The emergence of optical elastography in biomedicine

The authors thank their colleagues past and present who have contributed to the evolution of optical elastography; in particular, S. Adie, W. Allen, L. Chin, B. Quirk, A. Curatolo, S. Es'hagian, K. Kennedy, R. Kirk, R. McLaughlin and P. Munro. This work has been supported in part by the Australian Research Council, the National Health and Medical Research Council, the National Breast Cancer Foundation, and the Western Australian Department of Health. P.W. thanks the Schrader Trust for a studentship.Optical elastography, the use of optics to characterize and map the mechanical properties of biological tissue, involves measuring the deformation of tissue in response to a load. Such measurements may be used to form an image of a mechanical property, often elastic modulus, with the resulting mechanical contrast complementary to the more familiar optical contrast. Optical elastography is experiencing new impetus in response to developments in the closely related fields of cell mechanics and medical imaging, aided by advances in photonics technology, and through probing the microscale between that of cells and whole tissues. Two techniques-optical coherence elastography and Brillouin microscopy-have recently shown particular promise for medical applications, such as in ophthalmology and oncology, and as new techniques in cell mechanics.PostprintPeer reviewe

Optical coherence elastography for cellular-scale stiffness imaging of mouse aorta

We have developed a high-resolution optical coherence elastography system capable of estimating Young's modulus in tissue volumes with an isotropic resolution of 15 μm over a 1 mm lateral field of view and a 100 μm axial depth of field. We demonstrate our technique on healthy and hypertensive, freshly excised and intact mouse aortas. Our technique has the capacity to delineate the individual mechanics of elastic lamellae and vascular smooth muscle. Further, we observe global and regional vascular stiffening in hypertensive aortas, and note the presence of local micro-mechanical signatures, characteristic of fibrous and lipid-rich regions.Publisher PD

OCTAVA: An open-source toolbox for quantitative analysis of optical coherence tomography angiography images

Optical coherence tomography angiography (OCTA) performs non-invasive visualization and characterization of microvasculature in research and clinical applications mainly in ophthalmology and dermatology. A wide variety of instruments, imaging protocols, processing methods and metrics have been used to describe the microvasculature, such that comparing different study outcomes is currently not feasible. With the goal of contributing to standardization of OCTA data analysis, we report a user-friendly, open-source toolbox, OCTAVA (OCTA Vascular Analyzer), to automate the pre-processing, segmentation, and quantitative analysis of en face OCTA maximum intensity projection images in a standardized workflow. We present each analysis step, including optimization of filtering and choice of segmentation algorithm, and definition of metrics. We perform quantitative analysis of OCTA images from different commercial and non-commercial instruments and samples and show OCTAVA can accurately and reproducibly determine metrics for characterization of microvasculature. Wide adoption could enable studies and aggregation of data on a scale sufficient to develop reliable microvascular biomarkers for early detection, and to guide treatment, of microvascular disease

Fifty Years of ISCA: A data-driven retrospective on key trends

Computer Architecture, broadly, involves optimizing hardware and software for current and future processing systems. Although there are several other top venues to publish Computer Architecture research, including ASPLOS, HPCA, and MICRO, ISCA (the International Symposium on Computer Architecture) is one of the oldest, longest running, and most prestigious venues for publishing Computer Architecture research. Since 1973, except for 1975, ISCA has been organized annually. Accordingly, this year will be the 50th year of ISCA. Thus, we set out to analyze the past 50 years of ISCA to understand who and what has been driving and innovating computing systems thus far. Our analysis identifies several interesting trends that reflect how ISCA, and Computer Architecture in general, has grown and evolved in the past 50 years, including minicomputers, general-purpose uniprocessor CPUs, multiprocessor and multi-core CPUs, general-purpose GPUs, and accelerators.Comment: 17 pages, 11 figure

Volumetric quantitative optical coherence elastography with an iterative inversion method

It is widely accepted that accurate mechanical properties of three-dimensional soft tissues and cellular samples are not available on the microscale. Current methods based on optical coherence elastography can measure displacements at the necessary resolution, and over the volumes required for this task. However, in converting this data to maps of elastic properties, they often impose assumptions regarding homogeneity in stress or elastic properties that are violated in most realistic scenarios. Here, we introduce novel, rigorous, and computationally efficient inverse problem techniques that do not make these assumptions, to realize quantitative volumetric elasticity imaging on the microscale. Specifically, we iteratively solve the three-dimensional elasticity inverse problem using displacement maps obtained from compression optical coherence elastography. This is made computationally feasible with adaptive mesh refinement and domain decomposition methods. By employing a transparent, compliant surface layer with known shear modulus as a reference for the measurement, absolute shear modulus values are produced within a millimeter-scale sample volume. We demonstrate the method on phantoms, on a breast cancer sample ex vivo, and on human skin in vivo. Quantitative elastography on this length scale will find wide application in cell biology, tissue engineering and medicine.Publisher PDFPeer reviewe

Parametric imaging of attenuation by optical coherence tomography: review of models, methods, and clinical translation

SIGNIFICANCE: Optical coherence tomography (OCT) provides cross-sectional and volumetric images of backscattering from biological tissue that reveal the tissue morphology. The strength of the scattering, characterized by an attenuation coefficient, represents an alternative and complementary tissue optical property, which can be characterized by parametric imaging of the OCT attenuation coefficient. Over the last 15 years, a multitude of studies have been reported seeking to advance methods to determine the OCT attenuation coefficient and developing them toward clinical applications. AIM: Our review provides an overview of the main models and methods, their assumptions and applicability, together with a survey of preclinical and clinical demonstrations and their translation potential. RESULTS: The use of the attenuation coefficient, particularly when presented in the form of parametric en face images, is shown to be applicable in various medical fields. Most studies show the promise of the OCT attenuation coefficient in differentiating between tissues of clinical interest but vary widely in approach. CONCLUSIONS: As a future step, a consensus on the model and method used for the determination of the attenuation coefficient is an important precursor to large-scale studies. With our review, we hope to provide a basis for discussion toward establishing this consensus

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

This project is supported with funding from the Australian Research Council; and Cancer Council WA, which allowed us to develop the technology; Department of Health of Western Australia, National Breast Cancer Foundation (Australia); and the National Health and Medical Research Council, Australia, which allowed us to design and implement the clinical protocol, and to perform the clinical measurements.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. A method to image the micro-scale mechanical properties of lymph nodes could, thus, provide diagnostic information to aid in the assessment of lymph node involvement in metastatic cancer. In this study, we scan axillary lymph nodes, freshly excised from breast cancer patients, with optical coherence micro-elastography (OCME), a method of imaging micro-scale mechanical strain, to assess its potential for the intraoperative assessment of lymph node involvement. Methods : Twenty-six fresh, unstained lymph nodes were imaged from 15 patients undergoing mastectomy or breast-conserving surgery with axillary clearance. Lymph node specimens were bisected to allow imaging of the internal face of each node. Co-located OCME and optical coherence tomography (OCT) scans were taken of each sample, and the results compared to standard post-operative hematoxylin-and-eosin-stained histology. Results : The optical backscattering signal provided by OCT alone may not provide reliable differentiation by inspection between benign and malignant lymphoid tissue. Alternatively, OCME highlights local changes in tissue strain that correspond to malignancy and are distinct from strain patterns in benign lymphoid tissue. The mechanical contrast provided by OCME complements the optical contrast provided by OCT and aids in the differentiation of malignant tumor from uninvolved lymphoid tissue. Conclusion : The combination of OCME and OCT images represents a promising method for the identification of malignant lymphoid tissue. This method shows potential to provide intraoperative assessment of lymph node involvement, thus, preventing unnecessary removal of uninvolved tissues and improving patient outcomes.Publisher PDFPeer reviewe

Depth-encoded optical coherence elastography for simultaneous volumetric imaging of two tissue faces

Australian Research Council (ARC); National Health and Medical Research Council (NHMRC); National Breast Cancer Foundation (NBCF); Department of Health, Government of Western Australia.Depth-encoded optical coherence elastography (OCE) enables simultaneous acquisition of two three-dimensional (3D) elastograms from opposite sides of a sample. By the choice of suitable path-length differences in each of two interferometers, the detected carrier frequencies are separated, allowing depth-ranging from each interferometer to be performed simultaneously using a single spectrometer. We demonstrate depth-encoded OCE on a silicone phantom and a freshly excised sample of mouse liver. This technique minimizes the required spectral detection hardware and halves the total scan time. Depth-encoded OCE may expedite clinical translation in time-sensitive applications requiring rapid 3D imaging of multiple tissue surfaces, such as tumor margin assessment in breast-conserving surgery.PostprintPeer reviewe