Minimally Invasive Polarization Sensitive Optical Coherence Tomography (PS-OCT) for assessing Pre-OA, a pilot study on technical feasibility.

Objective: Efforts to develop chondroprotective approaches to halt osteoarthritis (OA) progression have recently increased. Current imaging techniques are critical in managing advanced OA, but greater resolution is needed to identify reversible stages (pre-OA). Optical coherence tomography (OCT) is a micron scale imaging technology widely used in ophthalmology, cardiology, and neurology. We previously demonstrated that polarization sensitive OCT (PS-OCT) can identify pre-OA in vitro, in animals, and in open surgical fields. This feasibility study examines performing intraarticular PS-OCT using a flexible endocatheter introduced through a stiff 18-gauge spinal needle. Results are critical for designing larger clinical trials examining minimally invasive PS-OCT's ability to identify pre-OA. Design: Fifteen patients undergoing arthroscopic partial medial meniscectomy were selected to confirm their risk for rapid progression to OA. Magnetic resonance imaging (MRI) was obtained at time 0 and at 2.5 years to determine if significant OA developed over this short period and for correlation with time zero PS-OCT results. Results: Over half of the patients developed frank OA by 2.65 ± 0.28 years. All cartilage surfaces were successfully imaged by PS-OCT, but endocatheter redesign is needed. Normal to severely abnormal areas by PS-OCT (all normal by MRI) were successfully identified. PS-OCT assessments were promising for predicting OA progression (p < 0.008). However, the study's low power prevented definite conclusions regarding predictive value. Conclusions: This pilot study produced at least two outcomes critical for future larger trial designs: medial meniscectomy patients are well-suited for studying PS-OCT's ability to predict future OA and substantial endocatheter redesign is needed.

Optical biopsy and imaging using optical coherence tomography.

Optical coherence tomography is a new imaging technique that can perform high-resolution, micrometre-scale, cross-sectional imaging in biological systems. The technology has been developed, and reduced to, preliminary clinical practice in ophthalmology. The challenging problem that OCT may address is the development of 'optical biopsy' techniques. These techniques can provide diagnostic imaging of tissue morphology without the need for excision of specimens. Many investigations remain to identify optimal areas for clinical application, and additional engineering must be done to integrate vertically the technology and to reduce it to clinical practice. Nevertheless, preliminary studies indicate the feasibility of developing this technology for a wide range of clinical and research diagnostic imaging applications. The ability to non-excisionally evaluate tissue morphology using a catheter or an endoscope could have a significant impact on the diagnosis and management of a wide range of diseases.

In vivo endoscopic optical biopsy with optical coherence tomography.

Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as "optical biopsy," was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.

A Quantum Field Approach for Advancing Optical Coherence Tomography Part I: First Order Correlations, Single Photon Interference, and Quantum Noise.

Optical coherence tomography has become an important imaging technology in cardiology and ophthalmology, with other applications under investigations. Major advances in optical coherence tomography (OCT) imaging are likely to occur through a quantum field approach to the technology. In this paper, which is the first part in a series on the topic, the quantum basis of OCT first order correlations is expressed in terms of full field quantization. Specifically first order correlations are treated as the linear sum of single photon interferences along indistinguishable paths. Photons and the electromagnetic (EM) field are described in terms of quantum harmonic oscillators. While the author feels the study of quantum second order correlations will lead to greater paradigm shifts in the field, addressed in part II, advances from the study of quantum first order correlations are given. In particular, ranging errors are discussed (with remedies) from vacuum fluctuations through the detector port, photon counting errors, and position probability amplitude uncertainty. In addition, the principles of quantum field theory and first order correlations are needed for studying second order correlations in part II.

Beneficial effects of tissue-type plasminogen activator in acute myocardial ischemia in cats.

Tissue-type plasminogen activator is a new thrombolytic agent that dissolves intravascular thrombi in coronary and peripheral vessels with less pronounced systemic lysis than that produced by streptokinase. Plasminogen activator was shown to induce reperfusion, and to salvage ischemic myocardium, by lysing experimentally induced coronary artery thrombi. The effect of a melanoma cell-derived tissue-type plasminogen activator was studied in cat myocardium rendered ischemic by coronary artery ligation for 2 hours and reperfused for another 4 hours. Plasminogen activator was infused at a rate of 500 IU X kg-1 X min-1 for the first 30 minutes of reperfusion. The marked increase in plasma creatine kinase activity during reperfusion was significantly lower in plasminogen activator-treated cats at 4, 5 and 6 hours, with 7.7 +/- 1.5 X 10(-3) IU X mg protein-1 (n = 8) in the plasminogen activator group versus 17.8 +/- 3.5 X 10(-3) IU X mg protein-1 (n = 7) in the vehicle group at 6 hours (mean +/- SEM). The area at risk in the two ischemic groups was not different, being 14.6 +/- 1.5 and 16.6 +/- 1.4% of total left ventricular mass for the treated and untreated groups, respectively. However, the mass of necrotic tissue determined histochemically was significantly lower in the plasminogen activator-treated group, accounting for 29.5 +/- 3.9% of the area at risk compared with 46.8 +/- 4.2% of area at risk in cats receiving only the vehicle (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Optical coherence tomography: an emerging technology for biomedical imaging and optical biopsy.

Optical coherence tomography (OCT) is an emerging technology for performing high-resolution cross-sectional imaging. OCT is analogous to ultrasound imaging, except that it uses light instead of sound. OCT can provide cross-sectional images of tissue structure on the micron scale in situ and in real time. Using OCT in combination with catheters and endoscopes enables high-resolution intraluminal imaging of organ systems. OCT can function as a type of optical biopsy and is a powerful imaging technology for medical diagnostics because unlike conventional histopathology which requires removal of a tissue specimen and processing for microscopic examination, OCT can provide images of tissue in situ and in real time. OCT can be used where standard excisional biopsy is hazardous or impossible, to reduce sampling errors associated with excisional biopsy, and to guide interventional procedures. In this paper, we review OCT technology and describe its potential biomedical and clinical applications.

Lipoxins stimulate prostacyclin generation by human endothelial cells.

Cultured human umbilical endothelial cells were incubated with lipoxins and their ability to generate prostacyclin (PGI2) was assessed and compared to that induced by either leukotriene C4 or an ionophore of divalent cations (A-23,187). When exposed to either lipoxin A4, lipoxin B4, or 7-cis,11-trans-lipoxin A4, endothelial cells generated prostacyclin detected as 6-keto-PGF1 alpha. Of the lipoxins examined, 7-cis,11-trans-lipoxin A4 proved to be the most effective with PGI2 production twice that induced by equimolar amounts of A-23,187 (5 microM). On a molar basis, lipoxin A4 and lipoxin B4 were less potent than leukotriene C4 although they were more efficacious. When either lipoxin A4 or lipoxin B4 was added to cells simultaneously with leukotriene C4, the formation of prostacyclin was greater than that induced by leukotriene C4 alone. During the time course of exposure to lipoxins (0-20 min, 37 degrees C), cultured endothelial cells did not further transform these compounds via omega-oxidation as determined by reverse-phase HPLC. These data indicate that lipoxins can stimulate PGI2 generation by human endothelial cells. Moreover, they suggest a role for these lipoxygenase products of arachidonic acid in the regulation of hemostasis, inflammation and vascular reactivity.

Imaging of coronary artery microstructure (in vitro) with optical coherence tomography.

OCT achieves high-resolution and image differentiation of vascular tissues to a degree that has not been previously possible with any method except excisional biopsy. Thus, OCT represents a promising new diagnostic technology for intracoronary imaging, which could permit the in vivo evaluation of critical vascular pathology.

Assessment of coronary plaque with optical coherence tomography and high-frequency ultrasound.

This study compares the ability of intravascular optical coherence tomography (OCT) and high-frequency intravascular ultrasound (IVUS) to image highly stenotic human coronary arteries in vitro. Current imaging modalities have insufficient resolution to perform risk stratification based on coronary plaque morphology. OCT is a new technology capable of imaging at a resolution of 5 to 20 microm, which has demonstrated the potential for coronary arterial imaging in prior experiments. Human postmortem coronary arteries with severely stenotic segments were imaged with catheter-based OCT and IVUS. The OCT system had an axial resolution of 20 microm and a transverse resolution of 30 microm. OCT was able to penetrate and image near-occlusive coronary plaques. Compared with IVUS, these OCT images demonstrated superior delineation of vessel layers and lack of ring-down artifact, leading to clearer visualization of the vessel plaque and intima. Histology confirmed the accuracy and high contrast of vessel layer boundaries seen on OCT images. Thus, catheter-based OCT systems are able to image near-occlusive coronary plaques with higher resolution than that of IVUS.

Cardioprotective actions of human superoxide dismutase in two reperfusion models of myocardial ischaemia in the rat.

1. In rats under ether anaesthesia, the left coronary artery was ligated and reperfused after 10 min of ischaemia. Forty-eight hours later the myocardium was analyzed for creatine kinase (CK) activity. 2. Human superoxide dismutase (h-SOD) given 1 min after occlusion and again 6 h later significantly improved survival and retarded the loss of myocardial CK. 3. In rat isolated hearts perfused at 15% of normal flow for 30 min followed by re-establishment of normal flow for 20 min, perfusion pressure increased by 72% and myocardial CK decreased by 44%. No significant changes occurred in wet-to-dry heart weight ratio. 4. Administration of h-SOD at 2.5 or 5.0 mg, significantly attenuated the elevated post-ischaemic perfusion pressure and the loss of myocardial CK activity in rat perfused hearts. 5. h-SOD appears to be an effective anti-ischaemic agent in the intact animal as well as the isolated perfused heart of the rat subjected to low flow followed by reperfusion at normal flow. The mechanism of this cardioprotective effect is not totally dependent upon the formed elements of the blood, but may be partially due to a direct cytoprotective effect.

Optical biopsy with optical coherence tomography.

A need exists in medicine for a technology capable of 'optical biopsy,' imaging at or near the resolution of histopathology without the need for excisional biopsy. Optical coherence tomography (OCT) is a recently developed imaging technology that uses infrared light to generate cross-sectional images on a micron scale. In this work, the feasibility of OCT for optical biopsy was confirmed with in vitro tissue from the skeletal and male reproductive systems. This work supports the hypothesis that OCT is an attractive technology for in vivo optical biopsy.

New technology for high-speed and high-resolution optical coherence tomography.

Optical coherence tomography (OCT) is an optical imaging technique that is capable of performing micron-scale, cross-sectional imaging of internal microstructure in biological systems. OCT is analogous to ultrasound B mode imaging except that it uses light rather than sound and performs imaging by measuring the back-scattered intensity of light from structures in tissue. We describe recent advances in OCT technology including the application of short pulse solid state lasers based on Ti: Al2O3 and Cr: Mg2SiO4 to enable high-resolution, high-speed imaging as well as the development of OCT catheter/endoscope delivery to permit imaging of internal organ systems. OCT enables the nonexcisional, in situ, real-time imaging of tissue microstructure and is thus a powerful and promising technique for optical biopsy.

High-resolution imaging of gynecologic neoplasms using optical coherence tomography.

BACKGROUND: A modality capable of imaging the female reproductive tract, at or near the cellular level, could lead to the detection of diseases at earlier stages than currently possible. Optical coherence tomography achieves high resolutions in the cellular range (4-20 microm) and could accomplish that level of detection. METHOD: Optical coherence tomography imaging of gynecologic tissue was studied in vitro on normal and neoplastic human cervical and uterine tissue. EXPERIENCE: The structures of the normal ectocervix and endocervix, including epithelium, basal membrane, and glands, were identified clearly. These findings were compared with changes associated with carcinoma in situ and invasive carcinoma. The optical coherence tomography images of the uterus also showed changes between microstructural features of normal tissue and endometrial adenocarcinoma. CONCLUSION: Optical coherence tomography of tissue microstructures showed potential for powerful, minimally invasive assessment of the female reproductive tract at a resolution greater than any current clinical imaging method.

Imaging developing neural morphology using optical coherence tomography.

Imaging technologies offer numerous possibilities to investigate the processes involved in neural development. The optical coherence tomography (OCT) technology is analogous to ultrasound backscatter microscopy except reflections of light are detected rather than sound. The OCT technology combines high-resolution in vivo imaging in a diode-based benchtop instrument capable of micron-scale resolution in transparent and non-transparent biological specimens. In this paper, we examine the potential of using OCT for the investigation of developing neural morphology. To demonstrate the capabilities of this technique in assessing neural development, we have chosen to image early normal and abnormal neural morphology in a common developmental biology model, Xenopus laevis. In vivo images clearly identify gross and subtle differences in neural structure and may offer an alternative to the costly and time-consuming process of repeated histological preparation for neural developmental studies. Because imaging can be performed rapidly and repeatedly, the morphological changes of single specimens can be followed throughout development. To illustrate the future potential of this technique, a state-of-the-art Cr4+:forsterite modelocked laser is used as a broad bandwidth light source to image individual cells in a developing specimen.

Anti-ischemic actions of a new thromboxane receptor antagonist, SQ-29,548, in acute myocardial ischemia.

Thromboxane A2 (TxA2) has been implicated as a mediator of ischemic damage to the myocardium. A new, selective thromboxane receptor antagonist, SQ-29,548 (2 mg/kg bolus + 2 mg/kg per h infusion) was studied for its effects on the extension of ischemic damage following acute myocardial ischemia (MI) in the rat. Administration of SQ-29,548 to sham MI rats had no significant effect on mean arterial blood pressure or heart rate over the 6 h experimental protocol. Ischemic damage was assessed by measurement of the depletion of creatine kinase (CK) activity and amino-nitrogen concentration from the myocardium. Six hours following ligation of the left main coronary artery, there was a significant loss of both CK (P less than 0.001) and amino-nitrogen (P less than 0.001) from the left ventricular free wall (LVFW). Administration of SQ-29,548 significantly blunted this loss of CK activity (P less than 0.01) and amino-nitrogen concentration (P less than 0.001) from the ischemic myocardium. Furthermore, the survival rate at 6 h following acute coronary artery ligation was 100% (7/7) for rats given SQ-29,548 and 58% (11/19) for rats given only the vehicle (P less than 0.05). These data indicate that SQ-29,548 significantly prevents the extension of ischemic damage in the myocardium and improves survival following acute coronary artery ligation, suggesting an important role for TxA2 in the pathophysiology of acute myocardial ischemia.

Mechanism of antagonism of thromboxane receptors in vascular smooth muscle.

The mechanism and profile of antagonism of thromboxane receptors were studied in isolated perfused cat coronary arteries and in rat aortic rings. In cat coronary arteries, the thromboxane receptor antagonist (TxRA) BM-13,505 at concentrations from 3 to 300 ng/ml, significantly attenuated the vasoconstrictor effects of both a thromboxane A2 analog (CTA2) and an endoperoxide analog (U-46,619) and did not alter the constrictor responses to leukotriene D4, arginine vasopressin, or angiotensin II. In rat aortic rings precontracted by CTA2 or U-46,619, the effective threshold concentration of BM-13,505 for relaxation was 5 ng/ml. Lower concentrations of BM-13,505 exerted no relaxation, and higher concentrations exhibited faster relaxation to the precontracted baseline levels. This relaxation was not observed in aortic rings precontracted by norepinephrine or angiotensin II. The action of TxRA was not influenced by the absence of the endothelium or by pretreatment with a selective guanylate cyclase inhibitor, methylene blue. Also, thromboxane receptor antagonists do not appear to block thromboxane induced constriction by action as free radical scavengers. It can be concluded that replacing thromboxane A2 on the vascular receptor by a TxRA is the main factor responsible for the antagonism of thromboxane induced vasoconstriction in vascular smooth muscle preparations, not, the presence of the endothelium, activation of guanylate cyclase, or scavenging of superoxide free radicals.

Two- and three-dimensional high-resolution imaging of the human oviduct with optical coherence tomography.

OBJECTIVE: To evaluate the feasibility of optical coherence tomography, a new method of micron-scale imaging, for high-resolution assessment of the oviduct. Optical coherence tomography is analogous to ultrasound except that it measures the backreflection of infrared light rather than acoustical waves. DESIGN: The ampulla of a human fallopian tube was imaged in vitro using optical coherence tomography. Images were generated in 2 and 3 dimensions. SETTING: University. PATIENT(S): Samples were obtained from women who had undergone hysterectomy for leiomyomatosis. INTERVENTION(S): None MAIN OUTCOME MEASURE(S): The ability to perform imaging on a micron scale, which is a level of resolution higher than that of any currently available clinical technology. RESULT(S): Two- and three-dimensional data sets of the reflectance of a human fallopian tube were acquired. A volume of 5 x 5 x 2.5 mm (length x width x depth) was scanned. The axial resolution was 11 microm, and the lateral resolution at the focus was 20 microm. The data sets showed detailed structures of the fallopian tube. CONCLUSION(S): Our ability to obtain micron-scale two- and three-dimensional images of an in vitro oviduct suggests that it may be possible to identify and surgically treat tubal causes of infertility.

High resolution in vivo intra-arterial imaging with optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) is a new method of catheter based micron scale imaging. OCT is analogous to ultrasound, measuring the intensity of backreflected infrared light rather than sound waves. OBJECTIVE: To demonstrate the ability of OCT to perform high resolution imaging of arterial tissue in vivo. METHODS: OCT imaging of the abdominal aorta of New Zealand white rabbits was performed using a 2.9 F OCT imaging catheter. Using an ultrashort pulse laser as a light source for imaging, an axial resolution of 10 micrometer was achieved. RESULTS: Imaging was performed at 4 frames/second and data were saved in either super VHS or digital format. Saline injections were required during imaging because of the signal attenuation caused by blood. Microstructure was sharply defined within the arterial wall and correlated with histology. Some motion artefacts were noted at 4 frames/second. CONCLUSIONS: In vivo imaging of the rabbit aorta was demonstrated at a source resolution of 10 micrometer, but required the displacement of blood with saline. The high resolution of OCT allows imaging to be performed near the resolution of histopathology, offering the potential to have an impact both on the identification of high risk plaques and the guidance of interventional procedures.

Assessing atherosclerotic plaque morphology: comparison of optical coherence tomography and high frequency intravascular ultrasound.

BACKGROUND: OCT can image plaque microstructure at a level of resolution not previously demonstrated with other imaging techniques because it uses infrared light rather than acoustic waves. OBJECTIVES: To compare optical coherence tomography (OCT) and intravascular ultrasound (IVUS) imaging of in vitro atherosclerotic plaques. METHODS: Segments of abdominal aorta were obtained immediately before postmortem examination. Images of 20 sites from five patients were acquired with OCT (operating at an optical wavelength of 1300 nm which was delivered to the sample through an optical fibre) and a 30 MHz ultrasonic transducer. After imaging, the microstructure of the tissue was assessed by routine histological processing. RESULTS: OCT yielded superior structural information in all plaques examined. The mean (SEM) axial resolution of OCT and IVUS imaging was 16 (1) and 110 (7), respectively, as determined by the point spread function from a mirror. Furthermore, the dynamic range of OCT was 109 dB compared with 43 dB for IVUS imaging. CONCLUSIONS: OCT represents a promising new technology for intracoronary imaging because of its high resolution, broad dynamic range, and ability to be delivered through intravascular catheters.