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Broadband hyperspectral imaging across visible and infrared biological windows using a single camera
Metalenses are ultrathin optical devices designed to replicate behavior of conventional refractive lenses, or lens arrays, utilizing nanoscale resonant structures to redirect incident light. These are often comprised of discrete meta-atoms such as nanoscale dielectric pillars. Achromatic focusing—associated with traditional multi-element refractive counterparts—is frequently attempted with single-layer metalens designs, which has proven difficult to achieve with bounded refractive indices and total lens thickness. A recent study (F.Presutti and F.Monticone, 2020) formalized this, applying optical delay-line limitations to metalenses, resulting in a generalized trade-off in achromaticity for focusing systems.
In this work, we (1) theoretically explore achromaticity in metalens design, and (2) propose a thin-film multilayer design as an alternative to the discrete meta-atom approach for large numerical aperture (NA) achromatic metalenses. It is shown that wavefront modulation can also be achieved with spectrally-varying transmission magnitudes, rather than purely matching a phase profile. In fact, even with a bounded refractive index, perfect achromatic operation over a given spectral range can be offset by imperfect operation elsewhere, resulting in a NA limited by the smallest general spectral feature controlled. These considerations lead to a generalized phase-matching optimization routine, and a thin-film metalens is simulated, utilizing layered TiO2/MgF2 with total thicknesses ≤1 μm (≤20 layers), focusing across 6 simultaneous wavelengths (350-740 nm, Δλ~65 nm). A significant proportion (>40% spectral average) of the reflected light is focused for moderate NA (~0.35). With the maturity of the optical coating industry, the conformal thin-film approach reduces manufacturing complexity from its discrete nanoscale meta-atom equivalents.
The erratum corrects an error in the article “Development of a blood oxygenation phantom for photoacoustic tomography combined with online pO2 detection and flow spectrometry.”
Phase and polarization of coherent light are highly perturbed by interaction with microstructural changes in premalignant tissue, holding promise for label-free detection of early tumors in endoscopically accessible tissues such as the gastrointestinal tract. Flexible optical multicore fiber (MCF) bundles used in conventional diagnostic endoscopy and endomicroscopy scramble phase and polarization, restricting clinicians instead to low-contrast amplitude-only imaging. We apply a transmission matrix characterization approach to produce full-field
Photoacoustic tomography (PAT) is intrinsically sensitive to blood oxygen saturation (sO2)
Wide-field phase imaging for the endoscopic detection of dysplasia and early-stage esophageal cancer
We performed MSOT on nude mice (n=8) bearing subcutaneous xenograft PC3 tumors using an inVision 256 (iThera Medical). The mice were maintained under inhalation anesthesia during imaging and respired oxygen content was modified from 21% to 100% and back. After imaging, Hoechst 33348 was injected to indicate vascular perfusion and permeability. Tumors were then extracted for histopathological analysis and fluorescence microscopy. The acquired data was analyzed to extract a bulk measurement of blood oxygenation (SO2MSOT) from the whole tumor using different approaches. The tumors were also automatically segmented into 5 regions to investigate the effect of depth on SO2MSOT.
Baseline SO2MSOT values at 21% and 100% oxygen breathing showed no relationship with ex vivo measures of vascular density or function, while the change in SO2MSOT showed a strong negative correlation to Hoechst intensity (r=- 0.92, p=0.0016). Tumor voxels responding to oxygen challenge were spatially heterogeneous. We observed a significant drop in SO2 MSOT value with tumor depth following a switch of respiratory gas from air to oxygen (0.323±0.017 vs. 0.11±0.05, p=0.009 between 0 and 1.5mm depth), but no such effect for air breathing (0.265±0.013 vs. 0.19±0.04, p=0.14 between 0 and 1.5mm depth).
Our results indicate that in subcutaneous prostate tumors, baseline SO2MSOT levels do not correlate to tumor vascular density or function while the magnitude of the response to oxygen challenge provides insight into these parameters. Future work will include validation using in vivo imaging and protocol optimization for clinical application.
To establish the relationship between MSOT derived imaging biomarkers and biological changes during tumor development, we performed MSOT on nude mice (n=10) bearing subcutaneous xenograft U87 glioblastoma tumors using a small animal optoacoustic tomography system. The mice were maintained under inhalation anesthesia during imaging and respired oxygen content was modified between 21% and 100%. The measurements from early (week 4) and late (week 7) stages of tumor development were compared. To further explore the functionality of the blood vessels, we examined the evolution of changes in the abundance of oxy- and deoxyhemoglobin in the tumors in response to a gas challenge. We found that the kinetics of the change in oxygen saturation (SO2) were significantly different between small tumors and the healthy blood vessels in nearby normal tissue (p=0.0054). Furthermore, we showed that there was a significant difference in the kinetics of the gas challenge between small and large tumors (p=0.0015). We also found that the tumor SO2 was significantly correlated (p=0.0057) with the tumor necrotic fraction as assessed by H&E staining in histology. In the future, this approach may be of use in the clinic as a method for tumor staging and assessment of treatment response.
A biomarker is a “defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention”. New sensing technologies seek to measure biomarkers, usually with the goal of improving patient management, however, there remains a widespread misunderstanding over how biomarkers can be used in the context of biomedical imaging.
This course covers the basics of imaging biomarkers from the perspective of biomedical optics. The course will underscore the importance of accurately defining and validating imaging biomarkers, drawing on examples from standard radiological imaging modalities as well as emerging optical modalities. Using several interactive activities, attendees will see examples of: how imaging biomarkers are currently used in clinical practice; the pitfalls often encountered when introducing new biomarkers; and where novel optical imaging biomarkers have the potential to impact future patient care.
Our community generates a vast amount of biomedical imaging data, ranging from super-resolution microscopy images on the nanometre scale, to diffuse optical tomography images on the millimetre scale. These data are increasingly complex, requiring quantitative analysis to extract imaging biomarkers, rather than simply visual interpretation. This course explains basic principles and applications of analysis techniques for biomedical imaging data, using several hands-on practical examples based on Fiji (ImageJ). <p> </p>
We will begin by examining the general principles of evaluating image quality and information content, by introducing important concepts such as contrast and modulation transfer. We will then consider how to process images containing noise or artifacts, for example, with the application of simple filters. Finally, we will discuss how best to identify appropriate regions of interest and measure a range of parameters from these that allow us to perform quantitative image analysis, considering precision and accuracy of our data. Anyone who wants to better understand their imaging data and develop skills in applying image processing software will benefit from taking this course.
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