Dosimetric validation for prospective clinical trial on GRID collimator-based spatially fractionated radiation therapy: Dose metrics consistency and heterogeneous pattern reproducibility.

PURPOSE: The purpose of this study is to characterize the dosimetric properties of a commercial brass GRID collimator for high energy photon beams including 15 and 10 MV. Then, the difference in dosimetric parameters of GRID beams among different energies and linacs was evaluated. METHOD: A water tank scanning system was used to acquire the dosimetric parameters, including the percentage depth dose (PDD), beam profiles, peak to valley dose ratios (PVDRs), and output factors (OFs). The profiles at various depths were measured at 100 cm source to surface distance (SSD), and field sizes of 10 × 10 cm2 and 20 × 20 cm2 on three linacs. The PVDRs and OFs were measured and compared with the treatment planning system (TPS) calculations. RESULTS: Compared with the open beam data, there were noticeable changes in PDDs of GRID fields across all the energies. The GRID fields demonstrated a maximal of 3 mm shift in dmax (Truebeam STX, 15MV, 10 × 10 cm2). The PVDR decreased as beam energy increases. The difference in PVDRs between Trilogy and Truebeam STx using 6MV and 15MV was 1.5% ± 4.0% and 2.1% ± 4.3%, respectively. However, two Truebeam linacs demonstrated less than 2% difference in PVDRs. The OF of the GRID field was dependent on the energy and field size. The measured PDDs, PVDRs, and OFs agreed with the TPS calculations within 3% difference. The TPS calculations agreed with the measurements when using 1 mm calculation resolution. CONCLUSION: The dosimetric characteristics of high-energy GRID fields, especially PVDR, significantly differ from those of low-energy GRID fields. Two Truebeam machines are interchangeable for GRID therapy, while a pronounced difference was observed between Truebeam and Trilogy. A series of empirical equations and reference look-up tables for GRID therapy can be generated to facilitate clinical applications.

Radiation therapy practice changes in the COVID-19 pandemic era: A pilot study in California.

PURPOSE: This study aims to investigate practice changes among Southern and Northern California's radiation oncology centers during the COVID-19 pandemic. METHODS: On the online survey platform SurveyMonkey, we designed 10 survey questions to measure changes in various aspects of medical physics practice. The questions covered patient load and travel rules; scopes to work from home; new protocols to reduce corona virus disease-2019 (COVID-19) infection risk; availability of telemedicine; and changes in fractionation schedules and/or type of treatment plans. We emailed the survey to radiation oncology centers throughout Northern and Southern California, requesting one completed survey per center. All responses were anonymized, and data were analyzed using both qualitative and quantitative research methods. RESULTS: At the end of a 4-month collection period (July 2, 2021 to October 11, 2021), we received a total of 61 responses throughout Southern and Northern California. On average, 4111 patients were treated per day across the 61 centers. New COVID-19-related department and hospital policies, along with hybrid workflow changes, infectious control policies, and changes in patient load have been reported. Results also showed changes in treatment methods during the pandemic, such as increased use of telemedicine, hypofractionation for palliative, breast cancer, and prostate cancer cases; and simultaneous boosts, compared to sequential boosts. CONCLUSION: Our California radiation oncology center population study shows changes in various aspects of radiation oncology practices during the COVID-19 pandemic. This study serves as a pilot study to identify possible correlations and new strategies that allow radiation oncology centers to continue providing quality patient care while ensuring the safety of both staff and patients.

Three IMRT advanced planning tools: A multi-institutional side-by-side comparison.

PURPOSE: To assess three advanced radiation therapy treatment planning tools on the intensity-modulated radiation therapy (IMRT) quality and consistency when compared to the clinically approved plans, referred as manual plans, which were planned without using any of these advanced planning tools. MATERIALS AND METHODS: Three advanced radiation therapy treatment planning tools, including auto-planning, knowledge-based planning, and multiple criteria optimization, were assessed on 20 previously treated clinical cases. Three institutions participated in this study, each with expertise in one of these tools. The twenty cases were retrospectively selected from Cleveland Clinic, including five head-and-neck (HN) cases, five brain cases, five prostate with pelvic lymph nodes cases, and five spine cases. A set of general planning objectives and organs-at-risk (OAR) dose constraints for each disease site from Cleveland Clinic was shared with other two institutions. A total of 60 IMRT research plans (20 from each institution) were designed with the same beam configuration as in the respective manual plans. For each disease site, detailed isodoseline distributions and dose volume histograms for a randomly selected representative case were compared among the three research plans and manual plan. In addition, dosimetric endpoints of five cases for each site were compared. RESULTS: Compared to the manual plans, the research plans using advanced tools showed substantial improvement for the HN patient cases, including the maximum dose to the spinal cord and brainstem and mean dose to the parotid glands. For the brain, prostate, and spine cases, the four types of plans were comparable based on dosimetric endpoint comparisons. CONCLUSION: With minimal planner interventions, advanced treatment planning tools are clinically useful, producing a plan quality similarly to or better than manual plans, improving plan consistency. For difficult cases such as HN cancer, advanced planning tools can further reduce radiation doses to numerous OARs while delivering adequate dose to the tumor targets.

Evaluation of auto-planning in IMRT and VMAT for head and neck cancer.

PURPOSE: The purposes of this work are to (a) investigate whether the use of auto-planning and multiple iterations improves quality of head and neck (HN) radiotherapy plans; (b) determine whether delivery methods such as step-and-shoot (SS) and volumetric modulated arc therapy (VMAT) impact plan quality; (c) report on the observations of plan quality predictions of a commercial feasibility tool. MATERIALS AND METHODS: Twenty HN cases were retrospectively selected from our clinical database for this study. The first ten plans were used to test setting up planning goals and other optimization parameters in the auto-planning module. Subsequently, the other ten plans were replanned with auto-planning using step-and-shoot (AP-SS) and VMAT (AP-VMAT) delivery methods. Dosimetric endpoints were compared between the clinical plans and the corresponding AP-SS and AP-VMAT plans. Finally, predicted dosimetric endpoints from a commercial program were assessed. RESULTS: All AP-SS and AP-VMAT plans met the clinical dose constraints. With auto-planning, the dose coverage of the low dose planning target volume (PTV) was improved while the dose coverage of the high dose PTV was maintained. Compared to the clinical plans, the doses to critical organs, such as the brainstem, parotid, larynx, esophagus, and oral cavity were significantly reduced in the AP-VMAT (P < 0.05); the AP-SS plans had similar homogeneity indices (HI) and conformality indices (CI) and the AP-VMAT plans had comparable HI and improved CI. Good agreement in dosimetric endpoints between predictions and AP-VMAT plans were observed in five of seven critical organs. CONCLUSION: With improved planning quality and efficiency, auto-planning module is an effective tool to enable planners to generate HN IMRT plans that are meeting institution specific planning protocols. DVH prediction is feasible in improving workflow and plan quality.

Volumetric-based image guidance is superior to marker-based alignments for stereotactic body radiotherapy of prostate cancer.

PURPOSES: The aim of this study was to evaluate a dual marker-based and soft-tissue based image guidance for inter-fractional corrections in stereotactic body radiotherapy (SBRT) of prostate cancer. METHODS/MATERIALS: We reviewed 18 patients treated with SBRT for prostate cancer. An endorectal balloon was inserted at simulation and each treatment. Planning margins were 3 mm/0 mm posteriorly. Prior to each treatment, a dual image guidance protocol was applied to align three makers using stereoscopic x ray images and then to the soft tissue using kilo-voltage cone beam CT (kV-CBCT). After treatment, prostate (CTV), rectal wall, and bladder were delineated on each kV-CBCT, and delivered dose was recalculated. Dosimetric endpoints were analyzed, including V36.25 Gy for prostate, and D0.03 cc for bladder and rectal wall. RESULTS: Following initial marker alignment, additional translational shifts were applied to 22 of 84 fractions after kV-CBCT. Among the 22 fractions, ten fractions exceeded 3 mm shifts in any direction, including one in the left-right direction, four in the superior-inferior direction, and five in the anterior-posterior direction. With and without the additional kV-CBCT shifts, the average V36.25 Gy of the prostate for the 22 fractions was 97.6 ± 2.6% with the kV x ray image alone, and was 98.1 ± 2.4% after applying the additional kV-CBCT shifts. The improvement was borderline statistical significance using Wilcoxon signed-rank test (P = 0.007). D0.03 cc was 45.8 ± 6.3 Gy vs. 45.1 ± 4.9 Gy for the rectal wall; and 49.5 ± 8.6 Gy vs. 49.3 ± 7.9 Gy for the bladder before and after applying kV-CBCT shifts. CONCLUSIONS: Marker-based alignment alone is not sufficient. Additional adjustments are needed for some patients based kV-CBCT.

Dosimetric impact of orthopedic metal artifact reduction (O-MAR) on Spine SBRT patients.

The dosimetric impact of orthopedic metal artifact reduction (O-MAR) on spine SBRT patients has not been comprehensively studied, particularly with spinal prostheses in high-dose gradient regions. Using both phantom and patient datasets, we investigated dosimetric effects of O-MAR in combination of various metal locations and dose calculation algorithms. A physical phantom, with and without a titanium insert, was scanned. A clinical patient plan was applied to the artifact-free reference, non-O-MAR, and O-MAR phantom images with the titanium located either inside or outside of the tumor. Subsequently, five clinical patient plans were calculated with pencil beam and Monte Carlo (iPlan) on non-O-MAR and O-MAR patient images using an extended CT-density table. The dose differences for phantom plans and patient plans were analyzed using dose distributions, dose-volume histograms (DVHs), gamma index, and selected dosimetric endpoints. From both phantom plans and patient plans, O-MAR did not affect dose distributions and DVHs while minimizing metal artifacts. Among patient plans, we found that, when the same dose calculation method was used, the difference in the dosimetric endpoints between non-O-MAR and O-MAR datasets were small. In conclusion, for spine SBRT patients with spinal prostheses, O-MAR image reconstruction does not affect dose calculation accuracy while minimizing metal artifacts. Therefore, O-MAR images can be safely used for clinical spine SBRT treatment planning.

Psychological stress induced zinc accumulation and up-regulation of ZIP14 and metallothionein in rat liver.

BACKGROUND: Zinc is necessary for normal liver function; and vice versa, the liver plays a central role in zinc homeostasis. The aim of present study is to assess the effects of repeated psychological stress (PS) on the zinc metabolism and related mechanism involved in zinc homeostasis in rat liver. METHODS: In present study, we used communication box to create PS model and investigated the serum corticosterone (CORT), zinc level in serum and liver, liver metallothionein (MT) content and ZRT/IRT-like Protein 14 (ZIP14) mRNA expression. RESULTS: The results showed that the serum CORT level increased and serum zinc level decreased significantly after 7 d and 14 d PS treatment. Meanwhile, zinc and MT contents in liver were elevated after 14 d PS exposure, while those in 7 d PS exposure group did not change. ZIP14 mRNA was expressed markedly at 7 d after the onset of PS, while Zip14 mRNA expression in the liver after 14 d PS exposure reached normal level compared with control group. CONCLUSIONS: The results suggest that PS exposure could induce hypozincemia, which might be related to liver zinc accumulation because of high level of MT through glucocorticoid-mediated MT synthesis and ZIP14 expression induced by interleukin-6.

A repository of grade 1 and 2 meningioma MRIs in a public dataset for radiomics reproducibility tests.

PURPOSE: Meningiomas are the most common primary brain tumors in adults with management varying widely based on World Health Organization (WHO) grade. However, there are limited datasets available for researchers to develop and validate radiomic models. The purpose of our manuscript is to report on the first dataset of meningiomas in The Cancer Imaging Archive (TCIA). ACQUISITION AND VALIDATION METHODS: The dataset consists of pre-operative MRIs from 96 patients with meningiomas who underwent resection from 2010-2019 and include axial T1post and T2-FLAIR sequences-55 grade 1 and 41 grade 2. Meningioma grade was confirmed based on the 2016 WHO Bluebook classification guideline by two neuropathologists and one neuropathology fellow. The hyperintense T1post tumor and hyperintense T2-FLAIR regions were manually contoured on both sequences and resampled to an isotropic resolution of 1 × 1 × 1 mm3 . The entire dataset was reviewed by a certified medical physicist. DATA FORMAT AND USAGE NOTES: The data was imported into TCIA for storage and can be accessed at https://doi.org/10.7937/0TKV-1A36. The total size of the dataset is 8.8GB, with 47 519 individual Digital Imaging and Communications in Medicine (DICOM) files consisting of 384 image series, and 192 structures. POTENTIAL APPLICATIONS: Grade 1 and 2 meningiomas have different treatment paradigms and are often treated based on radiologic diagnosis alone. Therefore, predicting grade prior to treatment is essential in clinical decision-making. This dataset will allow researchers to create models to auto-differentiate grade 1 and 2 meningiomas as well as evaluate for other pathologic features including mitotic index, brain invasion, and atypical features. Limitations of this study are the small sample size and inclusion of only two MRI sequences. However, there are no meningioma datasets on TCIA and limited datasets elsewhere although meningiomas are the most common intracranial tumor in adults.

Hippocampal sparing radiation therapy for brain metastases: treatment techniques and clinical implementation.

High doses of radiation to the hippocampus have been correlated with increased cognitive decline following radiation therapy for brain metastases. To mitigate these effects, a variety of hippocampal sparing techniques have been implemented for both whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS). The goal of this review article is to provide a practical resource for the clinical implementation of hippocampal-sparing radiation therapy, starting with a brief background on the function and delineation of the hippocampal structure, as well as radiation effects on the hippocampus and the most widely recommended dose constraints. Considerations for treatment simulation are discussed, including options for cranial immobilization and optional head tilt. Hippocampal sparing has been demonstrated for WBRT using helical TomoTherapy, static intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) with a variety of patient setup positions, beam arrangements, and planning parameters. Tomotherapy has been shown to achieve slightly greater hippocampal sparing in some studies, while VMAT enables the most efficient treatment delivery. Hippocampal sparing has also been evaluated in a wide range of studies for both GammaKnife and linear accelerator (LINAC)-based SRS, with the proximity of metastases to the hippocampus being the most significant predictor of hippocampal dose. The methods and resulting hippocampal doses from these studies on both WBRT and SRS are discussed, as well as the role of automation in hippocampal sparing radiation therapy.

Automatic segmentation of high-risk clinical target volume for tandem-and-ovoids brachytherapy patients using an asymmetric dual-path convolutional neural network.

PURPOSES: Preimplant diagnostic magnetic resonance imaging is the gold standard for image-guided tandem-and-ovoids (T&O) brachytherapy for cervical cancer. However, high dose rate brachytherapy planning is typically done on postimplant CT-based high-risk clinical target volume (HR-CTVCT ) because the transfer of preimplant Magnetic resonance (MR)-based HR-CTV (HR-CTVMR ) to the postimplant planning CT is difficult due to anatomical changes caused by applicator insertion, vaginal packing, and the filling status of the bladder and rectum. This study aims to train a dual-path convolutional neural network (CNN) for automatic segmentation of HR-CTVCT on postimplant planning CT with guidance from preimplant diagnostic MR. METHODS: Preimplant T2-weighted MR and postimplant CT images for 65 (48 for training, eight for validation, and nine for testing) patients were retrospectively solicited from our institutional database. MR was aligned to the corresponding CT using rigid registration. HR-CTVCT and HR-CTVMR were manually contoured on CT and MR by an experienced radiation oncologist. All images were then resampled to a spatial resolution of 0.5 × 0.5 × 1.25 mm. A dual-path 3D asymmetric CNN architecture with two encoding paths was built to extract CT and MR image features. The MR was masked by HR-CTVMR contour while the entire CT volume was included. The network put an asymmetric weighting of 18:6 for CT: MR. Voxel-based dice similarity coefficient (DSCV ), sensitivity, precision, and 95% Hausdorff distance (95-HD) were used to evaluate model performance. Cross-validation was performed to assess model stability. The study cohort was divided into a small tumor group (<20 cc), medium tumor group (20-40 cc), and large tumor group (>40 cc) based on the HR-CTVCT for model evaluation. Single-path CNN models were trained with the same parameters as those in dual-path models. RESULTS: For this patient cohort, the dual-path CNN model improved each of our objective findings, including DSCV , sensitivity, and precision, with an average improvement of 8%, 7%, and 12%, respectively. The 95-HD was improved by an average of 1.65 mm compared to the single-path model with only CT images as input. In addition, the area under the curve for different networks was 0.86 (dual-path with CT and MR) and 0.80 (single-path with CT), respectively. The dual-path CNN model with asymmetric weighting achieved the best performance with DSCV of 0.65 ± 0.03 (0.61-0.70), 0.79 ± 0.02 (0.74-0.85), and 0.75 ± 0.04 (0.68-0.79) for small, medium, and large group. 95-HD were 7.34 (5.35-10.45) mm, 5.48 (3.21-8.43) mm, and 6.21 (5.34-9.32) mm for the three size groups, respectively. CONCLUSIONS: An asymmetric CNN model with two encoding paths from preimplant MR (masked by HR-CTVMR ) and postimplant CT images was successfully developed for automatic segmentation of HR-CTVCT for T&O brachytherapy patients.

Viscoelastic properties of isolated collagen fibrils.

Understanding the viscoelastic behavior of collagenous tissues with complex hierarchical structures requires knowledge of the properties at each structural level. Whole tissues have been studied extensively, but less is known about the mechanical behavior at the submicron, fibrillar level. Using a microelectromechanical systems platform, in vitro coupled creep and stress relaxation tests were performed on collagen fibrils isolated from the sea cucumber dermis. Stress-strain-time data indicate that isolated fibrils exhibit viscoelastic behavior that could be fitted using the Maxwell-Weichert model. The fibrils showed an elastic modulus of 123 ± 46 MPa. The time-dependent behavior was well fit using the two-time-constant Maxwell-Weichert model with a fast time response of 7 ± 2 s and a slow time response of 102 ± 5 s. The fibrillar relaxation time was smaller than literature values for tissue-level relaxation time, suggesting that tissue relaxation is dominated by noncollagenous components (e.g., proteoglycans). Each specimen was tested three times, and the only statistically significant difference found was that the elastic modulus is larger in the first test than in the subsequent two tests, indicating that viscous properties of collagen fibrils are not sensitive to the history of previous tests.

Surviving Over a Decade With Glioblastoma: A Clinical Course Characterized by Multiple Recurrences, Numerous Salvage Treatments, and Novel Use of Cesium-131 Tiles.

The prognosis for patients diagnosed with recurrent glioblastoma (GBM) remains poor, with no clear standard of care regarding salvage therapy. Common approaches include chemotherapy, re-resection, tumor treating fields, and reirradiation. However, most studies have shown these to have limited benefits. Reirradiation is particularly difficult due to concern for increased risk of toxicity to surrounding normal brain tissue. A novel intracranial brachytherapy system called GammaTile® (GT Medical Technologies, Tempe, Arizona) involves the placement of Cesium-131 radioactive tiles in the tumor cavity following maximal safe resection. This allows for a highly conformal dose distribution with rapid fall-off to minimize overlap with prior radiation fields and for the application of radiation directly to the high-risk tumor bed. This case report highlights a patient with GBM who survived 11.5 years through multiple recurrences and discusses the many salvage treatments he received, including bevacizumab, irinotecan, and stereotactic radiosurgery (SRS). This case exemplifies that aggressive systemic and local therapies can work well in select patients allowing for long-term survival with a good quality of life. Further efforts should be made to identify which patients may benefit from these therapies. The case study additionally reports on the use of GammaTile therapy. Due to prior external beam radiation therapy and SRS to the treatment site, further external beam radiation options were limited, and the patient was offered GammaTile as local therapy. Although it did not provide a survival benefit in this case due to progressive disease outside of the field of treatment, GammaTile serves as a valuable option in providing local therapy to patients who can no longer receive further radiation. It should be used with careful consideration in lesions characterized by aggressive local invasion.

Automatic detection and segmentation of multiple brain metastases on magnetic resonance image using asymmetric UNet architecture.

Detection of brain metastases is a paramount task in cancer management due both to the number of high-risk patients and the difficulty of achieving consistent detection. In this study, we aim to improve the accuracy of automated brain metastasis (BM) detection methods using a novel asymmetric UNet (asym-UNet) architecture. An end-to-end asymmetric 3D-UNet architecture, with two down-sampling arms and one up-sampling arm, was constructed to capture the imaging features. The two down-sampling arms were trained using two different kernels (3 × 3 × 3 and 1 × 1 × 3, respectively) with the kernel (1 × 1 × 3) dominating the learning. As a comparison, vanilla single 3D UNets were trained with different kernels and evaluated using the same datasets. Voxel-based Dice similarity coefficient (DSCv), sensitivity (S v), precision (P v), BM-based sensitivity (S BM), and false detection rate (F BM) were used to evaluate model performance. Contrast-enhanced T1 MR images from 195 patients with a total of 1034 BMs were solicited from our institutional stereotactic radiosurgery database. The patient cohort was split into training (160 patients, 809 lesions), validation (20 patients, 136 lesions), and testing (15 patients, 89 lesions) datasets. The lesions in the testing dataset were further divided into two subgroups based on the diameters (small S = 1-10 mm, large L = 11-26 mm). In the testing dataset, there were 72 and 17 BMs in the S and L sub-groups, respectively. Among all trained networks, asym-UNet achieved the highest DSCv of 0.84 and lowest F BM of 0.24. Although vanilla 3D-UNet with a single 1 × 1 × 3 kernel achieved the highest sensitivities for the S group, it resulted in the lowest precision and highest false detection rate. Asym-UNet was shown to balance sensitivity and false detection rate as well as keep the segmentation accuracy high. The novel asym-UNet segmentation network showed overall competitive segmentation performance and more pronounced improvement in hard-to-detect small BMs comparing to the vanilla single 3D UNet.

In vitro fracture testing of submicron diameter collagen fibril specimens.

Mechanical testing of collagenous tissues at different length scales will provide improved understanding of the mechanical behavior of structures such as skin, tendon, and bone, and also guide the development of multiscale mechanical models. Using a microelectromechanical-systems (MEMS) platform, stress-strain response curves up to failure of type I collagen fibril specimens isolated from the dermis of sea cucumbers were obtained in vitro. A majority of the fibril specimens showed brittle fracture. Some displayed linear behavior up to failure, while others displayed some nonlinearity. The fibril specimens showed an elastic modulus of 470 ± 410 MPa, a fracture strength of 230 ± 160 MPa, and a fracture strain of 80% ± 44%. The fibril specimens displayed significantly lower elastic modulus in vitro than previously measured in air. Fracture strength/strain obtained in vitro and in air are both significantly larger than those obtained in vacuo, indicating that the difference arises from the lack of intrafibrillar water molecules produced by vacuum drying. Furthermore, fracture strength/strain of fibril specimens were different from those reported for collagenous tissues of higher hierarchical levels, indicating the importance of obtaining these properties at the fibrillar level for multiscale modeling.

GPR39 protects against corticosterone-induced neuronal injury in hippocampal cells through the CREB-BDNF signaling pathway.

BACKGROUND: The release of zinc from glutamatergic terminals in the hippocampal CA3 region can activate postsynaptic GPR39 receptors and regulate cognition and depression. However, the role and mechanism of GPR39 in the stress-induced depression is still poorly understood. METHODS: In this study, hippocampal cells (HT-22) were treated with corticosterone (CORT). Then the effects of stress on the activity, mitochondrial function and apoptosis of HT-22 cells were observed. The effects of GPR39 on CORT-induced stress injury were analyzed by both siRNA and agonist (TC-G-1008). RESULTS: Compared with the 500 nM CORT group, the cell viability, apoptosis, mitochondrial membrane potential, and expression levels of BCL-2, CREB and BDNF mRNA were significantly decreased in the GPR39 siRNA+500 nM CORT group, while the expression levels of caspase3, caspase9, AIF and BAX mRNA were significantly increased in the GPR39 siRNA+500 nM CORT group. Compared with the 1 µM CORTgroup, the cell viability, apoptosis, mitochondrial membrane potential, and expression levels of BCL-2, CREB and BDNF were significantly increased in the GPR39 agonist+1 µΜ CORT group, while the expression levels of caspase3, caspase9, AIF and BAX mRNA were significantly decreased in the GPR39 siRNA+500 nM CORT group. Compared with the control group, the mRNA and protein levels of GPR39, CREB and BDNF were significantly increased, and the mRNA and protein levels of CREB and BDNF were significantly decreased after 50 µM zinc sulfate treatment for 6 h. CONCLUSIONS: GPR39 may play a neuroprotective role in CORT-induced cell injury via the improvement of CREB-BDNF expression, by inhibiting pro-apoptotic proteins and by upregulating anti-apoptotic proteins.

Technical Note: Characterization of x-ray beam profiles for a fluoroscopic system incorporating copper filtration.

PURPOSE: The goal of this study was to investigate x-ray beam profiles at various water depths to characterize the two-dimensional x-ray dose distribution, allowing for off-axis and out-of-field radiation dose estimation for a wide range of x-ray beam spectra commonly encountered in fluoroscopically guided interventional procedures. METHODS: A Siemens Artis interventional fluoroscope was operated in a service mode to generate a continuous x-ray beam at fixed x-ray beam spectra, defined by their kVp and the thickness of additional copper filtration. A PTW scanning water tank with a diode detector was used to measure the x-ray beam profiles at several depths in water at various fields of view and x-ray beam spectra, both parallel and perpendicular to the anode-cathode axis direction. RESULTS: X-ray beam profiles, including out-of-field tails, were characterized for a wide range of beam qualities. The anode heel effect was pronounced even at depth, resulting in large dose variations across the x-ray field; this effect was even more definite at large fields of view, at higher kVps, and in the absence of additional copper filtration. CONCLUSIONS: This study investigated and characterized 2D radiation dose deposition in water from x-ray beam spectra commonly used by modern fluoroscopes in interventional procedures. This knowledge can be applied to manual dosimetry calculations or can be used to refine the accuracy of automated dose mapping tools or Monte Carlo simulations of the radiation dose to soft tissue within the x-ray field and to tissue adjacent to the primary beam. Additionally, this study illustrates a substantial reduction of the anode heel effect by using moderate amounts of additional copper filtration to harden the x-ray beam spectrum.

Stress-strain experiments on individual collagen fibrils.

Collagen, a molecule consisting of three braided protein helices, is the primary building block of many biological tissues including bone, tendon, cartilage, and skin. Staggered arrays of collagen molecules form fibrils, which arrange into higher-ordered structures such as fibers and fascicles. Because collagen plays a crucial role in determining the mechanical properties of these tissues, significant theoretical research is directed toward developing models of the stiffness, strength, and toughness of collagen molecules and fibrils. Experimental data to guide the development of these models, however, are sparse and limited to small strain response. Using a microelectromechanical systems platform to test partially hydrated collagen fibrils under uniaxial tension, we obtained quantitative, reproducible mechanical measurements of the stress-strain curve of type I collagen fibrils, with diameters ranging from 150-470 nm. The fibrils showed a small strain (epsilon < 0.09) modulus of 0.86 +/- 0.45 GPa. Fibrils tested to strains as high as 100% demonstrated strain softening (sigma(yield) = 0.22 +/- 0.14 GPa; epsilon(yield) = 0.21 +/- 0.13) and strain hardening, time-dependent recoverable residual strain, dehydration-induced embrittlement, and susceptibility to cyclic fatigue. The results suggest that the stress-strain behavior of collagen fibrils is dictated by global characteristic dimensions as well as internal structure.

miR-212 mediates counter-regulation on CRH expression and HPA axis activity in male mice.

The mechanisms of hypothalamic-pituitary-adrenal (HPA) axis regulation have been studied persistently but still are not elucidated. Considering the emerging roles of microRNA in stress response, we conducted a microRNA microarray in mice hypothalamus to identify the potential role of microRNAs in regulating the HPA axis. In total, 41 microRNAs changed during heat stress in which we found that miR-212 contains a binding sequence with corticotropin-releasing hormone (Crh) 3'UTR according to a sequence analysis. We observed that miR-212 expression in the hypothalamus was escalated by repeated heat and restraint stress. By overexpression or inhibition of miR-212 and the dual-luciferase reporter assay, we proved that miR-212 could bind with Crh 3'UTR to regulate its expression in mice hypothalamus primary cells and in the hippocampus neuron cell line HT-22. In addition, we injected miR-212 agomir or antagomir in mice hypothalamus to overexpress or inhibit miR-212, which leads to alterations of CRH expression and HPA axis activity in vivo Furthermore, miR-212 and CRH were both transcribed by the cAMP response element-binding protein (CREB). Overexpression and inhibition of miR-212 affect CREB-dependent CRH expression. Taken together, our results suggest an inhibitory role of miR-212 on the HPA axis, which acts in a counter-regulatory manner.

Percent depth doses and X-ray beam characterizations of a fluoroscopic system incorporating copper filtration.

PURPOSE: In this investigation, we sought to characterize X-ray beam qualities and quantitate percent depth dose (PDD) curves for fluoroscopic X-ray beams incorporating added copper (Cu) filtration, such as those commonly used in fluoroscopically guided interventions (FGI). The intended application of this research is for dosimetry in soft tissue from FGI procedures using these data. METHODS: All measurements in this study were acquired on a Siemens (Erlangen, Germany) Artis zeego fluoroscope. X-ray beam characteristics of first half-value layer (HVL), second HVL, homogeneity coefficients (HCs), backscatter factors (BSFs) and kVp accuracy and precision were determined to characterize the X-ray beams used for the PDD measurements. A scanning water tank was used to measure PDD curves for 60, 80, 100, and 120 kVp X-ray beams with Cu filtration thicknesses of 0.0, 0.1, 0.3, 0.6, and 0.9 mm at 11 cm, 22 cm, and 42 cm nominal fields of view, in water depths of 0 to 150 mm. RESULTS: X-ray beam characteristics of first HVLs and HCs differed from previous published research of fluoroscopic X-ray beam qualities without Cu filtration. PDDs for 60, 80, 100, and 120 kVp with 0 mm of Cu filtration were comparable to previous published research, accounting for differences in fluoroscopes, geometric orientation, type of ionization chamber, X-ray beam quality, and the water tank used for data collection. PDDs and X-ray beam characteristics for beam qualities with Cu filtration are presented, which have not been previously reported. CONCLUSIONS: The data sets of X-ray beam characteristics and PDDs presented in this study can be used to estimate organ or soft tissue doses at depth involving similar beam qualities or to compare with mathematical models.

Physiological stress-induced corticosterone increases heme uptake via KLF4-HCP1 signaling pathway in hippocampus neurons.

Iron overload has attracted much attention because of its adverse effect in increasing the risk of developing several neurodegenerative disorders. Under various pathologic conditions, a lot of heme are released. The aggregation of heme is more neurotoxic than that of iron released from the heme breakdown. Our previous studies demonstrated that psychological stress (PS) is a risk factor of cerebral iron metabolism disorders, thus causing iron accumulation in rat brains. In the present study, we found PS could increase heme uptake via heme carrier protein 1 (HCP1) in rat brains. We demonstrated that Glucocorticoid (GC), which is largely secreted under stress, could up-regulate HCP1 expression, thus promoting heme uptake in neurons. We also ascertained that HCP1 expression can be induced by GC through a transcription factor, Krüppel-like factor 4 (KLF4). These results may gain new insights into the etiology of heme uptake and iron accumulation in PS rats, and find new therapeutic targets of iron accumulation in Parkinson's disease or Alzheimer's disease.