We present optical coherence micro-elastography, an improved form of compression optical coherence elastography. We demonstrate the capacity of this technique to produce en face images, closely corresponding with histology, that reveal micro-scale mechanical contrast in human breast and lymph node tissues. We use phase-sensitive, three-dimensional optical coherence tomography (OCT) to probe the nanometer-to-micrometer-scale axial displacements in tissues induced by compressive loading. Optical coherence micro-elastography incorporates common-path interferometry, weighted averaging of the complex OCT signal and weighted least-squares regression. Using three-dimensional phase unwrapping, we have increased the maximum detectable strain eleven-fold over no unwrapping and the minimum detectable strain is 2.6 με. We demonstrate the potential of mechanical over optical contrast for visualizing micro-scale tissue structures in human breast cancer pathology and lymph node morphology.

We review the development of phantoms for optical coherence tomography (OCT) designed to replicate the optical, mechanical and structural properties of a range of tissues. Such phantoms are a key requirement for the continued development of OCT techniques and applications. We focus on phantoms based on silicone, fibrin and poly(vinyl alcohol) cryogels (PVA-C), as we believe these materials hold the most promise for durable and accurate replication of tissue properties.

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. As the tumor modifies the mechanical properties of breast tissue, OCME has the potential to identify, on the microscale, involved regions of fresh, unstained tissue. OCME is based on the use of optical coherence tomography (OCT) to measure tissue deformation in response to applied mechanical compression. In this feasibility study on 58 ex vivo samples from patients undergoing mastectomy or wide local excision, we demonstrate the performance of OCME as a means to visualize tissue microarchitecture in benign and malignant human breast tissues. Through a comparison with corresponding histology and OCT images, OCME is shown to enable ready visualization of features such as ducts, lobules, microcysts, blood vessels, and arterioles and to identify invasive tumor through distinctive patterns in OCME images, often with enhanced contrast compared with OCT. These results lay the foundation for future intraoperative studies. Cancer Res; 75(16); 3236–45. ©2015 AACR.

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Rationale: Our understanding of how airway remodeling affects regional airway elastic properties is limited due to technical difficulties in quantitatively measuring dynamic, in vivo airway dimensions. Such knowledge could help elucidate mechanisms of excessive airway narrowing. Objectives: To use anatomical optical coherence tomography (aOCT) to compare central airway elastic properties in control subjects and those with obstructive lung diseases. Methods: After bronchodilation, airway lumen area (Ai) was measured using aOCT during bronchoscopy in control subjects (n 5 10) and those with asthma (n 5 16), chronic obstructive pulmonary disease (COPD) (n 5 9), and bronchiectasis (n 5 8). Ai was measured in each of generations 0 to 5 while airway pressure was increased from 210 to 20 cm H 2 O. Airway compliance (Caw) and specific compliance (sCaw) were derived from the transpulmonary pressure (PL) versus Ai curves. Measurements and Main Results: Caw decreased progressively as airway generation increased, but sCaw did not differ appreciably across the generations. In subjects with asthma and bronchiectasis, Caw and sCaw were similar to control subjects and the PL-Ai curves were left-shifted. No significant differences were observed between control and COPD groups. Conclusions: Proximal airway elastic properties are altered in obstructive lung diseases. Although central airway compliance does not differ from control subjects in asthma, bronchiectasis, or COPD, Ai is lower in asthma and the PL-Ai relationship is left-shifted in both asthma and bronchiectasis, suggesting that airways are maximally distended at lower inflating pressures. Such changes reflect alteration in the balance between airway wall distensibility and radial traction exerted on airways by surrounding lung parenchyma favoring airway narrowing. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN12607000624482).

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. We performed wide-field quantitative micro-elastography on thirteen specimens of freshly excised tissue acquired from patients undergoing mastectomy. We present wide-field optical coherence tomography (OCT) images, qualitative (strain) micro-elastograms and quantitative (elasticity) micro-elastograms, acquired in 10 minutes. We demonstrate that wide-field quantitative micro-elastography can extend the range of tumors visible using OCT-based elastography by providing contrast not present in either OCT or qualitative microelastography and, in addition, can reduce imaging artifacts caused by a lack of contact between tissue and the imaging window. Also, we describe how the combined evaluation of OCT, qualitative micro-elastograms and quantitative micro-elastograms can improve the visualization of tumor.

In situ imaging of alveoli and the smaller airways with optical coherence tomography (OCT) has significant potential in the assessment of lung disease. We present a minimally invasive imaging technique utilizing an OCT needle probe. The side-facing needle probe comprises miniaturized focusing optics consisting of no-core and GRIN fiber encased within a 23-gauge needle. 3D-OCT volumetric data sets were acquired by rotating and retracting the probe during imaging. The probe was used to image an intact, fresh (not fixed) sheep lung filled with normal saline, and the results validated against a histological gold standard. We present the first published images of alveoli acquired with an OCT needle probe and demonstrate the potential of this technique to visualize other anatomical features such as bifurcations of the bronchioles.

Airway dimensions are difficult to quantify bronchoscopically because of optical distortion and a limited ability to gauge depth. Anatomical optical coherence tomography (aOCT), a novel imaging technique, may overcome these limitations. This study evaluated the accuracy of aOCT against existing techniques in phantom, excised pig and in vivo human airways.Three comparative studies were performed: 1) micrometer-derived area measurements in 10 plastic tubes were compared with aOCT-derived area; 2) aOCT-derived airway compliance curves from excised pig airways were compared with curves derived using an endoscopic technique; and 3) airway dimensions from the trachea to subsegmental bronchi were measured using aOCT in four anaesthetised patients during bronchoscopy and compared with computed tomography (CT) measurements.Measurements in plastic tubes revealed aOCT to be accurate and reliable. In pig airways, aOCTderived compliance measurements compared closely with endoscopic data. In human airways, dimensions measured with aOCT and CT correlated closely. Bland-Altman plots showed that aOCT diameter and area measurements were higher than CT measurements by 7.6% and 15.1%, respectively.Airway measurements using aOCT are accurate, reliable and compare favourably with existing imaging techniques. Using aOCT with conventional bronchoscopy allows real-time measurement of airway dimensions and could be useful clinically in settings where knowledge of airway calibre is required.