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.
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