Patent Application
20160143542
This invention relates to a method, system, and device for minimally invasive optical-resolution photoacoustic endoscopy. Particularly, it relates to using a multimode waveguide having optical-in and acoustic-out properties, to perform both optical excitation and remote acoustic detection at the same tip of the waveguide, in the context of photoacoustic endoscopy, for example photoacoustic imaging at depth into a sample such as biological tissue.
Photoacoustic microscopy (PAM) is a rapidly evolving imaging technique that is capable of delivering multi-scale images based on the optical absorption properties of the investigated sample. See Paul Beard. “Biomedical photoacoustic imaging,” Interface Focus, Vol. 1, No. 4, pp. 602-631, 2011. Absorption of laser pulses by the sample locally generates acoustic waves via the photoacoustic effect. An acoustic transducer is generally used to detect the generated acoustic waves enabling the formation of an image. One of the advantages of photoacoustic microscopy is that it can provide either label-free images of biological tissues, in which case the contrast rises from the intrinsic variation of optical absorption coefficient. See H. F. Zhang, K. Maslov, G. Stoica and L. V. Wang. “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nature Biotechnology, Vol. 24, No. 7, pp. 848-851, 2006. See also K. Maslov, H. F. Zhang, S. Hu and L. V. Wang. “Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries,” Optics Letters, Vol. 33, No. 9, pp. 929-931, 2008. Also, images of tissue based on exogenous contrast agents can be used to target and image specific structures and metabolisms. Photoacoustic microscopy approaches can be divided in two categories, based on the image resolution. In acoustic-resolution photoacoustic microscopy (AR-PAM), the image resolution is dictated by the frequency response of the ultrasound detection device. With this approach, images with resolution ranging from millimeter to less than a hundred microns can be obtained at depths much larger than the optical transport mean free path, typically 1 mm in biological tissue, where purely optical techniques are limited by multiple scattering. See V. Ntziachristos. “Going deeper than microscopy: the optical imaging frontier in biology,” Nature Methods, Vol. 7, No. 8, pp. 603-614, 2010. The image reconstruction is based on acquiring ultrasound signals for different positions of the transducers, either by scanning a single element transducer or by using multi-element probes.
In optical-resolution photoacoustic microscopy, the excitation light is focused into a diffraction-limited spot, usually with an objective lens. In this configuration the optical energy is deposited on the sample, and therefore the region that generates the acoustic waves, are limited only to the illuminated diffraction-limited voxel, yielding photoacoustic images with optical resolution. See Z. Xie, S. Jiao, H. F. Zhang and C. A. Puliafito. “Laser-scanning optical-resolution photoacoustic microscopy,” Optics Letters, Vol. 34, No. 12, pp. 1771-1773, 2009, see also P. Hajireza, W. Shi and R. J. Zemp. “Label-free in vivo fiber-based optical-resolution photoacoustic microscopy,” Optics Letters, Vol. 36, No. 20, pp. 4107-4109, 2011. The generation of full-sized images is based on the raster scanning of the optical excitation spot. However, as OR-PAM relies on the ability to focus light into the sample of interest, it is feasible only within the ballistic regime of optical propagation in scattering media, therefore generally limited to penetration depths smaller than 1 mm for biological tissue.
While the imaging depth of AR-PAM is limited by the so called hard limit of optical penetration, dominated by the absorption properties of the investigated tissue, the imaging depth of optical-resolution photoacoustic microscopy (OR-PAM) is limited by the optical transport mean free path. In order to overcome these limitations, endoscopic modalities have been deployed for the acquisition of photoacoustic images deep inside tissue cavities. Similar to conventional optical endoscopy, fiber bundle endoscopes have been adapted to add photoacoustic imaging capabilities. See P. Shao, W. Shi, P. Hajireza and R. J. Zemp. “Integrated micro-endoscopy system for simultaneous fluorescence and optical-resolution photoacoustic imaging,” Journal of Biomedical Optics, Vol. 17, No. 7, 2012. A different approach of a purely photoacoustic endoscope has also been proposed. See J.-M. Yang, K. Maslov, H.-C. Yang, Q. Zhou, K. K. Shung and L. V. Wang. “Photoacoustic endoscopy,” Optics Letters, Vol. 34, No. 10, pp. 1591-1593, 2009, see also Y. Yuan, S. Yang and D. Xing. “Preclinical photoacoustic imaging endoscope based on acousto-optic coaxial system using ring transducer array,” Optics Letters, Vol. 35, No. 13, pp. 2266-2268, 2010. In these publications, a single mode fiber is used for the delivery of a diffused excitation optical field and the integrated transducer picks up the acoustic signal. These devices are equipped with a rotational motor so that the excitation and detected field can be scanned around the endoscope's axis, and these devices are still limited in terms of resolution, ˜58 μm lateral resolution and the smallest achieved diameter of the endoscopic head was 2.5 mm. See J.-M. Yang, R. Chen, C. Favazza, J. Yao, C. Li, Z. Hu, Q. Zhou, K. K. Shung and L. V. Wang. “A 2.5-mm diameter probe for photoacoustic and ultrasonic endoscopy,” Optics Express, Vol. 20, No. 21, pp. 23944-23953, 2012.
Fiber bundle endoscopes, where each of the single mode fibers of the device acts as a single pixel of the final image, dominate the commercial domain, however the resolution is limited by the distance between adjacent fiber cores, usually ˜5 μm. See A. F. Gmitro and D. Aziz. “Confocal microscopy through a fiberoptic imaging bundle,” Optics Letters, Vol. 18, No. 8, pp. 565-567, 1993. Designs that combine optical fibers, conventional focusing optical elements and mechanical actuators have been used in versatile high resolution endoscopes. See D. Bird and M. Gu. “Two-photon fluorescence endoscopy with a micro-optic scanning head,” Optics Letters, Vol. 28, No. 17, pp. 1552-1554, 2003. Yet these designs remain relatively large, i.e. larger than 2 mm.
Recently, the possibility of building functional ultra-thin imaging devices has been explored, based solely on multimode optical fibers using the large number of degrees of freedom available in these waveguides. See S. Bianchi and R. Di Leonardo. “A multi-mode fiber probe for holographic micromanipulation and microscopy,” Lab on a Chip, Vol. 12, No. 3, pp. 635-639, 2012, see also Y. Choi, C. Yoon, M. Kim, T. D. Yang, C. Fang-Yen, R. R. Dasari, K. J. Lee and W. Choi. “Scanner-Free and Wide-Field Endoscopic Imaging by Using a Single Multimode Optical Fiber,” Physical Review Letters, Vol. 109, No. 20, 2012, see also T. Cizmar and K. Dholakia. “Exploiting multimode waveguides for pure fibre-based imaging,” Nature Communications, Vol. 3, 2012, see also I. N. Papadopoulos, S. Farahi, C. Moser and D. Psaltis. “Focusing and scanning light through a multimode optical fiber using digital phase conjugation,” Optics Express, Vol. 20, No. 10, pp. 10583-10590, 2012, see also R. N. Mahalati, R. Y. Gu and J. M. Kahn. “Resolution limits for imaging through multi-mode fiber,” Optics Express, Vol. 21, No. 2, pp. 1656-1668, 2013, see also I. N. Papadopoulos, S. Farahi, C. Moser and D. Psaltis. “High-resolution, lensless endoscope based on digital scanning through a multimode optical fiber,” Biomedical Optics Express, Vol. 4, No. 2, pp. 260-270, 2013.
In particular, researchers have recently proposed and demonstrated an optical-resolution photoacoustic imaging modality in which a multimode optical fiber is used as the source of the optical excitation field. See I. N. Papadopoulos, O. Simandoux, S. Farahi, J. P. Huignard, E. Bossy, D. Psaltis and C. Moser. “Optical-resolution photoacoustic microscopy by use of a multimode fiber,” Applied Physics Letters, Vol. 102, No. 21, 2013. Digital phase conjugation was used to focus and digitally scan a diffraction-limited spot at the distal tip of the multimode fiber, therefore eliminating the need for optical lenses and mechanical actuators. The small diameters of multimode fibers along with their ability to focus light into a micron-sized spot, pave the way for the implementation of optical resolution PAM, deeper than the ballistic regime of light propagation. In the configuration illustrated on
The above discussed approaches appear to address the problem of optical-focusing through a small diameter device inserted into tissue, ultrasound needs to be detected after is has been generated via the photoacoustic effect. Because OR-PAM generates photoacoustic waves with frequencies of typically several tens of MHz, the ability to detect externally the high frequency photoacoustic waves generated at depth in tissue is limited by the acoustic attenuation, typically 0.1-1.0 dB/cm/MHz. Also, OR-PAM endoscopy approaches have been introduced recently. See P. Hajireza, W. Shi and R. Zemp. “Label-free in vivo GRIN-lens optical resolution photoacoustic micro-endoscopy,” Laser Physics Letters, Vol. 10, No. 5, 2013. In this publication, ultrasound is detected from outside the sample either through a relatively thin tissue thickness in the MHz range, or through a non-absorbing tissue-mimicking samples. Internal detection can be considered, but ultrasound sensors have to be miniaturized, resulting in limited sensitivity, and requiring dedicated technological developments. See E. Z. Zhang and P. C. Beard. “A miniature all-optical photoacoustic imaging probe,” Photons Plus Ultrasound: Imaging and Sensing 2011, p. 7899, 2011.
Despite all these advancements in photoacoustic endoscopy, no endoscopic device is currently able to achieve both optical scanning and focusing and detection of the generated photoacoustic waves to generate an OR-PAM image at centimeters depth in tissue. Therefore, novel technologies and principles in photoacoustic microscopy are desired.
According to one aspect of the present invention, an endoscopic device for photoacoustic imaging is provided. The endoscopic device preferably includes a multimode waveguide having a distal end and a proximal end, a light source to provide a light beam to the proximal end of the multimode waveguide, and a transducer to capture acoustic radiation that is emitted from the proximal end of the multimode waveguide. Moreover, the endoscopic device preferably further includes a processing device to generate a photoacoustic image based on data from the captured acoustic radiation captured by the transducer, and the distal end of the multimode waveguide is configured to be inserted into a sample, the sample generating the acoustic radiation by a photoacoustic effect.
According to another aspect of the present invention, a method to generate a photoacoustic image from a sample with a multimode waveguide is provided. Preferably, the multimode waveguide penetrates into the sample such that a distal end of the multimode waveguide faces an area of the sample under test inside the sample. In addition, preferably the method includes the steps of radiating a proximal end of the multimode waveguide with light from a light source, and guiding the light through the multimode waveguide and guiding sound through the multimode waveguide, the sound being created by the light that exits the distal end of the multimode waveguide and impinges on the area of the sample under test, the area causing a photoacoustic effect generating acoustic radiation that enters the multimode waveguide by the distal end. Moreover, the method also preferably includes the step of emitting the sound from the proximal end of the multimode waveguide, and capturing the emitted sound by a transducer to generate the photoacoustic image.
According to yet another aspect of the present invention, an endoscopic system for photoacoustic imaging is provided. The system preferably includes a sample having an opening, a dual waveguide having a distal end and a proximal end, the distal end of the dual waveguide arranged inside the opening, an area of the sample facing the distal end of the dual wave guide being under test, and a light source to provide a light beam to the proximal end of the dual waveguide. Moreover, the system preferably includes a transducer to capture acoustic radiation that is emitted from the proximal end of the dual waveguide, and a processing device to generate a photoacoustic image based on data from the captured acoustic radiation captured by the transducer, and the acoustic radiation is generated by a photoacoustic effect at the area of the sample, by the acoustic radiation that enters the dual waveguide at the distal end.
The above and other objects, features and advantages of the present invention and the manner of realizing them will become more apparent, and the invention itself will best be understood from a study of the following description and appended claims with reference to the attached drawings showing some preferred embodiments of the invention.
The accompanying drawings, which are incorporated herein and constitute part of this specification, illustrate the presently preferred embodiments of the invention, and together with the general description given above and the detailed description given below, serve to explain features of the invention.
Herein, identical reference numerals are used, where possible, to designate identical elements that are common to the figures. Also, the images in the drawings are simplified for illustration purposes and may not be depicted to scale.
The embodiments of the present invention are directed to an endoscopic system, method, and device that is capable of achieving optical focusing and scanning on a sample, for example tissue, through a multimode waveguide and using the same multimode waveguide to pickup the generated photoacoustic waves, transporting the acoustic signal from the photoacoustic waves to the proximal side of the waveguide where the acoustic signal signal or wave can be detected by a transducer to thereby generate an OR-PAM image at centimeters depth in tissue. The embodiments of the present invention also describe a multimode waveguide that is configured to also pickup and transport optical fluorescence from the sample to the proximal side where the optical fluorescence can be detected to produce a fluorescence image. The embodiments of the present invention further describe a dual modality imaging scheme whereby a photoacoustic image and a fluorescence image are obtained from the sample at the same time by detecting with a transducer that can detect acoustic and fluorescent radiation.
Some of the main features of the embodiments of the present invention include, but are not limited to, a light injection and sound emission for detection that are performed at the same tip, being the proximal tip of the multimode waveguide that is located outside the sample under test, that the light is guided from the proximal tip of the waveguide that is located outside the sample to the distal tip that is located inside the sample. Moreover, sound is guided from the distal tip of the waveguide inside the sample to the proximal tip outside the sample. In addition, the distal tip can be free from any additional components, either optical or acoustical, and the multimode optical waveguide, for example a dual acousto-optic waveguide may have diameters as small as typically a hundred microns. This allows for a smaller area that is needed for insertion of the multimode waveguide into the sample, and allows for minimal invasion.
As schematically illustrated in
According to one aspect of the embodiments of the present invention, both light excitation and sound detection is combined into a single multimode waveguide, for example a dual-mode acousto-optic waveguide as described above, with both light excitation and sound detection located at the proximal tip that is located outside the sample under test, with a distal tip free of any acoustical or optical components located inside the sample. The distal tip is arranged such that an area of the sample under test is subject to emitted light that causes the photoacoustic effect in the area of the sample. In particular, a dual waveguide can be made of a cladding layer that is filled with fluid serving as the core, for example a fluid-filled silica capillary, with light guided in the cladding, for example the silica shell and sound guided in the fluid core, as further described below.
According to another aspect of the embodiments of the present invention, and innovative concept has been provided by using a dual waveguide to both guide light into the sample and to guide sound outside the sample, in the context of photoacoustic imaging by an endoscopic approach. More specifically, one aspect of the embodiments relies on guiding the light through the sample on the way in via multi-mode optical propagation and detecting ultrasound that was generated at an area of the sample via the photoacoustic effect, after it has propagated on the way out from the sample via mostly mono-mode acoustic propagation. According to another aspect, the multimode waveguide includes a cylindrical elongated component with a small transverse dimension, preferably a few hundred microns in diameter, and having a comparatively large length, preferably from several millimeters to meters. More particularly, the distal tip inserted into the sample under test, for instance biological tissue, is fully passive, which means that it is free of any additional components, such as any electrical conductors, acoustical transducer, optical elements, amplifiers, beam splitters, mirrors, etc., apart from the distal end of the multimode waveguide itself. According to embodiments of the present invention, examples of such multimode waveguide include, but are not limited to, fluid-filled capillaries, fluid-filled optical/acoustical hollow fibers, and fluid-filled needles.
Light 58 then exits at the distal end 12 of the waveguide 20 and impinges on an area of the sample 10, and by a photoacoustic effect of the sample 10. Sound radiation or waves are generated, and at least a portion of the sound generated by the photoacoustic effect propagates back inside the dual waveguide 20 an enters via the distal end 12 and is guided back through waveguide 20 along an acoustic part. The sound is then emitted as sound 33 from the proximal end 14 of waveguide. Sound 33 enters the acousto-optic coupler 30 and is redirected as sound 35 towards an acoustic transducer 40 or sound detection device that can capture the sound 35 and can convert it into data that is transmitted via a data link 45 to a data processing and visualization device 70.
The acousto-optic coupler 30 allows injecting light 58 that originates from light source 60 into waveguide 20 at the proximal end 14, and at the same time can receive the sound 33 from the same location, being the proximal end 14 of waveguide 20, and direct the sound towards a different location where the acoustic transducer 40 is located. Therefore, the proximal end 14 of multimode waveguide 20 has a dual functionality of emitting sound 33 and simultaneously receiving light 58. As a consequence, distal end 12 or distal tip inserted into the sample 10 can be free from any components, for example, it can be free from electrical circuits, ultrasound transducers, conductors, optical elements such as lenses, mirrors, and amplifiers, and this allows to keep the distal tip as small as possible.
While the invention has been disclosed with reference to certain preferred embodiments, numerous modifications, alterations, and changes to the described embodiments are possible without departing from the sphere and scope of the invention, as defined in the appended claims and their equivalents thereof. Accordingly, it is intended that the invention not be limited to the described embodiments, but that it have the full scope defined by the language of the following claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| PCT/IB2014/066289 | Nov 2014 | IB | international |
This application claims priority to the International Application PCT/IB2014/066289, with an international filing date of Nov. 24, 2014, the entire contents thereof are herewith incorporated by reference.
