Non-irradiated Regions Research Articles

Simultaneous imaging of telomerase activity and protein tyrosine kinase 7 in living cells during epithelial-mesenchymal transformation via a near-infrared light-activatable nanoprobe

Exploring the relationship between key regulation molecules (such as telomerase and protein tyrosine kinase 7) during epithelial-mesenchymal transformation of cells is beneficial for studying malignant tumor metastasis. Fluorescence is usually used for real-time monitoring the distribution and expression of regulatory molecules in living cells. However, the recognition function of these classical nanoprobes is “always active” due to the absence of exogenous control, which leads to the amplification of both the background signal and the response signal, making it difficult to distinguish changes in biomolecule expression levels. To improve the fluorescence ratio between tumor and normal cells, we constructed near-infrared light-activatable nanoprobes by engineering the functional units of catalytic hairpin assembly and integrating upconversion luminescence nanoparticles. Under near-infrared light irradiation, the nanoparticles, serving as a near-infrared-to-ultraviolet light transducer, induced the photolysis of the photo-cleavable linkers sealed in hairpins. The recognition function of the nanoprobes can be controlled by near-infrared light, preventing them from recognizing the targets in non-irradiated regions. By employing the nanoprobes, we realized simultaneous imaging of two regulatory molecules in living cells and observed an increase in telomerase activity and a decrease in protein tyrosine kinase 7 expression during drug-induced epithelial-mesenchymal transformation. This work provides a promising method for revealing changes and relationships of regulatory molecules during tumor metastasis.

De-intensification of postoperative radiotherapy in head and neck cancer irrespective of human papillomavirus status-results of a prospective multicenter phase II trial (DIREKHT Trial).

Current standard treatment concepts in head and neck squamous cell carcinoma (HNSCC) are based on former studies using 2D and 3D treatment plans. However, modern radiation techniques allow for a more precise and individual dose application. Therefore, in a clearly defined patient population, de-intensified risk-adapted radiation is investigated. Patients with newly diagnosed HNSCC after surgery (with resection margins ≥1 mm and cM0) with the following tumor stages (TNM 7th Edition) were eligible for the study: oral cavity, oropharynx, or larynx: pT1-3, pN0-pN2b; hypopharynx: pT1-2, pN1. The patients should have either a low risk of local recurrence [≤pT2, resection margin ≥5 mm, no peritumoral lymphangiosis (L0), and no perineural invasion] or contralateral lymph node metastasis (≤3 ipsilateral lymph node metastases, in case of well-lateralized oropharyngeal or oral cavity cancer contralateral cN0, otherwise pN0). Patients were assigned to three different treatment regimes with reduction of the treated volume, radiation dose, or both, according to tumor stage and results of surgery performed. The primary objective was to show an LRR of <10% after 2 years. A total of 150 patients were enrolled. Tumor localizations were as follows: n = 53 (35.3%), oral cavity; n = 94 (62.7%), oropharynx (82% HPV-positive); n = 2 (1.3%), hypopharynx; and n = 1 (0.7%), larynx. A total of 61 patients (41.0%) were stage IVA, 81 (54.0%) were stage III, and 8 (5.3%) were stage II. Median follow-up was 36 months. Cumulative incidence of 2y-LRR was 5.6% (95% CI: 1.7%-9.2%) in the whole study population and 14.1% (95% CI: 3.8%-23.2%) in patients with oral cavity cancer. Cumulative incidence of 2y-LRR in non-irradiated or dose-reduced regions was 3.5% (95% CI: 0.4%-6.5%). After 2 years, disease-free survival was 92% (95% CI: 87%-96%) and overall survival was 94% (95% CI: 90%-98%) for the complete study cohort. Acute III° toxicity was as follows: dysphagia, 30%; xerostomia, 7%; mucositis, 19%; and dermatitis, 4%. Dysphagia and xerostomia decrease over time. After 27 months, late dysphagia III° and xerostomia II° were 1% and 9%, respectively. The study met its primary objective. De-intensification of postoperative radiotherapy irrespective of HPV status in a predefined patient population is associated with a favorable toxicity profile without compromising LRR. In an unplanned subgroup analysis, a significantly increased risk of LRR was observed in patients with oral cavity cancer. In these patients, de-intensified radiotherapy should be applied with caution.

Optomechanical assessment of photorefractive corneal cross-linking via optical coherence elastography.

Purpose: Corneal cross-linking (CXL) has recently been used with promising results to positively affect corneal refractive power in the treatment of hyperopia and mild myopia. However, understanding and predicting the optomechanical changes induced by this procedure are challenging. Methods: We applied ambient pressure modulation based optical coherence elastography (OCE) to quantify the refractive and mechanical effects of patterned CXL and their relationship to energy delivered during the treatment on porcine corneas. Three different patterned treatments were performed, designed according to Zernike polynomial functions (circle, astigmatism, coma). In addition, three different irradiation protocols were analyzed: standard Dresden CXL (fluence of 5.4J/cm2), accelerated CXL (fluence of 5.4J/cm2), and high-fluence CXL (fluence of 16.2J/cm2). The axial strain distribution in the stroma induced by ocular inflation (Δp = 30mmHg) was quantified, maps of the anterior sagittal curvature were constructed and cylindrical refraction was assessed. Results: Thirty minutes after CXL, there was a statistically significant increase in axial strain amplitude (p < 0.050) and a reduction in sagittal curvature (p < 0.050) in the regions treated with all irradiation patterns compared to the non-irradiated ones. Thirty-6hours later, the non-irradiated regions showed compressive strains, while the axial strain in the CXL-treated regions was close to zero, and the reduction in sagittal curvature observed 30minutes after the treatment was maintained. The Dresden CXL and accelerated CXL produced comparable amounts of stiffening and refractive changes (p = 0.856), while high-fluence CXL produced the strongest response in terms of axial strain (6.9‰ ± 1.9‰) and refractive correction (3.4 ± 0.9 D). Tripling the energy administered during CXL resulted in a 2.4-fold increase in the resulting refractive correction. Conclusion: OCE showed that refractive changes and alterations in corneal biomechanics are directly related. A patient-specific selection of both, the administered UV fluence and the irradiation pattern during CXL is promising to allow customized photorefractive corrections in the future.

Nanoscale thinning of metal-coated polypropylene films by Helium-ion irradiation

Polypropylene (PP) films have a wide range of applications, e.g. as dielectric materials for metallized film capacitors. In this article, we present a method for thickness reduction of PP films by ion irradiation, which has a direct effect on device capacitance. We show that the thickness of PP layers can be reduced by irradiation with He+ ions and controlled on the nanometer scale by the irradiation dose. The effect of different thin metal film coatings on PP surface was also investigated. The metal coatings were used for two reasons: they function as one of the metal electrodes in the capacitor structure, and they minimize sample charging during ion irradiation. Three different metallization materials were investigated: 5 nm Pt60Pd40, 5 nm Au, and 15 nm Al. We studied two technologically relevant PP films: the thinnest commercially available biaxially oriented polypropylene (BOPP) and spin-coated polypropylene (SC-PP) thin films. The irradiation was done with a focused Helium-ion beam (He-FIB) in a Zeiss Orion NanoFab Microscope at a landing energy of 30 keV with doses in a range of 5.4 × 10–5 nC/μm2 to 8.1 × 10–3 nC/μm2. An atomic force microscope (AFM) was used to analyze the details of surface modification: the surface height of the irradiated regions and surface morphology changes caused by the irradiation. For all applied doses, the Al-coated samples demonstrated smaller surface-height reduction compared to the Pt60Pd40 and Au-coated samples. We speculate that the possible factors responsible for this effect include differences in the thickness and the crystalline-grain orientation (texture) of the metallization films. Both BOPP and spin-coated PP presented surface ridges at the borders between the irradiated and non-irradiated regions. It can be attributed to the mechanical strain induced by the material modification.

Analogous response of temperate terrestrial exoplanets and Earth’s climate dynamics to greenhouse gas supplement

Humanity is close to characterizing the atmospheres of rocky exoplanets due to the advent of JWST. These astronomical observations motivate us to understand exoplanetary atmospheres to constrain habitability. We study the influence greenhouse gas supplement has on the atmosphere of TRAPPIST-1e, an Earth-like exoplanet, and Earth itself by analyzing ExoCAM and CMIP6 model simulations. We find an analogous relationship between CO2 supplement and amplified warming at non-irradiated regions (night side and polar)—such spatial heterogeneity results in significant global circulation changes. A dynamical systems framework provides additional insight into the vertical dynamics of the atmospheres. Indeed, we demonstrate that adding CO2 increases temporal stability near the surface and decreases stability at low pressures. Although Earth and TRAPPIST-1e take entirely different climate states, they share the relative response between climate dynamics and greenhouse gas supplements.

Spatial Gene Expression Changes in the Mouse Heart After Base-Targeted Irradiation

Radiation cardiotoxicity (RC) is a clinically significant adverse effect of treatment for patients with thoracic malignancies. Clinical studies in lung cancer have indicated that heart substructures are not uniformly radiosensitive, and that dose to the heart base drives RC. In this study, we aimed to characterize late changes in gene expression using spatial transcriptomics in a mouse model of base regional radiosensitivity. An aged female C57BL/6 mouse was irradiated with 16 Gy delivered to the cranial third of the heart using a 6×9 mm parallel opposed beam geometry on a small animal radiation research platform, and a second mouse was sham-irradiated. After echocardiography, whole hearts were collected at 30 weeks for spatial transcriptomic analysis to map gene expression changes occurring in different regions of the partially irradiated heart. Cardiac regions were manually annotated on the capture slides and the gene expression profiles compared across different regions. Ejection fraction was reduced at 30 weeks after a 16 Gy irradiation to the heart base, compared with the sham-irradiated controls. There were markedly more significant gene expression changes within the irradiated regions compared with nonirradiated regions. Variation was observed in the transcriptomic effects of radiation on different cardiac base structures (eg, between the right atrium [n=86 dysregulated genes], left atrium [n=96 dysregulated genes], and the vasculature [n=129 dysregulated genes]). Disrupted biological processes spanned extracellular matrix as well as circulatory, neuronal, and contractility activities. This is the first study to report spatially resolved gene expression changes in irradiated tissues. Examination of the regional radiation response in the heart can help to further our understanding of the cardiac base's radiosensitivity and support the development of actionable targets for pharmacologic intervention and biologically relevant dose constraints.

Self-powered waveguide-integrated photodetector based on a defect-engineered WSe2/graphene heterojunction

With integration capability and excellent photoelectronic, two-dimensional materials have attracted increasing interest in photonic circuits as waveguide-integrated photodetectors. Here, we report a waveguide-integrated self-powered photodetector based on a defect-engineered WSe2/graphene (WSe2/G) heterostructure. The WSe2 side of the heterostructure is locally irradiated by the Ga+ ion beam generating S-vacancies (WSe2-0.18/G). The boundary of the irradiated and non-irradiated regions (WSe2/G-WS2-0.18/G) construct a Schottky-metal junction with the photovoltaic property. This WSe2/G-WS2-0.18/G heterostructure exhibits a broad spectral photoresponse from 450 nm to 1550 nm at 0 bias with on/off ratio of 104. As a self-powered photodetector, WSe2/G-WS2-0.18/G heterostructure is integrated with a polymer waveguide. It directly reads optical signal (100 kHz @ 1550 nm) in the waveguide. Our work paves a novel avenue to prepare the self-powered 2D photodetector for integration with photonic circuits.

35. Human Adipose-derived Stem Cells Decrease Skin Damage in Mice After Scalp Irradiation: A Pilot Experiment

Purpose: The treatment for radiation dermatitis ulcers is surgical reconstruction. We aimed to characterize the effects of human adipose-derived stem cells (hAdMSCs) to prevent complications of radiation dermatitis of the scalp in an immunocompetent mouse model. Methods: Two 4-week-old female C57BL/6 mice were delivered a dose of 60 Gy to a skin area between the coronal and lambdoid sutures using a 5 mm circular collimator. On day 12 after irradiation, 600,000 luciferase- and green fluorescent protein-labeled hAdMSCs in 300 µL of PBS were injected subcutaneously into the scalp of one mouse. Mice were photographed under standardized conditions and weighted daily. Bioluminescence imaging (BLI) was performed daily from the day after injection until there was no detectable signal. Both were euthanized on day 27 after irradiation, and the scalp tissue was collected. Staining with hematoxylin and eosin, Masson’s trichrome, and immunohistochemistry for CD31 were performed. The histological slides were digitalized and analyzed using ImageJ (NIH). Statistical analyses were performed using Excel 2010 (Microsoft Corp., United States). Results: Bioluminescence images showed that hAdMSCs survived in vivo for five days. While desquamation and ulceration appeared on day 14 and lasted for 12 days in the treated mouse, the control mouse did not show signs of improvement by the time of euthanasia. The treated mouse had a greater mean erythematous area than the control mouse (0.38 cm2 vs. 0.23 cm2, p<0.05). The mean ulceration areas did not differ between the treated and control mouse (0.12 cm2 vs. 0.14 cm2, p>0.05). The epidermis, total skin thickness, and hypodermis of the irradiated regions were significantly thicker than the non-irradiated regions in both the treatment and control mice. The vessel size (treated = 67.25 µm2, control = 72.27 µm2, p>0.05) and the difference in tissue area occupied by vessels (treated = 2.58%, control = 2.42%, p>0.05) of the radiated regions did not differ between mice. Collagen deposition in the irradiated region was decreased in the treated mouse compared to the control mouse (11% vs. 42%). Conclusion: Human adipose-derived stem cells decrease the duration of ulceration and improve the macroscopic quality of the skin, survive for only 5 days after transplantation, decrease collagen deposition in the irradiated area, increase micro vessel area and size, and decrease the thickness of the irradiated area of the skin compared to controls two weeks after transplantation.

Prospective Evaluation of Radiotherapy-Induced Immunologic and Genetic Effects in Colorectal Cancer Oligo-Metastatic Patients with Lung-Limited Disease: The PRELUDE-1 Study.

Simple SummaryThe management of advanced colorectal cancer (CRC) has been greatly improved with integrated strategies including stereotactic radiation therapy (SRT). It is a safe and effective option, particularly in oligo-metastatic (om) CRC patients. Interestingly, it has been demonstrated that SRT can induce regression of tumors in non-irradiated regions (“abscopal effect”) through stimulation of anti-tumor immune effects (“radiation-induced immunity”). We have recently shown that lung-limited omCRC is characterized by regression of tumor clones bearing specific key driver gene mutations. The aim of the PRELUDE-1 study is to assess the genetic and immunologic evolutions on tumor cancer/host cells induced by SRT in lung-limited omCRC through liquid biopsies and Next Generation Sequencing of tumor exome, HLA repertoire assessment, peripheral immune cells, and cytokine dynamics characterizations. An important secondary objective is the first prospective evaluation of the abscopal effect. The PRELUDE-1 results will help to identify subsets of patients more prone to show the abscopal effect. The PRELUDE-1 trial was registered into the clinicaltrials.gov registry on 22 April 2021, with identifier NCT04854213.Background: in recent years, the management of advanced colorectal cancer (CRC) has been greatly improved with integrated strategies including stereotactic radiation therapy (SRT). The administration of SRT has been demonstrated, particularly in oligo-metastatic (om) CRC, to be a safe and effective option. Interestingly, it has been demonstrated that SRT can induce regression of tumors in non-irradiated regions (“abscopal effect”) through stimulation of anti-tumor immune effects (“radiation-induced immunity”). We have recently shown that lung-limited omCRC is characterized by regression of tumor clones bearing specific key driver gene mutations. Aims: to assess the genetic evolution on tumor cancer cells induced by SRT in lung-limited omCRC. Secondary objectives included descriptions of the abscopal effect, responses’ duration, toxicity, and progression-free survival. A translational research will be performed to evaluate tumor genetic evolution (through liquid biopsies and Next Generation Sequencing), HLA class I repertoire, peripheral immune cells, and cytokine dynamics. Methods: PRELUDE-1 is a prospective translational study. SRT will be administered only to the largest nodule (with a maximum diameter ≤ 25 mm) in omCRC with two or three radiologically evident lesions. The sample size is based on the innovative hypothesis that radiation-induced immunity could induce regression of tumor clones bearing KRAS oncogene mutations. According to the binomial test, considering the frequency of KRAS mutations and assuming a probability of mutant KRAS→wild type KRAS of p0 = 0.0077, with α = 0.05 and 1-β = 0.60, the final sample size is 25 patients.

Lasing from MEH-PPV with a refractive index tunable by electron irradiation.

A simple one-step approach to producing a distributed feedback (DFB) laser through selective irradiation of the gain medium, MEH-PPV, is presented. Electron irradiation alters the refractive index of MEH-PPV, thus, direct patterning by electron irradiation can be applied to create a periodic diffraction grating. The non-irradiated regions of MEH-PPV serve as the primary gain medium, while the irradiated regions of MEH-PPV provide the refractive index difference required to fabricate a DFB laser. This method was successfully applied to achieve lasing with a relatively low lasing threshold of 3 kW/cm2or 1.8 µJ/cm2 (pulse width: 600 ps). Furthermore, the lasing wavelength can be finely tuned by simply adjusting the grating period. In stark contrast to the simple one-step process described in this work, conventional procedures for the fabrication of DFB lasers involve multiple steps of varying complexity, including mold creation and careful coating of the substrate with the gain medium.

Formation of the Ni31Si12 phase induced by the irradiation of nickel ions on the eutectic, α-Ni-Ni3Si-monoclinic, with a 380 dpa dose

This investigation has been developed to determine which microstructural changes on the eutectic α-Ni-Ni3Si- monoclinic, if any exist, result from the irradiation with Ni-ions. SRIM program has been used to simulate the interaction of the irradiation with both α-Ni and Ni3Si- monoclinic phases. X-ray diffraction studies of irradiated and non-irradiated regions have allowed us to establish that the ion irradiation promote the formation of the Ni31Si12-hexagonal intermetallic phase with hexagonal structure. An analysis of the irradiated region by High Resolution Transmission Electron Microscopy (HRTEM) confirmed the presence of the Ni31Si12-hexagonal intermetallic phase, establishing at the same time, its crystallographic relationship with the matrix. Evidently, radiation-induced segregation could cause significant changes in the chemical composition of concentrated alloys. This experimental discovery, in particular, is significant because the formation of the Ni31Si12-hexagonal phase under irradiation conditions had never been mentioned before. Nonetheless, the formation of the Ni31Si12-hexagonal intermetallic phase represents an advance in the field of the microstructural modification by ion beam irradiation, and as a consequence of this finding, it is possible to establish that the structural stability of the eutectic form of the α-Ni-Ni3Si-monoclinic phases under severe irradiation conditions, is questionable.

Molecular dynamics study of damage nearby silicon surface bombarded by energetic carbon ions

This paper investigates damage generation and evolution nearby silicon surface bombarded by energetic carbon ions by using molecular dynamics simulations. We experimentally measured elementary composition in defect regions based on energy dispersive spectrometer analysis. Using molecular dynamics simulations, point defects generation and evolution in monocrystalline silicon were illustrated. The percentage of carbon in defect regions is significantly more than that in non-irradiated regions of monocrystalline silicon. Point defects rapidly generate at the beginning of collision cascades between projective carbon ions and silicon atoms. The radial straggling and penetration along the depth direction are respectively dominant when projective ions with different kinetic energies implant into silicon target. These results can be used to better understand the interaction between projective energetic ions and target.

Anomalous Goos-Hänchen shift in the Floquet scattering of Dirac fermions

We study the inelastic scattering of two-dimensional massless Dirac fermions by an inhomogeneous time-dependent driving field. As a physical realization we consider a monolayer graphene normally illuminated with a circularly polarized laser of frequency $\Omega$ in a given region. The interaction Hamiltonian introduced by the laser, being periodic in time, can be treated with the Floquet method which naturally leads to a multi-channel scattering problem. We analyze planar and circular geometries of the interface separating the irradiated and non-irradiated regions and find that there is an anomalous Goos-H\"anchen shift in the inelastic channel. The latter is independent of the amplitude of the driving while its sign is determined by the polarization of the laser field. We related this shift with the appearance of topological edge states between two illuminated regions of opposite chiralities.

Conductivity Inversion in Thin n-InSe Films under Laser Irradiation

Conductivity inversion in thin n-InSe films under intense pulsed laser irradiation was obser. A p–n structure based on indium selenide formed between irradiated and nonirradiated regions of a thin-film sample. It was confirmed by EDAX analysis that the composition of the sample remained the same after irradiation. The conductivity inversion is attributed to a change in the dynamics of lattice defects under heating.

Инверсия типа проводимости тонких пленок n-InSe под действием лазерного излучения

AbstractConductivity inversion in thin n -InSe films under intense pulsed laser irradiation was obser. A p – n structure based on indium selenide formed between irradiated and nonirradiated regions of a thin-film sample. It was confirmed by EDAX analysis that the composition of the sample remained the same after irradiation. The conductivity inversion is attributed to a change in the dynamics of lattice defects under heating.

Study of the Effect of Laser Radiation on the Parameters of Alumina Films Formed by Atomic Layer Deposition

The effect of laser radiation with a wavelength of 970 nm and a power density of 0.29–2.10 W/cm2 on the process of atomic layer deposition of alumina films from precursors (trimethylaluminium + water vapor) is studied. Laser irradiation is performed at the stages of reactor purging after the introduction of precursors. The results of a comprehensive analysis involving spectral ellipsometry, atomic force microscopy, X-ray diffractometry, and secondary-ion mass spectrometry have revealed that laser irradiation (i) does not alter the rate of deposition of alumina films onto silicon slices; (ii) does not alter the surface relief (roughness) of alumina films; (iii) does not alter the depth profile of the chemical composition of alumina films; (iv) reduces the average density of irradiated regions of alumina films by 5–10% relative to the density of nonirradiated regions.

Minibeam radiotherapy with small animal irradiators; in vitro and in vivo feasibility studies

Minibeam radiation therapy (MBRT) delivers an ultrahigh dose of x-ray (⩾100 Gy) in 200–1000 µm beams (peaks), separated by wider non-irradiated regions (valleys) usually as a single temporal fraction. Preclinical studies performed at synchrotron facilities revealed that MBRT is able to ablate tumors while maintaining normal tissue integrity. The main purpose of the present study was to develop an efficient and accessible method to perform MBRT using a conventional x-ray irradiator. We then tested this new method both in vitro and in vivo. Using commercially available lead ribbon and polyethylene sheets, we constructed a collimator that converted the cone beam of an industrial irradiator to 44 identical beams (collimator size ≈ 4 × 10 cm). The dosimetry characteristics of the generated beams were evaluated using two different radiochromic films (beam FWHM = 246 ± 32 µm; center-to-center = 926 ± 23 µm; peak-to-valley dose ratio = 24.35 ± 2.10; collimator relative output factor = 0.84 ± 0.04). Clonogenic assays demonstrated the ability of our method to induce radiobiological cell death in two radioresistant murine tumor cell lines (TRP = glioblastoma; B16-F10 = melanoma). A radiobiological equivalent dose (RBE) was calculated by evaluating the acute skin response to graded doses of MBRT and conventional radiotherapy (CRT). Normal mouse skin demonstrated resistance to doses up to 150 Gy on peak. MBRT significantly extended the survival of mice with flank melanoma tumors compared to CRT when RBE were applied (overall p < 0.001). Loss of spatial resolution deep in the tissue has been a major concern. The beams generated using our collimator maintained their resolution in vivo (mouse brain tissue) and up to 10 cm deep in the radiochromic film. In conclusion, the initial dosimetric, in vitro and in vivo evaluations confirmed the utility of this affordable and easy-to-replicate minibeam collimator for future preclinical studies.

UV-Curable Antismudge Coatings

Current antismudge coatings that bear nano-pools of a grafted liquid ingredient for dewetting enablement (NP-GLIDE) are cured at high temperatures, which are undesirable for application on heat-sensitive substrates. Reported herein is the development of a NP-GLIDE coating that can be photocured at room temperature. Of the various formulations that have been tested, robust coatings were obtained from one recipe consisting of a photoinitiator, a trifunctional monomer that bears three double bonds, and a graft copolymer. The last bears pendent double bonds and a poly(dimethylsiloxane) (PDMS) side chain as the antismudge agent. Coatings were prepared by casting films from a solution containing these three components and then photolyzing the resultant films. A systematic study revealed that the liquid sliding property developed on the coating at a lower cross-linking density than that required for ink to contract. Further, retaining the ability to contract ink traces after many writing and erasing cycles was the most demanding of the three antismudge tests. For our optimized formulation, only 5 min of irradiation was required to yield a transparent coating with superior antismudge properties. Moreover, irradiating selected regions and then removing, with a solvent, reagents in the nonirradiated regions can yield a surface with patterned wettability. These advantageous properties of the new photocurable coating facilitate its applications.

Three dimensional approach to investigating biological effects along energetic ion beam pathways

Heavy ion beams have many exciting applications, including radiotherapy of deep-seated tumors and simulation tests of space irradiation for astronauts. These beams often use a feature that concentrates the energy deposition largely along the end of the energy pathway, leading to different distributions of biological effects along the axial direction. Currently, there is relatively little information regarding the radial directional difference of biological effects along the heavy ion paths. This study utilized a filter membrane that was quantatively applied with cells to demonstrate a 3D distribution model of irradiation on biological effects in living organisms. Some results have indicated that there is excitatory effect on the non-irradiated regions with energetic ions, which may give new insights into the distribution of biological effects along the paths of heavy ion beams with mid-high energy.

Diffusion radiomics analysis of intratumoral heterogeneity in a murine prostate cancer model following radiotherapy: Pixelwise correlation with histology.

To investigate the biological meaning of apparent diffusion coefficient (ADC) values in tumors following radiotherapy. Five mice bearing TRAMP-C1 tumor were half-irradiated with a dose of 15 Gy. Diffusion-weighted images, using multiple b-values from 0 to 3000 s/mm2 , were acquired at 7T on day 6. ADC values calculated by a two-point estimate and monoexponential fitting of signal decay were compared between the irradiated and nonirradiated regions of the tumor. Pixelwise ADC maps were correlated with histological metrics including nuclear counts, nuclear sizes, nuclear spaces, cytoplasmic spaces, and extracellular spaces. As compared with the nonirradiated region, the irradiated region exhibited significant increases in ADC, extracellular space, and nuclear size, and a significant decrease in nuclear counts (P < 0.001 for all). Optimal ADC to differentiate the irradiated from nonirradiated regions was achieved at a b-value of 800 s/mm2 by the two-point method and monoexponential curve fitting. ADC positively correlated with extracellular spaces (r = 0.74) and nuclear sizes (r = 0.72), and negatively correlated with nuclear counts (r = -0.82, P < 0.001 for all). As a radiomic biomarker, ADC maps correlating with histological metrics pixelwise could be a means of evaluating tumor heterogeneity and responses to radiotherapy. 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:483-489.