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开发的pH加权MRI作为表征急性人类缺血性中风的新的成像参数。自20世纪90年代以来，卒中治疗和影像学有了巨大的进步，但成功的预后需要早期干预。例如，重组组织型纤溶酶原激活剂(TPA)的传统治疗窗口是在卒中发病后3小时内，这大大限制了其临床应用。另一方面，如果能检测到可挽救的缺血组织，溶栓治疗可以个体化，使超出传统治疗窗口的患者受益。磁共振成像，特别是灌注和弥散成像，可以突出潜在的可挽救的缺血组织用于治疗，并被用作手术半暗带。然而，失配模型并不是最优的；部分弥漫性病变可以通过早期再灌注逆转，而灌注不足可能包含无梗死风险的低灌注区。因此，开发可靠和特异的可挽救组织的成像标志物来补充灌注和扩散MRI，将是非常有价值的。PH是一个受到严格调控的组织参数，在代谢受损时急剧下降，可能成为缺血组织的敏感代谢标记物。这项拟议的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的成像标记。在此之前，我们已经证明，pH加权成像提供了与磁共振灌注和扩散成像互补的信息；低灌注区的外边界显示无扩散异常的pH降低可能对应于缺血半暗带，而正常pH的低灌注区可能代表良性少血症。此外，最终的梗塞面积与PH值加权磁共振成像的缺损区(p=0.84)没有不同，但与使用永久性动物中风模型的灌注和弥散磁共振成像(p&lt；0.001)显著不同。在这项拟议的研究中，我们将开展一项初步研究，以翻译和评估人类急性缺血性卒中的pH加权MRI，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)评估作为补充灌注和扩散MRI的一种新的成像标志物的pH加权MRI。我们推测，pH加权MRI将提高多参数MRI的诊断价值，并辅助图像引导的卒中治疗。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受到不可逆转的损害之前挽救它。我们建议翻译和评估最近开发的pH加权MRI作为一种新的人类缺血组织的成像标志物，这有可能提高MRI的诊断价值，并辅助图像引导的卒中治疗。

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.