Opportunities to improve the in vivo measurement of manganese in human hands
Opportunities to improve the in vivo measurement of manganese in human hands
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DOI：
10.1088/0031-9155/54/1/002
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发表时间：
2009-01-07
影响因子：
3.5
通讯作者：
Waker, A. J.
中科院分区：
文献类型：
--
作者：
Aslam;Chettle, D. R.;Waker, A. J.
锰（Mn）是一种元素，它对调节人体神经和骨骼功能至关重要，当人类暴露于过量水平时也是有毒的。由于工业和环境排放物的暴露而导致的过量吸入会造成神经损伤，这可能表现为记忆缺陷、运动控制丧失和某些身体运动的精细化降低。许多临床研究表明，使用体液（特别是血液、血浆/血清和尿液）对锰暴露进行生物监测的用途非常有限，仅反映最近的暴露，并迅速恢复到正常范围内。在这种情况下，麦克马斯特大学加速器实验室开发了一种非侵入性中子活化技术，可以提供一种替代方法来测量暴露受试者骨骼中储存的锰。在我们最近对非暴露的人类受试者进行的第一项试点研究中，测量了手骨中Mn与Ca的比例，确定该技术需要进一步发展以提高测量的精度。可以通过将系统的最低检测限（MDL）从2.1 μ g Mn/g Ca提高到非接触人群的参考值0.6 μ g g g（-1）Ca（范围：0.16-0.78 μ g Mn/g Ca）来实现。然而，开发的程序仍然可能是筛选患者和暴露于过量Mn的人的合适手段，这些人可以通过各种动物研究证明骨骼中的Mn水平增加许多倍。为了提高该技术的MDL在参考人群中的预期水平的锰，本研究探讨进一步优化的照射条件，其中包括质子束能量，束流和照射时间的最佳选择和升级的4 π检测系统的效果。由于辐照而可能给予手部的最大局部剂量当量被限制在150 mSv以下，而先前规定的剂量当量限值为20 mSv。最大的束流，它可以传递到锂靶上产生中子，被限制在500 μ A。照射间隔的长度大于10分钟，被认为是不方便和不切实际的，以实现在人体中的Mn测量。为了满足开发体内骨Mn测量方案的要求，此处提供了剂量当量的修订估计值。确定1.98 MeV的射束能量对于使用500 μ A射束电流在10分钟内完成照射程序是最佳的。手部局部剂量当量估计为118 mSv，比2.00 MeV低1.5倍。优化的光束参数，预计目前获得的2.1 μ g Mn/g Ca的检测限提高到0.6 μ g Mn/g Ca。使用传递到手的中心位置的该剂量当量，相当于手的74 mSv的平均剂量和约70 mu Sv的有效剂量将伴随骨Mn的非侵入性体内测量，其略高于胸部X线照片检查剂量。
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 mu g Mn/g Ca to the reference value of 0.6 mu g g(-1) Ca (range: 0.16-0.78 mu g 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 4 pi 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 mu A. 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 mu A 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 mu g Mn/g Ca to 0.6 mu g 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 mu Sv will be accompanying the non-invasive, in vivo measurements of bone Mn, which is little over the chest radiograph examination dose.