IN VIVO DETECTION OF RADIATION-INDUCED TISSUE DAMAGE IN KIDNEY BY C13 MRSI

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 最近引入的核超极化技术的液体状态，使在体内检测的C-13标记的内源性代谢物的磁共振波谱成像（MRSI）。我们研究采用这种新技术来评估辐射引起的组织损伤的可行性，这可能导致中等剂量的放射治疗。我们选择肾脏组织，因为肾脏是一个放射敏感的器官，并提供内部控制。在这项研究中，我们使用Wistar雄性大鼠体重200-450克，通过单侧照射一个肾脏与准直束的X射线模型。最初，大鼠接受15戈伊的辐射剂量，并在辐射后21天进行C-13磁共振波谱成像（MRSI）。在MRSI中，给大鼠静脉注射80 mM的超极化溶液[113 C]丙酮酸盐。通过在HyperSenseTM偏振器（Oxford instruments）中使用DNP技术进行超偏振。在3 T下进行快速化学位移成像（CSI），每6秒采集一次通过双肾的轴向切片，以测量代谢物丙酮酸盐、乳酸盐和丙氨酸的动态和空间分布。在成像后处死动物以收获用于组织病理学的肾组织，以确认成像观察结果。在我们的初步数据中，与未辐照肾脏相比，辐照肾脏中观察到的乳酸产生减少表明超极化C-13代谢成像技术可能用于检测肾组织中的辐射效应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent introduction of nuclear hyperpolarization technique to liquid state enabled in vivo detection of C-13 labeled endogenous metabolites by MR spectroscopy imaging (MRSI). We investigate feasibility of employing this novel technique to assess radiation-induced tissue damage, which could result in radiotherapy, at moderate doses. We choose kidney tissues because kidney is a radiosensitive organ and provides internal control. In this study, we use Wistar male rats weighing 200-450 g to make the model by unilaterally irradiating one kidney with a collimated beam of X-rays. Initially, rats received radiation dose of 15 Gy and were subjected to C-13 magnetic resonance spectroscopy imaging (MRSI) at 21 days of postirradiation time. In MRSI, rats were intravenously injected with a hyperpolarized solution of 80 mM [113C]pyruvate. Hyperpolarization was performed by using DNP technique in HyperSenseTM polarizer (Oxford instruments). Fast chemical shift imaging (CSI) was performed at 3 T to acquire axial slices through both kidneys in every 6th second to measure both dynamic and spatial distribution of metabolites, pyruvate, lactate, and alanine. Animals are sacrificed after imaging to harvest kidney tissues for histopathology in order to confirm imaging observations. In our preliminary data, observed reduction of lactate production in the irradiated kidney in comparison to non-irradiated kidney suggests potential use of hyperpolarized C-13 metabolic imaging technique to detect radiation effects in kidney tissues.