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Title: | 利用擴散張量成像區分梗塞中心與缺血半影區: 動物模型 Differentiation of the Infarct Core from Ischemic Penumbra using Diffusion Tensor Imaging: A Rat Model |
Authors: | Duen-Pang Kuo 郭敦邦 |
Advisor: | 鍾孝文 |
Co-Advisor: | 陳震宇 |
Keyword: | 急性缺血性中風,缺血半影區,梗塞中心,擴散加權成像,灌注加權成像,擴散張量成像, acute ischemic stroke,ischemic penumbra,infarct core,diffusion-weighted imaging,perfusion-weighted imaging,diffusion tensor imaging, |
Publication Year : | 2017 |
Degree: | 博士 |
Abstract: | 急性缺血性中風佔所有中風型態約80%,主要是因為供應腦組織血流的血管阻塞而引起的,會造成病人死亡或癱瘓。若沒有及時將阻塞血管的血栓打通,缺血半影區(尚存活著的腦組織)將逐漸消失並轉變成不可逆的梗塞中心。 1995年,美國國家神經及中風疾病研究院的研究報告指出: 發生急性缺血性中風後3小時內,使用靜脈注射血栓溶解劑治療可以有效地改善病人的神經功能並得到有利的治療結果。近年來,更有臨床試驗(例如ECASS-III,SITS-ISTR)指出病人可以在發病後3至4.5小時內使用血栓溶解治療,亦可從中獲得治療效果。不幸的是,大多數中風病人,其確切的發病時間是不確定的,將會被排除在血栓溶解治療之外。 此外,在進行任何形式的血栓溶解治療之前,確定是否存在相當體積且能被救活的腦組織,也是一個重要的考量。對於不知道發病時間且將被排除在治療之外的病人,若能考量到其中風情況(例如:存在能救活組織的多寡),而不單以發病時間作為唯一考量,應可使血栓溶解治療嘉惠更多病人。而現今的造影科技例如電腦斷層攝影或磁振造影,都可幫助臨床醫生藉由影像選出適合血栓溶解的病人。在磁振造影的成像技術中,擴散加權成像和灌注加權成像是可用於評估是否存在能被救活的組織的技術。利用灌注與擴散影像不匹配的概念,臨床醫生可以找出尚存活著組織的多寡,參考並評估超過治療時限的病人是否也能接受溶栓治療。然而,在臨床實務上,病人能接受治療的時間非常急迫,目前的磁振造影後處理決定半影區的方法耗時耗力,對於病人時常緩不濟急,時間是關鍵,任何診斷方法必須快速地完成。 近年來,磁振造影的另一種成像技術,如擴散張量成像,已經成為研究缺血性中風的有利的工具。擴散張量成像能夠描繪出因缺血性中風所導致腦部微結構的細微變化,通常可用擴散張量的非等向性(fractional anisotropy, FA)來表示。在此研究中,我們認為缺血半影區和梗塞中心血流缺損不同,所引起的細胞損傷也應不同,所反映的FA是否也不同?是否可區分缺血半影區和梗塞中心?我們也進一步假設FA的變化可以用於推測中風的發病時間。為驗證假設,我們在7T磁振造影中建立大鼠永久中大腦動脈梗塞的模型,並重複擴散張量成像序列,分別觀察缺血半影區和梗塞中心FA的變化。另一方面,由於FA是由純擴散非等向性(pure anisotropic diffusion ,q) 和擴散強度(diffusion magnitude, L)的比例來定義,我們也分開研究q和L以更完整地描述缺血性中風環境的微結構變化。也測試了在純氧環境下q和L隨時間的變化。結果發現,可以利用L值的來區別缺血半影區和梗塞中心。此外,與正常半腦側相比,q值減少若小於44.6%可推測中風發生時間小於4.5小時。 我們的結論是,擴散張量成像可以快速且可靠的利用L值來區別缺血半影區和梗塞中心,並利用q值來估計中風時間,可提供臨床醫生在進行血栓溶解或要保守治療的參考資訊。 Acute ischemic stroke (AIS), which constitutes approximately 80% of overall strokes, is a major cause of death and disability due to blockage of blood supply to the brain tissue. Without early recanalization, the ischemic penumbra (IP) (i.e., the area that is at risk for infarction) will gradually diminish and then turn into irreversible infarct core (IC) with time. In 1995, the National Institute of Neurological Disorders and Stroke (NINDS) study group reported that treatment with intravenous recombinant tissue plasminogen activator (rtPA) within 3 hours of the onset of AIS can effectively improve the patients’ neurological function and result in a favorable outcome at3 months. In recent years, there have been a number of clinical trials (e.g. ECASS-III, SITS-ISTR) investigating the therapeutic time window beyond 3 of the onset of AIS. For a subgroup of patients with AIS, for example, wake-up stroke, the exact time of onset is uncertain and then would be excluded from rtPA treatment. In addition, an important consideration is to determine whether the substantial salvageable brain tissue is present before any form of thrombolytic therapy. For patients excluded from rtPA treatment according to current guidelines, the selection of patients for thrombolysis may be made more efficacious by considering individual salvageable tissue rather than relying solely on the onset time as the determinant of selection. The current imaging modality such as computed tomography (CT) or magnetic resonance imaging (MRI) can comprehensively detect and characterize AIS to help physicians with the selection of appropriate candidates for thrombolysis. In MRI techniques, diffusion-weighted imaging (DWI) and perfusion-weighted imagings (PWI) are two powerful techniques used to evaluate whether the salvageable brain tissue is present. With the use of concept of PWI/DWI mismatch of greater than 20%, clinicians can define the salvageable tissue, which may be considered for selecting patients eligible for thrombolysis beyond time windows. However, the image data processing could be very time-consuming and might not be appropriate in the AIS setting. Because time is critical, an effective diagnostic imaging method is desirable for clinical decision-making. In recent years, another imaging technique of MRI such as diffusion tensor imaging (DTI) has emerged as a promising tool to study AIS. DTI has shown to be capable of delineating in the micro-structural changes of brain due to ischemic stroke-induced damage, commonly expressed as the fractional anisotropy (FA). In this study, we first hypothesize that the DTI metric changes may differ in IP and IC regions due to ischemic injury as a result of different extents of perfusion deficit. We further hypothesize that the evolution of DTI metric changes may be used to predict the onset time of AIS. To verify hypotheses, we established permanent middle cerebral artery occlusion (MCAo) model in rat at 7T MRI and then DTI sequences were performed repeatedly after MCAo for longitudinal observation of FA changes from IP and IC, respectively. Because the FA is a relative scalar value defined by the ratio of pure anisotropic diffusion (q) and diffusion magnitude (L), we measured the parameters q and L separately in affected ipsilateral and unaffected contralateral sides and calculated differences between the ipsi- and contralateral side (r) for more complete picture of diffusion changes in AIS. We also test the effect of oxygenation in the evolution of q and L. The study found that discrimination of IP from IC by rL values showed comparable results to the conventional PWI/DWI mismatch. Additionally, by regression analysis, the stroke age of 4.5 hours can be estimated by an rq value of -44.6% (a 44.6% reduction) in the cortical IC regions. In conclusion, our preliminary results suggest that a single DTI could provide a quick and reliable measure to distinguish IP from IC based on the L values, and estimate stroke age using the q values, thus potentially provide valuable information to the treating physicians considering whether to treat acute stroke by means of thrombolytic therapy or conservative management. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7817 |
DOI: | 10.6342/NTU201700312 |
Fulltext Rights: | 同意授權(全球公開) |
Appears in Collections: | 電機工程學系 |
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