Translation of pH-weighted MRI to Image Human Acute Stroke

描述（由申请人提供）：我们的研究旨在翻译和评估最近发展的pH加权MRI作为表征急性缺血性脑卒中的新成像参数。自20世纪90年代以来，中风治疗和影像学已经取得了巨大的进步，但早期干预是取得成功的必要条件。例如，重组组织型纤溶酶原激活剂（tPA）的常规治疗窗口期是在中风发作后3小时内，这极大地限制了其临床应用。另一方面，如果能够检测到可挽救的缺血组织，则可以个体化溶栓治疗，使超出传统治疗窗口的患者受益。MRI，特别是灌注和扩散MRI，可以突出潜在的可挽救的缺血组织进行治疗，并被用作手术半影。然而，不匹配模型并不是最优的；部分弥漫性病变可通过早期再灌注得到逆转，而灌注缺陷可包含低灌注区，无梗死风险。因此，开发可靠和特异性的可修复组织成像标记，补充灌注和扩散MRI，将是非常有价值的。pH是一个受到严格调控的组织参数，在代谢损伤时急剧下降，可能作为缺血组织的敏感代谢标志物。这项工作将测试最近开发的pH加权MRI技术（酰胺质子转移（APT）成像）是否可以成为识别早期缺血组织的新成像标记。以前，我们已经表明，pH加权成像提供的信息与灌注和扩散MRI所获得的信息互补；低灌注区外边界pH值降低，无弥散异常，为缺血半暗带，pH值正常的低灌注区为良性低血凝区。此外，在永久性动物脑卒中模型中，最终梗死面积与pH加权MRI赤字无显著差异（p=0.84），但与灌注和扩散MRI差异显著（p<0.001）。在本研究中，我们将进行一项初步研究，以翻译和评估pH加权MRI对人类急性缺血性卒中的影响，我们的具体目标是：(1)在临床扫描仪上实现和优化快速多层pH加权MRI(2)评估pH加权MRI作为灌注和弥散MRI补充的新成像标志物。我们假设pH加权MRI将提高多参数MRI的诊断价值，并有助于图像引导的脑卒中治疗。公共卫生相关性：缺血性中风是一种严重的神经系统疾病，具有深远的健康和社会经济影响。有效治疗中风的关键是在缺血组织发生不可逆转的损伤之前挽救它。我们建议将新近发展的pH加权MRI作为一种新的人类缺血组织成像标志物进行翻译和评估，这有可能提高MRI的诊断价值，并有助于图像引导的脑卒中治疗。

DESCRIPTION (provided by applicant): Our research aims to translate and evaluate the recently developed pH weighted MRI as a new imaging parameter for characterizing acute human ischemic stroke. Since the 1990s, there has been enormous advancement in stroke therapeutics and imaging, but early intervention is required for successful outcome. For instance, the conventional treatment window for recombinant tissue plasminogen activator (tPA) is within 3 hrs of stroke onset, which significantly limits its clinical applications. On the other hand, could salvageable ischemic tissue be detected, the thrombolytic therapy can be individualized to benefit patients admitted beyond the traditional treatment window. MRI, particularly perfusion and diffusion MRI, may highlight potentially salvageable ischemic tissue for treatment, and is being used as operational penumbra. However, the mismatch model is not optimal; portions of the diffusion lesion can be reversed by early reperfusion, while the perfusion deficit may contain hypoperfused area at no risk of infarction. Consequently, the development of reliable and specific imaging markers for salvageable tissue that complement perfusion and diffusion MRI, will be extremely valuable. pH, a tightly regulated tissue parameter, falls sharply upon metabolic impairment and may potentially serve as a sensitive metabolic marker for ischemic tissue. The proposed work will test whether a recently developed pH weighted MRI technique (amide proton transfer (APT) imaging) can become a new imaging marker for identifying early ischemic tissue. Previously, we have shown that pH weighted imaging provides information complementary to that attained by perfusion and diffusion MRI; the outer boundary of the hypoperfused area showing a decrease in pH without diffusion abnormality may correspond to ischemic penumbra, while the hypoperfused region at normal pH may represent benign oligemia. In addition, the final infarction area was not different from the pH weighted MRI deficit (p=0.84), but significantly different from the perfusion and diffusion MRI (p<0.001) using a permanent animal stroke model. In the proposed research, we will perform a pilot study to translate and evaluate pH weighted MRI for human acute ischemic stroke and our specific aims are: (1) to implement and optimize a fast multi-slice pH weighted MRI on clinical scanners (2) to evaluate pH weighted MRI as a new imaging marker complementary to perfusion and diffusion MRI. We hypothesize the pH weighted MRI will improve the diagnostic value of multi-parametric MRI and assist with image-guided stroke therapy. PUBLIC HEALTH RELEVANCE: Ischemic stroke is a severe neurological disease with profound health and socioeconomic impact. The key for effective stroke therapy is to salvage ischemic tissue before it is irreversibly damaged. We propose to translate and evaluate the recently developed pH weighted MRI as a new imaging marker for human ischemic tissue, which has potential to improve the diagnostic value of MRI and assist with image-guided stroke therapy.