Tissue diagnostic features generated by a bimodal technique integrating scanning time-resolved fluorescence spectroscopy (TRFS) and ultrasonic backscatter microscopy (UBM) are investigated in an in vivo hamster oral carcinoma model. Tissue fluorescence is excited by a pulsed nitrogen laser and spectrally and temporally resolved using a set of filters/dichroic mirrors and a fast digitizer, respectively. A 41-MHz focused transducer (37-μm axial, 65-μm lateral resolution) is used for UBM scanning. Representative lesions of the different stages of carcinogenesis show that fluorescence characteristics complement ultrasonic features, and both correlate with histological findings. These results demonstrate that TRFS-UBM provide a wealth of co-registered, complementary data concerning tissue composition and structure as it relates to disease status. The direct co-registration of the TRFS data (sensitive to surface molecular changes) with the UBM data (sensitive to cross-sectional structural changes and depth of tumor invasion) is expected to play an important role in pre-operative diagnosis and intra-operative determination of tumor margins.
We report the development and validation of an intravascular rotary catheter for bimodal interrogation of arterial pathologies. This is based on a point-spectroscopy scanning time-resolved fluorescence spectroscopy technique enabling reconstruction of fluorescence lifetime images (FLIm) and providing information on arterial intima composition and intravascular ultrasound (IVUS) providing information on arterial wall morphology. The catheter design allows for independent rotation of the ultrasonic and optical channels within an 8 Fr outer diameter catheter sheath and integrates a low volume flushing channel for blood removal in the optical pathways. In the current configuration, the two channels consist of (a) a standard 3 Fr IVUS catheter with single element transducer (40 MHz) and (b) a side-viewing fiber optic (400 μm core). Experiments conducted in tissue phantoms showed the ability of the catheter to operate in an intraluminal setting and to generate coregistered FLIm and IVUS in one pull-back scan. Current results demonstrate the feasibility of the catheter for simultaneous bimodal interrogation of arterial lumen and for generation of robust fluorescence lifetime data under IVUS guidance. These results facilitate further development of a FLIm-IVUS technique for intravascular diagnosis of atherosclerotic cardiovascular diseases including vulnerable plaques.
We report the development and validation of an intravascular rotary catheter that enables bi-modal interrogation of
arterial pathologies based on fast-frame time-resolved fluorescence spectroscopy (TRFS) and intravascular ultrasound
(IVUS). The catheter is based on a parallel design that allows for independent rotation of the ultrasonic and optical
channels within an 8 Fr outer diameter catheter sheath and integrates a low volume flushing channel for blood removal
in the optical pathways. In current configuration, the two channels consist of a) a standard 8 Fr IVUS catheter with single
element transducer (15 MHz) and b) a side-viewing UV-grade silica/silica fiber optic (400 μm core). The catheter is
terminated by a small (0.82 mm internal diameter) polyimide tube to keep the fiber stable within the sheath. To clear the
field of view from blood, a saline solution can be flushed in a sheath channel, concentric with the fiber optic, through the
tube and in a radial opening aligned with the fiber's optical beam. The flushing function was optimized with a
computational fluid dynamics (CFD) model pursued in a parallel study. The ability of the catheter to operate in
intraluminal setting in blood flow, the effect of probe-to-tissue distance on optical signal and ability to generate co-registered
TRFS and IVUS data were demonstrated in blood vessel phantoms. Current results demonstrate the feasibility
of the described catheter for parallel interrogation of vessel walls based on TRFS and IVUS and to generate robust TRFS
data. These results facilitate further development of a bi-modal TRFS-IVUS technique for intravascular diagnosis of
atherosclerotic cardiovascular diseases including vulnerable plaques.
We demonstrate the feasibility of a time-resolved fluorescence spectroscopy (TRFS) technique for intraluminal investigation of arterial vessel composition under intravascular ultrasound (IVUS) guidance. A prototype 1.8-mm (5.4 Fr) catheter combining a side-viewing optical fiber (SVOF) and an IVUS catheter was constructed and tested with in vitro vessel phantoms. The prototype catheter can locate a fluorophore in the phantom vessel wall, steer the SVOF in place, perform blood flushing under flow conditions, and acquire high-quality TRFS data using 337-nm wavelength excitation. The catheter steering capability used for the coregistration of the IVUS image plane and the SVOF beam produce a guiding precision to an arterial phantom wall site location of 0.53±0.16 mm. This new intravascular multimodal catheter enables the potential for in vivo arterial plaque composition identification using TRFS.
A unique tissue phantom is reported here that mimics the optical and acoustical properties of biological tissue and
enables testing and validation of a dual-modality clinical diagnostic system combining time-resolved laser-induced
fluorescence spectroscopy (TR-LIFS) and ultrasound backscatter microscopy (UBM). The phantom consisted of contrast
agents including silicon dioxide particles with a range of diameters from 0.5 to 10 μm acting as optical and acoustical
scatterers, and FITC-conjugated dextran mimicking the endogenous fluorophore in tissue. The agents were encapsulated
in a polymer bead attached to the end of an optical fiber with a 200 μm diameter using a UV-induced polymerization
technique. A set of beads with fibers were then implanted into a gel-based matrix with controlled patterns including a
design with lateral distribution and a design with successively changing depth. The configuration presented here allowed
the validation of the hybrid fluorescence spectroscopic and ultrasonic system by detecting the lateral and depth
distribution of the contrast agents, as well as for coregistration of the ultrasonic image with spectroscopic data. In
addition, the depth of the beads in the gel matrix was changed to explore the effect of different concentration ratio of the
mixture on the fluorescence signal emitted.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.