Synchrotron Radiation Refraction-Contrast Computed Tomography Based on X-ray Dark-Field Imaging Optics of Pulmonary Malignancy: Comparison with Pathologic Examination.

Refraction-contrast computed tomography based on X-ray dark-field imaging (XDFI) using synchrotron radiation (SR) has shown superior resolution compared to conventional absorption-based methods and is often comparable to pathologic examination under light microscopy. This study aimed to investigate the potential of the XDFI technique for clinical application in lung cancer diagnosis. Two types of lung specimens, primary and secondary malignancies, were investigated using an XDFI optic system at beamline BL14B of the High-Energy Accelerator Research Organization Photon Factory, Tsukuba, Japan. Three-dimensional reconstruction and segmentation were performed on each specimen. Refraction-contrast computed tomographic images were compared with those obtained from pathological examinations. Pulmonary microstructures including arterioles, venules, bronchioles, alveolar sacs, and interalveolar septa were identified in SR images. Malignant lesions could be distinguished from the borders of normal structures. The lepidic pattern was defined as the invasive component of the same primary lung adenocarcinoma. The SR images of secondary lung adenocarcinomas of colorectal origin were distinct from those of primary lung adenocarcinomas. Refraction-contrast images based on XDFI optics of lung tissues correlated well with those of pathological examinations under light microscopy. This imaging method may have the potential for use in lung cancer diagnosis without tissue damage. Considerable equipment modifications are crucial before implementing them from the lab to the hospital in the near future.

Effects of gold nanoparticles on normal hepatocytes in radiation therapy.

Background: Gold nanoparticles (GNP, AuNPs) have received much attention as a tool to improve the therapeutic index of radiation therapy. This study aimed to evaluate the normal in vitro toxicity of AuNPs at kilovoltage energies on hepatocytes to provide scientific support for using AuNPs with radiotherapy. Methods: Using the same treatment protocol applied to tumor cell lines, hepatocytes were exposed to AuNPs and/or radiation at various time points. Results: The combination of X-ray irradiation and AuNPs did not have any significant effect on cell survival and apoptosis in normal hepatocytes. Furthermore, the combination treatment resulted in no or little change in the level of gamma-H2A histone family member X (γ-H2AX), a marker for DNA double-strand breaks (DSB), nor on the proportion of cells in the G2/M phase. Additionally, interleukin-8 (IL-8) secretion was measured using an enzyme-linked immunosorbent assay (ELISA) to assess its role in tumor progression and angiogenesis. The combination of irradiation and AuNP treatment revealed no significant reduction in hepatocyte viability, proliferation, or secretory capacity compared to cells receiving either treatment alone. According to this study, AuNPs in combination with radiation do have potentially in the treatment of hepatocellular carcinoma (HCC) with no critical cytotoxicity on normal tissue. Conclusions: Therefore, it is postulated that radiation and AuNPs are an effective combination therapy against HCC with no little cytotoxic effects on normal tissue, a hypothesis which warrants further investigation in in vivo, as well as in in vitro.

Assessing the Impact of a PrEP Aware Week Campaign on PrEP Prescription Fills in NYS.

CONTEXT: The New York State (NYS) Department of Health AIDS Institute engaged stakeholders across NYS to participate in the state's first "PrEP Aware Week" (PAW). PAW sought to increase the knowledge, interest, and number of PrEP (pre-exposure prophylaxis) prescriptions filled across NYS. PAW activities were designed to be easy to implement, with minimal cost. Stakeholders were provided activities to implement, along with a social media tool kit featuring videos, graphic ads, and sample social media posts in English and Spanish to use as is or modify. PAW included more than 750 distinct events and activities undertaken by more than 250 participating providers. OBJECTIVE: To assess the impact of PAW on PrEP prescription filling patterns in NYS. DESIGN: An interrupted time-series analysis was conducted to estimate the impact of PAW on overall and new PrEP prescription filling patterns. Separate models were developed by sex (male, female), race and ethnicity (White non-Hispanic, Black non-Hispanic, Hispanic, other, unknown), and region (New York City, rest of NYS). SETTING: PAW took place across NYS during the week beginning October 20, 2019. PARTICIPANTS: PAW was undertaken by more than 250 health care providers, nonmedical health & human services providers, local and state health department staff, and colleges and universities. MAIN OUTCOME MEASURES: The number of overall and new PrEP prescriptions. RESULTS: PAW was associated with modest increases (6%-9%) in the number of PrEP prescription fills in NYS. The PAW impact lasted for about 2 months, generated an estimated 2727 additional PrEP prescription fills statewide, and was realized across sex, region, and racial and ethnic subgroups. Increased prescription fills were driven by those previously prescribed PrEP. Increases in new prescriptions were noted among Latinx individuals (21% increase, 55 additional prescriptions) but not overall or across other groups. CONCLUSION: NYS's PAW was effective at increasing PrEP prescription refills in NYS.

Enhanced proton treatment with a LDLR-ligand peptide-conjugated gold nanoparticles targeting the tumor microenvironment in an infiltrative brain tumor model.

The tumor microenvironment (TME) of glioblastoma malforms (GBMs) contains tumor invasiveness factors, microvascular proliferation, migratory cancer stem cells and infiltrative tumor cells, which leads to tumor recurrence in the absence of effective drug delivery in a Blood Brain Barrier (BBB)-intact TME and radiological invisibility. Low-density lipoprotein receptor (LDLR) is abundant in the blood brain barrier and overexpressed in malignant glioma cells. This study aimed to treat the TME with transmitted proton sensitization of LDLR ligand-functionalized gold nanoparticles (ApoB@AuNPs) in an infiltrative F98 glioma rat model. BBB-crossing ApoB@AuNPs were selectively taken up in microvascular endothelial cells proliferation and pericyte invasion, which are therapeutic targets in the glioma TME. Proton sensitization treated the TME and bulk tumor volume with enhanced therapeutic efficacy by 67-75% compared to that with protons alone. Immunohistochemistry demonstrated efficient treatment of endothelial cell proliferation and migratory tumor cells of invasive microvessels in the TME with saving normal tissues. Taken together, these data indicate that the use of LDLR ligand-functionalized gold nanoparticles is a promising strategy to treat infiltrative malignant glioma while overcoming BBB crossing.

Tumor-treating fields as a proton beam-sensitizer for glioblastoma therapy.

Few advances in GBM treatment have been made since the initiation of the Stupp trials in 2005. Experimental studies on immunotherapy drugs, molecular inhibitors, radiation dosage escalation and vascular growth factor blockers have all failed to provide satisfactory outcomes. TTFields therapy, on the other hand, have emerged as a viable substitute to therapies like radiation in GBM patients having a highly immunosuppressive tumor microenvironment. To enhance the biofunctional impacts, we explored the combination events with TTFields and proton treatment in this study. We conducted a cell viability test, a cell death detection evaluation, a ROS analysis, a three-dimensional (3D) culture system, and a migration assay. The combination of proton radiation and TTFields therapy laid a substantial anticancer impact on the F98 and U373 as compared to the consequences of either of these therapies used separately. The combination proton beam therapy used by TTFields was very successful in curbing GBM from migrating. GBM cell metastasis is restricted by TTFields combined proton by downregulating the MAPK, NF-κB, and PI3K/AKT indicating pathways, caused by reduced EMT marker expression. These findings furnish biological proof for the molecular grounds of TTFields in combination with proton used for GBM therapy.

Proton Stimulation Targeting Plaque Magnetite Reduces Amyloid-ß Plaque and Iron Redox Toxicity and Improves Memory in an Alzheimer's Disease Mouse Model.

BACKGROUND: The coexistence of magnetite within protein aggregates in the brain is a typical pathologic feature of Alzheimer's disease (AD), and the formation of amyloid-ß (Aß) plaques induces critical impairment of cognitive function. OBJECTIVE: This study aimed to investigate the therapeutic effect of proton stimulation (PS) targeting plaque magnetite in the transgenic AD mouse brain. METHODS: A proton transmission beam was applied to the whole mouse brain at a single entrance dose of 2 or 4 Gy to test the effect of disruption of magnetite-containing Aß plaques by electron emission from magnetite. The reduction in Aß plaque burden and the cognitive function of the PS-treated mouse group were assayed by histochemical analysis and memory tests, respectively. Aß-magnetite and Aß fibrils were treated with PS to investigate the breakdown of the amyloid protein matrix. RESULTS: Single PS induced a 48-87%reduction in both the amyloid plaque burden and ferrous-containing magnetite level in the early-onset AD mouse brain while saving normal tissue. The overall Aß plaque burden (68-82%) and (94-97%) hippocampal magnetite levels were reduced in late onset AD mice that showed improvements in cognitive function after PS compared with untreated AD mice (p < 0.001). Analysis of amyloid fibrils after exposure to a single 2 or 4 Gy proton transmission beam demonstrated that the protein matrix was broken down only in magnetite-associated Aß fibrils. CONCLUSION: Single PS targeting plaque magnetite effectively decreases the amyloid plaque burden and the ferrous-containing magnetite level, and this effect is useful for memory recovery.

Improved bone regeneration using collagen-coated biphasic calcium phosphate with high porosity in a rabbit calvarial model.

Many growth factors have been paired with synthetic bone grafts to accelerate the healing process in vivo. Collagen has been particularly examined as a mediator of the enhancement of bone regeneration. This study investigated the new bone formation potential of micro-macroporous biphasic calcium phosphate (m-BCP), high porosity biphasic calcium phosphate (p-BCP), and collagen-coated p-BCP (cp-BCP) using a rabbit calvarial defect model. At 2 or 8 weeks after surgery, bone tissue was collected. The three-dimensional analysis of new bone formation using synchrotron radiation micro-computed tomography and histological study were conducted. The new bone formation values observed at 2 and 8 weeks in the negative control, m-BCP, p-BCP, and cp-BCP groups were 11.21 ± 1.36 mm3, 21.75 ± 1.18 mm3, 24.59 ± 1.26 mm3, and 29.54 ± 2.72 mm3, respectively, and 18.34 ± 3.99 mm3, 32.27 ± 3.78 mm3, 43.12 ± 1.61 mm3, and 58.20 ± 3.84 mm3, respectively. New bone formation was greatest in the cp-BCP group, while the amount of new bone at 8 weeks was higher than at 2 weeks in each group. The use of cp-BCP to enhance new bone formation during the healing period could improve bone regeneration.

In-situ analysis of the hydration ability of bone graft material using a synchrotron radiation X-ray micro-CT.

The conventional micro-computed tomography (µCT) is a non-destructive imaging technique used for obtaining 2D and 3D information for scaffolds. The main composition and internal structure are important in mimicking and designing the characteristics of natural bone. This study was three-dimensional evaluating the external or internal structures and the hydration effects of bone graft materials by using the in-situ image technique. Synchrotron radiation micro-computed tomography (SR-µCT) was used to extract information on the geometry of two biphasic calcium phosphates (BCP) with identical chemicals and different micro-macro porosity, pore size distribution, and pore interconnection pathways. Volume analysis by hydration was used to measure the two bone graft materials at 0, 5, and 10-min intervals. The SR-µCT image was achieved with information regarding the internal pore structure and hydration effects evaluated under 3D visualization. Both types of bone graft materials showed structures suitable for tissue engineering applications. The SR-µCT in-situ techniques with 3D information provided a detailed view of the structures. Thus, SR-µCT could be an available, unbiased 3D alternative to in-situ analysis.

Molecular mechanisms underlying the enhancement of carbon ion beam radiosensitivity of osteosarcoma cells by miR-29b.

Carbon ion radiotherapy (CIRT) is more effective than conventional photon beam radiotherapy in treating osteosarcoma (OSA); however, the outcomes of CIRT alone are still unsatisfactory. In this study, we aimed to investigate whether miR-29b acts as a radiosensitizer for CIRT. The OSA cell lines U2OS and KHOS were treated with carbon ion beam alone, γ-ray irradiation alone, or in combination with an miR-29b mimic. OSA cell death as well as invasive and migratory abilities were analyzed through viability, colony formation, Transwell, and apoptosis assays. miR-29 expression was downregulated in OSA tissues compared to that in normal tissues and was associated with metastasis and relapse in patients with OSA. Further, miR-29b was found to directly target the transcription factor Sp1 and suppress the activation of the phosphatase and tensin homolog (PTEN)-AKT pathway. Conversely, Sp1 was found to attenuate the inhibitory effects of miR-29b in OSA cells. When used in combination with miR-29b mimic, carbon ion beam markedly inhibited invasion, migration, and proliferation of OSA cells and promoted apoptosis by inhibiting AKT phosphorylation in a Sp1/PTEN-mediated manner. Taken together, miR-29b mimic improved the radiosensitivity of OSA cells via the PTEN-AKT-Sp1 signaling pathway, presenting a novel strategy for the development of carbon ion beam combination therapy.

Anti-Flt1 peptide and cyanine-conjugated gold nanoparticles for the concurrent antiangiogenic and endothelial cell proton treatment.

Anti-Flt1 peptide of GNQWFI binds to vascular endothelial growth factor receptor 1 (VEGFR1 or Flt1) and prevents binding of VEGF, inhibiting VEGFR1-mediated endothelial cell migration and tube formation. Bare gold nanoparticle (AuNP) was known to have anti-angiogenic properties by specific binding with VEGF. In this study, anti-Flt1 peptide (GGNQWFI) and cyanine were chemically conjugated to AuNPs (Flt1@AuNP-cyanine 5.5 or Flt1@AuNP-hydrocyanine 5.5 [HCy5.5]) to enhance antiangiogenic properties with targeting to VEGFR-1 as well as producing Coulomb nanoradiator therapeutic effect on the retinal endothelial cells. Anti-Flt1 AuNP complex showed binding with VEGFR-1 and showed more protein-induced fluorescence enhancement (PIFE) by various VEGFs compared with bare AuNPs, suggesting enhanced antiangiogenic properties compared to bare AuNP. Nonfluorescent Flt1@AuNP-HCy5.5 successfully reacted with reactive oxygen species (ROS) produced from Fenton reactions or a proton-induced Coulomb nanoradiator, enabling quenching-free oxidant fluorescence ROS imaging in HRMECs under oxidative stress. Flt1@AuNP-HCy5.5 alone induced 50% greater cytotoxicity for HRMECs compared to bare AuNPs and 80% greater cell death by the Au-nanoradiator effect. In conclusion, this study describes a new therapeutic anti-Flt1 gold nanocomplex with enhanced antiangiogenic properties and nanoradiator-mediated cytotoxicity on retinal endothelial cells. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1272-1283, 2019.

Photofunctionalizing effects of hydroxyapatite combined with TiO2 on bone regeneration in rabbit calvarial defects.

The hydrophilicity of bone graft material generally used as a carrier can play an important role in regulating bone morphogenetic protein (BMP) expression at the bone graft site. The hydrophilicity, altering physicochemical properties, and enhancing biological capabilities, can be increased via surface modification through ultraviolet (UV) photofunctionalization and the effect on de novo osteogenesis could be further improved. Therefore, this study aimed to assess the effects of UV-irradiated TiO2 -coated hydroxyapatite (HA) in combination with rhBMP-2 on bone regeneration in rabbit calvarial defects. The hydrophilicity of HA and TiO2 -coated HA pellets was evaluated by measuring the contact angle of water droplets with UV irradiation. To compare de novo osteogenesis in rabbit calvarial defects, the rabbits were segregated into four different groups: negative control, HA, TiO2 -coated HA, and TiO2 -coated HA with UV; histomorphometric analysis and micro-computed tomography (µCT) imaging were performed after 4 and 8 weeks. In vivo analysis revealed that de novo osteogenesis occurred on the critical size defects in all groups and was significantly increased in the TiO2 -coated HA with UV group than in other groups (p < 0.05). The present results indicate that UV photofunctionalization promotes de novo osteogenesis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1953-1959, 2019.

High-Throughput Analysis of New Bone Formation and Bone Substitutes After Maxillary Sinus Floor Elevation Using Synchrotron Radiation Micro-Computed Tomography.

This study addresses the usability of synchrotron radiation micro-computed tomography (SR-µCT) for the high-throughput examination of bone biopsy specimens harvested from maxillary sinus floor elevation (MSFE) patients. The experimental procedure devised for efficient data acquisition and volume analysis of bone biopsy specimens of sinus lift using SR-µCT is presented. The measuring was done in approximately one minute per field of view; 3D image visualization and volume analysis could be performed in one hour. Six months after the sinus floor augmentation procedure, bone biopsy specimens were collected. Six specimens were studied. The percentages of bone measured by 3D volumetric analysis using SR-µCT and 2D area analysis using conventional histomorphometry were compared. A specimen was measured in any cross section, and the analysis was readily extended to the entire volume of the specimen. Significant differences between the 2D and the 3D measurement results were revealed. Based on our observations, we report structural inhomogeneity in the grafted volume of the MSFE site. The new bone volume assessed by SR-µCT correlates with the percentage of bone as assessed by conventional 2D histologic photomicrographs. SR-µCT is thus a reliable technique to determine the volume of newly formed bone at the MSFE.

Effects of Enhanced Hydrophilic Titanium Dioxide-Coated Hydroxyapatite on Bone Regeneration in Rabbit Calvarial Defects.

The regeneration of bone defects caused by periodontal disease or trauma is an important goal. Porous hydroxyapatite (HA) is an osteoconductive graft material. However, the hydrophobic properties of HA can be a disadvantage in the initial healing process. HA can be coated with TiO2 to improve its hydrophilicity, and ultraviolet irradiation (UV) can further increase the hydrophilicity by photofunctionalization. This study was designed to evaluate the effect of 5% TiO2-coated HA on rabbit calvarial defects and compare it with that of photofunctionalization on new bone in the early stage. The following four study groups were established, negative control, HA, TiO2-coated HA, and TiO2-coated HA with UV. The animals were sacrificed and the defects were assessed by radiography as well as histologic and histomorphometric analyses. At 2 and 8 weeks postoperatively, the TiO2-coated HA with UV group and TiO2-coated HA group showed significantly higher percentages of new bone than the control group (p < 0.05). UV irradiation increased the extent of new bone formation, and there was a significant difference between the TiO2-coated HA group and TiO2-coated HA with UV group. The combination of TiO2/HA and UV irradiation in bone regeneration appears to induce a favorable response.

Intravitreal implantable magnetic micropump for on-demand VEGFR-targeted drug delivery.

In this paper, we propose an intravitreal implantable magnetic micropump integrated with micro check valve capable of on-demand vascular endothelial growth factor receptor (VEGFR)-targeted drug delivery for the treatment of age-related macular degeneration, diabetic retinopathy and other eye pathologies characterized by ocular neoangiogenesis. Precise on-demand drug release is realized by the deflection of the magnetic membrane assembly according to the external magnetic field, and the membrane assembly consists of a thin elastic polydimethylsiloxane (PDMS) membrane and a cylindrical magnetic nanoparticle-PDMS composite block. Additionally, a micro check valve composed of two PDMS layers was integrated into the micropump to realize a diode-like one-directional drug delivery and prevent undesired drug diffusion. For specifically targeting VEGFR and suppression of VEGF-induced proliferation of microvascular endothelial cells, anti-Flt1 gold nanocomplexes are synthesized. In vitro and in vivo experiments and quantitative analysis are carried out in order to verify our proposed concept: precise drug release control according to the external magnetic field, targeting to microvascular endothelial cells, and efficient and on-demand drug delivery from the proposed micropump to the macular area of rabbit's eye.

Reactive oxygen species-based measurement of the dependence of the Coulomb nanoradiator effect on proton energy and atomic Z value.

PURPOSE: The Coulomb nanoradiator (CNR) effect produces the dose enhancement effects from high-Z nanoparticles under irradiation with a high-energy ion beam. To gain insight into the radiation dose and biological significance of the CNR effect, the enhancement of reactive oxygen species (ROS) production from iron oxide or gold NPs (IONs or AuNPs, respectively) in water was investigated using traversing proton beams. METHODS AND MATERIALS: The dependence of nanoradiator-enhanced ROS production on the atomic Z value and proton energy was investigated. Two biologically important ROS species were measured using fluorescent probes specific to •OH or [Formula: see text] in a series of water phantoms containing either AuNPs or IONs under irradiation with a 45- or 100-MeV proton beam. RESULTS: The enhanced generation of hydroxyl radicals (•OH) and superoxide anions ([Formula: see text]) was determined to be caused by the dependence on the NP concentration and proton energy. The proton-induced Au or iron oxide nanoradiators exhibited different ROS enhancement rates depending on the proton energy, suggesting that the CNR radiation varied. The curve of the superoxide anion production from the Au-nanoradiator showed strong non-linearity, unlike the linear behavior observed for hydroxyl radical production and the X-ray photoelectric nanoradiator. In addition, the 45-MeV proton-induced Au nanoradiator exhibited an ROS enhancement ratio of 8.54/1.50 ([Formula: see text] / •OH), similar to that of the 100-KeV X-ray photoelectric Au nanoradiator (7.68/1.46). CONCLUSIONS: The ROS-based detection of the CNR effect revealed its dependence on the proton beam energy, dose and atomic Z value and provided insight into the low-linear energy transfer (LET) CNR radiation, suggesting that these factors may influence the therapeutic efficacy via chemical reactivities, transport behaviors, and intracellular oxidative stress.

Synchrotron tomographic images from human lung adenocarcinoma: Three-dimensional reconstruction and histologic correlations.

High-resolution tomographic images using synchrotron X-rays are expected to provide detailed reflection of microstructures, thereby allowing for the examination of histologic structures without destruction of the specimen. This study aims to evaluate the synchrotron tomographic images of mixed ground-glass opacity excised on 5-mm sections in comparison to pathologic examination. The Institutional Review Board of our institute approved this retrospective study, and written informed consent was obtained from each patient whose lung tissue would be used. Obtained lung cancer specimens were brought to the multiple Wiggler 6C beam line at the Pohang Light Source (PLS-II) in Korea, and phase contrast X-ray images were obtained in November 2016. The X-ray emanated from a bending magnet of the electron storage ring with electron energy of 3 GeV, and a typical beam current was 320 mA. Reconstructed tomographic images were compared with images from histologic slides obtained from the same samples. Pulmonary microstructures including terminal bronchioles, alveolar sacs, and vasculature were identified with phase contrast X-ray images. Images from normal lung tissue and mixed ground-glass opacity were clearly distinguishable. Hyperplasia of the interalveolar septum and dysplasia of microstructure were clearly identified. The imaging findings correlated well with hematoxylin-eosin stained specimens. Tomographic images using synchrotron radiation have the potential for clinical applications. With refinement, this technique may become a diagnostic tool for detection of lung cancer.

Effects of Escherichia Coli-derived Recombinant Human Bone Morphogenetic Protein-2 Loaded Porous Hydroxyaptite-based Ceramics on Calvarial Defect in Rabbits.

BACKGROUND: Recombinant human bone morphogenetic proteins (rhBMPs) have been widely used in regenerative therapies to promote bone formation. The production of rhBMPs using bacterial systems such as Escherichia coli (E. coli) is estimated to facilitate clinical applications by lowering the cost without compromising biological activity. In clinical practice, rhBMP-2 and osteoconductive carriers (e.g., hydroxyapatite [HA] and bovine bone xenograft) are used together. This study examined the effect of E. coli-derived rhBMP-2 combined with porous HA-based ceramics on calvarial defect in rabbits. METHODS: Six adult male New Zealand white rabbits were used in this study. The experimental groups were divided into the following 4 groups: untreated (NC), bovine bone graft (BO), porous HA (HA) and porous HA with rhBMP-2 (HA-BMP). Four transosseous defects of 8 mm in diameter were prepared using stainless steel trephine bur in the frontal and parietal bones. Histological and histomorphometric analyses at 4 weeks after surgery revealed significant new bone formation by porous HA alone. RESULTS: HA-BMP showed significantly higher degree of bone formation compared with BO and HA group (P<0.05). The average new bone formation % (new bone area per total defect area) of NC, BO, HA, and HA-BMP at 4-week after surgery were 12.65±5.89%, 29.63±6.99%, 28.86±6.17% and 49.56±8.23%, respectively. However, there was no statistical difference in the bone formation between HA and BO groups. CONCLUSIONS: HA-BMP promoted more bone formation than NC, BO and HA alone. Thus, using E. coli-derived rhBMP-2 combined with porous HA-based ceramics can promote new bone formation.

Dark-Field Imaging: Recent developments and potential clinical applications.

This paper describes an X-ray phase contrast imaging technique using analyzer-based optics called X-ray Dark-Field Imaging that has been under development for the past 10years. We describe the theory behind XDFI, the X-ray optics required for implementing it in practice, and algorithms used for 2D, 2.5D, and 3D image reconstruction. The XDFI optical chain consists of an asymmetrically cut, Bragg-type monochromator-collimator that provides a planar monochromatic X-ray beam, a positioning stage for the specimens, a Laue-case angle analyzer, and one or two cameras to capture the dark and bright field images. We demonstrate the soft-tissue discrimination capabilities of XDFI by reconstructing images with absorption and phase contrast. By using a variety of specimens such as breast tissue with cancer, joints with articular cartilage, ex-vivo human eye specimen, and others, we show that refraction-based contrast derived from XDFI is more effective in characterizing anatomical features, articular pathology, and neoplastic disease than conventional absorption-based images. For example, XDFI of breast tissue can discriminate between the normal and diseased terminal duct lobular unit, and between invasive and in-situ cancer. The final section of this paper is devoted to potential future developments to enable clinical and histo-pathological applications of this technique.

Coulomb nanoradiator-mediated, site-specific thrombolytic proton treatment with a traversing pristine Bragg peak.

Traversing proton beam-irradiated, mid/high-Z nanoparticles produce site-specific enhancement of X-ray photon-electron emission via the Coulomb nanoradiator (CNR) effect, resulting in a nano- to micro-scale therapeutic effect at the nanoparticle-uptake target site. Here, we demonstrate the uptake of iron oxide nanoparticles (IONs) and nanoradiator-mediated, site-specific thrombolysis without damaging the vascular endothelium in an arterial thrombosis mouse model. The enhancement of low-energy electron (LEE) emission and reactive oxygen species (ROS) production from traversing proton beam-irradiated IONs was examined. Flow recovery was only observed in CNR-treated mice, and greater than 50% removal of the thrombus was achieved. A 2.5-fold greater reduction in the thrombus-enabled flow recovery was observed in the CNR group compared with that observed in the untreated ION-only and proton-only control groups (p < 0.01). Enhancement of the X-ray photon-electron emission was evident from both the pronounced Shirley background in the electron yield and the 1.2- to 2.5-fold enhanced production of ROS by the proton-irradiated IONs, which suggests chemical degradation of the thrombus without potent emboli.

Comparison of the functional features of the pump organs of Anopheles sinensis and Aedes togoi.

Mosquitoes act as vectors for severe tropical diseases. Mosquito-borne diseases are affected by various factors such as environmental conditions, host body susceptibility, and mosquito feeding behavior. Among these factors, feeding behavior is affected by the feeding pump system located inside the mosquito head and also depends on the species of mosquito. Therefore, the 3D morphological structures of the feeding pumps of Aedes togoi and Anopheles sinensis were comparatively investigated using synchrotron X-ray microscopic computed tomography. In addition, the feeding behaviors of their pumping organs were also investigated using a 2D X-ray micro-imaging technique. An. sinensis, a malarial vector mosquito, had a larger feeding pump volume than Ae. togoi in the static or resting position. Interestingly, the two species of mosquitoes exhibited different feeding behaviors. Ae. togoi had a higher feeding frequency and expansion ratio than An. sinensis. Ae. togoi also exhibited F-actin localization more clearly. These distinctive variations in feeding volumes and behaviors provide essential insight into the blood-feeding mechanisms of female mosquitoes as vectors for tropical diseases.