Development of Biomedical Devices for the In Vivo Measurement of Toxic Elements

在加拿大，人们在医疗和环境方面都暴露在许多有毒元素中。我们经常通过血液和尿液监测暴露，但这些只报告最近的暴露，而健康影响往往是长期暴露的结果。在我的实验室里，我们设计和制造了基于辐射的生物医学设备，来测量体内元素的保留和存储。我们的设备可用于评估和监测与慢性暴露有关的健康影响。我建议开发安全、无痛的技术，用于安全、无痛地测量人们可能通过医学接触到的Gd、Cr、Co等元素，以及加拿大一些地区人们饮用水中的氟(F)、砷(As)和硒(Se)。*我和我的学生将使用既定的方法开发设备。我们将从研究元素的物理性质开始，以确定合适的辐射技术。这可能取决于危险的器官，例如，如果我们想要评估肾脏，这项技术必须穿透几厘米厚的组织，但如果我们想测量皮肤，它只能穿透几毫米，因为更深的测量没有提供信息，反而增加了辐射剂量。我们将探索多种技术，尽管我的研究小组通常使用两种来构建我们的设备：X射线荧光分析(XRF)和中子活化分析(NAA)。在XRF中，一个人受到低能X射线或射线的照射，我们测量发出的特征X射线。在NAA中，一个人受到低能中子束的照射，并测量X和射线发射。我们的设备通过将一个人的信号与适当的校准标准中的信号进行比较来量化一个人的元素含量。在选择了一种很有前途的技术后，我们开始组装一个简单的设备，并使用基本的校准标准收集实验数据。同时，我们将开发一个蒙特卡罗计算机代码的输入来模拟这个第一次通过的系统。我们将把蒙特卡罗结果与实验数据进行比较，并进行调整，直到代码得到验证。然后我们将在代码中运行一系列更改，以预测更好的设备，然后我们将构建和测试该设备。我们反复迭代，多次，从一个实验到一个模型，再回到实验，直到我们开发出一个具有我们所需的检测能力的系统。一个完美的生物医学设备可能需要数年时间才能开发出来，但一旦检测极限接近所需的水平，我们就会进行广泛的辐射剂量测量，这使我们能够证明我们的设备用于人体测量是可行的。然后，NSERC的开发完成并取得成功，该设备进行体内测试。*这些新生物医学设备的开发对加拿大很重要：它们将使医生和公共卫生政策制定者确保加拿大人免受由有毒元素引起的严重但可预防的疾病的保护。**

In Canada, people are exposed to a number of toxic elements both medically and environmentally. We often monitor exposure through blood and urine, but these only report recent exposure, while health effects are often a result of long term exposure. In my laboratory, we design and build radiation-based biomedical devices that measure retention and storage of elements in the body. Our devices can be used to assess and monitor health effects linked to chronic exposure. I propose to develop technology for the safe, painless measurement of gadolinium (Gd), chromium (Cr), cobalt (Co), elements that people can be exposed to medically, and for fluorine (F), arsenic (As) and selenium (Se), elements which are in people's drinking water in some areas of Canada. ***My students and I will develop the devices using an established methodology. We will start by investigating an element's physical properties to determine a suitable radiation technique. This may depend on the organ at risk, e.g., if we wish to assess the kidney, the technique must penetrate through several cm of tissue, but if we wish to measure skin, it must only penetrate a few mm, because deeper measurement provides no information but increases the radiation dose. We will explore multiple techniques, although my research group commonly uses 2 to build our devices: x-ray fluorescence analysis (XRF) and neutron activation analysis (NAA). In XRF, a person is irradiated with low energy x- or -rays, and we measure emitted characteristic x-rays. In NAA, a person is irradiated with a low energy neutron beam, and the x- and -ray emission measured. Our devices quantify a person's elemental content by comparing their signal to one from appropriate calibration standards. Having chosen a promising technique, we proceed by assembling a simple device, and collecting experimental data using basic calibration standards. At the same time, we will develop the input to a Monte Carlo computer code to model this first pass' system. We will compare the Monte Carlo result against the experimental data and adjust until the code is validated. We will then run a series of changes in the code to predict a better' device, which we will then build and test. We iterate back and forth, multiple times, from experiment to model, and back to experiment, until we develop a system that has the detection capability that we require. A perfected biomedical device can take years to develop, but once detection limits approach the level required, we perform extensive radiation dosimetry measurements, which allow us to show that our devices are feasible for measurements of people. The NSERC development is then complete and successful and the device proceeds to in vivo testing.***The development of these new biomedical devices is important to Canada: they will allow physicians and public health policy makers to ensure that Canadians are protected from the serious, yet preventable, disease caused by toxic elements.**