In cancer patients, determination of whether a malignancy has spread is the single most important factorused to develop a therapeutic plan and to predict prognosis. In most cases, cancer cells initially spread throughregional lymph nodes. Therefore, clinical evaluation for the presence of regional lymph node metastases is ofparamount importance. Unfortunately, there are no real-time, non-invasive clinical methods that can reliablydetect and diagnose micrometastases in lymph nodes. Therefore, there is an urgent clinical need for animaging technique that is widely available, is non-invasive and simple to perform, is safe, and can reliablydetect and adequately diagnose lymph node micrometastases in real time. The overall goal of our research program is to develop an advanced, in-vivo, noninvasive, molecularspecific imaging technology, i.e., integrated ultrasound and photoacoustic imaging combined with targetedplasmonic nanosensors, capable of immediate and accurate assessment of sentinel lymph nodemicrometastases in real time. The underlying hypothesis of this project is that photoacoustic imaging integratedwith widely used clinical ultrasound imaging is possible and both ultrasound and photoacoustic imaging can beperformed in real time, yielding an immediate diagnosis and allowing early implementation of treatment. A wide range of scientific and engineering, biomedical and clinical problems must be addressed to fullyexplore the capabilities of molecular specific ultrasound and photoacoustic lymphatic (MS-USPAL) imaging indetection and characterization of sentinel lymph node micrometastases. The current application is focused onimportant aspects of clinical translation of MS-USPAL imaging. We will develop and validate clinicallytranslatable plasmonic nanosensors for MS-USPAL. We will use ultra-small gold nanoparticles to targetepidermal growth factor receptor (EGFR), which is overexpressed in squamous carcinoma and in many otherepithelial neoplasms. For highly sensitive detection of cancer cells, we will explore EGF receptor mediatedendocytosis and the effect of plasmon resonance coupling between closely spaced molecular specificnanoparticles. The ultra-small size of nanoparticles will be highly favorable for rapid clearance from the bodywhich will allow safe transition into clinical practice. Additionally, 5 nm ligand capped gold nanoparticles willgreatly reduce nonspecific interactions and reduce the uptake of nanoparticles by immune cells such asmacrophages present due to lymph node inflammation, thus diminishing false positive results. Furthermore, wewill design and construct a prototype of the clinical MS-USPAL imaging system capable of imaging 5 nmnanoparticles in-vivo.

Public Health Relevance

In cancer patients; the determination of the spread of malignancy is the single most important factor to developa therapeutic plan and predict prognosis. In most cases; cancer cells initially spread through regional lymphnodes. Thus; a technology such as molecular specific ultrasound and photoacoustic lymphatic imaging;capable of in-vivo; noninvasive and accurate assessment of regional metastases in real time; can simplify andimprove management of patients with epithelial malignancies; significantly improve public health; and reducemedical costs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
7R01EB008101-09
Application #
9305626
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
King, Randy Lee
Project Start
2007-09-01
Project End
2018-02-28
Budget Start
2017-01-06
Budget End
2018-02-28
Support Year
9
Fiscal Year
2015
Total Cost
$553,938
Indirect Cost
$121,119
Name
Georgia Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30318
Yoon, Heechul; Hallam, Kristina A; Yoon, Changhan et al. (2018) Super-Resolution Imaging With Ultrafast Ultrasound Imaging of Optically Triggered Perfluorohexane Nanodroplets. IEEE Trans Ultrason Ferroelectr Freq Control 65:2277-2285
Chen, Yun-Sheng; Yoon, Soon Joon; Frey, Wolfgang et al. (2017) Dynamic contrast-enhanced photoacoustic imaging using photothermal stimuli-responsive composite nanomodulators. Nat Commun 8:15782
Hannah, Alexander S; Luke, Geoffrey P; Emelianov, Stanislav Y (2016) Blinking Phase-Change Nanocapsules Enable Background-Free Ultrasound Imaging. Theranostics 6:1866-76
Luke, Geoffrey P; Hannah, Alexander S; Emelianov, Stanislav Y (2016) Super-Resolution Ultrasound Imaging in Vivo with Transient Laser-Activated Nanodroplets. Nano Lett 16:2556-9
Qu, M; Mehrmohammadi, M; Emelianov, S Y (2015) Sensing the delivery and endocytosis of nanoparticles using magneto-photo-acoustic imaging. Photoacoustics 3:107-13
Luke, Geoffrey P; Emelianov, Stanislav Y (2015) Label-free Detection of Lymph Node Metastases with US-guided Functional Photoacoustic Imaging. Radiology 277:435-42
Mallidi, Srivalleesha; Kim, Seungsoo; Karpiouk, Andrei et al. (2015) Visualization of molecular composition and functionality of cancer cells using nanoparticle-augmented ultrasound-guided photoacoustics. Photoacoustics 3:26-34
Hannah, Alexander S; VanderLaan, Donald; Chen, Yun-Sheng et al. (2014) Photoacoustic and ultrasound imaging using dual contrast perfluorocarbon nanodroplets triggered by laser pulses at 1064 nm. Biomed Opt Express 5:3042-52
Luke, Geoffrey P; Myers, Jeffrey N; Emelianov, Stanislav Y et al. (2014) Sentinel lymph node biopsy revisited: ultrasound-guided photoacoustic detection of micrometastases using molecularly targeted plasmonic nanosensors. Cancer Res 74:5397-408
Qu, Min; Mehrmohammadi, Mohammad; Truby, Ryan et al. (2014) Contrast-enhanced magneto-photo-acoustic imaging in vivo using dual-contrast nanoparticles. Photoacoustics 2:55-62

Showing the most recent 10 out of 51 publications