Quantitative analysis of radiosensitizing effect for magnetic hyperthermia-radiation combined therapy on prostate cancer cells.

BACKGROUND: Magnetic hyperthermia (MHT) has emerged as a promising therapeutic approach in the field of radiation oncology due to its superior precision in controlling temperature and managing the heating area compared to conventional hyperthermia. Recent studies have proposed solutions to address clinical safety concerns associated with MHT, which arise from the use of highly concentrated magnetic nanoparticles and the strong magnetic field needed to induce hyperthermic effects. Despite these efforts, challenges remain in quantifying therapeutic outcomes and developing treatment plan systems for combining MHT with radiation therapy (RT). PURPOSE: This study aims to quantitatively measure the therapeutic effect, including radiation dose enhancement (RDE) in the magnetic hyperthermia-radiation combined therapy (MHRT), using the equivalent radiation dose (EQD) estimation method. METHODS: To conduct EQD estimation for MHRT, we compared the therapeutic effects between the conventional hyperthermia-radiation combined therapy (HTRT) and MHRT in human prostate cancer cell lines, PC3 and LNCaP. We adopted a clonogenic assay to validate RDE and the radiosensitizing effect induced by MHT. The data on survival fractions were analyzed using both the linear-quadradic model and Arrhenius model to estimate the biological parameters describing RDE and radiosensitizing effect of MHRT for both cell lines through maximum likelihood estimation. Based on these parameters, a new survival fraction model was suggested for EQD estimation of MHRT. RESULTS: The newly designed model describing the MHRT effect, effectively captures the variations in thermal and radiation dose for both cell lines (R2 > 0.95), and its suitability was confirmed through the normality test of residuals. This model appropriately describes the survival fractions up to 10 Gy for PC3 cells and 8 Gy for LNCaP cells under RT-only conditions. Furthermore, using the newly defined parameter r, the RDE effect was calculated as 29% in PC3 cells and 23% in LNCaP cells. EQDMHRT calculated through this model was 9.47 Gy for PC3 and 4.71 Gy for LNCaP when given 2 Gy and MHT for 30 min. Compared to EQDHTRT, EQDMHRT showed a 26% increase for PC3 and a 20% increase for LNCaP. CONCLUSIONS: The proposed model effectively describes the changes of the survival fraction induced by MHRT in both cell lines and adequately represents actual data values through residual analysis. Newly suggested parameter r for RDE effect shows potential for quantitative comparisons between HTRT and MHRT, and optimizing therapeutic outcomes in MHRT for prostate cancer.

Evaluation of commercial devices for patient specific QA of stereotactic radiotherapy plans.

Stereotactic radiotherapy (SRT) methods have become common for the treatment of small tumors in various parts of the body. Small field dosimetry has a unique set of challenges when it comes to the pre-treatment validation of a radiotherapy plan that involves film dosimetry or high-resolution detectors. Comparison of commercial quality assurance (QA) devices to the film dosimetry method for pre-treatment evaluation of stereotactic radiosurgery (SRS), fractionated SRT, and stereotactic body radiation therapy treatment plans have been evaluated in this study. Forty stereotactic QA plans were measured using EBT-XD film, IBA Matrixx Resolution, SNC ArcCHECK, Varian aS1200 EPID, SNC SRS MapCHECK, and IBA myQA SRS. The results of the commercial devices are compared to the EBT-XD film dosimetry results for each gamma criteria. Treatment plan characteristics such as modulation factor and target volume were investigated for correlation with the passing rates. It was found that all detectors have greater than 95% passing rates at 3%/3 mm. Passing rates decrease rapidly for ArcCHECK and the Matrixx as criteria became more strict. In contrast, EBT-XD film, SNC SRS MapCHECK, and IBA myQA SRS passing rates do not decline as rapidly when compared to Matrix Resolution, ArcCHECK, and the EPID. EBT-XD film, SNC SRS MapCHECK, and IBA myQA SRS maintain greater than 90% passing rate at 2%/1 mm and greater than 80% at 1%/1 mm. Additionally, the ability of these devices to detect changes in dose distribution due to MLC positioning errors was investigated. Ten VMAT SBRT/SRS treatment plans were created with 6 MV FFF or 10 MV FFF beam energies using Eclipse 15.6. A MATLAB script was used to create two MLC positioning error scenarios from the original treatment plan. It was found that errors in MLC positioning were most reliably detected at 2%/1 mm for high-resolution detectors and that lower-resolution detectors did not consistently detect MLC positioning errors.

The association of bone and blood manganese with motor function in Chinese workers.

Manganese (Mn) is an essential element. However, Mn overexposure is associated with motor dysfunction. This cross-sectional study assessed the association between bone Mn (BnMn) and whole blood Mn (BMn) with motor function in 59 Chinese workers. BnMn and BMn were measured using a transportable in vivo neutron activation analysis system and inductively coupled plasma mass spectrometry, respectively. Motor function (manual coordination, postural sway, postural hand tremor, and fine motor function) was assessed using the Coordination Ability Test System (CATSYS) and the Purdue Pegboard. Relationships between Mn biomarkers and motor test scores were analyzed with linear regression models adjusted for age, education, current employment, and current alcohol consumption. BMn was significantly inversely associated with hand tremor intensity (dominant hand (ß=-0.04, 95 % confidence interval (CI):-0.07, -0.01; non-dominant hand ß=-0.05, 95 % CI:-0.08, -0.01) hand tremor center frequency (non-dominant hand ß=-1.61, 95 % CI:-3.03, -0.19) and positively associated with the Purdue Pegboard Assembly Score (ß = 4.58, 95 % CI:1.08, 8.07). BnMn was significantly inversely associated with finger-tapping performance (non-dominant hand ß=-0.02, 95 % CI:-0.04,-0.004), mean sway (eyes closed and foam ß=-0.68, 95 % CI:-1.31,-0.04), and positively associated with hand tremor center frequency (dominant hand, ß = 0.40, 95 % CI:0.002, 0.80). These results suggest BMn is related to better postural hand tremor and fine motor control and BnMn is related to worse motor coordination and postural hand tremor but better (i.e., less) postural sway. The unexpected positive results might be explained by choice of biomarker or confounding by work-related motor activities. Larger, longitudinal studies in this area are recommended.

Preliminary Clinical Evaluation of Intrafraction Prostate Displacements for Two Immobilization Systems.

Immobilization systems and their corresponding set-up errors influence the clinical target volume to the planning target volume (CTV-PTV) margins, which is critical for hypofractionated prostate stereotactic body radiotherapy (SBRT). This preliminary study evaluates intrafraction prostate displacement for two immobilization systems (A and B). Six consecutive patients having localized prostate cancer and implanted prostate marker seeds were studied. Planar X-ray images were acquired pre- and post-treatment to find the intrafraction prostate displacement. The average absolute displacements (lateral, longitudinal, vertical) were 0.9 ± 0.4 mm, 1.7 ± 0.1 mm, 1.3 ± 0.3 mm (system A), and 0.5 ± 0.2 mm, 0.6 ± 0.1 mm, 0.8 ± 0.3 mm (system B), with average three-dimensional displacements of 2.6 ± 0.2 mm (system A) and 1.3 ± 0.2 mm (system B). The computed CTV-PTV margins (lateral, longitudinal, vertical) were 2.5 mm, 2.5 mm, 3.6 mm and 1.4 mm, 1.6 mm, 2.4 mm for systems A and B, respectively. This suggests that the immobilization system influences intrafraction prostate displacement and, therefore, the margins applied. However, the margins found for both systems are comparable to the margins used for hypofractionated prostate SBRT.

Characterization of bone aluminum, a potential biomarker of cumulative exposure, within an occupational population from Zunyi, China.

OBJECTIVES: Aluminum (Al) is a neurotoxicant; however, efforts to understand Al toxicity are limited by the lack of a quantitative biomarker of cumulative exposure. Bone Al measurements may address this need. Here, we describe and compare non-invasive bone Al measurements with fingernail Al and Al cumulative exposure indices (CEIs). METHODS: We completed a cross-sectional study of 43 factory workers in Zunyi, China. Bone Al measurements were taken with a compact in-vivo neutron activation analysis system (IVNAA). Fingernail samples were analyzed using inductively coupled plasma mass spectrometry. CEIs, based on self-reported work history and prior literature, were calculated for the prior 5, 10, 15, 20 years and lifetime work history. Linear regressions adjusted for age and education compared fingernail Al and Al CEIs with bone Al. RESULTS: Median (interquartile range (IQR)) Al measurements were: 15 µg/g dry bone (IQR = 28) for bone Al; 34.9 µg/g (43.3) for fingernail; and 24 (20) for lifetime CEI. In adjusted regression models, an increase in 15-year CEI was significantly associated with increased bone Al (ß = 0.91, 95% confidence interval (CI): 0.16, 1.66). Associations of bone Al with 10- and 20-year CEI were approaching statistical significance (ß = 0.98, 95% CI: -0.14, 2.1; ß = 0.59, 95% CI: -0.01, 1.18, respectively). Other models were not statistically significant. CONCLUSIONS: Bone Al was significantly associated with 15-year Al CEI, but not other Al CEIs or fingernail Al. Bone Al may be a useful measure of cumulative, rather than short-term, Al exposure. Additional refinement of this method is ongoing.

Serial T2-Weighted Magnetic Resonance Images Acquired on a 1.5 Tesla Magnetic Resonance Linear Accelerator Reveal Radiomic Feature Variation in Organs at Risk: An Exploratory Analysis of Novel Metrics of Tissue Response in Prostate Cancer.

"Delta-radiomics" investigates variations in quantitative image metrics over time and can yield important clinical information. We hypothesized that in patients undergoing active radiation therapy (RT) for prostate cancer (PCa), there would exist observable variation in the quantitative metrics that describe the T2-weighted (T2W) intensity histogram in the prostate and surrounding organs at risk (OAR) over time. We investigated the feasibility of acquisition and subsequent analysis of the delta-radiomic profiles of these regions of interest (ROI) in serial T2W magnetic resonance (MR) images obtained on a 1.5 Tesla (T) Magnetic Resonance Linear Accelerator (MRL). Principally, we sought to illustrate the significance of longitudinal radiomic data acquisition for tissue response monitoring and provide a framework for future hypothesis driven research. Patients with PCa undergoing treatment with RT were compiled from an ongoing prospective observational imaging trial using a 1.5 T MRL (NCT30500081). Contiguous axial slices of prostate parenchyma were contoured and temporally normalized to sections of Sartorius muscle which served as a control. Similarly, contiguous sections of rectal and bladder wall adjacent to the prostate were contoured and temporally normalized to regions of these organs further removed from the planning target volume (PTV). First order statistical descriptors of the T2W intensity histogram were extracted and evaluated for changes over time using linear mixed effects regression modeling and post-hoc contrasts. Benjamini-Hochberg corrections were employed to reduce the effects of multiple testing and control for the false discovery rate (FDR). Four patients with a median age of 69 comprised this exploratory cohort. One patient had low-risk disease, two had intermediate (one favorable, one unfavorable), and one had high risk disease. Three out of four patients underwent definitive radiation to 75.6 Gray (Gy) in 42 fractions and one received hypofractionated therapy to a total dose of 70 Gy over 28 fractions, and all received treatment on a conventional linear accelerator. The most significant acute toxicity event was grade 2 GU dysfunction observed in two patients. Follow up ranged from 1 month to 10 months post treatment, and no long-term complications were reported in patients who completed treatment at least one month prior. Bladder wall adjacent to the prostate demonstrated significant variation in the mean and median metric values after the first week of treatment. In addition, rectal wall adjacent to the prostate exhibited significant variation in the mean, median, and standard deviation metric values by the second week of treatment. No significant variation in any radiomic feature was observed in the Sartorius control. This exploratory study is one of the earliest examining the delta-radiomic characteristics of the T2W intensity histogram in OAR extracted from images acquired on a 1.5 T MRL in patients actively being treated with RT for PCa. We demonstrated a feasible approach to longitudinal radiomic data acquisition providing limitless opportunity for future research. Analysis of the delta-radiomic profiles in OAR revealed significant variation in metrics after only one week of RT in bladder and rectal wall adjacent to the prostate. These findings must be further investigated and validated with expanded data sets with long-term follow up and correlation to clinical outcomes including toxicity and tumor control.

The association of bone, fingernail and blood manganese with cognitive and olfactory function in Chinese workers.

Occupational manganese (Mn) exposure has been associated with cognitive and olfactory dysfunction; however, few studies have incorporated cumulative biomarkers of Mn exposure such as bone Mn (BnMn). Our goal was to assess the cross-sectional association between BnMn, blood Mn (BMn), and fingernail Mn (FMn) with cognitive and olfactory function among Mn-exposed workers. A transportable in vivo neutron activation analysis (IVNAA) system was designed and utilized to assess BnMn among 60 Chinese workers. BMn and FMn were measured using inductively coupled plasma mass spectrometry. Cognitive and olfactory function was assessed using Animal and Fruit Naming tests, World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test (AVLT) and the University of Pennsylvania Smell Identification Test (UPSIT). Additional data were obtained via questionnaire. Regression models adjusted for age, education, factory of employment, and smoking status (UPSIT only), were used to assess the relationship between Mn biomarkers and test scores. In adjusted models, increasing BnMn was significantly associated with decreased performance on average AVLT scores [ß (95% confidence interval (CI)) = -0.65 (-1.21, -0.09)] and Animal Naming scores [ß (95% CI) = -1.54 (-3.00, -0.07)]. Increasing FMn was significantly associated with reduced performance measured by the average AVLT [ß (95% CI) = -0.35 (-0.70, -0.006)] and the difference in AVLT scores [ß (95% CI) = -0.40 (-0.77, -0.03)]. BMn was not significantly associated with any test scores; no significant associations were observed with Fruit Naming or UPSIT tests. BnMn and FMn, but not BMn, are associated with cognitive function in Mn-exposed workers. None of the biomarkers were significantly associated with olfactory function.

Variations of MRI-assessed peristaltic motions during radiation therapy.

PURPOSE: Understanding complex abdominal organ motion is essential for motion management in radiation therapy (RT) of abdominal tumors. This study investigates abdominal motion induced by respiration and peristalsis, during various time durations relevant to RT, using various CT and MRI techniques acquired under free breathing (FB) and breath hold (BH). METHODS: A series of CT and MRI images acquired with various techniques under free breathing and/or breath hold from 37 randomly-selected pancreatic or liver cancer patients were analyzed to assess the motion in various time frames. These data include FB 4DCT from 15 patients (for motion in time duration of 5 sec), FB 2D cine-MRI from 4 patients (time duration of 1.7 min, 1 second acquisition time per slice), FB cine-MRI acquired using MR-Linac from 6 patients in various fractions (acquisition time is less than 0.6 seconds per slice), FB 4DMRI from 2 patients (time duration of 2 min), respiration-gated T2 with gating at the end expiration (time duration of 3-5 min), and BH T1 with multiphase dynamic contrast in acquisition times of 17 seconds for each of five phases (pre-contrast, arterial, venous, portal venous and delayed post-contrast) from 10 patients. Motions of various organs including gallbladder (GB) and liver were measured based on these MRI data. The GB motion includes both respiration and peristalsis, while liver motion is primarily respiration. By subtracting liver motion (respiration) from GB motion (respiration and peristalsis), the peristaltic motion, along with small residual motion, was obtained. RESULTS: From cine-MRI, the residual motion beyond the respiratory motion was found to be up to 0.6 cm in superior-inferior (SI) and 0.55 cm in anterior-posterior (AP) directions. From 2D cine-MRI acquired by the MR-Linac, different peristaltic motions were found from different fractions for each patient. The peristaltic motion was found to vary between 0.3-1 cm. From BH T1 phase images, the average motions that were primarily due to peristalsis movements were found to be 1.2 cm in SI, 0.7 cm in AP, and 0.9 cm in left-right (LR) directions. The average motions assessed from 4DCT were 1.0 cm in SI and 0.3 cm in AP directions, which were generally smaller than the motions assessed from cine-MRI, i.e., 1.8 cm in SI and 0.6 cm in AP directions, for the same patients. However, average motions from 4DMRI, which are coming from respiratory were measured to be 1.5, 0.5, and 0.4 cm in SI, AP, and LR directions, respectively. CONCLUSION: The abdominal motion due to peristalsis can be similar in magnitude to respiratory motion as assessed. These motions can be irregular and persistent throughout the imaging and RT delivery procedures, and should be considered together with respiratory motion during RT for abdominal tumors.

Feasibility of real-time lung tumor motion monitoring using intrafractional ultrasound and kV cone beam projection images.

PURPOSE: The ability to monitor intrafractional tumor motion is essential for radiation therapy of thoracic and abdominal tumors. This study aims to develop a method to track lung tumor motion using intrafractional continuous ultrasound (US) and periodic cone-beam projection images (CBPI). METHODS: Time-sequenced b-mode US and CBPI data were extracted from the data acquired with the Clarity® and XVI platforms on an Elekta linac, respectively. The data were synchronized through a video capture card (VCE-PRO, IMPERX Inc.) which was triggered by the XVI system. In this way, a system was configured to allow real-time acquisition of the diaphragm position synchronized with periodic acquisition of the lung tumor position. Feasibility of the system was demonstrated by acquiring synchronized data on an in-house motion platform with embedded spheres of different materials and US images of the diaphragm on 5 volunteers of various body sizes. Finally, ultrasound b-mode images and CBPI were also acquired simultaneously from 3 lung cancer patients. RESULTS: Diaphragm motion monitoring under free breathing (FB) was successful with intracostal US imaging. We observed that diaphragm visualization decreased with the increase in the body size of the volunteer. The US system was able to track the motion as small as 2 mm in the phantom. The intrafractional CBPI acquired during VMAT delivery was successfully synchronized with US acquisition in a phantom study. Collected patient data showed a significant correlation between diaphragm motion, an internal surrogate monitored by US, and the tumor motion in superior-inferior (SI) direction monitored by XVI (P Ë‚ 0.0001). CONCLUSIONS: The feasibility of real-time lung tumor motion tracking in SI direction with continuous ultrasound and periodic CBPI was demonstrated. The real-time estimation of the target position from the two streams for lung cancer patients would enable respiration gating or tracking during SBRT.

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.

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 (ß = 0.44, p = 0.047) and years of employment (ß = 0.05, p = 0.002), but not with natural log transformed MnB (ln(MnB)) (ß = 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.

We used neutron activation analysis (NAA) to measure hand bone manganese (BnMn) in 19 adult males. Median BnMn was 0.89µg/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: ß = -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.

Measurements of Strontium Levels in Human Bone In Vivo Using Portable X-ray Fluorescence (XRF).

Measurement of bone strontium (Sr) is vital to determining the effectiveness of Sr supplementation, which is commonly used for the treatment of osteoporosis. Previous technology uses radioisotope sources and bulky equipment to measure bone Sr. This study demonstrates the effectiveness of portable X-ray fluorescence (XRF) for bone Sr measurement and validates it using data from a population of 238 children. We identified correlations between bone Sr and age in our participants.

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.

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 Parkinson's 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: Mn's 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.

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.

A Dosimetry Study of Deuterium-Deuterium Neutron Generator-based In Vivo Neutron Activation Analysis.

A 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 × 10(8) ± 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.

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.