High-dose Radiation Research Articles

The effect of geometrical parameters of skin brachytherapy patch source on depth dose distribution using Monte Carlo simulation

Brachytherapy of superficial skin tumors using beta-emitting sources is a method that has been investigated by some researchers in both simulation and experimental studies with promising results. In the current study, the effect of geometrical parameters of some relevant radionuclides including Y-90, Re-188, P-32, and Ho-166 on the depth dose distribution in skin tissue has been investigated through Monte Carlo simulation.MCNPX Monte Carlo code was employed to model the above-mentioned patch sources in cylindrical format and then the effect of patch geometrical parameters including the source-to-skin distance (SSD), patch thickness, and patch diameter on depth dose distribution was assessed through modeling and calculation of the dose inside a cubic phantom mimicking the skin tissue.The obtained results demonstrated that increasing the SSD, patch thickness, and patch diameter (with the same activity) will reduce the depth dose distribution. Changing the SSD has a more significant effect on the dose gradient within the depth than other geometrical parameters. It was also observed that the effect of patch diameter on the skin-delivered dose gets less sensible as the patch size goes beyond the range of beta radiation inside tissue.Finally, it can be concluded that the patch source geometrical parameters can affect the depth dose distribution inside the skin tissue. This fact may be of concern regarding the delivery of a high radiation dose in a single treatment session. Therefore, variations of patch source geometrical parameters should be considered during the skin dose calculation plan.

Novel Deep Learning Denoising Enhances Image Quality and Lowers Radiation Exposure in Interventional Bronchial Artery Embolization Cone Beam CT

In interventional bronchial artery embolization (BAE), periprocedural cone beam CT (CBCT) improves guiding and localization. However, a trade-off exists between 6-second runs (high radiation dose and motion artifacts, but low noise) and 3-second runs (vice versa). This study aimed to determine the efficacy of an advanced deep learning denoising (DLD) technique in mitigating the trade-offs related to radiation dose and image quality during interventional BAE CBCT. This study included BMI-matched patients undergoing 6-second and 3-second BAE CBCT scans. The dose-area product values (DAP) were obtained. All datasets were reconstructed using standard weighted filtered back projection (OR) and a novel DLD software. Objective image metrics were derived from place-consistent regions of interest, including CT numbers of the Aorta and lung, noise, and contrast-to-noise ratio. Three blinded radiologists performed subjective assessments regarding image quality, sharpness, contrast, and motion artifacts on all dataset combinations in a forced-choice setup (-1=inferior, 0=equal; 1=superior). The points were averaged per item for a total score. Statistical analysis ensued using a properly corrected mixed-effects model with post hoc pairwise comparisons. Sixty patients were assessed in 30 matched pairs (age 64±15 years; 10 female). The mean DAP for the 6s and 3s runs was 2199±185 µGym² and 1227±90 µGym², respectively. Neither low-dose imaging nor the reconstruction method introduced a significant HU shift (p≥0.127). The 3s-DLD presented the least noise and superior contrast-to-noise ratio (CNR) (p<0.001). While subjective evaluation revealed no noticeable distinction between 6s-DLD and 3s-DLD in terms of quality (p≥0.996), both outperformed the OR variants (p<0.001). The 3s datasets exhibited fewer motion artifacts than the 6s datasets (p<0.001). DLD effectively mitigates the trade-off between radiation dose, image noise, and motion artifact burden in regular reconstructed BAE CBCT by enabling diagnostic scans with low radiation exposure and inherently low motion artifact burden at short examination times.

CTNI-14. NEOADJUVANT STEREOTACTIC RADIOSURGERY (NASRS) FOR LARGE BRAIN METASTASES (BRM): RESULTS OF AN INTERNATIONAL MULTICENTER PHASE II TRIAL

Abstract BACKGROUND We conducted an international multi-center phase II trial evaluating NASRS for BrM. We hypothesized that radiation necrosis (RN) would be lower than post-operative cavity radiotherapy since the tissues receiving the highest radiation dose are resected in NASRS. METHODS BrM patients with 1 index lesion ( &amp;gt;2 and &amp;lt;5 cm in greatest diameter) suitable for resection, and 9 or less additional BrM (&amp;lt; 3 cm in greatest diameter, not requiring resection) were recruited across 3 centres. SRS was administered a median 3 (range: 2-21) days prior to surgical resection. A single fraction of 15-21 Gy was delivered, targeting the index tumor with a 2mm margin. From a sample of 30 patients, the primary endpoint was the 1-year rate of grade 2+ (G2+) RN from the index lesion. Secondary endpoints included local failure (LF), leptomeningeal disease (LMD) and overall survival (OS). RESULTS We enrolled 35 patients [Mean age (SD): 58.9 (12.9) years, 46% female] between 2018 and 2022. The most common primary histologies were lung (40%), and gastrointestinal (20%) cancers. The median BrM volume prior to surgery was 16.6 cc (range 3.2 -38.0); median index lesion size was 3.2 (range: 1.9-4.5) cm. All participants received planned protocol treatment; n = 30 are currently available for 1 year outcomes. No patients developed G2+ RN; 5 had a LF (1-year rate 38%) at 5-12-months following surgery, all of whom had an en-bloc resection. One patient each developed classic LMD and pachymeningeal failure 3 and 11 months after surgery, respectively. Median OS was 11.5 months. CONCLUSION No patients in our study experienced G2+ RN. The 1-year rate of LF was higher than anticipated, indicating the potential benefit of considering a higher radiation dose or larger margins for improved outcomes.

Long-term Outcomes from a Phase 1 Dose Escalation Study Using Stereotactic Body Radiotherapy for Patients with Low- or Intermediate-risk Prostate Cancer

BackgroundUltrahypofractionated stereotactic body radiation therapy (SBRT) has become a standard treatment intervention for localized prostate cancer. ObjectiveTo report final long-term tumor control outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicities from a single-center phase 1 dose escalation study using SBRT for patients with low- or intermediate-risk prostate cancer. Design, setting and participantsBetween 2009 and 2012, 136 patients were enrolled and treated. The initial dose level was 32.5 Gy in five fractions. Doses were then sequentially escalated to 35 Gy, 37.5 Gy, and 40 Gy in five fractions delivered every other day. Outcome measurements and statistical analysisThe primary endpoint was late treatment-related toxicity. Secondary endpoints included prostate-specific antigen (PSA) failure. Results and limitationsThe median follow-up was 10.5 yr for the 32.5-Gy group, 9.9 yr for the 35-Gy group, 8.2 yr for the 37.5-Gy group, and 7.3 yr for the 40-Gy group. The 8-yr cumulative incidence of PSA failure was 26% for 32.5 Gy, 15% for 35 Gy, 3.4% for 37.5 Gy, and 6.6% for 40 Gy. Higher radiation dose (37.5–40 Gy) and favorable intermediate risk (vs unfavorable intermediate risk) were associated with better PSA recurrence rates (p = 0.011 and 0.002, respectively). The 8-yr actuarial probability rates for survival free from late grade ≥2 toxicity were 94% for GI toxicity and 86% for GU toxicity. No grade 4 events were recorded. Higher dose levels were not associated with higher rates of late grade ≥2 GI (p = 0.2) or GU (p > 0.9) toxicity. ConclusionsSBRT doses ranging from 32.5 to 40 Gy were associated with low incidence of moderate or severe toxicities. Higher doses resulted in superior disease control outcomes 8 yr after treatment. Patient summaryWe investigated the association between the radiotherapy dose used and the rate of control of prostate cancer. We found that higher doses resulted in more favorable outcomes without excess toxicity.This trial is registered on ClinicalTrials.gov as NCT00911118.

Abstract 17405: Biodistribution, Dosimetry, and Specificity of A 99m Tc-Labeled Matrix Metalloproteinase Targeted Radiotracer ( 99m Tc-RP805) for Myocardial Infarct Imaging

Introduction: Activation of matrix metalloproteinase (MMPs) post myocardial infarction (MI) predicts post-MI remodeling. MMP activation in the heart can be detected using 99mTc-RP805 a radiolabel peptidomimetic that binds to the catalytic site. The purpose of this study was to evaluate the biodistribution, dosimetry, and specificity of clinical grade 99mTc-RP805 for first-in-human studies. Methods: Male and female rats (n=24) were injected with 99m Tc-RP805 and euthanized at 1, 3, 7 or 12 hr post injection to determine biodistribution and estimate human dosimetry. Organ activity (%ID/g) was used to estimate whole body and organ effective dose using OLINDA. MI was induced in rats by LAD ligation (n=19) and injected with 99m Tc-RP805 3 days post MI, and rats were euthanized 3 hr after injection in absence (n=9) or presence (n=10) of a 100 x blocking dose of RP805 (257 ug/kg) 30 min prior to radiotracer injection to establish specificity. In vivo SPECT/CT imaging was performed with GMP grade 99m Tc-RP805 in rats post-MI (n=4). Results: The %ID/g for each organ is presented per time point (Fig 1 A). The highest radiation dose was found in male kidneys at 3 hr (%ID/g: 6.11 ± 0.54), female kidneys at 1hr (%ID/g: 6.31 ± 0.88). The estimated total body dose for human males was calculated at 0.172 mSv/mCi and 0.283 mSv/mCi for females, equaling a dose of 3.4 mSv and 5.7 mSv for a 30 mCi injection in males and females, respectively. There is 4 fold increase 99mTc-RP805 uptake in the infarct area compared to the normal LV (Fig 1B) and uptake was blocked with cold compound (ANOVA, p&lt;0.001). In vivo SPECT/CT imaging with a newly synthesized GMP compound demonstrates uptake in the anterior LV (Fig 1C). Conclusions: We have developed and evaluated clinical grade 99m Tc-RP805 for targeted MMP imaging post-MI and demonstrated favorable dosimetry, biodistribution, and specificity for first-in-human imaging.

Gamma-irradiated Aspergillus conidia show a growth curve with a reproductive death phase.

In this study, we evaluated the effects of gamma irradiation on the germination of Aspergillus conidia and mycelial growth using microscopy and predictive microbiological modeling methods. A dose of 0.4kGy reduced the germination rate by 20% compared to the untreated control, indicating interphase death due to the high radiation dose. The number of colonies formed (5.5%) was lower than the germination rate (69%), suggesting that most colonies died after germination. Microscopic observations revealed that mycelial elongation ceased completely in the middle of the growth phase, indicating reproductive death. The growth curves of irradiated conidia exhibited a delayed change in the growth pattern, and a decrease in slope during the early stages of germination and growth at low densities. A modified logistic model, which is a general purpose growth model that allows for the evaluation of subpopulations, was used to fit the experimental growth curves. Dose-dependent waveform changes may reflect the dynamics of the subpopulations during germination and growth. These methods revealed the occurrence of two cell death populations resulting from gamma irradiation of fungal conidia and contribute to the understanding of irradiation-induced cell death in fungi.

Genomics of predictive radiation mutagenesis in oilseed rape: modifying seed oil composition.

Rapeseed is a crop of global importance but there is a need to broaden the genetic diversity available to address breeding objectives. Radiation mutagenesis, supported by genomics, has the potential to supersede genome editing for both gene knockout and copy number increase, but detailed knowledge of the molecular outcomes of radiation treatment is lacking. To address this, we produced a genome re-sequenced panel of 1133 M2 generation rapeseed plants and analysed large-scale deletions, single nucleotide variants and small insertion-deletion variants affecting gene open reading frames. We show that high radiation doses (2000 Gy) are tolerated, gamma radiation and fast neutron radiation have similar impacts and that segments deleted from the genomes of some plants are inherited as additional copies by their siblings, enabling gene dosage decrease. Of relevance for species with larger genomes, we showed that these large-scale impacts can also be detected using transcriptome re-sequencing. To test the utility of the approach for predictive alteration of oil fatty acid composition, we produced lines with both decreased and increased copy numbers of Bna.FAE1 and confirmed the anticipated impacts on erucic acid content. We detected and tested a 21-base deletion expected to abolish function of Bna.FAD2.A5, for which we confirmed the predicted reduction in seed oil polyunsaturated fatty acid content. Our improved understanding of the molecular effects of radiation mutagenesis will underpin genomics-led approaches to more efficient introduction of novel genetic variation into the breeding of this crop and provides an exemplar for the predictive improvement of other crops.

Real-Time Two-Photon Microscopy Reveals Spatially Heterogeneous T Lymphocyte Trafficking in the GI Microenvironment Influenced By GI Tissue Damage Level

Introduction: The trafficking of immune cells in the GI is crucial for tissue immunity and can be targeted for the treatment of immune-related GI damage. Flow cytometry, as the primary technique to identify immune cells in organs such as the GI, has made substantial progress, offering valuable insights into a variety of immune cell subtypes and their microenvironments. However, one major limitation is the destruction of tissue samples during processing, lacking spatial information on immune cells in their microenvironment. Furthermore, there is a lack of information about how stress-induced tissue damage affects T-cell trafficking. In particular, the pre-HCT conditioning regime is essential for identifying the extent of organ damage and donor immune cell trafficking to the GI microenvironment and the subsequent occurrence of Graft vs Host Disease (GVHD). To address this need, it is necessary to develop a real-time imaging method for characterizing immune cells in the GI in an allogeneic bone marrow transplant (BMT) system. Here, we report developing a temperature-controlled Two-photon microscopy (TPM) setup investigating the pattern of T cell trafficking in the GI in real time and how modulating radiation dose affects immune cell trafficking in the preclinical mouse GVHD model of allogeneic BMT. Method: BALB/c Host mice were treated with 8 Gy TBI in 2 fractions, 6 h apart. For the GI dose reduction study (GI-4 Gy), Total Marrow Irradiation (TMI 8:4; 8 Gy to Bone marrow, 4 Gy to rest of the body including GI) was used as described (Darren et al. 2021). Donor B6 T cell Depleted bone marrow cells along with 1 million enriched tdtomato+ T cells were transplanted, and 7 days later, live T cell trafficking in GI was monitored by TPM (Prairie Ultima microscope). Vessels were labeled with QTracker 655, and TPM parameters were set as described (J Brooks et al. 2021). For imaging, a temperature-controlled externalized intestine's intravital imaging (EIII) window was developed (Fig 1.A) and was first evaluated to visualize the three-dimensional basis of Jejunum. It allows continuous blood flow while effectively controlling peristalsis, cardiac and respiratory motion artifacts with minimal tissue damage, delay in tissue degradation. A section of the intestine (Jejunum) was externalized from anesthetized mice and fixed on the EIII window's surface using n-butyl cyanoacrylate veterinary adhesive. The luminal surface was exposed by making an incision along the intestine, carefully avoiding the vascular plexus. The spatial distribution of vessels and tdtomato+ T-cells (green) at different z-stacks was evaluated by imaging through both serosa and luminal sides. GI samples were fixed in 10% NBF, OCT embedded, cryosection (5-10 m), and Anti-MAdCAM1 immunofluorescence (IF) performed using a standard protocol. Results: EIII window usage significantly reduced peristaltic movement, enabling T cells imaging at different depths from serosa to villi crypt (Fig 1.A-B). T cells reside preferentially in the lower crypt region and are affected by the radiation dose given to GI (Fig 1.D-G). T-cell localization at the crypt base region (~ 100µ from serosa) was significantly higher in TBI (8 Gy GI dose) mice than in TMI (4 Gy GI dose). Fig. 1 (F-G) shows T cell distribution at the top, middle, and base of the villi, and in the crypt, during luminal side imaging. Further, microvascular structures were affected at higher radiation dose, as seen by reduced vessel density in 8 Gy over 4 Gy treatments or control (Fig 1.C). Thus, ~50% dose reduction improved vasculature and reduced T cell trafficking. Histological analysis of intestinal tissue with lysozyme and anti-MAdCAM1 staining for confocal imaging further shows reduced crypt damage and T cell trafficking in lower radiation (Fig 1.H). Summary: TPM enabled us to visualize T cells in real-time within the GVHD mouse intestine. Radiation-induced tissue damage-dependent T-cell trafficking was evident in the mouse GI with GVHD and validated through the target receptor of MAdCAM1 endothelial cell expression. The spatial heterogeneity of T cells emphasizes the preferential niche of immune trafficking and associated GI environment and thus, the need for cautious interpretation of GVHD biopsies and warrants further studies on their spatial localization in immune cell-mediated GI diseases.

A Conceptual Model of Dual-Mode Tomography Technique for Dental Diagnostics: Ultrasound and Light Propagation Analysis.

Many advanced imaging modalities, such as magnetic resonance imaging (MRI), X-ray Computed Tomography, Positron Emission Tomography (PET), Ultrasound, Single Photon Emission Computed Tomography (SPECT), and the most recent, Optical Coherence Tomography (OCT), have been developed for identifying dental tissues images and detecting changes in early carious lesions. Some modalities use high doses of radiation and energy to obtain more information, which may be harmful to patient’s health. Most early commercial OCTs had drawbacks such as its bulky size and limited image resolution. In order to overcome these concerns, this paper presents a dual-mode tomography technique that combines OCT and ultrasound method using the COMSOL Multiphysics. The application of an ultrasound device helps overcome the limitation of OCT in detecting the penetration depth of a caries lesion. Several simulations were performed to analyse the light and ultrasonic propagated waves with different diameters of carious lesions. In response to this goal, the combination data of OCT and ultrasound provide a 3D image which offers the best approach for displaying and examining changes in the oral cavity.

Deep-learning soft-tissue decomposition in chest radiography using fast fuzzy C-means clustering with CT datasets

Chest radiography is the most routinely used X-ray imaging technique for screening and diagnosing lung and chest disease, such as lung cancer and pneumonia. However, the clinical interpretation of the hidden and obscured anatomy in chest X-ray images remains challenging because of the bony structures overlapping the lung area. Thus, multi-perspective imaging with a high radiation dose is often required. In this study, to address this problem, we propose a deep-learning soft-tissue decomposition method using fast fuzzy C-means (FFCM) clustering with computed tomography (CT) datasets. In this method, FFCM clustering is used to decompose a CT image into bone and soft-tissue components, which are synthesized into digitally reconstructed radiographs (DRRs) to obtain large amounts of X-ray decomposition datasets as ground truths for training. In the training stage, chest and soft-tissue DRRs are used as input and label data, respectively, for training the network. During the testing, a chest X-ray image is fed into the trained network to output the corresponding soft-tissue image component. To verify the efficacy of the proposed method, we conducted a feasibility study on clinical CT datasets available from the AAPM Lung CT Challenge. According to our results, the proposed method effectively yielded soft-tissue decomposition from chest X-ray images; this is encouraging for reducing the visual complexity of chest X-ray images. Consequently, the finding of our feasibility study indicate that the proposed method can offer a promising outcome for this purpose.

Changes in periapical status of root canal-treated teeth after head and neck IMRT: a retrospective study.

The objective of this retrospective study was to analyze the effect of the intensity modulated radiotherapy (IMRT) of the head and neck region on root canal-treated teeth and their periapical changes due to radiation. Patients undergoing IMRT of the head and neck region were evaluated. Different types of teeth (molars, premolars, incisors and canines) were compared. Panoramic and dental radiographs were used to assess the periapical region of root canal-treated teeth using the periapical index (PAI) before and after radiotherapy (RT) and put in relation to the radiation dose per tooth. Further parameters (patient-, therapy- and tooth-related factors) were included in this study. One hundred and twenty-four root canal-treated teeth (maxilla and mandible) of 51 patients were observed. A radiolucency in the periapical region was seen in 34.7% of the samples before IMRT and an increasing number of 46% after IMRT (p-value 0.092). Clinical or radiological signs of osteoradionecrosis could not be determined. The only statistically significant difference was detected in regions irradiated with less than 40 Gy (p-value 0.045). In regions irradiated with higher doses (>40 Gy), comparable pathologies increased in non-significant numbers. A statistically significant increase of periapical pathologies was detected in premolars of the maxilla. The observations reported here suggest that a high radiation dose during IMRT has no significant consequences on root canal-treated teeth. To compare the success of endodontic treatment before versus after IMRT, further research needs to be done.

Pilot Study: Short Term Impact of Radiation Therapy on Bone Mineral Density and Bone Metabolism

Despite the risk of complications, high dose radiation therapy is increasingly utilized in the management of selected bone malignancies. In this study, we investigate the impact of moderate to high dose radiation (over 50 Gy) on bone metabolism and structure. Between 2015 and 2018, patients with a primary malignant bone tumor of the sacrum that were either treated with high dose definitive radiation only or a combination of moderate to high dose radiation and surgery were prospectively enrolled at a single institution. Quantitative CTs were performed before and after radiation to determine changes in volumetric bone mineral density (BMD) of the irradiated and non-irradiated spine. Bone histomorphometry was performed on biopsies of the irradiated sacrum and the non-irradiated iliac crest of surgical patients using a quadruple tetracycline labeling protocol. In total, 9 patients were enrolled. Two patients received radiation only (median dose 78.3 Gy) and 7 patients received a combination of preoperative radiation (median dose 50.4 Gy), followed by surgery. Volumetric BMD of the non-irradiated lumbar spine did not change significantly after radiation, while the BMD of the irradiated sacrum did (pre-radiation median: 108.0 mg/cm3 (IQR 91.8–167.1); post-radiation median: 75.3 mg/cm3 (IQR 57.1–110.2); p = 0.010). The cancellous bone of the non-irradiated iliac crest had a stable bone formation rate, while the irradiated sacrum showed a significant decrease in bone formation rate [pre-radiation median: 0.005 mm3/mm2/year (IQR 0.003–0.009), post-radiation median: 0.001 mm3/mm2/year (IQR 0.001–0.001); p = 0.043]. Similar effects were seen in the cancellous and endocortical envelopes. This pilot study shows a decrease of volumetric BMD and bone formation rate after high-dose radiation therapy. Further studies with larger cohorts and other endpoints are needed to get more insight into the effect of radiation on bone. Level of evidence: IV.

GEOCHEMICAL VIEW ON “INOFFENSIVE” DEPLETED URANIUM

The interaction of alpha radiation from UO2 micro- and nanoparticles (uraninite) with the substance was visualized using alpha-autoradiography data on A-2 thick-layer nuclear photographic emulsions. The spherical area of action of alpha particles around UO2 micrograins, up to 100 microns in size, is a deeply transformed substance with a high density of radiation defects. The translation of these results on a living organism leads to the conclusion about the specific type of impact of micro- and nanoparticles of depleted uranium, in which prolonged internal irradiation in small doses of the whole organism is combined with catastrophically high doses of alpha radiation in local zones, near micro- and nanoparticles UO2.

Demographic differences in receiving external beam vs brachytherapy radiation in primary ocular cancers.

163 Background: Primary ocular cancers are rare but may be lethal if not treated appropriately. Previously, enucleation was commonly recommended as treatment but has been associated with increased psychosocial disturbances. More recently, brachytherapy and external beam radiation therapy (EBRT) have been used instead due to similar survival outcomes and the opportunity to salvage the eye. Brachytherapy allows for more precise, high dose radiation to be localized to the tumor and minimizes exposure to nearby tissues and, thus, secondary complications. Due to this possible variance of outcomes between radiation therapies, it would be beneficial to examine the demographic differences of those who undergo each modality in the treatment of primary eye cancers. Methods: 2,783 patients diagnosed with a primary ocular cancer that underwent phase I treatment via either EBRT or brachytherapy were isolated using the National Cancer Database from the years 2016 – 2020. Multivariate binary logistic regression and descriptive statistics were used to compare the demographics associated with those who underwent EBRT vs brachytherapy. A p-value of &lt; 0.05 was used to determine significance. Results: Private-insured and Medicare-insured patients were 224.9% and 155.2%, respectively, more likely than uninsured patients to receive brachytherapy. Patients in the third quartile for median household income were 28.4% less likely than those in the upper quartile to receive brachytherapy. Males were 40.2% less likely than females to receive brachytherapy. Compared to White patients, Black and Asian patients were less likely (81.6% and 83.8%) to undergo brachytherapy. Patients identifying as Hispanic/Spanish were 58.4% less likely than non-Hispanic/non-Spanish patients. There were no significant differences found when comparing Charlson-Deyo scores. Conclusions: Patients who are uninsured, in the third quartile for median household income, male, Black, Asian, or Hispanic/Spanish were less likely to undergo brachytherapy compared to EBRT. These findings illustrate that there are significant differences in the groups who undergo recommended radiation modalities for primary ocular cancers. Awareness of these disparities can help us understand the importance of ameliorating healthcare inequalities in the treatment of eye cancers.

MiR-765 as a promising biomarker for low-dose radiation-induced pulmonary fibrosis

High-dose radiation (HDR) is widely used for cancer treatment, but the effectiveness of low-dose radiation (LDR) in the treatment of various diseases is controversial. Therefore, to safely utilize LDR for therapeutic purposes, further research on its numerous biological effects of LDR is required. Interest in the increased use of medical imaging devices or the effects of surrounding living environmental radiation on the human body, particularly on fibrosis, is rapidly increasing. Therefore, this study aimed to verify the relationship between LDR and pulmonary fibrosis by evaluating the changes in fibroblasts after LDR treatment and their associated signaling mechanisms. LDR increased the expression of fibrosis markers COL1A1 and α-SMA, cell proliferation, and migration by activating YAP1 and Twist in fibroblasts. Meanwhile, miRNA was employed as a tool to inhibit LDR-induced fibrosis and it was found that miR-765 simultaneously targeted COL1A1, α-SMA, and YAP1. At the cellular level, miR-765 reduced the proliferation and migration of fibroblasts by suppressing the expression of LDR-induced fibrosis factors COL1A1, α-SMA, and YAP1. The efficacy of miR-765 in vivo was confirmed using bleomycin (BLM)-induced fibrotic mouse model. The characteristics of pulmonary fibrosis were reduced after injection of miR-765-overexpressing cells into BLM-induced fibrotic mice. In addition, the suppression of miR-765 expression in the plasma of patients with pulmonary fibrosis confirmed the negative relationship between pulmonary fibrosis and miR-765 expression. Therefore, this study demonstrates that miR-765 is a potential novel diagnostic biomarker and major target for the development of therapeutic agents to inhibit pulmonary fibrosis.

A comprehensive predictive model for radiation-induced brain injury in risk stratification and personalized radiotherapy of nasopharyngeal carcinoma

Background and purposeRadiation-induced brain injury (RBI) is a severe radiotoxicity for nasopharyngeal carcinoma (NPC) patients, greatly affecting their long-term life quality and survival. We aim to establish a comprehensive predictive model including clinical factors and newly developed genetic variants to improve the precision of RBI risk stratification. Materials and methodsBy performing a large registry-based retrospective study with magnetic resonance imaging follow-up on RBI development, we conducted a genome-wide association study and developed a polygenic risk score (PRS) for RBI in 1189 NPC patients who underwent intensity-modulated radiotherapy. We proposed a tolerance dose scheme for temporal lobe radiation based on the risk predicted by PRS. Additionally, we established a nomogram by combining PRS and clinical factors for RBI risk prediction. ResultsThe 38-SNP PRS could effectively identify high-risk individuals of RBI (P = 1.42 × 10−34). Based on genetic risk calculation, the recommended tolerance doses of temporal lobes should be 57.6 Gy for individuals in the top 10 % PRS subgroup and 68.1 Gy for individuals in the bottom 50 % PRS. Notably, individuals with high genetic risk (PRS > P50) and receiving high radiation dose in the temporal lobes (D0.5CC > 65 Gy) had an approximate 50-fold risk over individuals with low PRS and receiving low radiation dose (HR = 50.09, 95 %CI = 24.27–103.35), showing an additive joint effect (Pinteraction < 0.001). By combining PRS with clinical factors including age, tumor stage, and radiation dose of temporal lobes, the predictive accuracy was significantly improved with C-index increased from 0.78 to 0.85 (P = 1.63 × 10−2). ConclusionsThe PRS, together with clinical factors, could improve RBI risk stratification and implies personalized radiotherapy.

The radiation dose from whole body hybrid imaging (PET–CT) procedures in Sri Lanka: The initial approach towards establishing national diagnostic reference level

Positron emission tomography-Computed tomography (PET–CT) is a hybrid imaging modality that is increasingly used in the diagnosis and staging of cancer. However, due to its hybrid nature, PET–CT is associated with a high radiation dose, which is a concern for patient safety. The aim of this study is to assess the radiation dose from both components of PET and CT to establish diagnostic reference levels (DRLs) that can be used as a tool for dose optimization. This study presents the results of the initial attempt to establish DRLs for body PET–CT procedures among adults and children in Sri Lanka.Data on the injected activity (MBq) and CT radiation dose, volume CT dose index (CTDIvol) and dose length product (DLP) were collected from three PET–CT centers in Sri Lanka and the institutional diagnostic reference level (IDRL) has been established using the median dose distribution for each center and procedure. The median of the individual IDRLs was presented as the national diagnostic reference level (NDRL). Additionally, the mean, standard deviation, 25th, and 75th percentiles of the pooled dose distribution have been presented with and without weight restrictions for adults, as well as for several age and weight bins for pediatrics.The average injected activity of standard adult patients was 187 ± 37 MBq while for pediatric patients aged 1 to 15 years, it ranged between 105 ± 22 and 139 ± 43 MBq. The average CT dose based on CTDIvol and DLP for a standard adult were 3.81 ± 0.86 mGy and 668 ± 140 mGy.cm. The average CTDIvol and DLP ranged between 2.05 ± 0.76–3.65 ± 1.59 and 195 ± 50–411 ± 188 for pediatric patients. The NDRL based on injected activity for adults and pediatric was 198.3 203.3 MBq and 127.7 MBq. The levels of injected activity for adult patients were found to be lower than those published internationally. However, procedures involving both PET and CT in pediatric patients require dose optimization.The present study proposed IDRL and NDRL values for body PET–CT procedures in Sri Lanka. The findings indicate that these values can serve as an effective guide for achieving further optimization in dose, particularly in procedures involving both PET and CT in pediatric patients.

Low dose rate radiation impairs early follicles in young mice

Low-dose radiation is generally considered less harmful than high-dose radiation. However, its impact on ovaries remains debated. Since previous reports predominantly employed low-dose radiation delivered at a high dose rate on the ovary, the effect of low-dose radiation at a low dose rate on the ovary remains unknown. We investigated the effect of low-dose ionizing radiation delivered at a low dose rate on murine ovaries. Three- and ten-week-old mice were exposed to 0.1 and 0.5 Gy of radiation at a rate of 6 mGy/h and monitored after 3 and 30 days. While neither body weight nor ovarian area showed significant changes, ovarian cells were damaged, showing apoptosis and a decrease in cell proliferation after exposure to 0.1 and 0.5 Gy radiation. Follicle numbers decreased over time in both age groups proportionally to the radiation dose. Younger mice were more susceptible to radiation damage, as evidenced by decreased follicles in 3-week-old mice after 30 days of 0.1 Gy exposure, while 10-week-old mice showed reduced follicles only following 0.5 Gy exposure. Primordial or primary follicles were the most vulnerable to radiation. These findings suggest that even low-dose radiation, delivered at a low dose rate, can adversely affect ovarian function, particularly in the early follicles of younger mice.

Patterns of Failure, Low-Volume Relapse, and Subsequent Ablative Management in Locally Advanced Non-Small Cell Lung Cancer Treated With Definitive Chemoradiation and Consolidation Immune Checkpoint Inhibitors

The objective of this study was to describe the patterns of failure, frequency of low-volume relapse (LVR), and candidacy for ablative therapy at time of disease progression (PD) after chemoradiation and consolidative immunotherapy (CRT + ICI) in patients with stage III non-small cell lung cancer. We identified 229 consecutive patients with stage III non-small cell lung cancer treated with CRT + ICI between October 2017 and December 2021 at a single institution. PD was classified as isolated locoregional failure (LRF), isolated distant failure (DF), or synchronous LRF + DF. Any LRF was subclassified as in-field failure, marginal failure, or out-of-field failure. LVR was defined as 3 or fewer sites of PD in any number of organs. Ablative candidates were defined as having 5 or fewer sites of PD radiographically amenable to high-dose radiation or surgery. Time-to-event data were calculated using cumulative incidence analysis and Kaplan-Meier methods. Multivariable Cox modeling was used to examine the correlations between characteristics of relapse and postprogression survival. Of the 229 patients, 119 (52%) had PD. Of these 119 patients, 20 (21%) had isolated LRF, 28 (24%) had synchronous LRF + DF, and 71 (60%) had isolated DF. Of the 48 patients with any LRF, 28 (58%) had in-field failure, 10 (21%) marginal failure, and 10 (21%) out-of-field failure. The cumulative incidence of LRF and DF was 13% (95% CI, 9.2%-18%) and 32% (95% CI, 26%-38%) at 1 year and 19% (95% CI, 14%-24%) and 39% (95% CI, 33%-46%) at 2 years, respectively. Overall, 64 patients (54%) were considered to have LVR. At time of PD, 60 patients (50%) were eligible for ablative therapy. Patients with LVR had longer median survival versus with high-volume relapse (37.4 vs 15.2 months, P < .001). On multivariable analysis, LVR (hazard ratio, 0.32; 95% CI, 0.18-0.56; P < .001) was associated with improved postprogression survival. After CRT + ICI, approximately half of patients experience LVR at time of PD and are candidates for ablative therapies. Prospective trials are needed to validate the optimal treatment strategy for LVR.

Interleaved x-ray imaging: A method for simultaneous acquisition of quantitative and diagnostic digital subtraction angiography.

Flow altering angiographic procedures suffer from ill-defined, qualitative endpoints. Quantitative digital subtraction angiography (qDSA) is an emerging technology that aims to address this issue by providing intra-procedural blood velocity measurements from time-resolved, 2D angiograms. To date, qDSA has used 30 frame/s DSA imaging, which is associated with high radiation dose rate compared to clinical diagnostic DSA (up to 4 frame/s). The purpose of this study is to demonstrate an interleaved x-ray imaging method which decreases the radiation dose rate associated with high frame rate qDSA while simultaneously providing low frame rate diagnostic DSA images, enabling the acquisition of both datasets in a single image sequence with a single injection of contrast agent. Interleaved x-ray imaging combines low radiation dose image frames acquired at a high rate with high radiation dose image frames acquired at a low rate. The feasibility of this approach was evaluated on an x-ray system equipped with research prototype software for x-ray tube control. qDSA blood velocity quantification was evaluated in a flow phantom study for two lower dose interleaving protocols (LD1: and LD2: ) and one conventional (full dose) protocol ( . Dose was measured at the interventional reference point. Fluid velocities ranging from 24 to 45cm/s were investigated. Gold standard velocities were measured using an ultrasound flow probe. Linear regression and Bland-Altman analysis were used to compare ultrasound and qDSA. The LD1 and LD2 interleaved protocols resulted in dose rate reductions of -67.7% and -85.5%, compared to the full dose qDSA scan. For the full dose protocol, the Bland-Altman limits of agreement (LOA) between qDSA and ultrasound velocities were [0.7, 6.7] cm/s with a mean difference of 3.7cm/s. The LD1 interleaved protocol results were similar (LOA: [0.3, 6.9] cm/s, bias: 3.6cm/s). The LD2 interleaved protocol resulted in slightly larger LOA: [-2.5, 5.5] cm/s with a decrease in the bias: 1.5cm/s. Linear regression analysis showed a strong correlation between ultrasound and qDSA derived velocities using the LD1 protocol, with a of , a slope of and an offset of cm/s. Similar values were also found for the LD2 protocol, with a of , a slope of and an offset of cm/s. The interleaved method enables simultaneous acquisition of low-dose high-rate images for intra-procedural blood velocity quantification (qDSA) and high-dose low-rate images for vessel morphology evaluation (diagnostic DSA).