Feasibility of using a single MRI acquisition for fiducial marker localization and synthetic CT generation towards MRI-only prostate radiation therapy treatment planning.

Purpose.To investigate the feasibility of using a single MRI acquisition for fiducial marker identification and synthetic CT (sCT) generation towards MRI-only treatment planning for prostate external beam radiation therapy (EBRT).Methods.Seven prostate cancer patients undergoing EBRT, each with three implanted gold fiducial markers, participated in this study. In addition to the planning CT scan, all patients were scanned on a 3 T MR scanner with a 3D double-echo gradient echo (GRE) sequence. Quantitative susceptibility mapping (QSM) was performed for marker localization. QSM-derived marker positions were compared to those from CT. The bulk density assignment technique for sCT generation was adopted. The magnitude GRE images were segmented into muscle, bone, fat, and air using a combination of unsupervised intensity-based classification of soft tissue and convolutional neural networks (CNN) for bone segmentation.Results.All implanted markers were visualized and accurately identified (average error: 0.7 ± 0.5 mm). QSM generated distinctive contrast for hemorrhage, calcifications, and gold fiducial markers. The estimated susceptibility/HU values on QSM/CT for gold and calcifications were 31.5 ± 2.9 ppm/1220 ± 100 HU and 14.6 ± 0.9 ppm/440 ± 100 HU, respectively. The intensity-based soft tissue classification resulted in an average Dice score of 0.97 ± 0.02; bone segmentation using CNN resulted in an average Dice score of 0.93 ± 0.03.Conclusion.This work indicates the feasibility of simultaneous fiducial marker identification and sCT generation using a single MRI acquisition. Future works includes evaluation of the proposed method in a large cohort of patients with optimized acquisition parameters as well as dosimetric evaluations.

Modeling elemental strontium in human bone based on in vivo x-ray fluorescence measurements in osteoporotic females self-supplementing with strontium citrate.

An in-house custom I-125 excited in vivo x-ray fluorescence (IVXRF) system was used to perform bone strontium (Sr) measurements in individuals suffering from osteoporosis and/or osteopenia. These individuals, who were self-administering with Sr supplements of their choice, were measured frequently, ranging from weekly to biweekly to monthly, over four years, as part of the Ryerson and McMaster Sr in Bone Research Study. Based on these data collected, data from eight subjects were used to perform kinetic modeling of Sr in human bone. Power and exponential models were used to model the data based on one and two compartmental systems. Model parameters included: mean normalized baseline bone Sr signal, half-life and bone Sr uptake. A one compartmental exponential model applied to finger and ankle bone measurements gave half-lives of (508 ± 331) d and (232 ± 183) d, respectively, but did not show statistically significant differences (p = 0.087 96). However, the values fall within literature estimates. When a two compartmental model was applied to finger bone measurements, half-lives of (300 ± 163) d and (2201 ± 1662) d were observed. Ankle bone data gave half-lives of (156 ± 117) d and (1681 ± 744) d. A two sample t-test, assuming unequal variances, showed these half-lives to be statistically different in both the finger and ankle bone measurements (p = 0.0147 and p = 0.00711, respectively). Common kinetic parameters amongst the different subjects could not be unambiguously identified due to the wide scatter of data, leading to an inconclusive kinetic model. The wide distribution of data is suggested to be physiological since technical and positioning factors were eliminated as possible causes. This outcome indicates the need for a more controlled study and further understanding of the physiological mechanism of Sr absorption.

Feasibility of measuring arsenic and selenium in human skin using in vivo x-ray fluorescence (XRF)--a comparison of methods.

In recent years, in vivo measurement systems of arsenic in skin by K-shell x-ray fluorescence (XRF) have been developed, including one which was applied in a pilot study of human subjects. Improved tube-based approaches suggest the method can be further exploited for in vivo studies. Recently, it has been suggested that selenium deficiency is correlated with arsenic toxicity. A non-invasive measurement of both elements could therefore be of potential interest. The main aim of this current study was to evaluate and compare the performance of an upgraded portable XRF system and an advanced version of the benchtop XRF system for both selenium and arsenic. This evaluation was performed in terms of arsenic and selenium Kα detection limits for a 4W gold anode Olympus InnovX Delta portable analyzer (40 kVp) in polyester resin skin-mimicking phantoms. Unlike the polychromatic source earlier reported in the literature, the benchtop tube-based technique involves monochromatic excitation (25 W silver anode, manufactured by x-ray optics, XOS) and a higher throughput detector type. Use of a single exciting energy allows for a lower in vivo dose delivered and superior signal-noise ratio. For the portable XRF method, arsenic and selenium minimum detection limits (MDLs) of 0.59 ± 0.03 ppm and 0.75 ± 0.02 ppm respectively were found for 1 min measurement times. The MDLs for arsenic and selenium using the benchtop system were found to be 0.35 ± 0.01 ppm and 0.670 ± 0.004 ppm respectively for 30 min measurement times. In terms of a figure of merit (FOM), allowing for dose as well as MDL, the benchtop system was found to be superior for arsenic and the two systems were equivalent, within error, for selenium. We shall discuss the performance and possible improvements of each system, their ease of use and potential for field application.

Non Tumor Perfusion Changes Following Stereotactic Radiosurgery to Brain Metastases.

Purpose: To evaluate early perfusion changes in normal tissue following stereotactic radiosurgery (SRS). Methods: Nineteen patients harboring twenty-two brain metastases treated with SRS were imaged with dynamic susceptibility magnetic resonance imaging (DSC MRI) at baseline, 1 week and 1 month post SRS. Relative cerebral blood volume and flow (rCBV and rCBF) ratios were evaluated outside of tumor within a combined region of interest (ROI) and separately within gray matter (GM) and white matter (WM) ROIs. Three-dimensional dose distribution from each SRS plan was divided into six regions: (1) <2 Gy; (2) 2-5 Gy; (3) 5-10 Gy; (4) 10-12 Gy; (5) 12-16 Gy; and (6) >16 Gy. rCBV and rCBF ratio differences between baseline, 1 week and 1 month were compared. Best linear fit plots quantified normal tissue dose-dependency. Results: Significant rCBV ratio increases were present between baseline and 1 month for all ROIs and dose ranges except for WM ROI receiving <2 Gy. rCBV ratio for all ROIs was maximally increased from baseline to 1 month with the greatest changes occurring within the 5-10 Gy dose range (53.1%). rCBF ratio was maximally increased from baseline to 1 month for all ROIs within the 5-10 Gy dose range (33.9-45.0%). Both rCBV and rCBF ratios were most elevated within GM ROIs. A weak, positive but not significant association between dose, rCBV and rCBF ratio was demonstrated. Progressive rCBV and rCBF ratio increased with dose up to 10 Gy at 1 month. Conclusion: Normal tissue response following SRS can be characterized by dose, tissue, and time specific increases in rCBV and rCBF ratio.

Monitoring bone strontium levels of an osteoporotic subject due to self-administration of strontium citrate with a novel diagnostic tool, in vivo XRF: a case study.

A previously developed in vivo X-ray fluorescence (IVXRF) I-125 based system was used to measure bone strontium levels non-invasively in an osteoporotic female volunteer. The volunteer was recruited in December 2008, as part of the Ryerson and McMaster University Strontium in Bone Research Study and measured at twice weekly, weekly and monthly intervals. Thirty minute measurements were taken at the finger and ankle bone sites, representing primarily cortical and trabecular bone, respectively and the strontium K-alpha X-ray peak at 14.16 keV was used in the analysis. Since the volunteer had no prior history of strontium based medications or supplementation, baseline natural strontium levels were obtained followed by a 24h measurement of first intake of strontium citrate supplements (680 mg Sr/day). While the baseline levels of 0.38 ± 0.05 and 0.39 ± 0.10 for the finger and ankle, respectively, were on par with those previously reported in Caucasians among twenty-two healthy non-supplementing strontium individuals by our group, an increase began to be seen after 24 hrs of 0.62 ± 0.14 and 0.45 ± 0.12 for the finger and ankle, respectively. By 120 h, the increase was statistically significant at 0.68 ± 0.07 and 0.93 ± 0.05, respectively. Further increases occurred within an interval of 90-180 days, with the most recent, after 800 days, at the finger and ankle being 7 and 15 times higher than the initial baseline reading. The intriguing results show bone strontium incorporation and retention follow a pattern, suggesting strontium levels, at least in the ankle, do not plateau within two to three years and will continue to increase over time, as an individual takes strontium supplements. The ability of this IVXRF system to monitor and measure bone strontium levels over time provides a useful diagnostic tool to help gain insight into strontium bone kinetics.

Aluminium and strontium in calcium supplements and antacids: a concern to haemodialysis patients?

Trace elements, most notably aluminium and strontium, have been noted for their role in the development of secondary bone disorders in haemodialysis patients. Due to the large dosages of calcium required for the maintenance of dialysis patients, this study investigated whether the source of calcium chosen for supplementation, including the form of administration (i.e. chewable forms or capsules), has an influence on the total amount of strontium and aluminium ingested daily. A convenience sample of various calcium supplement tablets and antacids was acquired, and strontium and aluminium quantification was performed by wavelength-dispersive X-ray fluorescence spectrometry. The use of readily available oyster shell-based calcium was found potentially to increase the total amount of ingested strontium substantially with concentrations reaching (2.26 +/- 0.05) (mg Sr).(g Ca)(-1), while the use of antacids or chewable supplements was found to contain concentrations reaching as high as (1.2 +/- 0.3) (mg Al).(g Ca)(-1) in the supplements analysed within this work. It is recommended that the choice of calcium supplement prescribed to individuals undergoing haemodialysis be closely regulated and noted as a possible factor in the prevalence of bone disorders reported in these patients.

Evaluation of imaging technologies to correct for photon attenuation in the overlying tissue for in vivo bone strontium measurements.

The interpretation of measurements of bone strontium in vivo using energy dispersive x-ray fluorescence spectroscopy is presently hindered by overlying skin and soft-tissue absorption of the strontium x-rays. The use of imaging technologies to measure the overlying soft-tissue thickness at the index finger measuring site might allow correction of the strontium reading to estimate its concentration in bone. An examination of magnetic resonance (MR), computed tomography (CT) and high-frequency ultrasound (US) imaging technologies revealed that 55 MHz US had the smallest range of measurement uncertainty at 3.2% followed by 1 Tesla MR, 25 MHz US, 8 MHz US and CT at 4.3, 5.4, 6.6 and 7.1% uncertainty, respectively. Of these, only CT imaging appeared to underestimate total thickness (p < 0.05). Furthermore, an inter-study comparison on the accuracy of US measurements of the overlying tissue thickness at finger and ankle in nine subjects was investigated. The 8 MHz US system used in prior in vivo experiments was found to perform satisfactorily in a repeat study of ankle measurements, but indicated that finger thickness measurements may have been misread in previous studies by up to 17.7% (p < 0.025). Repeat ankle measurements were not significantly different from initial measurements at 2.2% difference.

Noninvasive measurement of aluminium in human bone: preliminary human study and improved system performance.

Aluminium has been measured in the hands of 18 referent subjects and six aluminium welders using the technique of in vivo neutron activation analysis. The minimal detection limit (MDL) in the human subjects was 28.0 microgAl/gCa, whereas it was 19.5 microgAl/gCa in calibration standards. On average the aluminium exposed subjects had higher levels of aluminium in their hands than did the referent subjects. However, this difference only just achieved significance at the 5% level and should be treated with caution, since the study had not been deliberately designed to assess this difference. Following the preliminary human study, improvements were made to the measurement system with respect to the gamma-ray detector array and to the timing sequence of irradiation-transfer-counting. These improvements were tested on the calibration standards, lowering the MDL from 19.5 microgAl/gCa to 8.32 microgAl/gCa. A similar improvement in human measurements would result in an in vivo MDL of 12.0 microgAl/gCa.

Opportunities to improve the in vivo measurement of manganese in human hands.

Manganese (Mn) is an element which is both essential for regulating neurological and skeletal functions in the human body and also toxic when humans are exposed to excessive levels. Its excessive inhalation as a result of exposure through industrial and environmental emissions can cause neurological damage, which may manifest as memory deficit, loss of motor control and reduction in the refinement of certain body motions. A number of clinical studies demonstrate that biological monitoring of Mn exposure using body fluids, particularly blood, plasma/serum and urine is of very limited use and reflect only the most recent exposure and rapidly return to within normal ranges. In this context, a non-invasive neutron activation technique has been developed at the McMaster University accelerator laboratory that could provide an alternative to measure manganese stored in the bones of exposed subjects. In a first pilot study we conducted recently on non-exposed human subjects to measure the ratio of Mn to Ca in hand bones, it was determined that the technique needed further development to improve the precision of the measurements. It could be achieved by improving the minimum detection limit (MDL) of the system from 2.1 microg Mn/g Ca to the reference value of 0.6 microg g(-1) Ca (range: 0.16-0.78 microg Mn/g Ca) for the non-exposed population. However, the developed procedure might still be a suitable means of screening patients and people exposed to excessive amounts of Mn, who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. To improve the MDL of the technique to the expected levels of Mn in a reference population, the present study investigates further optimization of irradiation conditions, which includes the optimal selection of proton beam energy, beam current and irradiation time and the effect of upgrading the 4pi detection system. The maximum local dose equivalent that could be given to the hand as a result of irradiation was constrained to be less than 150 mSv as opposed to the previously imposed dose equivalent limit of 20 mSv. A maximum beam current, which could be delivered on the lithium target to produce neutrons, was restricted to 500 microA. The length of irradiation intervals larger than 10 min, was considered inconvenient and impractical to implement with Mn measurements in humans. To fulfil the requirements for developing a protocol for in vivo bone Mn measurements, a revised estimate of the dose equivalent has been presented here. Beam energy of 1.98 MeV was determined to be optimal to complete the irradiation procedure within 10 min using 500 microA beam current. The local dose equivalent given to hand was estimated as 118 mSv, which is lower by a factor of 1.5 compared to that of 2.00 MeV. The optimized beam parameters are expected to improve the currently obtained detection limit of 2.1 microg Mn/g Ca to 0.6 microg Mn/g Ca. Using this dose equivalent delivered to the central location of the hand, the average dose equivalent to the hand of 74 mSv and an effective dose of approximately 70 microSv will be accompanying the non-invasive, in vivo measurements of bone Mn, which is little over the chest radiograph examination dose.

In vivo measurement of bone aluminum in population living in southern Ontario, Canada.

The harmful biological effect of excessive aluminum (Al) load in humans has been well documented in the literature. Al stored in bone, for instance due to dialysis treatment or occupational exposure, can interfere with normal bone remodeling leading to osteodystrophy, osteoarthritis, or osteomalacia. On the other hand, the relationship between chronic Al exposure and the risk of Alzheimer's disease remains controversial. In this work, the feasibility of in vivo neutron activation analysis (IVNAA) for measuring Al levels in the human hand bone, using the thermal neutron capture reaction 27Al(n, gamma)28 Al, is reported. This noninvasive diagnostic technique employs a high beam current Tandetron accelerator based neutron source, an irradiation/shielding cavity, a 47pi NaI(Tl) detector system, and a new set of hand bone phantoms. The photon spectra of the irradiated phantom closely resemble those collected from the hands of nonexposed healthy subjects. A protocol was developed using the newly developed hand phantoms, which resulted in a minimum detectable limit (MDL) of 0.29 mg Al in the human hand. Using the ratio of Al to Ca as an index of Al levels per unit bone mass, the MDL was determined as 19.5 +/- 1.5 microg Al/g Ca, which is within the range of the measured levels of 20-27 microg Al/g Ca [ICRP Report of the Task Group on Reference Man, Publication 23 (Pergamon, Oxford, 1975)] found in other in vivo and in vitro studies. Following the feasibility studies conducted with phantoms, the diagnostic technique was used to measure Al levels in the hand bones of 20 healthy human subjects. The mean hand bone Al concentration was determined as 27.1 +/- 16.1 (+/-1 SD) microg Al/g Ca. The average standard error (1sigma) in the Al/Ca is 14.0 microg Al/g Ca, which corresponds to an average relative error of 50% in the measured levels of Al/Ca. These results were achieved with a dose equivalent of 17.6 mSv to a hand and an effective dose of 14.4 microSv. This effective dose is approximately half of that received in a chest radiograph examination. It is recommended to investigate the use of the bone Al IVNAA diagnostic technique for in vivo measurements of patients with documented overload of Al in bone.

Quantification of manganese in human hand bones: a feasibility study.

Manganese is both an essential element to human health and also toxic when humans are exposed to excessive levels, particularly by means of inhalation. Biological monitoring of manganese exposure is problematic. It is subject to homeostasis; levels in blood (or serum/plasma) reflect only the most recent exposure and rapidly return to within normal ranges, even when there has been a temporary excursion in response to exposure. In this context, we have been developing a non-invasive technique for measurement of manganese stored in bone, using in vivo neutron activation analysis. Following preliminary feasibility studies, the technique has been enhanced by two significant infrastructure advances. A specially designed irradiation facility serves to maximize the activation of manganese with respect to the dose of ionizing radiation. Secondly, an array of eight NaI(Tl) crystals provides a detection system with very close to 4 pi geometry. This feasibility study, using neutron activation analysis to measure manganese in the bones of the hand, takes two features into account. Firstly, there is considerable magnesium present in the bone and this produces a spectral interference with the manganese. The 26 Mg(n,gamma)27 Mg reaction produces gamma -rays of 0.843 MeV from the decay of 27 Mg, which interfere with the 0.847 MeV gamma -rays from the decay of 56 Mn,produced by the 55 Mn(n,gamma)56 Mn reaction. Secondly, this work provides estimates of the levels of manganese to be expected in referent subjects. A revised estimate has been made from the most recent literature to explore the potential of the technique as a suitable means of screening patients and people exposed to excessive amounts of Mn who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. This report presents the enhancements to the neutron activation system, by which manganese can be measured, which resulted in a detection limit in the hand of human subjects of 1.6 microg/g Ca. It also provides a revised estimate of expected referent levels of manganese in bone, now estimated to be 0.63 microg/g Ca and highlights the extent to which technical improvements will be required to further extend the application of the technique for in vivo measurements in non-exposed human subjects.

A preliminary study for non-invasive quantification of manganese in human hand bones.

Manganese (Mn) is a nutrient essential for regulating neurological and skeletal functions in the human body, but it is also toxic when humans are excessively exposed to Mn. Blood (or serum/plasma) and other body fluids reflect only the most recent exposure and rapidly return to within normal ranges, even when there has been a temporary excursion in response to exposure. In this context, we have been developing a non-invasive measurement of Mn stored in bone, using in vivo neutron activation analysis. Following feasibility studies, a first pilot study, using neutron activation analysis to measure Mn in the bones of the hand of ten healthy male human subjects, was conducted with the approval of the concerned research ethics boards. The participants of this study had no known history of exposure to Mn. Two volunteers were excluded from this study due to technical problems with their measurements. The inverse variance weighted mean value of Mn/Ca for the participants of this study is 0.12+/-0.68 microg Mn/g Ca which is comparable within uncertainties with the estimated range of 0.16-0.78 microg Mn/g Ca and mean value of 0.63+/-0.30 microg Mn/g Ca derived from cadaver data. It is recommended to investigate the use of the diagnostic technique for in vivo measurements of workers exposed occupationally to excessive amounts of Mn who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. The technique needs further development to improve the precision of in vivo measurements in the non-exposed population.

Coherent normalization of finger strontium XRF measurements: feasibility and limitations.

A non-invasive in vivo x-ray fluorescence (XRF) method of measuring bone strontium concentrations has previously been reported as a potential diagnostic tool able to detect strontium concentration in the finger and ankle bones. The feasibility of coherent normalization for (125)I-source-based finger bone strontium x-ray fluorescence (XRF) measurements is assessed here by theoretical considerations and Monte Carlo simulations. Normalization would have several advantages, among which are the correction for the signal attenuation by the overlying soft tissue, and intersubject variability in the bone size and shape. The coherent normalization of bone strontium XRF measurements presents several challenges dictated by the behaviour of the coherent cross section and mass attenuation coefficient at the energies involved. It was found that the coherent normalization alone with either 22.1 keV or 35.5 keV photons was not successful in correcting for the overlying soft tissue attenuation. However, it was found that the coherent peak at 35.5 keV was able to correct effectively for variability in the finger bone size between people. Thus, it is suggested that, if the overlying soft tissue thickness can be obtained by means of an independent measurement, the 35.5 keV peak can be used to correct for the bone size, with an overall accuracy of the normalization process of better than 10%.

In vivo assessment of magnesium status in human body using accelerator-based neutron activation measurement of hands: a pilot study.

Magnesium (Mg) is an element essential for many enzymatic reactions in the human body. Various human and animal studies suggest that changes in Mg status are linked to diseases such as cardiac arrhythmia, coronary heart disease, hypertension, premenstrual syndrome, and diabetes mellitus. Thus, knowledge of Mg levels in the human body is needed. A direct measurement of human blood serum, which contains only 0.3% of the total body Mg, is generally used to infer information about the status of Mg in the body. However, in many clinical situations, Mg stored in large levels, for example in bones, muscles, and soft tissues, needs to be monitored either to evaluate the efficacy of a treatment or to study the progression of diseases associated with the deficiency of total body Mg. This work presents a feasibility study of a noninvasive, in vivo neutron activation analysis (IVNAA) technique using the 26Mg (n, gamma) 27Mg reaction to measure Mg levels in human hands. The technique employs the McMaster University high beam current Tandetron accelerator hand irradiation facility and an array of eight NaI (T1) detectors arranged in a 4 pi geometry for delayed counting of the 0.844 and 1.014 MeV gamma rays emitted when 27Mg decays in the irradiated hand. Mg determination in humans using IVNAA of hands has been demonstrated to be feasible, with effective doses as low as one-quarter of those delivered in chest x rays. The overall experimental uncertainty in the measurements is estimated to be approximately 5% (1 sigma). The results are found to be in the range of the in vitro measurements reported for other cortical bones collected from different sites of the human skeleton, which confirms that this technique mainly provides a measure of the amount of Mg in hand bones. The average concentration of Mg determined in human hands is 10.96 +/- 1.25 (+/- 1 SD) mg Mg/g Ca. The coefficient of variation (11%) observed in this study is comparable with or lower than several studies using in vitro measurements reported in the literature and therefore allows for a quantitative intersubject comparison, even if to a limited extent. The features of the developed technique such as its simplicity, rapidity, accuracy, robustness, noninvasive nature, and very effective use of radiation doses, present the technique as a viable diagnostic tool available for trial in a clinical environment.

In vivo study of an x-ray fluorescence system to detect bone strontium non-invasively.

An x-ray fluorescence (XRF) system using 125I as the source was developed to measure strontium in bone in vivo. As part of an in vivo pilot study, 22 people were measured at two bone sites, namely the index finger and the tibial ankle joint. Ultrasound measurements were used to obtain the soft tissue thickness at each site, which was necessary to correct the signal for tissue attenuation. For all 22 people, the strontium peak was clearly distinguishable from the background, proving that the system is able to measure Sr in vivo in people having normal bone Sr levels. Monte Carlo simulations were carried out to test the feasibility and the limitations of using the coherently scattered peak at 35.5 keV as a means to normalize the signal to correct for the bone size and shape. These showed that the accuracy of the normalized Sr signal when comparing different people is about 12%. An interesting result arising from the study is that, in the measured population, significantly higher measurements of bone Sr concentration were observed in continental Asian people, suggesting the possibility of a dietary or race dependence of the bone Sr concentration or a different bone biology between races.

Dosimetric characterization of the irradiation cavity for accelerator-based in vivo neutron activation analysis.

A neutron irradiation cavity for in vivo activation analysis has been characterized to estimate its dosimetric specifications. The cavity is defined to confine irradiation to the hand and modifies the neutron spectrum produced by a low energy accelerator neutron source to optimize activation per dose. Neutron and gamma-ray dose rates were measured with the microdosimetric technique using a tissue-equivalent proportional counter at the hand irradiation site and inside the hand access hole. For the outside of the cavity, a spherical neutron dose equivalent meter and a Farmer dosemeter were employed instead due to the low intensity of the radiation field. The maximum dose equivalent rate at the outside of the cavity was 2.94 microSv/100 microA min, which is lower by a factor of 1/2260 than the dose rate at the hand irradiation position. The local dose contributions from a hand, an arm and the rest of a body to the effective dose rate were estimated to be 1.73, 0.782 and 2.94 microSv/100 microA min, respectively. For the standard irradiation protocol of the in vivo hand activation, 300 microA min, an effective dose of 16.3 microSv would be delivered.

In vivo measurement of bone aluminium: recent developments.

A biomarker of aluminium accumulation in the human body can play a valuable role in determining health effects of chronic aluminium exposure, complementing other human and environmental monitoring data. In vivo neutron activation provides such a non-invasive biomarker. To date, the best in vivo neutron activation system used thermalised neutrons from a nuclear reactor at Brookhaven National Laboratory, which suffered only slightly from interference from other elements, primarily phosphorus, and from the disadvantage of restricted accessibility. At McMaster, we use a nuclear reaction on an accelerator to select neutron energy, which eliminates the interferences. Spectral decomposition analysis improved sensitivity. A new 4pi detection system also enhanced sensitivity. Together these improvements yield a minimum detection limit of 0.24 mgAl in a hand, slightly better than at Brookhaven and equivalent to "normal" levels. Further improvements should result from a new irradiation cavity and from using a higher proton current on the accelerator to shorten irradiation times. The system is now ready for pilot human studies.

Quantification of bone strontium levels in humans by in vivo x-ray fluorescence.

The need for in vivo bone strontium assessment arises because strontium may exert a number of effects on bone, which may be either beneficial or toxic. Measurements discussed here are noninvasive, no sample is taken, nor is there discomfort to patients. The developed source excited x-ray fluorescence system employs a 109Cd source to excite the strontium K x rays, with the source and detector in approximately 90 degree geometry relative to the sample position. The factors affecting the accuracy and minimal detectable limit for bone strontium in vivo measurements are discussed. A system calibration revealed a minimum detectible limit of approximately 0.25 mg Sr/g Ca, which is sufficient for the monitoring of strontium levels in healthy subjects and patients with elevated bone strontium concentrations. Preliminary in vivo measurements in ten healthy subjects at two bone sites (phalanx and tibia) indicated that this system can be applied for cumulative bone strontium estimation while delivering a low effective dose of 80 nSv during the measurement time. Future work will involve attempts to enhance system precision with alternative fluorescing sources and further optimization of the detection system.

Ultrasound measurements of overlying soft tissue thickness at four skeletal sites suitable for in vivo x-ray fluorescence.

Due to signal attenuation in overlying soft tissue, development of x-ray fluorescence systems to measure low atomic number elements, such as strontium, in human bone required a search for a skeletal site with thin overlying tissue. This paper reports ultrasound measurements of overlying tissue on 10 subjects, at four anatomical sites. The average tissue thickness at the finger was (2.9+/-0.7) mm. The average tissue thicknesses were (3.6+/-0.7) mm, (4.8+/-2.0) mm, and (8.4+/-1.7) mm at forehead, tibia and heel, respectively. Additionally, both parametric and nonparametric approaches to the relationship between body mass index (BMI) and tissue thickness suggest that there is a significant linear correlation between the subject's BMI and overlying tissue at the finger and heel bone. These correlations might be used as a criterion to perform XRF measurements, however a larger data set is required to address these correlations more clearly.

An accelerator based system for in vivo neutron activation analysis measurements of manganese in human hand bones.

Manganese (Mn) is an essential nutrient for growth and development. Unfortunately, overexposure can lead to neurological damage, which is manifested as a movement disorder marked by tremors. Preclinical symptoms have been found in populations occupationally exposed to the element, and it is suggested that in late stages of the disorder, removing the Mn exposure will not prevent symptoms from progressing. Hence, it is desirable to have a means of monitoring Mn body burden. In vivo neutron activation analysis (IVNAA) is a technique which allows the concentration of some elements to be determined within sites of the body without invasive procedures. Data in the literature suggests that the Mn concentration in bone is greater than other tissues, and that it may be a long term storage site following exposure. Therefore, using the McMaster KN-accelerator to produce neutrons through the 7Li(p,n)7Be reaction, the feasibility of IVNAA for measuring Mn levels in the human hand bone was investigated. Mn is activated through the 55Mn(n,gamma)56Mn reaction, and the 847 keV gamma rays emitted when 56Mn decays are measured outside the body using NaI(Tl) detectors. An optimal incident proton energy of 2.00 MeV was determined from indium foil and microdosimetry measurements. Hand phantom data suggest a minimum detectable limit of approximately 1.8 ppm could be achieved with a reasonably low dose of 50 mSv to the hand (normal manganese levels in the human hand are approximately 1 ppm). It is recommended the technique be developed further to make human in vivo measurements.