Kang Kim, PhD
Kang Kim, PhD
Associate Professor of Medicine,
Associate Professor of Bioengineering
BS, Seoul National University, Seoul, Korea
MS, University of Pierre & Marie Curie (Paris 6), Paris, France
PhD, Pennsylvania State University, PA
Postdoctoral, University of Michigan MI
Area of Specialization/Research
Linear/nonlinear ultrasound elasticity imaging
Thermal strain imaging
Photoacoustic molecular imaging
Non-invasive characterization of atherosclerotic plaques
Our laboratory seeks to develop and translate state of the art noninvasive imaging technologies to (1) improve disease diagnosis, (2) guide therapeutic strategies and (3) evaluate therapeutic efficacy. Our research emphasis is on development and application of hybrid ultrasound imaging systems that are based on a fundamental understanding of how sound and light interact with soft tissue, and are capable of capable of assessing their mechanical, compositional, and biological characteristics. Three independent, but related, imaging technologies are under active investigation:
(1) Ultrasound elasticity imaging (UEI)/shear wave elasticity imaging (SWEI) non-invasively assesses the global and regional mechanical properties of the soft tissues and organs.
(2) Ultrasound Thermal Strain Imaging (TSI) strongly contrasts lipids from the surrounding non-lipid tissues.
(3) Photoacoustic Imaging (PAI)/Photoacoustic molecular imaging (PMI) combines laser and ultrasound technologies to detect optical contrast in tissues and identify specific biomarkers that may enable early detection of disease and its treatment evaluation.
These three imaging modalities may also be combined to provide a more complete characterization of disease. Noninvasive imaging technologies such as these will also be pivotal for preclinical animal studies, significantly reducing animal numbers, variation between subjects, and shortening the study period. In my research laboratory, we envision a noninvasive hybrid imaging system, integrating all these technologies into a single bed-side ultrasound platform. This will provide a powerful, safe, and cost-effective adjunct to clinical practice by identifying patients at early stages of disease and improving treatment strategies.
Ultrasound elasticity imaging (UEI)
Previous attempts at noninvasive vascular elasticity imaging are limited by indirect and imprecise assessments of arterial wall motion. UEI can directly measure intramural wall strain using high resolution ultrasound speckle tracking, which results in a more precise regional assessment. Previous attempts at measuring arterial wall motion were also limited by the limited distention of arteries under physiologic pressure, and their resulting small strain. The arterial wall, however, is a highly nonlinear elastic medium. We have developed a novel "nonlinear" UEI technique that significantly increases the sensitivity of conventional UEI, and enables detection of very subtle changes in tissue stiffness that might occur at early stages of inflammation. Our nonlinear model has been validated by computer simulation as well as in vitro and ex vivo experiments using synthesized tissue phantoms and excised tissues. Preclinical in vivo studies using small animal models of various disease states are currently under active investigation or in planning stages. These disease states include atherosclerotic plaque, myocardial infarction, right ventricular failure related to pulmonary hypertension, inflammatory bowel disease, and engineered tissue constructs for abdominal repairs, vascular grafts, and cardiac patches.
Ultrasound-induced thermal strain imaging (TSI)
Several existing vascular imaging modalities can be used to measure the geometry of an atherosclerotic plaque, producing measurements such as luminal diameter, stenosis, wall thickness, and plaque volume. Few imaging modalities can accurately resolve plaque composition, which is an important indicator of plaque stability. We have developed ultrasound-induced thermal strain imaging (TSI) technology to detect lipid in plaque. The investigation of TSI is based on the findings that lipid-bearing tissue has a negative temperature dependence of sound speed change, while water-bearing tissue has a positive dependence. US-induced TSI uses focused ultrasound to increase the tissue temperature slightly (typically less than 1.5oC) and determines the sound speed before and after heating (rather "warming") using correlation-based speckle tracking. This system produces strong contrast between lipid-bearing and water-bearing tissue, which allows for accurate detection of the lipid-laden pool within a vulnerable plaque from surrounding water-based tissue. Translation of the technology may involve design of a hybrid ultrasound probe capable of heating tissue and imaging, preferably using an existing ultrasound scanner. A novel heating array transducer was developed and integrated into a commercial imaging ultrasound system. TSI has been validated in both in vitro and ex vivo experiments using synthesized tissue phantoms and excised tissues, including the surgical tissue samples from carotid endarterectomy and knee amputation. In vivo validation using a high fat high cholesterol rabbit model of atherosclerotic plaque has been studied. Excised human surgical tissue samples from carotid endarterectomy also has been examined. TSI to detect lipids in fatty liver is under active investigation using ob/ob mouse model.
Photoacoustic molecular imaging (PMI)
Current molecular imaging technologies such as PET, SPECT, CT, and MR, allow clinicians to identify and monitor physiological/biological changes at the cellular/molecular level, but widespread implementation is limited by 1) expense of equipment and specialized personal 2) time required for procedure and image processing and 3) risks associated with ionizing radiation and strong magnetic fields. Ultrasound is a very well-established and safe bed-side technology capable of obtaining real-time imaging of morphological features and hemodynamics. Combining conventional ultrasound imaging and laser technologies, photoacoustic (PA) molecular imaging has the potential to provide a noninvasive, real-time, bed-side molecular imaging system. Our interest in characterizing the inflammatory state of atherosclerotic plaques is based on recent advances in basic sciences that have established a fundamental link between inflammation and atherosclerotic plaque, as well as thrombotic complications of atherosclerosis. It is now known that increased expression of inflammatory markers at the molecular level predicts clinical outcomes in patients with acute coronary syndromes, independently of myocardial damage. In addition, low-grade chronic inflammation, as indicated by levels of the inflammatory marker ICAM-1, prospectively defines risk of atherosclerotic complications, thus adding to prognostic information provided by traditional risk factors. In our lab, using a mouse vascular injury model, we demonstrated that PMI using a commercial ultrasound scanner can detect gold nanoparticles bound to the vascular inflammatory biomarkers such as ICAM-1 and/or E-selectin. These principles and techniques have also successfully applied to a rat and mouse inflammatory bowel disease models.
Projects currently sponsored by:
- Ultrasound-induced thermal strain imaging for arterial plaque characterization (PI: Kim, NIH R01, NHLBI, 2010-2015)
- Noninvasive fat quantification of liver using ultrasound thermal strain imaging (PI: Kim, NIH R21, NIBIB, 2014-16)
- Biometric Coacervate Delivery of Muscle Stem Cell to Improve Cardiac Repair (Co-I, PI: Huard, NIH R21, NIBIB, 2014-16)
- Phase resolved ARF optical coherence elastography for intravascular imaging (Consultant, PI: Chen, UC Irvine, NIH R01, NIBIB, 2014-2018)
- A novel shear wave approach to non-invasively assess mechanical properties of liver for early diagnosis and 3D organ modeling (PI: Kim, Global Research Outreach (GRO) Program, Samsung, 2012-2015)
- Development of a novel multi-modal in-vivo imaging system for animal-to-human use (PI: Sogang University, Co-I: University of Pittsburgh, University of Toronto, Internationl Collaborative Program, Department of Knowledge & Economy, South Korea, 2010-2015)
- Noninvasive monitoring of tissue-engineered constructs by US elasticity imaging (PI: Kim, R21, NIBIB, 2011-2013)
- Cardiovascular inflammation function imaging by photoacoustics using gold nanorod (PI: Kim, R21, NHLBI, 2009-2012 with NCE)
- Non-invasive ultrasound elasticity imaging (UEI) in Crohn's disease (PI: Kim/Rubin, R21, NIDDK, 2009-2012 with NCE)
- High-resolution ultrasound in-vivo animal imaging system-Vevo2100 (PI: Kim, S10, NCRR, 2009-2010)
- Real-time arterial elasticity imaging (PI: Hamilton, R44 (SBIR-Phase II), NIBIB, 2010-2011; R43 (SBIR-Phase I), NIBIB, 2009-2010)
Yap CH, Park DW, Dutta D, Simon M, Kim K: Methods for Using 3D Ultrasound Speckle Tracking in Biaxial Mechanical Testing of Biological Tissue Samples. Ultrasound Med Biol 2014 (In press)
Ding X, Dutta D, Mahmoud A, Tillman B, Leers S and Kim K An Adaptive Displacement Estimation Algorithm for Improved Reconstruction of Thermal Strain. IEEE Trans Ultrason Ferroelectr Freq Control, 2014, (In press)
Park D, Ye S, Jiang H, Dutta D, Nonakad K, Wagner W and Kim K. In vivo monitoring of structural and mechanical changes of tissue scaffolds by multi-modality imaging. Biomaterials, 2014, September, Vol. 35, Issue 27, 7851-7859.
Kagan V.E, Kapralov A, St Croix CM, Watkins S, Kisin E, Kotchey G, Balasubramanian K, Yu J, Kim K, Seo W, Mallampalli R, Star A, Shvedova A. Lung Macrophages "Digest" Carbon Nanotubes Using a Superoxide/Peroxynitrite Oxidative Pathway. ACS Nano, 2014, Vol. 8, No. 6, 5610-5621, DOI: 10.1021/nn406484b.
Mahmoud A, Ding X, Dutta D, Singh VP and Kim K. Detecting hepatic steatosis using ultrasound-induced thermal strain imaging: an ex vivo animal studyPhysics in Medicine and Biology, 2014, Vol. 59, 881-895.
Allen RA, Wu W, Yao M, Dutta D, Duan X, Bachman TN, Champion HC, Donna B, Stolz DB, Robertson AM, Kim K, Isenberg JS and Wang Y. Nerve regeneration and elastin formation within poly(glycerol sebacate)-based synthetic arterial grafts one-year post-implantation in a rat model. Biomaterials 2014 Jan; Vol. 35, Issue 1:165-173
Stephens DN, Mahmoud A, Ding X, Lucero S, Dutta D, Yu FTH, Chen X and Kim K Flexible Integration of Both High Imaging Resolution and High Power Arrays for Ultrasound-Induced Thermal Strain Imaging (US-TSI). IEEE Trans Ultrason Ferroelectr Freq Control 2013 Dec;Vol.60, Issue 12:2456-2656
Dutta D, Mahmoud A, Leers S and Kim K. Motion Artifact Reduction in Ultrasound Based Thermal Strain Imaging of Atherosclerotic Plaques using Time Series Analysis. IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, 2013 Aug;Vol. 60, No. 8:1660-1668.
Dutta D, Lee K, Allen R, Wang Y, Brigham JC and Kim K. Non-invasive Monitoring of Mechanical Strength of Arterial Constructs During Cell Culture Using Ultrasound Elasticity Imaging. Ultrasound in Medicine and Biology 2013 Nov;39:2103-2115.
A. Mahmoud, D. Dutta, L. Lavery, D. Stephens, F. S. Villanueva and K. Kim. Noninvasive detection of lipids in atherosclerotic plaque using ultrasound thermal strain imaging: in vivo animal study. Journal of the American College of Cardiology, 2013 Nov;5, Vol. 62, Issue. 19:1804-1809.
Yu J, Takanari K, Hong Y, Lee K-W, Amoroso NJ, Wang Y, Wagner WR and Kim K. Non-invasive characterization of polyurethane-based tissue constructs in a rat abdominal repair model using high frequency ultrasound elasticity imaging. Biomaterials 2013;34(11):2701-2709, PMID:23347836, PMCID: PMC3565386.
Hollman KW, Shtein RM, Tripathy S and Kim K. Using an ultrasound elasticity microscope to map three-dimensional strain in a porcine cornea. Ultrasound Med Biol 2013 Aug;39:1451-1459.
Xu J, Tripathy S, Rubin JM, Stidham RW, Johnson LA, Higgins PDR, Kim K. A new nonlinear parameter in the developed strain-to-applied strain of the soft tissues and its application in ultrasound elasticity imaging. Ultrasound Med Biol 2012;38(3):511-523, PMID: 22266232, PMCID: PMC3273568.
Kim JS, Leeman JE, Kagemann L, Yu F, Chen X, Pacella JJ, Schuman JS, Villanueva FS and Kim K. Volumetric quantification of in vitro sonothrombolysis with microbubbles using high resolution optical coherence tomography (OCT). J Biomed Optics 2012;17(7):070502 1-3.
Leeman JE, Kim JS, Yu F, Chen X, Kim K, Villanueva FS and Pacella JJ. Effect of acoustic conditions on microbubble-mediated microvascular sonothrombolysis. Ultrasound Med Biol 2012 Sep;38:1589-1598.
Ha S, Carson A, Kim K. Ferritin as a novel reporter gene for photoacoustic molecular imaging. Cytometry Part A 2012;81(10):910-5, PMID: 22949299.
Kotchey GP, Hasan SA, Kapralov AA, Ha S, Kim K, Shvedova AA, Kagan VE, Star A. A natural vanishing act: The enzyme-catalyzed degradation of carbon nanomaterials. Acc Chem Res 2012;45(10):1770-81, PMID:22824066.
Wang Z, Ha S and Kim K. A new design of light illumination scheme for deep tissue photoacoustic Imaging. Opt Express 2012;20(20):22649-22659, PMID: 23037414.