Ultra-low Dose Research Articles

Ultra-low dose computed tomography of the chest in an emergency setting: A prospective agreement study.

Ultra-low dose computed tomography (ULD-CT) assessed by non-radiologists in a medical Emergency Department (ED) has not been examined in previous studies. To (i) investigate intragroup agreement among attending physicians caring for ED patients (i.e., radiologists, senior- and junior clinicians) and medical students for the detection of acute lung conditions on ULD-CT and supine chest X-ray (sCXR), and (ii) evaluate the accuracy of interpretation compared to the reference standard. In this prospective study, non-traumatic patients presenting to the ED, who received an sCXR were included. Between February and July 2019, 91 patients who underwent 93 consecutive examinations were enrolled. Subsequently, a ULD-CT and non-contrast CT were performed. The ULD-CT and sCXR were assessed by 3 radiologists, 3 senior clinicians, 3 junior clinicians, and 3 medical students for pneumonia, pneumothorax, pleural effusion, and pulmonary edema. The non-contrast CT, assessed by a chest radiologist, was used as the reference standard. The results of the assessments were compared within each group (intragroup agreement) and with the reference standard (accuracy) using kappa statistics. Accuracy and intragroup agreement improved for pneumothorax on ULD-CT compared with the sCXR for all groups. Accuracy and intragroup agreement improved for pneumonia on ULD-CT when assessed by radiologists and for pleural effusion when assessed by medical students. In patients with acute lung conditions ULD-CT offers improvement in the detection of pneumonia by radiologists and the detection of pneumothorax by radiologists as well as non-radiologists compared to sCXR. Therefore, ULD-CT may be considered as an alternative first-line imaging modality to sCXR for non-traumatic patients who present to EDs.

Comparison of the efficacy and cost-effectiveness of an immunologically targeted low-dose rituximab protocol with the conventional rheumatoid arthritis protocol in severe pemphigus.

Various dosing protocols of rituximab have been used in pemphigus. B-cell repopulation following rituximab treatment can be considered a forerunner of clinical relapse. Immunologically guided dosing may remove the need for fixed timepoint maintenance dosing, hence being more cost-effective and perhaps safer. To compare the overall efficacy and cost-effectiveness of a low-dose rituximab regimen (500 mg, 2 weeks apart) with immunologically guided, ultralow-dose (200 mg) top-up infusions on immunological relapse vs. the use of a rheumatoid arthritis (RA) protocol with rituximab 500 mg repeat infusion to treat clinical relapse in severe pemphigus, over a 1-year period, METHODS: In total, 23 patients with severe pemphigus were randomized into Group A (RA protocol: 1000 mg given as two doses, 2 weeks apart) and Group B (low-dose rituximab 500 mg given as two doses, 2 weeks apart). Both groups also received short-term oral corticosteroids, and underwent clinical and immunological (3-monthly flow cytometry assessments of B-cell subtypes) monitoring. Group A received a top-up dose of rituximab 500 mg upon clinical relapse, while Group B received an ultralow top-up dose (200 mg) following detection of B-cell repopulation, which was intended to prevent clinical relapse. Outcome parameters [complete remission off treatment (CROT), relapse (clinical and immunological), total corticosteroid dose and direct cost of therapy] were compared. The mean ± SD time to CROT (Group A, 27.1 ± 1.6 weeks; Group B, 26 ± 1.2 weeks, P = 0.09) and the cumulative prednisolone dose (P = 0.28) were comparable between the two groups. In Group A, 3 of 9 (33.3%) patients had clinical relapse (mean ± SD time of 9.3 ± 0.4 months). In Group B, B-cell repopulation was seen in 10 of 11 (90.9%) patients within a mean time of 8.4 ± 2.4 months, and a single top-up dose of 200 mg successfully prevented clinical relapse. The overall cost of therapy was 37.4% cheaper in Group B. An immunologically guided low-dose rituximab regimen can be an equally effective but more affordable alternative to conventional rituximab regimens in pemphigus.

Early results of ultra-low-dose CT-scan for extremity traumas in emergency room.

BackgroundUltra-low dose computed tomography (ULD-CT) was shown to be a good alternative to digital radiographs in various locations. This study aimed to assess the diagnostic sensitivity and specificity of ULD-CT versus digital radiographs in patients consulting for extremity traumas in emergency room.MethodsDigital radiography and ULD-CT scan were performed in patients consulting at the emergency department (February–August 2018) for extremity traumas. Fracture detection was evaluated retrospectively by two blinded independent radiologists. Sensitivity and specificity were evaluated using best value comparator (BVC) and a Bayesian latent class model (LCM) approaches and clinical follow-up. Image quality, quality diagnostic and diagnostic confidence level were evaluated (Likert scale). The effective dose received was calculated.ResultsSeventy-six consecutive patients (41 men, mean age: 35.2±13.2 years), with 31 wrists/hands and 45 ankles/feet traumas were managed by emergency physicians. According to clinical data, radiography had 3 false positive and 10 false negative examinations, and ULD-CT, 2 of each. Radiography and ULD-CT specificities were similar; sensitivities were lower for radiography, with BVC and Bayesian. With Bayesian, ULD-CT and radiography sensitivities were 90% (95% CI: 87–93%) and 76% (95% CI: 71–81%, P<0.0001) and specificities 96% (95% CI: 93–98%) and 93% (95% CI: 87–97%, P=0.84). The inter-observer agreement was higher for ULD-CT for all subjective indexes. The effective dose for ULD-CT and radiography was 0.84±0.14 and 0.58±0.27 µSv (P=0.002) for hand/wrist, and 1.50±0.32 and 1.44±0.78 µSv (P=NS) for foot/ankle.ConclusionsWith an effective dose level close to radiography, ULD-CT showed better detection of extremities fractures in the emergency room and may allow treatment adaptation. Further studies need to be performed to assess impact of such examination in everyday practice.Trial RegistrationClinicalTrials.gov Identifier: NCT04832490.

Strategy for optimizing experimental settings for studying low atomic number colloidal assemblies using liquid phase scanning transmission electron microscopy

Observing processes of nanoscale materials of low atomic number is possible using liquid phase electron microscopy (LP-EM). However, the achievable spatial resolution (d) is limited by radiation damage. Here, we examine a strategy for optimizing LP-EM experiments based on an analytical model and experimental measurements, and develop a method for quantifying image quality at ultra low electron dose De using scanning transmission electron microscopy (STEM). As experimental test case we study the formation of a colloidal binary system containing 30 nm diameter SiO2 nanoparticles (SiONPs), and 100 nm diameter polystyrene microspheres (PMs). We show that annular dark field (DF) STEM is preferred over bright field (BF) STEM for practical reasons. Precise knowledge of the material's density is crucial for the calculations in order to match experimental data. To calculate the detectability of nano-objects in an image, the Rose criterion for single pixels is expanded to a model of the signal to noise ratio obtained for multiple pixels spanning the image of an object. Using optimized settings, it is possible to visualize the radiation-sensitive, hierarchical low-Z binary structures, and identify both components.

Influence of Temperature and Humidity of the Environment where the Concrete Hardening Takes over on the Efficiency of Surface Microdosis Application

Studies have shown the effect of ultra-low doses of surfactants on the compressive strength of cement stone and fine-grained concrete, which harden under conditions of heat-wet treatment, due to lack of research and widespread use of such treatment in concrete technology. It is proved that in this case the effect of ultra-low doses of surfactants is to reduce the number of open pores in cement stone and concrete. Experimental studies have confirmed that the molecules of surfactants, such as sodium oleate, polyhydric alcohol or others, significantly changes the hydrogen content of water used for the manufacture of concrete. This increases the mechanical strength of cement stone and concrete. It is determined that the increase in temperature and humidity of the medium in which the concrete hardens leads to an increase in the effectiveness of ultra-low doses of surfactants on the formation of compressive strength

Evaluation of Ultra-Low-Dose Chest Computed Tomography Images in Detecting Lung Lesions Related to COVID-19: A Prospective Study.

Background: The present study aimed to evaluate the effectiveness of ultra-low-dose (ULD) chest computed tomography (CT) in comparison with the routine dose (RD) CT images in detecting lung lesions related to COVID-19.Methods: A prospective study was conducted during April-September 2020 at Shahid Faghihi Hospital affiliated with Shiraz University of Medical Sciences, Shiraz, Iran. In total, 273 volunteers with suspected COVID-19 participated in the study and successively underwent RD-CT and ULD-CT chest scans. Two expert radiologists qualitatively evaluated the images. Dose assessment was performed by determining volume CT dose index, dose length product, and size-specific dose estimate. Data analysis was performed using a ranking test and kappa coefficient (κ). P<0.05 was considered statistically significant.Results: Lung lesions could be detected with both RD-CT and ULD-CT images in patients with suspected or confirmed COVID-19 (κ=1.0, P=0.016). The estimated effective dose for the RD-CT protocol was 22-fold higher than in the ULD-CT protocol. In the case of the ULD-CT protocol, sensitivity, specificity, accuracy, and positive predictive value for the detection of consolidation were 60%, 83%, 80%, and 20%, respectively. Comparably, in the case of RD-CT, these percentages for the detection of ground-glass opacity (GGO) were 62%, 66%, 66%, and 18%, respectively. Assuming the result of real-time polymerase chain reaction as true-positive, analysis of the receiver-operating characteristic curve for GGO detected using the ULD-CT protocol showed a maximum area under the curve of 0.78.Conclusion: ULD-CT, with 94% dose reduction, can be an alternative to RD-CT to detect lung lesions for COVID-19 diagnosis and follow-up.An earlier preliminary report of a similar work with a lower sample size was submitted to the arXive as a preprint. The preprint is cited as: https://arxiv.org/abs/2005.03347

Radiation Dose Reduction in Head and Neck Computed Tomography Angiography.

The study aims to investigate the feasibility of further radiation dose reduction via the application of a high iodine delivery rate combined with automatic current modulation technology (high noise index) in head and neck computed tomography angiography. Sixty-four patients who underwent routine head and neck computed tomographic angiography were randomly divided into two groups: a low-dose group of 32 cases and an ultra-low-dose group of 32 cases. The same image reconstruction technique was applied in both groups using the 50% adaptive statistical iterative reconstruction method. Quantitative and qualitative image quality assessment of the carotid artery, computed tomographic dose index volume, dose length product, and effective dose of the two groups were analyzed. The two groups were not significantly (P>0.05) different in age, gender, and body mass index. Significant (P<0.001) reduction of radiation dose was observed in all the parameters of computed tomographic dose index volume (18.12%), dose length product (19.91%), and effective dose (19.84%) in the ultra-low-dose group. Quantitative and qualitative image assessment produced similar results between the two groups, except for the higher mean vascular computed tomographic values found in the ultra-low dose group. Application of a higher iodine delivery rate combined with automatic current modulation technology (high noise index) in an existing low tube voltage protocol can further decrease the radiation dose and the total volume of contrast agent while maintaining similar image quality for patients undergoing computed tomography angiography of the head and neck, which can be recommended as the conventional scanning method.

Feasibility of an ultra-low dose contrast media protocol for coronary CT angiography

To evaluate the feasibility of an ultra-low volume contrast media (CM) protocol for coronary computed tomography angiography (CTA). In total, 214 patients receiving coronary CTA were enrolled prospectively and divided into group A (n=107) receiving a conventional dose of CM and group B (n=107) receiving an ultra-low dose. CT values of the right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex artery (LCX) were measured and radiation doses recorded. The image quality was compared between the groups. Changes in renal function indices and proteinuria before, 24, and 72 hours after coronary CTA among those with chronic kidney disease (CKD) were also assessed. There were significant differences in CT values and radiation doses between groups A and B. In group A, the average RCA, LAD, and LCX CT values were 412.5±79.2, 423.5±73.7, and 422.0±88.1 HU, respectively. In group B, the average RCA, LAD, and LCX CT values were 275.2±16.2, 277.8±16.4, and 278.9±16.5 HU, respectively. The radiation dose in the ultra-low protocol recipients (118.70±18.52 mGy·cm) was significantly lower than that used in conventional coronary CTA (131.75±20.96 mGy·cm). The image quality of group B was comparable to that of group A, satisfying the diagnostic requirement. In patients with mild CKD, there were no significant differences in renal functions after coronary CTA. An ultra-low CM protocol was established for coronary CTA, providing comparable image quality and diagnostic yields but significantly lower radiation dose compared with a conventional protocol. This new protocol might be applicable to patients with mild CKD.

PH-Activatable Organic Nanoparticles for Efficient Low-Temperature Photothermal Therapy of Ocular Bacterial Infection.

Low-temperature photothermal therapy (PTT) systems constructed by integrating organic photothermal agents with other bactericidal components that initiate bacterial apoptosis at low hyperthermia possess a promising prospect. However, these multicomponent low-temperature PTT nanoplatforms have drawbacks in terms of the tedious construction process, suboptimal synergy effect of diverse antibacterial therapies, and high laser dose needed, compromising their biosafety in ocular bacterial infection treatment. Herein, a mild PTT nanotherapeutic platform is formulated via the self-assembly of a pH-responsive phenothiazinium dye. These organic nanoparticles with photothermal conversion efficiency up to 84.5% necessitate only an ultralow light dose of 36 J/cm2 to achieve efficient low-temperature photothermal bacterial inhibition at pH 5.5 under 650 nm laser irradiation. In addition, this intelligent mild photothermal nanoplatform undergoes negative to positive charge reversion in acid biofilms, exhibiting good penetration and highly efficient elimination of drug-resistant E. coli biofilms under photoirradiation. Further in vivo animal tests demonstrated efficient bacterial elimination and inflammatory mitigation as well as superior biocompatibility and biosafety of the photothermal nanoparticles in ocular bacterial infection treatment. Overall, this efficient single-component mild PTT system featuring simple construction processes holds great potential for wide application and clinical transformation.

Imaging strategies used in emergency departments for the diagnostic workup of COVID-19 patients during the first wave of the pandemic: a cost-effectiveness analysis

ObjectivesEmergency departments (EDs) were on the front line for the diagnostic workup of patients with COVID-19–like symptoms during the first wave. Chest imaging was the key to rapidly identifying COVID-19 before administering RT-PCR, which was time-consuming. The objective of our study was to compare the costs and organizational benefits of triage strategies in ED during the first wave of the COVID-19 pandemic. MethodsWe conducted a retrospective study in five EDs in France, involving 3712 consecutive patients consulting with COVID-like symptoms between 9 March 2020 and 8 April 2020, to assess the cost effectiveness of imaging strategies (chest radiography, chest computed tomography (CT) scan in the presence of respiratory symptoms, systematic ultra–low-dose (ULD) chest CT, and no systematic imaging) on ED length of stay (LOS) in the ED and on hospital costs. The incremental cost-effectiveness ratio was calculated as the difference in costs divided by the difference in LOS. ResultsCompared with chest radiography, workup with systematic ULD chest CT was the more cost-effective strategy (average LOS of 6.89 hours; average cost of €3646), allowing for an almost 4-hour decrease in LOS in the ED at a cost increase of €98 per patient. Chest radiography (extendedly dominated) and RT-PCR with no systematic imaging were the least effective strategies, with an average LOS of 10.8 hours. The strategy of chest CT in the presence of respiratory symptoms was more effective than the systematic ULD chest CT strategy, with the former providing a gain of 37 minutes at an extra cost of €718. DiscussionSystematic ULD chest CT for patients with COVID-like symptoms in the ED is a cost-effective strategy and should be considered to improve the management of patients in the ED during the pandemic, given the need to triage patients.

First-generation clinical dual-source photon-counting CT: ultra-low-dose quantitative spectral imaging.

Evaluation of image characteristics at ultra-low radiation dose levels of a first-generation dual-source photon-counting computed tomography (PCCT) compared to a dual-source dual-energy CT (DECT) scanner. A multi-energy CT phantom was imaged with and without an extension ring on both scanners over a range of radiation dose levels (CTDIvol 0.4-15.0 mGy). Scans were performed in different modes of acquisition for PCCT with 120 kVp and DECT with 70/Sn150 kVp and 100/Sn150 kVp. Various tissue inserts were used to characterize the precision and repeatability of Hounsfield units (HUs) on virtual mono-energetic images between 40 and 190 keV. Image noise was additionally investigated at an ultra-low radiation dose to illustrate PCCT's ability to remove electronic background noise. Our results demonstrate the high precision of HU measurements for a wide range of inserts and radiation exposure levels with PCCT. We report high performance for both scanners across a wide range of radiation exposure levels, with PCCT outperforming at low exposures compared to DECT. PCCT scans at the lowest radiation exposures illustrate significant reduction in electronic background noise, with a mean percent reduction of 74% (p value ~ 10-8) compared to DECT 70/Sn150 kVp and 60% (p value ~ 10-6) compared to DECT 100/Sn150 kVp. This paper reports the first experiences with a clinical dual-source PCCT. PCCT provides reliable HUs without disruption from electronic background noise for a wide range of dose values. Diagnostic benefits are not only for quantification at an ultra-low dose but also for imaging of obese patients. PCCT scanners provide precise and reliable Hounsfield units at ultra-low dose levels. The influence of electronic background noise can be removed at ultra-low-dose acquisitions with PCCT. Both spectral platforms have high performance along a wide range of radiation exposure levels, with PCCT outperforming at low radiation exposures.

The outcome of radiation therapy as a primary treatment in orbital lymphoma: a systematic review.

BackgroundThe extranodal marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) is the most common orbital and adnexal lymphomas. Radiotherapy is one of the most preferred treatment options for orbital lymphomas since they are localized and radiation sensitive. The objective of this study is to evaluate how radiation therapy affected the outcome of orbital MALT lymphoma.Materials and methodsPRISMA guideline was used to conduct this systematic review of electronic databases (PubMed, EMBASE and Cochrane Library), then we assessed the quality of evidence of each paper.ResultsTwenty-five studies were finally included. 94% studies were intended for definitive therapy and almost all of the studies used external radiation sources. The total doses given to the tumor bed ranged from 4 Gy to 55 Gy and were divided into three groups: ultra-low dose (4–6 Gy), standard-dose (24–30.6 Gy), and high-dose (> 30.6 Gy). 75–90% patients showed CR and local relapse was only reported at 3.5–5%. Higher 5-year PFS was reported in the patients group with lens shielding (90.1% vs. 82.1%) and an increase in Meiboscore after RT courses. Toxicities, including dry eye and cataract, were reported in several patients. Acute toxicities subsided gradually over a few months with artificial tears. The risk of early cataract formation increases in patients who received > 30 Gy and lower in the IMRT group.ConclusionRT is a successful primary definitive therapy for low-grade orbital MALT lymphoma, with a high survival rate, low recurrence rate, and typically acceptable toxicity.

ULTRA-LOW DOSE CONE-BEAM CT INCREASES POSITIVE DIAGNOSIS RATE OF PERIPHERAL NODULE BRONCHOSCOPY WHILE IMPROVING RADIATION SAFETY

TYPE: Late Breaking Abstract TOPIC: Procedures PURPOSE: Cone-beam CT (CBCT) can be used during electromagnetic navigation bronchoscopy (ENB) to improve accuracy and safety of biopsy. Although the added value of CBCT is recognized, there are concerns about radiation exposure. We investigate the impact of a ultra-low-dose CBCT protocol. METHODS: A single institution, retrospective, comparative study of CBCT-ENB for biopsies using two radiation protocols (standard (Gp1) vs ultra-low-dose (Gp2)). We estimated the total E, E attributed to CBCT (E1) and E attributed to fluoroscopy (E2) per lesion from the dose-area-product (conversion factor 0.16 mSv/Gy·cm2). Secondary outcomes were number of CBCT runs and positive diagnosis (PD) rate. RESULTS: From Jan 2015-22, 386 patients (mean age 68.3) underwent CBCT-ENB for biopsy of 452 pulmonary lesions (mean size 19.5 mm): Gp1 121 patients with 138 lesions, Gp2 258 patients with 306 lesions. Total E was 4.85 mSv (Gp1) vs 1.72 mSv (Gp2) (64.5% decrease, p<0.01). E1 was 3.57 mSv (Gp1) vs 1.46 mSv (Gp2) (p<0.01) and E2 was 1.28 mSv (Gp1) vs 0.29 mSv (Gp2) (p<0.01). The number of CBCT runs increased from 3.65 to 5.68 (55.6% increase, p<0.01, dose-per-CBCT-run 0.98 mSv vs 0.26 mSv). PD rate increased from 61.7% to 72.0% (16.7% increase, p=0.05). CONCLUSIONS: The ultra-low dose protocol reduced radiation exposure compared to standard dose protocol. This allowed for more CBCT runs, more accurate tool positioning, and an improved diagnostic rate. CLINICAL IMPLICATIONS: Ultra-low dose CBCT not only reduces radiation exposure, but allows more iterative CBCT runs and improved diagnostic rate and should be adopted more widely. DISCLOSURE: Funded student internship at Philips Image Guided Therapy Systems (Best, The Netherlands) (applies to submitter). Two co-authors are employee's of Philips Image Guided Therapy Systems (Best, The Netherlands). KEYWORD: Interventional pulmonology

PIMA-CT: Physical Model-Aware Cyclic Simulation and Denoising for Ultra-Low-Dose CT Restoration.

A body of studies has proposed to obtain high-quality images from low-dose and noisy Computed Tomography (CT) scans for radiation reduction. However, these studies are designed for population-level data without considering the variation in CT devices and individuals, limiting the current approaches' performance, especially for ultra-low-dose CT imaging. Here, we proposed PIMA-CT, a physical anthropomorphic phantom model integrating an unsupervised learning framework, using a novel deep learning technique called Cyclic Simulation and Denoising (CSD), to address these limitations. We first acquired paired low-dose and standard-dose CT scans of the phantom and then developed two generative neural networks: noise simulator and denoiser. The simulator extracts real low-dose noise and tissue features from two separate image spaces (e.g., low-dose phantom model scans and standard-dose patient scans) into a unified feature space. Meanwhile, the denoiser provides feedback to the simulator on the quality of the generated noise. In this way, the simulator and denoiser cyclically interact to optimize network learning and ease the denoiser to simultaneously remove noise and restore tissue features. We thoroughly evaluate our method for removing both real low-dose noise and Gaussian simulated low-dose noise. The results show that CSD outperforms one of the state-of-the-art denoising algorithms without using any labeled data (actual patients' low-dose CT scans) nor simulated low-dose CT scans. This study may shed light on incorporating physical models in medical imaging, especially for ultra-low level dose CT scans restoration.

POS0652 LONG-TERM EFFECTIVENESS OF ULTRA-LOW DOSES OF RITUXIMAB IN RHEUMATOID ARTHRITIS

BackgroundThe optimal rituximab (RTX) dose for the treatment of rheumatoid arthritis remains unclear. RTX treatment of 1000mg per 6 months and 2000mg per 6 months were shown to be similarly efficacious (1). The REDO trial showed comparable the 6-month efficacy of continued treatment with 500mg and 200mg compared to 1000mg, though formal non-inferiority could not be established (2).ObjectivesTo assess the long-term effects of ultra-low dose RTX (1×500mg and 1×200mg) in RA patients previously responding well to conventional low dose RTX (1×1000mg).MethodsPatients from the REDO trial were invited to participate in this study. Treatment decisions were left at the discretion of the rheumatologist and patient. Disease activity (DAS28-CRP), and medication use (b/tsDMARD, csDMARD, gluccocorticoids [GC]) were collected from start of the trial to censoring in April 2021. The primary outcome was disease activity, secondary outcomes were RTX persistence, RTX doses and intervals, and use of comedication.Disease activity was analyzed using a longitudinal mixed model with random intercepts to account for intra-patient correlations, in two ways: 1. By original randomization and stratification factors (RF/ACPA and csDMARD use). 2. By time-varying total RTX dose received in the year preceding each disease activity measurement, adjusted for current csDMARD or GC use, and RF/ACPA. The original DAS28-CRP non-inferiority (NI) margin of 0.6 was used.Results118 out of 142 REDO patients were included in current analyses (Table 1) Reasons for exclusion were: continuing treatment elsewhere (n=3), no informed consent (n=9) and data yet to be collected in 2 study centers (n=12). Mean follow up was 3.2 years (total of 377 patient-years), with 7 patients switching to another b/tsDMARD (Figure 1) upon which they were censored from disease activity analyses.Table 1.Patient characteristics by original randomization1000mg (n=24)500mg (n=48)200mg (n=46)Age (years)65 (9)64 (11)64 (12)Female15 (63%)28 (58%)34 (74%)Meeting ACR1987 or ACRU/EULAR 2010 RA criteria22 (92%)47 (98%)43 (93%)Disease duration (years)14 (9-24)14 (7-21)13 (8-20)RF or ACPA positive22 (92%)44 (92%)40 (87%)Duration of rituximab use (years)3.0 (1.6-5.5)2.0 (1.0-5.5)3.7 (2.0-5.7)Concomitant csDMARD17 (71%)29 (60%)27 (59%)Previous number of b/tsDMARDs used2 (2-2)2 (1-3)2 (1-2)Previous number of csDMARDs used3 (1-3)2 (1-4)3 (1-3)Oral GC use at baseline3 (13%)8 (17%)5 (11%)Baseline DAS28-CRP2.3 (0.9)2.3 (0.9)2.5 (1.1)Data are n (%), mean (SD), or median (IQR).Figure 1.Rituximab treatment persistence during follow up.Disease activity in both ultra-low dose groups was non-inferior to the 1000mg group, with a mean DAS28-CRP (95% CI) during follow-up of 2.2 (2.0-2.4) in the 1000mg group, 2.2 (2.1-2.4) in the 500mg group and 2.3 (2.2-2.5) in the 200mg group.Analyzed by received RTX dose, lower RTX dose was significantly associated with a higher DAS28-CRP: 0.15 (95% CI: 0.04-0.26) points higher per 1000mg more RTX. The upper limit for relevant RTX doses was below the prespecified NI margin, excluding a relevant effect of RTX dose on disease activity.Median (IQR) yearly RTX dose was 978mg (704mg-1425mg). Final RTX dose per infusion was 200mg in 37 patients (31%), 500mg in 47 (40%) and 1000mg in 34 (29%), with a median (IQR) final interval between infusions of 6.0 (5.7-6.5), 6.2 (6.0-7.4) and 6.4 (6.0-9.6) months respectively. The rate of GC injections was 0.38 (95% CI: 0.32-0.44) per patient-year and initiation rate of oral GC was 0.05 (0.03-0.08) per patient-year.ConclusionA majority of patients treated with ultra-low dose RTX remained on ultra-low doses for up to 4 years, while disease activity remained low and did not relevantly differ between RTX doses, either according to original randomization or by received dose. Switching to other b/tsDMARDS or use of GC was rarely required.

Three-dimensional stacked filter: A non-linear filter for series images obtained using a transmission electron microscope

De-noising is an important issue in quantitative high-resolution transmission electron microscopy (HRTEM), and its roles become even more important in applications such as beam-sensitive materials and dynamic characterisations, where the attainable signal-to-noise ratio (SNR) of HRTEM images is frequently limited. In this study, we introduce a three-dimensional stacked filter (3DSF), a novel non-linear filter in which a series of HRTEM images is stacked into a 3D data cube and then treated with the Wiener filter in the 3D domain. In comparison to the traditional Wiener filter, which is widely used for individual images, this filter can accurately estimate the power spectral density of noise and filter images with a higher SNR, fewer artefacts and greater computation efficiency, which works particularly well for HRTEM images containing periodic information and feature similarities in successive micrographs, as demonstrated by simulated and experimental images of graphene and metal–organic framework (MOF). When applied to an ultra-low dose (∼8 e/Å2) HRTEM image stack of MOF MIL-101, the 3DSF could distinguish 40 consecutive frames, revealing the trajectory of subtle lattice shrinkage during the exposure.

Efficacy and safety of ultra-low dose inhaled melphalan in the treatment of hospitalized patients with COVID-19

Background. One of the most important components of COVID-19 therapy is the suppression of the hyperergic immune response. There is an urgent need of creating the optimal tactics of efficient and safe anti-inflammatory therapy. A new method of treatment of COVID-19 with inhalation of ultra-low (non-cytotoxic) doses of the alkylating drug melphalan is proposed, based on previous experimental, preclinical, and clinical data on its use in severe bronchial asthma.The aim. To evaluate the efficacy and safety of inhalation of ultra-low doses of melphalan in hospitalized patients with COVID-19-associated lung damage.Materials and methods. A prospective, open, controlled, blind for the central expert study was conducted. Sixty adult patients were included, 30 patients were consecutively admitted to the hospital and received nebulized inhalations of 0.1 mg of melphalan for 7 days. Thirty patients of the control group were selected by an independent expert retrospectively using the computer algorithm for selecting «close» patients based on the «case-control» principle. The primary endpoints were the dynamics on the WHO Clinical Improvement Scale and the dynamics of dyspnea according to the modified Borg scale, secondary – assessment of adverse events, dynamics of indicators of clinical, biochemical blood tests, lungs computed tomography data from the beginning of inhalations in the melphalan group and from the corresponding day in the control group.Results. Inhalations of melphalan led to a significant improvement in the clinical condition of patients according to the WHO scale, decrease in the intensity of dyspnea on day 7 of treatment and by the time of discharge, a significant anti-inflammatory effect. Adverse events and dynamics of laboratory parameters did not differ from the control group.Conclusion. The method of treatment of COVID-19 by inhalation of ultra-low doses of the alkylating drug melphalan is safe and leads to a significant clinical improvement of hospitalized patients with COVID-19-associated lung damage.

The influence of a deep learning image reconstruction algorithm on the image quality and auto-analysis of pulmonary nodules at ultra-low dose chest CT: a phantom study

To investigate the effect of a new deep learning image reconstruction (DLIR) algorithm on the detection, characterization and image quality of pulmonary nodules (PNs) in ultra-low dose chest computed tomography (CT) in comparison with the adaptive statistical iterative reconstruction (ASIR-V) algorithm. Nine artificial pulmonary nodules [six ground glass nodules (GGNs) and three solid nodules (SNs); density: -800 HU, -630 HU, 100 HU; diameter: 12 mm, 10 mm, 8 mm] were randomly placed in a thorax anthropomorphic phantom (Lungman, Kyoto Kagaku Inc.) and scanned on a 256-row CT (Revolution CT, GE Healthcare). Eight scans were performed at 70 kVp with different tube currents (20, 30, 50, 70, 90, 100, 120, 150 mA). Raw data were reconstructed using the filtered back projection (FBP), ASIR-V (30%, 50%, 80%) and DLIR (Low, Medium, High; TrueFidelity™) at 0.625 mm thickness. The effective radiation dose was recorded. All images were automatically analyzed using a commercially available artificial intelligence software (Intelligent 4D Imaging System for Chest CT 5.5, YITU Healthcare) and CT value, standard deviation (SD), long and short diameters of each nodule and SD of air (background) were measured. The detection rate, deformation degree (long diameter/short diameter), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of pulmonary nodules were calculated. Nodule CT values were the same in all mA settings for all three types of reconstruction algorithms (all P>0.05). DLIR groups had significantly lower SD and higher SNR and CNR values, with better overall image quality than ASIR-V and FBP groups at each mA, ranging from 65-85% reduction in SD, 67-83% increase in SNR with DLIR-H over 50%ASIR-V and 75-91% reduction in SD and 77-89% increase in SNR with DLIR-H over FBP (all P<0.05). At ultra-low dose conditions (30 mA), the DLIR-H images had the highest detection rate of PNs (100%). In addition, the DLIR-M had a minimal negative effect on the characterization of PNs. DLIR algorithm can be a potential reconstruction technique to optimize image quality and improve detection rate of PNs in ultra-low dose lung screening.

MP06-19 ANTI-TUMOR EFFECT IN BLADDER CANCER MODEL OF TUMOR VASCULATURE-TARGETED 10 B DELIVERY MEDIATED BORON NEUTRON CAPTURE THERAPY

You have accessJournal of UrologyCME1 May 2022MP06-19 ANTI-TUMOR EFFECT IN BLADDER CANCER MODEL OF TUMOR VASCULATURE-TARGETED 10B DELIVERY MEDIATED BORON NEUTRON CAPTURE THERAPY Tohru Yoneyama, Shingo Hatakeyama, Mihoko Sutoh Yoneyama, Taku Yoshiya, Tsuyoshi Uemura, Takehiro Ishizu, Minoru Suzuki, Shingo Hachinohe, Shintaro Ishiyama, Motohiro Nonaka, Michiko N. Fukuda, and Chikara Ohyama Tohru YoneyamaTohru Yoneyama More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Mihoko Sutoh YoneyamaMihoko Sutoh Yoneyama More articles by this author , Taku YoshiyaTaku Yoshiya More articles by this author , Tsuyoshi UemuraTsuyoshi Uemura More articles by this author , Takehiro IshizuTakehiro Ishizu More articles by this author , Minoru SuzukiMinoru Suzuki More articles by this author , Shingo HachinoheShingo Hachinohe More articles by this author , Shintaro IshiyamaShintaro Ishiyama More articles by this author , Motohiro NonakaMotohiro Nonaka More articles by this author , Michiko N. FukudaMichiko N. Fukuda More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002523.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: p-Boronophenylalanine (10BPA) is a powerful 10B drug used in current clinical trials of BNCT. For BNCT to be successful, a high (500 mg/kg) dose of 10BPA must be administered over a few hours. Here, we report BNCT efficacy after rapid, ultralow-dose administration of either tumor vasculature-specific annexin A1-targeting IFLLWQR (IF7)-conjugated 10BPA or borocaptate sodium (10BSH). METHODS: IF7 conjugates of either 10B drugs intravenously injected into MBT2 bladder tumor-bearing mice and biodistribution of 10B in tumors and normal organs analyzed by prompt gamma-ray analysis. Therapeutic effect of IF7-10B drug-mediated BNCT was assessed by either MBT2 bladder tumor bearing C3H/He mice and YTS-1 tumor bearing nude mice. RESULTS: Intravenous injection of IF7C conjugates of either 10B drugs into MBT2 bladder tumor-bearing mice promoted rapid 10B accumulation in tumor tissues and suppressed tumor growth. Moreover, multiple treatments at ultralow (10–20 mg/kg) doses of IF7-10B drug-mediated BNCT significantly suppressed tumor growth in a mouse model of human YTS-1 bladder cancer, with increased Anxa1 expression in tumors and infiltration by CD8-positive lymphocytes. Our findings suggest BNCT treatment induces an immune response by the host against tumor cells, triggering a strong cytotoxic reaction and also inflammatory and immune responses that increase after BNCT upregulate Anxa1 expression in tumor tissues. Moreover, we hypothesize that if the first BNCT treatment upregulates Anxa1 in tumor tissues due to an inflammatory response or induced immunogenicity, more effective 10B accumulation in tumor tissues might occur following the second injection of IF7-10B drugs. Thus, multiple ultralow doses of IF7-10B drug-mediated BNCT likely boost BNCT therapeutic potential. CONCLUSIONS: We conclude that IF7 serves as an efficient 10B delivery vehicle by targeting bladder tumor tissues via the tumor vasculature and could serve as a relevant vehicle for BNCT drugs. Source of Funding: This study was supported by a Center of Innovation program grant for the young scientist collaborative research fund project (no. R02W16) from the Japan Science and Technology Agency and supported by the Japan Society for the Promotion of Science KAKENHI (grants nos. 17K11119, 20K09517, and 19H05556). The study was also supported by the Kobayashi Foundation for Cancer Research and by the Aomori Prefecture Quantum Science Center © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e84 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tohru Yoneyama More articles by this author Shingo Hatakeyama More articles by this author Mihoko Sutoh Yoneyama More articles by this author Taku Yoshiya More articles by this author Tsuyoshi Uemura More articles by this author Takehiro Ishizu More articles by this author Minoru Suzuki More articles by this author Shingo Hachinohe More articles by this author Shintaro Ishiyama More articles by this author Motohiro Nonaka More articles by this author Michiko N. Fukuda More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement PDF DownloadLoading ...

Ultralow-dose CT of the petrous bone using iterative reconstruction technique, tin filter and high resolution detectors allows an adequate assessment of the petrous bone structures

ObjectivesTo assess image quality and radiation dose in computed tomography (CT) studies of the petrous bone done with a scanner using a tin filter, high-resolution detectors, and iterative reconstruction, and to compare versus in studies done with another scanner without a tin filter using filtered back projection reconstruction. Material and methodsThirty two patients (group 1) were acquired with an ultra-low dose CT (32-MDCT, 130kV, tin filter and iterative reconstruction). Images and radiation doses were compared to 36 patients (group 2) acquired in a 16-MDCT (120kV and filtered back-projection). Muscle density, bone density, and background noise were measured. Signal-to-noise ratio (SNR) was calculated. To assess image quality, two independent radiologists subjectively evaluated the visualization of the different structures of the middle and inner ear (0=not visualized, 3=perfectly identified and delimited). Interobserver agreement was calculated. Effective dose at different anatomical levels with the dose-length product was recorded. ResultsIn the quantitative analysis, there were no significant differences in image noise between the two groups. In the qualitative analysis, a similar or slightly lower subjective score was obtained in the delimitation of different structures of the ossicular chain and cochlea in the 32-MDCT, compared to 16-MDCT, with statistically significant differences. Mean effective dose (±standard deviation) was 0.16±0.04mSv for the 32-MDCT and 1.25±0.30mSv for the 16-MDCT. ConclusionsThe use of scanners with tin filters, high-resolution detectors, and iterative reconstruction allows to obtain images with adequate quality for the evaluation of the petrous bone structures with ultralow doses of radiation (0.16±0.04mSv).