Analysis of spatial resolution in phase-sensitive compression optical coherence elastography

Funding: Australian Research Council; the Cancer Council Western Australia; OncoRes Medical; William and Marlene Schrader Trust of the University of Western Australia scholarship.Optical coherence elastography (OCE) is emerging as a method to image the mechanical properties of tissue on the microscale. However, the spatial resolution, a main advantage of OCE, has not been investigated and is not trivial to evaluate. To address this, we present a framework to analyze resolution in phase-sensitive compression OCE that incorporates the three main determinants of resolution: mechanical deformation of the sample, detection of this deformation using optical coherence tomography (OCT), and signal processing to estimate local axial strain. We demonstrate for the first time, through close correspondence between experiment and simulation of structured phantoms, that resolution in compression OCE is both spatially varying and sample dependent, which we link to the discrepancies between the model of elasticity and the mechanical deformation of the sample. We demonstrate that resolution is dependent on factors such as feature size and mechanical contrast. We believe that the analysis of image formation provided by our framework can expedite the development of compression OCE.Publisher PDFPeer reviewe

Impacts of increasing typhoons on the structure and function of a subtropical forest: reflections of a changing climate

Due to their destructive and sporadic nature, it is often difficult to evaluate and predict the effects of typhoon on forest ecosystem patterns and processes. We used a 21-yr record of litterfall rates to explore the influence of typhoon frequency and intensity, along with other meteorological variables, on ecosystem dynamics in a subtropical rainforest. Over the past half century there has been an increasing frequency of strong typhoons (category 3; >49.6 m s-1; increase of 1.5 typhoons/decade) impacting the Fushan Experimental Forest, Taiwan. At Fushan strong typhoons drive total litterfall mass with an average of 1100 kg ha-1 litterfall typhoon-1. While mean typhoon season litterfall has been observed to vary by an order of magnitude, mean litterfall rates associated with annual leaf senescence vary by <20%. In response to increasing typhoon frequency, total annual litter mass increased gradually over the 21-year record following three major typhoons in 1994. Monthly maximum wind speed was predictive of monthly litterfall, yet the influence of precipitation and temperature was only evident in non-typhoon affected months. The response of this subtropical forest to strong typhoons suggests that increasing typhoon frequency has already shifted ecosystem structure and function (declining carbon sequestration and forest stature)

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

Finger-mounted quantitative micro-elastography

Funding: Australian Research Council (ARC); the Cancer Council, Western Australia; OncoRes Medical; War Widows' Guild of Western Australia Scholarship.We present a finger-mounted quantitative micro-elastography (QME) probe, capable of measuring the elasticity of biological tissue in a format that avails of the dexterity of the human finger. Finger-mounted QME represents the first demonstration of a wearable elastography probe. The approach realizes optical coherence tomography-based elastography by focusing the optical beam into the sample via a single-mode fiber that is fused to a length of graded-index fiber. The fiber is rigidly affixed to a 3D-printed thimble that is mounted on the finger. Analogous to manual palpation, the probe compresses the tissue through the force exerted by the finger. The resulting deformation is measured using optical coherence tomography. Elasticity is estimated as the ratio of local stress at the sample surface, measured using a compliant layer, to the local strain in the sample. We describe the probe fabrication method and the signal processing developed to achieve accurate elasticity measurements in the presence of motion artifact. We demonstrate the probe's performance in motion-mode scans performed on homogeneous, bi-layer and inclusion phantoms and its ability to measure a thermally-induced increase in elasticity in ex vivo muscle tissue. In addition, we demonstrate the ability to acquire 2D images with the finger-mounted probe where lateral scanning is achieved by swiping the probe across the sample surfacePublisher PDFPeer reviewe

MatterGen: a generative model for inorganic materials design

The design of functional materials with desired properties is essential in driving technological advances in areas like energy storage, catalysis, and carbon capture. Generative models provide a new paradigm for materials design by directly generating entirely novel materials given desired property constraints. Despite recent progress, current generative models have low success rate in proposing stable crystals, or can only satisfy a very limited set of property constraints. Here, we present MatterGen, a model that generates stable, diverse inorganic materials across the periodic table and can further be fine-tuned to steer the generation towards a broad range of property constraints. To enable this, we introduce a new diffusion-based generative process that produces crystalline structures by gradually refining atom types, coordinates, and the periodic lattice. We further introduce adapter modules to enable fine-tuning towards any given property constraints with a labeled dataset. Compared to prior generative models, structures produced by MatterGen are more than twice as likely to be novel and stable, and more than 15 times closer to the local energy minimum. After fine-tuning, MatterGen successfully generates stable, novel materials with desired chemistry, symmetry, as well as mechanical, electronic and magnetic properties. Finally, we demonstrate multi-property materials design capabilities by proposing structures that have both high magnetic density and a chemical composition with low supply-chain risk. We believe that the quality of generated materials and the breadth of MatterGen's capabilities represent a major advancement towards creating a universal generative model for materials design.Comment: 13 pages main text, 35 pages supplementary informatio

Handheld probe for quantitative micro-elastography

Funding: Australian Research Council (ARC); Department of Health, Western Australia; Cancer Council, Western Australia; OncoRes Medical.Optical coherence elastography (OCE) has been proposed for a range of clinical applications. However, the majority of these studies have been performed using bulks, lab based imaging systems. A compact. handheld imaging probe would accelerate clinical translation, however, to date. tins had been inhibited by the slow scan rates of compact devices and the motion artifact induced by the user's hand. In this paper, we present a proof-of-concept. handheld quantitative micro-elastography (QME) probe capable of scanning a 6 x 6 x 1 mm volume of tissue in 3.4 seconds. This handheld probe is enabled by a novel QME acquisition protocol that incorporates a custom bidirectional scan pattern driving a microelectromechanical system (MEMS) scanner, synchronized with the sample deformation induced by an annular PZT actuator. The custom scan pattern reduces the total acquisition time and the time difference between B-scans used to generate displacement maps. minimizing the impact of motion artifact. We test the feasibility of the handheld QME probe on a tissue-mimicking silicone phantom, demonstrating comparable image quality to a bench-mounted setup. In addition, we present the first handheld QME scans performed on human breast tissue specimens. For each specimen, quantitative micro-elastograms are co-registered with, and validated by, histology, demonstrating the ability-to distinguish stiff cancerous tissue from surrounding soft benign tissue.Publisher PDFPeer reviewe

Quantitative Analysis and Comparison Study of [18F]AlF-NOTA-PRGD2, [18F]FPPRGD2 and [68Ga]Ga-NOTA-PRGD2 Using a Reference Tissue Model

With favorable pharmacokinetics and binding affinity for αvβ3 integrin, 18F-labeled dimeric cyclic RGD peptide ([18F]FPPRGD2) has been intensively used as a PET imaging probe for lesion detection and therapy response monitoring. A recently introduced kit formulation method, which uses an 18F-fluoride-aluminum complex labeled RGD tracer ([18F]AlF-NOTA-PRGD2), provides a strategy for simplifying the labeling procedure to facilitate clinical translation. Meanwhile, an easy-to-prepare 68Ga-labeled NOTA-PRGD2 has also been reported to have promising properties for imaging integrin αvβ3. The purpose of this study is to quantitatively compare the pharmacokinetic parameters of [18F]FPPRGD2, [18F]AlF-NOTA-PRGD2, and [68Ga]Ga-NOTA-PRGD2. U87MG tumor-bearing mice underwent 60-min dynamic PET scans following the injection of three tracers. Kinetic parameters were calculated using Logan graphical analysis with reference tissue. Parametric maps were generated using voxel-level modeling. All three compounds showed high binding potential (BpND = k3/k4) in tumor voxels. [18F]AlF-NOTA-PRGD2 showed comparable BpND value (3.75±0.65) with those of [18F]FPPRGD2 (3.39±0.84) and [68Ga]Ga-NOTA-PRGD2 (3.09±0.21) (p>0.05). Little difference was found in volume of distribution (VT) among these three RGD tracers in tumor, liver and muscle. Parametric maps showed similar kinetic parameters for all three tracers. We also demonstrated that the impact of non-specific binding could be eliminated in the kinetic analysis. Consequently, kinetic parameter estimation showed more comparable results among groups than static image analysis. In conclusion, [18F]AlF-NOTA-PRGD2 and [68Ga]Ga-NOTA-PRGD2 have comparable pharmacokinetics and quantitative parameters compared to those of [18F]FPPRGD2. Despite the apparent difference in tumor uptake (%ID/g determined from static images) and clearance pattern, the actual specific binding component extrapolated from kinetic modeling appears to be comparable for all three dimeric RGD tracers