Phase-contrast visualization of human tissues using superimposed wavefront imaging of diffraction-enhanced x-rays.

BACKGROUND: Phase-contrast computed tomography (CT) using high-brilliance, synchrotron-generated x-rays enable three-dimensional (3D) visualization of microanatomical structures within biological specimens, offering exceptionally high-contrast images of soft tissues. Traditional methods for phase-contrast CT; however, necessitate a gap between the subject and the x-ray camera, compromising spatial resolution due to penumbral blurring. Our newly developed technique, Superimposed Wavefront Imaging of Diffraction-enhanced x-rays (SWIDeX), leverages a Laue-case Si angle analyzer affixed to a scintillator to convert x-rays to visible light, capturing second-order differential phase contrast images and effectively eliminating the distance to the x-ray camera. This innovation achieves superior spatial resolution over conventional methods. PURPOSE: In this paper, the imaging principle and CT reconstruction algorithm based on SWIDeX are presented in detail and compared with conventional analyzer-based imaging (ABI). It also shows the physical setup of SWIDeX that provides the resolution preserving second-order differential images for reconstruction. We compare the spatial resolution and the sensitivity of SWIDeX to conventional ABI. METHODS: To demonstrate high-spatial resolution achievable by SWIDeX, the internal structures of four human tissues-ductal carcinoma in situ, normal stomach, normal pancreas, and intraductal papillary mucinous neoplasm of the pancreas-were visualized using an imaging system configured at the Photon Factory's BL14B beamline under the High Energy Accelerator Research Organization (KEK). Each tissue was thinly sliced after imaging, stained with hematoxylin and eosin (H&E) for conventional microscope-based pathology. RESULTS: A comparison of SWIDeX-CT and pathological images visually demonstrates the effectiveness of SWIDeX-CT for biological tissue imaging. SWIDeX could generate clearer 3D images than existing analyzer-based phase-contrast methods and accurately delineate tissue structures, as validated against histopathological images. CONCLUSIONS: SWIDeX can visualize important 3D structures in biological soft tissue with high spatial resolution and can be an important tool for providing information between the disparate scales of clinical and pathological imaging.

Capacitive Electrode-Based Electric Field Treatments on Redox-Toxic Iron Deposits in Transgenic AD Mouse Models: The Electroceutical Targeting of Alzheimer's Disease Feasibility Study.

Iron accumulation in the brain accelerates Alzheimer's disease progression. To cure iron toxicity, we assessed the therapeutic effects of noncontact transcranial electric field stimulation to the brain on toxic iron deposits in either the Aß fibril structure or the Aß plaque in a mouse model of Alzheimer's disease (AD) as a pilot study. A capacitive electrode-based alternating electric field (AEF) was applied to a suspension of magnetite (Fe3O4) to measure field-sensitized reactive oxygen species (ROS) generation. The increase in ROS generation compared to the untreated control was both exposure-time and AEF-frequency dependent. The frequency-specific exposure of AEF to 0.7-1.4 V/cm on a magnetite-bound Aß-fibril or a transgenic Alzheimer's disease (AD) mouse model revealed the degradation of the Aß fibril or the removal of the Aß-plaque burden and ferrous magnetite compared to the untreated control. The results of the behavioral tests show an improvement in impaired cognitive function following AEF treatment on the AD mouse model. Tissue clearing and 3D-imaging analysis revealed no induced damage to the neuronal structures of normal brain tissue following AEF treatment. In conclusion, our results suggest that the effective degradation of magnetite-bound amyloid fibrils or plaques in the AD brain by the electro-Fenton effect from electric field-sensitized magnetite offers a potential electroceutical treatment option for AD.

Development of an Auxiliary Device for Patellar and Femoral Joint Tangential Axial Radiographic Imaging and a Method for Obtaining an Optimal Radiographic Image Using the Development.

This study evaluated the accuracy of tangential axial radiography of the patellar and femoral joint using an auxiliary device based on three image evaluation criteria, which we named the patellofemoral joint radiography auxiliary device (PJR). To compare the PJR method with conventional radiographic methods, such as Laurin, Merchant, and Settegast, a whole-body phantom (PBU-31) was used and three image evaluation items were set. The radiographic method, the smallest inclination of the patellar and showed the best half lateral image of the patella, is Settegast, and the measurement is 9.40. The second-best PJR measurement is 9.97, and the difference between the two measures is 5.76% (p = 0.001). The radiographic method showing the image with the largest distance between the patellar and femoral joint space is PJR which a measurement is 12.35. The second best Merchant measure is 10.55, and the difference between the two measures is 14.54% (p = 0.001). The method in which the two bones were well overlapped (i.e., evaluate the distortion of the image by measured as the distance between the femoral trochlear groove and the tibial tuberosity) is the PJR and the measurement is -0.37. The second-best Merchant measure is 3.93, and the difference between the two measures is 91.4% (p = 0.001). The Settegast has the image with the smallest inclination of the patella, but the PJR has the image that best describes the patellar-femoral joint and the least distortion of the image. As a result of the comprehensive evaluation, when using PJR, bending the knee by 40° and setting a 140° angle between the long axis of the femur and the long axis of the lower leg were considered to be the most beneficial conditions. Therefore, we propose the use of PJR for tangential axial radiography of the patellar-femoral joint.

The Potential Neuroprotective Effects of Extracts from Oat Seedlings against Alzheimer's Disease.

The physiological or dietary advantages of germinated grains have been the subject of numerous discussions over the past decade. Around 23 million tons of oats are consumed globally, making up a sizeable portion of the global grain market. Oat seedlings contain more protein, beta-glucan, free amino acids, and phenolic compounds than seeds. The progressive neurodegenerative disorder of Alzheimer's is accompanied by worsening memory and cognitive function. A key indicator of this disorder is the unusual buildup of amyloid-beta protein (or Aß) in human brains. In this context, oat seedling extract (OSE) has been identified as a new therapeutic candidate for AD, due to its antioxidant activity and AD-specific mechanism of action. This study directly investigated how OSE affected AD and its impacts by examining the cognitive function and exploring the inflammatory response mechanism. The dried oat seedlings were grounded finely with a grinder, inserted with 50% fermented ethanol 10 times (w/v), and extracted by stirring for 10 h at 45 °C. After filtering the extract by 0.22 um filter, some of it was used for UHPLC analysis. The results indicated that the treatment with OSE protects against Aß25-35-induced cytotoxicity in BV2 cells. Tg-5Xfad AD mice had strong deposition of Aß throughout their brains, while WT mice did not exhibit any such deposition within their brains. A drastic reduction was observed in terms of numbers, as well as the size, of Aß plaques within Tg-5Xfad AD mice exposed to OSE. This study indicated OSE's neuroprotective impacts against neurodegeneration, synaptic dysfunction, and neuroinflammation induced by amyloid-beta. Our results suggest that OSE acts as a neuroprotective agent to combat AD-specific apoptotic cell death, neuroinflammation, amyloid-beta accumulation, as well as synaptic dysfunction in AD mice's brains. Furthermore, the study indicated that OSE treatment affects JNK/ERK/p38 MAPK signaling, with considerable inhibition in p-JNK, p-p38, and p-ERK levels seen in the brain of OSE-treated Tg-5Xfad AD mice.

Tumor-treating fields in combination with sorafenib restrain the proliferation of liver cancer in vitro.

Liver cancer is a common malignancy worldwide, with a poor prognosis and a high recurrence rate despite the available treatment methodologies. Tumor-treating fields (TTFields) have shown good preclinical and clinical results for improving the prognosis of patients with glioblastoma and malignant pleural mesothelioma. However, there is minimal evidence for the effect of TTFields on other cancer types. Thus, the present study aimed to investigate the therapeutic efficacy of TTFields in an in vitro model, and to further elucidate the underlying mechanisms. In the present study, two hepatocellular carcinoma (HCC) cell lines (Hep3B and HepG2) were treated with TTFields (intensity, 1.0 V/cm; frequency, 150 kHz) in order to determine the potential antitumor effects of this approach. TTFields significantly inhibited the proliferation and viability of HCC cell lines, as measured using Trypan blue and MTT assays, as well as colony formation in three-dimensional cultures. The TTFields also significantly inhibited the migration and invasion of HCC cells in Transwell chamber and wound-healing assays. Moreover, TTFields enhanced the production of reactive oxygen species in the cells and increased the proportion of apoptotic cells, as evidenced by increased caspase-3 activity, as well as PARP cleavage in western blotting experiments. All of these effects were increased following the application of TTFields in combination with the multi-kinase inhibitor sorafenib, which demonstrated a synergistic effect. Thus, to the best of our knowledge, these results demonstrate for the first time the potential of TTFields in improving the sensitivity of HCC cells to sorafenib, which may lay the foundation for future clinical trials for this combination treatment strategy.

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.

Tumor treating fields can effectively overcome trastuzumab resistant breast cancer multiplication.

The Human Epidermal Growth Receptor 2, or the HER2 is one of the highest expressed negative receptor that constitutes approximately 15-20% of malevolent breast cancerous tumors among women. The prevalence of HER2 has untimely and unfavorable consequences on breast cancer, and its underlying carcinomous cell processes, structures, and growth. Trastuzumab (TRZ), a humanized antibody that is rooted in relatively recent foundations, has been found operational in its construction of treatments against HER2-positive breast cancer. This drug is combined with radiotherapy or chemotherapy to deregulate HER2 genes in the body. However, patients who suffer from evolved tumors in advanced stages of cancer exhibit a good amount of tolerance towards singularly used TRZ treatment. Inversely, the factorization of Tumor Testing Fields (TTFields or TTFs) into cancer therapy revives the functions of a TRZ treatment plan, by sensitizing the HER2 genes to the drug. In turn, this facilitates TRZ to continue limiting cancerous cell multiplication and toxicity levels within the treatment. This research evaluates the aspects and effects of this pairing, both in vivo and in vitro through BT474 cells. The TTFields conduct an electromagnetic boundary, which generates sine-wave radiations to manipulate the HER2 gene structure. The methods followed in the research also examines the gene cell cultures and their viability through solutions like Tryptophan blue, or the Crystal violet which may or may not deliver certain testmants to the experiment. The Western Blot Test and the IHC confirm the presence of antibodies and negative receptors in the BT474 cells. These procedures contribute to the formulation of a treatment plan that overcomes the TRZ-resistant nature of the tumor, which is essentially the aim of the research. Thus, the paper substantiates that a healthy combination of TTF's with TRZ can enhance the penetration of TRZ after inducing apoptosis due to TTFields therapy. The success of a TTField in undertaking this pursuit makes room for more utilization of it in future cancerous treatment ventures.

X-ray dark-field phase-contrast imaging: Origins of the concept to practical implementation and applications.

The basic idea of X-ray dark-field imaging (XDFI), first presented in 2000, was based on the concepts used in an X-ray interferometer. In this article, we review 20 years of developments in our theoretical understanding, scientific instrumentation, and experimental demonstration of XDFI and its applications to medical imaging. We first describe the concepts underlying XDFI that are responsible for imparting phase contrast information in projection X-ray images. We then review the algorithms that can convert these projection phase images into three-dimensional tomographic slices. Various implementations of computed tomography reconstructions algorithms for XDFI data are discussed. The next four sections describe and illustrate potential applications of XDFI in pathology, musculoskeletal imaging, oncologic imaging, and neuroimaging. The sample applications that are presented illustrate potential use scenarios for XDFI in histopathology and other clinical applications. Finally, the last section presents future perspectives and potential technical developments that can make XDFI an even more powerful tool.

Stimulus-Responsive Contact Lens for IOP Measurement or Temperature-Triggered Drug Release.

Purpose: Continuous monitoring of elevated intraocular pressure and timely drug delivery for successful treatment of glaucoma are necessary to reduce intraocular pressure (IOP), which shows wide variations across the circadian pattern and in response to medication. This in vivo study presents a new contact lens-based method of optical IOP measurement or temperature-triggered drug elution. Methods: A contact lens with moiré patterns of concentric circles measures the changes in eyeball diameter of a rabbit glaucoma model due to changes in IOP by superimposing a camera-captured image onto the micro pattern of the contact lens with a computer-assisted virtual reference image. Drug elution from the nanoporous bicontinuous microemulsion contact lens (BME-CL) into the eye of the rabbit was triggered by a temperature-responsive nanogel drug carrier. Results: The moiré pattern change on the contact lens was proportional to the IOP increase in the rabbit eye either ex vivo or in vivo and was also correlated with imaging-based alterations in the anterior chamber angle at a range of IOP values (3-40 mm Hg). The cumulative drug absorbed reached as high as 10.6 µg/mL aqueous humor until 7 days after wearing the BME-CL, and a 33% decrease in IOP was observed at 3 hours after drug elution. Conclusions: The results suggest that continuous measurement and treatment of elevated IOP are feasible using moiré pattern-inscribed and thermosensitive drug-eluting contact lenses, respectively. Translational Relevance: Pressure-sensing or thermosensitive contact lenses enable monitoring IOP or drug release triggered by body temperature for the treatment of glaucoma patients.

Medulla loss of scalp hair in breast cancer patients determined by near-infrared microscopy.

Inexpensive near-infrared microscopy (NIRM) was developed as a convenient technique to detect the medulla loss of scalp hair while reducing analytical time with easy sample preparation, leading to a field screening tool for breast cancer. NIRM has been evaluated as an alternative to synchrotron-based nanoscopy and to the relatively expensive method of conventional infrared microscopy to determine the degree and pattern of medulla loss of scalp hairs of patients with breast cancer and benign diseases, as well as normal healthy individuals. NIR imaging showed a strong, scattering-based hyperintense contrast of the medulla compared to the fully attenuated cortex in medullated healthy hair. Complete medulla loss (CML) per hair strand was more extensively (60.9 ± 10.2 %) (p < 0.001) detected in the hair of all cancer patients than in the hair of either healthy individuals (less than 3.7 ± 7.5%) or those with benign disease (30.6 ± 5.9 % ), suggesting a potential biomarker for breast cancer diagnosis. The medulla structure was retained mostly in the hair of age-matched healthy individuals, but discontinuous medulla loss was observed concomitantly with less CML in fibroadenoma patients. Potentially, compact NIRM modules can be integrated into a mobile platform as point-of-care technology for breast cancer screening.

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.

Thermo-sensitive nanogel-laden bicontinuous microemulsion drug-eluting contact lenses.

The bicontinuous microemulsion contact lens (BMCL) has nanoporous biphasic structures (100-250 nm) that are interconnected via multiple nano-channels, providing suitable retention of various drugs for glaucoma. Timolol maleate (TM)-carried thermosensitive poly(N-isopropylacrylamide) (PNIPAM) nanogel (30-50 nm) was incorporated into BMCLs by soaking or by centrifuging plus soaking. Here, we present drug-loading and release in silicon- or polyethylene oxide-microemulsion BMCLs under various conditions. Nanoporous BMCLs containing thermosensitive TM-laden nanogel were capable of potent body-temperature-triggered release of TM. Daily drug release was controllable according to the initial volume of drug-loaded (VDL) and loading method for sustained drug release, making them reduce drug-loss during transportation or storage. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1159-1169, 2019.

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.

Enhanced production of reactive oxygen species in HeLa cells under concurrent low­dose carboplatin and Photofrin® photodynamic therapy.

Concurrent low­dose carboplatin/Photofrin® photodynamic therapy (ccPDT) has been shown to promote relapse­free complete tumor regression in cervical or endometrial cancer patients as a fertility­preservation therapy. This study aimed to investigate the molecular mechanism of the enhanced therapeutic efficacy of ccPDT by determining intracellular reactive oxygen species (ROS) and necrotic or apoptotic cell damage in HeLa cells loaded with fluorescent oxidant agents and Photofrin or/and carboplatin under light irradiation. The cytotoxic effects of ccPDT were compared when monitored with a light dose under carboplatin or Photofrin alone. Photofrin­PDT alone did not enhance either hydroxyl radicals (OH•) or superoxide anions (O2•-), but a slight enhancement of hydrogen peroxide (H2O2) production was observed. A larger enhancement of ROS production was obtained in a dose­dependent manner following ccPDT, especially OH• and H2O2, in conjunction with both necrotic and apoptotic cell death, compared with necrotic­prone PDT alone. The carboplatin­mediated Fenton reaction: 2[PtII]2 + H2O2 → [Pt2.25]4 + OH¯+ OH• was proposed to explain the dose­dependent enhancement of OH•. In conclusion, the therapeutic enhancement of ccPDT in vitro was attributable to the carboplatin­mediated synergetic production of OH▪ and apoptotic cellular damage, compared with Photofrin­PDT alone.

Development of Gallic Acid-Modified Hydrogels Using Interpenetrating Chitosan Network and Evaluation of Their Antioxidant Activity.

In this work, antioxidant hydrogels were prepared by the construction of an interpenetrating chitosan network and functionalization with gallic acid. The poly(2-hydroxyethyl methacrylate) p(HEMA)-based hydrogels were first synthesized and subsequently surface-modified with an interpenetrating polymer network (IPN) structure prepared with methacrylamide chitosan via free radical polymerization. The resulting chitosan-IPN hydrogels were surface-functionalized with gallic acid through an amide coupling reaction, which afforded the antioxidant hydrogels. Notably, gallic-acid-modified hydrogels based on a longer chitosan backbone exhibited superior antioxidant activity than their counterpart with a shorter chitosan moiety; this correlated to the amount of gallic acid attached to the chitosan backbone. Moreover, the surface contact angles of the chitosan-modified hydrogels decreased, indicating that surface functionalization of the hydrogels with chitosan-IPN increased the wettability because of the presence of the hydrophilic chitosan network chain. Our study indicates that chitosan-IPN hydrogels may facilitate the development of applications in biomedical devices and ophthalmic materials.

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.