The thesis deals with speckle suppression in images acquired by optical coherence tomograph. It is divided into four parts. The first part describes basic information about the medical imaging method. It also deals with principle of measurement. The second section discusses the formation of image speckle and selected methods to reduce them. Next part is practical and consists of data acquisition, determination of the evaluation methodology and the implementation of speckle reduction methods. The last part is focused on testing and reviews of algorithms and discussion about their results.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18499号 / 医博第3919号 / 新制||医||1005(附属図書館) / 31385 / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊藤 壽一, 教授 河野 憲二, 教授 富樫 かおり / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Final publication is available at http://journals.lww.com/otology-neurotology/Pages/default.aspx / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19574号 / 医博第4081号 / 新制||医||1013(附属図書館) / 32610 / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邉 大, 教授 伊佐 正, 教授 一山 智 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Yes / Combining information from optical coherence tomography (OCT) imaging and visual field testing is useful in the clinical assessment and monitoring of patients with glaucoma. Measurements of retinal nerve fibre layer thickness or neuroretinal rim width taken around the optic nerve head may be related to the visual field using a structure–function map. In this review, the structure–function mapping methods in clinical use are discussed. Typical clinical maps provide a population average, ‘one size fits all’ representation, but in recent years methods for customising structure–function maps to individual eyes have been developed and these are reviewed here. In the macula, visual field stimuli stimulate photoreceptors for which associated retinal ganglion cells are peripherally displaced. Recently developed methods that relate OCT measurements to visual field test locations in the macula are therefore also reviewed. The use of structure–function maps to relate OCT measurements to localised visual field sensitivity in new applications is also explored. These new applications include the selection of visual field test locations and stimulus intensities based on OCT data, and the formal post‐test combination of results across modalities. Such applications promise to exploit the structure–function relationship in glaucoma to improve disease diagnosis and monitoring of progression. Limitations in the validation and use of current structure–function mapping techniques are discussed. / >Heidelberg Engineering >Australian Research Council. Grant Number: LP130100055 >College of Optometrists. Grant Number: College of Optometrists Research Fellowship

No current imaging technology can directly and without significant distortion visualize the defining microscopic features of the human brain. Ex vivo histological techniques yield exquisite planar images, but the cutting, mounting and staining they require induce slice-specific distortions, introducing cross-slice differences that prohibit true 3D analysis. Clearing techniques have proven difficult to apply to large blocks of human tissue and cause dramatic distortions as well. Thus, we have only a poor understanding of human brain structures that occur at a scale of 1–100 μm, in which neurons are organized into functional cohorts. To date, mesoscopic features which are critical components of this spatial context, have only been quantified in studies of 2D histologic images acquired in a small number of subjects and/or over a small region of the brain, typically in the coronal orientation, implying that features that are oblique or orthogonal to the coronal plane are difficult to properly analyze. A serial sectioning optical coherence tomography (OCT) imaging infrastructure will be developed and utilized to obtain images of cyto- and myelo-architectural features and microvasculature network of post-mortem human brain tissue. Our imaging infrastructure integrates vibratome with imaging head along with pre and post processing algorithms to construct volumetric OCT images of cubic centimeters of brain tissue blocks. Imaging is performed on tissue block-face prior to sectioning, which preserves the 3D information. Serial sections cut from the block can be subsequently treated with multiplexed histological staining of multiple molecular markers that will facilitate cellular classification or imaged with high-resolution transmission birefringence microscope. The successful completion of this imaging infrastructure enables the automated reconstruction of undistorted volume of human tissue brain blocks and permits studying the pathological alternations arising from diseases. Specifically, the mesoscopic and microscopic pathological alternations, as well as the optical properties and cortical morphological alternations of the dorsolateral prefrontal cortical region of two difference neurodegeneration diseases, Chronic Traumatic Encephalopathy (CTE) and Alzheimer’s Disease (AD), were evaluated using this imaging infrastructure.

No description available.

青光眼作為一種慢性進展性視神經病變，已經成為世界眼科病變中導致不可逆盲的首要原因。青光眼的早期診斷和治療對於降低疾病進展的風險至關重要。光學相干斷層掃描（OCT）可以提供在體視網膜橫斷面的視圖，從而實現了對視網膜神經纖維層（RNFL）改變的客觀測量，這些改變已經被證明了與青光眼引起的視神經損害相關，並已成為診斷青光眼的重要參考依據。 / 頻域OCT是最新一代的光學相干斷層掃描，它具有比時域OCT更快的掃描速度和更高的圖像解析度，因此，頻域OCT可以提供更可靠的RNFL厚度測量和RNFL缺損評估。本文的研究目的在於評估頻域OCT對RNFL厚度的重測再現性，以及探討影響RNFL厚度測量的因素，這些因素包括（1）影像平均法的應用，（2）RNFL分層錯誤，和（3）視網膜血管的影響。此外，由於RNFL攝影是一個評估青光眼RNFL缺損的臨床參考標準，我們還將其對RNFL缺損的測量與頻域OCT的RNFL厚度偏差圖所作出的測量進行了比較。 / 首先，為了評估頻域OCT對RNFL厚度測量的重測再現性，15名正常人和15名青光眼患者連續四周每週均接受一次OCT掃描。正常組和青光眼組的RNFL厚度再現性係數分別為4.77-12.65微米和4.53-16.66微米，由於組內相關性係數均大於0.773，說明頻域OCT所作出的RNFL厚度測量是具備可重複性的。 / 其次，通過分析54隻眼（25名正常志願者和29名青光眼患者）的RNFL厚度測量值，本文對圖像平均法的應用是否會影響RNFL厚度的測量這一問題進行了探討。分析中，每一隻眼均接受了3次OCT掃描，3次掃描的圖像分別使用2、8、和16張連續的圖像進行影像平均。結果顯示，除了青光眼組的鼻下象限RNFL厚度測量值之外（P=0.036），不同的圖像幀數並不會對兩組的總體和其它各象限的RNFL厚度測量值產生顯著的影響（P≥0.055）。雖然圖像平均法的應用對RNFL厚度測量的影響並不顯著，但是視網膜血管和RNFL分層錯誤對青光眼,尤其是對RNFL非常薄的晚期青光眼患者的RNFL厚度測量有影響。結論來自對60個正常人，66個輕至中度青光眼（MD≥-6 dB）患者和54個嚴重青光眼（MD<-6 dB）患者的共180張OCT圖像的分析。視網膜血管相對於平均RNFL厚度的比例均值在正常組，輕至中度青光眼組，和嚴重青光眼組分別為11.2±2.3，12.6±2.5，和16.6±3.9。在人為調整了RNFL界限以糾正RNFL分層錯誤的前後，總體RNFL厚度的差異範圍在正常組為-3.0-2.5微米，輕至中度青光眼組為-2.5-5.0微米，嚴重青光眼組為-11.0-9.5微米組。 / 最後，通過對41名青光眼患者的51隻眼的RNFL缺損面積，位置，和覆蓋角度進行測量，本文將頻域OCT作出的測量結果和共焦鐳射掃描檢眼鏡（CSLO）RNFL反射影像圖的測量結果進行了比較，結果顯示：OCT不但可以檢測到所有出現在CSLO的RNFL反射影像圖上的RNFL缺損，更重要的是，OCT還可以檢測出額外的並未在RNFL反射影像圖上出現的RNFL缺損。 / 總之，頻域OCT是一種可提供高再現性RNFL厚度測量的影像方法。對青光眼,尤其是晚期青光眼的RNFL厚度測量值的詮釋，應當考慮到視網膜血管和RNFL分層錯誤的影響。OCT具備對RNFL缺損進行多維度量化（包括厚度，面積，位置，和覆蓋角度）的能力，在青光眼RNFL改變的檢測和監測方面，相對于傳統的RNFL攝影，OCT無疑是更有效的選擇。 / Glaucoma, a chronic progressive optic neuropathy, is the leading cause of irreversible blindness in the world. An early diagnosis and treatment of glaucoma is vital to reduce the risk of disease progression. Providing a cross-sectional view of the retina in vivo, optical coherence tomography (OCT) can objectively measure the changes of retinal nerve fiber layer (RNFL), which has been shown to be of relevance and importance in detecting glaucomatous damage of the optic nerve. / The latest generation of OCT, the spectral-domain OCT, has a faster scan speed and a higher image resolution compared to the time-domain OCT. It is expected that the spectral-domain OCT would allow a more reliable measurement of the RNFL thickness and assessment of RNFL defects. The objectives of this research project were to examine the test-retest reproducibility of spectral-domain OCT RNFL measurement and investigate factors including (1) image averaging, (2) segmentation failure, and (3) contribution of retinal blood vessels that might affect the measurement of RNFL thickness. As RNFL photography is a reference standard to evaluate RNFL defects in glaucoma, we also evaluated whether RNFL defects measured in the spectral-domain OCT RNFL thickness map would be comparable to those detected in RNFL photographs. / To evaluate the test-retest reproducibility of RNFL measurements obtained by the spectral-domain OCT, 15 normal individuals and 15 glaucoma patients were followed and imaged weekly for 4 consecutively weeks. The reproducibility coefficients of RNFL thicknesses ranged between 4.53 and 16.66 μm for the normal group, and 4.77 and 12.65 μm for the glaucoma group. The intraclass correlation coefficients were all above 0.773, indicating RNFL measurement with spectral-domain OCT was reproducible. / We then investigated if multiple-image averaging would influence the measurement of RNFL thickness. A total of 54 eyes from 25 normal volunteers and 29 glaucoma patients with RNFL images captured and averaged with 2, 8, and 16 consecutive image frames were analyzed. For both groups, there were no significant differences in global or sectoral RNFL thicknesses among the image series averaged with different number of image frames (all with P≥0.055) except for the inferonasal sector in the glaucoma group (P=0.036). Although the impact of image averaging on RNFL measurement was insignificant, the presence of retinal blood vessels and segmentation errors were influential on the measurement, particularly in advanced glaucoma patients when the RNFL was thin. Analyzing a total of 180 eyes from 60 normal individuals, 66 mild to moderate (MD≥-6 dB) and 54 advanced (MD<-6 dB) glaucoma patients, the mean proportion of retinal blood vessels relative to the average RNFL thickness was 11.2±2.3%, 12.6±2.5% and 16.6±3.9%, respectively. After correcting the segmentation errors by manually refining the RNFL boundaries, the differences in average RNFL thickness ranged from -3.0 to 2.5 m in the normal, -2.5 to 5.0 m in the mild to moderate glaucoma and -11.0 to 9.5 m in the advanced glaucoma groups. / Finally, we compared the area, the angular location, and the angular width of RNFL defects from 51 eyes of 41 glaucoma patients measured with the spectral-domain OCT and RNFL reflectance images obtained by a confocal scanning laser ophthalmoscope (CSLO). OCT was able to detect areas of RNFL abnormalities in all eyes with RNFL defects which were evident in the CSLO RNFL reflectance images. More important, OCT could identify additional RNFL thinning not apparent in RNFL reflectance images. / In summary, spectral-domain OCT could offer an effective approach in measuring RNFL with high reproducibility. Interpretation of RNFL measurement should take the contribution of the retinal blood vessels and segmentation errors into consideration, particularly in advanced glaucoma when the RNFL is thin. With the ability to quantify multiple dimensions of RNFL defects (thickness, area, angular location, and angular width), OCT could provide a useful alternative to detect and monitor RNFL changes in glaucoma. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Ye, Cong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 117-130). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / ABSTRACT --- p.i / 摘要 (ABSTRACT IN CHINESE) --- p.v / DEDICATION --- p.viii / ACKNOWLEDGEMENT --- p.ix / TABLE OF CONTENTS --- p.x / PUBLICATIONS --- p.xiv / ABBREVIATIONS --- p.xvi / Chapter CHAPTER 1: --- INTRODUCTION --- p.1 / Chapter 1.1 --- Glaucoma --- p.2 / Definition of Glaucoma --- p.2 / Epidemiology of Glaucoma --- p.3 / Pathogenesis of Glaucoma --- p.4 / Diagnosis of Glaucoma --- p.7 / Chapter 1.2 --- Retinal Nerve Fiber Layer --- p.13 / Anatomy of Retinal Nerve Fiber Layer --- p.13 / Visualization of Retinal Nerve Fiber Layer --- p.14 / Retinal Nerve Fiber Layer Defect in Glaucoma --- p.16 / Significance of Detecting Retinal Nerve Fiber Layer Defect in Glaucoma --- p.18 / Chapter 1.3 --- Optical Coherence Tomography --- p.20 / Principle of Optical Coherence Tomography --- p.20 / Retinal Nerve Fiber Layer Imaging with OCT --- p.21 / Optic Nerve Head Imaging with OCT --- p.27 / Advantages and Disadvantages of Optical Coherence Tomography --- p.29 / Chapter 1.4 --- Research Objectives --- p.30 / Chapter CHAPTER 2: --- GENERAL MATERIALS AND METHODS --- p.32 / Chapter 2.1 --- Subject Enrollments --- p.33 / Chapter 2.2 --- Clinical Ophthalmic Examination --- p.34 / Chapter 2.3 --- Visual Field Examination --- p.35 / Definition of Normal and Glaucoma Groups --- p.35 / Chapter 2.4 --- Optical Coherence Tomography Imaging --- p.37 / Cirrus HD-OCT Imaging --- p.37 / Spectralis OCT Imaging --- p.37 / Chapter 2.5 --- Statistical Analysis --- p.39 / Chapter CHAPTER 3: --- RETINAL NERVE FIBER LAYER IMAGING WITH SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY --- p.40 / Chapter 3.1 --- Reproducibility and Agreement of Retinal Nerve Fiber Layer Measurement --- p.41 / Introduction and Study Objectives --- p.41 / Methods --- p.42 / Results --- p.45 / Discussion --- p.47 / Tables and Figures --- p.51 / Chapter 3.2 --- Effect of Multiple B-scans Averaging on Retinal Nerve Fiber Layer Measurement --- p.58 / Introduction and Study Objectives --- p.58 / Methods --- p.59 / Results --- p.61 / Discussion --- p.62 / Tables and Figures --- p.67 / Chapter 3.3 --- Impact of Blood Vessels and Segmentation Failure on Retinal Nerve Fiber Layer Measurement --- p.73 / Introduction and Study Objectives --- p.73 / Methods --- p.75 / Results --- p.78 / Discussion --- p.80 / Tables and Figures --- p.84 / Chapter 3.4 --- Agreement of Localized Retinal Nerve Fiber Layer Defect Assessment with Confocal Scanning Laser Ophthalmoscopy --- p.95 / Introduction and Study Objectives --- p.95 / Methods --- p.97 / Results --- p.101 / Discussion --- p.103 / Tables and Figures --- p.108 / Chapter CHAPTER 4: --- GENERAL CONCLUSIONS --- p.115 / REFERENCES --- p.117

Optical coherence tomography (OCT) and optical coherence microscopy (OCM) are non-invasive optical coherence imaging techniques, which enable micron-scale resolution, depth resolved imaging capability. Both OCT and OCM are based on Michelson interferometer theory. They are widely used in ophthalmology, gastroenterology and dermatology, because of their high resolution, safety and low cost. OCT creates cross sectional images whereas OCM obtains en face images. In this dissertation, the design and development of three increasingly complicated analog signal processing (ASP) solutions for optical coherence imaging are presented.The first ASP solution was implemented for a time domain OCT system with a Rapid Scanning Optical Delay line (RSOD)-based optical signal modulation and logarithmic amplifier (Log amp) based demodulation. This OCT system can acquire up to 1600 A-scans per second. The measured dynamic range is 106dB at 200A-scan per second. This OCT signal processing electronics includes an off-the-shelf filter box with a Log amp circuit implemented on a PCB board.The second ASP solution was developed for an OCM system with synchronized modulation and demodulation and compensation for interferometer phase drift. This OCM acquired micron-scale resolution, high dynamic range images at acquisition speeds up to 45,000 pixels/second. This OCM ASP solution is fully custom designed on a perforated circuit board.The third ASP solution was implemented on a single 2.2 mm x 2.2 mm complementary metal oxide semiconductor (CMOS) chip. This design is expandable to a multiple channel OCT system. A single on-chip CMOS photodetector and ASP channel was used for coherent demodulation in a time domain OCT system. Cross-sectional images were acquired with a dynamic range of 76dB (limited by photodetector responsivity). When incorporated with a bump-bonded InGaAs photodiode with higher responsivity, the expected dynamic range is close to 100dB.

Optical Coherence Tomography (OCT) is a coherence-gated, micrometer-resolution imaging technique that focuses a broadband near-infrared laser beam to penetrate into optical scattering media, e.g. biological tissues. The OCT resolution is split into two parts, with the axial resolution defined by half the coherence length, and the depth-dependent lateral resolution determined by the beam geometry, which is well described by a Gaussian beam model. The depth dependence of lateral resolution directly results in the defocusing effect outside the confocal region and restricts current OCT probes to small numerical aperture (NA) at the expense of lateral resolution near the focus. Another limitation on OCT development is the presence of a mixture of speckles due to multiple scatterers within the coherence length, and other random noise. Motivated by the above two challenges, a multiple scattering model based on Rytov approximation and Gaussian beam optics is proposed for the OCT setup. Some previous papers have adopted the first Born approximation with the assumption of small perturbation of the incident field in inhomogeneous media. The Rytov method of the same order with smooth phase perturbation assumption benefits from a wider spatial range of validity. A deconvolution method for solving the inverse problem associated with the first Rytov approximation is developed, significantly reducing the defocusing effect through depth and therefore extending the feasible range of NA.

Ovarian cancer is the deadliest gynecologic cancer for women. Diagnosis at the local stage leads to 91% 5-year survival rates, but only 15% of cases are detected early. Existing screening methods have proven ineffective in large clinical trials. Screening is complicated by the heterogeneity of the disease with multiple types of ovarian cancer originating both on the ovary and in the fallopian tube. Early stage cancer is too subtle for non-invasive imaging techniques such as ultrasound or magnetic resonance imaging. This study evaluates the feasibility and design of dual modality, multispectral fluorescence imaging (MFI) and optical coherence tomography (OCT) endoscopes for improved ovarian cancer screening. The study is broken up into three sections. In the first study MFI is validated in an ex vivo imaging study of human ovarian and fallopian tube tissue samples. Tissue autofluorescence excited by ultraviolet and blue wavelengths is shown to be a promising discriminator between normal and cancerous tissue. The second study combines OCT and MFI into a sub millimeter diameter endoscope designed to screen for ovarian cancer by screening inside the fallopian tube and at the ovary. The small size is required for screening the full length of the fallopian tube. MFI is implemented as a wide-field navigational imaging technique with high sensitivity complemented by high resolution structural depth imaging of OCT over a limited field of view. The final study presents a novel lens design for a scanning fiber endoscope with forward-viewing navigation and side-viewing OCT. A piezo tube is used to scan an optical fiber providing both the navigation channel’s illumination and OCT imaging. The design spatially separates the forward-viewing illumination from the OCT. As the piezo fiber circularly scans at its maximum deviation the OCT beam focus is rotationally scanned out the side of the endoscope tip by a rotationally symmetric double reflection in the cover plate.