The present disclosure generally relates to imaging systems, and particularly, to photoacoustic microscopy systems.
Photoacoustic imaging modality has emerged as a new era of biomedical imaging which comprises a good balance between contrast, resolution, and penetration depth. Using a laser as an illumination source and an ultrasonic transducer as a receiver, both penetration depth and image contrast may be improved compared to ultrasonic or optical imaging systems. In a photoacoustic microscopy (PAM) regime, acoustic waves or an optical beam may be focused on a surface of an object utilizing an acoustic or an optical lens, respectively, with a high numerical aperture (NA). However, due to an inverse proportionality of depth-of-focus (DOF) and NA, a resultant lateral resolution and signal-to-noise ratio (SNR) in out-of-focus regions may be severely degraded. There is, therefore, a need for a method that may achieve improved and uniform lateral resolution in both focus and out-of-focus regions. There is also a need for a method that may afford depth-invariant lateral resolution in both focus and out-of-focus regions so that high-quality volumetric imaging may be provided.
This summary is intended to provide an overview of the subject matter of this patent, and is not intended to identify essential elements or key elements of the subject matter, nor is it intended to be used to determine the scope of the claimed implementations. The proper scope of this patent may be ascertained from the claims set forth below in view of the detailed description below and the drawings.
In one general aspect, the present disclosure describes an exemplary for super-resolution photoacoustic microscopy imaging of an object. An exemplary method may include optically exciting the object according to a plurality of excitation patterns utilizing a digital micromirror device (DMD), receiving a plurality of acoustic waves propagated from the object due to optically exciting the object, reconstructing each of a plurality of photoacoustic (PA) images from a respective acoustic wave of the plurality of acoustic waves, and obtaining a super-resolution PA image of the object from the plurality of PA images by applying a frequency domain reconstruction method to the plurality of PA images. In an exemplary embodiment, each of the plurality of acoustic waves may be associated with a respective excitation pattern of the plurality of excitation patterns.
In an exemplary embodiment, optically exciting the object may include emitting a laser beam to the DMD, generating a plurality of modulated light beams from the laser beam by producing a plurality of periodic square patterns (PSPs) via the DMD, generating a plurality of sinusoidal spatial fringe (SSF) patterns from the plurality of PSPs by filtering the plurality of modulated light beams, and exciting the object by emitting each of the plurality of SSF patterns to the object. In an exemplary embodiment, each of the plurality of PSPs may be associated with a respective excitation pattern of the plurality of excitation patterns and may include a respective orientation of a plurality of orientations and a respective phase shift of a plurality of phase shifts. In an exemplary embodiment, optically exciting the object may further include reflecting the laser beam to the object by the DMD.
In an exemplary embodiment, emitting the laser beam to the DMD may include generating the laser beam by a laser, reflecting the laser beam to a beam expander by a first mirror, generating an expanded laser beam from the laser beam by expanding a width of the laser beam utilizing the beam expander, and reflecting the expanded laser beam to the DMD by a second mirror.
In an exemplary embodiment, expanding the width of the laser beam may include converging the laser beam at a first focal point of a first optical lens and collimating a diverging light beam from the first focal point by placing a second focal point of a second optical lens at the first focal point.
In an exemplary embodiment, producing the plurality of PSPs may include producing each of the plurality of PSPs at a respective orientation of the plurality of orientations and a respective phase shift of the plurality of phase shifts. In an exemplary embodiment, producing each of the plurality of PSPs at a respective orientation of the plurality of orientations may include setting each of the plurality of orientations to one of 0, π/4, π/2, and 3π/4. In an exemplary embodiment, producing each of the plurality of PSPs at a respective phase shift of the plurality of phase shifts may include shifting each of the plurality of PSPs on the DMD by a phase shift equal to one of 0, π/2, and π.
In an exemplary embodiment, filtering the plurality of modulated light beams may include converging the plurality of modulated light beams at a third focal point of a third optical lens, filtering high-order spatial frequencies of the plurality of modulated light beams by passing the plurality of modulated light beams through a pinhole, and collimating a plurality of diverging light beams from the third focal point by placing a fourth focal point of a fourth optical lens at the third focal point. An exemplary pinhole may be placed at the third focal point. In an exemplary embodiment, collimating the plurality of diverging light beams may include reflecting the plurality of diverging light beams to the fourth optical lens by a third mirror.
In an exemplary embodiment, applying the frequency domain reconstruction method may include obtaining a plurality of filtered PA images by low-pass filtering each of the plurality of PA images, obtaining a plurality of down-shifted components from the plurality of filtered PA images by applying a phase compounding method to the plurality of filtered PA images, extracting a plurality of high-frequency components from the plurality of down-shifted components by high-pass filtering the plurality of down-shifted components, and generating the super-resolution PA image by applying an inverse Fourier transform to the plurality of high-frequency components. In an exemplary embodiment, each of the plurality of down-shifted components may be associated with a respective orientation of the plurality of orientations.
In an exemplary embodiment, low-pass filtering each of the plurality of PA images may include passing each of the plurality of PA images through a low-pass filter. In an exemplary embodiment, high-pass filtering the plurality of down-shifted components may include passing the plurality of down-shifted components through a high-pass filter.
Other exemplary systems, methods, features and advantages of the implementations will be, or will become, apparent to one of ordinary skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features and advantages be included within this description and this summary, be within the scope of the implementations, and be protected by the claims herein.
The drawing figures depict one or more implementations in accord with the present teachings, by way of example only, not by way of limitation. In the figures, like reference numerals refer to the same or similar elements.
In the following detailed description, numerous specific details are set forth by way of examples in order to provide a thorough understanding of the relevant teachings. However, it should be apparent that the present teachings may be practiced without such details. In other instances, well known methods, procedures, components, and/or circuitry have been described at a relatively high-level, without detail, in order to avoid unnecessarily obscuring aspects of the present teachings.
The following detailed description is presented to enable a person skilled in the art to make and use the methods and devices disclosed in exemplary embodiments of the present disclosure. For purposes of explanation, specific nomenclature is set forth to provide a thorough understanding of the present disclosure. However, it will be apparent to one skilled in the art that these specific details are not required to practice the disclosed exemplary embodiments. Descriptions of specific exemplary embodiments are provided only as representative examples. Various modifications to the exemplary implementations will be readily apparent to one skilled in the art, and the general principles defined herein may be applied to other implementations and applications without departing from the scope of the present disclosure. The present disclosure is not intended to be limited to the implementations shown, but is to be accorded the widest possible scope consistent with the principles and features disclosed herein.
Herein are disclosed an exemplary method for super-resolution photoacoustic microscopy. An exemplary method may generate sinusoidal spatial fringe patterns (SSFs) by emitting laser beams to a digital micromirror device (DMD). An exemplary DMD may be programmed to produce SSFs at several different orientations and phase shifts. Exemplary SSFs may be emitted to a target object. Exemplary acoustic waves may be generated at the target object due to optically exciting the object by the SSFs. The exemplary acoustic waves may be received by an ultrasound transducer (UST). Exemplary photoacoustic (PA) images may then be reconstructed from each acoustic wave received by the UST. Through optical excitation of the targeted object with exemplary SSF patterns, the object's frequency spectrum may shift in the spatial frequency domain. An exemplary down-shifted component may be extracted from the object's frequency spectrum by combining different PA images that correspond to different phase shifts. An exemplary frequency shifting may lead to the passage of high-frequency contents of the object through the passband of an acoustic diffraction frequency response of the UST. Low-frequency and high-frequency images that are captured at different orientations may then be combined as a wide-band image through a phase compounding method. As a result, an exemplary super-resolution image with an enhanced lateral resolution may be obtained.
In further detail regarding step 102,
For further detail with respect to step 110,
Referring to
In an exemplary embodiment, system 200 may further include a first mirror 216 and a beam expander 218. In an exemplary embodiment, first mirror 216 may reflect laser beam 210 to beam expander 218 in step 120. Using first mirror 216 may allow for reflecting laser beam 210 to beam expander 218 in a perpendicular direction to improve imaging quality.
In further detail regarding step 122,
In further detail regarding step 126,
In an exemplary embodiment, beam expander 218 may further include a second optical lens 306. In an exemplary embodiment, second optical lens 306 may collimate a diverging light beam 308 from first focal point 304. For this purpose, an exemplary second focal point of second optical lens 306 may be placed at first focal point 304 in step 128 so that diverging light beam 308 may be emitted to second optical lens 306 from the second focal point. As a result, in an exemplary embodiment, laser beam 210 may be converted to an expanded laser beam 310 which has a larger width compared to laser beam 210.
Referring again to
Referring again to
In further detail with respect to producing PSP 400 may be produced via DMD 202,
Referring again to
In further detail regarding step 130,
Referring to
where λ is a wavelength of plurality of SSF patterns 506, fL3 is a focal length of third optical lens 602 (i.e., a distance between third optical lens 602 and third focal point 606), fL4 is a focal length of fourth optical lens 604 (i.e., a distance between fourth optical lens 604 and an exemplary fourth focal point of fourth optical lens 604 that coincides with third focal point 606), and fSSF is a frequency of plurality of SSF patterns 506 that is given by fSSF=2πfL3/fL4.
In an exemplary embodiment, step 134 may include collimating plurality of diverging light beams 610 from third focal point 606. For this purpose, an exemplary fourth focal point of fourth optical lens 604 may be placed at third focal point 606 so that plurality of diverging light beams 610 may be emitted to fourth optical lens 604 from third focal point 606. As a result, exemplary collimated beams 612 that include 0th and ±1st diffraction order components of plurality of modulated light beams 212 may shrink in width (up to about 1.7) compared to plurality of modulated light beams 212, which may lead to improvement in the signal to noise ratio (SNR) of plurality of SSF patterns 506.
Due to the filtering effect of pinhole 608, in an exemplary embodiment, only the zero-order frequency, DC, and ±1 order frequency components of plurality of modulated light beams 212 may pass through pinhole 608. Therefore, after passage through setup 500, plurality of SSF patterns 506 may consist of a normal propagating plane-wave and two inclined plane-waves E+ and E− corresponding to the +1 order frequency component and −1 order frequency component, respectively. In an exemplary embodiment, inclined plane-waves E+ and E− may propagate in an inclined direction with respect to the normal direction and may be determined according to an operation defined by the following:
where i is the unit imaginary number, x, y, and z are horizontal, vertical, and axial coordinates, respectively, in a Cartesian coordinate system, kz is a spatial angular frequency of the propagating plane-waves, and φ is phase shift 405 that may be applied through shifting PSP 400 on DMD 202. Variables kx
where θ and fPSP represent orientation 404 and spatial frequency 406, respectively.
Based on Equations (2a) and (2b), in an exemplary embodiment, an interference ESSF of a normal propagating plane-wave Edc and two inclined plane-waves E+ and E− may become as follows:
According to Equation (4), in an exemplary embodiment, a 3-D profile ISSFφ of a produced SSF intensity pattern of plurality of SSF patterns 506 may be represented as:
Referring again to
Referring again to
In an exemplary embodiment, object 208 may be further excited by a normal illumination (NI) by laser beam 210 in step 117. For this purpose, in an exemplary embodiment, all micromirrors of DMD 202 may be set to the “on” state so that expanded laser beam 310 may be entirely reflected to object 208.
Referring again to
In an exemplary embodiment, step 106 may include reconstructing a PA image from an acoustic wave p0(x,y,z). An exemplary PA image may be reconstructed based on Equations (5) and (6) according to the following:
where P0φ (kx,ky,z) is a value of an exemplary PA image in a wavenumber (i.e., spatial frequency) domain (kx,ky) that is reconstructed from an acoustic wave produced at a depth z of object 208 in response to emitting an exemplary SSF pattern to object 208 that is generated from PSP 400 at orientation θ and phase shift φ, FT2D{⋅}x,y is a two dimensional (2-D) Fourier transform from spatial domain (x,y) to spatial frequency domain (kx,ky), Mα(kx,ky,z) is the wavenumber domain representation of optical absorption distribution μα(x,y,z), and ⊗ is the convolution operator.
According to Equations (5) and (7), illumination of object 208 by an exemplary SSF pattern may cause the spatial frequency spectrum of object 208 to become downshifted and upshifted with [kx
In further detail regarding step 108,
For further detail with respect to step 136, in an exemplary embodiment, frequency components of the plurality of PA images that are out of a diffraction limit (i.e., a limit out of which PA signals are diffracted) may be lower than the noise level of system 200 and thus may be invalid. Therefore, in an exemplary embodiment, each of the plurality of PA images may be passed through a low-pass filter. A cut-off frequency of an exemplary low-pass filter may be set equal to a spatial spectral bandwidth of UST 204 in
In further detail with regards to step 138, in an exemplary embodiment, the plurality of down-shifted components may be obtained from the plurality of filtered PA images by applying the phase compounding method to the plurality of filtered PA images. In an exemplary embodiment, applying the phase compounding method to the plurality of filtered PA images may include calculating a first down-shifted component of the plurality of down-shifted components. An exemplary first down-shifted component {circumflex over (M)}α(kx−kx
where {circumflex over (P)}0NI (kx,ky,z) is a representation of an exemplary PA image in wavenumber domain (kx,ky) that is reconstructed by UST 204 from an acoustic wave produced at depth z of object 208 due to normal illumination of object 208 by laser beam 210 through reflecting laser beam 310 to object 208 by DMD 202 and {circumflex over (P)}0φ
{circumflex over (P)}0NI(kx,ky,z)=P0NI(kx,ky,z)·PSF(kx,ky) Equation (9a)
{circumflex over (P)}0φ
where P0NI(kx,ky,z) is an exemplary representation of a PA image in wavenumber domain (kx,ky) that is reconstructed from an acoustic wave generated due to normal illumination of object 208 (discussed in step 117 above) and PSF(kx,ky) is a frequency domain representation of a point spread function (PSF) of UST 204. An exemplary value of P0φ
Referring again to
Considering the symmetry of absorption distribution spectrum Mα(kx,ky,z) in the Fourier domain, an exemplary second down-shifted component of the plurality of down-shifted components may be calculated at an orientation π+0 of the plurality of orientations by flipping and conjugating of first down-shifted component {circumflex over (M)}α(kx−kx
For further detail with respect to step 140, in an exemplary embodiment, high-frequency components of reconstructed PA images obtained for different orientation 404 values described above may overlap low-frequency components of NI reconstruction in Equation (8), causing disturbance in estimated low-frequency values of first down-shifted component {circumflex over (M)}α(kx−kx
In further detail with regarding step 142, to generate an exemplary super-resolution PA image, the plurality of high-frequency components that may be obtained at different orientations in steps 136-140 may be combined as a single image in spatial frequency domain (kx,ky). An exemplary super-resolution PA image may then be generated by applying an inverse Fourier transform to the frequency-domain image. In an exemplary embodiment, the abovementioned process may be performed for different depths of object 208 (i.e., along the z axis) to obtain a three-dimensional (3-D) image of object 208.
If programmable logic is used, such logic may execute on a commercially available processing platform or a special purpose device. One ordinary skill in the art may appreciate that an embodiment of the disclosed subject matter can be practiced with various computer system configurations, including multi-core multiprocessor systems, minicomputers, mainframe computers, computers linked or clustered with distributed functions, as well as pervasive or miniature computers that may be embedded into virtually any device.
For instance, a computing device having at least one processor device and a memory may be used to implement the above-described embodiments. A processor device may be a single processor, a plurality of processors, or combinations thereof. Processor devices may have one or more processor “cores.”
An embodiment of the invention is described in terms of this example computer system 700. After reading this description, it will become apparent to a person skilled in the relevant art how to implement the invention using other computer systems and/or computer architectures. Although operations may be described as a sequential process, some of the operations may in fact be performed in parallel, concurrently, and/or in a distributed environment, and with program code stored locally or remotely for access by single or multiprocessor machines. In addition, in some embodiments the order of operations may be rearranged without departing from the spirit of the disclosed subject matter.
Processor device 704 may be a special purpose (e.g., a graphical processing unit) or a general-purpose processor device. As will be appreciated by persons skilled in the relevant art, processor device 704 may also be a single processor in a multi-core/multiprocessor system, such system operating alone, or in a cluster of computing devices operating in a cluster or server farm. Processor device 704 may be connected to a communication infrastructure 706, for example, a bus, message queue, network, or multi-core message-passing scheme.
In an exemplary embodiment, computer system 700 may include a display interface 702, for example a video connector, to transfer data to a display unit 730, for example, a monitor. Computer system 700 may also include a main memory 708, for example, random access memory (RAM), and may also include a secondary memory 710. Secondary memory 710 may include, for example, a hard disk drive 712, and a removable storage drive 714. Removable storage drive 714 may include a floppy disk drive, a magnetic tape drive, an optical disk drive, a flash memory, or the like. Removable storage drive 714 may read from and/or write to a removable storage unit 718 in a well-known manner. Removable storage unit 718 may include a floppy disk, a magnetic tape, an optical disk, etc., which may be read by and written to by removable storage drive 714. As will be appreciated by persons skilled in the relevant art, removable storage unit 718 may include a computer usable storage medium having stored therein computer software and/or data.
In alternative implementations, secondary memory 710 may include other similar means for allowing computer programs or other instructions to be loaded into computer system 700. Such means may include, for example, a removable storage unit 722 and an interface 720. Examples of such means may include a program cartridge and cartridge interface (such as that found in video game devices), a removable memory chip (such as an EPROM, or PROM) and associated socket, and other removable storage units 722 and interfaces 720 which allow software and data to be transferred from removable storage unit 722 to computer system 700.
Computer system 700 may also include a communications interface 724. Communications interface 724 allows software and data to be transferred between computer system 700 and external devices. Communications interface 724 may include a modem, a network interface (such as an Ethernet card), a communications port, a PCMCIA slot and card, or the like. Software and data transferred via communications interface 724 may be in the form of signals, which may be electronic, electromagnetic, optical, or other signals capable of being received by communications interface 724. These signals may be provided to communications interface 724 via a communications path 726. Communications path 726 carries signals and may be implemented using wire or cable, fiber optics, a phone line, a cellular phone link, an RF link or other communications channels.
In this document, the terms “computer program medium” and “computer usable medium” are used to generally refer to media such as removable storage unit 718, removable storage unit 722, and a hard disk installed in hard disk drive 712. Computer program medium and computer usable medium may also refer to memories, such as main memory 708 and secondary memory 710, which may be memory semiconductors (e.g. DRAMs, etc.).
Computer programs (also called computer control logic) are stored in main memory 708 and/or secondary memory 710. Computer programs may also be received via communications interface 724. Such computer programs, when executed, enable computer system 700 to implement different embodiments of the present disclosure as discussed herein. In particular, the computer programs, when executed, enable processor device 704 to implement the processes of the present disclosure, such as the operations in method 100 illustrated by flowcharts of
Embodiments of the present disclosure also may be directed to computer program products including software stored on any computer useable medium. Such software, when executed in one or more data processing device, causes a data processing device to operate as described herein. An embodiment of the present disclosure may employ any computer useable or readable medium. Examples of computer useable mediums include, but are not limited to, primary storage devices (e.g., any type of random access memory), secondary storage devices (e.g., hard drives, floppy disks, CD ROMS, ZIP disks, tapes, magnetic storage devices, and optical storage devices, MEMS, nanotechnological storage device, etc.).
The embodiments have been described above with the aid of functional building blocks illustrating the implementation of specified functions and relationships thereof. The boundaries of these functional building blocks have been arbitrarily defined herein for the convenience of the description. Alternate boundaries can be defined so long as the specified functions and relationships thereof are appropriately performed.
In this example, lateral resolution of an implementation of method 100 in an axial imaging range is evaluated.
In this example, the performance of an implementation of method 100 for imaging a Ronchi-ruling test target with a spatial frequency of about 15 lp/mm and an about 135° orientation is demonstrated. The Ronchi-ruling test target is used as an imaging target (analogous to object 208 in
In order to image the down-shifted frequency content of the Ronchi-ruling test target, an implementation of the phase compounding method in step 138 of method 100 may be applied to three exemplary obtained images resulted from illuminations of an about 135° oriented pattern at about 0°, 90°, and 180° phase shifts.
While the foregoing has described what are considered to be the best mode and/or other examples, it is understood that various modifications may be made therein and that the subject matter disclosed herein may be implemented in various forms and examples, and that the teachings may be applied in numerous applications, only some of which have been described herein. It is intended by the following claims to claim any and all applications, modifications and variations that fall within the true scope of the present teachings.
Unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, including in the claims that follow, are approximate, not exact. They are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain.
The scope of protection is limited solely by the claims that now follow. That scope is intended and should be interpreted to be as broad as is consistent with the ordinary meaning of the language that is used in the claims when interpreted in light of this specification and the prosecution history that follows and to encompass all structural and functional equivalents.
Except as stated immediately above, nothing that has been stated or illustrated is intended or should be interpreted to cause a dedication of any component, step, feature, object, benefit, advantage, or equivalent to the public, regardless of whether it is or is not recited in the claims.
It will be understood that the terms and expressions used herein have the ordinary meaning as is accorded to such terms and expressions with respect to their corresponding respective areas of inquiry and study except where specific meanings have otherwise been set forth herein. Relational terms such as first and second and the like may be used solely to distinguish one entity or action from another without necessarily requiring or implying any actual such relationship or order between such entities or actions. The terms “comprises,” “comprising,” or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. An element proceeded by “a” or “an” does not, without further constraints, preclude the existence of additional identical elements in the process, method, article, or apparatus that comprises the element.
The Abstract of the Disclosure is provided to allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. In addition, in the foregoing Detailed Description, it can be seen that various features are grouped together in various implementations. This is for purposes of streamlining the disclosure, and is not to be interpreted as reflecting an intention that the claimed implementations require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed implementation. Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separately claimed subject matter.
While various implementations have been described, the description is intended to be exemplary, rather than limiting and it will be apparent to those of ordinary skill in the art that many more implementations and implementations are possible that are within the scope of the implementations. Although many possible combinations of features are shown in the accompanying figures and discussed in this detailed description, many other combinations of the disclosed features are possible. Any feature of any implementation may be used in combination with or substituted for any other feature or element in any other implementation unless specifically restricted. Therefore, it will be understood that any of the features shown and/or discussed in the present disclosure may be implemented together in any suitable combination. Accordingly, the implementations are not to be restricted except in light of the attached claims and their equivalents. Also, various modifications and changes may be made within the scope of the attached claims.
This application takes priority from U.S. Provisional Patent Application Ser. No. 63/230,841 filed on Aug. 9, 2021, and entitled “SUPER-RESOLUTION PHOTOACOSUTIC MICROSCOPY TO BEYOND DIFFRACTION LIMIT”, which is incorporated herein by reference in its entirety.
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