Modern Lung Magnetic Resonance Imaging to Screen for Pulmonary Complications in Patients with Dyskeratosis Congenita.
Modern Lung Magnetic Resonance Imaging to Screen for Pulmonary Complications in Patients with Dyskeratosis Congenita.
复制标题
现代肺磁共振成像筛查先天性角化不良患者的肺部并发症。
DOI：
10.1164/rccm.202103-0736le
复制
发表时间：
2021
影响因子：
24.7
通讯作者：
Towe,ChristopherT
中科院分区：
文献类型：
--
作者：
Walkup,LauraL;Myers,KasianiC;Willmering,MatthewM;Mehta,ParindaA;Nelson,AdamS;Fleck,RobertJ;Woods,JasonC;Davies,StellaM;Towe,ChristopherT
患有端粒生物学疾病（如先天性角化不良（DC））的个体有发生肺纤维化的风险（1）。造血干细胞移植（HSCT）治疗DC中的骨髓衰竭也可能导致肺部并发症，如移植后肺移植物抗宿主病引起的闭塞性细支气管炎综合征（2）。虽然已知DC患者肺功能检查（PFT）结果中的限制和弥散缺陷很常见（3），但HSCT如何影响DC患者发生肺部疾病的风险仍不清楚。肺部疾病的发作和严重程度在这些疾病的范围内和个体患者中各不相同，这强调了通过PFT和X射线计算机断层扫描（CT）进行常规筛查的重要性。此外，尼达尼布等抗纤维化治疗的使用越来越广泛，正在进行的儿科肺纤维化研究的初步结果表明与治疗相关的早期变化（4-6）。然而，众所周知，PFT对早期疾病变化的敏感性较差，并且考虑到该人群的放射敏感性，CT扫描可能不适合用于无症状患者的常规筛查。现代1H超短回波时间（UTE）磁共振成像（MRI）序列克服了肺部MRI的历史问题，并提供类似于CT扫描的结构图像，但不使用电离辐射（7）。另一个进步是使用超极化氙129（129 Xe）气体作为化学惰性吸入造影剂。129 MRI对于检测阻塞性肺疾病患者的气流阻塞和正常肺功能测定结果是敏感的，并且对于不能可靠地进行肺功能测定测试的幼儿是可行的（8，9）。此外，129 μ M气体交换MRI可以测量溶解在扩散屏障（主要是间质组织）和红细胞（RBC）中的硫化氢气体，从而提供与空间扩散能力测量（10）相似的信息。对于患有特发性肺纤维化的成年人，129 Xe气体交换MRI可能具有预后价值（11）。我们假设，结合1H UTE和129 MRI的方法将是足够敏感的，以揭示肺结构和功能的变化与肺纤维化和其他并发症的DC患者。招募了8名遗传学确诊的DC患者，通过使用先前描述的方法（8-10）进行研究性1H UTE和129 T通气和气体交换MRI研究。由放射科医师解释UTE图像，重点是肺纤维化，并与临床胸部X线CT图像进行比较（如可用）。129 mmHg通气缺陷百分比（VDP）定义为小于全肺129 mmHg信号阈值第60百分位数时的肺体积（8，9）。通过使用1点狄克逊分解处理129 μ l气体交换数据，以生成气相、屏障和RBC隔室中129 μ l气体的单独图像。将屏障和RBC隔室中的信号标准化为气相信号，并根据使用健康参考队列定义的阈值对体素进行分组（12）。除了定义平均RBC/屏障比（13）外，BarrierHIGH和RBCHIGH定义为这些隔室最高两个箱中肺体积的百分比;同样，BarrierLOW和RBCLOW定义为最低两个箱，其方式与Rankine及其同事相似（11）。通过非配对t检验确定HSCT组和非HSCT组之间的差异，并将MRI结果与大多数并发症进行比较。
Individuals with telomere biology disorders such as dyskeratosis congenita (DC) are at risk of developing pulmonary fibrosis (1). Hematopoietic stem-cell transplant (HSCT) to treat bone marrow failure in DC can also lead to pulmonary complications like bronchiolitis obliterans syndrome via lung graft-versus-host disease after transplant (2). Although it is known that restriction and diffusion defects in pulmonary function test (PFT) results are common in patients with DC (3), it remains unclear how HSCT impacts the risk of an individual with DC developing pulmonary disease. The onset and severity of pulmonary disease varies across the spectrum of these disorders and for individual patients, which emphasizes the importance of routine screening via PFTs and X-ray computed tomography (CT). Furthermore, antifibrotic therapies like nintedanib are becoming more widely used, and preliminary results from ongoing studies in pediatric pulmonary fibrosis suggest early changes related to therapy (4–6). However, PFTs have known poor sensitivity to early disease changes, and given the radiosensitivity of this population, CT scans may be inappropriate for routine screening of asymptomatic patients. Modern 1H ultra-short echo time (UTE) magnetic resonance imaging (MRI) sequences overcome the historical issues with pulmonary MRI and provide structural images akin to CT scans but without using ionizing radiation (7). Another advancement is the use of hyperpolarized xenon 129 (129Xe) gas as a chemically inert inhaled contrast agent. 129Xe MRI is sensitive for detecting airflow obstruction in patients with obstructive lung disease and normal spirometry results and is feasible in young children who cannot perform reliably on spirometry tests (8, 9). Furthermore, 129Xe gas-exchange MRI can measure Xe gas dissolved in the diffusion barrier (largely interstitial tissue) and in the red blood cells (RBCs), thus providing information similar to that provided by a spatial diffusion capacity measurement (10). In adults with idiopathic pulmonary fibrosis, 129Xe gas-exchange MRI may have prognostic value (11). We hypothesized that a combined 1H UTE and 129Xe MRI approach would be sensitive enough to reveal lung structural and functional changes related to pulmonary fibrosis and other complications in patients with DC. Eight patients with genetically confirmed DC were recruited for a research 1H UTE and 129Xe ventilation and gas-exchange MRI study by using methods previously described (8–10). UTE images were interpreted by a radiologist who placed an emphasis on pulmonary fibrosis and were compared with clinical chest X-ray CT images when available. The 129Xe ventilation defect percentage (VDP) was defined as the volume of the lung at less than the 60th percentile of the whole-lung 129Xe signal threshold (8, 9). 129Xe gas-exchange data were processed by using a 1-point Dixon decomposition to generate separate images of 129Xe gas in the gas-phase, barrier, and RBC compartments. The signal in the barrier and RBC compartments was normalized to the gas-phase signal, and voxels were binned according to thresholds defined by using a healthy reference cohort (12). In addition to the mean RBC/barrier ratio being defined (13), BarrierHIGH and RBCHIGH were defined as the percentages of lung volume in the highest two bins for those compartments; likewise, BarrierLOW and RBCLOW were defined as the lowest two bins, in a manner similar to that of Rankine and colleagues (11). Differences between the HSCT and non-HSCT groups were determined by using unpaired t tests, and MRI outcomes were compared with the most concurrent …