Typical Dose Research Articles

Integration of a dose management system in the public hospitals of Cyprus: Key areas and initial outcomes.

Despite the growing use of dose management systems (DMSs), there is limited guidance on their optimal setup. This study aims to fill this gap by outlining the process followed to integrate "DOSE" (Qaelum NV, Belgium) DMS within the Cypriot public hospitals. DOSE was connected to the available central PACS, followed by a thorough data and functioning validation. A preliminary study was also conducted to assess the DOSE's ability to establish typical dose values in diagnostic radiography. Overall, over 70 x-ray units were configured. For some connections, it was necessary to first adjust the unit's DICOM attributes or to utilise the DICOM coercion technique. The DICOM image header was sometimes preferred over the DICOM RDSR, as the chosen data source. This study underscored the importance of understanding the equipment's technical capabilities for a successful DMS integration, while personnel with expertise in diagnostic radiology and the IT aspects of medical physics proved to have a vital role in the process. The pilot study showed that DOSE is an effective tool for establishing typical dose values and assessing compliance with relevant dose levels.

Inhomogeneity detection within a head-sized phantom using tracking of charged nuclear fragments in ion beam therapy.

The highly conformal carbon-ion radiotherapy is associated with an increased sensitivity of the dose distributions to internal changes in the patient during the treatment course. Hence, monitoring methodologies capable of detecting such changes are of vital importance. We established experimental setup conditions to address the sensitivity of a monitoring approach based on secondary-fragment tracking for detecting clinically motivated air cavity dimensions in a homogeneous head-size PMMA phantom in 40 mm depth. The air cavities were positioned within the entrance channel of a treatment field of 50 mm diameter at three lateral positions. The measured secondary-fragment emission profiles were compared to a reference measurement without cavities. The experiments were conducted at the Heidelberg Ion-Beam Therapy Center in Germany at typical doses and dose rates. Significances above a detectability threshold of 2σ for the larger cavities (20 mm diameter and 4 mm thickness, and 20 mm diameter and 2 mm thickness) across the entire treatment field. The smallest cavity of 10 mm diameter and 2 mm thickness, which is on the lower limit of clinical interest, could not be detected at any position. We also demonstrated that it is feasible to reconstruct the lateral position of the cavity on average within 2.8 mm, once the cavity is detected. This is sufficient for the clinicians to estimate medical effects of such a cavity and to decide about the need for a control imaging CT. This investigation defines well-controlled reference conditions for the evaluation of the performance of any kind of treatment monitoring method and its capability to detect internal changes within head-sized objects. Air cavities with volumes from 0.31 cm3 to 1.26 cm3 were narrowed down around the detectability threshold of this secondary-fragment-based monitoring method.

Straightforward Phase I Dose-Finding Design for Healthy Volunteers Accounting for Surrogate Activity Biomarkers

Conventionally, a first-in-human phase I trial in healthy volunteers aims to confirm the safety of a drug in humans. In such situations, volunteers should not suffer from any safety issues and simple algorithm-based dose-escalation schemes are often used. However, to avoid too many clinical trials in the future, it might be appealing to design these trials to accumulate information on the link between dose and efficacy/activity under strict safety constraints. Furthermore, an increasing number of molecules for which the increasing dose-activity curve reaches a plateau are emerging. In a phase I dose-finding trial context, our objective is to determine, under safety constraints, among a set of doses, the lowest dose whose probability of activity is closest to a given target. For this purpose, we propose a two-stage dose-finding design. The first stage is a typical algorithm dose escalation phase that can both check the safety of the doses and accumulate activity information. The second stage is a model-based dose-finding phase that involves selecting the best dose-activity model according to the plateau location. Our simulation study shows that our proposed method performs better than the common Bayesian logistic regression model in selecting the optimal dose.

Understanding the risk of ionizing radiation in breast imaging: Concepts and quantities, clinical importance, and future directions

BackgroundConventional mammography remains the primary imaging modality for state-of-the-art breast imaging practice and its benefit (both on diagnostic and screening) was largely reported. In mammography, the typical Mean Glandular Dose (MGD) from X-ray radiation to the breast spans, on average, from 1 to 10 mGy, depending on breast thicknesses, percentage of fibroglandular tissue, and on the examination purpose. MethodsThe aim of this narrative review is to describe the extent of radiation risk in X-ray breast imaging and discuss the main steps and parameters (e.g. MGD, screening frequency and number of examination views) that may have an influence on the radiation risk assessment. ResultsEven though the radiation doses used with these examinations are very low, as compared to other medical or natural radiation exposures, there is a non-negligible associated risk of radiation-induced cancer. Accurate radiation risk assessment permits to better balance the overall estimation of the benefit-to-risk ratio in X-ray breast imaging. ConclusionsIt is expected that a better knowledge about radiation-induced cancer risk among population could improve the communications skills between patients and clinicians and could help to increase the awareness in women about radiation risk perception for a transparent and proper informed choice of imaging exam.

The fungal natural product fusidic acid demonstrates potent activity against Mycoplasma genitalium.

Antimicrobial resistance is extremely common in Mycoplasma genitalium, a frequent cause of urethritis in men and cervicitis, vaginitis, and pelvic inflammatory disease in women. Treatment of M. genitalium infections is difficult due to intrinsic and acquired resistance to many antibiotic classes. We undertook a program to identify novel antimicrobials with activity against M. genitalium from fungal natural products. Extracts of Ramularia coccinea contained a molecule with potent activity that was subsequently identified as fusidic acid, a fusidane-type antibiotic that has been in clinical use for decades outside the United States. We found that minimum inhibitory concentrations of fusidic acid ranged from 0.31 to 4 µg/mL among 17 M. genitalium strains including laboratory-passaged and low-passage clinical isolates. Time-kill data indicate that bactericidal killing occurs when M. genitalium is exposed to ≥10 µg/mL for 48 h, comparing favorably to serum concentrations obtained from typical loading dose regimens. Resistance to fusidic acid was associated with mutations in fusA consistent with the known mechanism of action in which fusidic acid inhibits protein synthesis by binding to elongation factor G. Interestingly, no mutants resistant to >10 µg/mL fusidic acid were obtained and a resistant strain containing a F435Y mutation in FusA was impaired for growth in vitro. These data suggest that fusidic acid may be a promising option for the treatment of M. genitalium infections.

Dose and timing effects of caffeine on subsequent sleep: A randomised clinical crossover trial.

To investigate the effect of a typical dose of caffeine and a high dose of caffeine consumed in the morning, afternoon, and evening on subsequent sleep. Using a placebo-controlled, double-blind, randomised crossover design, 23 males (25.3±5.0 years) with a moderate habitual caffeine intake (<300mg∙day-1) completed seven conditions: placebo, and 100 and 400mg of caffeine consumed 12, eight, and four hours prior to bedtime, with a 48-hour washout. In-home partial polysomnography and sleep diaries were used to assess sleep. Linear mixed models estimated the effect of each condition. No significant effect on objective or subjective sleep occurred with the 100mg dose of caffeine compared to the placebo (p>0.05) but significant effects occurred with the 400mg dose (p<0.05). Significant delays in sleep initiation and alterations to sleep architecture were observed when 400mg was consumed within 12 hours of bedtime (p<0.05), and significantly greater sleep fragmentation occurred when 400mg was consumed within eight hours of bedtime (p<0.05). Additionally, perceived sleep quality was significantly reduced when 400mg was consumed four hours prior to bedtime (-34.02%, p=.006) but not at eight or 12 hours. A 100mg dose of caffeine can be consumed up to four hours prior to bedtime, but 400mg may negatively impact sleep when consumed as one dose within 12 hours of bedtime, with the adverse influence on sleep increasing the closer consumption occurs to bedtime. The discrepancy between objective and subjective sleep quality suggests individuals may have difficulty accurately perceiving the influence of caffeine on sleep quality.

Reversible Interconversion between Ag2 and Ag6 Clusters and Their Responsive Optical Properties.

The exploration of structural interconversion in clusters triggered by external stimuli has attracted significant interest due to its potential to elucidate structure-property relationships of metal clusters. In this study, two types of silver clusters, Ag2 and Ag6, are synthesized. Interestingly, the clusters exhibit reversible transformations in response to changes in the solvent conditions. The structures and optical properties of these clusters are thoroughly characterized using techniques such as mass spectrometry, single-crystal X-ray diffraction, photoluminescence, and radioluminescence spectroscopy. While both Ag2 and Ag6 display excellent photoluminescence properties, Ag2 demonstrates superior performance in X-ray radioluminescence compared to Ag6. Flexible scintillator films fabricated from Ag2 clusters exhibit outstanding X-ray imaging capabilities, achieving a spatial resolution of 15.0 lp/mm and an impressive detection limit for an X-ray dose of 0.58 μGy s-1. This detection limit is nearly 10 times lower than the typical dose rate used in X-ray diagnostics (5.5 μGy s-1). This work introduces a novel approach for designing thiol-free silver clusters capable of solvent-dependent reversible interconversion, offering new insights into the development of silver clusters for advanced X-ray imaging applications.

Quantifying the effects of chlorine disinfection on microplastics by time-resolved inductively coupled plasma-mass spectrometry

Using current water treatment systems, significant amounts of microplastics (MPs) are passing through and being released into the aquatic environment. However, we do not clearly know what effects disinfection processes have had on these particles. In this study, we applied inductively coupled plasma-mass spectrometry (ICP-MS) operating in time-resolved analysis (TRA) mode for quantifying changes in the chlorine (Cl) content of MPs under a variety of water treatment scenarios. Our results illustrated that time-resolved ICP-MS offers a potential method for sensitive and direct analysis of Cl content, including Cl mass and chlorine association (%Cl/C), of discrete particles in the MP suspension by the fast sequential measurements of signals from 35Cl1H2 and 12C1H. Our research, across various water treatment scenarios, also showed that polystyrene (PS) MPs exhibited greater reactivity to Cl disinfectant after being pre-disinfected with UV light and in mildly acidic to neutral pH environments. It is noteworthy that about half of the particles in MP suspension exposed to 10 mg Cl2/L, a typical Cl dose applied in water treatment, were chlorinated, and had a Cl content comparable to that of particles subjected to extreme conditions. Of even greater concern is the fact that our cell viability tests revealed that chlorinated MPs induced considerably higher rates of cell death in both human A549 and Caco-2 cells, and that the effects were Cl dose- and polymer type-dependent. Overall, this study demonstrates the potential of time-resolved ICP-MS as a valuable technique for quantifying the Cl content of MP particles, which is crucial to assessing the fate and transformation of MPs in our water supply and treatment systems.

Opioid Dose Variation in Cardiac Surgery: A Multicenter Study of Practice.

Although high-opioid anesthesia was long the standard for cardiac surgery, some anesthesiologists now favor multimodal analgesia and low-opioid anesthetic techniques. The typical cardiac surgery opioid dose is unclear, and the degree to which patients, anesthesiologists, and institutions influence this opioid dose is unknown. We reviewed data from nonemergency adult cardiac surgeries requiring cardiopulmonary bypass performed at 30 academic and community hospitals within the Multicenter Perioperative Outcomes Group registry from 2014 through 2021. Intraoperative opioid administration was measured in fentanyl equivalents. We used hierarchical linear modeling to attribute opioid dose variation to the institution where each surgery took place, the primary attending anesthesiologist, and the specifics of the surgical patient and case. Across 30 hospitals, 794 anesthesiologists, and 59,463 cardiac cases, patients received a mean of 1139 (95% confidence interval [CI], 1132-1146) fentanyl mcg equivalents of opioid, and doses varied widely (standard deviation [SD], 872 µg). The most frequently used opioids were fentanyl (86% of cases), sufentanil (16% of cases), hydromorphone (12% of cases), and morphine (3% of cases). 0.6% of cases were opioid-free. 60% of dose variation was explainable by institution and anesthesiologist. The median difference in opioid dose between 2 randomly selected anesthesiologists across all institutions was 600 µg of fentanyl (interquartile range [IQR], 283-1023 µg). An anesthesiologist's intraoperative opioid dose was strongly correlated with their frequency of using a sufentanil infusion (r = 0.81), but largely uncorrelated with their use of nonopioid analgesic techniques (|r| < 0.3). High-dose opioids predominate in cardiac surgery, with substantial dose variation from case to case. Much of this variation is attributable to practice variability rather than patient or surgical differences. This suggests an opportunity to optimize opioid use in cardiac surgery.

Thyroid cancer incidence in cohorts exposed in childhood to 131I released during the Windscale nuclear reactor accident at Sellafield, England, in 1957.

A fire in one of the Windscale nuclear reactors at Sellafield (Cumbria, England) in October 1957 released 1,800 TBq of 131I (half-life, 8 days) to atmosphere. Measurements of 131I activity in thyroids of exposed children showed typical thyroid doses of tens of milligray, but with some exceeding 100 mGy. Radiation exposure in childhood is known to increase the risk of thyroid cancer. Consequently, an investigation was conducted into whether raised numbers of thyroid cancer cases occurred in those exposed to 131I as young children in Cumbria. A database of Cumbrian births from 1950 onwards allowed cohorts of 56,086 births during 1950-1958 and 137,444 births during 1959-1980 to be constructed, periods including children potentially exposed and unexposed, respectively, to 131I. Three areas of Cumbria with different 131I contamination levels were identified from monitoring data, and births assigned to these three areas for the two periods of birth. Members of these six sub-cohorts were linked to incident thyroid cancer cases in Great Britain during 1981-2020 using national cancer registration databases, providing thyroid cancer incidence rates. Incidence rate ratios (IRRs), with the lowest contamination area as a reference, were computed. No IRR differed discernibly from unity. For births during 1950-1958, the IRR for the combined highest and intermediate 131I contamination areas was 0.68 (95% confidence interval: 0.24, 1.56), and no case of thyroid cancer was found in the small cohort born in the highest contamination area. In conclusion, no increased risk of thyroid cancer in those exposed to 131I as young children in Cumbria in 1957 was detected. This study adds to the evidence on the long-term risk of thyroid cancer following childhood exposure to low and moderate levels of 131I, such as occurred following the Fukushima nuclear accident in 2011.

A pharmacokinetic framework describing antibiotic adsorption to cardiopulmonary bypass devices.

Cardiopulmonary bypass (CPB) can alter pharmacokinetic (PK) parameters and the drug may adsorb to the CPB device, altering exposure. Cefazolin is a beta-lactam antibiotic used for antimicrobial prophylaxis during cardiac surgery supported by CPB. Adsorption of cefazolin could result in therapeutic failure. An exvivo study was undertaken using CPB devices primed and then dosed with cefazolin and samples were obtained over 1 hour of recirculation. Twelve experimental runs were conducted using different CPB device sizes (neonate, infant, child, and adult), device coatings (Xcoating™, Rheoparin®, PH.I.S.I.O), and priming solutions. The time course of saturable binding, using Bmax (binding capacity), Kd (dissociation constant), and T2off (half-time of dissociation), described cefazolin adsorption. Bmax estimates for the device sizes were neonate 40.0 mg (95% CI 24.3, 67.4), infant 48.6 mg (95% CI 5.97, 80.2), child 77.8 mg (95% CI 54.9, 103), and adult 196 mg (95% CI 191, 199). The Xcoating™ Kd estimate was 139 mg/L (95% CI 27.0, 283) and the T2off estimate was 98.4 min (95% CI 66.8, 129). The Rheoparin® and PH.I.S.I.O coatings had similar binding parameters with Kd and T2off estimates of 0.169 mg/L (95% CI 0.01, 1.99) and 4.94 min (95% CI 0.17, 59.4). The Bmax was small (< 10%) relative to a typical total patient dose during cardiac surgery supported by CPB. A dose adjustment for cefazolin based solely on drug adsorption is not required. This framework could be extended to other PK studies involving CPB.

Degradation of the neonicotinoid insecticide imidacloprid by ozonation and the E-peroxone process: Mechanisms, transformation products, and toxicity

In this study, degradation of the neonicotinoid insecticide imidacloprid (IMI) by ozonation and the E-peroxone process was investigated. Results show that IMI is an O3-refractory compound with second-order rate constants for the reaction with O3 and •OH (kO3,IMI and k•OH,IMI) being 3.9 and 3.95 × 109 M−1 s−1 at pH 7, respectively. Due to its low O3 reactivity, IMI was only abated by < 20 % in a selected groundwater during ozonation with typical ozone doses applied in water treatment (1–5 mg/L). In comparison, the E-peroxone process considerably enhanced IMI removal efficiency to > 80 % under similar reaction conditions. During both ozonation and the E-peroxone process, IMI was mainly abated by •OH oxidation. The reaction mechanism of IMI with •OH was investigated with quantum computations, which show that H-abstraction at H23 site was the most favorable pathway. Sixteen transformation products (TPs) generated from IMI degradation were identified using various chromatographic and mass-spectrometric techniques. The acute and chronic toxicities of IMI and its TPs to different aquatic organisms were evaluated with Microtox bioassay and the ECOSAR program, which indicate that some TPs (e.g., TP2–TP5 and TP7–TP9) are even more toxic than IMI to aquatic organisms (e.g., daphnia). The results of this study suggest that IMI along with its TPs should be sufficiently abated during water treatment, and the E-peroxone process provides an efficient option to upgrade conventional ozonation for enhanced IMI abatement.

Effects of Irradiation During Computed Tomography Scanning on the Function of Implantable Cardioverter-defibrillators.

The effect of irradiation during computed tomography (CT) imaging on implantable cardioverter-defibrillators (ICDs) has not been fully evaluated in various settings. The purposes of this study were to evaluate the occurrence of electromagnetic interference (EMI) during CT irradiation in various clinically available ICDs with phantom experiments and to determine the potential risks related to irradiation during CT imaging. Five types of clinically available ICDs from five manufacturers were tested. An ICD was combined with an electrocardiogram (ECG) simulator, mounted in a chest phantom, and subjected to CT imaging. Each ICD was irradiated at the maximal power level (tube voltage, 135 kVp; tube current, 510 mA; rotation time, 1.5 s). EMI was defined as oversensing, ventricular tachycardia/ventricular fibrillation (VT/VF) detection, noise, or shock delivery during CT imaging. For ICDs in which EMI was observed, EMI was then evaluated under 144 different irradiation conditions (tube voltage [four patterns from 80-135 kVp], tube current [six patterns from 50-550 mA], and rotation time [six patterns from 0.35-1.5 s]). Testing was also performed during irradiation at the typical doses in three clinical settings and in two settings with inappropriate irradiation of ICDs due to incorrect setup. Among the five ICDs, a shock was delivered by one ICD manufactured by Medtronic (Minneapolis, MN, USA) due to oversensing during irradiation, which occurred at the maximal power level. No oversensing was observed in other ICDs. In the malfunctioned ICD, oversensing was observed in 134 of 144 irradiation patterns, even at a low power in the ICD. The VF-detection criterion was fulfilled in 20 of 134 tests and was significantly associated with tube voltage, tube current, ration time, and tube voltage × rotation time interaction. Although oversensing was observed in three clinical settings (typical chest CT, CT coronary angiography after coronary artery bypass graft, and dynamic assessment for pleural tumors) and one situation during an incorrect scan range on the chest for head perfusion CT, they were not recognized as tachycardia beats. Oversensing was observed when scans were incorrectly set over the ICD during bolus tracking of contrast-enhanced CT. Maximal power CT imaging induced VT/VF detection and shock delivery in one model of ICD placed in a chest phantom. VT/VF detection was observed when tube voltages were high and irradiation times were longer. Oversensing can occur during inappropriate CT imaging, particularly when slices are positioned over the ICD.

Development of rosuvastatin calcium nano-carrier patches by central composite design

Rosuvastatin (RS) is a statin medication used to lower cholesterol levels and reduce the risk of cardiovascular diseases. RS works by inhibiting an enzyme called HMG-CoA reductase, which helps decrease LDL cholesterol and increase HDL cholesterol. The typical dose range for rosuvastatin is 5-40 mg once daily, with the starting dose usually being 10 mg. However, the dosage may vary depending on the patient's cholesterol levels and individual response to the medication. Rosuvastatin has a half-life of approximately 19 hours and undergoes metabolism mainly in the liver. The aim of the study was to develop a transdermal patch containing Rosuvastatin in the form of niosomes (NP). The Rosuvastatin niosomes were prepared using the solvent casting method, and the optimized formulation showed a particle size of 211.6 nm with a polydispersity index (PDI) of 0.197. The zeta potential of the niosomes was found to be -44.7. These results indicate that the developed formulation has a uniform particle size distribution and a stable zeta potential, which are important factors for the effective delivery of Rosuvastatin through a transdermal patch. Invitro diffusion studies of the optimized patch RN-T6 released upto 24 hours with %CDR of 98.98% and the drug diffusion data is fitted into various mathematical models and RN-T6 followed zero order drug release kinetics and the diffusion mechanism was non-fickian diffusion.

Patient organ dose during multicycle radiation dosimetry in Lutetium −177 radionuclide therapy

Precise patient radiation dosimetry during theranostic procedures allows clinicians to tailor therapeutic procedures to each patient. Organ dose measurement aids in adjustment of the administered activity or number of treatment cycles to maximize tumor cell destruction while minimizing damage to healthy tissues. This study was aimed at quantifying patient organ doses during Lu-177 DOTATATE and Lu-177 PSMA theranostic procedures. Nine patients underwent Lu-177 radionuclide therapy, usually four cycles with 6–8 GBq administered activity per cycle. The typical dose is 7.5 GBq as a fixed activity. Using quantitative dosimetry, physicians can estimate the next dose cycle according to patient condition. The average dose per activity for critical organs were low, at 1.76, 1.96, 0.25, 0.5, and 2.43 mSv/MBq for the right kidney, left kidney, liver bladder, and spleen, respectively. The doses for the left and right kidneys, liver, urinary bladder, and spleen were lower than those in previously published studies. Wide variations were observed in patient organ doses for Lu-177 DOTATATE and Lu-177 PSMA procedures. Further studies are recommended to ensure organ safety during theransotic procedures, to minimize the radiogenic risks to healthy organs.

Radiochromic film EBT3 calibration for linear accelerator in 10 MV

Radiochromic film is used to applications in dosimetry have become increasingly significant for studies on radiotherapy. Due to sensitivity to exposure to ionizing radiation, radiochromic films are commonly used to obtain dose distribution maps and for calibration curves. The calibration curves in the radiochromic films can be use radiochromic films as a dosimetry method and then seek the generation of images with lower dose deposition and higher diagnostic quality. When ionizing radiation interacts with matter it generates energy deposition. Radiation dosimetry is important for medical applications of ionizing radiation due to the increasing demand for diagnostic radiology and radiotherapy. The film is a dose measurement method that records the energy deposition by the darkening of its emulsion. Radiochromic films have a little visible light sensitivity and respond better to ionizing radiation exposure. The aim of this study is to obtain the resulting calibration curve by the irradiation of radiochromic film strips, making it possible to relate the darkening of the film with the absorbed dose, to measure doses in experiments with X-ray beam of 10 MeV in Linear Accelerator. The objective of this study is to obtain the calibration curves of the radiographic film for exposure with X-ray beam in Linear Accelerator scanner for realize measures of typical doses found in radiotherapy. It was used Gafchromic EBT Radiochromic Film, which shows little sensitivity to visible light and a response in the range of 0.1 to 10 Gy for X-ray beam. In the experiments, a Solid Water Phantom, with a 30x30x2.0 cm³. The strips were scanned and processed using the ImageJ software to obtain the intensity values resulting from the absorbed radiation by grayscale. The darkening responses on film strips according to the doses were observed and they allowed obtaining the corresponding numeric values to the darkening for each specific dose value. From the numerical values of darkening, a calibration curve was obtained.

Development and validation of a noise insertion algorithm for photon-counting-detector CT.

Inserting noise into existing patient projection data to simulate lower-radiation-dose exams has been frequently used in traditional energy-integrating-detector (EID)-CT to optimize radiation dose in clinical protocols and to generate paired images for training deep-learning-based reconstruction and noise reduction methods. Recent introduction of photon counting detector CT (PCD-CT) also requires such a method to accomplish these tasks. However, clinical PCD-CT scanners often restrict the users access to the raw count data, exporting only the preprocessed, log-normalized sinogram. Therefore, it remains a challenge to employ projection domain noise insertion algorithms on PCD-CT. To develop and validate a projection domain noise insertion algorithm for PCD-CT that does not require access to the raw count data. A projection-domain noise model developed originally for EID-CT was adapted for PCD-CT. This model requires, as input, a map of the incident number of photons at each detector pixel when no object is in the beam. To obtain the map of incident number of photons, air scans were acquired on a PCD-CT scanner, then the noise equivalent photon number (NEPN) was calculated from the variance in the log normalized projection data of each scan. Additional air scans were acquired at various mA settings to investigate the impact of pulse pileup on the linearity of NEPN measurement. To validate the noise insertion algorithm, Noise Power Spectra (NPS) were generated from a 30cm water tank scan and used to compare the noise texture and noise level of measured and simulated half dose and quarter dose images. An anthropomorphic thorax phantom was scanned with automatic exposure control, and noise levels at different slice locations were compared between simulated and measured half dose and quarter dose images. Spectral correlation between energy thresholds T1 and T2, and energy bins, B1 and B2, was compared between simulated and measured data across a wide range of tube current. Additionally, noise insertion was performed on a clinical patient case for qualitative assessment. The NPS generated from simulated low dose water tank images showed similar shape and amplitude to that generated from the measured low dose images, differing by a maximum of 5.0% for half dose (HD) T1 images, 6.3% for HD T2 images, 4.1% for quarter dose (QD) T1 images, and 6.1% for QD T2 images. Noise versus slice measurements of the lung phantom showed comparable results between measured and simulated low dose images, with root mean square percent errors of 5.9%, 5.4%, 5.0%, and 4.6% for QD T1, HD T1, QD T2, and HD T2, respectively. NEPN measurements in air were linear up until 112mA, after which pulse pileup effects significantly distort the air scan NEPN profile. Spectral correlation between T1 and T2 in simulation agreed well with that in the measured data in typical dose ranges. A projection-domain noise insertion algorithm was developed and validated for PCD-CT to synthesize low-dose images from existing scans. It can be used for optimizing scanning protocols and generating paired images for training deep-learning-based methods.

The Use of Variance Reduction Techniques for Photon Dose Estimation in the Design of Radiotherapy Facilities at 10 and 15 MeV via Monte Carlo Simulations

In the context of designing radiotherapy facilities, typical dose estimation methods involve analytical approaches, as outlined in International Atomic Energy Agency (IAEA) Safety Reports Series No. 47 (IAEA 47). These methods are known for their ease of use and rapid calculations, but they could lead to either overestimation or underestimation of radiation doses. Hence, the integration of Monte Carlo (MC) methods is considered valuable. In this particular study, a radiotherapy facility was modeled using MCNP version 6.2, and dose calculations were conducted using analytical techniques following both IAEA 47 guidelines and MC simulations. The study focused on monoenergetic photon cone beams with energies of 10 and 15 MeV. Notably, the beam’s orientation prevented primary radiation from reaching the dose location at the entrance of the maze, allowing only scatter radiation to contribute to the tally. Given the challenges associated with obtaining reliable and accurate results through standard MCNP calculations, the investigation focused on the use of weight windows as a variance reduction technique. The findings revealed that the IAEA method tends to provide conservative results only when the same conditions were replicated in the MC simulations. In fact, approximately 50% of the final dose estimated through MC methods accounted for factors that were not considered in the analytical calculations. The primary contributor to scattering (averaging around 30%) was identified as the floor and ceiling. This study underscores the need for caution when relying solely on the analytical approach, as it may not consistently yield conservative outcomes.

Human brain 7Li-MRI following low-dose lithium dietary supplementation in healthy participants

BackgroundLithium is an effective mood stabiliser, but its mechanism of action is incompletely defined. Even at very low doses, lithium may have neuroprotective effects, but it is not clear if these relate to brain lithium concentration in vivo. We have developed magnetic resonance imaging (7Li-MRI) methods to detect lithium in the brain following supplementation at a very low dose. MethodsLithium orotate supplements were taken by nine healthy adult male subjects (5 mg daily) for up to 28 days, providing 2–7 % of the lithium content of a typical therapeutic lithium carbonate dose. One-dimensional 7Li-images were acquired on a 3.0 T MRI scanner. All subjects were scanned on day 14 or 28; seven were scanned on both, one at baseline and one after 7-days washout. Results7Li-MR signal amplitude was broadly stable between days 14 and 28. Two subjects had notably higher 7Li-signal intensities (approximately 2–4×) compared to other study participants. LimitationsLithium adherence was self-reported by all participants without formal validation. The coarse spatial resolution necessary for detection of low concentrations of 7Li exhibits imperfect spatial separation of signal from adjacent pixels. Conclusions7Li-MRI performed using a clinical 3T scanner demonstrated detection of lithium in the brain at very low concentration, in the range of approximately 10–60 mM. The methods are suited to studies assessing low dose lithium administration in psychiatric and neurodegenerative disorders, and permit the comparison of different lithium salt preparations at a time of emerging interest in the field.

Kratom addiction per DSM-5 SUD criteria, and kratom physical dependence: Insights from dosing amount versus frequency

BackgroundKratom products are widely used in the United States, with inadequate understanding of how dosing amounts/frequencies relate to outcomes. MethodsBetween July-November 2022, we enrolled 395 active US adult kratom consumers into a remote study with a baseline survey. We examined self-reported typical dose amounts and frequencies across people and product types, and their associations with outcomes: multiple regression was used to examine whether amounts and frequencies (doses/day) were associated with acute effects, withdrawal symptoms, scores on the Subjective Opioid Withdrawal Scale (SOWS), and addiction (operationalized as DSM-5-based symptoms of kratom-use disorder, KUD). ResultsParticipants were 54.9% male, aged 38.1 on average, and 81.3% White. Mean length of kratom use was 5.7 years. Most (95.9%) reported regularly using whole-leaf kratom products; 16 (4.1%) reported regular extract use. SOWS scores were mild to moderate on average (13.5, SD 11.9). KUD symptom counts were mostly in the mild/moderate range (80.7%). Withdrawal and KUD symptoms were more closely associated with dose frequency than dose amount. Men reported more acute effects, withdrawal symptoms with cessation, and KUD symptoms than women. ConclusionsGreater dose amount and frequency were systematically related to the number of withdrawal symptoms upon cessation and to KUD symptoms; the relationship was stronger for dose frequency than amount. Men may have more acute effects and more withdrawal and KUD symptoms than women. Although kratom may be used nonproblematically by some consumers, physical dependence (tolerance, withdrawal, or use to avoid withdrawal) and KUD become more likely with increasing dose frequency.