Portable deep-tissue photoacoustic imaging devices, systems, and methods of use

Abstract

A photoacoustic imaging device that allows for continuous and real-time two-dimensional monitoring of blood oxygenation at depths greater than 2 cm, including arrays of pulsed laser diodes of one or more distinct wavelengths. The diodes are configured to be focused at a desired depth and within a sensing window of the transducer.

Description

PORTABLE DEEP-TISSUE PHOTOACOUSTICIMAGING DEVICES, SYSTEMS, AND METHODS OF USECross-Reference to Related Application

[0001] This application claims the benefit under 35 U.S.C. § 119(e) to U.S. Provisional Application 63 / 777 ,374, filed March 25, 2025 and entitled “Portable Deep-Tissue Photoacoustic Imaging Devices, Systems, and Methods of Use,” which is hereby incorporated herein by reference in its entirety.Technical Field

[0002] This disclosure relates to embodiments of devices, systems, and methods for using a photoacoustic (PA) device for continuous monitoring of various health related characteristics, in the form of an integrated probe or wearable. In particular, certain such embodiments disclosed herein relate to devices having a linear arrangement of piezo elements with a unique distribution of high-power laser diode to generate usable 2D maps of blood oxygenation with acceptable signal-to-noise ratio thresholds at a desired depth (e.g., 2-5 cm) based on target imaging application.Background

[0003] Oxygenation saturation of hemoglobin is a vital physiological parameter for clinical applications in oncology, neurology, cardiology and obstetrics The target organs in these applications are often embedded deep within the human body (up to 10 cm). Currently, blood oxygen level dependent magnetic resonance imaging (BOLD-MRI) is among the best approaches to assess blood oxygenation (SO2) of deeply embedded tissue (e.g , placenta or other abdominal tissue). However, a combination of accessibility, long imaging times and operational cost makes functional MRI impractical for continuous longitudinal monitoring of blood oxygenation at the point-of-care or use in low resource environments.

[0004] Clinical ultrasound (US) remains the most widely used imaging modality for assessing anatomical changes and blood flow, with key applications in cardiology and obstetrics. Image contrast in traditional US arises from differences in mechanical properties between varying tissue types with no direct access to measure SO2. Doppler imaging captures changes in frequencies in US waves to make direct measurements of blood flow velocities, which are used as an indicator for the progression of vascular diseases (e.g., preeclampsia, hypertension, or other vascular diseases). However, Doppler shows poor sensitivity to smaller vessels limiting its use to larger vessels with high flow speeds.

[0005] Photoacoustic (PA) imaging is a rapidly emerging modality that operates on the photoacoustic effect, i.e., allowing direct visualization of light absorbing substances, or optical chromophores, using traditional ultrasound hardware. Typical chromophores in biological systems include melanin, lipids, and oxygenated or deoxygenated hemoglobin. By acquiring images at multiple optical wavelengths, spatial distributions of the desired chromophores can be retrieved. The first FDA-approved systems for breast imaging utilize this approach to assess tumor oxygenation.

[0006] Despite these advantages, spectroscopic photoacoustic imaging of tissue oxygenation at depths beyond approximately 2 cm remains technically challenging. Wavelength-dependent optical attenuation and scattering in heterogeneous tissue result in spatially varying optical fluence distributions, which introduce errors in estimating chromophore concentrations and reduce the accuracy of quantitative oxygenation measurements at increasing depths

[0007] Despite these advantages, spectroscopic photoacoustic imaging of tissue oxygenation at depths beyond approximately 2 cm remains technically challenging Wavelength-dependent optical attenuation and scattering in heterogeneous tissue result in spatially varying optical fluence distributions, which introduce errors in estimating chromophore concentrations and reduce the accuracy of quantitative oxygenation measurements at increasing depths.

[0008] Many existing PA imaging systems rely primarily on illumination within the first near-infrared window (NIR-I, <950 nm) where biological tissues exhibit relatively higher absorption and scattering, further limiting imaging depth and quantitative accuracy. Conventional clinical and preclinical PA imaging systems typically use bulk solid-state optical parametric oscillator (OPO) and Nd:YAG (neodymium-doped yttrium aluminum garnet) based laser sources capable of delivering high pulse energies (on the order of tens of millijoules per pulse) with short pulse durations (typically less than 10 ns) at low repetition rates (typically less than 20 Hz). These laser systems are typically categorized as a Class IV laser, requiring extensive laser safety controls for sage use in humans.

[0009] In addition to bulk solid-state lasers, prior photoacoustic systems have relied on high-power laser bar emitters or stacked diode bar assemblies to generate sufficient optical energy for signal generation. Laser bar emitters typically comprise multiple edge-emitting semiconductor laser stripes fabricated on a single substrate and driven at high current to achieve elevated peak optical power To further scale output, multiple laser bars are often vertically stacked, resulting in large emitting areas, high instantaneous currents, substantial thermal loads, and highly multimode optical output withpronounced fast- and slow-axis divergence. Such systems are commonly optimized for raw peak power delivery rather than beam coherence, spatial uniformity, or compact integration, and frequently require aggressive thermal management, complex packaging, and additional optical elements to condition the emitted light.

[0010] Light emitting diodes (LEDs) have also been employed in certain photoacoustic systems; however, LEDs operate by spontaneous emission rather than stimulated emission and lack a resonant optical cavity. As a result, LEDs emit light incoherently over a broad angular distribution, commonly approximating a Lambertian emission pattern. The emitting area of an LED is typically large relative to laser sources, producing light that is highly divergent and distributed over a wide solid angle. Consequently, LED based systems generally require additional optical elements, including but not limited to lenses, reflectors, or other focusing structures, to collect, redirect, or concentrate emitted light toward a target region. In contrast, quantum well laser diodes generate light through stimulated emission within an optical cavity, producing a substantially more directional output with significantly higher radiance than LEDs. At the time of invention, LEDs were widely regarded as unsuitable for applications demanding localized photoacoustic excitation from deep tissue without extensive optical conditioning. The recognition that quantum well laser diodes could be arranged and operated to provide adequate photoacoustic excitation without such optical elements represents a departure from conventional illumination design and was neither taught nor suggested by LED based approaches in the prior art.

[0011] Accordingly, there exists a need for PA imaging systems that enable deep-tissue functional assessment, including oxygenation monitoring, while operating at substantially lower optical pulse energies and higher repetition rates sufficient for continuous or near-continuous acquisition and monitoring of various health-related characteristics, such as oxygenation, and related systems and methods.Summary

[0012] In Example 1, a photoacoustic imaging system comprises a housing and one or more pulsed laser diodes configured to emit optical pulses at one or more wavelengths within 900-1900 nm. Each pulsed laser diode has a per-pulse energy between 0.1 pJ and 200 pJ and a pulse duration between 2 ns and 200 ns. The photoacoustic imaging system further includes at least one laser driver configuredto supply power and timing signals to the one or more pulsed laser diodes at a pulse repetition frequency between 20 Hz and 20,000 Hz, an acoustic transducer having a center frequency between 0.5 MHz and 60 MHz, and a data acquisition system operably coupled to the acoustic transducer and configured to receive photoacoustic signals generated in a target tissue.

[0013] Example 2 relates to the photoacoustic imaging system according to Example 1, wherein the optical pulses comprise wavelengths within 900 nm and 1400 nm.

[0014] Example 3 relates to the photoacoustic imaging system according to Example 2, wherein the optical pulses comprise wavelengths within 1000 nm and 1200 nm.

[0015] Example 4 relates to the photoacoustic imaging system according to Example 1, wherein the per-pulse energy is between 0.5 J and 100 pJ.

[0016] Example 5 relates to the photoacoustic imaging system according to Example 4, wherein the per-pulse energy is between 5 pJ and 20 pJ.

[0017] Example 6 relates to the photoacoustic imaging system according to Example 5, wherein the pulse duration is between 50 ns and 150 ns.

[0018] Example 7 relates to the photoacoustic imaging system according to Example 1, wherein the pulse repetition frequency is between 50 Hz and 10,000 Hz.

[0019] Example 8 relates to the photoacoustic imaging system according to Example 7, wherein the pulse repetition frequency is between 100 Hz and 5,000 Hz.

[0020] Example 9 relates to the photoacoustic imaging system according to Example 1, wherein the at least one laser driver is configured to generate electrical drive pulses having predetermined pulse duration and peak current selected to produce the optical pulses emitted by the one or more pulsed laser diodes.

[0021] Example 10 relates to the photoacoustic imaging system according to Example 1, wherein the optical pulses comprise wavelengths selected from about 905 nm and about 1060 nm.

[0022] Example 11 relates to the photoacoustic imaging system according to Example 1 , wherein each of the one or more pulsed laser diodes is selected from the group consisting of a surface-emitting laser diode and an edge-emitting laser diode.

[0023] Example 12 relates to the photoacoustic imaging system according to Example 1 , wherein each of the one or more pulsed laser diodes comprises an optical axis, and wherein the pulsed laser diodesare configured such that optical axes of opposing pulsed laser diodes intersect at a predetermined depth within a sensing window of the acoustic transducer.

[0024] Example 13 relates to the photoacoustic imaging system according to Example 12, wherein the predetermined depth is between 2 cm and 5 cm.

[0025] Example 14 relates to the photoacoustic imaging system according to Example 1, wherein the data acquisition system comprises a front-end preamplifier providing at least +40 dB of gain.

[0026] Example 15 relates to the photoacoustic imaging system according to Example 14, wherein the preamplifier has an input impedance of about 2 MQ.

[0027] Example 16 relates to the photoacoustic imaging system according to Example 1, wherein the system achieves a signal-to-noise ratio of at least 1.1 at a tissue depth between 2 cm and 3 cm.

[0028] Example 17 relates to the photoacoustic imaging system according to Example 1, wherein the system is configured to detect an exogenous contrast agent.

[0029] Example 18 relates to the photoacoustic imaging system according to Example 1, wherein a surface fluence delivered by each of the one or more pulsed laser diodes is sufficiently low to qualify as a Class 3B laser or lower

[0030] Example 19 relates to the photoacoustic imaging system according to Example 1, wherein the system is configured to differentiate between oxygenated and deoxygenated hemoglobin through spectral unmixing of two or more laser wavelengths.

[0031] Example 20 relates to the photoacoustic imaging system according to Example 1, wherein the system further comprises a casing having a handheld form factor, the casing further comprising internal power delivery circuitry and wireless communication electronics.

[0032] Example 21 relates to the photoacoustic imaging system according to Example 20, wherein the system is configured to be wearable and further comprises a flexible wrap configured to maintain contact with a patient’s tissue.

[0033] Example 22 relates to the photoacoustic imaging system according to Example 1, wherein the acoustic transducer comprises one or more capacitive micromachined ultrasonic transducer (CMUT) elements.

[0034] Example 23 relates to the photoacoustic imaging system according to Example 1, wherein the acoustic transducer is arranged as a linear array.

[0035] Example 24 relates to the photoacoustic imaging system according to Example 1, wherein the acoustic transducer is arranged as a two-dimensional array.

[0036] Example 25 relates to the photoacoustic imaging system according to Example 1, wherein the acoustic transducer is arranged as a matrix array.

[0037] Example 26 relates to the photoacoustic imaging system according to Example 1, wherein the optical pulses comprise wavelengths of about 905 nm and about 1060 nm, and wherein the 905 nm laser diodes have a power rating of about 120 W and the 1060 nm laser diodes have a power rating of about 50 W.

[0038] In Example 27, a photoacoustic imaging system is configured for deep-tissue imaging and includes a pair of opposing arrays of pulsed laser diodes arranged on opposite sides of an acoustic transducer. Each array includes one or more pulsed laser diodes configured to emit light at two or more wavelengths within a range of 900-1900 nm. The photoacoustic imaging system further includes an acoustic transducer having a center frequency between 05 MHz and 60 MHz and a data acquisition system configured to receive photoacoustic signals and to enable spectral differentiation of tissue chromophores The opposing arrays are oriented such that their optical axes intersect at a predetermined depth within a sensing window of the acoustic transducer, and the pulsed laser diodes are driven at pulse durations between 2 ns and 200 ns, per-pulse energies between 0.1 pJ and 200 pi J, and repetition frequencies between 20 Hz and 20,000 Hz.

[0039] Example 28 relates to the photoacoustic imaging system according to Example 27, wherein the pulsed laser diodes comprise wavelengths of about 905 nm and 1060 nm

[0040] Example 29 relates to the photoacoustic imaging system according to Example 27, wherein the predetermined depth is between 2 cm and 5 cm.

[0041] Example 30 relates to the photoacoustic imaging system according to Example 27, wherein the data acquisition system comprises a preamplifier providing at least +40 dB of gain.

[0042] Example 31 relates to the photoacoustic imaging system according to Example 30, wherein the preamplifier has an input impedance of about 2 MQ.

[0043] Example 32 relates to the photoacoustic imaging system according to Example 27, further comprising a casing having a handheld form factor, the casing further comprising internal power delivery circuitry and wireless communication electronics.

[0044] In Example 33, a method of performing photoacoustic imaging of a target tissue includes positioning a photoacoustic imaging system relative to the target tissue, the system including one or more pulsed laser diodes and an acoustic transducer driving the one or more pulsed laser diodes to emit optical pulses at one or more wavelengths within a range of 900 nm to 1900 nm. Each optical pulse has a pulse duration between 2 ns and 200 ns, a per-pulse energy between 0.1 J and 200 J, and a repetition frequency between 20 Hz and 20,000 Hz. The method further includes delivering the optical pulses into the target tissue to generate photoacoustic signals, receiving the photoacoustic signals with the acoustic transducer having a center frequency between 0.5 MHz and 60 MHz, and acquiring the photoacoustic signals from the acoustic transducer using a data acquisition system to produce photoacoustic imaging data representative of the target tissue.

[0045] Example 34 relates to the method according to Example 33, further comprising orienting opposing pulsed laser diodes such that optical axes of the pulsed laser diodes intersect at a predetermined depth within a sensing window of the acoustic transducer, the predetermined depth being between 2 cm and 5 cm.

[0046] Example 35 relates to the method according to Example 33, further comprising emitting optical pulses at two or more distinct wavelengths and spectrally unmixing the acquired photoacoustic imaging data to differentiate between oxygenated and deoxygenated hemoglobin or to identify an exogenous contrast agent within the target tissue.

[0047] Example 36 relates to the method according to Example 33, further comprising amplifying the photoacoustic signals using a front-end preamplifier providing at least +40 dB of gain prior to digitization by the data acquisition system.

[0048] Example 37 relates to the method according to Example 33, wherein delivering the optical pulses comprises limiting surface fluence such that emitted laser radiation qualifies as a Class 3B laser or lower while achieving a signal-to-noise ratio of at least 1.1 at a tissue depth between 2 cm and 3 cm.

[0049] The details of one or more examples of the disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the disclosure will be apparent from the description and drawings, and from the claimsBrief Description of the Drawings

[0050] The following drawings are illustrative of particular examples of the present invention and therefore do not limit the scope of invention. The drawings are not necessarily to scale, thoughembodiments can include the scale illustrated, and are intended for use in conjunction with the explanations in the following detailed description wherein like reference characters denote like elements. Examples of the present invention will hereinafter be described in conjunction with the appended drawings.

[0051] FIG 1 A is a schematic figure of a continuous deep-tissue imaging device of an embodiment of the present disclosure.

[0052] FIG 1 B is another schematic of a continuous deep-tissue imaging device of an embodiment of the present disclosure.

[0053] FIG 2A(a) is a bottom side picture of a continuous deep-tissue imaging device of an embodiment of the present disclosure.

[0054] FIG 2A(b) is a side view picture of a continuous deep-tissue imaging device of an embodiment of the present disclosure on a phantom tissue.

[0055] FIG 2A(c) is a display of a PA mode image of results of the use of a continuous deep-tissue imaging device of an embodiment of the present disclosure.

[0056] FIG 2B(a) is a graph showing experimental contrast to noise ratios at different depths of image data collected by a continuous deep-tissue imaging device utilizing a PLD of 1060 nm of an embodiment of the present disclosure.

[0057] FIG 2B(b) is a graph showing experimental contrast to noise ratios at different depths of image data collected by a continuous deep-tissue imaging device utilizing a PLD of 905 nm of an embodiment of the present disclosure.

[0058] FIG 2B(c) is a graph showing experimental blood oxygenation at different depths measured with a continuous deep-tissue imaging device of an embodiment of the present disclosure.

[0059] FIG 2B(d) is a display showing the visual outputs of a continuous deep-tissue imaging device of an embodiment of the present disclosure

[0060] FIG 20(a) is a graph showing another experimental signal to noise ratio at different depths of a continuous deep-tissue imaging device utilizing a PLD of 1060 nm of an embodiment of the present disclosure.

[0061] FIG 2C(b) is a graph showing another experimental signal to noise ratio at different depths of a continuous deep-tissue imaging device utilizing a PLD of 905 nm of an embodiment of the present disclosure

[0062] FIG 20(c) is a graph showing measured blood oxygenation at different depths of a continuous deep-tissue imaging device of an embodiment of the present disclosure.

[0063] FIG 2C(d) is a display showing another experimental visual output of a continuous deep-tissue imaging device of an embodiment of the present disclosure.

[0064] FIG 2D is a display showing another experimental visual output of a continuous deep-tissue imaging device utilizing PLDs of 905 nm and 1060 nm of an embodiment of the present disclosure.

[0065] FIG 3A is a bottom side picture of another embodiment of a continuous deep-tissue imaging device of the present disclosure.

[0066] FIG 3B is a side picture of another embodiment of a continuous deep-tissue imaging device of the present disclosure as it is placed on a phantom tissue.

[0067] FIG 4 is a schematic view of a handheld wireless embodiment of a continuous deep-tissue imaging device of the present disclosure.

[0068] FIG 5 is a schematic view of a benchtop embodiment of a continuous deep-tissue imaging device of the present disclosure.

[0069] FIG 6 is a schematic view of a compact integrated fiber embodiment of a continuous deeptissue imaging device of the present disclosure.

[0070] FIG 7 is a schematic view of a wearable embodiment of a continuous deep-tissue imaging device of the present disclosure.Detailed Description

[0071] For purposes of description herein, the terms “upper,” “lower,” “right,” “left,” “rear,” “front,” “vertical,” “horizontal,” and derivatives thereof shall relate to the disclosure as oriented in FIG. 1. However, it is to be understood that the disclosure may assume various alternative orientations, except where expressly specified to the contrary. It is also to be understood that the specific devices and processes illustrated in the attached drawings, and described in the following specification are simply exemplary embodiments of the inventive concepts defined in the appended claims. Hence, specific dimensions and other physical characteristics relating to the embodiments disclosed herein are not to be considered as limiting, unless the claims expressly state otherwise.

[0072] In the field of medical imaging, assessing tissue oxygenation plays a significant role in diagnosing and monitoring various health conditions. Traditional methods such as pulse oximetryprovide point measurements of blood oxygenation but are limited in their ability to offer comprehensive spatial information about tissue oxygenation. Other techniques, like near-infrared spectroscopy and magnetic resonance imaging (MRI), have been explored to overcome these limitations However, nearinfrared spectroscopy often struggles with accuracy at larger in vivo depths, while MRI, despite its detailed imaging capabilities, remains costly and less accessible for routine clinical use.

[0073] Quantum well laser diodes employ one or more thin active quantum well regions engineered to confine charge carriers and optical modes with high efficiency. Quantum well devices, such as edge or vertically-emitting diodes, have low threshold currents, improved electrooptical efficiency, reduced thermal burden, and more controlled emission profiles relative to laser bar emitters The confinement of optical modes within the quantum well structure yields emission that is inherently concentrated into a smaller angular spread and emitted from a substantially smaller effective source area As a result, quantum well laser diodes can deliver localized optical energy with minimal divergence in comparison to LED sources, even in the absence of external optical focusing components.

[0074] Historically, however, quantum well laser diodes have been viewed as unsuitable for photoacoustic illumination and similar applications requiring short-duration, high peak power optical pulses. Prevailing assumptions in the art held that quantum well devices could not deliver sufficient pulse energy, peak optical power, or tissue penetration depth without aggregating large numbers of emitters into laser bar or stacked architectures. The use of quantum well laser diodes as the primary pulsed illumination source, especially in configurations capable of generating diagnostically useful photoacoustic signals without resorting to laser bar emitters, optical beam shaping assemblies, or energy storage mechanisms such as Q-switching, was neither disclosed nor suggested by conventional approaches. Accordingly, the present systems depart from established design paradigms by demonstrating that quantum well laser diodes can be operated in pulse regimes and system architectures that achieve effective photoacoustic excitation while avoiding the drawbacks inherent to conventional laser solutions.

[0075] Photoacoustic imaging (PAI) has emerged as a promising modality that combines optical and ultrasound techniques to provide deeper imaging capabilities than purely optical methods. Conventional PAI systems rely on bulky, expensive benchtop lasers, such as optical parametric oscillating (OPO) lasers, with high optical throughput requiring dedicated laser rooms and protective equipment for safe usage This poses a significant challenge in the clinical translation of the modality Moreover, theyremain cumbersome, limiting their practical application in point-of-care settings. Additionally, the low pulse repetition rates of these lasers hinder real-time imaging, which is important for dynamic assessments such as visualizing arterial reperfusion. Recent advancements have introduced alternative light sources, such as light-emitting diodes (LEDs), which offer compact and cost-effective solutions. LED-based PA systems, while advantageous in terms of size and cost, often suffer from low optical power output, restricting their imaging depth.

[0076] At the time of invention, LEDs were widely regarded as unsuitable for applications demanding localized photoacoustic excitation from deep tissue without extensive optical conditioning The recognition that quantum well laser diodes could be arranged and operated to provide adequate photoacoustic excitation without such optical elements represents a departure from conventional illumination design and was neither taught nor suggested by LED-based approaches in the prior art Embodiments of the current disclosure address these limitations by introducing a photoacoustic imaging system that leverages a pulsed laser diode (PLD) array capable of emitting light in the second NIR spectrum. Pulsed laser diodes (PLDs) can serve as alternative light sources that generate strong optical pulses at high repetition rates in a portable form factor. Hence, developing an optimized array of PLDs allows deep tissue light delivery while making PA systems portable In some embodiments, such systems would employ compact light sources capable of emitting at wavelengths that reduce optical attenuation in biological tissue and would be amenable to integration within portable or wearable form factors without reliance on bulky laser hardware or complex safety infrastructure.

[0077] Embodiments of certain of the system are designed to enhance imaging depth and quality, providing real-time assessment of tissue oxygenation. By integrating multiple wavelengths, certain embodiments of the system facilitate spectral photoacoustic imaging, allowing for more accurate quantification of oxygenated and deoxygenated hemoglobin concentrations at deep imaging depths. The compact design and high pulse repetition rate of the system make the photoacoustic imaging system suitable for point-of-care applications, offering a practical and efficient solution for non-invasive tissue oxygenation assessment.

[0078] Because lipids, collagen, and hemoglobin exhibit distinct optical absorption spectra within the NIR and NIR-II wavelength bands, certain embodiments utilize multi-wavelength PLD excitation to perform chromophore-specific spectral unmixing. As described in the NIR-II literature, lipids andcollagen are strong absorbers in portions of the NIR-II window, enabling their detection using photoacoustic techniques when appropriate wavelengths are employed.

[0079] PA imaging using wavelengths from the second NIR window (950 - 1400 nm) may be beneficial due to the exponentially reduced tissue scattering and higher safety thresholds of laser exposure to tissues. As described in detail below, it may be demonstrated that contrast-enhanced imaging up to ~6.5 cm depths under porcine tissues and improved quantitative estimations of tissue oxygenation at larger in vivo depths are possible using wavelengths from the second NIR window. As used herein, “near-infrared" (NIR) encompasses the NIR-I window (e.g., -690-950 nm) and the second near-infrared (NIR-II) window (e.g., -950-1900 nm). In certain embodiments, the system employs excitation wavelengths within 900-1900 nm. Operation in the NIR-II can facilitate deeper light penetration and higher permissible exposure limits at the skin (e.g., wavelengths s~1050 nm), supporting imaging at larger depths than typical NIR-I implementations. Hence, an imaging system that utilizes second NIR wavelengths may surprisingly be used more effectively in deep tissue imaging of tissue SO2 compared to traditional wavelengths from the first NIR window.

[0080] In some embodiments, spectral photoacoustic images obtained at two or more wavelengths within the 900-1900 nm range may be processed to estimate spatial distributions of lipid content or collagen-rich structures, leveraging the wavelength-dependent absorption characteristics of these chromophores reported in NIR-II imaging studies.

[0081] As shown in FIG. 1, in some embodiments, the photoacoustic imaging device 10 includes a plurality of pulsed laser diodes (PLD) 20 and a transducer array 22. In some embodiments, the PLDs are second NIR PLDs of two wavelengths and power ratings, 905nm at 120 W, and 1060nm 50 W In still other embodiments, three or more different PLDs may be utilized at varying wavelengths and power ratings The transducer may be a linear array with a center frequency within about 05-60 MHz (e g , -6 MHz in certain examples), although other array topologies and center frequencies may be utilized to accommodate the depth and resolution requirements of the target application

[0082] In some embodiments, the PLDs are NIR PLDs at two or more wavelengths (e.g., 905 nm and 1060 nm), and in other embodiments additional wavelengths within 900-1900 nm may be used, singly or in combination, to enable spectral imaging. In still other embodiments, any number of piezo elements and corresponding center frequency may be utilized

[0083] The PLDs 20 may be arranged in a pair of arrays on either side of the transducer array 22. The PLDs 20 and the transducer array 22 may be pointed downwardly (+z direction as shown in FIG. 1 ) and into the region of interest (ROI) or target tissue 2 being observed. In some embodiments, the PLDs 20 are aligned such that each PLD 20 on opposite sides of the transducer array 22 is focused (i.e., the emissions of opposing PLDs 20 meet) at a depth of 3 cm or more and within the imaging window of the transducer 22. In still other embodiments, the PLD array may be focused at 2 cm, 4 cm, or any other depth with a discernable and achievable signal to noise ratio (e.g., a signal to noise ratio (SNR) up to about 5 cm or greater)

[0084] As shown in the non-limiting example of FIG 1 , the exemplary tissue that is observed is about 5 mm water, 10 mm fat, and about 15 mm muscle In some embodiments, opposing arrays with collimated or partially collimated beams are oriented such that their optical axes intersect at the selected depth (e.g., 2- cm or up to about 5 cm) within the transducer’s field of view.

[0085] In the non-limiting example shown, the integrated probe was used to assess the maximum imaging depth in porcine tissue phantoms. In the non-limiting example shown, PA images were acquired at depths of 2, 3 and 4 cm, although it should be known that images at greater depths may be acquired using the devices and methods disclosed herein. In the non-limiting example shown, light delivery was in plane to the to the acoustic detection PA images were collected with an optical energy of -4 pJ per diode, resulting in a total energy deposition of ~30 pJ at the surface of the porcine phantom. The packaging of the diode, results in wide beam divergence leading to a large beam areas at the sample surface. This results in low surface fluences of - 04.38 mJ / cm2for the entire array, ensuring safe operation under recognized laser safety thresholds. In some embodiments, the maximum surface fluence delivered by the PLD array was -11.5 pJ / cm2(based on the manufacture specifications of diode performance) focused to a region underneath the transducer to maximize light delivery to the imaging target.

[0086] In some embodiments, for deeper targets (e.g., 4-5 cm or more), delivered surface fluence and subsurface fluence profiles can be increased within applicable laser safety thresholds by expanding the number of synchronized PLDs, modulating beam overlap, and / or modestly increasing per-pulse energy while preserving low surface fluence via larger beam area and duty-cycle constraints. In certain embodiments, longer NIR-II wavelengths (e.g., >-1050 nm) can be used at higher permissible exposure levels while maintaining skin safety, enabling enhanced fluence delivery to deeper targets.Selection of wavelengths within 900-1900 nm may be application-specific, balancing absorption contrast of target chromophores against water absorption and tissue scattering, with -950-1300 nm often providing favorable performance for hemoglobin-based measurements.

[0087] In certain of these embodiments, per-pulse optical energy may vary widely depending on diode type and driver configuration In some embodiments, PLDs operate at 0.1-10 pJ per pulse, consistent with demonstrated operation at approximately 700 nJ-4 pJ per diode in phantom and in vivo studies. In other embodiments, higher-power diode packages and driver circuits may be employed to deliver 10-200 p J per pulse per diode while maintaining surface fluence within applicable maximum permissible exposure (MPE) thresholds in the NIR-II band. Such increased energy per diode can improve subsurface fluence and may facilitate deeper imaging depending on tissue optical properties. The pulse duration of each diode excitation may vary depending on driver design and desired imaging performance. In certain of these embodiments, the pulse duration is preferably between 50 ns and 150 ns and more preferably is defined as tp such that tp satisfies tp ~ L I c, where L is a desired spatial resolution and c is a speed of sound in the imaged medium.

[0088] In other embodiments, PLD drivers capable of producing shorter (e.g., 10-80ns) orlonger(e.g., 120-200 ns) nanosecond pulses may be employed. Shorter pulses can increase higher-frequency acoustic content, whereas longer nanosecond pulses can increase the relative contribution of lower-frequency components that attenuate less strongly with depth, potentially improving detectability at deeper tissue layers Adjusting pulse width is a known capability of PLD driver circuitry and may be selected based on application-specific trade-offs between resolution, penetration depth, and signal-to-noise performance.

[0089] As shown in FIGs. 2A-2D, in some embodiments, an imaging device 100 may include the same or similar elements as described in the imaging device 10 from FIG 1A above except as specifically described below, where similar reference numerals may indicate similar elements and structures. In certain of these embodiments, the device 100 includes a housing 110, a plurality of pulsed laser diodes (PLDs) 120 arrayed in sets 124 (in FIG. 2Athe set is indicated on right and the individual PLDs 120 are indicated on the left for ease of reference), and a transducer 122

[0090] While certain examples demonstrate discernable SNR at depths of 2- cm in porcine phantoms, in other embodiments, the system achieves discernable signals at depths up to about 5 cm or more by one or more of: (i) increasing the number of PLDs active per array; (ii) optimizing beamoverlap and focal depth beneath the transducer to concentrate fluence at the desired depth; (Hi) adjusting per-pulse energy within applicable safety limits; (iv) employing higher pulse repetition rates with frame-level averaging while preserving real-time operation; (v) selecting a lower transducer center frequency (e.g., 3-6 MHz) to reduce acoustic attenuation at depth; and / or (vi) incorporating low-noise preamplification and matched-filter reconstruction to improve effective SNR In some embodiments, these adjustments enable SNR > 3 at ~5 cm in tissue-mimicking phantoms and SNR > 5 at shallower depths (e.g., 2-3 cm) for visualization.

[0091] In some embodiments, the housing 110 may be a customized aluminum heatsink with sockets for the PLDs 120 and the transducer array 122. The housing may be any size, shape, and configuration to provide a stable platform for the PLDs 120 and the transducer array 122 and may provide for efficient heat dissipation from the electronic elements of the device 100 Although, in other embodiments, a heatsink may be omitted, and the housing may be made of any suitable material to stably hold the PLDs 120 and the transducer array 122 such as a plastic material, ecoflex or other metallic material.

[0092] In some embodiments, the PLDs 120 are of two wavelengths and power ratings, 905nm at 120 W, and 1060nm at 50 W. In still other embodiments, three or more different PLDs may be utilized at varying wavelengths and power ratings. The transducer 122 may be a linear array with a center frequency within about 0.5-40 MHz (e.g., ~6 MHz in certain examples), although other array topologies and center frequencies may be utilized to accommodate the depth and resolution requirements of the target application In some embodiments, the PLDs are NIR PLDs at two or more wavelengths (e g , 905 nm and 1060 nm), and in other embodiments additional wavelengths within 900-1900 nm may be used, singly or in combination, to enable spectral imaging.

[0093] In some embodiments, the ultrasound transducer may include piezoelectric elements (e.g., PZT-based elements) arranged as a linear array (e.g., ~6 MHz L7-4) to capture photoacoustic signals over the region of interest and optionally to transmit ultrasound for anatomical imaging. Selection of element material and array design may be based on depth and resolution requirements. In still other embodiments, any number of piezo elements and corresponding center frequency may be utilized.

[0094] The PLDs 120 may be arranged in a pair of arrays 124 on either side of the transducer array 122. The PLDs 120 and the transducer array 122 may be pointed downwardly (+z direction as shown in FIG. 1) and into the target tissue 102 being observed. In some embodiments, the PLDs 120 are aligned such that each PLD 120 on opposite sides of the transducer array 122 is focused (i.e., theemissions of opposing PLDs 120 meet) at a depth of 3 cm and within the imaging window of the transducer 122. In still other embodiments, the PLD array may be focused at 2cm, 4cm, or any other depth with an acceptable and achievable signal to noise ratio (e.g , In the non-limiting phantom example, a signal to noise ratio of about 5 or greater).

[0095] In some embodiments, opposing PLDs 120 on opposite sides of the transducer array 122 are wired in series followed by the two sets 124 connected in parallel prior to integration with the heatsink. In other embodiments, the diodes are wired to drive all diodes uniformly to generate the rated maximum optical power. In some embodiments, the diode array is driven using 100 ns pulses (100 Hz frequency) generated by a function generator integrated into a laser driver (not explicitly shown in the figures) In other embodiments, a printed circuit board (PCB) with appropriate driving circuitry will be used to drive the laser diodes (omitting the need for a function generator and / or laser driver) In such embodiments, PA image acquisition is performed using a data acquisition system (DAQ) In certain of these embodiments, the DAQ may be either open or closed architecture.

[0096] Although certain embodiments demonstrate operation at -100 Hz repetition rate, other embodiments may employ repetition rates between 100 Hz and 50,000 Hz, or even higher where supported by the diode driver. High-repetition-rate PLD drivers capable of >100 kHz operation have been described for compact PLD arrays and may be used to increase effective frame-rate or to enable multi-pulse averaging while maintaining real-time performance. Selection of repetition rate may depend on acceptable surface fluence, thermal loading, tissue MPE limits, desired SNR through pulse-averaging, or bandwidth of the paired acoustic transducer. In some embodiments, a front-end preamplifier (e.g., Legion AMP preamplifier (PhotoSound Inc., Houston, TX, USA) is coupled between the transducer output and the acquisition system to increase sensitivity to low-intensity photoacoustic signals generated at large imaging depths, improving effective SNR In a non-limiting example configuration, the light source comprises TO-56 packaged pulsed laser diodes at -905 nm and -1060 nm (e.g., OSRAM SPL UL90AT08 (Munich, Germany) and Brightlaser VD-1060I-050W (Hong Kong)), with multiple diodes connected in series to form each array mounted on either side of a linear ultrasound transducer.

[0097] In certain embodiments, the system includes a front-end preamplifier configured to amplify low-intensity photoacoustic signals with high sensitivity. The preamplifier may provide approximately +40 dB gain with a low-noise, flat input frequency response extending from about 40 kHz to about 45MHz, thereby enhancing detection of both low-frequency and high-frequency acoustic components. In some embodiments, the preamplifier includes an input impedance of about 2.2 MQ, an output impedance of about 50 Q, a compact 128-channel architecture (expandable to 256 or more channels), Cannon DLM260 input / output connectors, and approximately 2 * 25 mm preamplification per channel. The preamplifier may be powered by a 5 VDC, 2.5 A supply and is configured to minimize background noise to preserve weak signals generated at tissue depths of up to about 5 cm.

[0098] In use, in some embodiments, the PLDs 120 of the two different wavelengths generate an optical pulse (e.g., at regular intervals, at times generated by a function generator, or at any other pattern), irradiating the target tissue (e.g., in the non-limiting example shown in FIG. 2A, a hemoglobin loaded tube 104). As the target tissue 102 is stimulated, it vibrates giving off acoustic waves which are sensed by the transducer array 122. The piezo elements within the transducer array 122 translate the acoustic waves sensed into electrical signals, which are then translated into a visual view 126, using reconstruction algorithms as shown in FIG 2A(c)

[0099] In other embodiments, more robust algorithms that reduce computational load and enhance image quality based on desired application may be implemented FIG, 2B shows non-limiting example plots of the contrast-to-noise ratio (CNR) of oxy-Hb (circles), and deoxy-Hb (squares), as a function of imaging depth for data collected at 1060 nm, 700 nJ / pulse (a) & 905 nm, 700 nJ / pulse (b). The noise floor of the system is indicated with the dashed black lines, (c) A plot of the spectrally unmixed oxygenation as a function of imaging depth. The dashed lines in FIG. 2B(c) correspond to the true oxygenation of oxy-Hb and deoxy-Hb, respectively. FIG. 2B(d) shows unmixed oxygenation maps of oxy-Hb and deoxy-Hb at 3 cm imaging depth overlayed on the corresponding B-mode image.

[0100] FIG, 2C shows non-limiting example plots of the signal-to-noise ratio (SNR) of PA signals generated by rat kidney before (circles) and after (squares) euthanasia as a function of imaging depth collected at 1060 nm (a) & 905 nm (b). The noise floor of the system is indicated with the dashed black lines, (c) A plot of average spectrally unmixed renal oxygenation as a function of depth under porcine tissue layers. The dashed lines in FIG. 2C(c) correspond to the true oxygenation of pre- and posteuthanasia, respectively, measured using an oxygen probe. FIG. 2C(d) shows spectrally unmixed oxygenation maps of pre- and post-euthanasia at 3 cm imaging depth overlayed on the corresponding B-mode images.

[0101] As shown in FIG. 2B and FIG. 2C, simulations of the design show that a discernable signal to noise ratio is achievable at a depth of about 3 cm. FIGS. 2B and 2C show the visual outputs 126 at depths of 3cm or more with discernable visual signals. FIGS. 2B(d) and 2C(d) show these visual outputs 126 along with related signal to noise ratio outputs in FIGS. 2B(a-c) and 2C(a-c) from experiments assessing maximum imaging depth, showing that a discernable signal is achievable at a depth of about 3 cm or more. Although FIGS. 2B and 20 illustrate simulated SNR at depths up to 4 cm, in certain embodiments similar simulation frameworks and empirical measurements demonstrate discernable SNR at depths up to about 5 cm or more under comparable optical and acoustic configurations described herein

[0102] In some embodiments, it is demonstrated that the use of an optimized array of high-powered PLDs for deep tissue (~4 cm in phantoms) photoacoustic imaging is achievable Some embodiments demonstrate a clear visualization of perfusion up to depths of 3 cm (with signal to noise ratio up to ~5) without any signal averaging In some embodiments, certain signal processing techniques and amplification circuitry can be included to boost SNR of the PA images. The center frequency and bandwidth of the acoustic transducer may be selected based on depth-resolution trade-offs

[0103] In the non-limiting example as shown in FIG. 2B, the achievable maximum imaging depth using the PLD array coupled probe was assessed using porcine tissue phantoms with an embedded sample tube. Figure 2B(a) & 2A(b) shows the contrast to noise ratio (CNR) of the three target solutions (oxy-Hb and deoxy-Hb) at varying imaging depths using the 1060 nm and 905 nm PLD arrays, respectively. A CNR >1 was observed up to a depth of 4.26 cm when imaging oxy-Hb with both wavelengths. Doubling the fluence (-380 nJ / cm2) proportionally increased CNR 2x at all imaging depths. Estimations of blood oxygenation using spectral unmixing were performed using the images collected at 1060 nm and 905 nm at constant energy (-700 nJ). A parameter map of estimates of blood oxygenation from the spectrally-unmixed images collected at 1060 nm and 905 nm at constant energy (-700 nJ) is shown in Fig 3(d). The values within this map were averaged, omitting the pixels with values below 0% and over 100% (15-25% of pixels removed). Estimated oxygenation values match true oxygenation with accuracy diminishing as a function of imaging depth

[0104] In the non-limiting example shown in FIG. 2C, described is the phantom performance of the NIR-II PLD-PAI system in the environment of in-vivo imaging of rat kidney. Figure 2C(a) & 2C(b) show the signal to noise ratio (SNR) of PA signals generated from the rat kidney acquired at 1060 nm & 905nm, respectively, as a function of varying depths under porcine tissue layers. A 15% increase in PA signals was observed when imaging with 1060 nm compared to 905 nm (FIG. 20(a)). Additionally, a distinct increase in PA signal generated from the pre-euthanized kidney was observed throughout all imaging depths. A detectable PA signal from the rat kidney was observed up to a depth of 4.12 cm under porcine tissue phantoms (FIGS. 20(a) & 20(b)). Renal oxygenation was calculated using the images collected at 1060 nm and 905 nm at constant energy (-700 nJ). In the generated oxygenation map, values within the renal ROI were averaged, omitting the pixels with values below 0% and over 100%. Calculated oxygenation of pre-euthanized kidneys matched with true oxygenation measurements with minimal errors (FIG. 20(c)). Astrong distinction between pre- and post-euthanized renal oxygenation was observed up to a depth of 3.85 cm (FIG. 20(d)).

[0105] The non-limiting example shown in FIG 2D shows PA images collected with 905 nm and 1060 nm wavelengths at the skin surface of the forearm. In the example, the transducer was placed in the cubital fossa of the subject’s arm In the figure, the PAsignal is observed at highly vascularized regions and bone marroe in the forearm using 1060 nm (right image). B-mode ultrasound image collected for anatomical reference points (left image). Images show longitudinal view of the forearm. As shown, the reference bar in the lower left of the left image is 1 cm, although it should be known that the devices and methods described herein may be used for other depths

[0106] In some embodiments, lower-frequency arrays (e.g., -0.5-6 MHz) are favored for deep targets to reduce acoustic attenuation and wavefront distortion in tissue, consistent with the deep-tissue performance observed using a -6 MHz linear array. In other embodiments, higher-frequency arrays (e.g., -10-40 MHz) provide increased axial and lateral resolution for superficial targets at shallower depths. The PA signal’s broadband nature allows detection across these bands, with array selection tailored to the desired depth of field and resolution. The embodiments of this disclosure describe unique advantages that PLDs demonstrate over benchtop sources. Two key differences observed with PLDs compared to traditional nanosecond laser sources are a low pulse energy and larger pulse widths.

[0107] As shown in FIGs. 3A-3B, in some embodiments, an imaging device 200 may include the same or similar elements as described in the imaging devices 10, 100 from FIGs. 1A and 2A above except as specifically described below, where similar reference numerals may indicate similar elements and structures. In certain of these embodiments, the device 200 includes a housing 210, a plurality of pulsed laser diodes (PLDs) 220 arrayed in sets 224 (in FIG. 3Athe set is indicated on right and the individualPLDs 220 are indicated on the left for ease of reference), a transducer 222, and a data cable or data cables 230 in electrical communication with the PLDs 220 and the transducer 222.

[0108] As described in the embodiments herein, depth performance can be application-tuned. In some embodiments, the system is configured for 0-2 cm superficial monitoring (e.g., dermal or subcutaneous vasculature), 2-3 cm for placental or abdominal targets, 3-4 cm for deeper abdominal or musculoskeletal targets, and up to about 5 cm or more where SNR criteria are met (e.g., SNR > 3 at the region of interest). In some embodiments, temporal averaging over 5-50 frames at pulse repetition frequencies (PRF) sufficient to maintain real-time display enables deeper operation without exceeding laser safety guidelines

[0109] In some embodiments, the housing 210 may be a customized aluminum heatsink with sockets for the PLDs 220 and the transducer array 222. The housing may be any size, shape, and configuration to provide a stable platform for the PLDs 220 and the transducer array 222 and may provide for efficient heat dissipation from the electronic elements of the device 200 Although, in other embodiments, a heatsink may be omitted, and the housing may be made of any suitable material to stably hold the PLDs 220 and the transducer array 222 such as a plastic material or other metallic material.

[0110] In some embodiments, the PLDs 220 are of two wavelengths and power ratings, 905nm at 120 W, and 1060nm at 50 W. In still other embodiments, three or more different PLDs may be utilized at varying wavelengths and power ratings. The transducer 222 may be a linear array with a center frequency within about 0.5-40 MHz (e.g., ~6 MHz in certain examples), although other array topologies and center frequencies may be utilized to accommodate the depth and resolution requirements of the target application. In some embodiments, the PLDs are NIR PLDs at two or more wavelengths (e.g., 905 nm and 1060 nm), and in other embodiments additional wavelengths within 900-1900 nm may be used, singly or in combination, to enable spectral imaging.

[0111] The PLDs 220 may be arranged in a pair of arrays 224 on either side of the transducer array 222. The PLDs 220 and the transducer array 222 may be pointed downwardly (+z direction as shown in FIG. 1A) and into the target tissue 202 being observed. In some embodiments, the PLDs 220 are aligned such that each PLD 220 on opposite sides of the transducer array 222 is focused (i.e., the emissions of opposing PLDs 220 meet) at a depth of 3 cm and within the imaging window of the transducer 222. In still other embodiments, the PLD array may be focused at 2 cm, 4 cm, or any otherdepth based on application of interest with an acceptable and achievable signal to noise ratio (e.g., a signal to noise ratio of about 5 or greater)

[0112] In some embodiments, opposing PLDs 220 on opposite sides of the transducer array 222 are wired in series followed by the two sets 224 connected in parallel prior to integration with the heatsink. In some embodiments, the diode array is driven using 100 ns pulses (100 Hz frequency) generated by a function generator integrated to a laser driver (not explicitly shown in the figures) that is then communicated to the PLDs 220 and the transducer 222 through the data cable 230. In such embodiments, PA image acquisition is performed using an open-architecture data acquisition system (DAQ)

[0113] As shown in FIG. 4, in some embodiments, an imaging device 300 may include the same or similar elements as described in the imaging devices 10, 100, and / or 200 from FIGs 1A, 2A, and / or 3A above except as specifically described below, where similar reference numerals may indicate similar elements and structures. In certain ofthese embodiments, the device 300 is a handheld device includes a casing 340, a housing 310, a plurality of pulsed laser diodes (PLDs) 320 arrayed in sets 324 (in FIG.4 the set is indicated on top and the individual PLDs 320 are indicated on the bottom for ease of reference), and a transducer 322

[0114] In some embodiments, the housing 310 may be a customized aluminum heatsink with sockets for the PLDs 320 and the transducer array 322. The housing may be any size, shape, and configuration to provide a stable platform for the PLDs 320 and the transducer array 322 and may provide for efficient heat dissipation from the electronic elements of the device 300 Although, in other embodiments, a heatsink may be omitted, and the housing may be made of any suitable material to stably hold the PLDs 320 and the transducer array 322 such as a plastic material or other metallic material.

[0115] In some embodiments, the PLDs 320 are of two wavelengths and power ratings, 905 nm at 120 W, and 1060 nm at 50 W. In some embodiments, the PLDs are NIR PLDs at two or more wavelengths (e.g., 905 nm and 1060 nm), and in other embodiments additional wavelengths within 900-1900 nm may be used, singly or in combination, to enable spectral imaging. In still other embodiments, three or more different PLDs may be utilized at varying wavelengths and power ratings. The transducer 322 may be a linear array with a center frequency within about 05-40 MHz (e g , ~6 MHz in certain examples), although other array topologies and center frequencies may be utilized to accommodate the depth and resolution requirements of the target application

[0116] In some embodiments, the casing 340 of the imaging device 300 may be any size, shape, and configuration to provide an easy holding platform for a user while providing a stable platform for the housing 310, the PLDs 320, the transducer 322, and other on-board elements (not explicitly shown) such as a data acquisition system (DAQ), PLD drivers, and related electronics for wireless transmission to a display and / or other DAQ.

[0117] The PLDs 320 may be arranged in a pair of arrays 324 on either side of the transducer array 322. The PLDs 320 and the transducer array 322 may be pointed into the target tissue (not explicitly shown in this figure) being observed. In some embodiments, the PLDs 320 are aligned such that each PLD 320 on opposite sides of the transducer array 322 is focused ( i e , the emissions of opposing PLDs 320 meet) at a depth of 3 cm and within the imaging window of the transducer 322. In still other embodiments, the PLD array may be focused at 2 cm, 4 cm, or any other depth with an acceptable and achievable signal to noise ratio (e.g., a signal to noise ratio of about 5 or greater).

[0118] In some embodiments, opposing PLDs 320 on opposite sides of the transducer array 322 are wired in series followed by the two sets 324 connected in parallel prior to integration with the heatsink. In other embodiments, the diodes are wired to drive all diodes uniformly to generate the rated maximum optical power. In some embodiments, the diode array is driven using 100 ns pulses (100 Hz frequency) generated by a function generator integrated to a laser driver (not explicitly shown in the figures) that is on board the imaging device 300. In such embodiments, PA image acquisition is performed using an open-architecture data acquisition system (DAQ) on board the imaging device 300.

[0119] In use, in some embodiments, the PLDs 320 of the two different wavelengths are excited by the function generator, stimulating the target tissue. As the target tissue is stimulated, it vibrates giving off acoustic waves which are sensed by the transducer array 322. The transducer array 322 translates the acoustic waves sensed into electrical signals, which are then transferred to the on-board DAQ and wirelessly transmitted to a display and translated into a visual view (e.g., the view 126 as shown in FIG.2A(c)). It should be known that in some embodiments, only the wireless communication electronics may be on-board the device 300 and all other electronics may be on another device.

[0120] As shown in FIG. 5, in some embodiments, an imaging device 400 may include the same or similar elements as described in the imaging devices 10, 100, 200, and / or 300 from FIGs 1A, 2A, 3A and / or 4 above except as specifically described below, where similar reference numerals may indicate similar elements and structures In certain of these embodiments, the device 400 is a handheld deviceincluding a casing 440, a housing 410, a plurality of pulsed laser diodes (PLDs) 420 arrayed in sets 424 (in FIG. 5 the set is indicated on top and the individual PLDs 420 are indicated on the bottom for ease of reference), a transducer 422, and a data cable or data cables 430 in electrical communication with the PLDs 420, the transducer 422, and a data acquisition system (DAQ) 450.

[0121] In some embodiments, the housing 410 may be a customized aluminum heatsink with sockets for the PLDs 420 and the transducer array 422. The housing may be any size, shape, and configuration to provide a stable platform for the PLDs 420 and the transducer array 422 and may provide for efficient heat dissipation from the electronic elements of the device 400 Although, in other embodiments, a heatsink may be omitted, and the housing may be made of any suitable material to stably hold the PLDs 420 and the transducer array 422 such as a plastic material or other metallic material.

[0122] In some embodiments, the PLDs 420 are of two wavelengths and power ratings, 905 nm at 120 W, and 1060 nm at 50 W. In some embodiments, the PLDs are NIR PLDs at two or more wavelengths (e.g., 905 nm and 1060 nm), and in other embodiments additional wavelengths within 900-1900 nm may be used, singly or in combination, to enable spectral imaging. In still other embodiments, three or more different PLDs may be utilized at varying wavelengths and power ratings.

[0123] In some embodiments, the transducer 422 may include functionality for typical ultrasound techniques in addition to photoacoustic sensing and may have a center frequency between about 0.5 MHz and about 40 MHz, selected according to the intended imaging depth and resolution. The acoustic transducer may be implemented as a one-dimensional linear array integrated with the light delivery geometry to maintain overlap of the optical and acoustic fields of view. In dual-modality configurations, the array transmits ultrasound pulses for B-mode imaging and receives ultrasound and photoacoustic signals for co-registered visualization. In receive-only configurations, the array is operated to detect photoacoustic signals without emitting ultrasound.

[0124] In some embodiments, the casing 440 of the imaging device 400 may be any size, shape, and configuration to provide an easy holding platform for a user while providing a stable platform for the housing 410, the PLDs 420, the transducer 422, and the data cable 430 to reach to the DAQ 450.

[0125] In certain of these embodiments, the PLDs 420 may be arranged in a pair of arrays 424 on either side of the transducer array 422. The PLDs 420 and the transducer array 422 may be pointed into the target tissue (not explicitly shown in this figure) being observed. In some embodiments, the PLDs 420 are aligned such that each PLD 420 on opposite sides of the transducer array 422 is focused( i.e. , the emissions of opposing PLDs 420 meet) at a depth of 3 cm and within the imaging window of the transducer 422. In still other embodiments, the PLD array may be focused at 2 cm, 4 cm, or any other depth with an acceptable and achievable signal to noise ratio (e.g., a signal to noise ratio of about 5 or greater).

[0126] In some embodiments, opposing PLDs 420 on opposite sides of the transducer array 422 are wired in series followed by the two sets 424 connected in parallel prior to integration with the heatsink. In some embodiments, the diode array is driven using 100 ns pulses (100 Hz frequency) generated by a function generator integrated to a laser driver (not explicitly shown in the figures) that is on board the DAQ 450 and in electrical communication with the PLDs 420 and the transducer 422 through the data cable 430 In such embodiments, PA image acquisition is performed using an open architecture on the data acquisition system (DAQ) 450

[0127] In use, in some embodiments, the PLDs 420 of the two different wavelengths are excited by the function generator, stimulating the target tissue. As the target tissue is stimulated, it vibrates giving off acoustic waves which are sensed by the transducer array 422 In some embodiments, the transducer array 422 emits a standard ultrasound waveform and translates the acoustic waves and the ultrasound waves sensed into electrical signals, which are then transferred to the DAQ 450 and transmitted to a display and translated into one or more visual views (e.g., the PA view 426a and the ultrasound view 426b). In some embodiments, certain preamplification circuitry that boosts detection of small signals by while minimizing background noise, can be included. It should be known that in some embodiments, one or the other of the PA view 426a and ultrasound view 426b may be shown at one time. It should also be known that the transducer 422 may be similar to the transducer 22, 122, 222, and / or 322 as described above and only be configured to receive the PA excitation waves

[0128] As shown in FIG. 6, in some embodiments, an imaging or measurement device 500 may include the same or similar elements as described in the imaging devices 10, 100, 200, 300, and / or 400 from FIGs. 1A, 2A, 3A, 4, and / or 5 above except as specifically described below, where similar reference numerals may indicate similar elements and structures. In certain of these embodiments, the device 500 is a handheld device includes a casing 540, a housing 510, a plurality of pulsed laser diodes (PLDs) 520 arrayed around a transducer or piezo element 522, and a data cable or data cables 530 in electrical communication with the PLDs 520, the transducer 522, and a data acquisition system (DAQ) 550.

[0129] In some embodiments, the housing 510 may be a customized aluminum heatsink with sockets for the PLDs 520 and the transducer 522. The housing may be any size, shape, and configuration to provide a stable platform for the PLDs 520 and the transducer 522 and may provide for efficient heat dissipation from the electronic elements of the device 500. Although, in other embodiments, a heatsink may be omitted, and the housing may be made of any suitable material to stably hold the PLDs 520 and the transducer 522 such as a plastic material or other metallic material.

[0130] In some embodiments, the PLDs 520 are of two wavelengths and power ratings, 905 nm at 120 W, and 1060 nm at 50 W. In some embodiments, the PLDs are NIR PLDs at two or more wavelengths (e g , 905 nm and 1060 nm), and in other embodiments additional wavelengths within 900-1900 nm may be used, singly or in combination, to enable spectral imaging. In still other embodiments, three or more different PLDs may be utilized at varying wavelengths and power ratings The transducer 522 may be a single piezo element which may also include functionality for typical ultrasound techniques in addition to the photoacoustic sensing functions as described herein.

[0131] In some embodiments, the casing 540 of the imaging device 500 may be any size, shape, and configuration to provide an easy holding platform for a user while providing a stable platform for the housing 510, the PLDs 520, the transducer 522, and the data cable 530 to reach to the DAQ 550.

[0132] In some embodiments, the PLDs 520 may be arranged around the transducer 522. The PLDs 520 and the transducer 522 may be pointed into the target tissue (not explicitly shown in this figure) being observed. In some embodiments, the PLDs 520 are aligned such that each PLD 520 on opposite sides of the transducer 522 is focused (i.e., the emissions of opposing PLDs 520 meet) at a depth of 3 cm and within the imaging window of the transducer 522. In still other embodiments, the PLD array may be focused at 2 cm, 4 cm, or any other depth with an acceptable and achievable signal to noise ratio (e.g., a signal to noise ratio of about 5 or greater).

[0133] In some embodiments, the diode array is driven using 100 ns pulses (100 Hz frequency) generated by a function generator integrated to a laser driver (not explicitly shown in the figures) that is on board the DAQ 550 and in electrical communication with the PLDs 520 and the transducer 522 through the data cable 530. In such embodiments, PA image acquisition is performed using an open architecture on the data acquisition system (DAQ) 550 In some embodiments, certain preamplification circuitry that boost detection of small signals while minimizing background noise, can be included.

[0134] In use, in some embodiments, the PLDs 520 of the two different wavelengths are excited by the function generator, stimulating the target tissue. As the target tissue is stimulated, it vibrates giving off acoustic waves which are sensed by the transducer 522. In some embodiments, the transducer 522 emits a standard ultrasound waveform and translates the acoustic waves and the ultrasound waves sensed into electrical signals, which are then transferred to the DAQ 550 and transmitted to a display and translated into one or more visual views (e.g., the PA view 426a and the ultrasound view 426b from FIG. 5, a simple waveform akin to oximetry, or any other visual representation). It should be known that in some embodiments, one or the other of the PA view 426a and ultrasound view 426b may be shown at one time It should also be known that the transducer 522 may be similar to the transducer 22, 122, 222, and / or 322 as described above and only be configured to receive the PA excitation waves. It should also be noted that certain signal processing pipelines maybe implemented to perform real-time oximetry.

[0135] As shown in FIG. 7, in some embodiments, an imaging device 600 may include the same or similar elements as described in the imaging devices 10, 100, 200, 300, 400, and / or 500 from FIGs. 1A, 2A, 3A, 4, 5, and / or 6 above except as specifically described below, where similar reference numerals may indicate similar elements and structures. In certain of these embodiments, the device 600 is a wearable device that includes a flexible wrap 660, a housing 610, a plurality of pulsed laser diodes (PLDs) 620 arrayed in sets 624 (in FIG. 7 the set is indicated on right and the individual PLDs 620 are indicated on the left for ease of reference), a transducer 622, and a data cable or data cables 630 in electrical communication with the PLDs 620, the transducer 622, and a data acquisition system (DAQ) 650.

[0136] In some embodiments, the housing 610 may include customized aluminum heatsink with sockets for the PLDs 620 and the transducer array 622. The housing may be any size, shape, and configuration to provide a stable platform for the PLDs 620 and the transducer array 622 and may provide for efficient heat dissipation from the electronic elements of the device 600. Although, in other embodiments, a heatsink may be omitted, and the housing may be made of any suitable material to stably hold the PLDs 620 and the transducer array 622 such as a plastic material or other metallic material

[0137] In some embodiments, the PLDs 620 are of two wavelengths and power ratings, 905 nm at 120 W, and 1060 nm at 50 W In some embodiments, the PLDs are NIR PLDs at two or more wavelengths(e.g., 905 nm and 1060 nm), and in other embodiments additional wavelengths within 900-1900 nm may be used, singly or in combination, to enable spectral imaging. In still other embodiments, three or more different PLDs may be utilized at varying wavelengths and power ratings. The transducer 622 may be a linear array with a center frequency within about 0.5-40 MHz (e.g , ~6 MHz in certain examples), although other array topologies and center frequencies may be utilized to accommodate the depth and resolution requirements of the target application.

[0138] In some embodiments, the flexible wrap 660 of the imaging device 600 may be any size, shape, and configuration to provide a stable wrap around the target tissue to be observed while providing a stable platform and properly orienting the housing 610, the PLDs 620, and the transducer 622

[0139] The PLDs 620 may be arranged in a pair of arrays 624 on either side of the transducer array 622 The PLDs 620 and the transducer array 622 may be pointed into the target tissue (not explicitly shown in this figure) being observed. In some embodiments, the PLDs 620 are aligned such that each PLD 620 on opposite sides of the transducer array 622 is focused (i.e., the emissions of opposing PLDs 620 meet) at a depth of 3 cm and within the imaging window of the transducer 622. In still other embodiments, the PLD array may be focused at 2 cm, 4 cm, or any other depth with an acceptable and achievable signal to noise ratio (e.g., a signal to noise ratio of about 5 or greater).

[0140] In some embodiments, opposing PLDs 620 on opposite sides of the transducer array 622 are wired in series followed by the two sets 624 connected in parallel prior to integration with the heatsink. In some embodiments, the diode array is driven using 100 ns pulses (100 Hz frequency) generated by a function generator integrated to a laser driver (not explicitly shown in the figures) that is on board the DAQ 650 and in electrical communication with the PLDs 620 and the transducer 622 through the data cable 630. In such embodiments, PA image acquisition is performed using an open- or closed-architecture data acquisition system (DAQ) 650. In some embodiments, certain preamplification circuitry that boost detection of small signals while minimizing background noise, can be included.

[0141] In use, in some embodiments, the PLDs 620 of the two different wavelengths are excited by the function generator, stimulating the target tissue. As the target tissue is stimulated, it vibrates giving off acoustic waves which are sensed by the transducer array 622 In some embodiments, the transducer array 622 translates the acoustic waves sensed into electrical signals, which are then transferred to the DAQ 650 and transmitted to a display and translated into one or more visual views (e g , the PA view 426a of FIG 5)

[0142] In certain embodiments, the acoustic detection system comprises a two-dimensional (2D) array or a matrix array configured to receive photoacoustic signals over a volumetric field of view. Such arrays may optionally transmit ultrasound for three-dimensional B-mode imaging and receive both ultrasound and photoacoustic signals for co-registered volumetric imaging. The choice among 1D linear, 2D, or matrix arrays may be based on desired field of view, acquisition speed, and spatial resolution, as well as the depth of the target anatomy. In some embodiments, the acoustic transducer comprises capacitive micromachined ultrasonic transducer (CMUT) elements, implemented as a linear, 2D, or matrix array. CMUT arrays may be configured to receive photoacoustic signals and optionally to transmit ultrasound for co-registered B-mode imaging. In certain embodiments, the system may be configured to detect exogenous contrast agents, such as indocyanine green (ICG) or other NIR-absorbing dyes or nanoparticles, by selecting PLD wavelengths corresponding to their absorption spectra and performing multi-wavelength photoacoustic analysis.

[0143] It will be understood by one having ordinary skill in the art that construction of the described disclosure and other components is not limited to any specific material. Other exemplary embodiments of the disclosure disclosed herein may be formed from a wide variety of materials, unless described otherwise herein.

[0144] For purposes of this disclosure, the term "coupled" (in all of its forms, couple, coupling, coupled, etc.) generally means the joining of two components (electrical or mechanical) directly or indirectly to one another. Such joining may be stationary in nature or movable in nature. Such joining may be achieved with the two components (electrical or mechanical) and any additional intermediate members being integrally formed as a single unitary body with one another or with the two components Such joining may be permanent in nature or may be removable or releasable in nature unless otherwise stated.

[0145] It is also important to note that the construction and arrangement of the elements of the disclosure as shown in the exemplary embodiments is illustrative only. Although only a few embodiments of the present innovations have been described in detail in this disclosure, those skilled in the art who review this disclosure will readily appreciate that many modifications are possible (e.g., variations in sizes, dimensions, structures, shapes and proportions of the various elements, values of parameters, mounting arrangements, use of materials, colors, orientations, etc.) without materially departing from the novel teachings and advantages of the subject matter recited. For example, elementsshown as integrally formed may be constructed of multiple parts or elements shown as multiple parts may be integrally formed, the operation of the interfaces may be reversed or otherwise varied, the length or width of the structures and / or members or connector or other elements of the system may be varied, the nature or number of adjustment positions provided between the elements may be varied. It should be noted that the elements and / or assemblies of the system may be constructed from any of a wide variety of materials that provide sufficient strength or durability, in any of a wide variety of colors, textures, and combinations. Accordingly, all such modifications are intended to be included within the scope of the present innovations. Other substitutions, modifications, changes, and omissions may be made in the design, operating conditions, and arrangement of the desired and other exemplary embodiments without departing from the spirit of the present innovations.

[0146] It will be understood that any described processes or steps within described processes may be combined with other disclosed processes or steps to form structures within the scope of the present disclosure. The exemplary structures and processes disclosed herein are for illustrative purposes and are not to be construed as limiting.

[0147] It is also to be understood that variations and modifications can be made on the aforementioned structures and methods without departing from the concepts of the present disclosure, and further it is to be understood that such concepts are intended to be covered by the following claims unless these claims by their language expressly state otherwise.

[0148] While the various systems described above are separate implementations, any of the individual components, mechanisms, or devices, and related features and functionality, within the various system embodiments described in detail above can be incorporated into any of the other system embodiments herein.

[0149] The terms “about” and “substantially,” as used herein, refers to variation that can occur (including in numerical quantity or structure), for example, through typical measuring techniques and equipment, with respect to any quantifiable variable, including, but not limited to, mass, volume, time, distance, wavelength, frequency, voltage, current, and electromagnetic field. Further, there is certain inadvertent error and variation in the real world that is likely through differences in the manufacture, source, or precision of the components used to make the various components or carry out the methods and the like. The terms “about” and “substantially” also encompass these variations The term “about” and “substantially” can include any variation of 5% or 10%, or any amount - including any integer -between 0% and 10%, as + 20% with respect to power in W, as ± 50nm with respect to optical pulse wavelengths, and as ± 1 MQ with respect to output impedance. Further, whether or not modified by the term “about” or “substantially,” the claims include equivalents to the quantities or amounts. As used herein, “low divergence” refers to an emission profile with a reduced angular spread relative to the diode’s native divergence, obtained by device selection (e.g., surface or edge emitting laser diodes) and / or beam-shaping optics (e g., collimators), sufficient to increase delivered fluence at depth within applicable safety limits.

[0150] Numeric ranges recited within the specification are inclusive of the numbers defining the range and include each integer within the defined range Throughout this disclosure, various aspects of this disclosure are presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges, fractions, and individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1 , 2, 3, 4, 5, and 6, and decimals and fractions, for example, 1 2, 3.8, 11 / 2, and 4% This applies regardless of the breadth of the range As used herein, “discernable” photoacoustic signal refers to signal detectable above background noise according to common SNR metrics (e.g., SNR > 3 for detection, SNR > 5 for visualization), unless otherwise specified.

[0151] Although the various embodiments have been described with reference to preferred implementations, persons skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope thereof.

[0152] Although the various embodiments have been described with reference to preferred implementations, persons skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope thereof.

Claims

ClaimsWhat is claimed is:

1. A photoacoustic imaging system comprising:a housing;one or more pulsed laser diodes configured to emit optical pulses at one or more wavelengths within 900-1900 nm, each pulsed laser diode having a per-pulse energy between 0.1 pJ and 200 pJ and a pulse duration between 2 ns and 200 ns;at least one laser driver configured to supply power and timing signals to the one or more pulsed laser diodes at a pulse repetition frequency between 20 Hz and 20,000 Hz;an acoustic transducer having a center frequency between 0.5 MHz and 60 MHz; and a data acquisition system operably coupled to the acoustic transducer and configured to receive photoacoustic signals generated in a target tissue.

2. The system of claim 1 , wherein the optical pulses comprise wavelengths within 900 nm and 1400 nm.

3. The system of claim 2, wherein the optical pulses comprise wavelengths within 1000 nm and 1200 nm.

4. The system of claim 1, wherein the per-pulse energy is between 0.5 pJ and 100 pJ.

5. The system of claim 4, wherein the per-pulse energy is between 5 pJ and 20 pJ.6 The system of claim 5, wherein the pulse duration is preferably between 50 ns and 150 ns 7. The system of claim 1, wherein the pulse repetition frequency is between 50 Hz and 10,000 Hz8. The system of claim 7, wherein the pulse repetition frequency is between 100 Hz and 5,000 Hz9. The system of claim 1, wherein the at least one laser driver is configured to generate electrical drive pulses having predetermined pulse duration and peak current selected to produce the optical pulses emitted by the one or more pulsed laser diodes.10 The system of claim 1, wherein the optical pulses comprise wavelengths selected from about 905 nm and about 1060 nm.11 The system of claim 1 , wherein each of the one or more pulsed laser diodes are selected from the group consisting of a surface-emitting laser diode and an edge-emitting laser diode12. The system of claim 1, wherein each of the one or more pulsed laser diodes comprises an optical axis, and wherein each of the one or more pulsed laser diodes are configured to be oriented such that the optical axis of opposing pulsed laser diodes intersect at a predetermined depth within a sensing window of the acoustic transducer.

13. The system of claim 12, wherein the predetermined depth is between 2 cm and 5 cm.

14. The system of claim 1, wherein the data acquisition system comprises a front-end preamplifier providing at least +40 dB of gain15. The system of claim 14, wherein the preamplifier has an input impedance of about 2 MO.

16. The system of claim 1, wherein the system achieves a signal-to-noise ratio of at least 1.1 at a tissue depth between 2 cm and 3 cm.

17. The system of claim 1, wherein the system is configured to detect an exogenous contrast agent.

18. The system of claim 1, wherein a surface fluence delivered by each of the one or more pulsed laser diodes is sufficiently low to qualify as a Class 3B laser or lower.

19. The system of claim 1, wherein the system is configured to differentiate between oxygenated and deoxygenated hemoglobin through spectral unmixing of two or more laser wavelengths20. The system of claim 1, wherein the system further comprises a casing having a handheld form factor, the casing further comprising internal power delivery circuitry and wireless communication electronics.21 The system of claim 20, wherein the system is configured to be wearable and further comprises a flexible wrap configured to maintain contact with a patient’s tissue.

22. The system of claim 1 , wherein the acoustic transducer comprises one or more capacitive micromachined ultrasonic transducer (CMUT) elements.

23. The system of claim 1 , wherein the acoustic transducer is arranged as a linear array.

24. The system of claim 1 , wherein the acoustic transducer is arranged as a two-dimensional array.

25. The system of claim 1 , wherein the acoustic transducer is arranged as a matrix array.

26. The system of claim 1 , wherein the optical pulses comprise wavelengths of about 905 nm and about 1060 nm, and wherein the 905 nm laser diodes have a power rating of about 120 W and the 1060 nm laser diodes have a power rating of about 50 W.

27. A photoacoustic imaging system configured for deep-tissue imaging, comprising: a pair of opposing arrays of pulsed laser diodes arranged on opposite sides of an acoustic transducer, each array comprising one or more pulsed laser diodes configured to emit light at two or more wavelengths within a range of 900- 1900 nm;an acoustic transducer having a center frequency between 0.5-60 MHz; and a data acquisition system configured to receive photoacoustic signals and to enable spectral differentiation of tissue chromophores;wherein the opposing arrays are configured to be oriented such that their optical axes intersect at a predetermined depth within a sensing window of the acoustic transducer; andwherein the pulsed laser diodes are configured to be driven at:pulse durations between 2-200 ns;per-pulse energies between 0.1-200 pJ; andrepetition frequencies between 20 Hz and 20,000 Hz.

28. The system of claim 27, wherein the pulsed laser diodes comprise wavelengths of 905 nm and 1060 nm.

29. The system of claim 27, wherein the predetermined depth is between 2 cm and 5 cm.

30. The system of claim 27, wherein the data acquisition system comprises a preamplifier providing at least +40 dB of gain.

31. The system of claim 30, wherein the preamplifier has an input impedance of about 2 MQ.

32. The system of claim 27, further comprising a casing having a handheld form factor, the casing further comprising internal power delivery circuitry and wireless communication electronics.

33. A method of performing photoacoustic imaging of a target tissue, comprising:(a) positioning a photoacoustic imaging system relative to a target tissue, the system including one or more pulsed laser diodes and an acoustic transducer; (b) driving the one or more pulsed laser diodes to emit optical pulses at one or more wavelengths within a range of 900 nm to 1900 nm, each optical pulse having a pulse duration between 2 ns and 200 ns, a per-pulse energy between 0.1 pJ and 200 p J, and a repetition frequency between 20 Hz and 20,000 Hz;(c) delivering the optical pulses into the target tissue to generate photoacoustic signals;(d) receiving the photoacoustic signals with the acoustic transducer having a center frequency between 0.5 MHz and 60 MHz; and(e) acquiring the photoacoustic signals from the acoustic transducer using a data acquisition system to produce photoacoustic imaging data representative of the target tissue.

34. The method of claim 33, further comprising orienting opposing pulsed laser diodes such that optical axes of the pulsed laser diodes intersect at a predetermined depth within a sensing window of the acoustic transducer, the predetermined depth being between 2 cm and 5 cm.

35. The method of claim 33, further comprising emitting optical pulses at two or more distinct wavelengths and spectrally unmixing the acquired photoacoustic imaging data to differentiate between oxygenated and deoxygenated hemoglobin or to identify an exogenous contrast agent within the target tissue36. The method of claim 33, further comprising amplifying the photoacoustic signals using a front-end preamplifier providing at least +40 dB of gain prior to digitization by the data acquisition system.37 The method of claim 33, wherein delivering the optical pulses comprises limiting surface fluence such that emitted laser radiation qualifies as a Class 3B laser or lower while achieving a signal-to-noise ratio of at least 1.1 at a tissue depth between 2 cm and 3 cm.

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