2010-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/646577摘要：原發性肺動脈高壓是一種預後不良的疾病，患者會因逐漸升高的肺動脈阻抗而最後導致右心室的衰竭。眾所周知的顯微病變發生在肺微小動脈的管壁以及肺微血管前之最終肺小動脈。因病情嚴重的程度會依序有下列變化：動脈壁中層的肌肉肥厚、血管內壁的增生、血管腔的阻塞以及血管壁的壞死［1-3］，可使用的治療選項極為有限，這包括了血管擴張劑（如：前列環素、一氧化氮）、內皮激素接受體阻斷劑（如：Bosentan）或甚至肺移植［4-7］，目前針對這類病人臨床上的評估工具主要是經胸心臟超音波以及心導管檢查［8-10］，由於近幾年來，多片螺旋電腦斷層掃描攝影（MDCT）的快速進步，在空間及時間解析度上大大提昇，使得有可能僅只使用MDCT 這一項非侵襲性的檢查便能收集到完整的心肺整體的狀況，並用來評估此類的病人。本3 年度的計劃，希望能夠在以影像為基石的證據上達到（1）以MDCT 確定診斷肺高壓並能正確的分出其嚴重程度。（2）開發一些新的MDCT 參數（解剖型態上、微細構造上、血行動力上），用來預測這些肺高壓的預後，以及（3）建立一套可靠的MDCT 指標，成為藥物治療後追蹤評估的重要工具。病理上，肺高壓病患的肺動脈病灶可以再分級為：第一級是有動脈壁中層的肌肉肥厚；第二級為除了動脈壁中層肌肉肥厚外，再加上血管內膜細胞的異常增生；第三級則是血管內膜的纖維化及血管的血栓阻塞；第四級則是有叢狀的血管病變，加上時有壞死性的血管發炎。在組織學上，如果計算每單位面積肺組織的周邊微細肺動脈的密度，則可以發現到有明顯的下降。本計劃首先是要在MDCT 影像上，開發出新的參數，用來評估周邊肺微小動脈的數量及品質，並且用這些參數與臨床上的表徵，其它檢查（尤其是心導管）的結果以及可能之組織切片或檢體比對。並希望能以MDCT 達到虛擬組織切片的地步。在肺高壓的患者，需評估其是否為可逆的狀況，正確肺動脈阻抗的數值是一個非常重要的指標。臨床上，最常使用心導管的檢查，但由於心導管是一種侵入性的檢查，並不適合用來成為門診常規追蹤的工具，再加上檢查時，若打入顯影劑時會有急性肺高壓的風險，使得心導管檢查成為不得不檢查時的方法，並不能輕易的被大規模使用。多片螺旋電腦斷層掃描攝影中，使用動態的掃描，可以即時監控所打入之顯影劑如何流出右心室，又是如何流回左心房，由此便可以推斷這些顯影劑在肺臟經過的情形。換言之，以此一〝時間-密度〞曲線下的數據，本計劃希望能發掘一些有用參數，並和心導管的結界比對，希望依此便能以非侵襲性的方法，直接得到肺臟實質血管阻抗的訊息，以取代介入性之心導管檢查。合併上述兩種創新的結果，將會進一步應用到本院肺高壓的病人，其進入臨床試驗有關口服降低肺壓新藥的評估上。合併病患所有的臨床表徵、實驗室數據、心臟超音波、心導管檢查以及完整的MDCT 的結果，將會全部彙集在一齊，互相比較，以期建立一套標準流程和實用的參數來規律性且非侵襲性的追蹤和治療病人。<br> Abstract: Primary pulmonary arterial hypertension (PAH) is a condition of poor prognosischaracterized by progressive increase of pulmonary vascular resistance and finallyleading to right ventricular failure. There are well-known microscopic changes in thewall of pulmonary arterioles and pre-capillary arteries: media hypertrophy, intimalproliferation, obliteration and necrosis [1-3]. The option of treatment is limited byvasodilators (i.e. prostacyclins, NO), endothelin receptor antagonist (i.e. Bosentan) orlung transplantation [4-7]. Currently, the major clinical tool of evaluation istransthoracic echocardiography and followed by a cardiac catheterization [8-10]. Theadvance of MDCT technology allows improved temporal and spatial resolution thatcould be very reliably to collect a comprehensive cardiopulmonary status in only oneexamination and it is non-invasively [11,12]. This 3-year-project is try to getimage-based evidences to (1) classify the severity of PAH on MDCT, (2) exploreprognostic factors in PAH by MDCT, and (3) finally establishes reliable indicators fortreatment follow up.Pathologically, lesions in pulmonary arteries in PAH were further graded as:GradeI showed medial hypertrophy; Grade II medial hypertrophy and intimal cellularproliferation; Grade III intimal fibrosis or embolic occlusion; Grade IV plexiform lesionswith/without focal necrotizing arteritis. Histological, there was significant decrease thedensity of pulmonary artery by counting number of arterioles per cm2. We willinnovate new approaches to measure the quality and quantity of the pulmonaryarteriole on MDCT and will correlate to their histology specimen. Such result leads toa virtual biopsy on MDCT image.An accurate data of pulmonary vascular resistance is an important indicator ofreversibility in PAH. Risk of pulmonary hypertension crisis during catheterization andinvasiveness of this procedure prohibit its widely clinical usage in regular follow up.Dynamic scanning by MDCT could clearly trace the flow pattern of the contrastmedium between right ventricular outflow tract and left atrium. Using this time-densitycurves, we will create new parameters non-invasively to correlate with thehemodynamic by cardiac catheterization.共2 頁 第1 頁Combined with the first 2 years novel and the reported parameters, patients withPAH receive clinical try (randomized between placebo and medications [13,14]) in ourhospital will be included. Clinical manifestation, echocardiography, catheterization,and comprehensive MDCT information will gather together to compare and build afeasible standard protocol and useful parameters to monitor these patientsnon-invasively and regularly.