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Background Epidemiologic studies of radiation-exposed populations form the basis for human safety standards. They also help shape public health policy and evidence-based health practices by identifying and quantifying health risks of exposure in defined populations. For more than a century, epidemiologists have studied the consequences of radiation exposures, yet the health effects of low levels delivered at a low-dose rate remain equivocal. Materials and methods The Million Person Study (MPS) of U.S. Radiation Workers and Veterans was designed to examine health effects following chronic exposures in contrast with brief exposures as experienced by the Japanese atomic bomb survivors. Radiation associations for rare cancers, intakes of radionuclides, and differences between men and women are being evaluated, as well as noncancers such as cardiovascular disease and conditions such as dementia and cognitive function. The first international symposium, held November 6, 2020, provided a broad overview of the MPS. Representatives from four U.S. government agencies addressed the importance of this research for their respective missions: U.S. Department of Energy (DOE), the Centers for Disease Control and Prevention (CDC), the U.S. Department of Defense (DOD), and the National Aeronautical Space Agency (NASA). The major components of the MPS were discussed and recent findings summarized. The importance of radiation dosimetry, an essential feature of each MPS investigation, was emphasized. Results The seven components of the MPS are DOE workers, nuclear weapons test participants, nuclear power plant workers, industrial radiographers, medical radiation workers, nuclear submariners, other U.S. Navy personnel, and radium dial painters. The MPS cohorts include tens of thousands of workers with elevated intakes of alpha particle emitters for which organ-specific doses are determined. Findings to date for chronic radiation exposure suggest that leukemia risk is lower than after acute exposure; lung cancer risk is much lower and there is little difference in risks between men and women; an increase in ischemic heart disease is yet to be seen; esophageal cancer is frequently elevated but not myelodysplastic syndrome; and Parkinson's disease may be associated with radiation exposure. Conclusions The MPS has provided provocative insights into the possible range of health effects following low-level chronic radiation exposure. When the 34 MPS cohorts are completed and combined, a powerful evaluation of radiation-effects will be possible. This final article in the MPS special issue summarizes the findings to date and the possibilities for the future. A National Center for Radiation Epidemiology and Biology is envisioned.

This paper summarizes the dose to the eye lens of workers of Memorial Sloan Kettering Cancer Center, a high-volume US oncologic and associated diseases facility. The doses presented in this report were collected from personal dosemeter readings using optically stimulated luminescence badges to estimate Hp(3). Doses were collected for 5950 clinical and research workers between January 2012 and December 2017. The median eye lens dose for all monitored workers was 0.23 mSv y−1. Workers performing, or supporting, fluoroscopy procedures received the highest unprotected eye lens dose of all workers with a median eye dose of 10 mSv. The use of leaded glasses by this group reduced the actual doses to the lens. Nurses and technicians involved in positron emission tomography injections received median eye lens dose of 1.2 mSv.

BACKGROUND: The National Council on Radiation Protection and Measurements (NCRP) is coordinating an expansive epidemiologic effort entitled the Million Person Study of Low-Dose Radiation Health Effects (MPS). Medical workers constitute the largest occupational radiation exposed group whose doses are typically received gradually over time. METHODS: A unique opportunity exists to establish an Institutional Review Board/Privacy Board (IRB/PB) approved, retrospective feasibility sub-cohort of diseased Memorial Sloan Kettering Cancer Center (MSK) medical radiation workers to reconstruct occupational/work history, estimate organ-specific radiation absorbed doses, and review existing publicly available records for mortality from cancer (including leukemia) and other diseases. Special emphasis will be placed on dose reconstruction approaches as a means to provide valid organ dose estimates that are as accurate and precise as possible based on the available data, and to allow proper evaluation of accompanying uncertainties. Such a study that includes validated dose measurements and information on radiation exposure conditions would significantly reduce dose uncertainties and provided greatly improved information on chronic low-dose risks. RESULTS: The feasibility sub-cohort will include deceased radiation workers from MSK who worked during the nearly seventy-year timeframe from 1946 through 2010 and were provided individual personal radiation dosimetry monitors. A feasibility assessment focused on obtaining records for about 25–30,000 workers, with over 124,000 annual doses, including personnel/work histories, specific dosimetry data, and appropriate information for epidemiologic mortality tracing will be conducted. MSK radiation dosimetry measurements have followed stringent protocols complying with strict worker protection standards in order to provide accurate dose information for radiation workers that include detailed records of work practices (including specific task exposure conditions, radiation type, energy, geometry, personal protective equipment usage, badge position, and missed doses), as well as recorded measurements. These dose measurements have been ascertained through a variety of techniques that have evolved over the years, from film badges to thermoluminescent dosimetry technology to optically stimulated luminescent methodologies. It is expected that individual total doses for the sub-cohort will have a broad range from =1000 mSv. CONCLUSIONS: MSK has pioneered the use of novel radiation diagnostic and therapeutic approaches over time (including initial work with x-rays, radium and radon), with workplace safety in mind, resulting in a variety of radiation worker exposure scenarios. The results of this feasibility sub-cohort of deceased radiation workers, and associated lessons learned may potentially be applied to an expanded multicenter study of about 170,000 medical radiation worker component of the MPS.

Radiation reduction in the pediatric cardiac catheterization laboratory is well-suited for targeted quality improvement (QI) interventions. Transcatheter atrial septal defect (ASD) closure was chosen for this QI project based on a homogenous procedural population and inter-operator variability in radiation usage, with the aim to reduce radiation exposure during ASD device closure by 50% over 1 year. The aim for this project was defined and a Key Driver Diagram (KDD) was created with three domains for change: modification of procedural practice, reporting and monitoring/feedback, and team engagement. All patients undergoing attempted transcatheter ASD closure were considered for inclusion. The primary outcome, % reduction in median radiation dose (DAP/Kg), was determined through comparison with a historical cohort. Additional radiation metrics, procedural characteristics, and adverse events (AE) were compared to the historical cohort. Radiation exposure (DAP/kg) was reduced by 55% with a median dose reduction from 26 (15, 61) in a historical cohort to 12 (6, 22) in the intervention population (p

Estimate organ and effective doses from computed tomography scans of pediatric oncologic patients using patient-specific information.With IRB approval patient-specific scan parameters and patient size obtained from DICOM images and vendor-provided dose monitoring application were obtained for a cross-sectional study of 1250 pediatric patients from 0 through 20 y-olds who underwent head, chest, abdomen-pelvis, or chest-abdomen-pelvis CT scans. Patients were categorized by age. Organ doses and effective doses were estimated using VirtualDose™ CT based on patient-specific information, tube current modulation (TCM), and age-specific realistic phantoms. CTDIvol, DLP, and dose results were compared with those reported in the literature.CTDIvol and DLP varied widely as patient size varied. The 75th percentiles of CTDIvol and DLP were no greater than in the literature with the exception of head scans of 16-20 y-olds and of abdomen-pelvis scans of larger patients. Eye lens dose from a head scan was up to 69 mGy. Mean organ doses agreed with other studies at maximal difference of 38% for chest and 41% for abdomen-pelvis scans. Mean effective dose was generally higher for older patients. The highest effective doses were estimated for the 16-20 y-olds as: head 3.3 mSv, chest 4.1 mSv, abdomen-pelvis 10.0 mSv, chest-abdomen-pelvis 14.0 mSv.Patient-specific organ and effective doses have been estimated for pediatric oncologic patients from1 through 20 y-olds. The effect of TCM was successfully accounted for in the estimates. Output parameters varied with patient size. CTDIvol and DLP results are useful for future protocol optimization.

The workload for shielding purposes of modern linear accelerators (linacs) consists of primary and scatter radiation which depends on the dose delivered to isocenter (cGy) and leakage radiation which depends on the monitor units (MUs). In this study, we report on the workload for 10 treatment vaults in terms of dose to isocenter (cGy), monitor units delivered (MUs), number of treatment sessions (Txs), as well as, use factors (U) and modulation factors (CI) for different treatment techniques. The survey was performed for the years between 2006 and 2015 and included 16 treatment machines which represent different generations of Varian linear accelerators (6EX, 600C, 2100C, 2100EX, and TrueBeam) operating at different electron and x‐ray energies (6, 9, 12, 16 and 20 MeV electrons and, 6 and 15 MV x‐rays). An institutional review board (IRB) approval was acquired to perform this study. Data regarding patient workload, dose to isocenter, number of monitor units delivered, beam energies, gantry angles, and treatment techniques were exported from an ARIA treatment management system (Varian Medical Systems, Palo Alto, Ca.) into Excel spreadsheets and data analysis was performed in Matlab. The average (± std‐dev) number of treatment sessions, dose to isocenter, and number of monitor units delivered per week per machine in 2006 was 119 ± 39 Txs, (300 ± 116) × 102 cGys, and (78 ± 28) × 103 MUs respectively. In contrast, the workload in 2015 was 112 ± 40 Txs, (337 ± 124) × 102 cGys, and (111 ± 46) × 103 MUs. 60% of the workload (cGy) was delivered using 6 MV and 30% using 15 MV while the remaining 10% was delivered using electron beams. The modulation factors (MU/cGy) for IMRT and VMAT were 5.0 (± 3.4) and 4.6 (± 1.6) respectively. Use factors using 90° gantry angle intervals were equally distributed (~0.25) but varied considerably among different treatment techniques. The workload, in terms of dose to isocenter (cGy) and subsequently monitor units (MUs), has been steadily increasing over the past decade. This increase can be attributed to increased use of high dose hypo‐fractionated regimens (SBRT, SRS) and the increase in use of IMRT and VMAT, which require higher MUs per cGy as compared to more conventional treatment (3DCRT). Meanwhile, the patient workload in terms of treatment sessions per week remained relatively constant. The findings of this report show that variables used for shielding purposes still fall within the recommendation of NCRP Report 151.

Background Computed Tomography (CT) contributes up to 50% of the medical exposure to the United States population. Children are considered to be at higher risk of developing radiation-induced tumors due to the young age of exposure and increased tissue radiosensitivity. Organ dose estimation is essential for pediatric and adult patient cancer risk assessment. The objective of this study is to validate the VirtualDose software in comparison to currently available software and methods for pediatric and adult CT organ dose estimation. Methods Five age groups of pediatric patients and adult patients were simulated by three organ dose estimators. Head, chest, abdomen-pelvis, and chest-abdomen-pelvis CT scans were simulated, and doses to organs both inside and outside the scan range were compared. For adults, VirtualDose was compared against ImPACT and CT-Expo. For pediatric patients, VirtualDose was compared to CT-Expo and compared to size-based methods from literature. Pediatric to adult effective dose ratios were also calculated with VirtualDose, and were compared with the ranges of effective dose ratios provided in ImPACT. Results In-field organs see less than 60% difference in dose between dose estimators. For organs outside scan range or distributed organs, a five times’ difference can occur. VirtualDose agrees with the size-based methods within 20% difference for the organs investigated. Between VirtualDose and ImPACT, the pediatric to adult ratios for effective dose are compared, and less than 21% difference is observed for chest scan while more than 40% difference is observed for head-neck scan and abdomen-pelvis scan. For pediatric patients, 2 cm scan range change can lead to a five times dose difference in partially scanned organs. Conclusions VirtualDose is validated against CT-Expo and ImPACT with relatively small discrepancies in dose for organs inside scan range, while large discrepancies in dose are observed for organs outside scan range. Patient-specific organ dose estimation is possible using the size-based methods, and VirtualDose agrees with size-based method for the organs investigated. Careful range selection for CT protocols is necessary for organ dose optimization for pediatric and adult patients.

Background:Chronic disease in older adults is estimated to account for 84% of annual health care spending in the United States, with many preventable costs expected to rise as the population continues to age. Introduction:Telehealth Intervention Programs for Seniors (TIPS) is a community-embedded program targeting low-income older adults, providing weekly assessment of vital signs and subjective wellness, and wrap-around aging services. Materials and Methods:TIPS recruited 765 volunteers over 55 years, who were Medicaid and/or Medicare eligible. Data were collected from 2014 to 2016 [median enrollment 343 days (105–435)] using 12 TIPS sites. This observational study evaluated the efficacy of TIPS by measuring within-subject changes in self-reported hospital visits and

OBJECTIVE. Patient-specific organ and effective dose provides essential information for CT protocol optimization. However, such information is not readily available in the scan records. The purpose of this study was to develop a method to obtain accurate examination- and patient-specific organ and effective dose estimates by use of available scan data and patient body size information for a large cohort of patients. MATERIALS AND METHODS. The data were randomly collected for 1200 patients who underwent CT in a 2-year period. Physical characteristics of the patients and CT technique were processed as inputs for the dose estimator. Organ and effective doses were estimated by use of the inputs and computational human phantoms matched to patients on the basis of sex and effective diameter. Size-based ratios were applied to correct for patient-phantom body size differences. RESULTS. Patients received a mean of 59.9 mGy to the lens of the eye per brain scan, 10.1 mGy to the thyroid per chest scan, 17.5 mGy to the liver per abdomen and pelvis scan, and 19.0 mGy to the liver per body scan. A factor of 2 difference in dose estimates was observed between patients of various habitus. CONCLUSION. Examination- and patient-specific organ and effective doses were estimated for 1200 adult oncology patients undergoing CT. The dose conversion factors calculated facilitate rapid organ and effective dose estimation in clinics. Compared with nonspecific dose estimation methods, patient dose estimations with data specific to the patient and examination can differ by a factor of 2.

The purpose of this study was to measure juvenile patient radiation dose to organs of the head and neck during digital panoramic and cephalometric radiography using anthropomorphic CIRS phantoms at 5 and 10-years-old with nanoDot optically stimulated luminescent dosimeters (OSLDs). OSLDs were placed at 21 head and neck organ sites of the phantom heads. Phantom heads were subjected to panoramic and cephalometric imaging protocols using manufacturers’ predefined exposure settings. Radiation dose fractions to various organ sites were determined using reference values from the ICRP-89 document. Organ equivalent doses and overall effective doses were based on ICRP-103 tissue weighting factors. Overall measured organ doses were higher for the 5-year-old than for the 10-year-old for both the panoramic and the cephalometric imaging protocols. The highest doses seen were in the salivary glands, extrathoracic airway, and the oral mucosa. The organ equivalent dose in microsieverts (µSv) also yielded similar results. The effective dose for the 5-year-old was 27.8 µSv for the panoramic and 6.5 µSv for the cephalometric, while the 10-year-old results were 26.3 µSv for the panoramic and 3.8 µSv for the cephalometric. The effective doses estimated for this study for the 5-year-old and 10-year-old during cephalometric procedures are lower than the US natural background reading of 8.5 µSv per day and lower than the US average exposure per day of 17 µSv. The effective doses estimated in this study for the panoramic procedure for both phantoms were above the natural background and above the national average per day. These data support the notion that child-appropriate technique factors and geometry factors should be used for panoramic and cephalometric imaging protocols.

Focal cortical dysplasia (FCD) is the most common cause of pediatric epilepsy and the third most common lesion in adults with treatment-resistant epilepsy. Advances in MRI have revolutionized the diagnosis of FCD, resulting in higher success rates for resective epilepsy surgery. However, many patients with histologically confirmed FCD have normal presurgical MRI studies ('MRI-negative'), making presurgical diagnosis difficult. The purpose of this study was to test whether a novel MRI postprocessing method successfully detects histopathologically verified FCD in a sample of patients without visually appreciable lesions. We applied an automated quantitative morphometry approach which computed five surface-based MRI features and combined them in a machine learning model to classify lesional and nonlesional vertices. Accuracy was defined by classifying contiguous vertices as "lesional" when they fell within the surgical resection region. Our multivariate method correctly detected the lesion in 6 of 7 MRI-positive patients, which is comparable with the detection rates that have been reported in univariate vertex-based morphometry studies. More significantly, in patients that were MRI-negative, machine learning correctly identified 14 out of 24 FCD lesions (58%). This was achieved after separating abnormal thickness and thinness into distinct classifiers, as well as separating sulcal and gyral regions. Results demonstrate that MRI-negative images contain sufficient information to aid in the in vivo detection of visually elusive FCD lesions.

The brain morphometry of 21 children, who were followed from birth and underwent structural brain magnetic resonance imaging at 8-10 years, was studied. This cohort included 11 children with prenatal cocaine exposure (CE) and 10 noncocaine-exposed children (NCE). We compared the CE versus NCE groups using FreeSurfer to automatically segment and quantify the volume of individual brain structures. In addition, we created a pediatric atlas specifically for this population and demonstrate the enhanced accuracy of this approach. We found an overall trend towards smaller brain volumes among CE children. The volume differences were significant for cortical gray matter, the thalamus and the putamen. Here, reductions in thalamic and putaminal volumes showed a robust inverse correlation with exposure levels, thus highlighting effects on dopamine-rich brain regions that form key components of brain circuitry known to play important roles in behavior and attention. Interestingly, head circumferences (HCs) at birth as well as at the time of imaging showed a tendency for smaller size among CE children. HCs at the time of imaging correlated well with the cortical volumes for all subjects. In contrast, HCs at birth were predictive of the cortical volume only for the CE group. A subgroup of these subjects (6 CE, 4 NCE) was also scanned at 13-15 years of age. In subjects who were scanned twice, we found that the trend for smaller structures continued into teenage years. We found that the differences in structural volumes between the CE and NCE groups are largely diminished when the HCs are controlled for or matched by study design. Participants in this study were drawn from a unique longitudinal cohort and, while the small sample size precludes strong conclusions regarding the longitudinal findings reported, the results point to reductions in HCs and in specific brain structures that persist through teenage years in children who were exposed to cocaine in utero.

Background Despite recommendations to do so, few orthopaedists wear leaded glasses when performing operative fluoroscopy. Radiation exposure to the ocular lens causes cataracts, and regulatory limits for maximum annual occupational exposure to the eye continue to be revised downward. Methods Using anthropomorphic patient and surgeon phantoms, radiation dose at the surgeon phantom's lens was measured with and without leaded glasses during fluoroscopic acquisition of sixteen common pelvic and hip views. The magnitude of lens dose reduction from leaded glasses was calculated by dividing the unprotected dose by the dose measured behind leaded glasses. Results On average, the use of leaded glasses reduced radiation to the surgeon phantom's eye by tenfold, a 90% reduction in dose. However, there was widespread variation in the amount of radiation that reached the phantom surgeon's eye among the various radiographic projections we studied. Without leaded glasses, the dose measured at the surgeon's lens varied more than 250-fold among these sixteen different views. Conclusions In addition to protecting the surgeon's eye from the deleterious effects of radiation, the use of leaded glasses could permit an orthopaedist to perform fluoroscopic views on up to ten times more patients before reaching the annual dose limit of 20 mSv of radiation to the eye recommended by the International Commission on Radiological Protection. Personal safety and adherence to limits of occupational radiation exposure should compel orthopaedists to wear leaded glasses for fluoroscopic procedures if other protective barriers are not in use. Clinical relevance Leaded glasses are a powerful tool for reducing the orthopaedic surgeon's lens exposure to radiation during acquisition of common intraoperative fluoroscopic views.

Objective: To measure the volume of basal forebrain septal nuclei in patients with temporal lobe epilepsy (TLE) as compared to patients with extratemporal epilepsy and controls. In animal models of TLE, septal lesions facilitate epileptogenesis, while septal stimulation is antiepileptic. Method: Subjects were recruited from 2 sites and consisted of patients with pharmacoresistant focal epilepsy (20 with TLE and mesial temporal sclerosis [MTS], 24 with TLE without MTS, 23 with extratemporal epilepsy) and 114 controls. Septal volume was measured using high-resolution MRI in association with newly developed probabilistic septal nuclei maps. Septal volume was compared between subject groups while controlling for relevant factors. Results: Patients with TLE without MTS had significantly larger septal nuclei than patients with extratemporal epilepsy and controls. This was not true for patients with MTS. These results are interpreted with reference to prior studies demonstrating expansion of the septo-hippocampal cholinergic system in animal models of TLE and human TLE surgical specimens. Conclusion: Septal nuclei are enlarged in patients with TLE without MTS. Further investigation of septal nuclei and antiepileptic septo-hippocampal neurocircuitry could be relevant to development of new therapeutic interventions such as septal stimulation for refractory TLE.

Background Whole body fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is the standard of care in oncologic diagnosis and staging, and patient radiation dose must be well understood to balance exam benefits with the risk from radiation exposure. Although reference PET/CT patient doses are available, the potential for widely varying total dose prompts evaluation of clinic-specific patient dose. The aims of this study were to use exam-specific information to characterize the radiation dosimetry of PET/CT exams that used two different CT techniques for adult oncology patients and evaluate the practicality of employing an exam-specific approach to dose estimation. Methods Whole body PET/CT scans from two sets of consecutive adult patients were retrospectively reviewed. One set received a PET scan with a standard registration CT and the other a PET scan with a diagnostic quality CT. PET dose was calculated by modifying the standard reference phantoms in OLINDA/EXM 1.1 with patient-specific organ mass. CT dose was calculated using patient-specific data in ImPACT. International Commission on Radiological Protection publication 103 tissue weighting coefficients were used for effective dose. Results One hundred eighty three adult scans were evaluated (95 men, 88 women). The mean patient-specific effective dose from a mean injected 18F-FDG activity of 450 ± 32 MBq was 9.0 ± 1.6 mSv. For all standard PET/CT patients, mean effective mAs was 39 ± 11 mAs, mean CT effective dose was 5.0 ± 1.0 mSv and mean total effective dose was 14 ± 1.3 mSv. For all diagnostic PET/CT patients, mean effective mAs was 120 ± 51 mAs, mean CT effective dose was 15.4 ± 5.0 mSv and mean total effective dose was 24.4 ± 4.3 mSv. The five organs receiving the highest organ equivalent doses in all exams were bladder, heart, brain, liver and lungs. Conclusions Patient-specific parameters optimize the patient dosimetry utilized in the medical justification of whole body PET/CT referrals and optimization of PET and CT acquisition parameters. Incorporating patient-specific data into dose estimates is a worthwhile effort for characterizing patient dose, and the specific dosimetric information assists in the justification of risk and optimization of PET/CT.

Purpose: Patient exposure rate measurements verify published patient dose rate data and characterize dose rates near 2-18-fluorodeoxyglucose ({sup 18}F-FDG) patients. A specific dose rate constant based on patient exposure rate measurements is a convenient quantity that can be applied to the desired distance, injection activity, and time postinjection to obtain an accurate calculation of cumulative external radiation dose. This study reports exposure rates measured at various locations near positron emission tomography (PET) {sup 18}F-FDG patients prior to PET scanning. These measurements are normalized for the amount of administered activity, measurement distance, and time postinjection and are compared with other published data. Methods: Exposure rates were measured using a calibrated ionization chamber at various body locations from 152 adult oncology patients postvoid after a mean uptake time of 76 min following injection with a mean activity of 490 MBq {sup 18}F-FDG. Data were obtained at nine measurement locations for each patient: three near the head, four near the chest, and two near the feet. Results: On contact with, 30 cm superior to and 30 cm lateral to the head, the mean (75th percentile) dose rates per unit injected activity at 60 min postinjection were 0.482 (0.511), 0.135 (0.155), and 0.193 (0.223)more » {mu}Sv/MBq h, respectively. On contact with, 30 cm anterior to, 30 cm lateral to and 1 m anterior to the chest, the mean (75th percentile) dose rates per unit injected activity at 60 min postinjection were 0.623 (0.709), 0.254 (0.283), 0.190 (0.218), and 0.067 (0.081) {mu}Sv/MBq h respectively. 30 cm inferior and 30 cm lateral to the feet, the mean (75th percentile) dose rates per unit injected activity at 60 min postinjection were 0.024 (0.022) and 0.039 (0.044) {mu}Sv/MBq h, respectively. Conclusions: The measurements for this study support the use of 0.092 {mu}Sv m{sup 2}/MBq h as a reasonable representation of the dose rate anterior from the chest of patients immediately following injection. This value can then be reliably scaled to the desired time and distance for planning and staff dose evaluation purposes. At distances closer than 1 m, a distance-specific dose rate constant of 0.367 {mu}Sv/MBq h at 30 cm is recommended for accurate calculations. An accurate patient-specific dose rate constant that accounts for patient-specific variables (e.g., distribution and attenuation) will allow an accurate evaluation of the dose rate from a patient injected with an isotope rather than simply utilizing a physical constant.« less

Background: Controversy exists regarding the safety of cardiac catheterizations, particularly interventions, in the early post-operative period following congenital heart surgery. We sought to determine if adverse events are more frequent in patients undergoing early post-operative catheterizations

Measles remains an important cause of childhood mortality worldwide. Sustained high vaccination coverage is the key to preventing measles deaths. Because measles vaccine is delivered by injection, hurdles to high coverage include the need for trained medical personnel and a cold chain, waste of vaccine in multidose vials and risks associated with needle use and disposal. Respiratory vaccine delivery could lower these barriers and facilitate sustained high coverage. We developed a novel single unit dose, dry powder live-attenuated measles vaccine (MVDP) for respiratory delivery without reconstitution. We tested the immunogenicity and protective efficacy in rhesus macaques of one dose of MVDP delivered either with a mask or directly intranasal with two dry powder inhalers, PuffHaler and BD Solovent. MVDP induced robust measles virus (MeV)-specific humoral and T-cell responses, without adverse effects, which completely protected the macaques from infection with wild-type MeV more than one year later. Respiratory delivery of MVDP was safe and effective and could aid in measles control.

Purpose: Effective dose ( E ) is useful as a dose index for patient exposures in interventional radiology; therefore, the authors estimated E from the kerma-area product ( P K A ) utilized during hepatic embolization interventional radiology cases performed at a cancer center and determined the variation of such doses over a representative patient population. Methods: A single-center, IRB-approved retrospective study was performed to estimate doses from consecutive hepatic embolization procedures performed during 2006. Organdoses E and E / P K A were determined from patient height, weight, P K A , procedure geometry factors, beam quality, the PCXMC Monte Carlo model, and the International Commission on Radiological Protection organ weighting factors. Results: One hundred thirteen patients were included in the study population, 72 males and 41 females, with a median age of 63 yr (29–89 yr), weight of 79 kg (42–111 kg), height of 170 cm (147–188 cm), and P K A of 233 Gy cm 2 ( 9 – 1020 Gy cm 2 ) . E was directly correlated with P K A r 2 = 0.8 ( p 0.01 ) , with a median E / P K A of 0.18 mSv Gy − 1 cm − 2 ( 0.12 – 0.33 mSv Gy − 1 cm − 2 ) . The E / P K A ratio was inversely and exponentially correlated with weight r 2 = 0.9 ( p 0.001 ) . The median E (mSv) for the study patient population was 44 mSv (2.0–255 mSv). Conclusions: Values of E can be estimated utilizing patient-specific and procedure-specific parameters. The strong inverse correlation of E / P K A with patient weight allows simple estimation of E from P K A and patient weight. There is a wide variation in effective dose in oncologic hepatic embolizations with doses up to an order of magnitude higher than diagnostic imaging of the abdomen by CT radiology. Variation is likely due to patient geometry, clinical technique factors, and procedure complexity.

Although observational findings linking breast milk to higher scores on cognitive tests may be confounded by factors associated with mothers' choice to breastfeed, it has been suggested that one or more constituents of breast milk facilitate cognitive development, particularly in preterms. Because cognitive scores are related to head size, we hypothesized that breast milk mediates cognitive effects by affecting brain growth. We used detailed data from a randomized feeding trial to calculate percentage of expressed maternal breast milk (%EBM) in the infant diet of 50 adolescents. MRI scans were obtained (mean age=15 y 9 mo), allowing volumes of total brain (TBV) and white and gray matter (WMV, GMV) to be calculated. In the total group, %EBM correlated significantly with verbal intelligence quotient (VIQ); in boys, with all IQ scores, TBV and WMV. VIQ was, in turn, correlated with WMV and, in boys only, additionally with TBV. No significant relationships were seen in girls or with gray matter. These data support the hypothesis that breast milk promotes brain development, particularly white matter growth. The selective effect in males accords with animal and human evidence regarding gender effects of early diet. Our data have important neurobiological and public health implications and identify areas for future mechanistic study.

Objective: To report 4 cases of hyperfamiliarity for faces (HFF) and review 5 previously reported cases. Methods: We identified cases of HFF from PubMed search and references in prior reports. Results: Three of our 4 cases had pathologic findings that were most extensive in the left temporal lobe. HFF occurred after a tonic-clonic seizure (cases 1 and 3), during simple partial seizures (case 2), and in the setting of an increase in simple partial seizure frequency but not during seizures (case 4). All 9 cases were adults with 1 or more seizures; symptoms first occurred after seizures in 5 cases and during seizures in 1 case. Ictal symptoms lasted from seconds to minutes and from 2 days to more than 7 years in the other 6 cases. The duration of HFF was not associated with the presence or extent of a structural lesion. While in several cases HFF appears to result from a postictal Todd paralysis, the mechanism underlying persistent cases is uncertain. Conclusions: This modality (visual)–specific and stimulus (face)–specific syndrome is associated with diverse structural, functional imaging, and neurophysiologic findings. Lesions are more often left-sided and involve the temporal lobe. Epilepsy and seizures were present in all 9 cases, suggesting a pathophysiologic relationship, which likely varies among cases. Although only reported in 9 patients, HFF is probably much more common than it is diagnosed.

Early adversity, for example poor caregiving, can have profound effects on emotional development. Orphanage rearing, even in the best circumstances, lies outside of the bounds of a species-typical caregiving environment. The long-term effects of this early adversity on the neurobiological development associated with socio-emotional behaviors are not well understood. Seventy-eight children, who include those who have experienced orphanage care and a comparison group, were assessed. Magnetic resonance imaging (MRI) was used to measure volumes of whole brain and limbic structures (e.g. amygdala, hippocampus). Emotion regulation was assessed with an emotional go-nogo paradigm, and anxiety and internalizing behaviors were assessed using the Screen for Child Anxiety Related Emotional Disorders, the Child Behavior Checklist, and a structured clinical interview. Late adoption was associated with larger corrected amygdala volumes, poorer emotion regulation, and increased anxiety. Although more than 50% of the children who experienced orphanage rearing met criteria for a psychiatric disorder, with a third having an anxiety disorder, the group differences observed in amygdala volume were not driven by the presence of an anxiety disorder. The findings are consistent with previous reports describing negative effects of prolonged orphanage care on emotional behavior and with animal models that show long-term changes in the amygdala and emotional behavior following early postnatal stress. These changes in limbic circuitry may underlie residual emotional and social problems experienced by children who have been internationally adopted.

Combined whole-body dual-tracer (18F-FDG and 11C-acetate) PET/CT is increasingly used for staging hepatocellular carcinoma, with only limited studies investigating the radiation dosimetry data of these scans. The aim of the study was to characterize the radiation dosimetry of combined whole-body dual-tracer PET/CT protocols. Methods: Consecutive adult patients with hepatocellular carcinoma who underwent whole-body dual-tracer PET/CT scans were retrospectively reviewed with institutional review board approval. OLINDA/EXM 1.1 was used to estimate patient-specific internal dose exposure in each organ. Biokinetic models for 18F-FDG and 11C-acetate as provided by ICRP (International Commission on Radiological Protection) publication 106 were used. Standard reference phantoms were modified to more closely represent patient-specific organ mass. With patient-specific parameters, organ equivalent doses from each CT series were estimated using VirtualDose. Dosimetry capabilities for tube current modulation protocols were applied by integrating with the latest anatomic realistic models. Effective dose was calculated using ICRP publication 103 tissue-weighting coefficients for adult male and female, respectively. Results: Fourteen scans were evaluated (12 men, 2 women; mean age ± SD, 60 ± 19.48 y). The patient-specific effective dose from 18F-FDG and 11C-acetate was 6.08 ± 1.49 and 1.56 ± 0.47 mSv, respectively, for male patients and 6.62 ± 1.38 and 1.79 ± 0.12 mSV, respectively, for female patients. The patient-specific effective dose of the CT component, which comprised 2 noncontrast whole-body scans, to male and female patients was 21.20 ± 8.94 and 14.79 ± 3.35 mSv, respectively. Thus, the total effective doses of the combined whole-body dual-tracer PET/CT studies for male and female patients were 28.84 ± 10.18 and 23.19 ± 4.61 mSv, respectively. Conclusion: Patient-specific parameters allow for more accurate estimation of organ equivalent doses. Considering the substantial radiation dose incurred, judicious medical justification is required with every whole-body dual-tracer PET/CT referral. Although radiation risks may have less impact for the population with cancer because of their reduced life expectancy, the information is of interest and relevant for both justification, to evaluate risk/benefit, and protocol optimization.

Previous research indicates that long-term meditation practice is associated with altered resting electroencephalogram patterns, suggestive of long lasting changes in brain activity. We hypothesized that meditation practice might also be associated with changes in the brain’s physical structure. Magnetic resonance imaging was used to assess cortical thickness in 20 participants with extensive Insight meditation experience, which involves focused attention to internal experiences. Brain regions associated with attention, interoception and sensory processing were thicker in meditation participants than matched controls, including the prefrontal cortex and right anterior insula. Between-group diierences in prefrontal cortical thickness were most pronounced in older participants, suggesting that meditation might oiset age-related cortical thinning. Finally, the thickness of two regions correlated with meditation experience. These data provide the ¢rst structural evidence for experience-dependent cortical plasticity associated with meditation practice. NeuroReport 16:1893^1897 � c 2005 Lippincott Williams & Wilkins.

People differ in their personality traits and in their ability to modulate fear. Does our personality determine how well we extinguish conditioned fear responses? Or is the opposite true? Herein, we examine the relationships between personality traits, memory for fear extinction, and cortical thickness as a measure of brain structure. We found that in healthy humans, extinction retention and thickness of the medial orbitofrontal cortex are positively correlated with extraversion. Path analysis indicates that extinction retention mediates the relationship between the medial orbitofrontal cortex thickness and extraversion, thereby illustrating one path through which brain structure influences personality.

The effect of age was investigated in and compared across 16 automatically segmented brain measures: cortical gray matter, cerebral white matter, hippocampus, amygdala, thalamus, the accumbens area, caudate, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, the lateral ventricle, the inferior lateral ventricle, and the 3rd and 4th ventricle. Significant age effects were found for all volumes except pallidum and the 4th ventricle. Heterogeneous age responses were seen in that age relationships for cortex, amygdala, thalamus, the accumbens area, and caudate were linear, while cerebral white matter, hippocampus, brainstem, cerebellar white, and gray matter, as well as volume of the lateral, inferior lateral, and 3rd ventricles showed curvilinear relationships with age. In general, the findings point to global and large effects of age across brain volumes.

The ventromedial prefrontal cortex (vmPFC) has been implicated in fear extinction [Phelps, E. A., Delgado, M. R., Nearing, K. I. & Ledoux, J. E. (2004) Neuron 43, 897-905; Herry, C. & Garcia, R. (2003) Behav. Brain Res . 146, 89-96]. Here, we test the hypothesis that the cortical thickness of vmPFC regions is associated with how well healthy humans retain their extinction memory a day after having been conditioned and then extinguished. Fourteen participants underwent a 2-day fear conditioning and extinction protocol. The conditioned stimuli (CSs) were pictures of virtual lights, and the unconditioned stimulus (US) was an electric shock. On day 1, participants received 5 CS+US pairings (conditioning), followed by 10 CS trials with no US (extinction). On day 2, the CS was presented alone to test for extinction memory. Skin conductance response (SCR) was the behavioral index of conditioning and extinction. Participants underwent MRI scans to obtain structural images, from which cortical thickness was measured. We performed a vertex-based analysis across the entire cortical surface and a region-of-interest analysis of a priori hypothesized territories to measure cortical thickness and map correlations between this measure and SCR. We found significant, direct correlation between thickness of the vmPFC, specifically medial orbitofrontal cortex, and extinction retention. That is, thicker medial orbitofrontal cortex was associated with lower SCR to the conditioned stimulus during extinction recall (i.e., greater extinction memory). These results suggest that the size of the vmPFC might explain individual differences in the ability to modulate fear among humans.

Objective: To study the morphometric determinants of recall of verbal material for an extended period in an adult lifespan sample. Methods: Healthy adults of varying ages were studied using automated segmentation of MRI scans with volumes of hippocampus, cortex, and white matter, and verbal memory tests assessing recall after 5 minutes, 30 minutes, and a mean period of 11 weeks. Stepwise regression analyses were performed with 5 minutes, 30 minutes, and 11-week recall as the dependent variables. Hippocampal, cortical, and white matter volumes were included in the initial set of predictor variables in each case, and the analyses were repeated with age as an additional predictor variable. Results: When age was not included, cortical volume was the only variable predicting recall after 5 and 30 minutes, whereas hippocampal and cortical volumes predicted recall after 11 weeks. When age was included in the model, this was the only variable predicting recall after 5 and 30 minutes, whereas age and hippocampus gave contributions in prediction of recall after several weeks. Conclusion: This study supports a critical role of cortical and hippocampal size in recall. Hippocampal size seems more important in recall after 11 weeks than after a shorter time interval.

We present a set of techniques for embedding the physics of the imaging process that generates a class of magnetic resonance images (MRIs) into a segmentation or registration algorithm. This results in substantial invariance to acquisition parameters, as the effect of these parameters on the contrast properties of various brain structures is explicitly modeled in the segmentation. In addition, the integration of image acquisition with tissue classification allows the derivation of sequences that are optimal for segmentation purposes. Another benefit of these procedures is the generation of probabilistic models of the intrinsic tissue parameters that cause MR contrast (e.g., T1, proton density, T2*), allowing access to these physiologically relevant parameters that may change with disease or demographic, resulting in nonmorphometric alterations in MR images that are otherwise difficult to detect. Finally, we also present a high band width multiecho FLASH pulse sequence that results in high signal-to-noise ratio with minimal image distortion due to B0 effects. This sequence has the added benefit of allowing the explicit estimation of T2* and of reducing test-retest intensity variability.

Abnormalities in cortical structure are commonly observed in children with dyslexia in key regions of the “reading network.” Whether alteration in cortical features reflects pathology inherent to dyslexia or environmental influence (e.g., impoverished reading experience) remains unclear. To address this question, we compared MRI-derived metrics of cortical thickness (CT), surface area (SA), gray matter volume (GMV), and their lateralization across three different groups of children with a historical diagnosis of dyslexia, who varied in current reading level. We compared three dyslexia subgroups with: (1) persistent reading and spelling impairment; (2) remediated reading impairment (normal reading scores), and (3) remediated reading and spelling impairments (normal reading and spelling scores); and a control group of (4) typically developing children. All groups were matched for age, gender, handedness, and IQ. We hypothesized that the dyslexia group would show cortical abnormalities in regions of the reading network relative to controls, irrespective of remediation status. Such a finding would support that cortical abnormalities are inherent to dyslexia and are not a consequence of abnormal reading experience. Results revealed increased CT of the left fusiform gyrus in the dyslexia group relative to controls. Similarly, the dyslexia group showed CT increase of the right superior temporal gyrus, extending into the planum temporale, which resulted in a rightward CT asymmetry on lateralization indices. There were no group differences in SA, GMV, or their lateralization. These findings held true regardless of remediation status. Each reading level group showed the same “double hit” of atypically increased left fusiform CT and rightward superior temporal CT asymmetry. Thus, findings provide evidence that a developmental history of dyslexia is associated with CT abnormalities, independent of remediation status., Highlights • Rightward superior temporal cortical thickness asymmetry in dyslexia • Increased left fusiform gyrus thickness in dyslexia • Primary effects present across three subgroups with differing reading levels • Cortical thickness findings were independent from volume and surface area. • “Double hit” of left fusiform anomaly and rightward temporal asymmetry in dyslexia

Sensory integration of touch and sight is crucial to perceiving and navigating the environment. While recent evidence from other sensory modality combinations suggests that low-level sensory areas integrate multisensory information at early processing stages, little is known about how the brain combines visual and tactile information. We investigated the dynamics of multisensory integration between vision and touch using the high spatial and temporal resolution of intracranial electrocorticography in humans. We present a novel, two-step metric for defining multisensory integration. The first step compares the sum of the unisensory responses to the bimodal response as multisensory responses. The second step eliminates the possibility that double addition of sensory responses could be misinterpreted as interactions. Using these criteria, averaged local field potentials and high-gamma-band power demonstrate a functional processing cascade whereby sensory integration occurs late, both anatomically and temporally, in the temporo–parieto–occipital junction (TPOJ) and dorsolateral prefrontal cortex. Results further suggest two neurophysiologically distinct and temporally separated integration mechanisms in TPOJ, while providing direct evidence for local suppression as a dominant mechanism for synthesizing visual and tactile input. These results tend to support earlier concepts of multisensory integration as relatively late and centered in tertiary multimodal association cortices.

Four anthropomorphic phantoms (an adult male, an adult female, a 10-y-old child and a 5-y-old child) were exposed to bitewing radiographs at film and digital settings using both rectangular and round collimation. Optically stimulated dosemeters were used. For children, average organ doses were

PURPOSE: To quantify radiation exposure to the primary operator and staff during PET/CT-guided interventional procedures. METHODS: In this prospective study, 12 patients underwent PET/CT-guided interventions over a 6 month period. Radiation exposure was measured for the primary operator, the radiology technologist, and the nurse anesthetist by means of optically stimulated luminescence dosimeters. Radiation exposure was correlated with the procedure time and the use of in-room image guidance (CT fluoroscopy or ultrasound). RESULTS: The median effective dose was 0.02 (range 0–0.13) mSv for the primary operator, 0.01 (range 0–0.05) mSv for the nurse anesthetist, and 0.02 (range 0–0.05) mSv for the radiology technologist. The median extremity dose equivalent for the operator was 0.05 (range 0–0.62) mSv. Radiation exposure correlated with procedure duration and with the use of in-room image guidance. The median operator effective dose for the procedure was 0.015 mSv when conventional biopsy mode CT was used, compared to 0.06 mSv for in-room image guidance, although this did not achieve statistical significance as a result of the small sample size (p = 0.06). CONCLUSION: The operator dose from PET/CT-guided procedures is not significantly different than typical doses from fluoroscopically guided procedures. The major determinant of radiation exposure to the operator from PET/CT-guided interventional procedures is time spent in close proximity to the patient.

Idiopathic generalized epilepsy (IGE) is associated with widespread cortical network abnormalities on electroencephalography. Resting state functional connectivity (RSFC), based on fMRI, can assess the brain's global functional organization and its disruption in clinical conditions. We compared RSFC associated with the 'default mode network' (DMN) between people with IGE and healthy controls. Strength of functional connectivity within the DMN associated with seeds in the posterior cingulate cortex (PCC) and medial prefrontal cortices (MPFC) was compared between people with IGE and healthy controls and was correlated with seizure duration, age of seizure onset and age at scan. Those with IGE showed markedly reduced functional network connectivity between anterior and posterior cortical seed regions. Seizure duration positively correlates with RSFC between parahippocampal gyri and the PCC but negatively correlates with connectivity between the PCC and frontal lobe. The observed pattern of disruption provides evidence for integration- and segregation-type network abnormalities and supports aberrant network organization among people with IGE.