under conditions mimicking real imaging scenarios. This work demonstrates that networks can cope with some of the confounding effects present in real images such as limited-view artefacts, and have the potential to produce accurate estimates in vivo.
Photoacoustic imaging (PAI) is a promising approach to realize in vivo transcranial cerebral vascular imaging. However, the strong attenuation and distortion of the photoacoustic wave caused by the thick porous skull greatly affect the imaging quality. In this study, we designed a convolutional neural network (CNN) with a U-Net architecture to extract the effective photoacoustic information hidden in the speckle patterns; obtained vascular network images datasets under porous media through simulation and experiment, and trained the network weights respectively. The results show that the propos…
Photoacoustic computed tomography (PACT) is a hybrid imaging modality, which combines the high optical contrast of pure optical imaging and the high penetration depth of ultrasound imaging. However, photoacoustic image dataset with good quality and large quantity is lacking. In this paper, we mainly talk about how to generate a practical photoacoustic dataset. Firstly, we extracted 389 3D vessel volumes from CT whole-lung scan database, and enhanced the blood vessel structures. Then for each 3D vessel volume, we embedded it into a three-layer cubic phantom to formulate a skin tissue model, whi…
We present a photoacoustic computed tomography investigation on a healthy human finger, to image blood vessels with a focus on vascularity across the interphalangeal joints. The cross-sectional images were acquired using an imager specifically developed for this purpose. The images show rich detail of the digital blood vessels with diameters between 100 $μ$m and 1.5 mm in various orientations and at various depths. Different vascular layers in the skin including the subpapillary plexus could also be visualized. Acoustic reflections on the finger bone of photoacoustic signals from skin were vis…
Photoacoustic tomography (PAT) is intrinsically sensitive to blood oxygen saturation (sO2) in vivo. However, making accurate sO2 measurements without knowledge of tissue- and instrumentation-related correction factors is extremely challenging. We have developed a low-cost flow phantom system to facilitate validation of photoacoustic tomography systems. The phantom is composed of a flow circuit, which is partially embedded within a tissue mimicking phantom, with independent sensors providing online monitoring of the optical absorption spectrum and partial pressure of oxygen in the tube. We firs…
Estimation of blood oxygenation with spectroscopic photoacoustic imaging is a promising tool for several biomedical applications. For this method to be quantitative, it relies on an accurate method of the light fluence in the tissue. This is difficult deep in heterogeneous tissue, where different wavelengths of light can experience significantly different attenuation. In this work, we developed a new deep neural network to simultaneously estimate the oxygen saturation in blood vessels and segment the vessels from the surrounding background tissue. The network was trained on estimated initial p…
Non-invasive imaging of deep blood vessels for mapping hemodynamics remains an open quest in biomedical optical imaging. Although pure optical imaging techniques offer rich optical contrast of blood and have been reported to measure blood flow, they are generally limited to surface imaging within the optical diffusion limit of about one millimeter. Herein, we present photoacoustic vector tomography (PAVT), breaking through the optical diffusion limit to image deep blood flow with speed and direction quantification. PAVT synergizes the spatial heterogeneity of blood and the photoacoustic contra…
German Cancer Research Center (DKFZ)（德国癌症研究中心）；Heidelberg University（海德堡大学）
One of the main applications of photoacoustic (PA) imaging is the recovery of functional tissue properties, such as blood oxygenation (sO2). This is typically achieved by linear spectral unmixing of relevant chromophores from multispectral photoacoustic images. Despite the progress that has been made towards quantitative PA imaging (qPAI), most sO2 estimation methods yield poor results in realistic settings. In this work, we tackle the challenge by employing learned spectral decoloring for quantitative photoacoustic imaging (LSD-qPAI) to obtain quantitative estimates for blood oxygenation. LSD…
We developed a Bessel-beam photoacoustic microscopical simulation platform by using the k-Wave: MATLAB toolbox. The simulation platform uses the ring slit method to generate Bessel beam. By controlling the inner and outer radius of the ring slit, the depth-of-field (DoF) of Bessel beam can be controlled. And the large volumetric image is obtained by point scanning. The simulation experiments on blood vessels was carried out to demonstrate the feasibility of the simulation plat-form. This simulation work can be used as an auxiliary tool for the research of Bessel-beam photoacoustic microscopy.
A new approach for continuous and non-invasive monitoring of the glucose concentration in human epidermis has been suggested recently. This method is based on photoacoustic (PA) analysis of human interstitial fluid. The measurement can be performed in vitro and in vivo and, therefore, may form the basis for a non-invasive monitoring of the blood sugar level for diabetes patients. It requires a windowless PA cell with an additional opening that is pressed onto the human skin. Since signals are weak, advantage is taken of acoustic resonances of the cell. Recently, a numerical approach based on t…
Multispectral photoacoustic (PA) imaging is a prime modality to monitor hemodynamics and changes in blood oxygenation (sO2). Although sO2 changes can be an indicator of brain activity both in normal and in pathological conditions, PA imaging of the brain has mainly focused on small animal models with lissencephalic brains. Therefore, the purpose of this work was to investigate the usefulness of multispectral PA imaging in assessing sO2 in a gyrencephalic brain. To this end, we continuously imaged a porcine brain as part of an open neurosurgical intervention with a handheld PA and ultrasonic (U…
Photoacoustic tomography (PAT) is a newly developed medical imaging modality, which combines the advantages of pure optical imaging and ultrasound imaging, owning both high optical contrast and deep penetration depth. Very recently, PAT is studied in human brain imaging. Nevertheless, while ultrasound waves are passing through the human skull tissues, the strong acoustic attenuation and aberration will happen, which causes photoacoustic signals' distortion. In this work, we use 10 magnetic resonance angiography (MRA) human brain volumes, and manually segment them to obtain the 2D human brain n…
Contemporary paradigm of vascular hemodynamics considers normal blood flow to be pulsatile laminar flow. Transition to turbulence can cause diseases such as atherosclerosis or brain aneurysms. Recently, we demonstrated the existence of turbulence in experimental models of brain aneurysm; in the aneurysm sac as well as in the main artery. Thus, we were intrigued to explore if such a long-standing assumption of the laminarity of blood flow could be challenged. We have used methods and tools from chaos theory, hydrodynamic stability theory and turbulence physics to explore the existence of turbul…
Photoacoustic (PA) imaging systems based on clinical linear ultrasound arrays have become increasingly popular in translational PA research. Such systems can be more easily integrated in a clinical workflow due to the simultaneous access to ultrasonic imaging and their familiarity of use to clinicians. In contrast to more complex setups, hand held linear probes can be applied to a large variety of clinical use cases. However, most translational work with such scanners is based on proprietary development and as such not accessible to the community. In this contribution, we present a custom-buil…
Simultaneous 3D co-registered perfusion and oxygenation with ULM, photoacoustic imaging, and a planar matrix array
Sorbonne Université（索邦大学）；CNRS（法国国家科学研究中心）；Inserm（法国国家健康与医学研究院）；Laboratoire d’Imagerie Biomédicale, LIB（生物医学成像实验室）；Université Paris Cité（巴黎西岱大学）；Centre de Recherche des Cordeliers（科尔德洛耶研究中心）；Institut Cochin（科尚研究所）；Department of Nuclear Medicine, Hôpital Pitié Salpêtrière, APHP（皮蒂埃-萨尔佩特里埃医院核医学科）；PARCC（PARCC研究中心）；Service de Radiologie, AP-HP, Hôpital européen Georges Pompidou（乔治·蓬皮杜欧洲医院放射科）
Vascular adhesion of circulating tumor cells (CTCs) is a key step in cancer spreading. If inflammation is recognized to favor the formation of vascular metastatic niches, little is known about the contribution of blood rheology to CTC deposition. Herein, a microfluidic chip, covered by a confluent monolayer of endothelial cells, is used for analyzing the adhesion and rolling of colorectal (HCT 15) and breast (MDA MB 231) cancer cells under different biophysical conditions. These include the analysis of cell transport in a physiological solution and whole blood; over a healthy and a TNF alpha i…
We proposed a deconvolution optical-resolution photoacoustic microscope for high -resolution imaging of brain. The focal spot of the photoacoustic microscopy is measured to obtain the lateral PSF (point spread function) of the system. Making the measured PSF as the initial system PSF to perform Lucy- Richardson (LR) deconvolution. The image resolution of cerebral vasculature obtained by this method is higher. The full width at half maximum (FWHM) of the width of blood vessel before and after deconvolution are 7 micrometers and 3.6 micrometers, respectively, and the image definition is increase…
The clinical need for vascular grafts is associated with cardiovascular diseases frequently leading to fatal outcomes. Artificial vessels based on bioresorbable polymers can replace the damaged vascular tissue or create a bypass path for blood flow while stimulating regeneration of a blood vessel in situ. However, the problem of proper conditions for the cells to grow on the vascular graft from the adventitia while maintaining its mechanical integrity of the luminal surface remains a challenge. In this work, we propose a two-stage technology for processing electrospun vascular graft from polyc…
Measures of vascular tortuosity--how curved and twisted a vessel is--are associated with a variety of vascular diseases. Consequently, measurements of vessel tortuosity that are accurate and comparable across modality, resolution, and size are greatly needed. Yet in practice, precise and consistent measurements are problematic--mismeasurements, inability to calculate, or contradictory and inconsistent measurements occur within and across studies. Here, we present a new method of measuring vessel tortuosity that ensures improved accuracy. Our method relies on numerical integration of the Frenet…
This paper reports an aluminum nitride (AlN) multi-frequency piezoelectric micromachined ultrasound transducers (MF-PMUT) array for photoacoustic (PA) imaging, where the broadened bandwidth is beneficial to improve imaging resolution. Specifically, PMUT based on micro-electromechanical systems (MEMS) technology is suitable for PA endoscopic imaging of blood vessels and bronchi due to its miniature size. More importantly, AlN is a non-toxic material, which makes it harmless for biomedical applications. In this work, a MF-PMUT array are designed and fabricated for PAI. The device's vibration mod…
Tumor growth relies heavily on the continuous blood and nutrients supply. Theoretically, it is an ideal therapeutic way of killing tumor by only vascular embolization. However, most of the existing vascular embolic agents are still rather insufficient to fulfill the real clinical need due to the reasons like: incomplete filling of target vasculature, being easily washed away by blood or body solution, or just producing toxicity to tissues. Here from an alternative way, the body temperature liquid metal, a kind of soft and highly compliant material, was proposed for the first time as blood vess…
Significance: Quantitative measurement of blood oxygen saturation (sO$_2$) with photoacoustic (PA) imaging is one of the most sought after goals of quantitative PA imaging research due to its wide range of biomedical applications. Aim: A method for accurate and applicable real-time quantification of local sO$_2$ with PA imaging. Approach: We combine multiple illumination (MI) sensing with learned spectral decoloring (LSD); training on Monte Carlo simulations of spectrally colored absorbed energy spectra, in order to apply the trained models to real PA measurements. We validate our combined MI-…
Spreading depolarization (SD) is a self-propagating wave of near-complete neuronal depolarization that is abundant in a wide range of neurological conditions, including stroke. SD was only recently documented in humans and is now considered a therapeutic target for brain injury, but the mechanisms related to SD in complex brains are not well understood. While there are numerous approaches to interventional imaging of SD on the exposed brain surface, measuring SD deep in brain is so far only possible with low spatiotemporal resolution and poor contrast. Here, we show that photoacoustic imaging …
Multiscale modeling of blood circulation with cerebral autoregulation and network pathway analysis for hemodynamic redistribution in the vascular network with anatomical variations and stenosis conditions
Photoacoustic imaging has shown great promise for medical imaging, where optical energy absorption by blood haemoglobin is used as the contrast mechanism. A numerical method was developed for the in-silico assessment of the photoacoustic image reconstruction of the brain. Image segmentation techniques were used to prepare a digital phantom from MR images. Light transport through brain tissue was modelled using a Finite Element approach. The resulting acoustic pressure was then estimated by pulsed photoacoustics considerations. The forward acoustic wave propagation was modelled by the linearize…
Photoacoustic tomography (PAT) combines the advantages of the spectroscopic optical absorption contrast and acoustic resolution with deep penetration, and becomes an important novel biomedical imaging technology for scientific research and clinical diagnosis. In this paper, an imaging size-adjustable PAT system is proposed for clinical applications, which can adapt for different size imaging targets. Comparing with the conventional PAT system setup which with a fixed radius ring shape ultrasound transducer (UT) array, the proposed system, which is based on sectorial ultrasound transducer array…
Fully three-dimensional sound speed-corrected multi-wavelength photoacoustic breast tomography
University of Twente（特温特大学）；Centrum Wiskunde & Informatica（数学与计算机科学中心）；University College London（伦敦大学学院）；Medisch Spectrum Twente Hospital（特温特医学频谱医院）；P.A. Imaging R&D B.V.；Brno University of Technology（布尔诺理工大学）；Imasonic SAS；Ekspla UAB；Leiden University Medical Center（莱顿大学医学中心）；Center for Physical Science and Technology（物理科学与技术中心）；Ziekenhuisgroep Twente（特温特医院集团）
Photoacoustic (PA) endoscopy has shown significant potential for clinical diagnosis and surgical guidance. Multimode fibres (MMFs) are becoming increasing attractive for the development of miniature endoscopy probes owing to ultrathin size, low cost and diffraction-limited spatial resolution enabled by wavefront shaping. However, current MMF-based PA endomicroscopy probes are either limited by a bulky ultrasound detector or a low imaging speed which hindered their usability. In this work, we report the development of a highly miniaturised and high-speed PA endomicroscopy probe that is integrat…
Perturbations to the homeostatic distribution of mechanical forces exerted by blood on the endothelial layer have been correlated with vascular pathologies including intracranial aneurysms and atherosclerosis. Recent computational work suggests that in order to correctly characterise such forces, the shear-thinning properties of blood must be taken into account. To the best of our knowledge, these findings have never been compared against experimentally observed pathological thresholds. In the current work, we apply the three-band diagram (TBD) analysis due to Gizzi et al. to assess the impact…
German Cancer Research Center (DKFZ)（德国癌症研究中心）；Heidelberg University（海德堡大学）
Real-time monitoring of functional tissue parameters, such as local blood oxygenation, based on optical imaging could provide groundbreaking advances in the diagnosis and interventional therapy of various diseases. While photoacoustic (PA) imaging is a novel modality with great potential to measure optical absorption deep inside tissue, quantification of the measurements remains a major challenge. In this paper, we introduce the first machine learning based approach to quantitative PA imaging (qPAI), which relies on learning the fluence in a voxel to deduce the corresponding optical absorption…
Existing methods to reconstruct vascular structures from a computed tomography (CT) angiogram rely on injection of intravenous contrast to enhance the radio-density within the vessel lumen. However, pathological changes can be present in the blood lumen, vessel wall or a combination of both that prevent accurate reconstruction. In the example of aortic aneurysmal disease, a blood clot or thrombus adherent to the aortic wall within the expanding aneurysmal sac is present in 70-80% of cases. These deformations prevent the automatic extraction of vital clinically relevant information by current m…
German Cancer Research Center（德国癌症研究中心）；Heidelberg University（海德堡大学）；University of Bern（伯尔尼大学）
Multispectral photoacoustic imaging (PAI) is an emerging imaging modality which enables the recovery of functional tissue parameters such as blood oxygenation. However, the underlying inverse problems are potentially ill-posed, meaning that radically different tissue properties may - in theory - yield comparable measurements. In this work, we present a new approach for handling this specific type of uncertainty by leveraging the concept of conditional invertible neural networks (cINNs). Specifically, we propose going beyond commonly used point estimates for tissue oxygenation and converting si…
Acoustic-resolution photoacoustic microscopy (AR-PAM) is a promising tool for microvascular imaging. In the focal region, resolution of AR-PAM is determined by the ultrasound transducer and ultimately limited by acoustic diffraction. In the out-of-focus region, resolution deteriorates with increasing distance from the focal plane, which restricts depth of focus (DOF). Besides, a trade-off exists between resolution and DOF. Previously, synthetic aperture focusing technique (SAFT) and/or deconvolution methods have been demonstrated to enhance AR-PAM images. However, they suffer from issues in lo…
In vivo real-time epifluorescence imaging of mouse hindlimb vasculatures in the second near-infrared region (NIR-II, 1.1~1.4 microns) is performed using single-walled carbon nanotubes (SWNTs) as fluorophores. Both high spatial resolution (~30 microns) and temporal resolution (<200 ms/frame) for small vessel imaging are achieved 1-3 mm deep in the tissue owing to the beneficial NIR-II optical window that affords deep anatomical penetration and low scattering. This spatial resolution is unattainable by traditional NIR imaging (NIR-I, 0.75~0.9 microns) or microscopic computed tomography (micro-CT…
Photoacoustic (PA) imaging is an emerging hybrid imaging modality that combines rich optical spectroscopic contrast and high ultrasonic resolution and thus holds tremendous promise for a wide range of pre-clinical and clinical applications. Compact and affordable light sources such as light-emitting diodes (LEDs) and laser diodes (LDs) are promising alternatives to bulky and expensive solid-state laser systems that are commonly used as PA light sources. These could accelerate the clinical translation of PA technology. However, PA signals generated with these light sources are readily degraded …
In many clinical conditions, such as head trauma, stroke, and low cardiac output states, the brain is at risk for hypoxic-ischemic injury. The metabolic rate and oxygen consumption of the brain are reflected in internal jugular venous oxygen saturation (sijvO2). The current gold standard for monitoring brain oxygenation is invasive; it requires jugular vein catheterization under fluoroscopic guidance and therefore is rarely used. Photoacoustic (PA) measurement, on the other hand, can estimate the oxygen consumption of the brain non-invasively in real time. Such a convenient method can potentia…
Focused ultrasound stimulated microbubbles have been shown to be capable of inducing blood flow shutdown and necrosis in a range of tissue types in an approach termed antivascular ultrasound or mechanical ablation. In oncology, this approach has demonstrated tumor growth inhibition, and profound synergistic antitumor effects when combined with traditional platforms of chemo, radiation and immune therapies. However, the exposure schemes employed have been broad and underlying mechanisms remain unclear with fundamental questions about exposures, vessel types and sizes involved, and the nature of…
Cardiovascular networks span the body by branching across many generations of vessels. The resulting structure delivers blood over long distances to supply all cells with oxygen via the relatively short-range process of diffusion at the capillary level. The structural features of the network that accomplish this density and ubiquity of capillaries are often called space-filling. There are multiple strategies to fill a space, but some strategies do not lead to biologically adaptive structures by requiring too much construction material or space, delivering resources too slowly, or using too muc…
Application of a Virtual Imaging Framework for Investigating a Deep Learning-Based Reconstruction Method for 3D Quantitative Photoacoustic Computed Tomography
organization= Department of Electrical \& Computer Engineering, University of Illinois Urbana-Champaign , postcode= 61801 , state= IL , country= USA；organization= Department of Bioengineering, University of Illinois Urbana-Champaign , postcode= 61801 , state= IL , country= USA；organization= Oden Institute for Computational Engineering；Sciences, The University of Texas at Austin , postcode= 78712 , state= TX , country= USA；organization= Department of Biomedical Engineering, The University of Texas at Austin , postcode= 78712 , state= TX , country= USA
