Proposed local diagnostic reference levels in angiography and interventional neuroradiology and a preliminary analysis according to the complexity of the procedures

The aim of this study was to propose local diagnostic reference levels (DRL) for exposure to radiation during diagnostic procedures and neuroradiological interventions such as cerebral angiography and embolisation of cerebral aneurysms (intra-cranial aneurysms and arteriovenous malformations). Hospitals should adopt the national DRLs for use locally or establish their own DRLs based on local practice, if sufficient local data are available.For this purpose we studied a sample of 113 cerebral angiography procedures and 82 embolisations of cerebral aneurysms. The data recorded included the kerma-area product (KAP), the fluoroscopy time and the number of frames for each procedure: third quartiles from the total dosimetric databank were calculated and proposed as provisional local DRL. Since the complexity of a procedure must be taken into account when evaluating the radiation dose, in the case of embolisation of aneurysms (intra-cranial), in this initial phase we assessed whether the complexity of the embolisation procedure is related to the size of the aneurysm and/or its site. We, therefore, re-calculated the DRL for only intra-cranial aneurysms, leaving aside the arteriovenous malformations. Considering that the DRL calculated for all the therapeutic procedures are similar to those calculated considering only intra-cranial aneurysms, at the moment we propose, besides the DRL for cerebral angiography, a single DRL for all interventional procedures, even when the clinical pictures are very different. Local preliminary DRLs were proposed as follows: 180 Gy cm², 12 min and 317 frames for cerebral angiography and 487 Gy cm², 46 min and 717 frames for interventional procedures (intra-cranial aneurysms and arteriovenous malformations).     

Radiation dose and risks to fetus from nuclear medicine procedures

This article discusses issues regarding administration of radiopharmaceuticals to pregnant women. Standardized dose estimates and possible biological effects on the unborn child are presented. Current and future mathematical models (phantoms) are discussed. Standardized dose estimates for pregnant women at several stages of gestation based on the current generation of phantoms are given. Issues related to administration of radioiodines, particularly ¹³¹I-NaI, are presented. Iodine concentrates in the fetal thyroid and therefore can give very high doses, even resulting in complete destruction of the fetal thyroid. Strategies for preventing unwanted administrations of radiopharmaceuticals to these patients, and for strategies for mitigating radiation doses, should an unwanted administration occur, are discussed.     

Establishment of trigger levels to steer the follow-up of radiation effects in patients undergoing fluoroscopically-guided interventional procedures in Belgium

The accumulated dose to the skin of the patient during fluoroscopically-guided procedures can exceed the thresholds for tissue reactions. In practice, interventionalists have no direct information about the local procedure-related skin doses in their patient, causing suboptimal or delayed treatment. In current study, the accumulated Kerma-Area-Product (KAP) values were registered, as well as the reference air kerma (K_a,r) values, if available, for almost 200 cases undergoing seven different procedures. A sheet filled with 50 thermoluminescent dosemeters was wrapped around each patient to measure the peak skin dose. In a significant part of the Transjugular Intrahepatic Portosystemic Shunt (TIPSS) procedures, chemo-embolizations of the liver and cerebral embolizations, the threshold values for deterministic skin damage (2 Gy) were attained. Trigger values in terms of KAP, corresponding to a peak skin dose of 2 Gy, were determined. In general, our results comply reasonably well with the values proposed in the NCRP 168 report, with a KAP value of 425 Gy cm² and a K_a,r value of 3 Gy, corresponding to a peak skin dose of 3 Gy. Only for the TIPSS procedure a considerably lower value of 2 Gy was obtained at the published K_a,r and for the RF ablations we obtained a considerably lower value of 250 Gy cm² in terms of KAP.     

Peri-gestational risk factors for pediatric brain tumors in Neurofibromatosis Type 1

BackgroundIndividuals with Neurofibromatosis Type 1 (NF1) are strongly predisposed to developing pediatric brain tumors (PBTs), especially optic pathway gliomas (OPGs). Although developmental factors have been implicated in the origins of PBTs in both human and animal studies, associations between early-life factors and PBTs have not been evaluated in individuals with NF1. Our objective was to evaluate associations between peri-gestational characteristics and PBTs in this population.MethodsWe conducted a cross-sectional study, ascertaining questionnaire and medical record data for 606 individuals <18 years old who enrolled in the NF1 Patient Registry Initiative (NPRI) from 6/9/2011-6/29/2015. One hundred eighty-four individuals had reported PBT diagnoses, including 65 who were identified with OPG diagnoses. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between PBT and OPG diagnoses and peri-gestational characteristics (prematurity, birth weight, parental age, plurality, family history of NF1, assisted reproductive technology, maternal vitamin supplementation, and parental smoking).ResultsWe observed no significant associations between any of the assessed characteristics and PBTs overall or OPGs with the exception of birth weight. After controlling for potential confounding variables, we observed a significant positive association between birth weight quartile and OPGs with a HR of 3.32 (95% CI 1.39⿿7.94) for the fourth (⿥3915.5 g) compared to the first (⿤3020 g) quartile (p for trend = 0.001).ConclusionsConsistent with results for PBTs in the general population, these results suggest that higher birth weights increase OPG risk in individuals with NF1.     

Radiation dose and second cancer risk in patients treated for cancer of the cervix

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.     

Radiation dose to the fetus during CyberKnife radiosurgery for a brain tumor in pregnancy

PurposePregnancy during radiosurgery is extremely rare in clinical practice. We report fetal dose results during CyberKnife radiosurgery for a brain tumor in pregnancy.Methods and materialsA 26 year old pregnant woman with a rapidly growing deep-seated grade-III glioma was treated during the third trimester of gestation using CyberKnife. Ultrasound imaging was used to determine the position of the embryo prior to treatment. A dose of 1400 cGy was prescribed aiming to control tumor growth until delivery of the child. Prior to radiosurgery, the treatment was simulated on an anthropomorphic phantom. Radiation dose to the embryo was measured using a Farmer chamber and EBT3 films.ResultsFetal doses of 4.4 cGy and 4.1 cGy were measured for the embryo's head and legs, lying at 56 cm and 72 cm from the isocenter, respectively, using the Farmer chamber situated at 8.5 cm depth beneath the phantom surface. Dose results of 4.4 cGy, 3.5 cGy and 2.0 cGy were measured with the films situated at depths of 6.5 cm, 9.5 cm and 14.5 cm, respectively. An average dose of 4.2 cGy to the fetus was derived from the above values. A corresponding dose of 3.2 cGy was also calculated based on results obtained using EBT3 films situated upon the patient skin.ConclusionsThe measured fetal doses are below the threshold of 10 cGy for congenital malformations, mental and growth retardation effects. The radiogenic cancer risk to the live-born embryo was estimated less than 0.3% over the normal incidence. The treatment was administered successfully, allowing the patient to deliver a healthy child.     

Scattered dose to radiosensitive organs and associated risk for cancer development from head and neck radiotherapy in pediatric patients

The purpose of this study was to measure the scattered dose to out-of-field organs from head and neck radiotherapy in pediatric patients and to estimate the risk for second cancer induction to individual organs. Radiotherapy for thalamic tumor, brain tumor, acute leukemia and Hodgkin's disease in the neck region was simulated on 5 and 10-year-old pediatric phantoms with a 6 MV photon beam. The radiation dose to thyroid, breast, lung, stomach, ovaries, bladder, liver, uterus, prostate and colon was measured using thermoluminescent dosimeters. The methodology, provided by the BEIR VII report was used for the second cancer risk estimations. Peripheral dose range for a simulated 5-year-old patient was 0.019%–1.572% of the given tumor dose. The corresponding range at the advanced patient age was reduced to 0.018%–1.468%. The second cancer risk per fraction for male patients varied from 3 to 215 per 1,000,000 patients depending upon the age at the time of exposure, primary cancer site and organ scattered dose. The corresponding risk for females was 1–1186 per 1,000,000 patients. The higher risk values were found for breast, thyroid and lung cancer development. The current data concerning the risk magnitude for developing subsequent neoplasms to various out-of-field organs may be of value for health care professionals in the follow-up studies of childhood cancer survivors.     

Characterisation of grids of point detectors in maximum skin dose measurement in fluoroscopically-guided interventional procedures

PurposePoint detectors are frequently used to measure patient's maximum skin dose (MSD) in fluoroscopically-guided interventional procedures (IP). However, their performance and ability to detect the actual MSD are rarely evaluated. The present study investigates the sampling uncertainty associated with the use of grids of point detectors to measure MSD in IP.MethodChemoembolisation of the liver (CE), percutaneous coronary intervention (PCI) and neuroembolisation (NE) procedures were studied. Spatial dose distributions were measured with XR-RV3 Gafchromic^® films for 176 procedures. These distributions were used to simulate measurements performed using grids of detectors such as thermoluminescence detectors, with detector spacing from 1.4 up to 10 cm.ResultsThe sampling uncertainty was the highest in PCI and NE procedures. With 40 detectors covering the film area (36 cm × 44 cm), the maximum dose would be on average 86% and 63% of the MSD measured with Gafchromic^® films in CE and PCI procedures, respectively. In NE procedures, with 27 detectors covering the film area (14 cm × 35 cm), the maximum dose measured would be on average 82% of the MSD obtained with the Gafchromic^® films.ConclusionThermoluminescence detectors show good energy and dose response in clinical beam qualities. However the poor spatial resolution of such point-like dosimeters may far outweigh their good dosimetric properties. The uncertainty from the sampling procedure should be estimated when point detectors are used in IP because it may lead to strong underestimation of the MSD.     

Immunohistochemical detection of nestin in pediatric brain tumors.

Nestin is an intermediate filament protein (IFP) expressed in undifferentiated cells during CNS development and in CNS tumors. Previous studies have arrived at different conclusions in terms of which types of CNS tumors express nestin. In this report we establish an immunohistochemical protocol using antigen retrieval, which significantly enhances staining with two polyclonal anti-nestin antisera, #130 and #4350. The staining pattern was identical for the two nestin antisera and very similar to that of vimentin, while glial fibrillary acidic protein (GFAP), immunoreactivity was absent from 9.5-week-old forebrain. The current study of 20 primary CNS tumors from pediatric patients included seven ependymomas, seven primitive neuroectodermal tumors (PNETs), five pilocytic astrocytomas, and one glioblastoma multiforme (GBM). All these tumors expressed nestin to various extents, in contrast to five brain metastases tested. Strong nestin immunoreactivity was found in malignant primary CNS tumors, whereas benign pilocytic astrocytomas showed low but consistent nestin expression. In all tumors nestin immunoreactivity was confined to the cytoplasm of tumor cells and was co-expressed with astrocyte markers vimentin, GFAP, and S-100. Vascular endothelial cells of all neoplasms also showed marked immunoreactivity for nestin and vimentin, whereas they were negative for GFAP and S-100. In conclusion, antiserum #4350 detected nestin in formalin-fixed, paraffin-embedded tissue sections by heat-induced antigen retrieval immunohistochemistry. Nestin was expressed in both highly malignant and low malignant gliomas, indicating the potential use of nestin as a diagnostic tumor marker in surgical pathology.     

Radiation dose to patients and staff during angiography of the lower limbs. Derivation of local dose reference levels

BackgroundThe Euratom directive 97/43 recommends the use of patient dose surveys in diagnostic radiology and the establishment of reference dose levels (DRLs).PurposeTo perform measurements of the dose delivered during diagnostic angiography of the lower limbs using thermoluminescence dosimeters (TLDs), extraction of DRLs and estimation of the effective dose and radiation risk for this particular examination.MethodsDose measurement was performed on 30 patients by using TLD sachets attached in 5 different positions not only on the patient, but also to the radiologist. All the appropriate factors were recorded. Measurement of the ESD was performed after each examination.ResultsThe mean entrance skin dose (ESD) was calculated to be 70.8, 67.7, 24.3, 18.4, 9.7 mGy at the level of aorta bifurcation, pelvis, femur, knees, and at feet, respectively. The average effective dose is 9.8 mSv with the radiation risks for fatal cancer to be 5.4 × 10^?4. The effective dose of the radiologist was calculated to be 0.023 mSv per procedure.ConclusionRadiation dose variation depends on the physical characteristics of the patient, on the procedure preferences by radiologists and the difficulties in conducting procedures. The main reason for the increased patient dose, compared to other studies, is the number of frames rather than the duration of fluoroscopy. For DSA of the lower limbs, the DRL was chosen to be an entrance skin dose of 96.4 mGy in the pelvic region. The dose to the radiologist is negligible.     

Patient exposure data and operator dose in coronary interventional procedures: Impact of body-mass index and procedure complexity

PurposeThe aim of this study was to assess patient exposure data and operator dose in coronary interventional procedures, when considering patient body-mass index and procedure complexity.MethodsTotal air kerma area product (P_KA), Air-Kerma (AK), Fluoroscopy time (FT), operator dose and patient body-mass index (BMI) from 97 patients’ procedures (62 coronary angiography (CA) and 35 Percutaneous Coronary Intervention (PCI) were collected for one year. For PCI procedures, also the complexity index-CI was collected. Continuous variables for each of the 2 groups procedures (CA and PCI) were compared as medians with interquartile range and using Mann-Whitney U test. Multiple group data were compared using Kruskal-Wallis test (significance: p < 0.05).ResultsMedian P_KA was 63 and 125 Gy cm² for CA and PCI respectively (p < 0.001); FT was 3 and 14 min, respectively (p < 0.001). P_KA and FT significantly increased (p < 0.05) with BMI class for CA procedures. P_KA and FT also increased in function of CI class for PCI, thought significantly only for FT (p < 0.001), possibly because of the low number of PCI procedures included; cine mode contributed most to P_KA. Significant dose variability was observed among cardiologists for CA procedures (p < 0.001).ConclusionsDose references levels for P_KA and FT in interventional cardiology should be defined - on a sufficient number of procedures- in function of CI and BMI classes. These could provide an additional tool for refining a facility’s quality assurance and optimization processes. Dose variability associated with cardiologists underlines the importance of continuous training.     

Comparative performance evaluation of a flat detector and an image intensifier angiographic system both used for interventional cardiology procedures in adult and pediatric patients

PurposeTo compare two angiography systems of different image capture technology, one with flat detector (FD) and one with image intensifier (II), in terms of entrance surface air kerma (ESAK) rate, detector dose (DD) rate and image quality (IQ), in interventional cardiology procedures concerning both adult and pediatric patients.Materials and methodsIn order to determine ESAK and DD rates, a digital dosimeter and polymethylmethacrylate (PMMA) plates were used. For the evaluation of IQ, two contrast objects (the Leeds TOR 18FG and a 5 mm-thick Aluminum plate) were used and two figures of merit were defined in fluoroscopy and cine acquisition modes. Measurements of ESAK, DD rates and IQ were made for various fields of view, pulse and frame acquisition rates.ResultsFor the particular setup used in this study was noted that ESAK values in the II system were generally larger than the respective values in the FD system (on average 70% for fluoro mode, 5 times for cine mode). When halving the fluoroscopy pulse rate, reduction in ESAK was not proportional, in fluoroscopy mode. Image quality evaluations indicated that II performs better in terms of low contrast sensitivity (LCS) and signal-to-noise ratio (SNR) than the FD system which performs better regarding high contrast resolution (HCR). However, when considering image quality in relation to ESAK the FD system performs better than the II system (with the exception of low thicknesses and zooms for high pulse rates in the fluoroscopy mode).ConclusionsThe FD system, generally, provides a better image quality–dose relation than the II system although II unit provides better LCS and SNR. This means that with the right adjustments to both systems, FD unit is able to provide same image quality with lower dose. However, newer technology does not automatically imply better image quality and further investigation is necessary for deriving safe conclusions for units which utilize different capture technology.     

Clinical relevance of tumor cells with stem-like properties in pediatric brain tumors

Background

Primitive brain tumors are the leading cause of cancer-related death in children. Tumor cells with stem-like properties (TSCs), thought to account for tumorigenesis and therapeutic resistance, have been isolated from high-grade gliomas in adults. Whether TSCs are a common component of pediatric brain tumors and are of clinical relevance remains to be determined.

Methodology/Principal Findings

Tumor cells with self-renewal properties were isolated with cell biology techniques from a majority of 55 pediatric brain tumors samples, regardless of their histopathologies and grades of malignancy (57% of embryonal tumors, 57% of low-grade gliomas and neuro-glial tumors, 70% of ependymomas, 91% of high-grade gliomas). Most high-grade glioma-derived oncospheres (10/12) sustained long-term self-renewal akin to neural stem cells (>7 self-renewals), whereas cells with limited renewing abilities akin to neural progenitors dominated in all other tumors. Regardless of tumor entities, the young age group was associated with self-renewal properties akin to neural stem cells (P = 0.05, chi-square test). Survival analysis of the cohort showed an association between isolation of cells with long-term self-renewal abilities and a higher patient mortality rate (P = 0.013, log-rank test). Sampling of low- and high-grade glioma cultures showed that self-renewing cells forming oncospheres shared a molecular profile comprising embryonic and neural stem cell markers. Further characterization performed on subsets of high-grade gliomas and one low-grade glioma culture showed combination of this profile with mesenchymal markers, the radio-chemoresistance of the cells and the formation of aggressive tumors after intracerebral grafting.

Conclusions/Significance

In brain tumors affecting adult patients, TSCs have been isolated only from high-grade gliomas. In contrast, our data show that tumor cells with stem cell-like or progenitor-like properties can be isolated from a wide range of histological sub-types and grades of pediatric brain tumors. They suggest that cellular mechanisms fueling tumor development differ between adult and pediatric brain tumors.     

The mechanism of reducing thiopentone dose in elderly patients undergoing surgery

The dose of thiopentone required to induce anesthesia in adults decreasing with age is not due to pharmacodynamic change. The change of pharmacokinetic properties of thiopentone with age in undergoing surgery patient's arterial blood was investigated in seven elderly (67-82 yr) and six young (21-33 yr) patients of both sexes. Thiopentone (3 mg kg-1) was administered intravenously and arterial blood samples were obtained immediately after the injection to measure plasma and red blood cell thiopentone concentrations by an HPLC method. Plasma protein binding was studied using ultracentrifuge method. The disappearance of thiopentone from the arterial blood was described by a two-compartment open model. The distribution rate constant (alpha) was significantly larger in the young patients (p less than 0.001). The distribution half-life was longer in the elderly (p less than 0.05). Both the input microscopic rate constant, K21, and the exit microscopic rate constant, K12, with the central compartment were significantly larger in the young patients. (p less than 0.02 and p less than 0.001, respectively). The difference between the exit and input microscopic rate constant, K12-K21, was much larger in the young patients (p less than 0.001). The plasma protein binding was significantly reduced in the elderly (p less than 0.05). The apparent overall volume of distribution, Vd was not significantly different between young and elder patients. However, the volume of distribution of the central compartment was smaller in the young patients (p less than 0.05). This was probably due to the difficulty of estimation of initial thiopentone plasma concentration post-equilibrium in the central compartment after administration of thiopentone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of eye doses to staff involved in interventional cardiology procedures in Kuwait

In this study, which is the first of its kind in the gulf region, eye doses of interventional cardiologists and nurses were measured using active dosimeters for left and right eyes, in 60 percutaneous coronary interventions in three main hospitals in Kuwait. The dose given in terms of H_p(0.07) per procedure when ceiling suspended screens were used by main operators ranged from 18.5 to 30.3 µSv for the left eye and from 12.6 to 23.6 µSv for the right eye. Taking into account typical staff workload, the results show that the dose limit of 20 mSv/year to the eyes can be exceeded for interventional cardiologists in some situations, which demonstrates the need of using additional effective radiation protection tools, e.g. protective eye spectacles, in addition to the regular and proper use of ceiling suspended screens. With indications of increase in workload, the need for availability of a dedicated active dosimeter for the regular monitoring of eye doses is emphasized.

     

Effect of patient positioning on carbon-ion therapy planned dose distribution to pancreatic tumors and organs at risk

PurposePancreatic tumor treatment dose distribution variations associated with supine and prone patient positioning were evaluated.MethodsA total of 33 patients with pancreatic tumors who underwent CT in the supine and prone positions were analyzed retrospectively. Gross tumor volume (GTV), planning target volume (PTV), and organs at risk (OARs) (duodenum and stomach) were contoured. The prescribed dose of 55.2 Gy (RBE) was planned from four beam angles (0°, 90°, 180°, and 270°). Patient collimator and compensating boli were designed for each field. Dose distributions were calculated for each field in the supine and prone positions. To improve dose distribution, patient positioning was selected from supine or prone for each beam field.ResultsCompared with conventional beam angle and patient positioning, D2cc of 1st-2nd portion of duodenum (D1-D2), 3rd-4th portion of duodenum (D3-D4), and stomach could be reduced to a maximum of 6.4 Gy (RBE), 3.5 Gy (RBE), and 4.5 Gy (RBE) by selection of patient positioning. V10 of D1-D2, D3-D4, and stomach could be reduced to a maximum of 7.2 cc, 11.3 cc, and 11.5 cc, respectively. D95 of GTV and PTV were improved to a maximum of 6.9% and 3.7% of the prescribed dose, respectively.ConclusionsOptimization of patient positioning for each beam angle in treatment planning has the potential to reduce OARs dose maintaining tumor dose in pancreatic treatment.