Dose calculation accuracy in proximity of a pacemaker: A multicenter study with threecommercial treatment planning systems

This study compares Treatment Planning System (TPS) out of field dose calculation on a pacemaker (PMK) during external beam radiotherapy treatment. We consider four TPSs (Elekta-Monaco, Oncentra- Masterplan and two Philips-Pinnacle3) commissioned for two linacs (Elekta Sinergy and Varian Clinac) delivering two test beams (a highly modulated one and a square field) and two clinical breast plans. To calculate and measure dose to a PMK we built a Real Water3 phantom with a PMK embedded in it. Measures are performed with thermo-luminescent dosimeters and Mosfet dosimeters. We evaluate differences between TPS calculated values for the dose to the PMK (both point dose and dose-volume histogram parameters) when the PMK is positioned in the first 10 cm outside the radiation fields. TPS calculation accuracy is evaluated comparing such values with measures. Differences in TPS calculations are on average 3.5 cGy Gy^-1 for the modulated beam, and always lower than 2 cGy Gy^-1 for the square beam. TPS dose calculation depends mostly on the TPS algorithm and model rather than the linac commissioned. TPSs considered show different degrees of calculation accuracy. In the first 4 cm to the field edge three out of four TPSs are in good agreement with measurements in the square beam, but only one keeps the agreement in the modulated beam: the others show over and underestimations up to +20% −40%. The same accuracy is found considering a homogeneous phantom. Our results confirm what reported in previous studies and highlight the impact of TPS commissioning.     

Effect of ligand congeniality on energy transfer reaction between photo-excited tris(bipyridine)ruthenium(II) and chromate(III) complexes in aqueous solutions

Energy-transfer rate-constants from photo-excited [Ru(N–N)₃]²⁺ (N–N = 2,2′-bipyridine (bpy), 4,4′-dimethyl-2,2′-bipyridine (4dmb), 5,5′-dimethyl-2,2′-bipyridine (5dmb)) to [Cr(O–O)₃]³⁻ (O–O²⁻ = ox²⁻ ((COO⁻)₂), mal²⁻ (CH₂(COO⁻)₂)) and [Cr(CN)₆]³⁻ in encounter complexes were evaluated in aqueous solutions containing alkali metal ion. The rate constant depends on the molecular size of the ruthenium(II) complex: 1.8 × 10⁸ s⁻¹ for [Ru(bpy)₃]²⁺ (molecular radius, r = 5.8 Å), 1.4 × 10⁸ s⁻¹ for [Ru(5dmb)₃]²⁺ (r = 6.1 Å) and 0.96 × 10⁸ s⁻¹ for [Ru(4dmb)₃]²⁺ (r = 6.7 Å) in the system of [Ru(N–N)₃]²⁺–[Cr(ox)₃]³⁻ in aqueous solution. However, the rate constant is much more sensitive to the chromate(III) complex than to ruthenium(II) complex; 1.8 × 10⁸ s⁻¹ and 0.43 × 10⁸ s⁻¹ for [Cr(ox)₃]³⁻ (r = 4.0 Å) and [Cr(mal)₃]³⁻ (r = 4.2 Å) in the [Ru(bpy)₃]²⁺–[Cr(O–O)₃]³⁻ systems, respectively. We conclude that the congeniality between the donor’s and acceptor’s ligands in encounter complex plays an important role in energy transfer in aqueous solution.     

Eye lens dose correlations with personal dose equivalent and patient exposure in paediatric interventional cardiology performed with a fluoroscopic biplane system

PurposeTo analyse the correlations between the eye lens dose estimates performed with dosimeters placed next to the eyes of paediatric interventional cardiologists working with a biplane system, the personal dose equivalent measured on the thorax and the patient dose.MethodsThe eye lens dose was estimated in terms of H_p(0.07) on a monthly basis, placing optically stimulated luminescence dosimeters (OSLDs) on goggles. The H_p(0.07) personal dose equivalent was measured over aprons with whole-body OSLDs. Data on patient dose as recorded by the kerma-area product (P_KA) were collected using an automatic dose management system. The 2 paediatric cardiologists working in the facility were involved in the study, and 222 interventions in a 1-year period were evaluated. The ceiling-suspended screen was often disregarded during interventions.ResultsThe annual eye lens doses estimated on goggles were 4.13 ± 0.93 and 4.98 ± 1.28 mSv. Over the aprons, the doses obtained were 10.83 ± 0.99 and 11.97 ± 1.44 mSv. The correlation between the goggles and the apron dose was R² = 0.89, with a ratio of 0.38. The correlation with the patient dose was R² = 0.40, with a ratio of 1.79 μSv Gy⁻¹ cm⁻². The dose per procedure obtained over the aprons was 102 ± 16 μSv, and on goggles 40 ± 9 μSv. The eye lens dose normalized to P_KA was 2.21 ± 0.58 μSv Gy⁻¹ cm⁻².ConclusionsMeasurements of personal dose equivalent over the paediatric cardiologist’s apron are useful to estimate eye lens dose levels if no radiation protection devices are typically used.     

Utilisation des gels de polymères MAGIC pour la dosimétrie d’une source non scellée d’yttrium 90

Polymer gels are relative chemical dosimeters. They allow to access to three-dimensional dose distribution. The aim of this study has been to investigate the preparation and the use of a polymer gel with a tissue equivalent density known as MAGIC gel from magnetic resonance imaging and x-ray computed tomography for non-sealed source dosimetry. This kind of gel is “normoxic” because it can be manufactured and used in normal room atmosphere. In the first part of this study, its accuracy and sensibility were studied using external beam irradiation by photons. Spin-spin relaxation rate (R₂) and Computed Tomography (CT) number had been used to record gel responses. Using the same manufacture process, radiolabelled gels composed of 95% MAGIC gel and 5% of ⁹⁰Y termed ⁹⁰Y-MAGIC₉₅, with varying activity ranged from 0 to 30 MBq were made. In case of photon external beam irradiation, a linear response is observed whatever the calibration method and the imaging system used (the correlation coefficient r² > 0.98 in all cases). ⁹⁰Y-MAGIC₉₅ radiolabelled gel responses were recorded after 28, 76 and 124 h. The R₂/dose curves are not linear; three phases can be described, the first being linear with a slow slope (0.14 s⁻¹ Gy⁻¹ instead of 0.41 s⁻¹ Gy⁻¹ for external beam irradiation of the same gel batch). This study shows safety of radiolabelled MAGIC gels manufacturing process and their large dosimetric feasibility. ⁹⁰Y-MAGIC₉₅ gel response appears to be reproducible and related to the absorbed dose, thus this gel is a promising tool for non-sealed source dosimetry.     

Commissioning and performance testing of the first prototype of AlignRT InBore™ a Halcyon™ and Ethos™-dedicated surface guided radiation therapy platform

PurposeTo commission and assess the performance of AlignRT InBore™, a Halcyon™ and Ethos™-dedicated Surface Guided Radiation Therapy (SGRT) platform which combines ceiling-mounted cameras for patient setup and bore-mounted cameras for in-bore tracking.MethodsTo check the potential impact of InBore™ cameras on dose delivery, 16 SRS, H&N, breast and pelvis patients’ quality assurance (QA) treatment plans were measured with/without AlignRT InBore™ and using ArcCHECK® and SRS MapCHECK®. Impact on image quality was determined using Catphan® 540 phantom and considering all available MV and CBCT protocols (head, breast, chest and pelvis). The stability, accuracy and overall performance of AlignRT InBore™ was assessed using an MV Cube and anthropomorphic phantoms.ResultsComparison of 2D dose distributions with/without AlignRT InBore™ showed no impact on treatment delivery for all 16 QA checks (p-value > 0.25). 2D and CBCT images showed no artefacts or change in the contrast-to-noise ratio, resolution and noise values measured with Catphan® 540. Anti-collision sensors were unaffected by the bore-mounted cameras. Additionally, AlignRT InBore™ cameras allowed for motion detection with sub-0.5 mm accuracy and sub-0.4 mm stability with surface coverage of >50 × 60 × 35 cc. Accurate transition (sub-0.3 mm) from virtual to treatment isocentres was achieved. Finally, Halcyon™ rotations during CBCT and beam delivery resulted in limited camera vibrations with translation uncertainty <0.5 mm in left-right and anterior-posterior directions and <0.1 mm in head-feet direction.ConclusionAlignRT InBore™ provides SGRT setup and intrafraction monitoring capabilities with a performance comparable to standard SGRT solutions while having no adverse effect on Halcyon™.     

Dosimetric characterization of a novel 90Y source for use in the conformal superficial brachytherapy device

PurposeTo characterize the dose distribution in water of a novel beta-emitting brachytherapy source for use in a Conformal Superficial Brachytherapy (CSBT) device.Methods and materialsYttrium-90 (⁹⁰Y) sources were designed for use with a uniquely designed CSBT device. Depth dose and planar dose measurements were performed for bare sources and sources housed within a 3D printed source holder. Monte Carlo simulated dose rate distributions were compared to film-based measurements. Gamma analysis was performed to compare simulated and measured dose rates from seven ⁹⁰Y sources placed simultaneously using the CSBT device.ResultsThe film-based maximum measured surface dose rate for a bare source in contact with the surface was 3.35 × 10^–7 cGy s⁻¹ Bq⁻¹. When placed in the source holder, the maximum measured dose rate was 1.41 × 10^–7 cGy s⁻¹ Bq⁻¹. The Monte Carlo simulated depth dose rates were within 10% or 0.02 cm of the measured dose rates for each depth of measurement. The maximum film surface dose rate measured using a seven-source configuration within the CSBT device was 1.78 × 10⁻⁷ cGy s⁻¹ Bq⁻¹. Measured and simulated dose rate distribution of the seven-source configuration were compared by gamma analysis and yielded a passing rate of 94.08%. The gamma criteria were 3% for dose-difference and 0.07056 cm for distance-to-agreement. The estimated measured dose rate uncertainty was 5.34%.Conclusions⁹⁰Y is a unique source that can be optimally designed for a customized CSBT device. The rapid dose falloff provided a high dose gradient, ideal for treatment of superficial lesions. The dose rate uncertainty of the ⁹⁰Y-based CSBT device was within acceptable brachytherapy standards and warrants further investigation.     

Comparison between two treatment planning systems for volumetric modulated arc therapy optimization for prostate cancer

PurposeTo investigate the performances of two commercial treatment planning systems (TPS) for Volumetric Modulated Arc Therapy (VMAT) optimization regarding prostate cancer. The TPS were compared in terms of dose distributions, treatment delivery parameters and quality control results.Materials and methodsFor ten patients, two VMAT plans were generated: one with Monaco TPS (Elekta) and one with Pinnacle TPS (Philips Medical Systems). The total prescribed dose was 78 Gy delivered in one 360° arc with a Synergy^® linear accelerator equipped with a MLCi2^®.ResultsVMAT with Monaco provided better homogeneity and conformity indexes but lower mean dose to PTVs than Pinnacle. For the bladder wall (p = 0.019), the femoral heads (p = 0.017), and healthy tissues (p = 0.005), significantly lower mean doses were found using Monaco. For the rectal wall, VMAT with Pinnacle provided a significantly (p = 0.047) lower mean dose, and lower dose into 50% of the volume (p = 0.047) compared to Monaco. Despite a greater number of monitor units (factor 1.5) for Monaco TPS, the total treatment time was equivalent to that of Pinnacle. The treatment delivery parameter analysis showed larger mean MLC area for Pinnacle and lower mean dose rate compared to Monaco. The quality control results gave a high passing rate (>97.4%) for the gamma index for both TPS but Monaco provided slightly better results.ConclusionFor prostate cancer patients, VMAT treatment plans obtained with Monaco and Pinnacle offered clinically acceptable dose distributions. Further investigations are in progress to confirm the performances of the two TPS for irradiating more complex volumes.     

Investigation of Foscan® interactions with plasma proteins

The present study investigates the interaction of the second generation photosensitizer Foscan® with plasma albumin and lipoproteins. Spectroscopic studies indicated the presence of monomeric and aggregated Foscan® species upon addition to plasma protein solutions. Kinetics of Foscan® disaggregation in albumin-enriched solutions were very sensitive to the protein concentration and incubation temperature. Kinetic analysis demonstrated that two types of Foscan® aggregated species could be involved in disaggregation: dimers with a rate constant of k₁ = (2.30 ± 0.15) × 10⁻³ s⁻¹ and higher aggregates with rate constants varying from (0.55 ± 0.04) × 10⁻³ s⁻¹ for the lowest to the (0.17 ± 0.02) × 10⁻³ s⁻¹ for the highest albumin concentration. Disaggregation considerably increased with the temperature rise from 15 °C to 37 °C. Compared to albumin, Foscan® disaggregation kinetics in the presence of lipoproteins displayed poorer dependency on lipoprotein concentrations and smaller variations in disaggregation rate constants. Gel-filtration chromatography analysis of Foscan® in albumin solutions demonstrated the presence of aggregated fraction of free, non-bound to protein Foscan® and monomeric Foscan®, bound to protein.     

Oxytocin receptors in the porcine endometrium during the estrous cycle and early pregnancy

Oxytocin (OT) receptors in the porcine endometrium were investigated at four stages of the estrous cycle (Days (D) 0, 5, 10 and 15, n = 3), and at two stages of early pregnancy (D5 and D15 after mating, n = 3) by a radioreceptor assay using ¹²⁵I-labeled OT antagonist [d(CH₂)₅,Tyr(Me)²,Thr⁴,Tyr-NH⁹₂]-vasotocin. Binding specificity was demonstrated by displacement with four peptides related to oxytocin ([Arg⁷]-vasopressin, [Thr⁴,Gly⁷]-OT, OVT, OT) and two peptides unrelated to oxytocin (luteinizing hormone-releasing hormone, [Ile³]-pressinoic acid (tocinoic acid)). The dissociation constant (K_d) of endometrial OT receptors on D0 (0.59 ± 0.10 nM) was similar to those on D10 and D15 (D10, 0.75 ± 0.21; D15, 0.60 ± 0.14 nM; mean ± SEM). In the early luteal stage (D5), K_d (2.41 ± 0.24 nM) was higher than on D0, D10 and D15 (P < 0.01). In early pregnancy, K_d values were 3.25 ± 0.29 nM on D5 and 2.44 ± 0.44 nM on D15. Binding site concentration (B_max) on D0 (910.0 ± 25.1 fmol mg⁻¹ protein) was significantly higher than on D5 and D10 (D5, 322.5 ± 71.7; D10, 147.5 ± 25.8 fmol mg⁻¹ protein; P < 0.01) of the estrous cycle and D5 and D15 (D5, 302.5 ± 82.6; D15, 315.0 ± 20.1 fmol mg⁻¹ protein; P < 0.01) of early pregnancy. In the two stages of early pregnancy, B_max values were constant and similar to that on D5 of the early luteal stage.Our results reveal the existence of specific OT binding sites in the porcine endometrium during the estrous cycle and early pregnancy. Furthermore, the fluctuation in the binding of OT to the endometrium during the different stages of the estrous cycle suggests that OT plays an important role in regulating the estrous cycle of the pig as seen in other animals.     

Response of the ArcCHECK® device at 6 MV and 15 MV for VMAT and IMRT quality control

PurposeTo study the response of the ArcCHECK® device as VMAT and IMRT verification system.MethodsVarious tests analyzing the linearity, the repeatability and the angular dependence of the device response, its dependence with the pulse repetition rate and the leakage losses were performed. The long-term response in dose measurements and the uniformity of the detectors conforming the system were controlled using a statistical process control program. The Elekta Infinity™ 6 and 15 MV photon beams were used.ResultsThe device showed excellent repeatability and linearity. The differences between the responses obtained for any pair of angular incidences were less than 2%. The absorbed dose increased by 3% when the pulse repetition rate varied from 50 to 600 MU/min. Results are in overall agreement with those found in previous works for the ArcCHECK®, in which a reduced number of the device diodes were analyzed, and for the MapCheck®, an older 2D device that used the same diodes. Charge losses were found to be negligible except for some of the diodes of the device. The statistical process control program is a very useful tool to control the correct functioning of the device in the long term.ConclusionsThe results of the analysis carried out indicate that the working and stability conditions of the ArcCHECK® device are adequate for its purpose. The dependence with the pulse repetition rate should be considered when VMAT or similar treatments are evaluated. A control program for the statistical monitoring of the device would be desirable and useful.     

Effects of acute cigarette smoke concentrate exposure on mitochondrial energy transfer in fast- and slow-twitch skeletal muscle

The mechanisms underlying cigarette smoke-induced mitochondrial dysfunction in skeletal muscle are still poorly understood. Accordingly, this study aimed to examine the effects of cigarette smoke on mitochondrial energy transfer in permeabilized muscle fibers from skeletal muscles with differing metabolic characteristics. The electron transport chain (ETC) capacity, ADP transport, and respiratory control by ADP were assessed in fast- and slow-twitch muscle fibers from C57BL/6 mice (n = 11) acutely exposed to cigarette smoke concentrate (CSC) using high-resolution respirometry. CSC decreased complex I-driven respiration in the white gastrocnemius (CONTROL:45.4 ± 11.2 pmolO₂.s⁻¹.mg⁻¹ and CSC:27.5 ± 12.0 pmolO₂.s⁻¹.mg⁻¹; p = 0.01) and soleus (CONTROL:63.0 ± 23.8 pmolO₂.s⁻¹.mg⁻¹ and CSC:44.6 ± 11.1 pmolO₂.s⁻¹.mg⁻¹; p = 0.04). In contrast, the effect of CSC on Complex II-linked respiration increased its relative contribution to muscle respiratory capacity in the white gastrocnemius muscle. The maximal respiratory activity of the ETC was significantly inhibited by CSC in both muscles. Furthermore, the respiration rate dependent on the ADP/ATP transport across the mitochondrial membrane was significantly impaired by CSC in the white gastrocnemius (CONTROL:-70 ± 18 %; CSC:-28 ± 10 %; p < 0.001), but not the soleus (CONTROL:47 ± 16 %; CSC:31 ± 7 %; p = 0.08). CSC also significantly impaired mitochondrial thermodynamic coupling in both muscles. Our findings underscore that acute CSC exposure directly inhibits oxidative phosphorylation in permeabilized muscle fibers. This effect was mediated by significant perturbations of the electron transfer in the respiratory complexes, especially at complex I, in both fast and slow twitch muscles. In contrast, CSC-induced inhibition of the exchange of ADP/ATP across the mitochondrial membrane was fiber-type specific, with a large effect on fast-twitch muscles.     

The Added and Interpretative Value of CGM-Derived Parameters in Type 1 Diabetes Depends on the Level of Glycemic Control

ObjectiveIn type 1 diabetes mellitus (T1DM) management, continuous glucose monitoring (CGM)-derived parameters can provide additional insights, with time in range (TIR) and other parameters reflecting glycemic control and variability being put forward. This study aimed to examine the added and interpretative value of the CGM-derived indices TIR and coefficient of variation (CV%) in T1DM patients stratified according to their level of glycemic control by means of HbA1C.MethodsT1DM patients with a minimum disease duration of 10 years and without known macrovascular disease were enrolled. Patients were equipped with a blinded CGM device for 7 days. TIR and time spent in hypoglycemia and hyperglycemia were determined, and CV% was used as a parameter for glycemic variability. Pearson (r) and Spearman correlations (r_s) and a regression analysis were used to examine associations.ResultsNinety-five patients (age: 45 ± 10 years; HbA1C level: 7.7% ± 0.8% [61 ± 7 mmol/mol]) were included (mean blood glucose [MBG]: 159 ± 31 mg/dL; TIR: 55.8% ± 14.9%; CV%: 43.5% ± 7.8%) and labeled as having good (HbA1C level ≤7% [≤53 mmol/mol]; n = 20), moderate (7%-8%; n = 44), or poor (>8% [>64 mmol/mol]; n = 31) glycemic control. HbA1C was significantly associated with MBG (r_s = 0.48, P < .001) and time spent in hyperglycemia (total: r_s = 0.52; level 2: r = 0.46; P < .001) but not with time spent in hypoglycemia and CV%, even after an analysis of the HbA1C subgroups. Similarly, TIR was negatively associated with HbA1C (r = −0.53; P < .001), MBG (r_s = −0.81; P < .001), and time spent in hyperglycemia (total: r_s = −0.90; level 2: r_s = −0.84; P < .001) but not with time in hypoglycemia. The subgroup analyses, however, showed that TIR was associated with shorter time spent in level-2 hypoglycemia in patients with good (r_s = −0.60; P = .007) and moderate (r_s = −0.25; P = .047) glycemic control. In contrast, CV% was strongly positively associated with time in hypoglycemia (total: r_s = 0.78; level 2: r_s = 0.76; P < .001) but not with TIR or time in hyperglycemia in the entire cohort, although the subgroup analyses showed that TIR was negatively associated with CV% in patients with good glycemic control (r = −0.81, P < .001) and positively associated in patients with poor glycemic control (r = +0.47; P < .01).ConclusionThe CGM-derived metrics TIR and CV% are related to clinically important situations, TIR being strongly dependent on hyperglycemia and CV% being reflective of hypoglycemic risk. However, the interpretation and applicability of TIR and CV% and their relationship depends on the level of glycemic control of the individual patient, with CV% generally adding less clinically relevant information in those with poor control. This illustrates the need for further research and evaluation of composite measures of glycemic control in T1DM.     

A Deep Learning-based correction to EPID dosimetry for attenuation and scatter in the Unity MR-Linac system

PurposeEPID dosimetry in the Unity MR-Linac system allows for reconstruction of absolute dose distributions within the patient geometry. Dose reconstruction is accurate for the parts of the beam arriving at the EPID through the MRI central unattenuated region, free of gradient coils, resulting in a maximum field size of ~10 × 22 cm² at isocentre. The purpose of this study is to develop a Deep Learning-based method to improve the accuracy of 2D EPID reconstructed dose distributions outside this central region, accounting for the effects of the extra attenuation and scatter.MethodsA U-Net was trained to correct EPID dose images calculated at the isocenter inside a cylindrical phantom using the corresponding TPS dose images as ground truth for training. The model was evaluated using a 5-fold cross validation procedure. The clinical validity of the U-Net corrected dose images (the so-called DEEPID dose images) was assessed with in vivo verification data of 45 large rectum IMRT fields. The sensitivity of DEEPID to leaf bank position errors (±1.5 mm) and ±5% MU delivery errors was also tested.ResultsCompared to the TPS, in vivo 2D DEEPID dose images showed an average γ-pass rate of 90.2% (72.6%–99.4%) outside the central unattenuated region. Without DEEPID correction, this number was 44.5% (4.0%–78.4%). DEEPID correctly detected the introduced delivery errors.ConclusionsDEEPID allows for accurate dose reconstruction using the entire EPID image, thus enabling dosimetric verification for field sizes up to ~19 × 22 cm² at isocentre. The method can be used to detect clinically relevant errors.     

Virtual patient 3D dose reconstruction using in air EPID measurements and a back-projection algorithm for IMRT and VMAT treatments

PurposeAt our institute, a transit back-projection algorithm is used clinically to reconstruct in vivo patient and in phantom 3D dose distributions using EPID measurements behind a patient or a polystyrene slab phantom, respectively. In this study, an extension to this algorithm is presented whereby in air EPID measurements are used in combination with CT data to reconstruct ‘virtual’ 3D dose distributions. By combining virtual and in vivo patient verification data for the same treatment, patient-related errors can be separated from machine, planning and model errors.Methods and materialsThe virtual back-projection algorithm is described and verified against the transit algorithm with measurements made behind a slab phantom, against dose measurements made with an ionization chamber and with the OCTAVIUS 4D system, as well as against TPS patient data. Virtual and in vivo patient dose verification results are also compared.ResultsVirtual dose reconstructions agree within 1% with ionization chamber measurements. The average γ-pass rate values (3% global dose/3 mm) in the 3D dose comparison with the OCTAVIUS 4D system and the TPS patient data are 98.5 ± 1.9%(1SD) and 97.1 ± 2.9%(1SD), respectively. For virtual patient dose reconstructions, the differences with the TPS in median dose to the PTV remain within 4%.ConclusionsVirtual patient dose reconstruction makes pre-treatment verification based on deviations of DVH parameters feasible and eliminates the need for phantom positioning and re-planning. Virtual patient dose reconstructions have additional value in the inspection of in vivo deviations, particularly in situations where CBCT data is not available (or not conclusive).     

Rates of intercalator-driven platination of DNA determined by a restriction enzyme cleavage inhibition assay

A restriction enzyme cleavage inhibition assay was designed to determine the rates of DNA platination by four non-cross-linking platinum–acridine agents represented by the formula [Pt(am₂)LCl](NO₃)₂, where am is a diamine nonleaving group and L is an acridine derived from the intercalator 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea (ACRAMTU). The formation of monofunctional adducts in the target sequence 5′-CGA was studied in a 40-base-pair probe containing the EcoRI restriction site GAATTC. The time dependence of endonuclease inhibition was quantitatively analyzed by polyacrylamide gel electrophoresis. The formation of monoadducts is approximately 3 times faster with double-stranded DNA than with simple nucleic acid fragments. Compound 1 (am₂ is ethane-1,2-diamine, L is ACRAMTU) reacts with a first-order rate constant of k _obs = 1.4 ± 0.37 × 10⁻⁴ s⁻¹ (t _1/2 = 83 ± 22 min). Replacement of the thiourea group in ACRAMTU with an amidine group (compound 2) accelerates the rate by fourfold (k _obs = 5.7 ± 0.58 × 10⁻⁴ s⁻¹, t _1/2 = 21 ± 2 min), and introduction of a propane-1,3-diamine nonleaving group results in a 1.5-fold enhancement in reactivity (compound 3, k _obs = 2.1 ± 0.40 × 10⁻⁴ s⁻¹, t _1/2 = 55 ± 10 min) compared with the prototype. Derivative 4, containing a 4,9-disubstituted acridine threading intercalator, was the least reactive compound in the series (k _obs = 1.1 ± 0.40 × 10⁻⁴ s⁻¹, t _1/2 = 104 ± 38 min). The data suggest a correlation may exist between the binding rates and the biological activity of the compounds. Potential pharmacological advantages of rapid formation of cytotoxic monofunctional adducts over the common purine–purine cross-links are discussed.     

Surgivisio® and O-arm®O2 cone beam CT mobile systems for guidance of lumbar spine surgery: Comparison of patient radiation dose

PurposeTo compare patient radiation doses in cone beam computed tomography (CBCT) of two mobile systems used for navigation-assisted mini-invasive orthopedic surgery: O-arm®O2 and Surgivisio®.MethodsThe study focused on imaging of the spine. Thermoluminescent dosimeters were used to measure organs and effective doses (ED) during CBCT. An ionization-chamber and a solid-state sensor were used to measure the incident air-kerma (K_i) at the center of the CBCT field-of-view and K_i during 2D-imaging, respectively. The PCXMC software was used to calculate patient ED in 2D and CBCT configurations. The image quality in CBCT was evaluated with the CATPHAN phantom.ResultsThe experimental ED estimate for the low-dose 3D-modes was 2.41 and 0.35 mSv with O-arm®O2 (Low Dose 3D-small-abdomen) and Surgivisio® (3DSU-91 images), respectively. PCXMC results were consistent: 1.54 and 0.30 mSv. Organ doses were 5 to 12 times lower with Surgivisio®. K_i at patient skin were comparable on lateral 2D-imaging (0.5 mGy), but lower with O-arm®O2 on anteroposterior (0.3 versus 0.9 mGy). Both systems show poor low contrast resolution and similar high contrast spatial resolution (7 line-pairs/cm).ConclusionsThis study is the first to evaluate patient ED and organ doses with Surgivisio®. A significant difference in organs doses was observed between the CBCT systems. The study demonstrates that Surgivisio® used on spine delivers approximately five to six times less patient ED, compared to O-arm®O2, in low dose 3D-modes. Doses in 2D-mode preceding CBCT were higher with Surgivisio®, but negligible compared to CBCT doses under the experimental conditions tested.     

A multicenter study of radiation doses to the eye lenses of medical staff performing non-vascular imaging and interventional radiology procedures in Japan

PurposeThis study aimed to measure the eye lens doses received by physicians and other medical staff participating in non-vascular imaging and interventional radiology procedures in Japan.Material and methodsFrom October 2014 to March 2017, 34 physicians and 29 other medical staff engaged in non-vascular imaging and interventional radiology procedures at 18 Japanese medical facilities. These professionals wore radioprotective lead glasses equipped with small, optically stimulated luminescence dosimeters and additional personal dosimeters at the neck during a 1-month monitoring period. The H_p(3) and the H_p(10) and H_p(0.07) were obtained from these devices, respectively. The monthly H_p(3), H_p(10), and H_p(0.07) for each physician and other medical staff member were then rescaled to a 12-month period to enable comparisons with the revised occupational equivalent dose limit for the eye lens.ResultsAmong physicians, the average annual H_p(3) values measured by the small luminescence dosimeters on radioprotective glasses were 25.5 ± 38.3 mSv/y (range: 0.4–166.8 mSv/y) and 9.3 ± 16.6 mSv/y (range: 0.3–82.4 mSv/y) on the left and right sides, respectively. The corresponding values for other medical staff were 3.7 ± 3.1 mSv/y (range: 0.4–10.4 mSv/y) and 3.2 ± 2.7 mSv/y (range: 0.5–11.5 mSv/y), respectively.ConclusionsThe eye lens doses incurred by physicians and other medical staff who engaged in non-vascular imaging and interventional radiology procedures in Japan were provided. Physicians should wear radioprotective glasses and use additional radioprotective devices to reduce the amount of eye lens doses they receive.     

Kinetics of CO substitution in Co4(CO)12 and Rh4(CO)12

The kinetics of rapid CO substitution by PPh₃ in Co₄(CO)₁₂ and Rh₄(CO)₁₂ have been examined by stopped-flow and low temperature FT-IR methods. In Co₄(CO)₁₂ rapid (k_obs ∼ 1.8 s⁻¹) substitution of CO occurs after a 1–15 s induction period at 28 °C in C₆H₅Cl solvent by a catalytic process. Addition of PPh₃ to Rh₄(CO)₁₂ yields Rh₄(CO)₁₁(PPh₃) according to a predominantly second order rate law k₁[Rh₄- (CO)₁₂] + k₂[Rh₄(CO)₁₂][PPh₃] with k₁ = 25 ± 11 s⁻¹ and k₂ = 2.97 ± 0.27 X 10⁴ M⁻¹ s⁻¹ at 28 °C. Substitution of a second CO ligand also occurs rapidly with k₁ = 0.15 ± 0.09 s⁻¹ and k₂ = 6.54 ± 0.07 X 10² M⁻¹ s⁻¹ at 28 °C. The reactivity of Rh₄(CO)₁₂ toward associative substitution is 10⁴– 10¹¹ faster than for the Co and Ir analogues, In Rh₄(CO)₁₁(PPh₃) the increase in CO substitution rates over Co and Rh analogues is 10²–10⁷. The ordering of associative substitution rates Co << Rh >>> Ir in these clusters exaggerates the trend seen in mononuclear metal complexes.     

Genetic variants entail type 2 diabetes as an innate immune disorder

Type 2 Diabetes (T2D) is characterized by alteration in the circulatory levels of key inflammatory proteins, where our body strives to eliminate the perturbing factor through inflammation as a final resort to restore homeostasis. Plasma proteins play a crucial role to orchestrate this immune response. Over the past two decades, rigorous genetic efforts taken to comprehend T2D physiology have been partially successful and have left behind a dearth of knowledge of its causality. Here, we have investigated how the reported genetic variants of T2D are associated with circulatory levels of key plasma proteins. We identified 99 T2D genetic variants that serve as strong pQTL (protein Quantitative Trait Loci) for 72 plasma proteins, of which 4 proteins namely Small nuclear ribonucleoprotein F [SNRPF] (p = 2.99 × 10⁻¹⁴), Platelet endothelial cell adhesion molecule [PECAM1] (p = 1.9 × 10⁻⁴⁵), Trypsin-2 [PRSS2] (p = 7.6 × 10⁻⁴³) and Trypsin-3 [PRSS3] (p = 5.7 × 10⁻⁸) were previously not reported for association to T2D. The genes that encode these 72 proteins were observed to be highly expressed in at least one of the four T2D relevant tissues - liver, pancreas, adipose and whole blood. Comparative analysis of interactions of the studied proteins amongst these four tissues revealed distinct molecular connectivity. Assessment of biological function by gene-set enrichment highlighted innate immune system as the lead process enacted by the identified proteins (FDR q = 3.7 × 10⁻¹⁶). To validate the findings, we analyzed Coronary Artery Disease (CAD) and Rheumatoid Arthritis (RA) individually and as expected, we observed innate immune system as a top enriched pathway for RA but not for CAD. Our study illuminates strong regulation of plasma proteome by the established genetic variants of T2D.     

Dose uncertainty and resolution of polymer gel dosimetry using an MRI guided radiation therapy system’s onboard 0.35 T scanner

Magnetic Resonance Imaging (MRI) scanners are widely used for 3D gel dosimeters readout. However, limited access to MRI scanners is a challenge in MRI-based gel dosimetry. Recent clinical implementation of MRI-guided radiation therapy machines provides potential opportunities for onboard gel dosimetry using its MRI subsystem. The objective of this study was to investigate the feasibility of gel dosimetry using ViewRay’s onboard 0.35 T MRI scanner. A BANG® polymer gel dosimeter was irradiated by three beams of 3 × 3 cm² field size. The T₂ relaxation rate (R₂) of the irradiated gel was measured using a Philips 1.5 T Ingenia MRI and a ViewRay 0.35 T onboard MRI and spin-echo pulse sequences. The number of signal averages (NSA) was set to 16 for the ViewRay acquisitions and one for the Philips 1.5 T MRI to achieve similar signal-to-noise ratios. The in-plane spatial resolution was 1.5 × 1.5 mm² and the slice thickness was 5 mm. The relative dose uncertainty was obtained using R₂ versus dose curves to compare the performance of dosimetry using the two different MRIs and field strengths. The dose uncertainty decreased from 12% at 2 Gy to 3.5% at 7.5 Gy at 1.5 T. The dose uncertainty decreased from 13% at 2 Gy to 4% at 7.5 Gy with NSA = 16 and 3 × 3 mm² pixel size, and from 10.5% at 2 Gy to 3.2% at 7.5 Gy with NSA = 16 and denoised R₂ maps (1.5 × 1.5 mm² pixel size) at 0.35 T. The mean of dose resolution was 0.4 Gy at 1.5 T while the mean of dose resolution was 0.8 Gy and 0.64 Gy at 0.35 T by downsampling and denoising the R2 map, respectively. Therefore, comparable dose uncertainty was achievable using the ViewRay’s onboard 0.35 T and Philips 1.5 T MRI scanners. 3D gel dosimetry using onboard low-field MRI scanner provides ViewRay users a 3D high resolution dosimetry option besides film and ionization chamber.