Patent Application
20240241239
Certain aspects generally pertain to photoacoustic imaging and, more specifically, to 3D photoacoustic imaging systems, devices, and methods.
Vascular diseases, such as atherosclerosis, thrombosis, aneurysms, and peripheral vascular diseases, pose serious health risks such as heart attack, stroke, organ failure, and complications in the lower extremities. Imaging of hemodynamics, especially monitoring the blood supply to lower extremities is a valuable tool in early detection and intervention in these diseases. Moreover, measuring factors like blood flow velocity can also evaluate an individual's risk of developing vascular diseases, aiding preventive measures and facilitating personalized treatment plans.
Certain embodiments pertain to an ergodic relay comprising an acoustic delay line (e.g., an optical rod or acoustic waveguide) configured to temporally separate one or more initial photoacoustic signals and one or more reflected photoacoustic signals. The ergodic relay further comprises an acoustic cavity (e.g., glass prism) coupled to the acoustic delay line and an integrated single-element ultrasonic transducer fabricated onto a surface of the acoustic cavity.
Certain embodiments pertain to a photoacoustic computed tomography system comprising a housing and an ergodic relay at least partially located within the housing. The ergodic relay comprising an acoustic delay line configured to temporally separate one or more initial photoacoustic signals and one or more reflected photoacoustic signals, an acoustic cavity coupled to the acoustic delay line, and an integrated single-element ultrasonic transducer fabricated onto a surface of the acoustic cavity. The photoacoustic computed tomography system further comprising one or more optical fibers coupled to the acoustic cavity, wherein the one or more optical fibers are configured to receive an illumination beam. In one case, the photoacoustic computed tomography system is a handheld device.
Certain embodiments pertain to photoacoustic computed tomography imaging methods. In some cases, a method receives encoded photoacoustic data based on photoacoustic signals detected by an integrated single-element ultrasonic transducer fabricated directly onto a surface of a prism of an ergodic relay. The ergodic relay includes an optical rod fused to the prism. The optical rod is configured to temporally separate the photoacoustic signals and the reflected photoacoustic signals. The method also reconstructs one or more 3D photoacoustic images from the photoacoustic data using a plurality of calibrated virtual transducers.
These and other features and embodiments will be described in more detail with reference to the drawings.
Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.
The figures and components therein may not be drawn to scale.
Different aspects are described below with reference to the accompanying drawings. The features illustrated in the drawings may not be to scale. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the presented embodiments. The disclosed embodiments may be practiced without one or more of these specific details. In other instances, well-known operations have not been described in detail to avoid unnecessarily obscuring the disclosed embodiments. While the disclosed embodiments will be described in conjunction with the specific embodiments, it will be understood that it is not intended to limit the disclosed embodiments.
3D imaging methods can be generally classified into two categories. The first category includes, e.g., photoacoustic microscopy, confocal microscopy, two-photon microscopy, and radar, and requires the sequentially scanning of the probing beam across the object. This first category of 3D imaging methods uses single- or few-element detectors but suffers a low imaging speed due to a required sequential scanning scheme. The second category includes, e.g., photoacoustic computed tomography, light-sheet microscopy, ultrasonography, and sonar, and can capture a 3D image of an object using one or a few exposures of the probing beam. However, the methods of this second category usually require multiple detectors or multi-element detector arrays, which are often complex, expensive, bulky, and not particularly suitable for portable or wearable applications. These problems may thus limit the translation of these 3D imaging methods that can be used for biomedical research, such as photoacoustic computed tomography, to clinical settings.
Certain embodiments pertain to photoacoustic computed tomography through an ergodic relay (PACTER) methods, systems, and devices. Certain PACTER techniques can acquire a 3D image of an object with a single exposure using a single-element ultrasonic detector that can function as multiple virtual detectors (e.g., thousands of virtual detectors). In some cases, the single-element element detector is an integrated detector fabricated directly onto a surface of the ergodic relay. Distinct from other 3D imaging methods, PACTER techniques can provide a 3D image of an object with a single exposure of a probing beam, using a single-element ultrasonic detector. This single-shot imaging capability may provide faster imaging speeds as compared to other methods that require sequential scanning, such as photoacoustic microscopy, confocal microscopy, two-photon microscopy, and radar. In one aspect, a PACTER system can provide up to a 1 kHz volumetric imaging speed. In another aspect, a PACTER system using a laser with a high repetition rate such as a repetition rate of 1 MHz can have a volumetric imaging speed of 1 MHz. The single element ultrasonic detector may also significantly reduce system complexity, cost, and form factor as compared with other 3D imaging methods that use multiple(-element) detectors such as light-sheet microscopy, ultrasonography, and sonar. Also, certain PACTER techniques do not require re-calibration for different objects.
Certain embodiments are directed to an ergodic relay (ER) with an acoustic cavity such as a glass prism, an acoustic delay line such as an optical rod (e.g., glass rod) or an acoustic waveguide, and a single element transducer element. In some cases, the single-element transducer element is an integrated component of the ergodic relay fabricated directly onto a surface of the acoustic cavity. In one embodiment, the ergodic relay includes a glass prism fused to a silica optical rod and an integrated ultrasonic transducer based on a lead magnesium niobate-lead titanate (PMN-PT) single crystal. In other embodiments, alternative materials may be used to fabricate the ergodic relay and/or the transducer, which may provide improved 3D single-shot imaging performance. For example, the acoustic cavity can be fabricated with other transparent materials including, but not limited to, polymethyl methacrylate, epoxy, and polycarbonate. As another example, the ultrasonic transducer can be implemented with other materials, including, but not limited to, lead zirconium titanate, lithium niobate, and polyvinylidene fluoride.
Alternatively, or additionally, the shapes and dimensions of the ergodic relay in the PACTER devices and systems can be variated. In one example, the ergodic relay may include a glass rod that functions as an acoustic delay line to temporally separate the initial photoacoustic signals and the reflected photoacoustic signals. In alternative embodiments, the glass rod may be replaced with an acoustic waveguide with different designs. In another example, the ergodic relay may include a prism as an acoustic cavity for scrambling or encoding acoustic waves. In alternative embodiments, the prism be replaced with any type of acoustic cavity that can scramble the acoustic waves such as, e.g., glass/quartz plates (e.g., slides, coverslips), silicon wafers, etc. Alternatively, the ergodic relay can be a whole piece of material that functioning as both the acoustic delay line and the acoustic cavity.
In various embodiments, the PACTER imaging procedure uses photoacoustic signals from a single-element transducer element. Although many embodiments of PACTER systems include only a single transducer element, it would be understood that one or more additional transducer elements may be included in other implementations for, e.g., redundancy.
As provided in Section IV, PACTER techniques have been demonstrated to image vital signs in small animals and 3D hemodynamics in humans. Possible applications of PACTER techniques include, but are not limited to, biometrics, home-care monitoring (home care of diabetic-foot ulcer or carotid-artery disease), point-of-care testing (point-of-care screening for hypertension), and noninvasive hemodynamic monitoring (simultaneous oximetry of both arterial and venous blood) in intensive care units.
Other possible applications of the single-detector technique in PACTER that implements a single-element detector to function as potentially thousands of virtual detectors are other imaging technologies including, but not limited to, medical ultrasonography, underwater sonar, and airborne radar.
There are several techniques available to image hemodynamics in the human body, each with its own strengths and limitations. Magnetic resonance imaging (MRI), computed tomography (CT) angiography, and positron emission tomography (PET) are all capable of producing high-resolution images of the vascular system and blood flow dynamics, but they require the use of ionizing radiation and the injection of contrast agents, which can have adverse health effects. Moreover, relying on strong ionizing sources and numerous detector elements, these techniques are bulky and expensive, making them inaccessible to mobile clinics or small healthcare facilities. Optical imaging techniques, such as fluorescence imaging and optical coherence tomography (OCT), offer noninvasive visualization of hemodynamics, but their penetration depths are constrained by the optical diffusion limit (˜1-2 mm) and do not have sufficient specificity to hemoglobin. However, even with recent improvements in minimizing ultrasound probes, state-of-the-art ultrasound imaging techniques still require burdensome and costly data acquisition systems due to hundreds to thousands of detector elements.
Photoacoustic tomography (PAT), also referred to as optoacoustic tomography, offers a promising solution to the limitations faced by other imaging techniques for hemodynamic imaging. Unlike other techniques, PAT utilizes the photoacoustic (PA) effect to absorb the energy of incident photons by optical absorbers, such as hemoglobin, in biological tissue and re-emit them as ultrasonic waves (PA waves) to generate optical contrast tomographic images. As a result, PAT does not rely on ionizing radiation or contrast agents. Moreover, due to the weak scattering of ultrasound in biological tissue, PAT provides a depth-to-resolution ratio of approximately 200, enabling high spatial resolution at depths up to several centimeters. Two primary forms of PAT are photoacoustic microscopy (PAM) and photoacoustic computed tomography (PACT). PAM requires sequential scanning of the probing beam and PACT captures a 3D image using one or a few pulses of the probing beam. PAM utilizes a single-element detector, which requires a simple data acquisition system but suffers from low imaging speed. In contrast, while PACT can offer higher imaging speeds of up to kilohertz, PACT generally necessitates a number of detection elements and corresponding data acquisition systems. This results in systems that are complex, costly, and bulky.
Some PACT systems have a reduced number of detector elements. For example, one PACT approach utilizes the principles of compressive sensing and single-pixel imaging. This approach uses acoustic scatterers to achieve PA or ultrasound tomography with just a single detector element. However, these PACT techniques are time-consuming, as they require a sequence of measurements with different mask configurations, limiting their speed. To try to address this issue, researchers have developed methods that take advantage of the spatiotemporal encoding of an ergodic relay (ER) or a chaotic cavity. These techniques can produce single-shot images while using fewer detector elements. However, these PACT systems only perform 2D imaging and require recalibration for different objects, which can be time-consuming. Additionally, they may not be suitable for long-term imaging in unstable environments due to their sensitivity to boundary conditions. As discussed above, other techniques for imaging hemodynamics use ionizing radiation or contrast agents, or are limited to imaging depths within approximately 1 millimeter, by complex and expensive data-acquisition systems, or by low imaging speeds, complexity, or cost.
Certain embodiments described herein pertain to PACTER techniques that implement photoacoustic tomography using a single laser pulse and a single transducer element that can function as thousands of virtual detectors, which allows for the volumetric capture of fast hemodynamic changes in, for example, human feet. Certain embodiments described herein pertain to PACTER techniques that can have ultrafast volumetric photoacoustic imaging of hemodynamics in the human body where high imaging rate (e.g., up to 1 MHz when using high repetition rate laser of 1 MHz can be achieved by using a single laser pulse and a single element functioning a plurality of detectors (e.g., 6,400 virtual detectors). PACTER techniques, which do not require re-calibration for different objects or during long-term operation, allows for longitudinal volumetric imaging of hemodynamics in vasculature a few-millimeters below the skin's surface as discussed in Section IV where in healthy humans, hemodynamic changes in vessels in their feet in response to vascular occlusion have been captured. Single-shot volumetric photoacoustic imaging using a single-element detector may facilitate the early detection and monitoring of peripheral vascular diseases and may find advantageous uses in biometrics and in point-of-care testing.
Certain embodiments pertain to PACTER techniques that can address challenges faced by previous 3D imaging techniques. PACTER techniques provide a highly accessible and efficient solution, paving the way for noninvasive, label-free, and ultrafast volumetric imaging of hemodynamics at depth in humans. With PACTER techniques, a single-element detector encodes information equivalent to that of a large number (e.g., 6400 or larger) of virtual ones, enabling the reconstruction of a tomographic image of vasculature in 3D with just a single laser pulse. PACTER techniques can achieve longitudinal volumetric imaging at a high rate (e.g., 1 kHz to 1 MHz), making it possible to capture fast hemodynamics in the human body in real-time.
Section IV provides demonstrations of PACTER systems showing capability in monitoring vital signs in small animals and visualizing human hemodynamics in response to cuffing, capturing the variability in blood flow speeds. In addition, these demonstrations show that PACTER systems can capture the hemodynamic changes in human foot vessels during vascular occlusion, demonstrating potential as a powerful tool for assessing vascular function in the lower extremities. Enabled by the integrated ultrasonic transducer and the object-independent universal calibration, PACTER systems only need to be calibrated once and are suitable for long-term imaging in unstable environments. PACTER's single-element detector design makes it convenient, affordable, and compact, thus translatable to clinical applications such as home-care monitoring, biometrics, point-of-care testing, and noninvasive hemodynamic monitoring in intensive care units. PACTER's capacity to capture dynamic changes in vascular occlusion presents clinical potential for early detection, enhanced assessment, and more personalized treatment of peripheral vascular diseases. The single-element detector concept in PACTER techniques can also be generalized to other imaging technologies, such as ultrasonography.
Returning to
The illustrated example is shown during an image acquisition procedure during which an optional (denoted by dashed line) object 20 is present. During this procedure, object 20 is acoustically coupled to acoustic delay line 154 with, for example, water, acoustic gel, etc. The optical system 120 includes a homogenizer 121 configured to homogenize the light pulse from light source(s) 110 and one or more optical elements configured to focus and propagate the homogenized light to acoustic cavity 152. Acoustic cavity 152 is configured to scramble or encode the acoustic waves generated by the photoacoustic effect at the object 20 and acoustic delay line 154 temporally separates the initial and reflected photoacoustic signals.
PACTER system 100 also includes an optional (denoted by dashed line) one or more amplifiers 170 (e.g., ZKL-1R5+ amplifier sold by Mini-Circuits) for boosting one or more photoacoustic signals communicated from ultrasonic transducer 160 and a data acquisition system (DAQ) 174 for digitizing and/or recording the photoacoustic signal(s). Amplifier(s) 170 is in electrical communication with ultrasonic transducer 160 to receive one or more photoacoustic signals and DAQ 174 is in electrical communication with optional amplifier(s) 170 to receive one or more boosted photoacoustic signals.
PACTER system 100 also includes a computing device 180 in electronic communication with DAQ 174 to send control signals and to receive photoacoustic data. Computing device 180 includes one or more processors or other circuitry 184 to perform operations such as image reconstruction, an optional (denoted by dashed line) display 182 in electrical communication with the processor(s) or other circuitry 184, and a computer readable media (CRM) 186 in electronic communication with the processor(s) or other circuitry 184. Computing device 180 is also in electronic communication with light source(s) 110 to send control signals and/or to receive trigger signals. In one aspect, to synchronize recording of photoacoustic signal by DAQ 174 with the light pulse transmission, light source(s) 110 is configured to transmit a trigger signal to computing device 180 that triggers transmission of a control signal to the DAQ 174 to record a photoacoustic signal. In another aspect, the computing device 280 or a separate I/O device sends control signals that trigger the light source(s) 210 to send pulses of light and control the DAQ 274 to simultaneously sample data from the photoacoustic signal received from the photoacoustic element. The electrical communication between system components of the PACTER system 100 may be in wired and/or wireless form.
During an imaging procedure, the object 20 is in contact with the acoustic delay line 154 of the ergodic relay 150 and an acoustic medium such as water or an ultrasound gel is applied between the object 20 and the acoustic delay line 154 to facilitate acoustic coupling. During operation, a pulse of light from the light source(s) 110 is sent through a homogenizer 121 which homogenizes the illumination beam in the imaging volume. The acoustic delay line 154 receives acoustic waves from regions in a field-of-view of object 20 illuminated by the homogenized beam. The acoustic delay line 154 temporally separates the initial photoacoustic signals and the reflected photoacoustic signals. The acoustic cavity 152 further scrambles or encodes acoustic waves received from acoustic delay line 154. The PACTER signals detected by the ultrasonic transducer 160 are amplified by the one or more amplifiers 170 and digitized by DAQ 174. The computing device 180 receives the digitized data and uses the calibrated virtual transducers (photoacoustic signals from calibration pixels of calibration field-of-view) to reconstruct a 3D image for each pulse of light. The computing device 180 may also process the reconstructed image. In some cases, a plurality of pulses of light are triggered over time and a 3D image reconstructed based on each light pulse to generate a sequence of 3D images. The sequence of 3D images can be used to determine a 4D image of the dynamics of the object such as speed of fluid flow.
The illustrated example is shown during a calibration procedure during which an optional (denoted by dashed line) calibration target 201 is present. During the calibration procedure, calibration target 201 is acoustically coupled to acoustic delay line 254 with, for example, water, acoustic gel, etc. PACTER system 200 also includes a scanning mechanism 230 such as one or more translational stages (e.g., PLS-85 translational stage by PI). The optical system 220 is configured to focus and propagate the light beam to acoustic cavity 252. The scanning mechanism 230 is coupled to one or more components of the optical system 220 to steer incident light beam across the field-of-view of the calibration target 201. Acoustic cavity 252 is configured to scramble or encode the acoustic waves generated by the photoacoustic effect at the object 20 and acoustic delay line 254 temporally separates the initial and reflected photoacoustic signals.
PACTER system 200 also includes an optional (denoted by dashed line) one or more amplifiers 270 (e.g., ZKL-1R5+ amplifier sold by Mini-Circuits) for boosting one or more photoacoustic signals communicated from ultrasonic transducer 260 and a data acquisition system (DAQ) 274 for digitizing and/or recording the photoacoustic signal(s). Amplifier(s) 270 is in electrical communication with ultrasonic transducer 260 to receive one or more photoacoustic signals and DAQ 274 is in electrical communication with optional amplifier(s) 270 to receive one or more boosted photoacoustic signals.
PACTER system 200 also includes a computing device 280 in electronic communication with DAQ 274 to send control signals and to receive photoacoustic data. Computing device 280 includes one or more processors or other circuitry 284 to perform operations such as image reconstruction, an optional (denoted by dashed line) display 282 in electrical communication with the processor(s) or other circuitry 284, and a computer readable media (CRM) 286 in electronic communication with the processor(s) or other circuitry 284. Computing device 280 is also in electronic communication with light source(s) 210 to send control signals and/or to receive trigger signals. In one aspect, to synchronize recording of photoacoustic signal by DAQ 274 with the light pulse transmission, light source(s) 210 is configured to transmit a trigger signal to computing device 280 that triggers transmission of a control signal to the DAQ 274 to record a photoacoustic signal. In another aspect, the computing device 280 or a separate I/O device sends control signals that trigger the light source(s) 210 to send pulses of light, control the scanning mechanism 230 to scan the light beam across the calibration field-of-view, and control the DAQ 274 to simultaneously sample data from the photoacoustic signal received from the photoacoustic element. The electrical communication between system components of the PACTER system 200 may be in wired and/or wireless form.
During a calibration procedure, a calibration target 201 is in contact with acoustic delay line 254 of the ergodic relay 250 and an acoustic medium such as water or an ultrasound gel is applied between calibration target 201 and acoustic delay line 254 to facilitate acoustic coupling. During operation, an illumination beam from the light source(s) 210 is steered to illuminate over time different calibration pixel locations in the calibration field-of-view. The acoustic delay line 254 receives acoustic waves from the different pixel locations. The acoustic delay line 254 temporally separates the initial photoacoustic signals and the reflected photoacoustic signals. The acoustic cavity 152 further scrambles or encodes acoustic waves received from acoustic delay line 254. The PACTER signals detected by the ultrasonic transducer 260 are amplified by the one or more amplifiers 270 and digitized by DAQ 274. The computing device 280 uses the photoacoustic signals at the calibration pixel locations as calibrated virtual transducers.
In certain embodiments, a PACTER system requires calibration only once prior to its utilization for imaging. In these cases, the PACTER system does not require calibration for different objects.
In certain embodiments, a PACTER system includes, or is in communication with, one or more light sources that can provide a pulse of light. Some examples of suitable light sources include pulsed lasers, light emitting diodes, flash lamps, stroboscopes, and pulse-modulated continuous light sources. Any wavelength that can be absorbed by the object being imaged can be used. An example of a suitable light source is a 5-ns pulsed laser beam at 532 nm (e.g., INNOSLAB IS8II-DE pulsed laser with a 1 kHz pulse repetition rate sold by EdgeWave). In implementations using a pulsed laser source, the laser repletion rate employed may be limited by the duration of the photoacoustic signals. In one example, the laser repetition rate is lower than 4 kHz. In hemodynamic implementations, a high speed pulse laser (e.g., Q-switched laser with a variable repetition rate from 0 to 3.5 MHz such as Spectra-Physics Quasar GR95) may be used to be able to rapidly capture multiple 3D images over time. In implementations using a laser source, the laser source may include an iris to adjust the beam diameter. In some cases, a PACTER system includes the one or more light sources. In other cases, the one or more light sources may be a separate component. For example, a PACTER system may include a multi-mode fiber (e.g., multi-mode fiber 2912 in
In imaging configurations, widefield homogenized light is provided to the acoustic cavity of the ergodic relay during operation. In these implementations, the optical system may include a homogenizer (e.g., homogenizer 121 in
A PACTER system includes an ergodic relay (ER) having an acoustic cavity (e.g., a silica prism) configured to scramble or encode acoustic waves and an acoustic delay line (e.g., an optical rod or an acoustic waveguide) acoustic coupled to the acoustic cavity. The acoustic delay line is configured to temporally separate the initial photoacoustic signals and the reflected photoacoustic signals. In one example, an ergodic relay includes a silica optical rod fused to a silica prism. The ergodic relay can be used as an encoder to transform photoacoustic signals from acoustic waves at different input positions into unique temporal signals. The ergodic relay not only introduces a characteristic delay between the delivery of the illumination beam and the reception of the photoacoustic signal by the ultrasonic transducer element but also stretches and scrambles the signal in time, encoding the spatial location of the photoacoustic signal's source in a complex temporal pattern.
The acoustic cavity is generally configured to scramble or encode acoustic waves, e.g., generated by the photoacoustic effect (photoacoustic waves) at the object being imaged. The acoustic cavity may be of various shapes and dimensions that can scramble acoustic waves. An example of an acoustic cavity is a prism such as a right-angle prism. Other suitable acoustic cavities include glass/quartz plates (e.g., slides, coverslips), silicon wafers, etc. An example of a suitable prism is the PS611 prism sold Thorlabs, Inc. of Newton, New Jersey with a 25 mm right-angle edge length. Other suitable prisms are the PS612 prism, the PS608 prism, the PS613 prism, etc. sold Thorlabs, Inc. of Newton, New Jersey. The acoustic cavity may be fabricated of one or more transparent materials. Some examples of suitable transparent materials include glass, polymethyl methacrylate, epoxy, and polycarbonate.
The acoustic delay line is generally configured to temporally separate the initial photoacoustic signals and the reflected photoacoustic signals. Some examples of suitable acoustic delay lines are an optical rod and an acoustic waveguide. The acoustic delay line may be made of various materials and have different dimensions. In one example, the acoustic delay line has a length between 50 mm and 300 mm. In another aspect, the acoustic delay line has a length in a range of 5 mm and 30 mm. In one example, the acoustic delay line has a circular cross section with a diameter in range between 10 mm and 50 mm. An example of a suitable optical rod is the optical rod sold by VY Optoelectronics having an 18 mm diameter, 175 mm length, top and bottom surfaces polished to 60-40 surface quality. The acoustic delay line may be fused directly to the acoustic cavity or coupled via an adhesive material (e.g., polyester resin) to the acoustic cavity. The acoustic delay line may have an object surface configured to contact an object being imaged during operation.
In certain embodiments, the ergodic relay includes one or more acoustic impedance-matching layers between the object being imaged and the other portion of the ergodic relay. For example, the one or more acoustic impedance-matching layers may be located at a surface of the ergodic delay that is designed to contact the object being imaged. An example of a suitable acoustic impedance-matching layer is a quarter-wavelength impedance-matching layer (Zmatch=√{square root over (ZobjectZER)}) where Zobject and ZER are the acoustic impedances of the object and the ergodic relay, respectively. Another example of a suitable acoustic impedance-matching layer is a cascaded impedance-matching layer. Another example of a suitable acoustic impedance-matching layer is a gradient impedance-matching layer.
In some embodiments, an ergodic relay includes a prism and an optical rod (e.g., 18 mm diameter, 175 mm length, top and bottom surfaces polished to 60-40 surface quality). The prism may be a right-angle prism such as, e.g., PS611 prism having 25 mm right-angle edge length sold by Thorlabs. In some cases, the prism and the optical rod are both made of ultraviolet (UV) fused silica, which has good optical transparency and low acoustic attenuation. In some cases, one or more edges of the prism are ground by a saw such as a diamond saw (e.g., SYJ-150 saw sold by MTI Co.) following a sawtooth pattern to obtain chaotic boundaries. The prism and the optical rod may be glued by UV-curing optical adhesive (e.g., NOA68 adhesive sold by Norland Products), following exposure under UV light for 12 hr.
In calibration implementations, a PACTER system may also include a scanning mechanism (e.g., one or more translational stages) coupled to one or more components of the optical system to be able to steer the illumination light beam to different locations along a field-of-view of the calibration target (calibration FOV). An example of a suitable translation stage is a PLS-85 translational stage by PI. Each translation stage may be controller by a motor driver such as, e.g., CW215 motor driver sold by Circuit Specialists. According to one aspect, the scanning mechanism includes a first motorized stage and a second motorized stage (e.g., first motorized stage 337 and second motorized stage 338 in
In certain embodiments, a PACTER system includes a data acquisition system (DAQ) for digitizing and/or recording photo acoustic signals. In one aspect, the DAQ is a single channel DAQ that provide one-to-one mapped association to a single element ultrasonic transducer. Although the PACTER systems of certain implementations include a DAQ (e.g., a DAQ card) for data acquisition, other implementations may include other devices such as one or more microcontrollers. An example of a suitable DAQ is ATS9350 data acquisition card sold by AlazarTech. In some cases, the DAQ may be installed on the computing device.
Optionally, a PACTER system includes one or more amplifiers (e.g., amplifier(s) 170 in
In certain embodiments, a PACTER system includes a computing device having one or more processors or other circuitry, an optional display in electrical communication with the processor(s), and a computer readable media (CRM) in electronic communication with the processor(s) or other circuitry. The computing device may include an input/output (I/O) device (e.g., multifunctional input/output (I/O)) for controlling the one or more light sources, the scanning mechanism, and/or the DAQ.
The computer readable media (CRM) may be, e.g., a non-transitory computer readable media. The computing device 180 is in electronic communication with the light source(s) to send control signals to trigger the illumination (e.g., triggering laser pulses). The computing device is in electrical communication with the one or more DAQs to receive data transmissions and/or to send control signal(s). The computing device 180 may also be in electronic communication with the one or more pre-amplifiers to send control signal(s), e.g., to adjust amplification. The electrical communication between system components of the PACTER system may be in wired and/or wireless form. One or more of the electrical communications between components of the PACTER system may be able to provide power in addition to communicate signals. The computing device may be, for example, a personal computer, an embedded computer, a single board computer (e.g., Raspberry Pi or similar), a portable computation device (e.g., tablet), a controller, or any other computation device or system of devices capable of performing the functions described herein. The computing device may also be in electronic communication with a scanning mechanism to send control signals to control the movement and/or hold positions of the one or more optical components. The processor(s) are in electrical communication with the CRM to store and/or retrieve data such as the photoacoustic signal data. The one or more processor(s) and/or other circuitry are in electrical communication with the optional display to display data. The computing device may also include a user input component for receiving data from a user. In one embodiment, a computing device includes a GPU.
The one or more processors and/or other circuitry may execute instructions stored on the CRM to perform one or more operations of PACTER methods. In certain implementations, the processor(s) and/or other circuitry execute instructions to perform one or more of: 1) reconstruction of 3D PACTER images and 2) generation of 4D image data. For example, the processor(s) and/or other circuitry and/or one or more external processors may execute instructions that communicate control signals to a scanning mechanism to scan the light beam across field-of-view of a calibration target and send control signals to the DAQ(s) to simultaneously record photoacoustic signals detected by the ultrasonic transducer element.
In one embodiment, a PACTER system includes a multifunctional input/output (I/O) device (e.g., PCIe-6321 I/O device sold by National Instruments) configured to execute instructions to (1) trigger the one or more light sources such a pulsed laser, (2) drive the scanning device (e.g., motorized stages) during calibration, and/or (3) acquire the data by the DAQ. In one example with one or more motorized stages and a pulsed laser, the PACTER signals were acquired at a sampling rate of 250 megasamples per second, and a sampling length of 65,532 data points per acquisition. In this example, due to the distance between the object and the ultrasonic transducer, a 28-μs delay was added to the data acquisition following the laser trigger. During calibration, to improve the signal-to-noise ratio (SNR) of the signal, the acquisition was repeated 500 times at each calibrated virtual transducer and the averaged signal used for PACTER reconstruction. To prevent motor backlash, the data was acquired only when the motor was moving forward; the acquisition stopped when the motor returned. During imaging, to improve the temporal resolution of the system, no signal averaging was used, and the motor scanning was disabled.
In some implementations, the PACTER system includes one or more communication interfaces (e.g., a universal serial bus (USB) interface). Communication interfaces can be used, for example, to connect various peripherals and input/output (I/O) devices such as a wired keyboard or mouse or to connect a dongle for use in wirelessly connecting various wireless-enabled peripherals. Such additional interfaces also can include serial interfaces such as, for example, an interface to connect to a ribbon cable. It should also be appreciated that the various system components can be electrically coupled to communicate with various components over one or more of a variety of suitable interfaces and cables such as, for example, USB interfaces and cables, ribbon cables, Ethernet cables, among other suitable interfaces and cables.
In certain embodiments, the PACTER system may include a temperature stabilizing system (e.g., temperature stabilizing box 3990 in
In one embodiment, the temperature stabilizing system includes a temperature stabilizing box (e.g., temperature stabilizing device 3090 in
The illustrated example is shown at an instant during a calibration procedure during which a calibration target 301, which is generally a uniform optical absorber, is placed in acoustic communication (e.g., via acoustic gel or water) with a distal end of silica right-angle silica prism 352. PACTER system 300 also has a scanning mechanism that includes a first motorized stage 337 (x-direction) (e.g., PLS-85 translational stage by PI) and a second motorized stage 338 (z-direction) (e.g., PLS-85 translational stage by PI). The third mirror 330, fourth mirror 332, and third lens 334 are mounted to first motorized stage 337 (x-direction) and a second motorized stage 338 (z-direction) to steer the focused laser beam across a calibration field-of-view (FOV) in an x-y plane to a plurality of scanning locations at calibration target 301 during a calibration procedure. The illustration shows the optical path of the light beam through components of PACTER system 300.
An acoustic medium such as water or an ultrasound gel (e.g., Aquasonic 100 ultrasound gel sold by ParkerLabs) may be applied between the calibration target 301 and a surface of a distal end of ergodic relay 350 to facilitate acoustic coupling. In PACTER system 300, the power of the laser beam from pulsed laser 310 is controlled by the half-wave plate 322 and polarizing beam splitter 323. During operation, the beam reflected by the polarizing beam splitter 323 is sent to beam trap 324. The beam transmitted through the polarizing beam splitter 323 is expanded by a beam expander consisting of first lens 326 and second lens 327. During the calibration procedure, the expanded beam is steered across the calibration FOV by the third mirror 330, fourth mirror 332, and third lens 334 mounted to the first motorized stage 337 (x-direction) and a second motorized stage 338 (z-direction). An iris (not shown) is used to adjust the beam diameter (e.g., to be about 2 mm) and the beam is sent through lens 334 and focused at, or near, a distal end of the ergodic relay 350. The PACTER signals detected by the ultrasonic transducer 360 were amplified by the one or more low-noise amplifiers 370, filtered by the low-pass filter (not shown), and digitized by DAQ (e.g., ATS9350 data acquisition card sold by AlazarTech). The DAQ 374 may be installed on the computing device 350. In one embodiment, the PACTER system 300 includes a multifunctional input/output (I/O) device (e.g., PCIe-6321 I/O device sold by National Instruments) to control the one or more light sources 310, the first motorized stage 337, the second motorized stage 338, and/or the DAQ 374.
The calibration target 301 is typically a uniform optical absorber such as lysed bovine blood. In one implementation, the calibration target 301 includes a container with a window at its bottom sealed with an optically and ultrasonically transparent disposable polyethylene membrane. The container is filled with bovine blood, which is used as a uniform optical absorber for calibration. Lysed bovine blood may be useful as a calibration target particularly where primary imaging objects are blood vessels. Using first motorized stage 337 and second motorized stage 338, the positions of the pair of mirrors 332 and 334 is controlled to steer the focused laser beam across the field-of-view (FOV) in an x-y plane and the PACTER signals are recorded by DAQ 374 at each of a plurality of scanning positions.
After calibration, the calibration target can be removed from the PACTER system to ready the system for imaging once a homogenizer such as a fly's eye homogenizer is introduced. Section V(A) describes an example of a fly's eye homogenizer. The homogenizer converts the incident laser beam into a widefield, homogenized illumination pattern. In some cases, the homogenized illumination pattern has the same shape and width as that of the calibration field-of-view (FOV) as discussed in Section V(A). In other cases, the illumination pattern is larger or smaller than the calibration FOV.
During the imaging procedure, to acquire imaging data, the object 402 is placed directly in contact the optical rod 454 and an acoustic medium such as water or an ultrasound gel (e.g., Aquasonic 100, ParkerLabs) is applied between the object 402 and a surface of a distal end of ergodic relay 450 to facilitate acoustic coupling. In PACTER system 400, the power of the laser beam from pulsed laser 410 is controlled by the half-wave plate 422 and polarizing beam splitter 423. During operation, the beam reflected by the polarizing beam splitter 423 is sent to beam trap 424. The beam transmitted through the polarizing beam splitter 423 is expanded by a beam expander consisting of first lens 426 and second lens 427. An iris (not shown) is used to adjust the beam diameter (e.g., to be about 6 mm) and the beam is sent through a homogenizer including first microlens array 435, second microlens array 436, and lens 437 (e.g., AC254-250-A lens sold by Thorlabs), which homogenized the beam in the imaging volume. The PACTER signals detected by the ultrasonic transducer 460 are amplified by the one or more low-noise amplifiers 470, filtered by the low-pass filter (not shown), and digitized by DAQ (e.g., ATS9350 data acquisition card sold by AlazarTech) 374. The DAQ 474 may be installed on the computing device 450. In one embodiment, the PACTER system includes a multifunctional input/output (I/O) device (e.g., PCIe-6321 I/O device sold by National Instruments) to control the light source 410, and the DAQ 474.
A PACTER signal is recorded by DAQ 474 from acoustic waves generated by the object 402 and detected by integrated ultrasonic transducer 460 following a laser light pulse. The DAQ 474 digitizes the photoacoustic signal. The computing device 480 uses the calibrating photoacoustic signals from a plurality of calibrating pixels generated from a calibration process as a plurality of virtual detectors to reconstruct a 3D image of the object 402.
In certain embodiments, an ergodic relay of a PACTER system includes an integrated single-element ultrasonic transducer, e.g., that is fabricated (e.g., sputtered) directly onto an outer surface of an acoustic cavity. The single-element ultrasonic transducer may be based on a lead magnesium niobate-lead titanate (PMN-PT) single crystal, for example. The single-element ultrasonic transducer may be fabricated directly onto the surface of the acoustic cavity in a region where the single-element ultrasonic transducer does not interact with the illumination laser beam. Fabricating the ultrasonic transducer directly onto the surface may enhance the detection sensitivity and improve the stability of the PACTER system for long-term imaging in unstable environments. In other embodiments, a single-element ultrasonic transducer element may be a separate pre-fabricated component that is coupled to the acoustic cavity with, e.g., a resin.
An example of a suitable single-element ultrasonic transducer element is a pin-shaped ultrasound transducer. A commercially-available example of a single-element ultrasonic transducer element is a VP-0.5 transducer made by CTS Electronics, Inc., which has a 10 MHz central frequency and 0.5 mm element size. Another commercially-available example is the VP-0.5−20 MHz transducer made by CTS Electronics, Inc., which has a 20 MHz central frequency, 56% one-way bandwidth, and 0.5 mm element size.
In some examples, the single-element ultrasonic transducer is based on a lead magnesium niobate-lead titanate (PMN-PT) single crystal, which may achieve exceptional piezoelectric performance, such as high piezoelectric constant (d33) and electromechanical coupling coefficient (kt).
A single-element ultrasonic transducer generally acquires a 1D signal in the time domain as shown in the three graphs 590 of
(A) Method of Fabricating Ergodic Relay with Integrated Single-Element Ultrasonic Transducer
At operation 1910, a piezoelectric crystal is obtained. In some cases, a PMN-PT piezoelectric single crystal (e.g., PMN-PT piezoelectric single crystal sold by CTS Corporation) is the core component for acoustic-electrical conversion due to the excellent piezoelectric coefficient and high permittivity, which is suitable for high-frequency transducers with small aperture sizes because of the general electrical impedance matching (e.g., 50 ohms). Based on the material parameters, a transducer modeling software (e.g., PiezoCAD) based on Krimboltz, Leedom, and Mattaei (KLM) equivalent circuit model was employed to simulate and optimize the design of the transducer. In one example, 30 MHz PMN-PT transducer with a small active aperture size of 0.4× 0.4 mm2 was determined and obtained. The piezoelectric element has a central frequency of 30 MHz.
At operation 1920, the piezoelectric crystal is lapped to the required thickness (e.g., 40-μm). At operation 1930, gold electrodes are deposited (e.g., sputter deposited) onto both sides of the piezoelectric crystal. Some examples of a thickness of the gold electrodes include 100 nm, 150 nm, etc.
At operation 1940, a layer of conductive silver paste (e.g., E-solder 3022) is deposited onto the acoustic stack as a backing layer.
At operation 1950, the acoustic stack is diced into designed piezoelectric element size. Some examples of a designed piezoelectric element size include 0.4×0.4 mm2.
At operation 1960, using Kapton tape or other tape as a mask, a gold electrode is deposited (e.g., sputtered) on a region (e.g., a corner) of a surface of a prism of an ergodic relay. The prism may be fused to an optical rod or an acoustic waveguide. In one example, the gold electrode is deposited on the hypotenuse surface of the prism. In one aspect, the gold electrode is deposited in a region in which there is no interference with the illumination beam.
At operation 1970, the piezoelectric element is then affixed directly to the gold electrode on the prism using a thin layer of conductive silver paste. At operation 1980, wires are connected to the piezoelectric element to read the photoacoustic signals. At operation 1990, a protective layer (e.g., a thin parylene layer) is deposited onto the transducer element. As shown in the zoomed-in-view in
(B) Calibration method and Calibrated Virtual Transducers
According to various embodiments, a PACTER system may only need a one-time universal calibration as discussed in Section V(B). With these embodiments, a PACTER system may be calibrated one time, e.g., at a factory before being passed onto the customer.
In the calibration procedure depicted in
When source points 660, 661 in the 3D volume (r′m, m=1, 2, . . . ) are illuminated by a light pulse, the photoacoustic signals they generate propagate to the calibrated virtual transducers (rn, n=1, 2, . . . ) after time tm,n=∥r′m−rn∥/c, where c is the speed of the sound in the medium. Then, these photoacoustic signals would follow the same acoustic path inside the ergodic relay 650 to the ultrasonic transducer as that of the calibration signals. From the transducer's perspective, compared with the calibration signal kn(t) acquired at In, the signal from the source point r′m relayed through rn is proportional to kn(t) delayed by tm,n, i.e., kn(t−∥r′m−rn∥/c).
At operation 2020, at each light pulse the acoustic delay line (e.g., optical rod) temporally separates the initial photoacoustic signals from the reflected photoacoustic signals. For example, for an acoustic delay line with a length of 175 mm, the length of the delay will be 58 microseconds (175 mm×2 [round-trip]/speed of sound in glass [6000 m/s]).
At operation 2030, at each light pulse the acoustic cavity (e.g., prism) scrambles or encodes the photoacoustic signals received from the acoustic delay line. For each calibration pixel, the photoacoustic signal will be scrambled by the complex shape of the acoustic cavity and become a unique temporal pattern.
At operation 2040, while each calibration pixel location is illuminated by a focused light beam, a calibration photoacoustic signal is detected by the single-element ultrasonic transducer fabricated directly on a surface of the acoustic delay line of the ergodic relay. The single-element ultrasonic transducer may be fabricated in a region of the surface that will not be in interference with the focused illumination beam. In one aspect, the single-element ultrasonic transducer takes measurements at a rate of 100 MHz. In another aspect, the single-element ultrasonic transducer takes measurements at a rate of 250 MHz. In yet another aspect, the single-element ultrasonic transducer takes measurements at a rate of 500 MHz.
At operation 2050, the calibration photoacoustic signal detected at the plurality of calibration pixel locations are used as a corresponding plurality of photoacoustic virtual calibrated detectors. These virtual calibrated detectors are used in the image reconstruction method described in Section III(C)(1).
(C) PACTER Imaging method
In a PACTER system, the signal s(t) detected by the ultrasonic transducer at time t in a homogeneous medium is expressed as:
Here, M and N are the numbers of the source points and the calibrated virtual transducers, respectively; kn(t) is the normalized impulse response from the calibration at the n- the virtual transducer; r′m and rn are the locations of the m-th source point and the n-th virtual transducer, respectively; p0,m is a value proportional to the initial pressure at r′m; θm,n denotes the incidence angle satisfying
with n being the normal vector of the calibration plane; θ1 is the critical angle the ultrasonic refraction from water to fused silica; 1[0, θ
Discretizing Eqn. 1 obtains the forward model:
where s represents a vector of length L, P0 denotes a vector of length M(=M1M2M3) which consists of all voxels in a 3D image of size M1×M2× M3, and H is the system matrix of size L×M. This forward model has a computational complexity of max{O(MN), O(NLlog2L)}. To obtain an image from the signals s, the forward model is inverted by solving the regularized optimization problem:
Here, |P0|TV denotes the total variation (TV) of the 3D image corresponding to p0, and 1 is the regularization parameter. TV regularization aids in transforming an image into a new one with piecewise smoother structures, essentially constituting a form of sparseness. Utilizing TV regularization allows the incorporation of the piecewise smoothness of blood vessels into the iterative reconstruction, considerably stabilizing the iterations. Numerically, this optimization problem is solved through a Fast Iterative Shrinkage-Thresholding Algorithm (FISTA). An example of a FISTA algorithm can be found in Beck, A. & Teboulle, M. A, “fast iterative shrinkage-thresholding algorithm for linear inverse problems. SIAM,” Imaging Sci. 2, 183-202 (2009). An iteration number of 8 was chosen for the FISTA algorithm, considering the trade-off between the reconstruction image quality and the image reconstruction time. This choice was determined through a series of experiments, in which the impact of different iteration numbers was analyzed for both the quality of the reconstructed image and the computational time required for reconstruction. For a 3D volume comprising 80×80×120 voxels, the image reconstruction time was approximately 600 s running on a CentOS Linux 7 system with Intel® Xeon® Gold 6130 CPU @ 2.10 GHz.
In some embodiments, the reconstructed images are processed. In one embodiment, the reconstructed images are first denoised using a 3D median filter (e.g., in the 3-by-3-by-3 neighborhood) and smoothed using a 3D Gaussian filter (e.g., with a 0.1-by-0.1-by-2 standard deviation kernel). A Hessian-matrix-based vesselness filter may be applied to the denoised images to improve the contrast of vascular structures in 3D. The vesselness-enhanced images (self-normalized) with a weighting factor of 0.8 is added back to the filtered images with a weighting factor of 0.2 and obtained the final images. The images may be rendered in 3D or in 4D (e.g., time lapse 3D) using various algorithms such as, e.g., the Imaris (Bitplane) software.
In one embodiment, the speed of fluid flow may be calculated from PACTER data by differentiating the PA amplitudes along a fluid path and fitting the relationship between the travelling distance of the fluid front over time. For example, the speed of bovine blood flushing through a tube may be calculated by differentiating PA amplitudes along the tube and fitting the relationship between the traveling distance of the blood front versus time. In FIGS. 11D-E and
At operation 2120, at the acoustic delay line (e.g., optical rod) temporally separates the initial photoacoustic signals from the reflected photoacoustic signals. For example, for an acoustic delay line with a length of 175 mm, the length of the delay will be 58 microseconds (175 mm×2 [round-trip]/speed of sound in glass [6000 m/s]).
At operation 2130, at each light pulse the acoustic cavity (e.g., prism) scrambles or encodes the photoacoustic signals received from the acoustic delay line. The photoacoustic signal is scrambled by the complex shape of the acoustic cavity and becomes a temporal pattern that is a function (following Eqn. 1) of the calibration pixel signals captured at operation 2030.
At operation 2140, while each the field-of-view of the object being imaged is illuminated by the homogenized illumination pattern, a photoacoustic signal is detected by a single-element ultrasonic transducer fabricated directly on a surface of the acoustic delay line of the ergodic relay. A DAQ records and digitizes the photoacoustic signal over an exposure time. The single-element ultrasonic transducer may be fabricated in a region of the surface that will not be in interference with the illumination beam. In one aspect, the single-element ultrasonic transducer takes measurements at a rate of 100 MHz. In another aspect, the single-element ultrasonic transducer takes measurements at a rate of 250 MHz. In yet another aspect, the single-element ultrasonic transducer takes measurements at a rate of 500 MHz.
At operation 2150, a 3D photoacoustic image is reconstructed using the recorded data from the encoded photoacoustic signal and the photoacoustic virtual calibrated detectors from a calibration procedure performed on the PACTER system. The recorded data and the virtual calibrated detectors are used in the image reconstruction method described in Section III(C)(1).
(A) Spatiotemporal characterization of PACTER images
A PACTER system can be used to image the 3D structure of an object and the 4D dynamics of a moving object (e.g, fluid flow) when illuminated by multiple light pulses. For example, using the signals acquired by a single-element ultrasonic detector, the PACTER system 400 of
Second, the PACTER system 400 in
To quantify the spatial resolution of the PACTER system 400 in
To demonstrate that a PACTER system can be used to image 4D dynamics, i.e., time-lapse movements of 3D objects, PACTER system 400 in
(B) 4D In Vivo Imaging of Mouse Hemodynamics with PACTER
Enabled by the capability of noninvasive, label-free, and ultrafast 3D imaging, PACTER techniques may be suitable for monitoring hemodynamics in vivo. The PACTER system 400 in
The PACTER system 400 in
When multiple laser pulses were used, PACTER system 400 was able to capture the 4D dynamics of the blood vessels. Based on the 4D PACTER datasets, individual blood vessels were isolated from the cross sections of the 3D volumes were isolated and visualized their motions and structural changes were visualized.
By recording the time-lapse changes of the center positions and widths of the blood vessels, the respiratory motion could be tracked and identified. Using Fourier analysis, it was found that the center position of the blood vessel of mouse 1 fluctuated periodically, exhibiting a respiratory frequency of 1.8 Hz, whereas the width of the vessel was relatively stable. In comparison, a respiratory frequency of 1.4 Hz could be observed from both the center position and width of the blood vessel of mouse 2.
(C) 4D In Vivo Imaging of Hemodynamics in Human Hands with PACTER
To demonstrate PACTER techniques being used to monitor hemodynamics in humans, PACTER system 400 in
The thenar vasculature was imaged and responses to cuffing, which was induced by a sphygmomanometer wrapped around the upper arm was imaged.
Using the PACTER system 400, the thenar vasculature of Subject 1 and Subject 2 was imaged in 3D with single laser pulses and the 4D dynamics of the blood vessels in response to cuffing was reconstructed.
As shown in the maximum amplitude projections of the 4D datasets shown in in the top portions of
For Subject 1, the occlusion rate of the vessel was found to be 1.3+0.1 m/s, significantly slower than the blood flow speed of 16.1+3.1 m/s extracted from the recovery phase as shown in
(D) 4D In Vivo Imaging of Hemodynamic Changes in Human Foot Vessels with PACTER
Imaging of hemodynamics in the lower extremities, specifically in the human feet, plays a pivotal role in the diagnosis, treatment, and prevention of peripheral vascular diseases and diabetes.
To evaluate the clinical applicability of PACTER, PACTER system 400 in
Using PACTER system 400, 3D images of blood vessels in the instep area were captured with single laser pulses both before and after vascular occlusion and the 4D dynamics of the blood vessels in response to the occlusion was reconstructed.
The maximum amplitude projections of the 3D volumes before and after vascular occlusion shown in
These results demonstrate the potential for PACTER techniques being a tool for assessing vascular function in the lower extremities. The detailed and localized information PACTER techniques provide could prove invaluable in early-stage screening, leading to more sensitive detection or early prevention of conditions such as ischemia or ulcer development. Moreover, with PACTER's ability to accurately monitor hemodynamic changes, PACTER techniques could facilitate the measurement of treatment efficacy for peripheral vascular diseases and diabetes. PACTER techniques could prove valuable for guiding wound treatment in vascular clinics and could facilitate post-surgical decision-making and provide longitudinal monitoring of functional wound healing. Ultimately, PACTER techniques hold substantial promise for enhancing patient outcomes and advancing medical research in peripheral vascular diseases and diabetes.
(E) Comparison with Other Techniques that Use Other Ergodic Relays
Table 1 is a comparison of PACTER techniques of certain embodiments with PA topography through an ER (PATER) and PA microscopy through an ER (PAMER) that use other types of ergodic relays. First, other techniques only allow for 2D imaging and do not provide depth information about the object. PACTER techniques enables both 3D and 4D in vivo imaging in animals and humans. Second, other techniques are not suited for long-term imaging in unstable environments. For example, PA topography through an ER (PATER) and PA microscopy through an ER (PAMER) are sensitive to boundary condition between the object and the ER, necessitating recalibration for different objects. PACTER techniques employs an integrated transducer that is directly fabricated on the ER, enhancing sensitivity over a broadband while enabling long-term in vivo imaging in unstable environments. Third, all other techniques employ a two-step iterative shrinkage/thresholding (TwIST) algorithm for reconstruction, which can be orders of magnitude slower than the Fast Iterative Shrinkage-Thresholding Algorithm (FISTA) algorithm used in PACTER techniques. An example of the FISTA algorithm may be found in Beck, A. & Teboulle, M. A, “fast iterative shrinkage-thresholding algorithm for linear inverse problems, SIAM,” Imaging Sci. 2, 183-202 (2009). For the substantial number of voxels 80×80×120 in the 3D volumes that may be imaged by PACTER techniques, the reconstruction becomes computationally intensive. PACTER reconstruction may employ FISTA and temporal convolution implemented through fast Fourier transform (FFT)f or 3D and 4D imaging through ERs to improve the computations. Finally, due to the issues associated with other techniques that use other ergodic relays, they may not be able to provide human imaging. In comparison, PACTER techniques have the ability to capture dynamic changes in vascular occlusion which offers clinical potential for early detection, enhanced assessment, and personalized treatment of peripheral vascular diseases.
Although certain implementations of a PACTER system employ one or more motorized stages for calibration, a pulsed laser for illumination, and a DAQ card for data acquisition, other components may be used for less expensive and compact alternative implementations. For example, given the system's universal calibration capability and the fact that a single calibration dataset could remain effective for at least a year as discussed in Section II (A) with respect to
In certain embodiments, a PACTER system is configured for handheld operation. Handheld operation offers the flexibility for imaging different body parts in both animals and humans. In some cases, a PACTER system includes one or more optical fibers to enable handheld operation. For example, a PACTER system may implement a multi-mode fiber to deliver a light beam, which may add flexibility for animal and human imaging.
PACTER system 2900 also includes a multi-mode optical fiber 2912 coupled to a fiber collimator 2911, which is in optical communication with prism 2952. In this embodiment, the pulsed light source is a separate component and one or more laser pulses are delivered to the prism 2952 via the multi-mode optical fiber 2912. A homogenizer may also be a separate component. Although not shown, PACTER system 2900 includes additional system components such as, e.g., data acquisition system or one or more microcontrollers and an optical system. A computing device may also be a separate component. Photoacoustic data may be communicated to the computing device via a communication cable or in wireless form.
Due to the large dimensions of the ergodic relay as compared with the acoustic wavelength, the photoacoustic waves need to propagate a long distance inside the ergodic relay. A slight change in the speed of sound due to temperature fluctuations=might cause large differences in a measured PACTER signal. Certain implementations employee a temperature control system with one or more elements for maintaining the temperature of the ergodic relay, e.g., at 30° C., to maintain a constant speed of sound during operation. For example, in one implementation, a PACTER system includes a temperature stabilizing box to maintain the temperature of the ergodic relay.
According to various implementations, the light source may provide various wavelengths. In one example, the wavelength may be in the range of 400 nm to 1064 nm. In one example, the wavelength of a laser light pulse is 532 nm. The strong attenuation of 532 nm light by endogenous chromophores in biological tissue can limit the penetration depth of the PACTER system to 3.6 mm in vivo. In certain implementations, a wavelength of 1064 nm or larger is used to increase the penetration depth to several centimeters.
The field-of-view of an ergodic relay with an optical rod is based on the diameter of the optical rod. In some cases, the dimensions of the prism and optical rod are selected based on: (1) the rod's diameter, which determines the FOV, should be substantially smaller than the right-angle edge length of the prism to ensure that the PA signals can be effectively scrambled; In one example, the rod's diameter can be 10 mm to 26 mm, whereas the right-angle edge length of the prism can be 40 mm. (2) the rod's length should greatly exceed the right-angle edge length of the prism to extend the duration of the object-independent signal (unaffected by the boundary condition), thereby ensuring the universal calibration capability. In one example, the rod's length can be 125 mm to 225 mm, whereas the right-angle edge length of the prism can be 20 mm to 40 mm. In certain implementations, a PACTER system may have an ergodic relay with dimensions designed for a large field-of-view, which may enable new applications such as vascular biometrics. In one example, the rod's diameter can be extended to 100 mm, allowing a field-of-view of 70×70 mm2.
In one embodiment, the PACTER reconstruction instructions are implemented on a GPU. The 3D reconstruction in PACTER may be computationally intensive. For example, image reconstruction for a 3D volume of 80×80×120 voxels may take 10 min when using a CPU. Implementing the reconstruction instructions on a GPU may significantly improve computational time.
An acoustic impedance mismatch between the object and the ergodic relay can cause a limited-view effect that limits spatial resolution. In certain embodiments, the ergodic relay of a PACTER system includes one or more acoustic impedance-matching layers disposed between the object being imaged and the ergodic relay, e.g., on a distal end of an optical rod of the ergodic relay. For example, a quarter-wavelength impedance-matching layer (Zmatch=√{square root over (Zobject ZER)}) may be implemented where Zobject and ZER are the acoustic impedances of the object and the ergodic relay, respectively. As another example, a cascaded impedance-matching layer may be used. As another example, a cascaded impedance-matching layer may be used. As another example, a gradient impedance-matching layer may be used. Some examples of suitable acoustic impedance-matching layers may be described in Zhao, J. et al., “Ultrawide Bandwidth High-Frequency Ultrasonic Transducers With Gradient Acoustic Impedance Matching Layer for Biomedical Imaging,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 69, 1952-1959 (2022), Zhao, J. et al., “Ultrawide Bandwidth High-Frequency Ultrasonic Transducers With Gradient Acoustic Impedance Matching Layer for Biomedical Imaging,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 69, 1952-1959 (2022)), and Li, Z. et al. Broadband gradient impedance matching using an acoustic metamaterial for ultrasonic transducers. Sci. Rep. 7, 42863 (2017). Some examples of materials of an acoustic impedance-matching layer include polymethyl methacrylate and polymethylpentene.
PACTER may impact a wide range of applications in biomedical research and clinical settings, including home care of diabetic-foot ulcers or peripheral vascular diseases, point-of-care screening for hypertension, and simultaneous oximetry of both arterial and venous blood in intensive care units. PACTER's single-shot volumetric imaging concept using a single-element detector can extend beyond optical imaging, aiding fields such as medical ultrasonography, underwater sonar, and airborne radar. For instance, PACTER can potentially replace the transduce array for detection in ultrasonography, thereby substantially reducing the system's cost and complexity.
In some embodiments, the one or more light pulses are provided to the object being imaged directly from the one or more light sources or via one or more optical elements in optical communication with the one or more light sources. For example, in the ultrasonography PACTER system 3400 of
In summary, PACTER techniques are noninvasive, label-free, and ultrafast imaging techniques that enable 4D imaging of hemodynamics in humans using the 1D signal captured by a single detector, achieving an imaging speed of up to a thousand volumes per second. PACTER's capability to visualize the 4D hemodynamics in humans and small animals, particularly the hemodynamic changes in human foot vessels during vascular occlusion are discussed in Section IV. PACTER techniques can image different objects, including human hands and mouse abdomens, without the need for recalibration. PACTER high imaging speed allows for immediate intervention in case of abnormal hemodynamic changes. Additionally, PACTER's low cost and compact form factor may be ideal for point-of-care testing, facilitating quick and easy assessment of hemodynamic parameters at the bedside or in remote locations.
In certain embodiments, a PACTER system includes a homogenizer to convert light to uniform light that can be provided to the acoustic cavity of the ergodic relay. An example of a suitable homogenizer is a fly's eye homogenizer.
As shown in
The width of the homogenized beam, dH, is given by:
where pM and fM are the pitch and focal length of the lenslets in the two identical microlens arrays, fL is the focal length of the spherical lens, and a is the separation between the microlens arrays. In PACTER techniques, a is set to be identical to fM, leading to:
The divergence half-angle after the homogenization plane, θ, is given by:
where dO is the diameter of the original beam.
In one example, a PACTER system implements a microlens arrays with pM=0.5 mm and fM=15 mm, a spherical lens with fL=250 mm, and an original beam with a diameter of dO=6 mm. Therefore, the homogenized beam has a width of dH≈8 mm, matching the size of the calibration pattern (80 by 80 steps with a step size of 0.1 mm), and the divergence half-angle θ≈2°. The small divergence ensures homogenous illumination across the whole 3D volume (8 mm×8 mm×3.6 mm) for in vivo imaging. Within the 3.6 mm depth, the illumination beam merely diverges laterally by 0.13 mm, which is much smaller than the lateral resolution (0.56 mm) of the PACTER system. Hence, the beam divergence within the imaging volume may be ignored.
In some embodiments, a PACTER system is universally calibratable.
Ergodic relay 2550 of a PACTER system includes a prism 2552 and a fused silica rod 2554, where the silica rod 2554 functions as an acoustic delay line that temporally separates the initial and reflected PA signals as shown in
During a calibration procedure, calibrations at pixels on a 2D plane are performed. These calibration pixels can then be used as virtual ultrasonic transducers for 3D imaging. If non-zero initial pressure exists only on the calibration plane, the detected signal s(t) at time t can be expressed as:
where N is the number of calibrated virtual transducers, kn(t) is the normalized impulse response from the calibration at the n-th virtual transducer, and pn, is the root-mean-squared PA amplitude proportional to the initial pressure at the n-th virtual transducer.
For initial pressure in a 3D volume, it is assumed M source points located at r′m, m=1,2, . . . , M, in an acoustically homogeneous 3D region attached to the calibration plane. The PA wave generated from the source point at r′m propagates to the calibrated virtual transducer rn with the speed of sound c after time
which, through the ER, adds
to the detected signal, with the PA amplitude pm,n quantified as
Here, θm,n denotes the incidence angle satisfying
with n being the normal vector of the calibration plane; function w(θm,n) describes a virtual transducer's angle-dependent sensitivity; and P0,m is proportional to the initial pressure at r′m. pnkn(t) is replaced in Eqn. 7 with
from all the M source points and the detected widefield PA signal is obtained:
Here, define kn(t)=0, n=1,2 . . . , N, t<0. For sufficiently small virtual ultrasonic transducers, it is assumed that:
Here, the following indicator function is used:
to rejection detections with incidence angles greater than the critical angle θ1 which is quantified in Section V(D). Substituting Eqn. 9 into Eqn. 8 yields
L is set to the number of time points after temporal discretization. Then the computational complexity of a forward model based on Eqn. 11 is O(MNL).
To accelerate the forward model in Eqn. 11, the delay term
is split from function kn(t) through temporal convolution:
Substituting Eqn. 12 into Eqn. 11, the following is obtained:
The inner summation in Eqn. 13 has a complexity of O(MN) and each temporal convolution is implemented through three fast Fourier transforms (FFTs) with a complexity of O(Llog2L). Thus, the forward model based on Eqn. 13 has a computational complexity of max{O(MN), O(NLlog2L)}.
Numerical simulations were performed to quantify the improvement of computational efficiency brought by the fast algorithm. Considering that the complexities of both the slow (Eqn. 11) and fast (Eqn. 13) algorithms are linearly dependent on the number of virtual detectors N, the problem is simplified to a single virtual detector (N=1) with, e.g., L=65,536 and M=80×80×120, and only consider the computation time of a forward simulation. In a Windows 11 Home system with Intel® Core™ 19-10900T CPU @ 1.90 GHz, single-CPU-core forward simulations were performed based on the slow and fast algorithms, respectively, 36 times in Matlab. The average computation times of the simplified forward simulation are 20 s and 2.2×10−3 s (×9, 100 acceleration), respectively, which correspond to 35.6 h and 14.1 s for a true forward simulation (N=80×80).
Modifications, additions, or omissions may be made to any of the above-described embodiments without departing from the scope of the disclosure. Any of the embodiments described above may include more, fewer, or other features without departing from the scope of the disclosure. Additionally, the steps of described features may be performed in any suitable order without departing from the scope of the disclosure. Also, one or more features from any embodiment may be combined with one or more features of any other embodiment without departing from the scope of the disclosure. The components of any embodiment may be integrated or separated according to particular needs without departing from the scope of the disclosure.
It should be understood that certain aspects described above can be implemented in the form of logic using computer software in a modular or integrated manner. Based on the disclosure and teachings provided herein, a person of ordinary skill in the art will know and appreciate other ways and/or methods to implement the present invention using hardware and a combination of hardware and software.
Any of the software components or functions described in this application, may be implemented as software code using any suitable computer language and/or computational software such as, for example, Java, C, C #, C++ or Python, Lab VIEW, Mathematica, or other suitable language/computational software, including low level code, including code written for field programmable gate arrays, for example in VHDL. The code may include software libraries for functions like data acquisition and control, motion control, image acquisition and display, etc. Some or all of the code may also run on a personal computer, single board computer, embedded controller, microcontroller, digital signal processor, field programmable gate array and/or any combination thereof or any similar computation device and/or logic device(s). The software code may be stored as a series of instructions, or commands on a CRM such as a random access memory (RAM), a read only memory (ROM), a magnetic media such as a hard-drive or a floppy disk, or an optical media such as a CD-ROM, or solid stage storage such as a solid state hard drive or removable flash memory device or any suitable storage device. Any such CRM may reside on or within a single computational apparatus, and may be present on or within different computational apparatuses within a system or network. Although the foregoing disclosed embodiments have been described in some detail to facilitate understanding, the described embodiments are to be considered illustrative and not limiting. It will be apparent to one of ordinary skill in the art that certain changes and modifications can be practiced within the scope of the appended claims.
The terms “comprise,” “have” and “include” are open-ended linking verbs. Any forms or tenses of one or more of these verbs, such as “comprises,” “comprising,” “has,” “having,” “includes” and “including,” are also open-ended. For example, any method that “comprises,” “has” or “includes” one or more steps is not limited to possessing only those one or more steps and can also cover other unlisted steps. Similarly, any composition or device that “comprises,” “has” or “includes” one or more features is not limited to possessing only those one or more features and can cover other unlisted features.
All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the present disclosure and does not pose a limitation on the scope of the present disclosure otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the present disclosure.
Groupings of alternative elements or embodiments of the present disclosure disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.
This application claims benefit of and priority to U.S. Provisional Patent Application No. 63/438,644, titled “SINGLE-SHOT 3D IMAGING USING A SINGLE DETECTOR,” and filed on Jan. 12, 2023, which is incorporated by reference herein in its entirety and for all purposes.
This invention was made with government support under Grant No(s). EB028277 & CA220436 & EB029823 awarded by the National Institutes of Health. The government has certain rights in the invention.
| Number | Date | Country | |
|---|---|---|---|
| 63438654 | Jan 2023 | US |
