Yingzi Liu

A compact DD neutron generator–based NAA system to quantify manganese (Mn) in bone in vivo

A deuterium-deuterium (DD) neutron generator-based neutron activation analysis (NAA) system has been developed to quantify metals, including manganese (Mn), in bone in vivo. A DD neutron generator with a flux of up to 3*10(9) neutrons s(-1) was set up in our lab for this purpose. Optimized settings, including moderator, reflector, and shielding material and thickness, were selected based on Monte Carlo (MC) simulations conducted in our previous work. Hand phantoms doped with different Mn concentrations were irradiated using the optimized DD neutron generator irradiation system. The Mn characteristic γ-rays were collected by an HPGe detector system with 100% relative efficiency. The calibration line of the Mn/calcium (Ca) count ratio versus bone Mn concentration was obtained (R(2) = 0.99) using the hand phantoms. The detection limit (DL) was calculated to be about 1.05 μg g(-1) dry bone (ppm) with an equivalent dose of 85.4 mSv to the hand. The DL can be reduced to 0.74 ppm by using two 100% HPGe detectors. The whole body effective dose delivered to the irradiated subject was calculated to be about 17 μSv. Given the average normal bone Mn concentration of 1 ppm in the general population, this system is promising for in vivo bone Mn quantification in humans.

Customized compact neutron activation analysis system to quantify manganese (Mn) in bone in vivo

OBJECTIVE In the US alone, millions of workers, including over 300 000 welders, are at high risk of occupational manganese (Mn) exposure. Those who have been chronically exposed to excessive amount of Mn can develop severe neurological disorders similar, but not identical, to the idiopathic Parkinsons disease. One challenge of identifing the health effects of Mn exposure is to find a reliable biomarker for exposure assessment, especially for long-term cumulative exposure. APPROACH Mns long biological half-life as well as its relatively high concentration in bone makes bone Mn (BnMn) a potentially valuable biomarker for Mn exposure. Our group has been working on the development of a deuterium-deuterium (D-D)-based neutron generator to quantify Mn in bone in vivo. Main results and significance: In this paper, we report the latest advancements in our system. With a customized hand irradiation assembly, a fully characterized high purity germanium (HPGe) detector system, and an acceptable hand dose of 36 mSv, a detection limit of 0.64 µg Mn/g bone (ppm) has been achieved.

Compact DD generator-based neutron activation analysis (NAA) system to determine fluorine in human bone in vivo: a feasibility study.

The subject of whether fluorine (F) is detrimental to human health has been controversial for many years. Much of the discussion focuses on the known benefits and detriments to dental care and problems that F causes in bone structure at high doses. It is therefore advantageous to have the means to monitor F concentrations in the human body as a method to directly assess exposure. F accumulates in the skeleton making bone a useful biomarker to assess long term cumulative exposure to F. This study presents work in the development of a non-invasive method for the monitoring of F in human bone. The work was based on the technique of in vivo neutron activation analysis (IVNAA). A compact deuterium-deuterium (DD) generator was used to produce neutrons. A moderator/reflector/shielding assembly was designed and built for human hand irradiation. The gamma rays emitted through the (19)F(n,γ)(20)F reaction were measured using a HPGe detector. This study was undertaken to (i) find the feasibility of using DD system to determine F in human bone, (ii) estimate the F minimum detection limit (MDL), and (iii) optimize the system using the Monte Carlo N-Particle eXtended (MCNPX) code in order to improve the MDL of the system. The F MDL was found to be 0.54 g experimentally with a neutron flux of 7   ×   10(8) n s(-1) and an optimized irradiation, decay, and measurement time scheme. The numbers of F counts from the experiment were found to be close to the (MCNPX) simulation results with the same irradiation and detection parameters. The equivalent dose to the irradiated hand and the effective dose to the whole body were found to be 0.9 mSv and 0.33 μSv, respectively. Based on these results, it is feasible to develop a compact DD generator based IVNAA system to measure bone F in a population with moderate to high F exposure.

A dosimetry study of deuterium-deuterium neutron generator-based in vivo neutron activation analysis

AbstractA neutron irradiation cavity for in vivo neutron activation analysis (IVNAA) to detect manganese, aluminum, and other potentially toxic elements in human hand bone has been designed and its dosimetric specifications measured. The neutron source is a customized deuterium-deuterium neutron generator that produces neutrons at 2.45 MeV by the fusion reaction 2H(d, n)3He at a calculated flux of 7 × 108 ± 30% s−1. A moderator/reflector/shielding [5 cm high density polyethylene (HDPE), 5.3 cm graphite and 5.7 cm borated (HDPE)] assembly has been designed and built to maximize the thermal neutron flux inside the hand irradiation cavity and to reduce the extremity dose and effective dose to the human subject. Lead sheets are used to attenuate bremsstrahlung x rays and activation gammas. A Monte Carlo simulation (MCNP6) was used to model the system and calculate extremity dose. The extremity dose was measured with neutron and photon sensitive film badges and Fuji electronic pocket dosimeters (EPD). The neutron ambient dose outside the shielding was measured by Fuji NSN3, and the photon dose was measured by a Bicron MicroREM scintillator. Neutron extremity dose was calculated to be 32.3 mSv using MCNP6 simulations given a 10‐min IVNAA measurement of manganese. Measurements by EPD and film badge indicate hand dose to be 31.7 ± 0.8 mSv for neutrons and 4.2 ± 0.2 mSv for photons for 10 min; whole body effective dose was calculated conservatively to be 0.052 mSv. Experimental values closely match values obtained from MCNP6 simulations. These are acceptable doses to apply the technology for a manganese toxicity study in a human population.

In vivo neutron activation analysis of bone manganese in workers

OBJECTIVE Manganese (Mn) is a neurotoxin. However, the impact of elevated, chronic Mn exposure is not well understood, partially due to the lack of a cumulative exposure biomarker. To address this gap, our group developed a compact in vivo neutron activation analysis (IVNAA) system to quantify Mn concentration in bone (MnBn). APPROACH In this study, we used this system and determined MnBn among male Chinese workers and compared results to their blood Mn (MnB), a measure of recent exposure, and the years of employment, a measure of cumulative exposure. A cross-sectional study was conducted with 30 ferroalloy smelters (exposed) and 30 general manufacturing workers (controls). MnBn was assessed using IVNAA, MnB was measured with inductively coupled plasma mass spectrometry, and occupational history and demographics were obtained via questionnaire. Mn-doped phantoms were used to generate a calibration curve; spectra from these phantoms were consistent with in vivo spectra. MAIN RESULTS The median (interquartile range (IQR)) values for Mn biomarkers were 2.7 µg g-1 (7.2) for MnBn and 14.1 µg l-1 (4.0) for MnB. In regression models adjusted for age and education, the natural log transformed MnBn (ln(MnBn)) was significantly associated with the exposed/control status (β  =  0.44, p  =  0.047) and years of employment (β  =  0.05, p  =  0.002), but not with natural log transformed MnB (ln(MnB)) (β  =  0.54, p  =  0.188). SIGNIFICANCE Our results support the use of IVNAA to quantify MnBn and the use of MnBn as a biomarker of cumulative Mn exposure.

In vivo measurement of bone manganese and association with manual dexterity: A pilot study

Abstract We used neutron activation analysis (NAA) to measure hand bone manganese (BnMn) in 19 adult males. Median BnMn was 0.89 &mgr;g/g dry bone (interquartile range = 1.07). After adjustment for age and occupation, higher ln(BnMn) was significantly associated with lower manual dexterity based on the Purdue Pegboard assembly task: &bgr; = −1.77, standard error = 0.79, p = 0.04. Due to the small sample size, these results should be interpreted cautiously. BnMn appears to be a promising biomarker, and should be further studied. Graphical abstract Figure. No Caption available. HighlightsIn vivo hand bone manganese was measured using neutron activation analysis.Bone manganese was higher among men who reported working with metals.Those with higher bone manganese tended to have less manual dexterity.Future studies should evaluate bone manganese as a cumulative exposure biomarker.

A feasibility study of a deuterium–deuterium neutron generator-based boron neutron capture therapy system for treatment of brain tumors

Purpose: Boron neutron capture therapy (BNCT) is a binary treatment modality that uses high LET particles to achieve tumor cell killing. Deuterium–deuterium (DD) compact neutron generators have advantages over nuclear reactors and large accelerators as the BNCT neutron source, such as their compact size, low cost, and relatively easy installation. The purpose of this study is to design a beam shaping assembly (BSA) for a DD neutron generator and assess the potential of a DD‐based BNCT system using Monte Carlo (MC) simulations. Methods: The MC model consisted of a head phantom, a DD neutron source, and a BSA. The head phantom had tally cylinders along the centerline for computing neutron and photon fluences and calculating the dose as a function of depth. The head phantom was placed at 4 cm from the BSA. The neutron source was modeled to resemble the source of our current DD neutron generator. A BSA was designed to moderate and shape the 2.45‐MeV DD neutrons to the epithermal (0.5 eV to 10 keV) range. The BSA had multiple components, including moderator, reflector, collimator, and filter. Various materials and configurations were tested for each component. Each BSA layout was assessed in terms of the in‐air and in‐phantom parameters. The maximum brain dose was limited to 12.5 Gray‐Equivalent (Gy‐Eq) and the skin dose to 18 Gy‐Eq. Results: The optimized BSA configuration included 30 cm of lead for reflector, 45 cm of LiF, and 10 cm of MgF2 for moderator, 10 cm of lead for collimator, and 0.1 mm of cadmium for thermal neutron filter. Epithermal flux at the beam aperture was 1.0 × 105 nepi/cm2‐s; thermal‐to‐epithermal neutron ratio was 0.05; fast neutron dose per epithermal was 5.5 × 10−13 Gy‐cm2/Φepi, and photon dose per epithermal was 2.4 × 10−13 Gy‐cm2/Φepi. The AD, AR, and the advantage depth dose rate were 12.1 cm, 3.7, and 3.2 × 10−3 cGy‐Eq/min, respectively. The maximum skin dose was 0.56 Gy‐Eq. The DD neutron yield that is needed to irradiate in reasonable time was 4.9 × 1013 n/s. Conclusions: Results demonstrated that a DD‐based BNCT system could be designed to produce neutron beams that have acceptable in‐air and in‐phantom characteristics. The parameter values were comparable to those of existing BNCT facilities. Continuing efforts are ongoing to improve the DD neutron yield.

Compact DD generator-based in vivo neutron activation analysis (IVNAA) system to determine sodium concentrations in human bone

OBJECTIVE This study presents the development of a noninvasive method for monitoring Na in human bone. Many diseases, such as hypertension and osteoporosis, are closely associated with sodium (Na) retention in the human body. Na retention is generally evaluated by calculating the difference between dietary intake and excretion. There is currently no method to directly quantify Na retained in the body. Bone is a storage for many elements, including Na, which renders bone Na an ideal biomarker to study Na metabolism and retention. APPROACH A customized compact deuterium-deuterium (DD) neutron generator was used to produce neutrons for in vivo neutron activation analysis (IVNAA), with a moderator/reflector/shielding assembly optimized for human hand irradiation in order to maximize the thermal neutron flux inside the irradiation cave and to limit radiation exposure to the hand and the whole body. MAIN RESULTS The experimental results show that the system is able to detect sodium levels in the bone as low as 16 µg Na g-1 dry bone with an effective dose to the body of about 27 µSv. The simulation results agree with the numbers estimated from the experiment. SIGNIFICANCE This is expected to be a feasible method for measuring the change of Na in bone. The low detection limit indicates this will be a useful system to study the association between Na retention and related diseases.

Development of a Cumulative Exposure Index (CEI) for Manganese and Comparison with Bone Manganese and Other Biomarkers of Manganese Exposure

Manganese (Mn) exposure can result in parkinsonism. However, understanding of manganese neurotoxicity has been limited by the lack of a cumulative Mn biomarker. Therefore, the current goal was to develop Mn cumulative exposure indices (MnCEI), an established method to estimate cumulative exposure, and determine associations of MnCEI with blood Mn (BMn), fingernail Mn (FMn), and bone Mn (BnMn). We completed a cross-sectional study of 60 male Chinese workers. Self-reported occupational history was used to create two MnCEIs reflecting the previous 16 years (MnCEI16) and total work history (MnCEITOT). An in vivo neutron activation analysis system was used to quantify BnMn. BMn and FMn were measured using ICP-MS. Mean (standard deviation) MnCEITOT and MnCEI16 were 37.5 (22.0) and 25.0 (11.3), respectively. Median (interquartile range) BMn, FMn, and BnMn were 14.1 (4.0) μg/L, 13.5 (58.5) μg/g, and 2.6 (7.2) μg/g dry bone, respectively. MnCEI16 was significantly correlated with FMn (Spearman’s ρ = 0.44; p = 0.02), BnMn (ρ = 0.44; p < 0.01), and MnCEITOT (ρ = 0.44; p < 0.01). In adjusted regression models, MnCEI16 was significantly associated with BnMn (β = 0.03; 95% confidence interval = 0.001, 0.05); no other biomarkers were associated with MnCEI. This suggests BnMn may be a useful biomarker of the previous 16 years of Mn exposure, but larger studies are recommended.

The study of in vivo quantification of aluminum (Al) in human bone with a compact DD generator-based neutron activation analysis (NAA) system.

The feasibility and methodology of using a compact DD generator-based neutron activation analysis system to measure aluminum in hand bone has been investigated. Monte Carlo simulations were used to simulate the moderator, reflector, and shielding assembly and to estimate the radiation dose. A high purity germanium (HPGe) detector was used to detect the Al gamma ray signals. The minimum detectable limit (MDL) was found to be 11.13 μg g(-1) dry bone (ppm). An additional HPGe detector would improve the MDL by a factor of 1.4, to 7.9 ppm. The equivalent dose delivered to the irradiated hand was calculated by Monte Carlo to be 11.9 mSv. In vivo bone aluminum measurement with the DD generator was found to be feasible among general population with an acceptable dose to the subject.