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At least 235 records · Page 13

Far-field speckle correlations as a function of object position for microscopically distinguishing objects hidden in a randomly scattering medium

Super-resolution optical sensing is of critical importance in science and technology and has required prior information about an imaging system or obtrusive near-field probing. Additionally, coherent imaging and sensing in heavily scattering media such as biological tissue has been challenging, and practical approaches have either been restricted to measuring the field transmission of a single point source, or to where the medium is thin. We present the concept of far-subwavelength spatial sensing with relative object motion in speckle as a means to coherently sense through heavy scatter. Experimental results demonstrate the ability to distinguish nominally identical objects with nanometer-scale translation while hidden in randomly scattering media, without the need for precise or known location and with imprecise replacement. The theory and supportive illustrations presented provide the basis for super-resolution sensing and the possibility of virtually unlimited spatial resolution, including through thick, heavily scattering media with relative motion of an object in a structured field. This work provides enabling opportunities for material inspection, security, and biological sensing.

Hastings, Ryan L. (ORCID:0009000095977807)↗

Accurate in vivo tumor detection using plasmonic-enhanced shifted-excitation Raman difference spectroscopy (SERDS)

For the majority of cancer patients, surgery is the primary method of treatment. In these cases, accurately removing the entire tumor without harming surrounding tissue is critical; however, due to the lack of intraoperative imaging techniques, surgeons rely on visual and physical inspection to identify tumors. Surface-enhanced Raman scattering (SERS) is emerging as a non-invasive optical alternative for intraoperative tumor identification, with high accuracy and stability. However, Raman detection requires dark rooms to work, which is not consistent with surgical settings. Methods: Herein, we used SERS nanoprobes combined with shifted-excitation Raman difference spectroscopy (SERDS) detection, to accurately detect tumors in xenograft murine model. Results: We demonstrate for the first time the use of SERDS for in vivo tumor detection in a murine model under ambient light conditions. We compare traditional Raman detection with SERDS, showing that our method can improve sensitivity and accuracy for this task. Conclusion: Our results show that this method can be used to improve the accuracy and robustness of in vivo Raman/SERS biomedical application, aiding the process of clinical translation of these technologies.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Regional changes in muscle mass following 17 weeks of bed rest

This work reports on the muscle loss and recovery after 17 wk of continuous bed rest and 8 wk of reambulation in eight normal male volunteers. Muscle changes were assessed by urinary levels of 3-methylhistidine (3-MeH), nitrogen balance, dual-photon absorptiometry (DPA), magnetic resonance imaging (MRI), and isokinetic muscle performance. The total body lean tissue loss during bed rest calculated from nitrogen balance was 3.9 +/- 2.1 kg. Although the total loss is minimal, DPA scans showed that nearly all of the lean tissue loss occurred in the lower limbs. Similarly, MRI muscle volume measurements showed greater percent loss in the limbs relative to the back muscles. MRI, DPA, and nitrogen balance suggest that muscle atrophy continued throughout bed rest with rapid recovery after reambulaton. Isokinetic muscle strength decreased significantly in the thigh and calf with no loss in the arms and with rapid recovery during reambulation.

Leblanc, Adrian D.↗

Extracellular vesicles of calcifying turkey leg tendon characterized by immunocytochemistry and high voltage electron microscopic tomography and 3-D graphic image reconstruction

To gain insight into the structure and possible function of extracellular vesicles in certain calcifying vertebrate tissues, normally mineralizing leg tendons from the domestic turkey, Meleagris gallopavo, have been studied in two separate investigations, one concerning the electron microscopic immunolocalization of the 66 kDa phosphoprotein, osteopontin, and the other detailing the organization and distribution of mineral crystals associated with the vesicles as determined by high voltage microscopic tomography and 3-D graphic image reconstruction. Immunolabeling shows that osteopontin is related to extracellular vesicles of the tendon in the sense that its initial presence appears coincident with the development of mineral associated with the vesicle loci. By high voltage electron microscopy and 3-D imaging techniques, mineral crystals are found to consist of small irregularly shaped particles somewhat randomly oriented throughout individual vesicles sites. Their appearance is different from that found for the mineral observed within calcifying tendon collagen, and their 3-D disposition is not regularly ordered. Possible spatial and temporal relationships of vesicles, osteopontin, mineral, and collagen are being examined further by these approaches.

NASA Discipline Musculoskeletal↗

Trabecular Bone Mechanical Properties and Fractal Dimension

Countermeasures for reducing bone loss and muscle atrophy due to extended exposure to the microgravity environment of space are continuing to be developed and improved. An important component of this effort is finite element modeling of the lower extremity and spinal column. These models will permit analysis and evaluation specific to each individual and thereby provide more efficient and effective exercise protocols. Inflight countermeasures and post-flight rehabilitation can then be customized and targeted on a case-by-case basis. Recent Summer Faculty Fellowship participants have focused upon finite element mesh generation, muscle force estimation, and fractal calculations of trabecular bone microstructure. Methods have been developed for generating the three-dimensional geometry of the femur from serial section magnetic resonance images (MRI). The use of MRI as an imaging modality avoids excessive exposure to radiation associated with X-ray based methods. These images can also detect trabecular bone microstructure and architecture. The goal of the current research is to determine the degree to which the fractal dimension of trabecular architecture can be used to predict the mechanical properties of trabecular bone tissue. The elastic modulus and the ultimate strength (or strain) can then be estimated from non-invasive, non-radiating imaging and incorporated into the finite element models to more accurately represent the bone tissue of each individual of interest. Trabecular bone specimens from the proximal tibia are being studied in this first phase of the work. Detailed protocols and procedures have been developed for carrying test specimens through all of the steps of a multi-faceted test program. The test program begins with MRI and X-ray imaging of the whole bones before excising a smaller workpiece from the proximal tibia region. High resolution MRI scans are then made and the piece further cut into slabs (roughly 1 cm thick). The slabs are X-rayed again and also scanned using dual-energy X-ray absorptiometry (DEXA). Cube specimens are then cut from the slabs and tested mechanically in compression. Correlations between mechanical properties and fractal dimension will then be examined to assess and quantify the predictive capability of the fractal calculations.

Hogan, Harry A.↗

Scalable method for micro-CT analysis enables large scale quantitative characterization of brain lesions and implants

Anatomic evaluation is an important aspect of many studies in neuroscience; however, it often lacks information about the three-dimensional structure of the brain. Micro-CT imaging provides an excellent, nondestructive, method for the evaluation of brain structure, but current applications to neurophysiological or lesion studies require removal of the skull as well as hazardous chemicals, dehydration, or embedding, limiting their scalability and utility. Here we present a protocol using eosin in combination with bone decalcification to enhance contrast in the tissue and then employ monochromatic and propagation phase-contrast micro-CT imaging to enable the imaging of brain structure with the preservation of the surrounding skull. Instead of relying on descriptive, time-consuming, or subjective methods, we develop simple quantitative analyses to map the locations of recording electrodes and to characterize the presence and extent of hippocampal brain lesions.

3-D reconstruction↗

Single-Objective Airy Light-Sheet Imaging

Despite its massive potential, standard light-sheet imaging (LSI) faces key challenges, such as the incompatibility with common sample mounting techniques and low-resolution imaging. Single-objective LSI attempts to address these issues but often suffers from limited fields-of-view and throughput rates, or requires multiple optics that increase costs, alignment complexity, and losses. To overcome these challenges of standard single-objective LSI, we introduce single-objective Airy light-sheet imaging (SoALSI). SoALSI leverages the extraordinary self-acceleration properties of the Airy beam, achieving 5× higher imaging rates and enhanced imaging efficiency than standard single-objective LSI. Here, we demonstrate SoALSI’s versatility through rigorous contrast and resolution characterizations and by high-resolution imaging of diverse biological specimens, including malaria parasite-infected red blood cells and plant root tissue. SoALSI seamlessly integrates with any standard inverted microscope frame, enabling broader accessibility for the bioimaging community to explore biological processes in a wide range of specimens with enhanced resolution and imaging contrast.

airy beam↗

Particle classification by image analysis improves understanding of corn stover degradation mechanisms during deconstruction

Biomass feedstock heterogeneity is a principal roadblock to implementation of the biorefinery concept. Even within an identical cultivar of corn stover, different bales contain not only varying abundance moisture, ash, glucan, and other chemical compounds, but also varying abundance of tissue anatomies (e.g., leaf, husk, cob, or stalk). These different anatomical components not only differ in their response to pretreatment and enzymatic hydrolysis to glucose, but also vary in their mechanical and conveyance properties. Although this heterogeneous nature of corn stover feedstock has been identified as a challenge, a fundamental knowledge gap of how these tissues behave during biorefining processing remains. Here, we demonstrate the use of a commercial fiber image analyzer typically used for wood fiber characterization to monitor the particle size and shapes of non-woody feedstock during milling, pretreatment, and hydrolysis. Additionally, we present novel use of Gaussian process classification to distinguish bundle, parenchyma, and fiber particles to an accuracy of 96.4%. Quantitative probability distribution plots for characteristics such as length and roundness allow elucidation of particle morphology as pretreatment and enzymatic hydrolysis progress. In both stalk pith and stalk rind, particles peel into individual cells whose walls are subsequently fragmented during enzymatic hydrolysis.

09 BIOMASS FUELS↗

Imaging and speciation of intracellular metallic implant debris using synchrotron-based X-ray fluorescence micro-spectroscopy: a study of two cases

Debris generated from total hip arthroplasty (THA) components made from metal alloys can cause, in some cases, inflammatory cell (e.g., macrophages) responses that lead to adverse local tissue reactions (ALTR) and implant failure. The lack of information on intracellular chemical alterations of metal debris has hindered the understanding of the pathogenesis of ALTR. The goal of this study was to characterize intracellular debris within macrophages using Synchrotron imaging and spectroscopy. We studied periprosthetic tissues of two retrieved THAs with (1) a metal-on-metal (MoM) articulation and (2) a metal-on-polyethylene (MoP) articulation exhibiting corrosion of the metal femoral head. The MoM-THA exhibited different valence states of chromium- and cobalt-containing debris, suggesting three different moieties: Cr 2 O 3 , CrPO 4 , and an alloy-oxide mixture. The findings further suggest that Cr 2 O 3 formed in the tribological interfaces of the implant, while CrPO 4 is a by-product of the phagocytosis process of cobalt alloy-containing debris. Titanium debris appeared to occur in a mixed crystalline/amorphous oxide state. It remains unclear if this chemical state results from the tribochemical processes at the implant surface or intracellular alterations. The MoP-THA specimen exhibited no intracellular particulate debris associated with macrohpages, indicating that the ALTR may be entirely triggered by metal ionic species in this case. A better understanding of in vivo chemical alteration of implant debris will aid in assessing the risk for ALTR during implant design and material choice. However, various techniques are needed to accurately determine the interaction between metal particles and the inta- and extra-cellular environment.

60 APPLIED LIFE SCIENCES↗

Compositions for therapeutics, targeted PET imaging and methods of their use

Described herein is a chelator for radiolabels (e.g., 89Zr) for targeted PET imaging that is an alternative to DFO. In certain embodiments, the chelator for 89Zr is the ligand, 3,4,3-(LI-1,2-HOPO) (“HOPO”), which exhibits equal or superior stability compared to DFO in chemical and biological assays across a period of several days in vivo. As shown in FIG. 1, the HOPO is an octadentate chelator that stabilizes chelation of radiolabels (e.g., 89Zr). A bifunctional ligand comprising p-SCN-Bn-HOPO is shown in FIG. 4 and FIG. 5. Such a bifunctional ligand can eliminate (e.g., 89Zr) loss from the chelate in vivo and reduce uptake in bone and non-target tissue. Therefore, the bifunctional HOPO ligand can facilitate safer and improved PET imaging with radiolabeled antibodies.

Lewis, Jason S.↗

Use of X-Ray Fluorescence Microscopy for Studies on Research Models of Hepatocellular Carcinoma

Introduction: TheraSphere ® microspheres containing yttrium 90 Y are among many radioembolization agents used clinically to reduce liver tumor burden, and their effects on cancer volume reduction are well-established. At the same time, concerns about off target tissue injury often limit their use. Deeper investigation into tissue distribution and long-term impact of these microspheres could inform us about additional ways to use them in practice. Methods: Healthy rat liver and rabbit liver tumor samples from animals treated with TheraSpheres were sectioned and their elemental maps were generated by X-ray fluorescence microscopy (XFM) at the Advanced Photon Source (APS) synchrotron at Argonne National Laboratory (ANL). Results: Elemental imaging allowed us to identify the presence and distribution of TheraSpheres in animal tissues without the need for additional sample manipulation or staining. Ionizing radiation produced by 90 Y radioactive contaminants present in these microspheres makes processing TheraSphere treated samples complex. Accumulation of microspheres in macrophages was observed. Conclusions: This is the first study that used XFM to evaluate the location of microspheres and radionuclides in animal liver and tumor samples introduced through radioembolization. XFM has shown promise in expanding our understanding of radioembolization and could be used for investigation of human patient samples in the future.

60 APPLIED LIFE SCIENCES↗

Modeling of polychromatic attenuation using computed tomography reconstructed images

This paper presents a procedure for estimating an accurate model of the CT imaging process including spectral effects. As raw projection data are typically unavailable to the end-user, we adopt a post-processing approach that utilizes the reconstructed images themselves. This approach includes errors from x-ray scatter and the nonidealities of the built-in soft tissue correction into the beam characteristics, which is crucial to beam hardening correction algorithms that are designed to be applied directly to CT reconstructed images. We formulate this approach as a quadratic programming problem and propose two different methods, dimension reduction and regularization, to overcome ill conditioning in the model. For the regularization method we use a statistical procedure, Cross Validation, to select the regularization parameter. We have constructed step-wedge phantoms to estimate the effective beam spectrum of a GE CT-I scanner. Using the derived spectrum, we computed the attenuation ratios for the wedge phantoms and found that the worst case modeling error is less than 3% of the corresponding attenuation ratio. We have also built two test (hybrid) phantoms to evaluate the effective spectrum. Based on these test phantoms, we have shown that the effective beam spectrum provides an accurate model for the CT imaging process. Last, we used a simple beam hardening correction experiment to demonstrate the effectiveness of the estimated beam profile for removing beam hardening artifacts. We hope that this estimation procedure will encourage more independent research on beam hardening corrections and will lead to the development of application-specific beam hardening correction algorithms.

NASA Discipline Musculoskeletal↗

The development and use of metal-based probes for X-ray fluorescence microscopy

Abstract X-ray fluorescence microscopy (XFM) has become a widely used technique for imaging the concentration and distribution of metal ions in cells and tissues. Recent advances in synchrotron sources, optics, and detectors have improved the spatial resolution of the technique to <10 nm with attogram detection sensitivity. However, to make XFM most beneficial for bioimaging—especially at the nanoscale—the metal ion distribution must be visualized within the subcellular context of the cell. Over the years, a number of approaches have been taken to develop X-ray-sensitive tags that permit the visualization of specific organelles or proteins using XFM. In this review, we examine the types of X-ray fluorophore used, including nanomaterials and metal ions, and the approaches used to incorporate the metal into their target binding site via antibodies, genetically encoded metal-binding peptides, affinity labeling, or cell-specific peptides. We evaluate their advantages and disadvantages, review the scientific findings, and discuss the needs for future development.

36 MATERIALS SCIENCE↗

Learning fuzzy information in a hybrid connectionist, symbolic model

An instance-based learning system is presented. SC-net is a fuzzy hybrid connectionist, symbolic learning system. It remembers some examples and makes groups of examples into exemplars. All real-valued attributes are represented as fuzzy sets. The network representation and learning method is described. To illustrate this approach to learning in fuzzy domains, an example of segmenting magnetic resonance images of the brain is discussed. Clearly, the boundaries between human tissues are ill-defined or fuzzy. Example fuzzy rules for recognition are generated. Segmentations are presented that provide results that radiologists find useful.

Romaniuk, Steve G.↗

Digital Mammography with a Mosaic of CCD-Arrays

The present invention relates generally to a mammography device and method and more particularly to a novel digital mammography device and method to detect microcalcifications of precancerous tissue. A digital mammography device uses a mosaic of electronic digital imaging arrays to scan an x-ray image. The mosaic of arrays is repositioned several times to expose different portions of the image, until the entire image is scanned. The data generated by the arrays during each exposure is stored in a computer. After the final exposure, the computer combines data of the several partial images to produce a composite of the original x-ray image. An aperture plate is used to reduce scatter and the overall exposure of the patient to x-rays. The novelty of this invention is that it provides a digital mammography device with large field coverage, high spatial resolution, scatter rejection, excellent contrast characteristics and lesion detectability under clinical conditions. This device also shields the patient from excessive radiation, can detect extremely small calcifications and allows manipulation and storage of the image.

Jalink, Antony, Jr.↗

Biomedical Investigations with Laser-Polarized Noble Gas Magnetic Resonance

We are developing laser-polarized noble gas nuclear magnetic resonance (NMR) as a novel biomedical imaging tool for ground-based and eventually space-based application. This emerging multidisciplinary technology enables high-resolution gas-space magnetic resonance imaging (MRI) (e.g., of lung ventilation) as well as studies of tissue perfusion. In addition, laser-polarized noble gases (He-3 and Xe-129) do not require a large magnetic field for sensitive detection, opening the door to practical MRI at very low magnetic fields with an open, lightweight, and low-power device. We are pursuing two specific aims in this research. The first aim is to develop a low-field (< 0.01 T) instrument for noble gas MRI of humans, and the second aim is to develop functional MRI of the lung using laser-polarized Xe-129 and related techniques.

Walsworth, Ronald L.↗

Current Status of Radiopharmaceutical Therapy

In radiopharmaceutical therapy (RPT), a radionuclide is systemically or locally delivered with the goal of targeting and delivering radiation to cancer cells while minimizing radiation exposure to untargeted cells. Examples of current RPTs include thyroid ablation with the administration of {sup 131}I, treatment of liver cancer with {sup 90}Y microspheres, the treatment of bony metastases with {sup 223}Ra, and the treatment of neuroendocrine tumors with {sup 177}Lu-DOTATATE. New RPTs are being developed where radionuclides are incorporated into systemic targeted therapies. To assure that RPT is appropriately implemented, advances in targeting need to be matched with advances in quantitative imaging and dosimetry methods. Currently, radiopharmaceutical therapy is administered by intravenous or locoregional injection, and the treatment planning has typically been implemented like chemotherapy, where the activity administered is either fixed or based on a patient’s body weight or body surface area. RPT pharmacokinetics are measurable by quantitative imaging and are known to vary across patients, both in tumors and normal tissues. Therefore, fixed or weight-based activity prescriptions are not currently optimized to deliver a cytotoxic dose to targets while remaining within the tolerance dose of organs at risk. Methods that provide dose estimates to individual patients rather than to reference geometries are needed to assess and adjust the injected RPT dose. Accurate doses to targets and organs at risk will benefit the individual patients and decrease uncertainties in clinical trials. Imaging can be used to measure activity distribution in vivo, and this information can be used to determine patient-specific treatment plans where the dose to the targets and organs at risk can be calculated. The development and adoption of imaging-based dosimetry methods is particularly beneficial in early clinical trials. In this work we discuss dosimetric accuracy needs in modern radiation oncology, uncertainties in the dosimetry in RPT, and best approaches for imaging and dosimetry of internal radionuclide therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue

Myelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelin’s nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the method’s sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures.

36 MATERIALS SCIENCE↗