Quantitative Micro-Elastography Enables In Vivo Detection of Residual Cancer in the Surgical Cavity during Breast-Conserving Surgery.

Unlabelled: Breast-conserving surgery (BCS) is commonly used for the treatment of early-stage breast cancer. Following BCS, approximately 20% to 30% of patients require reexcision because postoperative histopathology identifies cancer in the surgical margins of the excised specimen. Quantitative micro-elastography (QME) is an imaging technique that maps microscale tissue stiffness and has demonstrated a high diagnostic accuracy (96%) in detecting cancer in specimens excised during surgery.

Multi-class classification of breast tissue using optical coherence tomography and attenuation imaging combined via deep learning.

We demonstrate a convolutional neural network (CNN) for multi-class breast tissue classification as adipose tissue, benign dense tissue, or malignant tissue, using multi-channel optical coherence tomography (OCT) and attenuation images, and a novel Matthews correlation coefficient (MCC)-based loss function that correlates more strongly with performance metrics than the commonly used cross-entropy loss. We hypothesized that using multi-channel images would increase tumor detection performance compared to using OCT alone. 5,804 images from 29 patients were used to fine-tune a pre-trained ResNet-18 network.

Coherence function-encoded optical palpation.

Optical palpation maps stress at the surface of biological tissue into 2D images. It relies on measuring surface deformation of a compliant layer, which to date has been performed with optical coherence tomography (OCT). OCT-based optical palpation holds promise for improved clinical diagnostics; however, the complexity and cost hinder broad adoption.

Diagnostic concordance among pathologists interpreting breast core biopsies on secondary review over a 1-year period at an Australian tertiary hospital.

This study provides data on the diagnostic concordance between initial and review diagnoses of all breast core biopsy cases at a single tertiary hospital in Western Australia over a 1-year period. A retrospective review of all breast core biopsy cases between January 1 and December 31, 2016, was carried out at PathWest, Fiona Stanley Hospital in Perth, Western Australia. Each biopsy is reported by a single pathologist and then reviewed within 1 week by a panel of intradepartmental subspecialist breast pathologists, who either agree with the original diagnosis, have a minor discordant diagnosis, or a major discordant diagnosis.

Optical palpation for tumor margin assessment in breast-conserving surgery.

Intraoperative margin assessment is needed to reduce the re-excision rate of breast-conserving surgery. One possibility is optical palpation, a tactile imaging technique that maps stress (force applied across the tissue surface) as an indicator of tissue stiffness. Images (optical palpograms) are generated by compressing a transparent silicone layer on the tissue and measuring the layer deformation using optical coherence tomography (OCT).

Camera-based optical palpation.

Optical elastography is undergoing extensive development as an imaging tool to map mechanical contrast in tissue. Here, we present a new platform for optical elastography by generating sub-millimetre-scale mechanical contrast from a simple digital camera. This cost-effective, compact and easy-to-implement approach opens the possibility to greatly expand applications of optical elastography both within and beyond the field of medical imaging.

Diagnostic Accuracy of Quantitative Micro-Elastography for Margin Assessment in Breast-Conserving Surgery.

Inadequate margins in breast-conserving surgery (BCS) are associated with an increased likelihood of local recurrence of breast cancer. Currently, approximately 20% of BCS patients require repeat surgery due to inadequate margins at the initial operation. Implementation of an accurate, intraoperative margin assessment tool may reduce this re-excision rate.

Three-dimensional mapping of the attenuation coefficient in optical coherence tomography to enhance breast tissue microarchitecture contrast.

Effective intraoperative tumor margin assessment is needed to reduce re-excision rates in breast-conserving surgery (BCS). Mapping the attenuation coefficient in optical coherence tomography (OCT) throughout a sample to create an image (attenuation imaging) is one promising approach. For the first time, three-dimensional OCT attenuation imaging of human breast tissue microarchitecture using a wide-field (up to ~45 × 45 × 3.

Handheld volumetric manual compression-based quantitative microelastography.

Compression optical coherence elastography (OCE) typically requires a mechanical actuator to impart a controlled uniform strain to the sample. However, for handheld scanning, this adds complexity to the design of the probe and the actuator stroke limits the amount of strain that can be applied. In this work, we present a new volumetric imaging approach that utilizes bidirectional manual compression via the natural motion of the user's hand to induce strain to the sample, realizing compact, actuator-free, handheld compression OCE.

Activation of Canonical BMP4-SMAD7 Signaling Suppresses Breast Cancer Metastasis.

Metastasis is the major cause of death in patients with cancer; with no therapeutic cure, treatments remain largely palliative. As such, new targets and therapeutic strategies are urgently required. Here, we show that bone morphogenetic protein-4 (BMP4) blocks metastasis in animal models of breast cancer and predicts improved survival in patients.

Handheld probe for quantitative micro-elastography.

Optical coherence elastography (OCE) has been proposed for a range of clinical applications. However, the majority of these studies have been performed using bulky, lab-based imaging systems. A compact, handheld imaging probe would accelerate clinical translation, however, to date, this had been inhibited by the slow scan rates of compact devices and the motion artifact induced by the user's hand.

Clinical feasibility of optical coherence micro-elastography for imaging tumor margins in breast-conserving surgery.

It has been demonstrated that optical coherence micro-elastography (OCME) provides additional contrast of tumor compared to optical coherence tomography (OCT) alone. Previous studies, however, have predominantly been performed on mastectomy specimens. Such specimens typically differ substantially in composition and geometry from the more clinically relevant wide-local excision (WLE) specimens excised during breast-conserving surgery.

Review of diagnostic error in anatomical pathology and the role and value of second opinions in error prevention.

Aims: Diagnostic/interpretative accuracy can be challenging in anatomical pathology due to the subjective element of the diagnostic process. This can lead to false-negative or false-positive diagnoses of malignancy, variations in grading and diagnostic misclassification of a condition.It is imperative that an accurate diagnosis is achieved so that an appropriate and timely treatment is administered to the patient, for example, the success of targeted molecular therapeutic options for treatment of cancer is dependent on accurate anatomical pathology diagnoses being issued.

Optical palpation for the visualization of tumor in human breast tissue.

Accurate and effective removal of tumor in one operation is an important goal of breast-conserving surgery. However, it is not always achieved. Surgeons often utilize manual palpation to assess the surgical margin and/or the breast cavity.

Wide-field quantitative micro-elastography of human breast tissue.

Currently, 20-30% of patients undergoing breast-conserving surgery require a second surgery due to insufficient surgical margins in the initial procedure. We have developed a wide-field quantitative micro-elastography system for the assessment of tumor margins. In this technique, we map tissue elasticity over a field-of-view of ~46 × 46 mm.

InForm software: a semi-automated research tool to identify presumptive human hepatic progenitor cells, and other histological features of pathological significance.

Hepatic progenitor cells (HPCs) play an important regenerative role in acute and chronic liver pathologies. Liver disease research often necessitates the grading of disease severity, and pathologists' reports are the current gold-standard for assessment. However, it is often impractical to recruit pathologists in large cohort studies.

False-negative contrast-enhanced spectral mammography: use of more than one imaging modality and application of the triple test avoids misdiagnosis.

A 50-year-old woman presented with chest tenderness. On examination, both breasts were lumpy. Bilateral mammography showed heterogeneously dense parenchyma, with possible stromal distortion laterally on the right at the 0900 position.

Wide-field optical coherence micro-elastography for intraoperative assessment of human breast cancer margins.

Incomplete excision of malignant tissue is a major issue in breast-conserving surgery, with typically 20 - 30% of cases requiring a second surgical procedure arising from postoperative detection of an involved margin. We report advances in the development of a new intraoperative tool, optical coherence micro-elastography, for the assessment of tumor margins on the micro-scale. We demonstrate an important step by conducting whole specimen imaging in intraoperative time frames with a wide-field scanning system acquiring mosaicked elastograms with overall dimensions of ~50 × 50 mm, large enough to image an entire face of most lumpectomy specimens.

Investigation of optical coherence micro-elastography as a method to visualize micro-architecture in human axillary lymph nodes.

Background: Evaluation of lymph node involvement is an important factor in detecting metastasis and deciding whether to perform axillary lymph node dissection (ALND) in breast cancer surgery. As ALND is associated with potentially severe long term morbidity, the accuracy of lymph node assessment is imperative in avoiding unnecessary ALND. The mechanical properties of malignant lymph nodes are often distinct from those of normal nodes.

Simplifying the assessment of human breast cancer by mapping a micro-scale heterogeneity index in optical coherence elastography.

Surgical treatment of breast cancer aims to identify and remove all malignant tissue. Intraoperative assessment of tumor margins is, however, not exact; thus, re-excision is frequently needed, or excess normal tissue is removed. Imaging methods applicable intraoperatively could help to reduce re-excision rates whilst minimizing removal of excess healthy tissue.

Quantitative micro-elastography: imaging of tissue elasticity using compression optical coherence elastography.

Probing the mechanical properties of tissue on the microscale could aid in the identification of diseased tissues that are inadequately detected using palpation or current clinical imaging modalities, with potential to guide medical procedures such as the excision of breast tumours. Compression optical coherence elastography (OCE) maps tissue strain with microscale spatial resolution and can delineate microstructural features within breast tissues. However, without a measure of the locally applied stress, strain provides only a qualitative indication of mechanical properties.

Investigation of Optical Coherence Microelastography as a Method to Visualize Cancers in Human Breast Tissue.

An accurate intraoperative identification of malignant tissue is a challenge in the surgical management of breast cancer. Imaging techniques that help address this challenge could contribute to more complete and accurate tumor excision, and thereby help reduce the current high reexcision rates without resorting to the removal of excess healthy tissue. Optical coherence microelastography (OCME) is a three-dimensional, high-resolution imaging technique that is sensitive to microscale variations of the mechanical properties of tissue.

Predictors of re-excision in wire-guided wide local excision for early breast cancer: a Western Australian multi-centre experience.

Background: A significant proportion of breast cancers present as impalpable lesions requiring radiological guidance prior to surgical excision, commonly by hook-wire placement. Complete lesion excision is an essential part of treatment, and re-excision may be needed to ensure this and minimize local recurrence. We explore a 1-year audit of re-excision of hook-wire-guided excisions in two large public breast units in Western Australia and define factors associated with the requirement for re-excision.

Radioguided occult lesion localisation using iodine-125 seeds ('ROLLIS') for removal of impalpable breast lesions: First Australian experience.

Introduction: Approximately one-third of breast cancers are impalpable and require pre-operative image-guided localisation. Hook-wire localisation (HWL) is commonly used but has several disadvantages. Use of a low-activity radioactive iodine-125 seed is a promising alternative technique used in the USA and the Netherlands.

Nottingham Clinico-Pathological Response Index (NPRI) after neoadjuvant chemotherapy (Neo-ACT) accurately predicts clinical outcome in locally advanced breast cancer.

Purpose: There is a need to identify more sensitive clinicopathologic criteria to assess the response to neoadjuvant chemotherapy (Neo-ACT) and guide subsequent adjuvant therapy.

Experimental Design: We performed a clinicopathologic assessment of 426 patients who had completed Neo-ACT for locally advanced breast cancer (LABC) with a median follow-up of 70 months. Patients were divided into a training set treated with anthracycline combination chemotherapy (n = 172); an internal validation set treated with anthracycline and taxane (n = 129); and an external validation set treated with anthracycline with or without taxane (n = 125).