Simultaneous Morphological and Flow Imaging Enabled by Megahertz Intravascular Doppler Optical Coherence Tomography

We demonstrate three-dimensional intravascular flow imaging compatible with routine clinical image acquisition workflow by means of megahertz (MHz) intravascular Doppler Optical Coherence Tomography (OCT). The OCT system relies on a 1.1 mm diameter motorized imaging catheter and a 1.5 MHz Fourier Domain Mode Locked (FDML) laser. Using a post processing method to compensate the drift of the FDML laser output, we can resolve the Doppler phase shift between two adjoining OCT A-line datasets. By interpretation of the velocity field as measured around the zero phase shift, the flow direction at specific angles can be qualitatively estimated. Imaging experiments were carried out in phantoms, micro channels, and swine coronary artery in vitro at a speed of 600 frames/s. The MHz wavelength sweep rate of the OCT system allows us to directly investigate flow velocity of up to 37.5 cm/s while computationally expensive phase-unwrapping has to be applied to measure such high speed using conventional OCT system. The MHz sweep rate also enables a volumetric Doppler imaging even with a fast pullback at 40 mm/s. We present the first simultaneously recorded 3D morphological images and Doppler flow profiles. Flow pattern estimation and three-dimensional structural reconstruction of entire coronary artery are achieved using a single OCT pullback dataset

Thermo-elastic optical coherence tomography

The absorption of nanosecond laser pulses induces rapid thermo-elastic deformation in tissue. A sub-micrometer scale displacement occurs within a few microseconds after the pulse arrival. In this Letter, we investigate the laser-induced thermo-elastic deformation using a 1.5 MHz phase-sensitive optical coherence tomography (OCT) system. A displacement image can be reconstructed, which enables a new modality of phase-sensitive OCT, called thermo-elastic OCT. An analysis of the results shows that the optical absorption is a dominating factor for the displacement. Thermo-elastic OCT is capable of visualizing inclusions that do not appear on the structural OCT image, providing additional tissue type information

Clone-specific expression, transcriptional regulation, and action of interleukin-6 in human colon carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Many cancer cells produce interleukin-6 (IL-6), a cytokine that plays a role in growth stimulation, metastasis, and angiogenesis of secondary tumours in a variety of malignancies, including colorectal cancer. Effectiveness of IL-6 in this respect may depend on the quantity of basal and inducible IL-6 expressed as the tumour progresses through stages of malignancy. We therefore have evaluated the effect of <it>IL-6 </it>modulators, i.e. IL-1β, prostaglandin E₂, 17β-estradiol, and 1,25-dihydroxyvitamin D₃, on expression and synthesis of the cytokine at different stages of tumour progression.</p> <p>Methods</p> <p>We utilized cultures of the human colon carcinoma cell clones Caco-2/AQ, COGA-1A and COGA-13, all of which expressed differentiation and proliferation markers typical of distinct stages of tumour progression. IL-6 mRNA and protein levels were assayed by RT-PCR and ELISA, respectively. DNA sequencing was utilized to detect polymorphisms in the <it>IL-6 </it>gene promoter.</p> <p>Results</p> <p><it>IL-6 </it>mRNA and protein concentrations were low in well and moderately differentiated Caco-2/AQ and COGA-1A cells, but were high in poorly differentiated COGA-13 cells. Addition of IL-1β (5 ng/ml) to a COGA-13 culture raised IL-6 production approximately thousandfold via a prostaglandin-independent mechanism. Addition of 17β-estradiol (10^-7M) reduced basal IL-6 production by one-third, but IL-1β-inducible IL-6 was unaffected. Search for polymorphisms in the <it>IL-6 </it>promoter revealed the presence of a single haplotype, i.e., -597A/-572G/-174C, in COGA-13 cells, which is associated with a high degree of transcriptional activity of the <it>IL-6 </it>gene. IL-6 blocked differentiation only in Caco-2/AQ cells and stimulated mitosis through up-regulation of c-<it>myc </it>proto-oncogene expression. These effects were inhibited by 10^-8M 1,25-dihydroxyvitamin D₃.</p> <p>Conclusion</p> <p>In human colon carcinoma cells derived from well and moderately differentiated tumours, IL-6 expression is low and only marginally affected, if at all, by PGE₂, 1,25-dihydroxyvitamin D₃, and 17β-estradiol. However, IL-6 is highly abundant in undifferentiated tumour cells and is effectively stimulated by IL-1β. In case of overexpression of an <it>IL-6 </it>gene variant with extreme sensitivity to IL-1β, massive release of the cytokine from undifferentiated tumour cells may accelerate progression towards malignancy by paracrine action on more differentiated tumour cells with a still functioning proliferative IL-6 signalling pathway.</p

Intravascular optical coherence tomography imaging at 3200 frames per second

We demonstrate intravascular optical coherence tomography (OCT) imaging with frame rate up to 3.2 kHz (192,000 rpm scanning). This was achieved by using a custom-built catheter in which the circumferential scanning was actuated by a 1.0 mm diameter synchronous motor. The OCT system, with an imaging depth of 3.7 mm (in air), is based on a Fourier domain mode locked laser operating at an A-line rate of 1.6 MHz. The diameter of the catheter is 1.1 mm at the tip. Ex vivo images of human coronary artery (78.4 mm length) were acquired at a pullback speed of 100 mm/s. True 3D volumetric imaging of the entire artery, with dense and isotropic sampling in all dimensions, was performed in <1 second acquisition time