Optical biopsy of lymph node morphology using optical coherence tomography

Optical diagnostic imaging techniques are increasingly being used in the clinical environment, allowing for improved screening and diagnosis while minimizing the number of invasive procedures. Diffuse optical tomography, for example, is capable of whole-breast imaging and is being developed as an alternative to traditional X-ray mammography. While this may eventually be a very effective screening method, other optical techniques are better suited for imaging on the cellular and molecular scale. Optical Coherence Tomography (OCT), for instance, is capable of high-resolution cross-sectional imaging of tissue morphology. In a manner analogous to ultrasound imaging except using optics, pulses of near-infrared light are sent into the tissue while coherence-gated reflections are measured interferometrically to form a cross-sectional image of tissue. In this paper we apply OCT techniques for the high-resolution three-dimensional visualization of lymph node morphology. We present the first reported OCT images showing detailed morphological structure and corresponding histological features of lymph nodes from a carcinogen-induced rat mammary tumor model, as well as from a human lymph node containing late stage metastatic disease. The results illustrate the potential for OCT to visualize detailed lymph node structures on the scale of micrometastases and the potential for the detection of metastatic nodal disease intraoperatively.     

Integrated optical coherence tomography and microscopy for ex vivo multiscale evaluation of human breast tissues

Three-dimensional (3D) tissue imaging methods are expected to improve surgical management of cancer. In this study, we examined the feasibility of two 3D imaging technologies, optical coherence tomography (OCT) and optical coherence microscopy (OCM), to view human breast specimens based on intrinsic optical contrast. Specifically, we imaged 44 ex vivo breast specimens including 34 benign and 10 malignant lesions with an integrated OCT and OCM system developed in our laboratory. The system enabled 4-μm axial resolution (OCT and OCM) with 14-μm (OCT) and 2-μm (OCM) transverse resolutions, respectively. OCT and OCM images were compared with corresponding histologic sections to identify characteristic features from benign and malignant breast lesions at multiple resolution scales. OCT and OCM provide complimentary information about tissue microstructure, thus showing distinctive patterns for adipose tissue, fibrous stroma, breast lobules and ducts, cysts and microcysts, as well as in situ and invasive carcinomas. The 3D imaging capability of OCT and OCM provided complementary information to individual 2D images, thereby allowing tracking features from different levels to identify low-contrast structures that were difficult to appreciate from single images alone. Our results lay the foundation for future in vivo optical evaluation of breast tissues, using OCT and OCM, which has the potential to guide core needle biopsies, assess surgical margins, and evaluate nodal involvement in breast cancer.     

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.     

恶性肿瘤的光学分子影像手术导航*

光学分子影像是利用生物体自发荧光和荧光素酶的探针对分子和分子作用途径监测的一种无创技术,具有操作简单、无创伤、即时性、高敏感性、成像价格低的优点,被越来越多地应用于生物学、医学等生命科学领域。常用的光学分子影像研究的荧光探针主要有内源性的荧光素酶、外源性的绿色荧光蛋白及近红外荧光染料等。外科手术是恶性肿瘤的主要治疗方法之一,如何在手术中实时动态检测前哨淋巴结、确定肿瘤浸润和转移范围、判定肿瘤切缘是否安全及保护神经等功能是肿瘤外科医生面临的临床挑战。光学分子影像手术导航正在逐步应用到以上领域,期待可以解决以上问题,最终可以使恶性肿瘤被精准切除。本文就目前国内外光学分子影像技术在恶性肿瘤手术导航领域的应用进行综述。      

Monitoring the response to primary medical therapy for breast cancer using three- dimensional time-resolved optical mammography

Primary medical therapy is used to reduce tumour size prior to surgery in women with locally advanced breast cancer. Optical tomography is a functional imaging technique using near- infrared light to produce three-dimensional breast images of tissue oxygen saturation and haemoglobin concentration. Its advantages include the ability to display quantitative physiological information, and to allow repeated scans without the hazards associated with exposure to ionising radiation. There is a need for a non-invasive functional imaging tool to evaluate response to treatment, so that non-responders can be given the opportunity to change their treatment regimen. Here, we evaluate the use of optical tomography for this purpose. Four women with newly diagnosed breast cancer who were about to undergo primary medical therapy gave informed and voluntary consent to take part in the study. Changes in physiological and optical properties within the tumour were evaluated during the course of neoadjuvant chemotherapy. Optical imaging was performed prior to treatment, after the first cycle of chemotherapy, halfway through, and on completion of chemotherapy. Images of light absorption and scatter at two wavelengths were produced, from which images of total haemoglobin concentration and oxygen saturation were derived. All patients that showed a good or complete response to treatment on MRI showed a corresponding recovery in the haemoglobin concentration images. Changes in mean tumour total haemoglobin concentration could be seen four weeks into treatment. The tumour oxygen saturation was low compared to background in three out of four patients, and also showed a return to baseline over treatment. Optical imaging of the breast is feasible during primary medical therapy and can be used to assess response to treatment over six months.     

活体动物体内成像技术及其在生物医学中的应用进展

活体动物体内成像是近年来新兴的检测活体动物体内基因表达及细胞活动的光学成像技术，具有操作简便，直观性强的特点。这项技术包括生物发光成像和荧光成像，采用报告基因产生的生物发光、荧光蛋白质或染料产生的荧光作为体内生物光源，与新型冷CCD成像相结合，实时探测活体动物体内生理或病理条件下的细胞和分子事件。本文简要综述了活体动物体内成像技术的原理、应用领域及发展前景。     

分子影像学在神经胶质瘤的诊断与治疗中的应用

分子影像学是医学影像技术和分子生物学相结合的学科，利用现有的一些医学影像技术，如核医学（PET）、核磁共振（MRI）和光学成像方法（OCT）．对人体内部生理或病理过程在分子水平上进行无损伤的、实时的成像，对神经胶质瘤的诊断和治疗是分子影像学研究的一大方面，全文就分子影像学的原理及技术、分子影像学在胶质瘤诊疗中的应用加以综述。     

Optical tomography with ultrasound localization for breast cancer diagnosis and treatment monitoring

Optical tomography with ultrasound (US) localization uses coregistered ultrasound images to guide optical imaging reconstruction. To simultaneously acquire US images and optical measurements, the authors used a hand-held probe consisting of a commercial US transducer and near-infrared optical imaging sensors of multiple wavelengths. A novel image scheme was used to map the ultrasound-visible lesions for optical imaging reconstruction. As a result, the problem of intense light scattering caused by breast tissue was overcome and reliable tumor hemoglobin concentration and blood oxygen saturation distributions from a group of patients were obtained. These functional parameters are valuable for aiding US diagnosis and for assessing chemotherapy response.     

In vivo time-serial multi-modality optical imaging in a mouse model of ovarian tumorigenesis

Identification of the early microscopic changes associated with ovarian cancer may lead to development of a diagnostic test for high-risk women. In this study we use optical coherence tomography (OCT) and multiphoton microscopy (MPM) (collecting both two photon excited fluorescence [TPEF] and second harmonic generation [SHG]) to image mouse ovaries in vivo at multiple time points. We demonstrate the feasibility of imaging mouse ovaries in vivo during a long-term survival study and identify microscopic changes associated with early tumor development. These changes include alterations in tissue microstructure, as seen by OCT, alterations in cellular fluorescence and morphology, as seen by TPEF, and remodeling of collagen structure, as seen by SHG. These results suggest that a combined OCT-MPM system may be useful for early detection of ovarian cancer.     

Comparative Efficacy of Four Imaging Instruments for Breast Cancer Screening

Sensitivity and specificity are the two most important indicators in selection of medical imaging devices forcancer screening. Breast images taken by conventional or digital mammography, ultrasound, MRI and opticalmammography were collected from 2,143,852 patients. They were then studied and compared for sensitivityand specificity results. Optical mammography had the highest sensitivity (p<0.001 and p<0.006) except withMRI. Digital mammography had the highest specificity for breast cancer imaging. A comparison of specificitybetween digital mammography and optical mammography was significant (p<0.021). If two or more breastdiagnostic imaging tests are requested the overall sensitivity and specificity will increase. In this literature reviewstudy patients at high-risk of breast cancer were studied beside normal or sensitive women. The image modalityperformance of each breast test was compared for each.     

Novel endoscopic diagnosis for bladder cancer

Advances in endoscopic imaging technology may improve sensitivity for the detection of bladder cancer and provide a more complete understanding of the urothelial landscape, and it also may lead to improved short‐term and long‐term cancer control. Fluorescence cystoscopy requires intravesical administration of a photosensitizing agent (5‐aminolevulinic acid or hexaminolevulinate), and imaging with a blue‐light endoscopy system demonstrably improves the detection of papillary and flat bladder lesions compared with conventional white‐light cystoscopy. Prospective phase 3 clinical trials have demonstrated improved diagnostic ability, enhanced tumor resection, and a small but significant reduction in recurrence‐free survival. Optical coherence tomography delineates subsurface microarchitecture information about bladder lesions in real time and has the ability to discriminate between noninvasive and invasive cancers. Narrow‐band imaging may augment white‐light cystoscopy by providing increased contrast between normal and abnormal tissue on the basis of neovascularity. Confocal laser endoscopy has been applied to the urinary tract using thinner probes adapted from use in gastrointestinal malignancies and provides exquisite images at microscopic resolution. More technology is on the horizon that may further enhance our ability to detect and accurately stage bladder tumors and distinguish benign from malignant or dysplastic lesions. Cancer 2015;121:169–78 . © 2014 American Cancer Society.     

In vivo optical coherence tomography imaging of preinvasive bronchial lesions.

PURPOSE: Optical coherence tomography (OCT) is an optical imaging method that can visualize cellular and extracellular structures at and below tissue surface. The objective of the study was to determine if OCT could characterize preneoplastic changes in the bronchial epithelium identified by autofluorescence bronchoscopy. EXPERIMENTAL DESIGN: A 1.5-mm fiberoptic probe was inserted via a bronchoscope into the airways of 138 volunteer heavy smokers participating in a chemoprevention trial and 10 patients with lung cancer to evaluate areas that were found to be normal or abnormal on autofluorescence bronchoscopy. Radial scanning of the airways was done to generate OCT images in real time. Following OCT imaging, the same sites were biopsied for pathologic correlation. RESULTS: A total of 281 OCT images and the corresponding bronchial biopsies were obtained. The histopathology of these areas includes 145 normal/hyperplasia, 61 metaplasia, 39 mild dysplasia, 10 moderate dysplasia, 6 severe dysplasia, 7 carcinoma in situ, and 13 invasive carcinomas. Quantitative measurement of the epithelial thickness showed that invasive carcinoma was significantly different than carcinoma in situ (P=0.004) and dysplasia was significantly different than metaplasia or hyperplasia (P=0.002). In addition, nuclei of the cells corresponding to histologic results became more discernible in lesions that were moderate dysplasia or worse compared with lower-grade lesions. CONCLUSION: Preliminary data suggest that autofluorescence bronchoscopy-guided OCT imaging of bronchial lesions is technically feasible. OCT may be a promising nonbiopsy tool for in vivo imaging of preneoplastic bronchial lesions to study their natural history and the effect of chemopreventive intervention.     

Diffuse optical imaging of the healthy and diseased breast: A systematic review

Screening X-ray mammography is limited by false positives and negatives leading to unnecessary physical and psychological morbidity. Diffuse Optical Imaging using harmless near infra red light, provides lesion detection based on functional abnormalities and represents a novel diagnostic arm that could complement traditional mammography. Reviews of optical breast imaging have not been systematic, are focused mainly on technological developments, and have become superseded by rapid technological advancement. The aim of this study is to review clinically orientated studies involving approximately 2,000 women in whom optical mammography has been used to evaluate the healthy or diseased breast. The results suggest that approximately 85% of breast lesions are detectable on optical mammography. Spectroscopic resolution of tissue haemoglobin composition and oxygen saturation may improve the detectability of breast diseases. Results suggest that breast lesions contain approximately twice the haemoglobin concentration of background tissue. Current evidence suggests that it is not possible to distinguish benign from malignant disease using optical imaging techniques in isolation. Methods to improve the performance of Diffuse Optical Imaging, such as better spectral coverage with additional wavelengths, improved modelling of light transport in tissues and the use of extrinsic dyes may augment lesion detection and characterisation. Future research should involve large clinical trials to determine the overall sensitivity and specificity of optical imaging techniques as well as to establish patient satisfaction and economic viability.     

Spectral discrimination of breast pathologies in situ using spatial frequency domain imaging

Introduction

Nationally, 25% to 50% of patients undergoing lumpectomy for local management of breast cancer require a secondary excision because of the persistence of residual tumor. Intraoperative assessment of specimen margins by frozen-section analysis is not widely adopted in breast-conserving surgery. Here, a new approach to wide-field optical imaging of breast pathology in situ was tested to determine whether the system could accurately discriminate cancer from benign tissues before routine pathological processing.

Methods

Spatial frequency domain imaging (SFDI) was used to quantify near-infrared (NIR) optical parameters at the surface of 47 lumpectomy tissue specimens. Spatial frequency and wavelength-dependent reflectance spectra were parameterized with matched simulations of light transport. Spectral images were co-registered to histopathology in adjacent, stained sections of the tissue, cut in the geometry imaged in situ. A supervised classifier and feature-selection algorithm were implemented to automate discrimination of breast pathologies and to rank the contribution of each parameter to a diagnosis.

Results

Spectral parameters distinguished all pathology subtypes with 82% accuracy and benign (fibrocystic disease, fibroadenoma) from malignant (DCIS, invasive cancer, and partially treated invasive cancer after neoadjuvant chemotherapy) pathologies with 88% accuracy, high specificity (93%), and reasonable sensitivity (79%). Although spectral absorption and scattering features were essential components of the discriminant classifier, scattering exhibited lower variance and contributed most to tissue-type separation. The scattering slope was sensitive to stromal and epithelial distributions measured with quantitative immunohistochemistry.

Conclusions

SFDI is a new quantitative imaging technique that renders a specific tissue-type diagnosis. Its combination of planar sampling and frequency-dependent depth sensing is clinically pragmatic and appropriate for breast surgical-margin assessment. This study is the first to apply SFDI to pathology discrimination in surgical breast tissues. It represents an important step toward imaging surgical specimens immediately ex vivo to reduce the high rate of secondary excisions associated with breast lumpectomy procedures.     

光学分子影像学在肿瘤外科应用的前景

随着光学分子成像技术和靶向光学分子显影剂的不断成熟,以靶向分子显影剂标记,术中光学分子影像引导的外科手术必将成为继开放手术、微创外科手术之后第三代外科手术新理论和新技术。本文结合国内外研究进展和我们的前期研究,对荧光染料与荧光诊断;荧光成像和光学分子影像;光学分子影像和光学分子影像诊疗设备初步进行了概念性讨论。提出了光学分子影像外科学的学科方向,明确指出光学分子影像外科学将是精准外科的前沿理论和先进诊疗技术,光学分子影像外科学主要由靶向光学分子显影剂、光学分子成像设备及其临床诊疗技术构成。     

荧光蛋白活体成像系统在肿瘤研究中的应用

活体动物体内光学成像作为一项新兴的分子、基因表达的分析检测技术,已成功应用于生命科学、生物医学、分子生物学和药物研发等领域。荧光技术介导的活体动物光学成像在活体肿瘤研究中的应用已日趋深入,包括应用荧光蛋白对肿瘤内环境、肿瘤转移过程、休眠肿瘤细胞以及肿瘤治疗应答成像,本文对这些研究进展作一综述。     

Optical coherence tomography in tamoxifen retinopathy

Summary Optical coherence tomography (OCT) is a non-invasive, transpupillary imaging technology that allows detailed analysis of the retinal structures. In a recent article, Gualino et al. reported that OCT revealed a foveolar cystoid space with focal disruption of the photoreceptors line that explains the irreversible loss of central vision in tamoxifen retinopathy. In addition to providing a better understanding of the pathogenesis of tamoxifen retinopathy, OCT screening is advisable in patients treated with tamoxifen over long periods in order to detect and prevent drug-induced retinal damage.An erratum to this article can be found at     

乳腺MRI图像纹理分析在乳腺癌中的研究进展

乳腺癌具有高度异质性,其异质性是造成患者误诊率较高、治疗反应较差及预后不理想等方面的主要原因。纹理分析通过提取不同序列图像纹理特征来评价瘤体及其周围基质的异质性,并将结果与临床、组织病理学和基因组信息相结合,让其能无创地对乳腺病变进行前瞻性评估和预测。随着医学成像领域的高速发展,纹理分析技术不断进步,能够更准确地判断乳腺病变的性质及预后,为临床精准治疗提供更多的信息。本文就纹理分析在鉴别乳腺肿瘤良恶性、预测乳腺癌分子亚型及评估乳腺肿瘤新辅助化疗疗效等方面展开综述。     

Optical mammography: Diffuse optical imaging of breast cancer

Existing imaging modalities for breast cancer screening, diagnosis and therapy monitoring, namely X-ray mammography and magnetic resonance imaging, have been proven to have limitations. Diffuse optical imaging is a set of non-invasive imaging modalities that use near-infrared light, which can be an alternative, if not replacement, to those existing modalities. This review covers the background knowledge, recent clinical outcome, and future outlook of this newly emerging medical imaging modality.     

Ultrasound-guided optical tomographic imaging of malignant and benign breast lesions: initial clinical results of 19 cases

The diagnosis of solid benign and malignant tumors presents a unique challenge to all noninvasive imaging modalities. Ultrasound is used in conjunction with mammography to differentiate simple cysts from solid lesions. However, the overlapping appearances of benign and malignant lesions make ultrasound less useful in differentiating solid lesions, resulting in a large number of benign biopsies. Optical tomography using near-infrared diffused light has great potential for imaging functional parameters of 1) tumor hemoglobin concentration, 2) oxygen saturation, and 3) metabolism, as well as other tumor distinguishing characteristics. These parameters can differentiate benign from malignant lesions. However, optical tomography, when used alone, suffers from low spatial resolution and target localization uncertainty due to intensive light scattering. Our aim is to combine diffused light imaging with ultrasound in a novel way for the detection and diagnosis of solid lesions. Initial findings of two early-stage invasive carcinomas, one combined fibroadenoma and fibrocystic change with scattered foci of lobular neoplasia/lobular carcinoma in situ, and 16 benign lesions are reported in this paper. The invasive cancer cases reveal about two-fold greater total hemoglobin concentration (mean 119 micromol) than benign cases (mean 67 micromol), and suggest that the discrimination of benign and malignant breast lesions might be enhanced by this type of achievable optical quantification with ultrasound localization. Furthermore, the small invasive cancers are well localized and have wavelength-dependent appearance in optical absorption maps, whereas the benign lesions appear diffused and relatively wavelength-independent.