A Novel Quantitative 500-MHz Acoustic Microscopy System for Ophthalmologic Tissues

<italic>Objective:</italic> This paper describes development of a novel 500-MHz scanning acoustic microscope (SAM) for assessing the mechanical properties of ocular tissues at fine resolution. The mechanical properties of some ocular tissues, such as lamina cribrosa (LC) in the optic nerve head, are believed to play a pivotal role in eye pathogenesis. <italic>Methods:</italic> A novel etching technology was used to fabricate silicon-based lens for a 500-MHz transducer. The transducer was tested in a custom-designed scanning system on human eyes. Two-dimensional (2-D) maps of bulk modulus (K) and mass density (ρ) were derived using improved versions of current state-of-the-art signal processing approaches. <italic>Results:</italic> The transducer employed a lens radius of 125 μm and had a center frequency of 479 MHz with a –6-dB bandwidth of 264 MHz and a lateral resolution of 4 μm. The LC, Bruch's membrane (BM) at the interface of the retina and choroid, and Bowman's layer (BL) at the interface of the corneal epithelium and stroma, were successfully imaged and resolved. Analysis of the 2-D parameter maps revealed average values of LC, BM, and BL with <inline-formula><tex-math notation="LaTeX">${\rm{KLC}} = 2.81 \pm 0.17$</tex-math></inline-formula>; GPa, <inline-formula><tex-math notation="LaTeX">${\rm{KBM}} = 2.89 \pm 0.18$</tex-math></inline-formula>; GPa, <inline-formula><tex-math notation="LaTeX">${\rm{KBL}} = 2.6 \pm 0.09$ </tex-math></inline-formula>; GPa, ρ <inline-formula><tex-math notation="LaTeX">${\rm{LC}} = 0.96 \pm 0.03$ </tex-math></inline-formula> g/cm<sup>3</sup>; ρ <inline-formula><tex-math notation="LaTeX">${\rm{BM}} = 0.97 \pm 0.04$</tex-math></inline-formula> g/cm<sup>3</sup>; ρ <inline-formula><tex-math notation="LaTeX">${\rm{BL}} = 0.98 \pm 0.04$</tex-math></inline-formula> g/cm<sup>3</sup>. <italic>Significance:</italic> This novel SAM was shown to be capable of measuring mechanical properties of soft biological tissues at microscopic resolution; it is currently the only system that allows simultaneous measurement of K, ρ, and attenuation in large lateral scales (field area >9 mm<sup>2</sup>) and at fine resolutions.

[1]  C. Quate,et al.  Acoustic microscopy with mechanical scanning—A review , 1979, Proceedings of the IEEE.

[2]  Jonathan Mamou,et al.  Speed of sound in diseased liver observed by scanning acoustic microscopy with 80 MHz and 250 MHz. , 2016, The Journal of the Acoustical Society of America.

[3]  R. Lemor,et al.  P2E-5 Silicon Based GHz Acoustic Lenses For Time Resolved Acoustic Microscopy , 2007, 2007 IEEE Ultrasonics Symposium Proceedings.

[4]  Jost B Jonas,et al.  Anatomic relationship between lamina cribrosa, intraocular space, and cerebrospinal fluid space. , 2003, Investigative ophthalmology & visual science.

[5]  R. Ritch,et al.  Exfoliation syndrome. , 2001, Survey of ophthalmology.

[6]  C. Quate,et al.  Acoustic microscope—scanning version , 1974 .

[7]  Calvin F. Quate,et al.  Acoustic Microscopy with Microwave Frequencies , 1979 .

[8]  J. Mamou,et al.  Chirp-coded excitation imaging with a high-frequency ultrasound annular array , 2008, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[9]  M. Oelze,et al.  A novel coded excitation scheme to improve spatial and contrast resolution of quantitative ultrasound imaging , 2009, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[10]  M F Marmor,et al.  Acoustic microscopy of the human retina and pigment epithelium. , 1977, Investigative ophthalmology & visual science.

[11]  Brian Derby,et al.  Scanning Acoustic Microscopy for Mapping the Microelastic Properties of Human Corneal Tissue , 2013, Current eye research.

[12]  Yoshifumi Saijo,et al.  Multimodal ultrasound microscopy for biomedical imaging , 2013 .

[13]  M. Oelze Bandwidth and resolution enhancement through pulse compression , 2007, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[14]  M. Oelze,et al.  Small Lesion Detection with Resolution Enhancement Compression , 2010, Ultrasonic imaging.

[15]  C. R. Ethier,et al.  Factors influencing optic nerve head biomechanics. , 2005, Investigative ophthalmology & visual science.

[16]  Jonathan Mamou,et al.  Fine-resolution maps of acoustic properties at 250 MHz of unstained fixed murine retinal layers. , 2015, The Journal of the Acoustical Society of America.

[17]  Seiji Yamamoto,et al.  Scanning acoustic microscopy for characterization of neoplastic and inflammatory lesions of lymph nodes , 2013, Scientific Reports.

[18]  J. Marshall,et al.  An experimental study of the elastic properties of the human Bruch’s membrane-choroid complex: relevance to ageing , 2006, British Journal of Ophthalmology.

[19]  W D O'Brien,et al.  Frequency dependence of tissue attenuation measured by acoustic microscopy. , 1989, The Journal of the Acoustical Society of America.

[20]  R. Shinomura,et al.  Thin-film ZnO ultrasonic transducers for tissue characterization , 1996, ISAF '96. Proceedings of the Tenth IEEE International Symposium on Applications of Ferroelectrics.

[21]  J. Marshall,et al.  Age-related variation in the hydraulic conductivity of Bruch's membrane. , 1995, Investigative ophthalmology & visual science.

[22]  Pedro Gonzalez,et al.  Circumferential tensile stiffness of glaucomatous trabecular meshwork. , 2014, Investigative ophthalmology & visual science.

[23]  K. Raum,et al.  Microelastic imaging of bone , 2008, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[24]  Erwan Filoux,et al.  Pulse-encoded ultrasound imaging of the vitreous with an annular array. , 2012, Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye.

[25]  P T de Jong,et al.  Morphometric analysis of Bruch's membrane, the choriocapillaris, and the choroid in aging. , 1994, Investigative ophthalmology & visual science.

[26]  G. Briggs,et al.  The elastic microstructure of various tissues. , 1989, The Journal of the Acoustical Society of America.

[27]  Jonathan Mamou,et al.  High-frequency chirp ultrasound imaging with an annular array for ophthalmologic and small-animal imaging. , 2009, Ultrasound in medicine & biology.

[28]  O Aristizabal,et al.  Characterization of the spatial resolution of different high-frequency imaging systems using a novel anechoic-sphere phantom , 2011, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[29]  Kazushi Yamanaka,et al.  IN ACOUSTIC MICROSCOPY , 1982 .

[30]  T. Schäffer,et al.  Evaluation of lamina cribrosa and peripapillary sclera stiffness in pseudoexfoliation and normal eyes by atomic force microscopy. , 2012, Investigative ophthalmology & visual science.

[31]  N. Mcbrien,et al.  Form deprivation myopia: elastic properties of sclera. , 1995, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[32]  N Tanaka,et al.  Time-frequency analysis for pulse driven ultrasonic microscopy for biological tissue characterization. , 2004, Ultrasonics.

[33]  Yoshifumi Saijo,et al.  Measurement of soft tissue elasticity in the congenital clubfoot using scanning acoustic microscope , 2007, Journal of pediatric orthopedics. Part B.

[34]  Ahmed Elsheikh,et al.  Effect of glucose on the stress-strain behavior of ex-vivo rabbit cornea. , 2011, Experimental eye research.

[35]  M Tanaka,et al.  Ultrasonic tissue characterization of infarcted myocardium by scanning acoustic microscopy. , 1997, Ultrasound in medicine & biology.

[36]  C.M.W. Daft,et al.  Wideband acoustic microscopy of tissue , 1988, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[37]  A. Elsheikh,et al.  Regional variation in the biomechanical properties of the human sclera. , 2010, Experimental eye research.

[38]  G. Jeffery,et al.  Age-related changes in the thickness of the human lamina cribrosa , 2006, British Journal of Ophthalmology.

[39]  Y. Saijo,et al.  Ultrasonic Tissue Characterization of Atherosclerosis by a Speed-of-Sound Microscanning System , 2007, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[40]  K. Sato,et al.  Silicon acoustic lens for scanning acoustic microscope (SAM) , 1991, TRANSDUCERS '91: 1991 International Conference on Solid-State Sensors and Actuators. Digest of Technical Papers.

[41]  N. Mcbrien,et al.  Biomechanics of the Sclera in Myopia: Extracellular and Cellular Factors , 2009, Optometry and vision science : official publication of the American Academy of Optometry.

[42]  J Marshall,et al.  The 2014 Bowman Lecture—Bowman’s and Bruch’s: a tale of two membranes during the laser revolution , 2015, Eye.

[43]  P. Luthert,et al.  Decreased Thickness and Integrity of the Macular Elastic Layer of Bruch's Membrane Correspond to the , 2005 .

[44]  Gadi Wollstein,et al.  Imaging of the Lamina Cribrosa in Glaucoma: Perspectives of Pathogenesis and Clinical Applications , 2013, Current eye research.