Functional MRI of the transplanted kidney

描述（由申请人提供）：自50多年前首次成功移植肾脏以来，肾脏移植挽救了许多生命。尽管手术技术和免疫抑制治疗的进步导致1年生存率超过90%。移植后早期移植物功能障碍发生率高达30%。这是决定同种异体移植最终命运的一个重要因素，因为那些移植功能延迟的受者的急性排斥反应导致5年移植存活率仅为35%。这一观察结果表明，如果我们要限制肾元损失和维持同种异体功能，急性排斥发作的早期诊断是必要的。磁共振成像（MRI）是非常适合评估肾移植解剖和功能。MRI使用非肾毒性造影剂，具有独立评估不同解剖区域的空间分辨率。新的磁共振成像技术，称为功能性磁共振成像，可以评估肾小球的过滤能力，肾脏内的局部血流，以及组织水平上的氧生物利用度。到目前为止，还没有其他方式可以结合技术来提供如此全面的肾脏评估。如果MRI可以非侵入性地识别功能障碍的根本原因，我们就有可能避免活检并仍然适当地靶向治疗。该提案的R21阶段侧重于优化MR灌注，血氧水平依赖（BOLD） MRI和单肾滤过率（skGFR）序列。将对成年志愿者进行MR灌注、BOLD MRI和skGFR的重复测量，以确定其可重复性和自然变异性。如果成功，这一建议将导致一种无创的肾功能评估方法，然后可以应用于移植肾功能障碍的研究。该提案的R33阶段将利用MR灌注，BOLD MRI和skGFR在移植功能延迟的人群中区分急性排斥反应和ATN。除了使用功能性MRI诊断移植功能障碍外，我们还将简化图像分析以减少后处理时间，并允许我们的技术广泛应用于临床。

DESCRIPTION (provided by applicant): Kidney transplantation has saved many lives since the first successful transplant more than 50 years ago. Although advances in surgical technique and immunosuppressive therapy have resulted in 1-year survival rates greater than 90%. graft dysfunction in the early post-transplant period occurs in up to 30% of transplant recipients. This is an important factor in the ultimate fate of the allograft, as acute rejection in those recipients with delayed graft function results in a 5-year graft survival of only 35%. This observation alone suggests that early diagnosis of acute rejection episodes is imperative if we are to limit nephron loss and maintain allograph function. Magnetic Resonance Imaging (MRI) is well-suited for assessing renal transplant anatomy and function. MRI uses non-nephrotoxic contrast agents and has the spatial resolution to independently assess different anatomical regions. New MR techniques, termed functional MRI, can assess the filtration capacity of glomeruli, regional blood flow within the kidney, and the oxygen bioavailability at the tissue level. To date, no other modality can combine techniques to provide such a comprehensive evaluation of the kidney. If MRI can non-invasively identify the underlying cause of dysfunction, we could potentially avoid biopsy and still target therapy appropriately. The R21 phase of this proposal focuses on optimizing MR perfusion, blood oxygen level dependent (BOLD) MRI, and single kidney filtration rate (skGFR) sequences. Repetitive measurements of MR perfusion, BOLD MRI and skGFR will be performed on adult volunteers in order to determine their reproducibility and natural variability. If successful, this proposal will result in a non-invasive method for evaluating kidney function, which then can be applied to the study of transplanted kidney dysfunction. The R33 phase of this proposal will utilize MR perfusion, BOLD MRI and skGFR in the differentiation of acute rejection from ATN in a population with delayed graft function. In addition to using functional MRI in the diagnosis of transplant dysfunction, we will streamline image analysis to reduce post-processing time and allow widespread clinical application of our techniques.