This work presents hybrid photoacoustic and ultrasound tomography, which enables three-dimensional panoramic imaging of the human body’s morphological and angiographic information to provide dual-contrast images of representative parts of human body (i.e., head, breast, and hand) with a single system. Through in vivo human application, we present our hybrid tomography system as a powerful tool for high-speed, three-dimensional, dual-contrast imaging of the human body with potential for rapid clinical translation.
Combining functional optical contrast with high spatiotemporal resolution, photoacoustic computed tomography (PACT) benefits mainstream cardiac imaging modalities for preclinical research. However, PACT has not revealed detailed vasculature or hemodynamics of the whole heart without surgical tissue penetration. Here, we present non-invasive imaging of rat hearts using the recently developed three-dimensional PACT (3D-PACT) platform. 3D-PACT utilizes optimized illumination and detection schemes to reduce the effects of optical attenuation and acoustic distortion through the chest wall, thus visualizing cardiac anatomy and intracardiac hemodynamics within a 10-second scan. We then applied 3D-PACT to investigate different structural and functional variations in healthy, hypertensive, and obese rat hearts. 3D-PACT provides high imaging speed and nonionizing penetration to capture the whole heart for diagnosing animal models, holding promises for clinical translation to human neonatal cardiac imaging without sedation or ionizing radiation.
As the most prevalent hepatic disorder worldwide, non-alcoholic fatty liver disease strongly correlates to obesity and encompasses a broad spectrum from steatosis to carcinoma. Complementary to established diagnostic modalities, photoacoustic tomography (PAT) can provide high-speed images with endogenous optical contrast. However, none of the PAT systems has investigated fatty liver non-invasively with detailed angiograms. With the newly developed noninvasive PAT (termed 3D-PAT) system, we study the livers of multiple rats in vivo. The system provides isotropically high spatial resolution in 3D space, presenting clear anatomical and dynamical details of the rat livers. Moreover, we propose several PAT image features to quantify the difference between the livers of lean and obese rats. Statistical differences between the two groups have been observed, demonstrating the capabilities of 3D-PAT to provide hematogenous information for fatty liver diagnosis. The preclinical hepatic research using 3D-PAT warrants clinical translation towards human pediatric liver imaging.
Photoacoustic computed tomography (PACT) has been extensively explored in animal brains but never in the human brain due to its limited field of view (FOV), imaging speed, penetration depth, and sensitivity. Here, we present the first application of PACT in functional human brain imaging. Motor and language functional tasks were employed and performed by post-hemicraniectomy patients. The brain activities were recorded at a 10-cm–diameter FOV, 350-μm/2-s spatiotemporal resolution, and ~2-cm penetration depth using a newly developed massively parallel three-dimensional PACT system. Quantitative validation of the PACT results against 7 Tesla MRI revealed comparable angiographic structures and functional activation in the same FOV. The obtained results represent a critical step toward broader-scope human brain imaging applications using PACT technology.
We introduce a three-dimensional photoacoustic computed tomography (3D-PACT) system with unparalleled imaging depth, clarity, and speed, and demonstrate that the imaged structural and functional optical contrast provide a unique tool for preclinical research and an appealing prototype for clinical translation. 3D-PACT allows for multipurpose imaging of biological tissues ranging from the rodent brain to the human breast. In the rat brain, we visualized whole brain vasculatures, oxygenation dynamics, intrinsic functional connectivity, and electrical-stimulation-induced hemodynamics. In the human breast, an in vivo imaging depth of 4 cm has been achieved by scanning the breast within a single breath hold of 10 seconds. 3D-PACT holds a high reliability to reproducibly generate detailed images with a contrast similar to that provided by contrast enhanced magnetic resonance imaging, yet with higher spatiotemporal resolution and without using exogenous contrast agents.
At present, there is no reliable non-invasive imaging modality accepted as the routine method to assess response to neoadjuvant chemotherapy (NAC). Using photoacoustic computed tomography (PACT), we imaged breast cancer patients at three time points: before, during, and after NAC. We measured the tumor size, blood vascular density, and irregularity in the distribution and morphology of the blood vessels on PACT. We used these measurements to accurately identify response to NAC as confirmed by the histopathological diagnosis. We demonstrate PACT’s near-term potential as a diagnostic tool for assessing breast cancer response to systemic treatment by non-invasively measuring the changes in cancer-associated angiogenesis.
Full-ring ultrasonic transducer array is widely used in photoacoustic computed tomography (PACT) due to its high inplane resolution and full-view fidelity. Image in PACT is often contaminated by spatial aliasing, which has not been studied in detail for full-ring geometry. In this research, using spatiotemporal analysis, we clarified the sources of spatial aliasing. Based this clarification, we demonstrated that the combination of spatial interpolation and temporal filtering can effectively mitigate artifacts caused by aliasing in image reconstruction and spatial sampling. We validated our theory using numerical simulations and in vivo experiments.
Diffuse optical tomography has demonstrated significant potential for clinical utility in the diagnosis and prognosis of breast cancer, and its use in combination with other structural imaging modalities improves lesion localization and the quantification of functional tissue properties. Here, we introduce a hybrid diffuse optical imaging system that operates concurrently with magnetic resonance imaging (MRI) in the imaging suite, utilizing commercially available MR surface coils. The instrument acquires both continuous-wave and time-domain diffuse optical data in the parallel-plate geometry, permitting both absolute assignment of tissue optical properties and three-dimensional tomography; moreover, the instrument is designed to incorporate diffuse correlation spectroscopic measurements for probing tissue blood flow. The instrument is described in detail here. Image reconstructions of a tissue phantom are presented as an initial indicator of the system’s ability to accurately reconstruct optical properties and the concrete benefits of the spatial constraints provided by concurrent MRI. Last, we briefly discuss how various data combinations that the instrument could facilitate, including tissue perfusion, can enable more comprehensive assessment of lesion physiology.
KEYWORDS: Breast, Photoacoustic tomography, In vivo imaging, Breast cancer, Angiography, Temporal resolution, 3D image reconstruction, Tumors, Elastography, Computing systems
We have developed a single-breath-hold photoacoustic computed tomography (SBH-PACT) system to detect tumors and reveal detailed angiographic information about human breasts. SBH-PACT provides high spatial and temporal resolutions with a deep in vivo penetration depth of over 4 cm. A volumetric breast image can be acquired by scanning the breast within a single breath hold (~15 sec). We imaged a healthy female volunteer and seven breast cancer patients. SBH-PACT clearly identified all tumors by revealing higher blood vessel densities and lower compliance associated with the tumors
The brain has been likened to a great stretch of unknown territory consisting of a number of unexplored continents. Small animal brain imaging plays an important role charting that territory. By using 1064 nm illumination from the side, we imaged the full coronal depth of rat brains in vivo. The experiment was performed using a real-time full-ring-array photoacoustic computed tomography (PACT) imaging system, which achieved an imaging depth of 11 mm and a 100 μm radial resolution.
Because of the fast imaging speed of the full-ring-array PACT system, no animal motion artifact was induced. The frame rate of the system was limited by the laser repetition rate (50 Hz). In addition to anatomical imaging of the blood vessels in the brain, we continuously monitored correlations between the two brain hemispheres in one of the coronal planes. The resting states in the coronal plane were measured before and after stroke ligation surgery at a neck artery.
Imaging of small animals, especially rodents provides physiological, pathological, and phenotypical insights into the most relevant milieu—an intact, living system. Currently, non-optical small-animal wholebody imaging approaches lack either spatiotemporal resolution or functional contrasts, whereas pure optical imaging suffers from either shallow penetration (up to ~1 mm) or a poor resolution-to-depth ratio (~1/3). Here, we present a standalone system that breaks all the above limitations. Our system features high spatiotemporal resolution and deep penetration, and can capture anatomical and functional contrasts. We imaged mouse wholebody dynamics in real time with clear sub-organ anatomical and functional details.
Optical-resolution photoacoustic microscopy (OR-PAM) offers label-free in vivo imaging with high spatial resolution by acoustically detecting optical absorption contrasts via the photoacoustic effect. We developed a compact handheld OR-PAM probe for fast photoacoustic imaging. Different from benchtop microscopes, the handheld probe provides flexibility in imaging various anatomical sites. Resembling a cup in size, the probe uses a two-axis water-immersible microelectromechanical system mirror to scan both the illuminating optical beam and resultant acoustic beam. The system performance was tested in vivo by imaging the capillary bed in a mouse ear and both the capillary bed and a mole on a human volunteer.
While lasers have been commonly used as illumination sources in photoacoustic (PA) imaging, their high purchase and maintenance costs, as well as their bulkiness, have hindered the rapid clinical dissemination of PA imaging. With this in mind, we explore an alternative illumination source for PA tomography—a xenon flash lamp with high pulse energy and a microsecond pulse width. We demonstrate that, by using a single xenon flash lamp, we can image both a black latex cord placed in chicken breast tissue at a depth of up to 3.5 cm ex vivo and an entire mouse body in vivo. Our findings indicate that the xenon flash lamp, producing optical illumination that is safe for humans, can be potentially applied to human tissue imaging.
Microwave-based thermoacoustic tomography (TAT), based on the measurement of ultrasonic waves induced by microwave pulses, can reveal tissue dielectric properties that may be closely related to the physiological and pathological status of the tissues. Using microwaves as the excitation source improved imaging depth because of their deep penetration into biological tissues.
We demonstrate, for the first time, in vivo microwave-based thermoacoustic imaging in rats. The transducer is rotated around the rat in a full circle, providing a full two-dimensional view. Instead of a flat ultrasonic transducer, we used a virtual line detector based on a cylindrically focused transducer. A 3 GHz microwave source with 0.6 µs pulse width and an electromagnetically shielded transducer with 2.25 MHz central frequency provided clear cross-sectional images of the rat’s body. The high imaging contrast, based on the tissue’s rate of absorption, and the ultrasonically defined spatial resolution combine to reveal the spine, kidney, muscle, and other deeply seated anatomical features in the rat’s abdominal cavity. This non-invasive and non-ionizing imaging modality achieved an imaging depth beyond 6 cm in the rat’s tissue.
Cancer diagnosis based on information about tissue properties from microwave band TAT can potentially be more accurate than has previously been achievable.
Myoglobin is an essential oxygen-binding hemoprotein in skeletal and cardiac muscles that buffers intracellular oxygen (O2) concentration in response to hypoxia or elevated muscle activities. We present a method that uses photoacoustic computed tomography to measure the distribution of myoglobin in tissue and the oxygen saturation of myoglobin (sO2-Mb). From photoacoustic measurements of mice in different oxygenation states, we performed calibration-free quantification of the sO2-Mb change in the backbone muscle in vivo.
We demonstrate, by means of internal light delivery, photoacoustic imaging of the deep brain of rats in vivo. With fiber illumination via the oral cavity, we delivered light directly into the bottom of the brain, much more than can be delivered by external illumination. The study was performed using a photoacoustic computed tomography (PACT) system equipped with a 512-element full-ring transducer array, providing a full two-dimensional view aperture. Using internal illumination, the PACT system provided clear cross sectional photoacoustic images from the palate to the middle brain of live rats, revealing deep brain structures such as the hypothalamus, brain stem, and cerebral medulla.
Using internal illumination with an optical fiber in the oral cavity, we demonstrate, for the first time, photoacoustic computed tomography (PACT) of the deep brain of rats in vivo. The experiment was performed on a full-ring-array PACT system, with the capability of providing high-speed cross-sectional imaging of the brain. Compared with external illumination through the cranial skull, internal illumination delivers more light to the base of the brain. Consequently, in vivo photoacoustic images clearly reveal deep brain structures such as the hypothalamus, brain stem, and cerebral medulla.
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