Optical Coherence Tomography: Feasibility for Basic Research and Image-guided Surgery of Breast Cancer

Diagnostic trends in medicine are being directed toward cellular and molecular processes, where treatment regimens are more amenable for cure. Optical imaging is capable of performing cellular and molecular imaging using the short wavelengths and spectroscopic properties of light. Diffuse optical tomography is an optical imaging technique that has been pursued as an alternative to X-ray mammography. While this technique permits non-invasive optical imaging of the whole breast, to date it is incapable of resolving features at the cellular level. Optical coherence tomography (OCT) is an emerging high-resolution biomedical imaging technology that for larger and undifferentiated cells can perform cellular-level imaging at the expense of imaging depth. OCT performs optical ranging in tissue and is analogous to ultrasound except reflections of near-infrared light are detected rather than sound. In this paper, an overview of the OCT technology is provided, followed by images demonstrating the feasibility of using OCT to image cellular features indicative of breast cancer. OCT images of a well-established carcinogen-induced rat mammary tumor model were acquired. Images from this common experimental model show strong correlation with corresponding histopathology. These results illustrate the potential of OCT for a wide range of basic research studies and for intra-operative image-guidance to identify foci of tumor cells within surgical margins during the surgical treatment of breast cancer.     

Thermoacoustic and photoacoustic tomography of thick biological tissues toward breast imaging

Microwave-based thermoacoustic tomography (TAT) and laser-based photoacoustic tomography (PAT) in a circular scanning configuration were both developed to image deeply seated lesions and objects in biological tissues. Because malignant breast tissue absorbs microwaves more strongly than benign breast tissue, cancers were imaged with good spatial resolution and contrast by TAT in human breast mastectomy specimens. Based on the intrinsic optical contrast between blood and chicken breast muscle, an embedded blood object that was 5 cm deep in the tissue was also detected using PAT at a wavelength of 1064 nm.     

MRI-guided diffuse optical spectroscopy of malignant and benign breast lesions

We present the clinical implementation of a novel hybrid system that combines magnetic resonance imaging (MRI) and near-infrared (NIR) optical measurements for the noninvasive study of breast cancer in vivo. Fourteen patients were studied with a MR-NIR prototype imager and spectrometer. A diffuse optical tomographic scheme employed the MR images as a priori information to implement an image-guided NIR localized spectroscopic scheme. All patients who entered the study also underwent gadolinium-enhanced MRI and biopsy so that the optical findings were cross-validated with MR readings and histopathology. The technique quantified the oxy- and deoxyhemoglobin of five malignant and nine benign breast lesions in vivo. Breast cancers were found with decreased oxygen saturation and higher blood concentration than most benign lesions. The average hemoglobin concentration ([H]) of cancers was 0.130+/-0.100 mM, and the average hemoglobin saturation (Y) was 60+/-9% compared to [H]=0.018+/-0.005 mM and Y=69+/-6% of background tissue. Fibroadenomas exhibited high hemoglobin concentration [H]=0.060+/-0.010 mM and mild decrease in oxygen saturation Y=67+/-2%. Cysts and other normal lesions were easily differentiated based on intrinsic contrast information. This novel optical technology can be a significant add-on in MR examinations and can be used to characterize functional parameters of cancers with diagnostic and treatment prognosis potential. It is foreseen that the technique can play a major role in functional activation studies of brain and muscle as well.     

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.     

Structural validation of oral mucosal tissue using optical coherence tomography

Background

Optical coherence tomography (OCT) is a non-invasive optical technology using near-infrared light to produce cross-sectional tissue images with lateral resolution.

Objectives

The overall aims of this study was to generate a bank of normative and pathological OCT data of the oral tissues to allow identification of cellular structures of normal and pathological processes with the aim to create a diagnostic algorithm which can be used in the early detection of oral disorders.

Material and methods

Seventy-three patients with 78 suspicious oral lesions were referred for further management to the UCLH Head and Neck Centre, London. The entire cohort had their lesions surgically biopsied (incisional or excisional). The immediate ex vivo phase involved scanning the specimens using optical coherence tomography. The specimens were then processed by a histopathologist. Five tissue structures were evaluated as part of this study, including: keratin cell layer, epithelial layer, basement membrane, lamina propria and other microanatomical structures. Two independent assessors (clinician and pathologist trained to use OCT) assessed the OCT images and were asked to comment on the cellular structures and changes involving the five tissue structures in non-blind fashion.

Results

Correct identification of the keratin cell layer and its structural changes was achieved in 87% of the cohort; for the epithelial layer it reached 93.5%, and 94% for the basement membrane. Microanatomical structures identification was 64% for blood vessels, 58% for salivary gland ducts and 89% for rete pegs. The agreement was ??good?? between the clinician and the pathologist. OCT was able to differential normal from pathological tissue and pathological tissue of different entities in this immediate ex vivo study. Unfortunately, OCT provided inadequate cellular and subcellular information to enable the grading of oral premalignant disorders.

Conclusion

This study enabled the creation of OCT bank of normal and pathological oral tissues. The pathological changes identified using OCT enabled differentiation between normal and pathological tissues, and identification of different tissue pathologies. Further studies are required to assess the accuracy of OCT in identification of various pathological processes involving the oral tissues.     

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.     

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.     

A Prospective Evaluation of T2-Weighted First-Pass Perfusion MR Imaging In Diagnosing Breast Neoplasms

Objective To compare the results from breast cancer patients who undergo T2-weighted first-pass perfusion imaging after dynamic contrast-enhanced T1-weighted imaging during the same examination, and to evaluate if T2-weighted imaging can provide additional diagnostic information over that obtained with T1-weighted imaging. Methods Twenty-nine patients with breast lesions verified by pathology (benign 12, malignant 17.) underwent MR imaging with dynamic contrast-enhanced T1-weighted imaging of the entire breasts, immediately followed by 6-sections of T2-weighted first-pass perfusion imaging of the lesions. The diagnostic indices were acquired by individual 3D T1-weighted enhancement rate criterion and the T2 signalintensity loss rate criterion. The sensitivity and specificity were calculated and the 2 methods were compared. Results With the dynamic.contrast-enhanced T1-weighted imaging, there was a significant differences between the benign and malignant breast lesions (t =2.563,P=0.016). However we found a considerable overlap between the signal intensity increase in the carcinomas and that in the benign lesions, for a sensitivity of 94% and a specificity of 25%. With T2-weighted first-pass perfusion imaging, there was a very significant difference between the benign and malignant breast lesions(t =4.777,P< 0.001), and the overlap between the signal intensity decrease in the carcinomas and that of the benign lesions on the T2-weighted images was less pronounced than the overlap in the T1-weighted images, for a sensitivity of 88% and a specificity of 75%. Conclusion T2-weighted first-pass perfusion imaging may help differentiate between benign and malignant breast lesions with a higher level of specificity. The combination of T1-weighted and T2-weighted imaging is feasible in a single patient examination and may improve breast MR imaging.     

超声成像联合光散射成像系统对乳腺肿瘤良恶性鉴别的应用价值

目的：探讨超声成像联合光散射成像系统（简称“超声光子”）对鉴别乳腺良、恶性肿瘤的临床应用价值。方法：随机选取74例乳腺肿物患者行超声光子检查，通过高频超声引导对肿物定位，以多波段的光子对肿物内血氧代谢、新生血管密度等生理参数进行功能成像，将结果量化规入北美放射协会制定的BI—RADS分级，（1～3级）为良性可能性大，（4～5级）为恶性可能性大，与术后病理对照分析，评价其诊断符合率。结果：超声光子诊断结果良性（1—3级）30例，恶性（4～5级）44例。术后病理诊断良性病变34例，恶性病变40例。敏感性95％（38／40），特异性82．4％（28／34），准确度89．2％（66／74）。结论：超声光散射成像系统能够有效区分乳腺良、恶性肿瘤。其不仅能够从超声二维的结构成像对肿瘤获取信息进行评价；又可以通过光学系统，从肿瘤的功能成像上获取更为深入的诊断。超声光散射成像系统开辟了早期乳腺癌检测的新领域，对提高乳腺癌的早期诊断，减少漏诊、误诊率具有重要价值。     

声辐射脉冲成像技术鉴别肝脏肿瘤良恶性的临床研究

 目的　探讨声辐射脉冲成像（ARFI）技术检测肝脏肿瘤组织硬度、评价肿瘤性质的临床价值。方法　对91例肝肿瘤患者的103个病灶进行ARFI检测,其中良性肿瘤55个,恶性肿瘤48个,所有病灶均进行声触诊组织成像（VTI）及声触诊组织定量（VTQ）检测及分析,比较良恶性肿瘤VTI图像特征及VTQ值差异,分析受试者工作特征曲线（ROC）的最佳临界值。结果　VTI图像上,硬度高于周围肝组织的恶性肿瘤占79.17 %（38／48）,良性肿瘤占56.36 %（31／55）,两者差异有统计学意义（χ2＝0.627,P＜0.01）。良性肿瘤VTQ值为（1.72±0.39）m／s,恶性肿瘤VTQ值为（2.64±0.65）m／s,两者比较差异有统计学意义（t＝8.638,P＜0.01）。以2.10 m／s为VTQ截断值,诊断ROC曲线上最佳临界点,其诊断肝脏恶性肿瘤的敏感度、特异度分别为83.3 %、81.8 %。结论　ARFI弹性成像技术提供的组织硬度信息有助于良恶性肝脏肿瘤的鉴别诊断,有望成为未来新的成像模式。     

Elevated tissue sodium concentration in malignant breast lesions detected with non-invasive <Superscript>23</Superscript>Na MRI

BACKGROUND: The hypothesis that physiological and biochemical changes associated with proliferating malignant tumors may cause an increase in total tissue sodium concentration (TSC) was tested with non-invasive, quantitative sodium ((23)Na) magnetic resonance imaging (MRI) in patients with benign and malignant breast tumors. METHODS: (23)Na and (1)H MRI of the breast was performed on 22 women with suspicious breast lesions (> or =1 cm) at 1.5 Tesla. A commercial proton ((1)H) phased array breast coil and custom solenoidal (23)Na coil were used to acquire (1)H and (23)Na images during the same MRI examination. Quantitative 3-dimensional (23)Na projection imaging was implemented with negligible signal loss from MRI relaxation, or from radio-frequency field inhomogeneity, in less than 15 min. Co-registered (1)H and (23)Na images permitted quantification of TSC in normal and suspicious tissues on the basis of (1)H MRI contrast enhancement and anatomy, with histology confirmed by biopsy. RESULTS: Sodium concentrations were consistently elevated in (N = 19) histologically proven malignant breast lesions by an average of 63% compared to glandular tissue. The increase in sodium concentration in malignant tissue was highly significant compared to unaffected glandular tissue (P < 0.0001, paired t-test), adipose tissue, and TSC in three patients with benign lesions. CONCLUSION: Elevated TSC in breast lesions measured by non-invasive (23)Na MRI appears to be a cellular-level indicator associated with malignancy. This method may have potential to improve the specificity of breast MRI with only a modest increase in scan time per patient.     

Ultrasound-guided fine-needle aspiration (FNA) of nonpalpable breast lesions: a review of 1885 FNA cases using the National Cancer Institute-supported recommendations on the uniform approach to breast FNA

BACKGROUND: A probabilistic approach to the classification of fine-needle aspirates (FNAs) of the breast recently was recommended and received endorsement from the National Cancer Institute (NCI). In this system, FNAs are classified as benign, indeterminate/atypical, suspicious/probably malignant, and malignant, but to the authors' knowledge the use of these diagnostic categories has not been evaluated on a large scale. Furthermore, this classification scheme has not been applied to FNAs of nonpalpable lesions of the breast obtained under imaging guidance. Thus, the current study focused on whether the diagnostic categories could be applied usefully to ultrasound-guided FNAs (US-FNAs) of nonpalpable breast lesions. METHODS: Between 1988-1996, 1885 US-FNAs were performed on 1639 patients. The original FNA diagnoses were reclassified into the NCI-supported recommendations for diagnostic categories of breast FNAs. The cytologic findings were correlated with the tissue specimens, which were available in 851 cases, or with clinical follow-up of a minimum of 2 years in 127 of the 274 patients with benign solid lesions. RESULTS: The 1885 cases were categorized as follows: 1057 (56.1%) as benign, 86 (4.6%) as atypical, 79 (4.2%) as probably malignant, 502 (26.6%) as malignant, and 161 (8.5%) as unsatisfactory (defined as < 6 epithelial cell groups on all slides). The benign US-FNAs included 480 (45.4%) cysts and 577 (54.6%) solid lesions. Combined clinical and surgical follow-up showed that the frequency of malignancy was 3.7% in US-FNAs classified as benign, 52.9% in those designated as atypical, 75.8% in those designated as suspicious, and 98.9% in those classified as malignant. Based on combined histologic and clinical follow-up, a sensitivity of 97.1% and specificity of 99.1% were found for US-FNAs when definitive benign and malignant diagnoses were considered. A false-negative rate of 3.7% was attributed to sampling error. A false-positive rate of 0.68% was secondary to interpretative error of proliferative lesions. CONCLUSIONS: Application of the NCI-supported diagnostic categories to US-FNA of nonpalpable breast lesions is useful in stratifying aspirates based on the likelihood of underlying malignancy. The subcategories of US-FNAs diagnosed as atypical have similar probabilities of malignancy; this justifies their being grouped as a single category wherein tissue biopsy would be required to exclude carcinoma. Benign and inadequate FNA diagnoses must be correlated with the clinical and imaging findings and in noncorrelative cases the patient should undergo biopsy. US-FNA is a sensitive and specific means with which to diagnose nonpalpable breast lesions.     

磁共振扩散张量成像在乳腺癌诊断中的应用

目的 探讨磁共振扩散张量成像(DTI)对乳腺癌的诊断价值.方法 回顾性分析116例乳腺病变(包括乳腺癌54例,乳腺良性病变62例)患者的影像学资料,所有患者均行磁共振成像(MRI)常规扫描、增强扫描和DTI检查,比较病变部位与健侧腺体组织的DTI参数,并分析不同DTI参数对乳腺癌诊断的敏感度和特异度.结果乳腺癌组织的平均扩散程度(MD)、各向异性指数(FA)、λ1值及乳腺良性病变组织的MD、λ1值均明显低于自身健侧腺体组织,差异均有统计学意义(P﹤0.01);乳腺癌组织的MD、λ1值分别为(1.00±0.30)×10-3、(1.12±0.24)×10-3 mm2/s,均明显低于乳腺良性病变组织的(1.51±0.22)×10-3、(1.80±0.21)×10-3 mm2/s,差异均有统计学意义(P﹤0.01);MD、FA、λ1值对乳腺良、恶性病变诊断的ROC曲线下面积(AUC)分别为0.945、0.640、0.988;MD、FA、λ1值诊断乳腺良、恶性病变的敏感度和特异度分别为83.50％和91.20％,45.00％和80.00％,100％和95.80％.结论DTI对乳腺良、恶性病变的诊断鉴别有重要的意义,MD、λ1值对乳腺癌诊断敏感度、特异度较高.     

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.     

磁共振扩散加权成像在乳腺病变鉴别诊断中的应用价值

背景与目的:磁共振扩散加权成像(diffusion weighted imaging,DWI)是目前惟一能观察活体水分子微观运动的成像方法,能够检测出与组织含水量改变有关的形态学和病理学的早期改变,已广泛应用于脑部病变的诊断和鉴别诊断,但在乳腺病变诊断中的应用目前仍处于研究探索阶段.本文目的在于探讨DWI在乳腺病变鉴别诊断中的价值.方法:分析52例经手术病理学检查证实的乳腺疾病患者的DWI资料,包括恶性病灶27个,良性病变36个.DWI采用单次激发平面回波成像(echo planar imaging,EPI)技术.以10例正常乳腺为对照组.测量病灶的表观扩散系数(apparent diffusion coefficient,ADC)值,比较良恶性病变、正常腺体ADC值是否具有显著性差异.采用接收者工作特征曲线(receiver operating characteristic curve,ROC)确定ADC值的诊断阈值,并用于诊断.结果:DWI对乳腺病变的显示良好.良性病变平均ADC值为(1.59±0.26)×10-3 mm2/s,95%参考值范围为(1.07～2.11)×10-3 mm2/s;恶性病灶平均ADC值为(0.87±0.23)×10-3 mm2/s,95%参考值范围(0.42～1.32)×10-3 mm2/s;正常腺体ADC值为(1.98±0.31)×10-3mm2/s.95%参考值范围(1.38～2.58)×10-3 mm2/s,三组ADC值之间均有显著性差异(P＜0.05).ROC曲线下面积(Az值)为0.96(95%可信区间0.92～1.00),诊断阈值为1.22×10-3 mm2/s.以此值作为良、恶性判断标准,敏感性88.9%,特异性87.9%,准确性85.0%.结论:ADC值有助于乳腺病变的鉴别诊断,DWI在乳腺癌的诊断上具有临床应用前景.     

声脉冲辐射力成像技术在乳腺病灶诊断中的初步研究

目的 探讨声脉冲辐射力成像（ARFI） 技术在乳腺病灶良恶性鉴别诊断中的应用价值。方法应用基于ARFI研制的超声弹性成像新技术声触诊组织定量分析（VTQ）, 对146例患者共150个乳腺病灶进行超声弹性量化检测,所有病灶均经手术或穿刺活检病理证实。采用受试者工作特征（ROC）曲线评价VTQ值对乳腺病灶良恶性的鉴别诊断价值,并确定临界值。结果150个乳腺病灶中有55个良性和95个恶性。乳腺病灶良性组与恶性组的VTQ值分别为（2.05±1.58）m/s和（6.94±2.11）m/s,两组差异有统计学意义（P＜0.01）。以VTQ值2.5m／s为临界值诊断乳腺病灶的良恶性,诊断恶性的敏感度为79％,特异度为71％,准确度为75％;以VTQ值28m／s为临界值诊断最小径≥8mm乳腺病灶的敏感度为90％,特异度为82％,准确度为85％。结论 ARFI技术为乳腺病灶的超声诊断提供了一个新的定量指标VTQ值,其对鉴别乳腺病灶,特别是最小径≥8mm病灶的良恶性有较高的诊断价值。     

Silver nucleolar organizer region assessment in tumor-cells from breast-cancer patients treated by extremely-low-frequency magnetic-field

This study assessed the value of silver staining of nucleolar organizer regions (AgNORs) in tumor cells as a potential technique for the estimation of the action of ELF magnetic field on breast cancer. The light and electron microscopy was used for analysis of tissue specimens from 4 breast cancer patients after ELF magnetotherapy and 18 untreated persons with malignant and benign breast lesions. All patients had surgical removal of neoplasms. The mean number of AgNORs and the distribution of cells according to the AgNOR number in tissue samples from patients after successful ELF magnetotherapy were closer to those of persons with benign tumors, as compared to malignant ones. The effect of ELF magnetic field at the electron microscopic level is discussed.     

Role of aspiration cytology in the diagnosis and management of mammary lesions in office practice

Sixteen hundred and eighty breast aspiration specimens obtained from 1410 patients seen in office practice were reviewed. The cytologic diagnosis was unsatisfactory in 230 cases, benign in 1019 cases, atypical in 198 cases, suspicious for malignancy in 102 cases, and malignant in 131 cases. All cases diagnosed as cytologically malignant had a subsequent tissue diagnosis of malignant neoplasm. Four percent of the cytologically benign cases and 17% of the cytologically atypical cases had malignant neoplasms. Clinical and cytologic examination detected more cancers (87%) than did clinical and mammographic examination (79%). Ninety-three percent of malignant neoplasms were detected by the combination of clinical, cytologic, and mammographic examination. Aspiration cytology significantly contributes to the clinical evaluation of mammary lesions in office practice, but it does not replace tissue biopsy or careful follow-up of mammary lesions of clinical concern. Proof of the presence of breast cancer by aspiration in the office may obviate the need for a two-stage procedure in the surgical management of breast cancer. Aspiration of minimally suspicious lesions often is helpful in initiating excisional biopsy in some occult, clinically unrecognized breast cancers.     

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.     

Immunological analysis of 17 beta-hydroxysteroid dehydrogenase in benign and malignant human breast tissue.

The expression of 17 beta-hydroxysteroid dehydrogenase (17-HSD) enzyme protein was studied in benign and malignant human breast tissue using the time-resolved immunofluorometric assay (IFMA), immunoblotting and immunohistochemistry. The presence and distribution of estrogen and progestin receptors was also analyzed immunohistochemically. Cytosolic 17-HSD concentrations in malignant breast specimens were highly variable (less than or equal to 0.2-311 ng/mg protein). As was previously found for the placental enzyme, the molecular weight of the 17-HSD expressed in malignant breast tissue was 35 kDa, estimated following polyacrylamide gel electrophoresis and immunoblotting. The cellular distribution of 17-HSD was further studied by immunohistochemistry. Immunostaining for 17-HSD was observed in 71% of the benign breast lesions (fibroadenomas and cases of mastopathia chronica) and in 47% of the cancer specimens (intra-ductal carcinomas, invasive ductal carcinomas). In benign lesions, the staining was exclusively localized in the cytoplasm of epithelial cells, with no immunoreactivity in the stromal cells. The staining in the cancer specimens was also detected only in the cytoplasm of malignant epithelial cells. A strong or moderate expression of 17-HSD was related to the presence of PR in the specimen (chi 2 = 4.657, p = 0.031). However, the expression of PR was not a prerequisite for expression of 17-HSD in all the cancer specimens. Our data suggest that, in addition to the reported regulation of 17-HSD by progestins, other factors are also involved in this process in breast tissue.