Determination of characteristics of degenerative joint disease using optical coherence tomography and polarization sensitive optical coherence tomography

BACKGROUND AND OBJECTIVES: Previous studies have demonstrated that optical coherence tomography (OCT) could be used to delineate alterations in the microstructure of cartilage, and have suggested that changes in the polarization state of light as detected by OCT could provide information on the birefringence properties of articular cartilage as influenced by disease. In this study we have used both OCT and polarization sensitive optical coherence tomography (PS-OCT) technologies to evaluate normal and abnormal bovine articular cartilage according to established structural, organizational, and birefringent characteristics of degenerative joint disease (DJD) in order to determine if this technology can be used to differentiate various stages of DJD as a minimally invasive imaging tool. MATERIALS AND METHODS: Fresh bovine femoral-tibial joints were obtained from an abattoir, and 45 cartilage specimens were harvested from 8 tibial plateaus. Whole ex vivo specimens of normal and degenerative articular cartilage were imaged by both OCT and PS-OCT, then fixed and processed for histological evaluation. OCT/PS-OCT images and corresponding histology sections of each specimen were scored according to a modified Mankin structural grading scale and compared. RESULTS: OCT and PS-OCT imaging allowed structural evaluation of intact articular cartilage along a 6 mm surface length to a depth of 2 mm with a transverse resolution of 12 microm and an axial resolution of 10 microm. The OCT and PS-OCT images demonstrated characteristic alterations in the structure of articular cartilage with a high correlation to histological evaluation (kappa = 0.776). The OCT images were able to demonstrate early to advanced structural changes of articular cartilage while the optical phase retardation images obtained by PS-OCT imaging were able to discriminate areas where disorganization of the cartilage matrix was present, however, these characteristics are much different than those reported where OCT images alone were used to characterize tissue birefringence. No evidence of differences in OCT or PS-OCT images were detected between specimens of similar structural characteristics where proteoglycan was judged present or absent by safranin-O Fast Green staining. CONCLUSIONS: The combined use of OCT and PS-OCT technologies to obtain images from a single system is able to demonstrate and discriminate between characteristics of very early stages of surface irregularities not previously reported for OCT imaging, to deep clefts and collagen matrix disorganization for tissue at depths of up to 2 mm with good correlation to histology. PS-OCT and accumulated optical phase retardation images of articular cartilage as constructed from alterations in Stokes vector parameters appear to give a valuable but different assessment of alterations in tissue birefringence and organization than have been reported for OCT images obtained with the use of polarized or non-polarized light sources. This is the first time that alterations in the polarization state of light reflected from within the tissue have been demonstrated to be consistent with changes observed in the orientation and organization of the collagen matrix in advanced stages of DJD. The degree of phase transformation of light reflected from within the tissue as determined by PS-OCT imaging does not appear to be altered by the presence or absence of proteoglycan.     

Feasibility study of normal and septic tracheal imaging using optical coherence tomography

BACKGROUND AND OBJECTIVES: Optical coherence tomography (OCT) is an imaging technology that may be adapted for use with flexible fiberoptic bronchoscopy, potentially allowing it to play an important role in pulmonary diagnostics. The goal of this study was to evaluate the feasibility of OCT to image tracheal pathology. STUDY DESIGN/MATERIALS AND METHODS: Tracheas were harvested from normal and septic New Zealand White rabbits and imaged using OCT. Two delivery devices were employed. One was a moving stage with an objective lens and collimator, the other a linear scanning flexible fiberoptic catheter using a GRIN lens and prism for endoscopic OCT. After OCT images were obtained from normal and septic tracheas, the excised tissues were prepared for standard histologic examination. Areas imaged by OCT were compared with corresponding histology slides. RESULTS: OCT images demonstrated in detail tracheal sub-surface structures such as the epithelium, lamina propria, submucosa, and cartilage. The appearance of structures imaged by OCT corresponded very well with histologic pictures obtained by light microscopy. The OCT images from septic tracheas showed marked swelling of the mucosal and submucosal layers. Such pathology was equally imaged by either the moving stage or fiberoptic catheter for endoscopic OCT. CONCLUSIONS: OCT images of the trachea can distinguish many sub-surface structural features usually requiring biopsy and light microscopy for visualization. Marked differences between normal and septic trachea were apparent in OCT images. In the future, OCT may be a valuable tool for evaluating tracheal pathology in situ with high image resolution.     

Time-domain and spectral-domain optical coherence tomography in the analysis of brain tumor tissue

INTRODUCTION: Detection of residual tumor during resection of glial brain tumors remains a challenge because of a low inherent contrast of adjacent edematous brain, the surrounding infiltration zone, and the solid tumor. Therefore, new technologies that may facilitate an intraoperative analysis of the tissue at the resection edge are of great interest to neurosurgeons. MATERIALS AND METHODS: For ex vivo imaging of gliomas in a mouse model and human biopsy specimens of brain tumors and nervous system tissue we have used a time-domain Sirius 713 Tomograph with a central wavelength of 1,310 nm and a coherence length of 15 microm equipped with a mono mode fiber and a modified optical coherence tomography (OCT) adapter containing a lens system for imaging at a working distance of 2.5 cm. A spectral-domain tomograph using 840 nm and 930 nm superluminescence diodes (SLD) with a central wavelength of 900 nm was used as a second imaging modelity. RESULTS: Both time-domain and spectral-domain coherence tomography delineated normal brain, the infiltration zone and solid tumor in murine intracerebral gliomas. Histological evaluation of H&E sections parallel to the optical plain demonstrated that tumor areas of less than a millimeter could be detected and that not only solid tumor, but also brain invaded by a low-density single tumor cells produced an OCT signal different from normal brain. Spectral-domain OCT (SD-OCT) demonstrated a significantly more detailed microstructure of tumor and normal brain up to a tissue depth of 1.5-2.0 mm, whereas the interpretation of time-domain OCT (TD-OCT) was difficult at a tissue depth >1.0 mm. Because of rapid scanning times SD-OCT data could be acquired as 3D data maps, which allowed a multi-planar analysis of the tumor to brain interface. Similar to our findings in experimental gliomas, images of human nervous system tissue acquired using SD-OCT showed a characteristic signal of normal brain tissue and a detailed microstructure of tumor parenchyma. CONCLUSION: Spectral-domain OCT of experimental gliomas and human brain tumor specimens differentiates solid tumor, diffusely invaded brain tissue, and adjacent normal brain based on microstructure and B-scan signal characteristics. In conjunction with the rapid image acquisition rates of SD-OCT, this technology carries the potential of a novel intraoperative imaging tool for the detection of residual tumor and guidance of neurosurgical tumor resections.     

Imaging the cavernous nerves in the rat prostate using optical coherence tomography

INTRODUCTION: Improvements in identification, imaging, and visualization of the cavernous nerves (CNs) during radical prostatectomy, which are responsible for erectile function, may improve nerve preservation and post-operative potency. Optical coherence tomography (OCT) is capable of real-time, high-resolution, cross-sectional, in vivo tissue imaging. The rat prostate serves as an excellent model for studying the use of OCT for imaging the CNs, as the rat CN is a large, visible, and distinct bundle allowing for easy identification with OCT in addition to histologic confirmation. MATERIALS AND METHODS: Imaging was performed with the Niris OCT system and a handheld 8 Fr probe, capable of acquiring real-time images with 11-microm axial and 25-microm lateral resolution in tissue. Open surgical exposure of the prostate was performed on a total of six male rats, and OCT images of the prostate, CN, pelvic plexus ganglion, seminal vesicle, blood vessels, and periprostatic fat were acquired. CN electrical stimulation with simultaneous intracorporeal pressure measurements was performed to confirm proper identification of the CNs. The prostate and CNs were also processed for histologic analysis and further confirmation. RESULTS: Cross-sectional and longitudinal OCT images of the CNs were acquired and compared with histologic sections. The CN and ganglion could be differentiated from the surrounding prostate gland, seminal vesicle, blood vessels, bladder, and fatty tissue. CONCLUSIONS: We report preliminary results of OCT images of the rat CNs with histologic correlation and erectile stimulation measurements, thus providing interpretation of prostate structures as they appear in OCT images.     

High-resolution imaging of the thyroid gland using optical coherence tomography

BACKGROUND: Current diagnostic imaging modalities of the thyroid gland cannot reliably distinguish benign from malignant lesions, primarily because of their inability to visualize microscopic structure. A high-resolution imaging technique capable of examining thyroid tissue architectural morphology in real time is needed. Optical coherence tomography (OCT) has been shown to achieve high resolutions approaching the cellular range (1-15 microm). The feasibility of optical coherence tomography for imaging thyroid tissue was explored ex vivo on the human thyroid gland. METHODS: High-resolution OCT was performed in real time at 2 to 4 frames per second on three postmortem and 15 surgically excised thyroid glands containing normal, hyperplastic, and neoplastic tissue. OCT images acquired were compared with those obtained using standard histopathologic methods. RESULTS: The microstructure of the normal thyroid gland, including colloid-filled follicles as small as 15 microm and their supporting stroma, was clearly identified. OCT images of degenerative, hyperplastic, adenomatous, and malignant change within the thyroid gland were shown to correlate well with corresponding histopathologic findings. CONCLUSIONS: The ability of OCT to image thyroid tissue microarchitecture makes it a potentially powerful technology that can be used to assess the thyroid gland at a resolution greater than currently available clinical imaging modalities.     

光学相干断层成像诊断肺动脉高压研究进展

肺动脉高压(PAH)严重威胁健康,诊断困难,治疗棘手,患者预后不良。光学相干断层成像(OCT)是近年来发展的光学成像技术,其图像分辨率可达微米级别,被称为"光活检"。OCT可用于评估PAH患者肺动纤维化程度和判断预后。本文综述OCT诊断和评估PAH的研究进展。     

Ex vivo imaging of chronic total occlusions using forward-looking optical coherence tomography

BACKGROUND AND OBJECTIVES: Percutaneous coronary interventions (PCI) of chronic total occlusions (CTOs) of arteries are more challenging lesions to treat with angioplasty and stenting than stenotic vessels due primarily to the difficulty in guiding the wire across the lesion. Angiography alone is unable to differentiate between the occluded lumen and the vessel wall and to characterize the content of the occlusion. New technologies to aid in interventional guidance are therefore highly desirable. We sought to evaluate tissue characterization in arterial (CTOs) by imaging ex vivo peripheral arterial samples with optical coherence tomography (OCT). STUDY DESIGN/MATERIALS AND METHODS: Ex vivo arterial samples were obtained from patients undergoing peripheral limb amputation. Samples were imaged in an enface orientation using an OCT system, enabling sequential acquisition of longitudinal images and volumetric reconstruction of cross-sectional views of the occluded arteries. Histology was performed for comparison. RESULTS: OCT imaging reliably differentiated between the occluded lumen and the underlying arterial wall in peripheral CTOs. OCT correctly identified tissue composition within the CTO, such as the presence of collagen and calcium and was also able to identify intraluminal microchannels. CONCLUSIONS: OCT imaging of CTO anatomy and tissue characteristics may potentially lead to substantial improvements in PCI interventions by providing novel guiding capabilities.     

Imaging of human brain tumor tissue by near-infrared laser coherence tomography

Introduction

Intraoperative detection of residual tumor remains an important challenge in surgery to treat gliomas. New developments in optical techniques offer non-invasive high-resolution imaging that may integrate well into the workflow of neurosurgical operations. Using an intracranial glioma model, we have recently shown that time domain optical coherence tomography (OCT) allows discrimination of normal brain, diffusely invaded brain tissue, and solid tumor. OCT imaging allowed acquisition of 2D and 3D data arrays for multiplanar analysis of the tumor to brain interface. In this study we have analyzed biopsy specimens of human brain tumors and we present the first feasibility study of intraoperative OCT and post-image acquisition processing for non-invasive imaging of the brain and brain tumor.

Methods

We used a Sirius 713 Tomograph with a superluminescence diode emitting light at a near infrared central wavelength of 1,310 nm and a coherence length of 15 µm. The light is passed through an optical mono mode fiber to a modified OCT adapter containing a lens system with a working distance of 10 cm and an integrated pilot laser. Navigation-registered tumor biopsies were imaged ex vivo and the intraoperative site of optical tissue analysis was registered by marker acquisition using a neuronavigation system.

Results

Optical coherence tomography non-contact measurements of brain and brain tumor tissue produced B-scan images of 4 mm in width and 1.5–2.0 mm in depth at an axial and lateral optical resolution of 15 µm. OCT imaging demonstrated a different microstructure and characteristic signal attenuation profiles of tumor versus normal brain. Post-image acquisition processing and automated detection of the tissue to air interface was used to realign A-scans to compensate for image distortions caused by pulse- and respiration-induced movements of the target volume. Realigned images allowed monitoring of intensity changes within the scan line and facilitated selection of areas for the averaging of A-scans and the calculation of attenuation coefficients for specific regions of interest.

Conclusion

This feasibility study has demonstrated that OCT analysis of the tissue microstructure and light attenuation characteristics discriminate normal brain, areas of tumor infiltrated brain, solid tumor, and necrosis. The working distance of the OCT adapter and the A-scan acquisition rate conceptually allows integration of the OCT applicator into the optical path of the operating microscopes. This would allow a continuous analysis of the resection plain, providing optical tomography, thereby adding a third dimension to the microscopic view and information on the light attenuation characteristics of the tissue.

     

In vivo optical coherence tomography feasibility for bladder disease

PURPOSE: Optical coherence tomography is a new imaging modality capable of imaging luminal surface of biological tissue in the near infrared range with a spatial resolution close to the cellular level. We identified characteristic optical coherence tomography patterns for nonproliferative and proliferative inflammation, and malignant alterations of the bladder. MATERIALS AND METHODS: Optical coherence tomography was performed to image the bladder of 66 patients. The probe passed through the operating channel of a cystoscope and was pressed onto the mucosal site of interest. A mucosal biopsy of the image site was obtained. Optical coherence tomography was used to construct 680 images of the bladder and the images were compared with histology slides. RESULTS: Optical coherence tomography images of normal bladder showed 3 layers, namely the mucosa or transitional epithelium, submucosa and smooth muscle. In exudative processes there were poor light scattering areas in the connective tissue layer. Images of bladders with proliferative cystitis revealed nonuniform thickening of the epithelium or hyperplasia. Squamous metaplasia appeared as thicker and less transparent epithelium with a jagged boundary. Images of transitional cell carcinoma were characterized by the complete loss of a regular layered structure of the bladder wall and the penetration depth of optical imaging was slight. CONCLUSIONS: This study provides the characteristic optical coherence tomography pattern of nonproliferative and proliferative inflammation, and the characteristic appearance of severe dysplasia and transitional cell carcinoma. This technique may be useful as a guide for biopsy and for assisting in establishing resection margins.     

Clinical use of optical coherence tomography to identify angiographic silent stent thrombosis

Objectives. Patients previously treated with coronary stents may suffer an acute coronary syndrome (ACS) without any evidence of thrombus formation on coronary angiography (CAG). This may be due to partial, nonocclusive stent thrombosis with microembolization. In this paper, we illustrate possible mechanisms both with optical coherence tomography (OCT) and histology. Design. We present two cases with ACS from very late stent thrombosis who have been previously treated with first-generation drug-eluting stents (DES). Results. The first patient had ACS 15 months after DES implantation. The angiogram (CAG) was near normal with slight peri-stent contrast staining. OCT revealed abnormalities including thrombus not visible on CAG. These are findings that may explain the ACS. The second patient had subclinical episodes with chest pain after DES implantation. The patient died from stent thrombosis in a DES. Postmortem histological examination of the coronary arteries revealed stent struts with little or no neointimal coverage, persistent peri-strut fibrin deposition, inflammatory cells, malapposition, and small luminal platelet-rich thrombi. Old spotty myocardial infarctions were found in the supplied territory possibly caused by earlier episodes of embolizing thrombus. Conclusions. In patients with previous implanted DES presenting with ACS, OCT may detect abnormalities and thrombus formation not visible on CAG. Such findings may impact the treatment strategy in these patients.     

Feasibility of optical coherence tomography imaging to characterize renal neoplasms: limitations in resolution and depth of penetration

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Optical coherence tomography has been used for the diagnosis of retinal disease and has been used experimentally for imaging of vascular plaques, gastrointestinal pathology, bladder cancer, prostate cancer, and recently to examine benign kidney microanatomy. It has not been previously used to image kidney cancer. This study presents the first data on the utility of OCT in the imaging for renal neoplasms. It found that OCT was most successful in distinguishing AML and TCC from normal parenchyma. OCT had more limited success at differentiating oncocytoma. Clear cell tumors and other renal cancer subtypes had a more heterogenous appearance, precluding reliable identification using OCT. The study shows that higher resolution versions of OCT, such as OCM, will be needed to allow optical coherence imaging to reach clinical utility in the assessment of renal neoplasms.

OBJECTIVEs

? To determine the appearance of normal and neoplastic renal tissue when imaged with optical coherence tomography (OCT). ? To preliminarily assess the feasibility of using OCT to differentiate normal and neoplastic renal tissue.

PATIENTS AND METHODS

? After radical or partial nephrectomy in 20 subjects, normal renal parenchyma and neoplastic tissue samples were obtained. ? The tissue was evaluated with light microscopy and using a bench‐top laboratory OCT system with a lateral resolution of 10 µm. ? OCT images were compared with histological slides to evaluate the ability of OCT to differentiate renal neoplasms.

RESULTS

? Pathological subtypes included eight clear‐cell, three papillary and two chromophobe renal carcinomas; two oncocytomas; one angiomyolipoma (AML); two transitional cell carcinomas (TCCs); and one haematoma. ? Using OCT, benign renal parenchyma showed recognizable glomeruli and tubules. ? TCC had a distinctive appearance on OCT whereas AML showed a unique identifiable signature because of its fat content. Oncocytomas had a lobulated appearance, which appeared subtly different from renal carcinoma. ? Renal carcinoma lacked recognizable anatomical elements and had a heterogeneous appearance making differentiation from normal parenchyma at times difficult. ? Subtypes of renal cancer appeared to vary on OCT imaging although discrimination was unreliable.

CONCLUSIONS

? OCT imaging for renal neoplasms was most successful in distinguishing AML and TCC from normal parenchyma and malignant tumours. Oncocytoma differed subtly from renal carcinoma, making distinction more challenging. ? Clear‐cell tumours and other renal carcinoma subtypes had a heterogeneous appearance on OCT, which precluded reliable differentiation from normal parenchyma and between renal carcinoma subtypes. ? Higher resolution versions of optical coherence imaging, such as optical coherence microscopy, will be necessary to achieve clinical utility.