Academic Appointments

Honors & Awards

  • Pathway to Independence Award (K99/R00), NIH/NIBIB (2014-2019)

Professional Education

  • MS, University of Massachusetts, Boston, Applied Physics (2004)
  • PhD, Washington University in St.Louis, Biomedical Engineering (2009)

Community and International Work

  • Reviewer



    Ongoing Project


    Opportunities for Student Involvement



  • Sri Rajasekhar Kothapalli. "United States Patent 20120220870 Optical Molecular Imaging Method and Systems for Radioactive Materials", Stanford Univeristy, Aug 12, 2012
  • Sri Rajasekhar Kothapalli. "United States Patent 7,738,047 Systems and methods of all-optical Fourier phase contrast imaging using dye doped liquid crystals", University of Massachusetts, Nov 6, 2007
  • Sri Rajasekhar Kothapalli. "United States Patent 20060291707. Phase based digital imaging", University of Massachusetts, Nov 25, 2005

Research & Scholarship

Current Research and Scholarly Interests

My current research is focused on developing non-ionizing and low cost medical technologies that reliably detect the disease and also capable of predicting the prognosis. Towards this goal, I work at the interface of Photonics, Acoustics, MEMS, Molecular Imaging, Medical Imaging and Computing. Equal emphasis is on translating these technologies for pre-clinical and clinical applications in cancer and neurological diseases.

At Stanford, I invented a transrectal ultrasound and photoacoustic (TRUSPA) device for imaging human prostate using capacitive micromachined ultrasonic transducer (CMUT) array technology. Pilot clinical studies on prostate cancer patients demonstrated that the device is capable of simultaneously displaying anatomical and molecular information of the prostate. Currently, relevant molecular imaging approaches are being investigated to further improve the sensitivity and the specificity of the prostate cancer detection. Similarly, I also developed an intra-operative ultrasound and photoacoustic (iUSPA) device that is in the path to clinical translation for various applications.

My other research interests include Cerenkov luminescence imaging, and developing novel microscopy and in vitro diagnostic techniques for probing complex cell signaling pathways.

Clinical Trials

  • Photoacoustic Imaging (PAI) of the Prostate: A Clinical Feasibility Study Recruiting

    The purpose of our study is to image human prostate tissue using a transrectal photoacoustic imaging probe.

    View full details


All Publications

  • Construction and Validation of Nano Gold Tripods for Molecular Imaging of Living Subjects JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Cheng, K., Kothapalli, S., Liu, H., Koh, A. L., Jokerst, J. V., Jiang, H., Yang, M., Li, J., Levi, J., Wu, J. C., Gambhir, S. S., Cheng, Z. 2014; 136 (9): 3560-3571


    Anisotropic colloidal hybrid nanoparticles exhibit superior optical and physical properties compared to their counterparts with regular architectures. We herein developed a controlled, stepwise strategy to build novel, anisotropic, branched, gold nanoarchitectures (Au-tripods) with predetermined composition and morphology for bioimaging. The resultant Au-tripods with size less than 20 nm showed great promise as contrast agents for in vivo photoacoustic imaging (PAI). We further identified Au-tripods with two possible configurations as high-absorbance nanomaterials from various gold multipods using a numerical simulation analysis. The PAI signals were linearly correlated with their concentrations after subcutaneous injection. The in vivo biodistribution of Au-tripods favorable for molecular imaging was confirmed using small animal positron emission tomography (PET). Intravenous administration of cyclic Arg-Gly-Asp-d-Phe-Cys (RGDfC) peptide conjugated Au-tripods (RGD-Au-tripods) to U87MG tumor-bearing mice showed PAI contrasts in tumors almost 3-fold higher than for the blocking group. PAI results correlated well with the corresponding PET images. Quantitative biodistribution data revealed that 7.9% ID/g of RGD-Au-tripods had accumulated in the U87MG tumor after 24 h post-injection. A pilot mouse toxicology study confirmed that no evidence of significant acute or systemic toxicity was observed in histopathological examination. Our study suggests that Au-tripods can be reliably synthesized through stringently controlled chemical synthesis and could serve as a new generation of platform with high selectivity and sensitivity for multimodality molecular imaging.

    View details for DOI 10.1021/ja412001e

    View details for Web of Science ID 000332684700036

    View details for PubMedID 24495038

  • Single-Cell Photonic Nanocavity Probes NANO LETTERS Shambat, G., Kothapalli, S., Provine, J., Sarmiento, T., Harris, J., Gambhir, S. S., Vuckovic, J. 2013; 13 (11): 4999-5005


    In this report, we demonstrate for the first time photonic nanocavities operating inside single biological cells. Here we develop a nanobeam photonic crystal (PC) cavity as an advanced cellular nanoprobe, active in nature, and configurable to provide a multitude of actions for both intracellular sensing and control. Our semiconductor nanocavity probes emit photoluminescence (PL) from embedded quantum dots (QD) and sustain high quality resonant photonic modes inside cells. The probes are shown to be minimally cytotoxic to cells from viability studies, and the beams can be loaded in cells and tracked for days at a time, with cells undergoing regular division with the beams. We present in vitro label-free protein sensing with our probes to detect streptavidin as a path towards real-time biomarker and biomolecule detection inside single cells. The results of this work will enable new areas of research merging the strengths of photonic nanocavities with fundamental cell biology.

    View details for DOI 10.1021/nl304602d

    View details for Web of Science ID 000327111700001

  • Activatable Oligomerizable Imaging Agents for Photoacoustic Imaging of Furin-Like Activity in Living Subjects JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Dragulescu-Andrasi, A., Kothapalli, S., Tikhomirov, G. A., Rao, J., Gambhir, S. S. 2013; 135 (30): 11015-11022


    Photoacoustic (PA) imaging is continuing to be applied for physiological imaging and more recently for molecular imaging of living subjects. Owing to its high spatial resolution in deep tissues, PA imaging holds great potential for biomedical applications and molecular diagnostics. There is however a lack of probes for targeted PA imaging, especially in the area of enzyme-activatable probes. Here we introduce a molecular probe, which upon proteolytic processing is retained at the site of enzyme activity and provides PA contrast. The probe oligomerizes via a condensation reaction and accumulates in cells and tumors that express the protease. We demonstrate that this probe reports furin and furin-like activity in cells and tumor models by generating a significantly higher PA signal relative to furin-deficient and nontarget controls. This probe could report enzyme activity in living subjects at depths significantly greater than fluorescence imaging probes and has potential for molecular imaging in deep tumors.

    View details for DOI 10.1021/ja4010078

    View details for Web of Science ID 000322752900032

    View details for PubMedID 23859847

  • Molecular Photoacoustic Imaging of Follicular Thyroid Carcinoma CLINICAL CANCER RESEARCH Levi, J., Kothapalli, S., Bohndiek, S., Yoon, J., Dragulescu-Andrasi, A., Nielsen, C., Tisma, A., Bodapati, S., Gowrishankar, G., Yan, X., Chan, C., Starcevic, D., Gambhir, S. S. 2013; 19 (6): 1494-1502


    To evaluate the potential of targeted photoacoustic imaging as a noninvasive method for detection of follicular thyroid carcinoma.We determined the presence and activity of two members of matrix metalloproteinase family (MMP), MMP-2 and MMP-9, suggested as biomarkers for malignant thyroid lesions, in FTC133 thyroid tumors subcutaneously implanted in nude mice. The imaging agent used to visualize tumors was MMP-activatable photoacoustic probe, Alexa750-CXeeeeXPLGLAGrrrrrXK-BHQ3. Cleavage of the MMP-activatable agent was imaged after intratumoral and intravenous injections in living mice optically, observing the increase in Alexa750 fluorescence, and photoacoustically, using a dual-wavelength imaging method.Active forms of both MMP-2 and MMP-9 enzymes were found in FTC133 tumor homogenates, with MMP-9 detected in greater amounts. The molecular imaging agent was determined to be activated by both enzymes in vitro, with MMP-9 being more efficient in this regard. Both optical and photoacoustic imaging showed significantly higher signal in tumors of mice injected with the active agent than in tumors injected with the control, nonactivatable, agent.With the combination of high spatial resolution and signal specificity, targeted photoacoustic imaging holds great promise as a noninvasive method for early diagnosis of follicular thyroid carcinomas.

    View details for DOI 10.1158/1078-0432.CCR-12-3061

    View details for Web of Science ID 000316188900021

    View details for PubMedID 23349314

  • Endoscopic imaging of Cerenkov luminescence BIOMEDICAL OPTICS EXPRESS Kothapalli, S., Liu, H., Liao, J. C., Cheng, Z., Gambhir, S. S. 2012; 3 (6): 1215-1225


    We demonstrate feasibility of endoscopic imaging of Cerenkov light originated when charged nuclear particles, emitted from radionuclides, travel through a biological tissue of living subjects at superluminal velocity. The endoscopy imaging system consists of conventional optical fiber bundle/ clinical endoscopes, an optical imaging lens system, and a sensitive low-noise charge coupled device (CCD) camera. Our systematic studies using phantom samples show that Cerenkov light from as low as 1 µCi of radioactivity emitted from (18)F-Fluorodeoxyglucose (FDG) can be coupled and transmitted through conventional optical fibers and endoscopes. In vivo imaging experiments with tumor bearing mice, intravenously administered with (18)F-FDG, further demonstrated that Cerenkov luminescence endoscopy is a promising new tool in the field of endoscopic molecular imaging.

    View details for Web of Science ID 000304965700007

    View details for PubMedID 22741069

  • Deep Tissue Photoacoustic Imaging Using a Miniaturized 2-D Capacitive Micromachined Ultrasonic Transducer Array IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Kothapalli, S., Ma, T., Vaithilingam, S., Oralkan, O., Khuri-Yakub, B. T., Gambhir, S. S. 2012; 59 (5): 1199-1204


    In this paper, we demonstrate 3-D photoacoustic imaging (PAI) of light absorbing objects embedded as deep as 5 cm inside strong optically scattering phantoms using a miniaturized (4 mm × 4 mm × 500 ?m), 2-D capacitive micromachined ultrasonic transducer (CMUT) array of 16 × 16 elements with a center frequency of 5.5 MHz. Two-dimensional tomographic images and 3-D volumetric images of the objects placed at different depths are presented. In addition, we studied the sensitivity of CMUT-based PAI to the concentration of indocyanine green dye at 5 cm depth inside the phantom. Under optimized experimental conditions, the objects at 5 cm depth can be imaged with SNR of about 35 dB and a spatial resolution of approximately 500 ?m. Results demonstrate that CMUTs with integrated front-end amplifier circuits are an attractive choice for achieving relatively high depth sensitivity for PAI.

    View details for DOI 10.1109/TBME.2012.2183593

    View details for Web of Science ID 000303201000001

    View details for PubMedID 22249594

  • A photonic crystal cavity-optical fiber tip nanoparticle sensor for biomedical applications Applied Physics Letters Shambat G, Kothapalli SR, Khurana A, Provine J, Sarmiento T, Cheng K, Zhen C, Gambhir SS, Vuckovic J 2012; 100 (21): 213702-3
  • Design, Synthesis, and Imaging of an Activatable Photoacoustic Probe JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Levi, J., Kothapalli, S. R., Ma, T., Hartman, K., Khuri-Yakub, B. T., Gambhir, S. S. 2010; 132 (32): 11264-11269


    Photoacoustic tomography is a rapidly growing imaging modality that can provide images of high spatial resolution and high contrast at depths up to 5 cm. We report here the design, synthesis, and evaluation of an activatable probe that shows great promise for enabling detection of the cleaved probe in the presence of high levels of nonactivated, uncleaved probe, a difficult task to attain in absorbance-based modality. Before the cleavage by its target, proteolytic enzyme MMP-2, the probe, an activatable cell-penetrating peptide, Ceeee[Ahx]PLGLAGrrrrrK, labeled with two chromophores, BHQ3 and Alexa750, shows photoacoustic signals of similar intensity at the two wavelengths corresponding to the absorption maxima of the chromophores, 675 and 750 nm. Subtraction of the images taken at these two wavelengths makes the probe effectively photoacoustically silent, as the signals at these two wavelengths essentially cancel out. After the cleavage, the dye associated with the cell-penetrating part of the probe, BHQ3, accumulates in the cells, while the other dye diffuses away, resulting in photoacoustic signal seen at only one of the wavelengths, 675 nm. Subtraction of the photoacoustic images at two wavelengths reveals the location of the cleaved (activated) probe. In the search for the chromophores that are best suited for photoacoustic imaging, we have investigated the photoacoustic signals of five chromophores absorbing in the near-infrared region. We have found that the photoacoustic signal did not correlate with the absorbance and fluorescence of the molecules, as the highest photoacoustic signal arose from the least absorbing quenchers, BHQ3 and QXL 680.

    View details for DOI 10.1021/0104000a

    View details for Web of Science ID 000280861300058

    View details for PubMedID 20698693

  • Nonlinear photoacoustics for measuring the nonlinear optical absorption coefficient OPTICS EXPRESS Yelleswarapu, C. S., Kothapalli, S. 2010; 18 (9): 9020-9025


    We report a novel photoacoustic Z-scan (PAZ-scan) technique that combines the advantages offered by the conventional Z-scan method and the sensitivity of the photoacoustic detection. The sample is scanned through the focused laser beam and the generated photoacoustic signal is recorded using a 10 MHz focused ultrasound transducer. Since the signal strength is directly proportional to the optical absorption, PAZ-scan displays nonlinear behavior depicting the nonlinear optical absorption of the material. Among many advantages, our experiments on mouse blood show that PAZ-scan can potentially be used as a standard technique to calibrate contrast agents used in theranostics in general and photoacoustics in particular.

    View details for Web of Science ID 000277082200032

    View details for PubMedID 20588748

  • Spectral hole burning for ultrasound-modulated optical tomography of thick tissue Journal of Biomedical Optics [Xiao X, K., Liu H, Wang LV 2010; 15 (6): 066018
  • Ex vivo blood vessel imaging using ultrasound-modulated optical microscopy Journal of Biomedical Optics Kothapalli SR, Wang LV 2009; 14: 014015
  • Common-path multimodal optical microscopy Optics Letters Yelleswarapu CS, Marla Tipping, Kothapalli SR, Veraksa A, Rao DVGLN 2009; 39: 1243
  • Ultrasound-modulated optical microscopy Journal of Biomedical Optics Kothapalli SR, Wang LV 2008; 13: 054046
  • Optical Fourier techniques for medical image processing and phase contrast imaging Optics Communications, Invited Review Article, . Yelleswarapu CS, Kothapalli SR, Rao DVGLN 2008; 281: 1876
  • Imaging optically scattering objects with ultrasound-modulated optical tomography Optics Letters Kothapalli SR, Sakadzic S, Kim C, Wang LV 2007; 32: 2351
  • Phase contrast imaging using photo-thermally induced phase transitions in liquid crystals Applied Physics Letters. Yelleswarapu CS, Kothapalli SR, Vaillancourt Y, Aranda FJ, Kimball BR, Rao DVGLN 2006; 89: 2111161
  • All optical spatial filtering with power limiting materials Optics Express Yelleswarapu CS, Wu P, Kothapalli SR, Rao DVGLN, Kimball BR, Sai SS, Gowrishankar R, Sivaramakrishnan S 2006; 14: 1451
  • Nonlinear optical image processing with bacteriorhodopsin polymer films Molecular Crystals & Liquid Crystals Yelleswarapu CS, Wu P, Kothapalli SR, Rao DVGLN 2006; 446: 273
  • Nonlinear optical Fourier filtering for medical image processing Journal of Biomedical Optics Kothapalli SR, Wu P, Yelleswarapu CS, Rao DVGLN 2005; 10: 0440281
  • Spectral phase based medical image processing Academic Radiology. 2005;12():708. Kothapalli SR, Yelleswarapu CS, Naraharisetty SG, Wu P, Rao DVGLN 2005; 12: 708
  • Medical image processing using transient Fourier holography in bacteriorhodopsin films Applied Physics Letters Kothapalli SR, Wu P, Yelleswarapu CS, Rao DVGLN. 2004; 85: 5836
  • Self-diffraction in bacteriorhodopsin films for low power optical limiting Optics Express Narayana Rao D, Yelleswarapu CS, Kothapalli SR, Rao DVGLN, Kimball BR 2003; 11: 2848