This competitive renewal application will advance the development of an intravascular bi-modal technology for diagnosis of arterial wall pathologies including rupture-prone (vulnerable) atherosclerotic plaques. We propose to optimize, construct and test a unique clinically-compatible system that combines fast, time-resolved fluorescence spectroscopy (TRFS) to dynamically evaluate atherosclerotic plaque composition under pull-back motion, with intravascular ultrasound (IVUS) that allows for both visual reconstruction of plaque microanatomy and guidance of TRFS measurements. The resulting system will enable detection and monitoring of biochemical, functional and structural features of atherosclerotic lesions with clinical relevance (e.g. predictive of plaque rupture). In this renewal application, we propose to advance the integration and in-vivo validation of this bi-modal technology and prepare for clinical intravascular evaluation through the following specific aims:
Aim 1. To design, construct and optimize prototype bi-modal (TRFS-IVUS) intravascular catheters to demonstrate (1) the technical feasibility of integrating the TRFS with single element transducer IVUS catheters and (2) the ability of the bi-modal system to provide real-time diagnostic feedback information concerning arterial wall composition and structure. To achieve this we will build two catheter systems and validate their technical performance in-vitro (tissue phantoms, arterial segments).
Aim 2. To demonstrate in-vivo the validity of continuous/radial TRFS data acquisition under pull-back motion and under IVUS guidance. To achieve this we will conduct transluminal procedures in an atherosclerotic pig model using Catheter Assembly I. We will determine optimal experimental parameters for dynamic TRFS acquisition in pulsatile blood flow conditions, evaluate the limiting design factors for the bi-modal catheter, and determine design and experimental parameters to optimize co-registration of TRFS and IVUS data.
Aim 3. To determine the ability of optimized Catheter Assembly II to operate intravascularly in various arterial beds, including coronary arteries, and to determine its diagnostic capability. This will be achieved by testing the bi-modal technique in an atherosclerotic pig model (in-vivo) and in human coronary segments (ex-vivo). This will demonstrate the feasibility of the catheter prototype to operate effectively intravascularly under conditions of blood flow and motion, to collect co-registered TRFS/IVUS, and to generate diagnostic information.
Aim 4. Establish the feasibility of TRFS-IVUS to dynamically and in near-real time (few seconds) characterize, discriminate and visualize relevant intravascular pathologies. To achieve this we will develop computational/classification models employing features derived from TRFS-data, IVUS RF-data (""""""""virtual histology"""""""") and IVUS greyscale (""""""""echogenicity"""""""") images;apply these models to data derived from bi-modal measurements (Aims 2 &3) to determine the sensitivity, specificity, and overall predictive value of the proposed method;and validate this data against tissue histopathology.
Aim 5. Prepare and submit an application for an FDA Sponsor-Investigator Investigational Device Exemption (IDE) for future clinical evaluation of the bi-modal system. This will make use of experimental data and results obtained in Aim 3 and Aim 4 and additional tests for evaluation of safety, effectiveness, and diagnostic capabilities as required by the FDA.

Public Health Relevance

The proposed bi-modal technique targets development of new paradigms for diagnosis and management of atherosclerotic cardiovascular disease that affects >80 million individuals in the US and represents the leading cause of death (>830,000/year). The proposed approach of integrating TRFS with IVUS should improve the diagnostic ability of IVUS, the most widely used intravascular imaging technique in interventional cardiology. Examples of important applications for this bimodal technology in patients who are candidates for transluminal interventional procedures include: a) If a plaque is more accurately classified with TRFS-IVUS and the risk of rupture can be predicted, patients could be identified and treated prior to symptoms or rupture. b) If the TRFS- IVUS system allows better understanding of atherosclerotic plaque pathologies it could be used to predict which patients would benefit from therapy. c) In the large number of patients who undergo repeat catheterization, it should allow the clinician to monitor the effects of various pharmacologic (e.g lipid lowering drugs) interventions.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Buxton, Denis B
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Davis
Biomedical Engineering
Schools of Engineering
United States
Zip Code
Bec, Julien; Phipps, Jennifer E; Gorpas, Dimitris et al. (2017) In vivo label-free structural and biochemical imaging of coronary arteries using an integrated ultrasound and multispectral fluorescence lifetime catheter system. Sci Rep 7:8960
Fereidouni, Farzad; Gorpas, Dimitris; Ma, Dinglong et al. (2017) Rapid fluorescence lifetime estimation with modified phasor approach and Laguerre deconvolution: a comparative study. Methods Appl Fluoresc 5:035003
Bourantas, Christos V; Jaffer, Farouc A; Gijsen, Frank J et al. (2017) Hybrid intravascular imaging: recent advances, technical considerations, and current applications in the study of plaque pathophysiology. Eur Heart J 38:400-412
Mitra, Debika; Fatakdawala, Hussain; Nguyen-Truong, Michael et al. (2017) Detection of Pentosidine Cross-Links in Cell-Secreted Decellularized Matrices Using Time Resolved Fluorescence Spectroscopy. ACS Biomater Sci Eng 3:1944-1954
Ma, Dinglong; Liu, Jing; Qi, Jinyi et al. (2017) Reply to Comment: 'A novel method for fast and robust estimation of fluorescence decay dynamics using constrained least-square deconvolution with Laguerre expansion'. Phys Med Biol 62:1637-1641
Dochow, Sebastian; Fatakdawala, Hussain; Phipps, Jennifer E et al. (2016) Comparing Raman and fluorescence lifetime spectroscopy from human atherosclerotic lesions using a bimodal probe. J Biophotonics 9:958-66
Dochow, Sebastian; Ma, Dinglong; Latka, Ines et al. (2015) Combined fiber probe for fluorescence lifetime and Raman spectroscopy. Anal Bioanal Chem 407:8291-301
Ma, Dinglong; Bec, Julien; Gorpas, Dimitris et al. (2015) Technique for real-time tissue characterization based on scanning multispectral fluorescence lifetime spectroscopy (ms-TRFS). Biomed Opt Express 6:987-1002
Gorpas, Dimitris; Fatakdawala, Hussain; Bec, Julien et al. (2015) Fluorescence lifetime imaging and intravascular ultrasound: co-registration study using ex vivo human coronaries. IEEE Trans Med Imaging 34:156-66
Fatakdawala, Hussain; Gorpas, Dimitris; Bishop, John W et al. (2015) Fluorescence Lifetime Imaging Combined with Conventional Intravascular Ultrasound for Enhanced Assessment of Atherosclerotic Plaques: an Ex Vivo Study in Human Coronary Arteries. J Cardiovasc Transl Res 8:253-63

Showing the most recent 10 out of 54 publications