Photoacoustic Imaging of Human Vasculature Using LED versus Laser Illumination: A Comparison Study on Tissue Phantoms and In Vivo Humans

Vascular diseases are becoming an epidemic with an increasing aging population and increases in obesity and type II diabetes. Point-of-care (POC) diagnosis and monitoring of vascular diseases is an unmet medical need. Photoacoustic imaging (PAI) provides label-free multiparametric information of deep vasculature based on strong absorption of light photons by hemoglobin molecules. However, conventional PAI systems use bulky nanosecond lasers which hinders POC applications. Recently, light-emitting diodes (LEDs) have emerged as cost-effective and portable optical sources for the PAI of living subjects. However, state-of-art LED arrays carry significantly lower optical energy (<0.5 mJ/pulse) and high pulse repetition frequencies (PRFs) (4 KHz) compared to the high-power laser sources (100 mJ/pulse) with low PRFs of 10 Hz. Given these tradeoffs between portability, cost, optical energy and frame rate, this work systematically studies the deep tissue PAI performance of LED and laser illuminations to help select a suitable source for a given biomedical application. To draw a fair comparison, we developed a fiberoptic array that delivers laser illumination similar to the LED array and uses the same ultrasound transducer and data acquisition platform for PAI with these two illuminations. Several controlled studies on tissue phantoms demonstrated that portable LED arrays with high frame averaging show higher signal-to-noise ratios (SNRs) of up to 30 mm depth, and the high-energy laser source was found to be more effective for imaging depths greater than 30 mm at similar frame rates. Label-free in vivo imaging of human hand vasculature studies further confirmed that the vascular contrast from LED-PAI is similar to laser-PAI for up to 2 cm depths. Therefore, LED-PAI systems have strong potential to be a mobile health care technology for diagnosing vascular diseases such as peripheral arterial disease and stroke in POC and resource poor settings.

[1]  Guan Xu,et al.  Detecting joint inflammation by an LED-based photoacoustic imaging system: a feasibility study , 2018, Journal of biomedical optics.

[2]  René Skov Hansen Using high-power light emitting diodes for photoacoustic imaging , 2011 .

[3]  Jesse V. Jokerst,et al.  Construction and Validation of Nano Gold Tripods for Molecular Imaging of Living Subjects , 2014, Journal of the American Chemical Society.

[4]  Bo Norrving,et al.  The global burden of stroke and need for a continuum of care , 2013, Neurology.

[5]  A. Oraevsky,et al.  Clinical optoacoustic imaging combined with ultrasound for coregistered functional and anatomical mapping of breast tumors , 2018, Photoacoustics.

[6]  S. Emelianov,et al.  Photoacoustic imaging in cancer detection, diagnosis, and treatment guidance. , 2011, Trends in biotechnology.

[7]  Ali Hariri,et al.  Development of low-cost photoacoustic imaging systems using very low-energy pulsed laser diodes , 2017, Journal of biomedical optics.

[8]  V. Ntziachristos,et al.  Molecular imaging by means of multispectral optoacoustic tomography (MSOT). , 2010, Chemical reviews.

[9]  Benjamin A. Rockwell,et al.  A procedure for multiple-pulse maximum permissible exposure determination under the Z136.1-2000 American National Standard for Safe Use of Lasers , 2001 .

[10]  Christopher M Kramer,et al.  Multimodality Imaging of Lower Extremity Peripheral Arterial Disease: Current Role and Future Directions , 2012, Circulation. Cardiovascular imaging.

[11]  Javier Ena,et al.  Use of pocket pulse oximeters for detecting peripheral arterial disease in patients with diabetes mellitus , 2013 .

[12]  Wei Liu,et al.  High-speed widefield photoacoustic microscopy of small-animal hemodynamics. , 2018, Biomedical optics express.

[13]  A. Kole,et al.  Comparative Quantification of Arterial Lipid by Intravascular Photoacoustic-Ultrasound Imaging and Near-Infrared Spectroscopy-Intravascular Ultrasound , 2018, Journal of Cardiovascular Translational Research.

[14]  Visweshwar Srinivasan,et al.  Towards a Low-Cost and Portable Photoacoustic Microscope for Point-of-Care and Wearable Applications , 2020, IEEE Sensors Journal.

[15]  Sanjiv S. Gambhir,et al.  Simultaneous transrectal ultrasound and photoacoustic human prostate imaging , 2019, Science Translational Medicine.

[16]  Manojit Pramanik,et al.  Molecular photoacoustic imaging of angiogenesis with integrin‐targeted gold nanobeacons , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[17]  Stanislav Y. Emelianov,et al.  Biomedical Applications of Photoacoustic Imaging with Exogenous Contrast Agents , 2011, Annals of Biomedical Engineering.

[18]  Meng Zhou,et al.  Review of Low-Cost Photoacoustic Sensing and Imaging Based on Laser Diode and Light-Emitting Diode , 2018, Sensors.

[19]  M. Uder,et al.  Detection of collagens by multispectral optoacoustic tomography as an imaging biomarker for Duchenne muscular dystrophy , 2019, Nature Medicine.

[20]  Jefferson C Frisbee,et al.  Obesity and vascular dysfunction. , 2008, Pathophysiology : the official journal of the International Society for Pathophysiology.

[21]  Christopher Fadden,et al.  Light-Emitting-Diode-Based Multispectral Photoacoustic Computed Tomography System , 2019, Sensors.

[22]  Paul C. Beard,et al.  High power visible light emitting diodes as pulsed excitation sources for biomedical photoacoustics , 2016, Biomedical optics express.

[23]  Boris Murmann,et al.  A Pixel Pitch-Matched Ultrasound Receiver for 3-D Photoacoustic Imaging With Integrated Delta-Sigma Beamformer in 28-nm UTBB FD-SOI , 2017, IEEE Journal of Solid-State Circuits.

[24]  Wiendelt Steenbergen,et al.  Tomographic imaging with an ultrasound and LED-based photoacoustic system. , 2020, Biomedical optics express.

[25]  Paul Kumar Upputuri,et al.  Fast photoacoustic imaging systems using pulsed laser diodes: a review , 2018, Biomedical Engineering Letters.

[26]  Jeehyun Kim,et al.  In vitro photoacoustic measurement of hemoglobin oxygen saturation using a single pulsed broadband supercontinuum laser source. , 2014, Applied optics.

[27]  Sri-Rajasekhar Kothapalli,et al.  Lithium niobate-based transparent ultrasound transducers for photoacoustic imaging. , 2019, Optics letters.

[28]  Paul C Beard,et al.  Pulsed near-infrared laser diode excitation system for biomedical photoacoustic imaging. , 2006, Optics letters.

[29]  L V Wang,et al.  Anisotropy in the absorption and scattering spectra of chicken breast tissue. , 1998, Applied optics.

[30]  Srivalleesha Mallidi,et al.  In Vivo Tumor Vascular Imaging with Light Emitting Diode-Based Photoacoustic Imaging System , 2020, Sensors.

[31]  Jin U. Kang,et al.  Enabling fast and high quality LED photoacoustic imaging: a recurrent neural networks based approach. , 2018, Biomedical optics express.

[32]  Qifa Zhou,et al.  In vivo label-free photoacoustic microscopy of cell nuclei by excitation of DNA and RNA. , 2010, Optics letters.

[33]  Photoacoustic Imaging of Gene Expression in Small Animals In Vivo , 2017 .

[34]  F. D. de Mul,et al.  Three-dimensional photoacoustic imaging of blood vessels in tissue. , 1998, Optics letters.

[35]  Jesse V. Jokerst,et al.  Dictionary learning technique enhances signal in LED-based photoacoustic imaging. , 2020, Biomedical optics express.

[36]  Quing Zhu,et al.  In vivo photoacoustic tomography of mouse cerebral edema induced by cold injury. , 2011, Journal of biomedical optics.

[37]  Guodong Liu,et al.  Low-cost photoacoustic imaging systems based on laser diode and light-emitting diode excitation , 2017 .

[38]  Martin Frenz,et al.  Fourier reconstruction in optoacoustic imaging using truncated regularized inverse k-space interpolation , 2007 .

[39]  Naoto Sato,et al.  Towards Clinical Translation of LED-Based Photoacoustic Imaging: A Review , 2020, Sensors.

[40]  Roy G. M. Kolkman,et al.  In vivo photoacoustic imaging of blood vessels with a pulsed laser diode , 2006, Lasers in Medical Science.

[41]  S. Ourselin,et al.  Photoacoustic imaging of the human placental vasculature , 2019, Journal of biophotonics.

[42]  Christopher Fadden,et al.  A Deep Learning Approach to Photoacoustic Wavefront Localization in Deep-Tissue Medium , 2020, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[43]  Rui Li,et al.  Photoacoustic tomography of intact human prostates and vascular texture analysis identify prostate cancer biopsy targets , 2018, Photoacoustics.

[44]  Peripheral Arterial Disease in People With Diabetes , 2003 .

[45]  Jan Laufer,et al.  In vitro measurements of absolute blood oxygen saturation using pulsed near-infrared photoacoustic spectroscopy: accuracy and resolution. , 2005, Physics in medicine and biology.

[46]  Liming Nie,et al.  In vivo photoacoustic imaging dynamically monitors the structural and functional changes of ischemic stroke at a very early stage , 2020, Theranostics.

[47]  Sanjiv S. Gambhir,et al.  Activatable oligomerizable imaging agents for photoacoustic imaging of furin-like activity in living subjects. , 2013, Journal of the American Chemical Society.

[48]  Rudra Pratap,et al.  A Photoacoustic Imaging Device Using Piezoelectric Micromachined Ultrasound Transducers (PMUTs) , 2019, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[49]  Adrien E. Desjardins,et al.  Imaging of human peripheral blood vessels during cuff occlusion with a compact LED-based photoacoustic and ultrasound system , 2019, BiOS.

[50]  Shonit Punwani,et al.  Photoacoustic imaging of human lymph nodes with endogenous lipid and hemoglobin contrast. , 2015, Journal of biomedical optics.

[51]  Eunji Jeong,et al.  Smartphone-based portable ultrasound imaging system: Prototype implementation and evaluation , 2015, 2015 IEEE International Ultrasonics Symposium (IUS).

[52]  Jie Yuan,et al.  Light Emitting Diodes based Photoacoustic Imaging and Potential Clinical Applications , 2018, Scientific Reports.

[53]  Mohammad R. N. Avanaki,et al.  Photoacoustic/Ultrasound/Optical Coherence Tomography Evaluation of Melanoma Lesion and Healthy Skin in a Swine Model , 2019, Sensors.

[54]  Huabei Jiang,et al.  In vivo photoacoustic imaging of vasculature with a low-cost miniature light emitting diode excitation. , 2017, Optics letters.

[55]  Jie Yuan,et al.  LED-based photoacoustic imaging for monitoring angiogenesis in fibrin scaffolds. , 2019, Tissue engineering. Part C, Methods.

[56]  Butrus T. Khuri-Yakub,et al.  Deep Tissue Photoacoustic Imaging Using a Miniaturized 2-D Capacitive Micromachined Ultrasonic Transducer Array , 2012, IEEE Transactions on Biomedical Engineering.

[57]  T. Bharathan,et al.  Pulse Oximetry in the Evaluation of Peripheral Vascular Disease , 1997, Angiology.

[58]  Hsiao-Chun Amy Lin,et al.  Brilliant cresyl blue enhanced optoacoustic imaging enables non-destructive imaging of mammalian ovarian follicles for artificial reproduction , 2020, Journal of the Royal Society Interface.

[59]  The rate of missed diagnosis of lower-limb DVT by ultrasound amounts to 50% or so in patients without symptoms of DVT: A meta-analysis: Erratum , 2019, Medicine.

[60]  Yuanjin Zheng,et al.  Toward Wearable Healthcare: A Miniaturized 3D Imager With Coherent Frequency-Domain Photoacoustics , 2019, IEEE Transactions on Biomedical Circuits and Systems.

[61]  Sarah E Bohndiek,et al.  Contrast agents for molecular photoacoustic imaging , 2016, Nature Methods.