Local Dose Research Articles

Quantifying the spatial distribution of the accumulated dose uncertainty using the novel delta index.

Inter- and intra-fractional anatomical changes during a radiotherapy treatment can cause differences between the initially planned dose and the delivered dose. The total delivered dose can be accumulated over all fractions by using Deformable Image Registration (DIR). However, there is uncertainty in this process which should be accounted for. The aim of this study is to propose a novel metric estimating the spatial distribution of the accumulated dose uncertainty and to evaluate its performance for multi-fraction online adaptive treatments.

Approach: We postulate a new metric, the delta (δ) index, to estimate the uncertainties associated with the dose accumulation process. This metric is calculated for each voxel and takes into account the spatial uncertainty in DIR and local dose differences. For the spatial uncertainty of the DIR, the Distance Discordance Metric (DDM) was used. The accumulated dose and the δ index were determined for ten lung Stereotactic Body Radiation Therapy (SBRT) patients. The δ index was complemented by a more understandable metric, the δ index passing rate, which is the percentage of points satisfying the passing criteria in a region. 

Main Results: The spatial distribution of the δ index and the δ index passing rates showed that voxels failing the criteria were predominantly in lower-dose regions. The mean percentage of voxels passing the criterion increased from 65% to 78%, for threshold doses of 20% and 90% of the prescription doses, respectively. 

Significance: The δ index was postulated to quantify the spatial distribution of the uncertainties associated with the dose accumulation process. The metric gives an intuitive understanding of the reliability of accumulated dose distributions and derived DVH metrics. The performance of the δ index was evaluated for multi-fraction online adaptive treatments, where a case of sub-optimal image registration was identified by the metric.

The anesthetic and recovery profiles of low-dose hypobaric mepivacaine and bupivacaine for spinal anesthesia in total hip and knee arthroplasty: a prospective observational study.

Same-day mobilization and early hospital discharge is increasingly emphasized following hip and knee arthroplasty. One challenge of spinal anesthesia in this setting is achieving adequate block height while avoiding excessively large local anesthetic doses and prolonged motor and sensory blockade. Using a hypobaric local anesthetic solution is one potential strategy, as its intrathecal distribution can be reliably manipulated by patient positioning to achieve adequate block height independent of dose. We conducted a prospective observational study to determine the clinical characteristics of spinal anesthesia with low-dose hypobaric mepivacaine and bupivacaine in patients undergoing hip and knee arthroplasty. Thirty patients scheduled for same-day discharge received 51mg of hypobaric 1.5% mepivacaine and 30 patients scheduled for inpatient stay received 10mg of hypobaric 0.33% bupivacaine. The mean (standard deviation) time to achieve sensory blockade at or above L1 and T10 in the operative limb was 5.7 (1.8) and 7.3 (3.3) min with mepivacaine and 6.2 (2.6) and 8.1 (4.8) min with bupivacaine, respectively. Anesthesia was adequate for surgical commencement in all patients regardless of spinal injection level. Four patients required anesthetic supplementation for surgical completion. Sensory block duration at or above T10 and L1 in the operative limb was 97 (27) and 115 (37) min with mepivacaine and 127 (32) and 161 (34) min with bupivacaine, respectively. Motor function returned by 145 (37) and 217 (43) min in mepivacaine and bupivacaine groups, respectively. The anesthetic profiles of low-dosehypobaric mepivacaine and bupivacaine were favorable for fast-track hip and knee arthroplasty with short and predictable operating times.

Local Single-Dose Teriparatide Administration for BRONJ Prevention: Insights from a Rat Model Study.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) presents significant clinical challenges with uncertain treatment outcomes. Teriparatide, a fragment of human parathyroid hormone, shows potential in prevention strategies for BRONJ. This study investigates the impact of a single local dose of teriparatide on BRONJ prevention in an animal model. BRONJ was induced on 26 male Wistar rats via intraperitoneal injections of 0.06mg/kg Zoledronic acid weekly for four weeks. Following tooth extraction under general anesthesia, rats were divided into two groups: one received teriparatide via Gelatamp in the tooth socket and the other as a local injection in the vestibule. Control groups received the treatment without teriparatide. Histopathological assessments for bone remodeling, osteoclast number, inflammation, angiogenesis, and necrosis were performed after four weeks. Histopathological analysis indicated a significant improvement in bone remodeling and new bone formation in both treatment groups compared to controls, with notably better outcomes in the injection group (p = 0.01). Necrosis in the Gelatamp group was significantly higher in the control group than in the treatment group (p = 0.01), and bone formation was significantly higher in the injection group compared to the Gelatamp group (p = 0.03). Local administration of teriparatide significantly enhances bone remodeling and reduces necrosis, suggesting a potential role in the prevention of BRONJ. These findings support further clinical investigation into teriparatide as a preventive strategy against BRONJ.

Development of patient-specific pre-treatment verification procedure for FLASH proton therapy based on time resolved film dosimetry.

Pre-clinical studies demonstrate that delivering a high dose at a high dose rate result in less toxicity while maintaining tumor control, known as the FLASH effect. In proton therapy, clinical trials have started using 250MeV transmission beams and more trials are foreseen. A novel aspect of FLASH treatments, compared to conventional radiotherapy, is the importance of dose rate next to dose and geometry. Therefore, to ensure the safety and quality of FLASH treatments, patient-specific dose-rate verification before treatment is an important additional prerequisite. Various definitions of dose rate have been reported, however, the scanning proton beam (PBS) dose rate definition of Folkerts 2020 is currently the most used. It is the ratio between delta dose (ΔD) and delta time (Δt), subject to a predefined threshold, for a given position. Gafchromic film is a widely available detector used to perform relative and absolute integrated dose measurements. Since the response time of film is in the order of micro seconds it could also be suitable for pre-treatment verification of FLASH proton therapy. Development of a patient-specific pre-treatment verification procedure for FLASH proton therapy based on time resolved film dosimetry. The detector design is presented and validated using three tests. A dedicated setup was built that holds a Gafchromic film and a high-speed camera to record the film during the irradiations. The red color channel of the camera's readings was converted into optical density (OD) and an OD-to-dose calibration curve was applied to determine the relative dose accumulation over time. To undo the film measurement (film response) of the post-irradiation coloration process, it is assumed that each dose deposit (pulse) results in a similar film response function. The convolution of the film response function over the pulse provides the film response. First the film response function was obtained by fitting this parameter onto a known film response and corresponding pulse. Post-irradiation coloration correction was performed by deconvoluting all film measurement by the obtained film response function. From the integral of each measured pulse, the Δt was obtained. Several validation tests were conducted: compare the Δt film measurement to a reference detector, exclude that revisiting spots result in an unwanted artefact on the dose accumulation measurement and thereby Δt, and compare Δt distributions of film measurement and simulation (local gamma evaluation, criteria 10%/2 mm) for nine QA fields (dose values; 12, 15, and 20Gy, and, nozzle currents; 25, 120, and 215nA). A similar analysis was performed for three dose optimized treatment beams, with and without scan patterns optimized on local dose rate. Good agreement was found for Δt comparing film to the reference detector, but for Δt values smaller than ∼20ms the error becomes larger (≥15%). Dose accumulation measured with film over time from a single spot is independent of whether the dose is delivered at once, twice or thrice. All gamma evaluations resulted in a gamma pass rate of ≥90%. Time resolved film dosimetry to perform patient-specific pre-treatment verification in FLASH proton therapy is feasible.

RADT-48. ANALYSIS OF PROTON RADIATION THERAPY INDUCED CONTRAST ENHANCEMENT: A SINGLE INSTITUTION, RETROSPECTIVE STUDY

Abstract Proton radiotherapy (PRT) has superior physical dose distribution with a lesser integral off target radiation dose exposure compared with standard photon radiotherapy resulting in reduced toxicity of uninvolved normal tissues. However, there may be toxicity in areas targeted for high dose treatment as a result of uncertainty about the relative radiobiologic effect (RBE) of proton radiotherapy compared with photon radiotherapy and the potential for localized high doses at the end of the proton beam range (Bragg peak). This may result in radiation-induced contrast enhancement (RICE) reflecting transient toxicity or permanent injury, particularly when associated with concurrent chemotherapy. We analyzed 150 consecutive adult patients, with a histopathologic diagnosis of CNS malignancy, who underwent only PRT at Johns Hopkins Hospital between 2019 – 2023 with least 1 year of follow-up imaging. RICE was defined as a new post-treatment contrast enhancement on MRI within the radiation field. The determination of disease progression or RICE was confirmed with additional follow-up MRI or pathology. RICE was identified in 14 cases (9.3%). The median age was 48 y (range 19 – 72 years), sex 50% female. Diagnosis was 5 astrocytoma, 3 meningioma, 2 glioblastoma, 1 medulloblastoma, 2 oligodendroglioma, 1 tectal glioma. 4/5 astrocytoma patients were grade 2, 2/3 meningioma was grade 1, 1/3 was grade 2, 2/2 oligodendroglioma was grade 2. The median time since completing PRT to development of RICE was 3.5 months. The median radiation dose was 52.20 Gye (range 23.40 - 60.06). Dexamethasone was used in 11 patients (78 %) and in bevacizumab was used 2. Chemotherapy with temozolomide 7 (50%), PCV 1, and none in 5. 12 (85%) patients were still alive. PRT can also be associated with radiation injury in the target, and more information is needed about the incidence, natural history, and associations with localized dosimetry.

DDEL-17. INTRA-TUMORAL CONVECTION ENHANCED DELIVERY OF DEXAMETHASONE REDUCES INFLAMMATORY SIGNATURES AND EXTENDS SURVIVAL IN GBM MODEL

Abstract Dexamethasone is the most widely utilized drug for glioblastoma (GBM). However, systemic delivery of dexamethasone in GBM patients is associated with significant side effects and increasing doses with worse survival. Convection-enhanced delivery (CED) can deliver high doses of immunotherapy directly into the tumor microenvironment (TME) while avoiding systemic toxicity. Here, we report that high doses of dexamethasone can be delivered locally by CED without side effects and increase survival in a GBM model along with reduced inflammatory myeloid signatures. We investigated CED of dexamethasone treatment on survival(n=40), adverse side effects, and the immunological TME through peripheral analyses, liquid chromatography–mass spectrometry, and histology in a preclinical syngeneic mouse model. Additionally, we assessed the transcriptional responses of human GBM slices and stem-cell-derived human microglia after steroid treatment through bulk and single-cell RNA sequencing. We found that 7-day treatment with CED of dexamethasone produced a significant survival advantage in glioma-bearing mice compared to non-treated control(p=0.03). Systemic dexamethasone achieved low levels of drug in the TME and caused dysregulated blood glucose, blood counts, and peripheral organ weights, while high CED doses avoided these side effects(p< 0.05 each). Steroid treatment of acute GBM slices and lipopolysaccharide-activated microglia in-vitro both reversed inflammatory myeloid signatures associated with poor survival and recurrence on RNA sequencing analyses. We demonstrate the preclinical efficacy of delivering high local doses of dexamethasone in a GBM model through CED and observed prolonged survival along with reduced adverse inflammatory myeloid signatures. No side effects were demonstrated after chronic CED treatment of dexamethasone while systemic delivery achieved poor tumor penetration and caused known hematologic and metabolic side effects supporting the potential to optimize the clinical use of this therapy. CED of dexamethasone provides us a new treatment paradigm to locally control inflammatory signatures in the glioma TME in a controlled fashion.

NIMG-61. TRANSVENTRICULAR MIGRATION OF CESIUM-131 BRACHYTHERAPY SEEDS TO THE SACRAL THECAL SAC IN A PATIENT TREATED FOR RECURRENT GLIOBLASTOMA

Abstract Cesium-131 brachytherapy (GammaTileTM) is a relatively new form of surgically targeted radiation therapy for recurrent glioblastoma. While seed migration is a well-documented complication of solid tumor brachytherapy, it has not been reported in the treatment of glioblastoma. Here, we describe a rare occurrence of seed migration in a 71-year-old patient treated for recurrent left temporal lobe glioblastoma. The GammaTile is comprised of a resorbable collagen matrix containing four titanium-encapsulated radioactive Cs-131 seeds. Each seed emits a localized dose of radiation with a 9.7-day half-life. To prevent displacement from the resection cavity, oxidized regenerated cellulose (SurgicelTM) was applied to the cavity surface under the tiles and fibrin sealant (TisseelTM) was applied over the tiles. Margins of the lateral ventricles were not breached during the surgery and surface was non-ulcerated. The tiles remained in place on follow-up imaging for at least 7 weeks. At least 97% of the prescribed dose was delivered before seed migration. Bevacizumab systemic treatment was initiated. Abdominal CT obtained after 3 months incidentally noted migration of 2 seeds to the sacral spinal canal. Additional seeds had migrated to the suprasellar region, left lateral ventricle, and lateral cerebellomedullary cistern. Despite seed migration, the patient maintained progression-free survival for at least 10 months, with at least 30 months of overall survival from the time of diagnosis. Although the patient did not experience any symptoms related to seed migration, this has the potential to cause radiation-related toxicity to healthy tissue, particularly if it occurs early after surgery. The use of bevacizumab may have contributed to penetration of the lateral ventricle. Despite meticulous surgical technique, the potential for seed migration should be considered during treatment planning when using anti-angiogenic therapies. Further research is needed to better understand the factors contributing to seed migration and to develop strategies for minimizing this risk.

Ultrasound guided pediatric caudal dose: a two-center randomized controlled trial

BackgroundThe drug volume to be used in caudal in pediatric patients has remained an unmet issue since long. We determined the minimum drug volume required to reach T10 level in pediatric patients using ultrasonography and compared it with the already established volume by Armitage formula.AimTo determine the minimum effective caudal local anesthetic dose using ultrasound guidance.MethodsStudy was performed at two centres and at each centre, 50 pediatric patients (Total 100 patients), aged 1 to 3 years, undergoing below umbilical surgeries were included and randomised into two groups of 25 each (Total 50) to receive ultrasound guided drug volume vs. Armitage formula based volume. The volume required to reach T10 level was assessed with ultrasound in one group. Also, maximum height achieved, cutaneous level achieved after 15 min, FLACC scores 30 min post extubation and parental satisfaction scores were noted.ResultsThe mean drug volume required to reach T10 level in Group U was 0.755 ± 0.053 ml/kg with a P value < 0.001. (Compared to the drug volume of 1 ml/kg using one sample t test). The highest level achieved in both groups were calculated as the mode value of T8 and T7 in Group U and Group A respectively. The highest cutaneous level achieved after 15 min was also calculated as the mode value of T4 in both groups. FLACC scores at 30 min were also comparable. Satisfaction scores were comparable in both groups.ConclusionA volume of 0.7 ml/kg of local anaesthetic in pediatric caudal block is sufficient to achieve a target of T10 level for infraumblical surgeries.

DETERMINATION OF DOSE REFERENCE LEVELS AT BENDAN PEKALONGAN REGIONAL HOSPITAL FOR INTERNAL DOSE AUDIT AS AN EFFORT TO OPTIMIZE RADIATION PROTECTION FOR PATIENTS

Unnecessary exposure is less of a concern because it is considered not to cause injury to patients. Radiation protection optimization is carried out for patients to reduce unnecessary exposure. Following BAPETEN Regulation No. 4 of 2020 Article 46, permit holders are required to implement radiation protection optimization [1]. This study aimed to obtain the local dose reference level (TPD) value through an internal dose audit to optimize patient radiation protection. This optimization is carried out in several steps, including conducting an internal dose audit, determining the local TPD, and evaluating the examination. This study is expected to motivate documentation of radiation parameters to obtain sufficient data for analysis. The method used in this study is a literature study through related references and X-ray radiation output data to calculate the dose in the form of incident air kerma (INAK) and entrance surface air kerma (ESAK). The results showed that the local INAK TPD value was 52% below the national TPD, and the local ESAK TPD value was 57% below the national TPD. The expected local TPD value is a TPD value that is lower than the national TPD value. This indicates that the imaging protocol at RSUD Bendan has been well-optimized. However, there are still several types of examinations where the local TPD value exceeds the national TPD, indicating the need to review further the imaging techniques and protocols used. The influence of body weight and radiological image diagnosis was analyzed as a basis for further optimization. Thus, the determination of this local TPD can be an essential reference in efforts to improve patient safety and optimize radiation protection in health facilities. Keywords: radiation protection optimization of patient, Dose Reference Level (DRL), patient dose.

Fast onset of thrombolytic effect of efficiently inhalable spray-dried rivaroxaban powder formulations

Pulmonary embolism is a critical medical condition and can lead to cardiovascular arrest or death if left untreated. Pulmonary delivery of an anti-coagulant therapeutic could provide a locally limited and efficient therapy, moreover combined with a potentially fast onset of the therapeutic effect that is demanded in emergency situations. Rivaroxaban (riva) was formulated as an inhalable dry powder that can be administered directly to the lungs in order to reach high local drug doses. Particles obtained spray drying dichloromethane-methanol mixtures yielded an aerodynamic diameter of about or smaller than 5 µm and were found to reach an emitted fine particle fraction (FPFEF) of at least 60 %. Pulmonary administration to rats using a dry powder insufflator revealed a nearly immediate therapeutic onset confirmed by the anticoagulant effects after 5 min in the plasma, followed by a plateau over the next 4 h. Such rivaroxaban particles were further formulated in binary blends using different lactose carriers (Inhalac® 70/251/400). These interactive blends resulted in high emitted fractions of at least 87 %, and furthermore, the highest fine particle fraction − total dose (FPFTD) (60 %) of all tested formulations was achieved by using Inhalac® 400 as a carrier. The data strongly suggest a significant therapeutic potential of a rivaroxaban dry powder formulation, combining fast onset and a plateau of plasma concentrations turning it into a potential first aid therapeutic.

Design and Construction of Experimental System for Validation of a New Image Reconstruction Technique with Limited-view-angle Projection Data for BNCT-SPECT

Abstract. Boron Neutron Capture Therapy (BNCT) is expected to be a promising radiation therapy for cancer, and research on various issues associated with it is still in progress. One of the unsolved issues is the construction of a system for observing the effect of the treatment (local boron dose) in real time under high-background circumstances. Thus, we set out to establish a method for measuring gamma-rays emitted promptly from the body following the boron neutron capture reaction and reconstructing images in a SPECT-like manner. We call this method BNCT-SPECT. We have been developing a new image reconstruction method based on Bayesian estimation for the BNCT-SPECT method. In the present study, the aims were to design and construct an experimental system capable of validating BNCT-SPECT and its image reconstruction method and to confirm BNCT-SPECTs performance. The crucial takeaway from this study is that we should consider the use of extremely high background radiation during BNCT. For the validation of BNCT-SPECT, we attempted to reproduce these conditions, despite this being quite challenging. We first constructed an experimental system capable of reproducing such conditions. Theoretical investigation was carried out to facilitate the design of the system using the Monte Carlo transport calculation code MCNP. Finally, we performed experiments with some standard gamma-ray sources to complete the system.

Evaluation of radiation dose and cancer risk for paediatric digital radiography in a Moroccan hospital

Pediatric radiography is the first line of most diagnostic examinations and an effective tool that provides important information about the patient's health status.This study aims to investigate the Entrance Surface Dose (ESD) and organ doses for pediatric patients undergoing imaging procedures of the abdomen, chest, pelvis, and nasopharynx using Optically Stimulated Luminescence Dosimeters OSLDs and an anthropomorphic phantom.An ATOM pediatric 5-year-old phantom was imaged using a Digital Radiography (DR) based on similar conditions of routine radiography (exposure parameters kVp, mAs, SID: Source Image receptor Distance). The OSLDs were inserted at the appropriate sites to measure localized doses in the sensitive organs.The results showed that the entrance surface doses for the pediatric patients were 0.17 ± 0.03 mGy, 0.10 ± 0.00 mGy, 0.46 ± 0.00 mGy, and 0.42 ± 0.02 mGy, respectively, for the abdomen (AP), chest (AP), pelvis (AP), and nasopharynx (LAT). The range of organ doses were 0.05–0.45 mGy, 0.01–0.44 mGy, 0.13–1.05 mGy, and 0.084–0.99 mGy for the abdomen, chest, pelvis, and nasopharynx examination, respectively. Effective doses (ED) were 0.088 ± 0.021 mSv, 0.011 ± 0.004 mSv, 0.058 ± 0.007 mSv, and 0.044 ± 0.024 mSv for the abdomen, chest, pelvis, and nasopharynx examination, respectively.The likelihood of cancer, as determined by the ICRP health risk model with a rate of 500 cases per 10 000 person-Sv (5% per sievert), estimated that a 0.015 case of health risk (0.3 person-Sv × 5% per sievert) may in the future be attributable to four X-ray pediatric procedures conducted in 2022.The ESD, ED, and organ dose values are deemed acceptable compared to those reported in the literature. Although the risk of incidence and mortality from cancer during life is minimal, it should not be ignored.

A Comparative Study between Ultrasound-guided Concomitant Infraclavicular Plus Distal Median, Radial, and Ulnar Nerve Blockade Versus Infraclavicular Block Alone

Abstract Background: Peripheral nerve blocks can be used alone as the sole “surgical” anesthetic technique as the initial step in providing prolonged postoperative analgesia. There are studies, where accurate deposition of local anesthetic perineurally has the potential to improve the success rate and reduce the incidence of complications of the infraclavicular block. We hypothesized whether a combined block of the infraclavicular brachial plexus and distal median, radial, and ulnar nerves would accelerate upper extremity anesthesia compared with an infraclavicular block alone. Materials and Methods: This study was a prospective randomized control study conducted among 60 patients undergoing elective and emergency wrist and hand surgeries. A group of 30 patients received an infraclavicular block with 30 mL of a local anesthetic mixture containing 1% lignocaine with adrenaline and 0.25% bupivacaine from Group A. Group B received an infraclavicular block with 15 mL of local anesthetic mixture containing 1% lignocaine with adrenaline and 0.25% bupivacaine along with distal median, radial, and ulnar nerve blockade with 5 mL each of local anesthetic mixture containing 1% lignocaine with adrenaline and 0.25% bupivacaine. Pain score, assessment of sensory and motor functions, block performance time, and surgical anesthesia were observed. Results: The mean block performance time of Group A was 10.9 ± 1.1 min and Group B was 14.7 ± 0.5 min. The difference between the two groups’ block performance minutes was statistically significant (P &lt; 0.001). The difference in the onset of the sensory block between the two groups was statistically significant (P &lt; 0.001). The mean onset of motor blockade between the two groups was statistically very highly significant (P &lt; 0.001). The mean of Group A was 5.0 ± 0.2 and Group B was 2.1 ± 0.4. Conclusion: From this study, we conclude that using an approximately equivalent dose of local anesthetics, combining ultrasound-guided infraclavicular block with distal median, radial, and ulnar nerve blockade shortens the onset time of sensory and motor block with improved block consistency compared to infraclavicular block alone.

Sustainable production of radionuclidically pure antimony-119

BackgroundRadiopharmaceutical therapy (RPT) uses radionuclides that decay via one of three therapeutically relevant decay modes (alpha, beta, and internal conversion (IC) / Auger electron (AE) emission) to deliver short range, highly damaging radiation inside of diseased cells, maintaining localized dose distribution and sparing healthy cells. Antimony-119 (119Sb, t1/2 = 38.19 h, EC = 100%) is one such IC/AE emitting radionuclide, previously limited to in silico computational investigation due to barriers in production, chemical separation, and chelation. A theranostic (therapeutic/diagnostic) pair can be formed with 119Sb’s radioisotopic imaging analogue 117Sb (t1/2 = 2.80 h, Eγ = 158.6 keV, Iγ = 85.9%, β+ = 262.4 keV, Iβ+ = 1.81%).ResultsWithin, we report techniques for sustainable and cost-effective production of pre-clinical quality and quantity, radionuclidically pure 119Sb and 117Sb, novel low energy photon measurement techniques for 119Sb activity determination, and physical yields for various tin target isotopic enrichments and thicknesses using (p, n) and (d, n) nuclear reactions. Additionally, we present a two-column separation providing a radioantimony yield of 73.1% ± 6.9% (N = 3) and tin separation factor of (6.8 ± 5.5) x 105 (N = 3). Apparent molar activity measurements for deuteron produced 117Sb using the chelator TREN-CAM were measured at 42.4 ± 25 MBq 117Sb/µmol (1.14 ± 0.68 mCi/µmol), and we recovered enriched 119Sn target material at a recycling efficiency of 80.2% ± 5.5% (N = 6) with losses of 11.6 mg ± 0.8 mg (N = 6) per production.ConclusionWe report significant steps in overcoming barriers in 119Sb production, chemical isolation and purification, enriched target material recycling, and chelation, helping promote accessibility and application of this promising therapeutic radionuclide. We describe a method for 119Sb activity measurement using its low energy gamma (23.87 keV), negating the need for attenuation correction. Finally, we report the largest yet-measured 119Sb production yields using proton and deuteron irradiation of natural and enriched targets and radioisotopic purity > 99.8% at end of purification.

Real-World Experience of Erenumab in Patients with Migraine in Germany: The SPECTRE Study.

To provide real-world insights into migraine patient population in Germany treated with erenumab, focusing on the prescription patterns and reasons for the initial dosage choice. SPECTRE was an observational, non-interventional, multicenter, open-label, single-arm study in patients treated with erenumab according to approved local dose and guidelines. The study enrolled adult patients (n = 571; Germany: 105 sites) with migraine who had received erenumab for not more than 3months before the start of the study. The mean (standard deviation) patient age was 45.0 (12.3) years, and most patients were female (89.0%), Caucasian (97.6%), and non-smokers (85.1%). The starting dose of erenumab was 70mg in 68.5% of patients and 140mg in 31.5%. The proportion of patients with 140mg as the starting dose was the highest (43.5%) in those aged 30-40years. The most common reason for starting a higher dose of erenumab 140mg was severity of migraine (47.4%). During the observational period, the proportion of patients taking erenumab 140mg increased to 64.6% (visit 5; V5) after 12months. Due to attrition of patients towards the end of the study (V9: 90 participants), data at V9 must be interpreted with caution. At least one dose change was performed in 45.3% of patients (i.e., erenumab 70 to 140mg or 140 to 70mg), 21.2% of patients attempted at least once to discontinue treatment (i.e., period with erenumab discontinuation and no other antibody treatment for migraine prevention), and 15.3% discontinued erenumab treatment, mainly because of no or insufficient treatment response (13.5%). The mean time until the first omission attempt was 332.3 (range 37-633) days. Constipation (12.1%) was the most frequently reported adverse event, in line with the summary of product characteristics (SmPC) of erenumab. Most patients with migraine were prescribed erenumab 70mg as the starting dose. No new safety signals were observed for erenumab versus the previous trials.

Comparison of combined deep and superficial serratus anterior block with thoracic paravertebral block for postoperative pain in patients undergoing video-assisted thoracoscopic surgery.

Thoracic paravertebral block (TPVB) is a well-established procedure for the management of postoperative pain in patients undergoing video-assisted thoracic surgery (VATS). In recent years, there have been studies suggesting that fascial plane blocks may be an alternative to TPVB. The objective of our study was to determine the efficacy of combined deep and superficial serratus anterior block (C-SAPB) as an alternative to TPVB in the management of postoperative analgesia in VATS. The patients were divided into two groups: the TPVB group and the C-SAPB group. Both groups were administered the same dose of local anesthetics. Multimodal analgesia was achieved for the groups. The primary outcome measure was visual analog scale (VAS) pain scores recorded within the first 48 h of the postoperative period in each group. The secondary outcomes were analgesic requirement, rescue analgesics, complications rate, and postoperative patient satisfaction. Thirty patients with C-SAPB and 30 patients with TPVB were analysed. VAS rest and VAS coughing scores were similar between the groups (p > 0.05). Demographic and side effect conditions, total morphine use, additional analgesic needs, vital parameters, block procedure time, and patient satisfaction were also similar between the groups (p > 0.05). Additionally, although block application times were comparable, the time was slightly shorter in C-SAPB. Similar analgesic efficacy was observed between C-SAPB and TPVB. TPVB maintains its place among the first choices in VATS. The efficacy of C-SAPB is comparable to that of TPVB. While the duration of C-SAPB application is not a significant factor, the brief nature of the procedure and its straightforward administration suggest that it may be an effective method.

Carbon ion beam dosimetry in magnetic fields using Farmer-type ionization chambers of different radii: measurements and simulations

Objective.To investigate magnetic field effects on the dose distribution and ionization chambers response in carbon ion reference fields and determine magnetic field correction factors for chambers of different volumes.Approach.The response of six Farmer-type chambers with varying radii (1-6 mm, termed as R1-R6) was measured in magnetic fields up to 1 T in 0.1 T increments using an experimental electromagnet and compared with Monte Carlo simulations. Chamber readings were measured in the entrance region of a monoenergetic carbon ion beam of 390.75 MeV u-1. A lower energy of 200.28 MeV u-1was applied to chamber R3 for comparison. Polarity and recombination corrections were investigated for the R3 chamber. The local dose change induced by the magnetic field was calculated by Monte Carlo, which together with change of the chamber's response, was used to calculate the final magnetic field correction factors.Main results.The dependence of the chamber response on the magnetic field was non-linear and volume-dependent. Maximum changes ranged from 0.30% (R4) to 0.62% (R5) at 0.2 T. For R3, the response for the lower energy was systematically decreased by 0.2% in the range of 0.2 T to 0.7 T. No significant effect of the magnetic field on polarity and ion recombination correction was found. The maximum variation of the local dose was found to be (0.03 ± 0.08) % at 0.2 T for beam energy of 390.75 MeV u-1. Magnetic field correction factors for the different chambers ranged from 0.28% (R4) to 0.60% (R5).Significance.This study provides the first detailed analysis of chambers' response to magnetic flux densities of up to 1 T using chambers of different radii and comparison with simulations. By combining the chamber response alterations with local dose changes magnetic field correction factors were calculated for all six chambers, including the commercial Farmer-type chamber.

Quantitative CT imaging and radiation-absorbed dose estimations of 166Ho microspheres: paving the way for clinical application

BackgroundMicrobrachytherapy enables high local tumor doses sparing surrounding tissues by intratumoral injection of radioactive holmium-166 microspheres (166Ho-MS). Magnetic resonance imaging (MRI) cannot properly detect high local Ho-MS concentrations and single-photon emission computed tomography has insufficient resolution. Computed tomography (CT) is quicker and cheaper with high resolution and previously enabled Ho quantification. We aimed to optimize Ho quantification on CT and to implement corresponding dosimetry.MethodsTwo scanners were calibrated for Ho detection using phantoms and multiple settings. Quantification was evaluated in five phantoms and seven canine patients using subtraction and thresholding including influences of the target tissue, injected amounts, acquisition parameters, and quantification volumes. Radiation-absorbed dose estimation was implemented using a three-dimensional 166Ho specific dose point kernel generated with Monte Carlo simulations.ResultsCT calibration showed a near-perfect linear relation between radiodensity (HU) and Ho concentrations for all conditions, with differences between scanners. Ho detection during calibration was higher using lower tube voltages, soft-tissue kernels, and without a scanner detection limit. The most accurate Ho recovery in phantoms was 102 ± 11% using a threshold of mean tissue HU + (2 × standard deviation) and in patients 98 ± 31% using a 100 HU threshold. Thresholding allowed better recovery with less variation and dependency on the volume of interest compared to the subtraction of a single HU reference value. Corresponding doses and histograms were successfully generated.ConclusionCT quantification and dosimetry of 166Ho should be considered for further clinical application with on-site validation using radioactive measurements and intra-operative Ho-MS and dose visualizations.Relevance statementImage-guided holmium-166 microbrachytherapy currently lacks reliable quantification and dosimetry on CT to ensure treatment safety and efficacy, while it is the only imaging modality capable of quantifying high in vivo holmium concentrations.Key PointsLocal injection of 166Ho-MS enables high local tumor doses while sparing surrounding tissue.CT enables imaging-based quantification and radiation-absorbed dose estimation of concentrated Ho in vivo, essential for treatment safety and efficacy.Two different CT scanners and multiple acquisition and reconstruction parameters showed near-perfect linearity between radiodensity and Ho concentration.The most accurate Ho recoveries on CT were 102 ± 11% in five phantoms and 98 ± 31% in seven canine patients using thresholding methods.Dose estimations and volume histograms were successfully implemented for clinical application using a dose point kernel based on Monte Carlo simulations.Graphical

Supra-inguinal fascia iliaca block versus peri-capsular nerve group (PNEG) block for pain management in patients with hip fracture: A double-blind randomised comparative trial

BackgroundRegional analgesia has been recommended to alleviate pain caused by hip fractures. Both the supra-inguinal fascia iliaca block (S-FIB) and the peri‑capsular nerve group (PENG) block provide better analgesia than conventional fascia iliaca block for patients with hip fractures, but which one is superior remains equivocal. This study aimed to determine the superiority of S-FIB or PENG block for patients awaiting hip surgery. MethodsIn this prospective, double-blind, randomised comparative trial, patients with hip fractures awaiting operation were randomly allocated to receive either S-FIB with 30 ml 0.35 % ropivacaine or PENG block with 20 ml 0.35 % ropivacaine. Primary outcomes were pain scores (numeric rating scale, NRS, 0–10) at rest and during passive movement 30 min after nerve block. Secondary outcomes included pain scores at rest and during movement 10 and 20 min after nerve block and during positioning for spinal anaesthesia, time spent for performing nerve block and spinal anaesthesia, and the quality of positioning for spinal anaesthesia. ResultsOne-hundred patients were enrolled and 91 patients completed the trial (S-FIB group n = 46, PENG group n = 45). No significant difference was noted between these two groups in the pain scores (median [interquartile range]) either at rest (0 [0–0] vs 0 [0–0], P = 0.151) or during passive movement (3 [1-6] vs 3 [2-5], P = 0.99) at 30 min after nerve block. However, within-group analysis revealed that a significant reduction in pain score at rest was noted as early as 20 min after PENG block while that was noted only at 30 min after S-FIB. In addition, less time was required to perform PENG than S-FIB the block (3.1 [2.3–3.9] vs. 4.6 [3.1–5.6] minutes, P < 0.001). ConclusionsOur result suggests that with a lower dose of local anaesthetic, a shorter procedure time and earlier analgesic effect, PENG block may be preferred to S-FIB for patients with hip fracture awaiting surgery.

Minimum Local Anesthetic Dose of Ropivacaine in Cesarean Section for Real-Time Ultrasound-Guided Spinal Anesthesia Using 24-Gauge versus 26-Gauge Needles Based on Fluid Simulation Technology: A Randomized Controlled Trial.

Previous research has demonstrated that real-time ultrasound-guided (UG) spinal anesthesia requires a higher minimum local anesthetic dose (MLAD) compared to traditional methods. However, the precise MLAD of ropivacaine for UG cesarean sections remains undetermined. In this study, we ascertained the MLAD of ropivacaine for cesarean section. We also investigated the mechanism underlying the diffusion of ropivacaine within the spinal canal using fluid simulation technology. We randomly placed 60healthy parturients undergoing elective cesarean section with real-time UG spinal anesthesia into Groups I (26-gauge spinal needle) and II (24-gauge spinal needle). For the first parturient in both groups, 15 mg of ropivacaine was administered intrathecally. Based on the effective or ineffective response of the previous parturient, the dose for the subsequent parturient was increased or decreased by 1 mg. Spinal anesthesia characteristics and side effects were recorded. A computer-generated spinal canal model was developed. Leveraging fluid dynamics simulation technology, we documented the diffusion of ropivacaine in the spinal canal using 26-and 24-gauge spinal needles. The MLADs in Groups I and II were 12.728 mg (12.339-13.130 mg) and 9.795 mg (9.491-10.110 mg), respectively. No significant difference was observed in the onset times and durations of sensory or motor blocks, incidence of complications, or neonatal Apgar scores between both groups. Fluid simulation modeling indicated that the 26-gauge spinal needle achieved a higher distribution level more quickly; however, its peak drug concentration was lower compared to the 24-gauge spinal needle. For cesarean section anesthetization, the required MLAD of ropivacaine when using a real-time UG 26-gauge spinal needle is significantly greater than that with a 24-gauge needle. The spinal needle diameter influences ropivacaine's MLAD by markedly affecting its diffusion rate within the spinal canal.