Proton MRI as a noninvasive tool to assess elastase-induced lung damage in spontaneously breathing rats.

Elastase-induced changes in lung morphology and function were detected in spontaneously breathing rats using conventional proton MRI at 4.7 T. A single dose of porcine pancreatic elastase (75 U/100 g body weight) or vehicle (saline) was administered intratracheally (i.t.) to male Brown Norway (BN) rats. MRI fluid signals were detected in the lungs 24 hr after administration of elastase and resolved within 2 weeks. These results correlated with perivascular edema and cellular infiltration observed histologically. Reductions in MRI signal intensity of the lung parenchyma, and increases in lung volume were detected as early as 2 weeks following elastase administration and remained uniform throughout the study, which lasted 8 weeks. Observations were consistent with air trapping resulting from emphysema detected histologically. In a separate experiment, animals were treated daily intraperitoneally (i.p.) with all-trans-retinoic acid (ATRA; 500 microg/kg body weight) or its vehicle (triglyceride oil) starting on day 21 after elastase administration and continuing for 12 days. Under these conditions, ATRA did not elicit a reversal of elastase-induced lung damage as measured by MRI and histology. The present approach complements other validated applications of proton MRI in experimental lung research as a method for assessing drugs in rat models of respiratory diseases.     

Direct imaging of hyperpolarized 129Xe alveolar gas uptake in a mouse model of emphysema

MRI of hyperpolarized ¹²⁹Xe dissolved in pulmonary tissues, and blood has the potential to offer a new tool for regional evaluation of pulmonary gas exchange and perfusion; however, the extremely short T and low magnetization density make it difficult to acquire the image. In this study, an ultrashort echo‐time sequence was introduced, and its feasibility to quantitatively assess emphysema‐like pulmonary tissue destruction by a combination of dissolved‐ and gas‐phase ¹²⁹Xe lung MRI was investigated. The ultrashort echo‐time has made it possible to acquire dissolved ¹²⁹Xe images with reasonably high spatial resolution of 0.625 × 0.625 mm² and to obtain T of 0.67 ± 0.30 ms in a spontaneously breathing mouse at 9.4 T. The regional dynamic alveolar gas uptake as well as subsequent transport by pulmonary blood flow was also visualized. The ratio of ¹²⁹Xe magnetization that diffused into the septa relative to the gas‐phase magnetization F was regionally evaluated. The mean F value of elastase‐treated mice was 2.28 ± 0.46%, which was significantly reduced from that of control mice 3.41 ± 0.48% (P = 0.0052). This reflects the reduced uptake efficiency due to alveolar tissue destruction and is correlated with the histologically derived alveolar surface‐to‐volume ratio. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Quantitative assessment of emphysema using hyperpolarized 3He magnetic resonance imaging.

In this experiment, Sprague-Dawley rats with elastase-induced emphysema were imaged using hyperpolarized (3)He MRI. Regional fractional ventilation r, the fraction of gas replaced with a single tidal breath, was calculated from a series of images in a wash-in study of hyperpolarized gas. We compared the regional fractional ventilation in these emphysematous rats to the regional fractional ventilations we calculated from a previous baseline study in healthy Sprague-Dawley rats. We found that there were differences in the maps of fractional ventilation and its associated frequency distribution between the healthy and emphysematous rat lungs. Fractional ventilation tended to be much lower in emphysematous rats than in normal rats. With this information, we can use data on fractional ventilation to regionally distinguish between healthy and emphysematous portions of the lung. The successful implementation of such a technique on a rat model could lead to work toward the future implementation of this technique in human patients.     

COPD患者肺气肿程度对气道径线与肺功能相关性的影响

目的：定量分析肺气肿程度对气道径线及其与肺功能相关性的影响。方法对73例慢性阻塞性肺疾病(COPD)患者行呼气相 CT 扫描,测量肺气肿指数(LAA%)以及右肺上叶尖段(RB1)、右肺下叶后基底段(RB10)、左肺上叶尖后段(LB1)、左肺下叶后基底段(LB10)亚段支气管的气道径线,包括管壁厚度(WT),管壁厚度/气道直径(WT/AD),管壁面积比值(WA%);以 LAA%=15%为界限,将 COPD 患者分为2组,即轻度肺气肿组(34例)和重度肺气肿组(39例)。分别比较不同亚段支气管的轻度、重度肺气肿组 WA%、WT/AD、WT 与 FEV1%的相关性。结果除外 RB10亚段支气管的轻度肺气肿组中 WT 及重度肺气肿组的气道径线与 FEV1%无明显相关(P >0.05),其余各亚段支气管(RB1,LB1,LB10)的轻度肺气肿组气道径线指标与 FEV1%均呈负相关(r=-0.382~-0.799,P <0.05),均优于重度肺气肿组(r =-0.371~-0.687,P <0.05)。RB1、LB1、LB10气道径线均与FEV1%呈负相关,其中 RB1的气道径线与 FEV1%相关性最好;各亚段支气管中轻度肺气肿组气道径线与 FEV1%的相关性均优于重度肺气肿组。结论肺气肿的严重程度会影响气道径线与气流受限的相关性,在 COPD 患者的 CT 定量研究中,需将这一相互影响的过程考虑入内。     

Ultra‐short echo time (UTE) MR imaging of the lung: Comparison between normal and emphysematous lungs in mutant mice

Purpose:

To investigate the utility of ultra‐short echo time (UTE) sequence as pulmonary MRI to detect non‐uniform disruption of lung architecture that is typical of emphysema.

Materials and Methods:

MRI of the lungs was conducted with a three‐dimensional UTE sequence in transgenic mice with severe emphysema and their wild‐type littermates in a 3 Tesla clinical MR system. Measurements of the signal intensity (SI) and transverse relaxation time (T2*) of the lung parenchyma were performed with various echo times (TEs) ranging from 100 μs to 2 ms.

Results:

Much higher SI of the lung parenchyma was observed at an UTE of 100 μs compared with longer TEs. The emphysematous lungs had reduced SIs and T2* than the controls, in particular at end‐expiratory phase. The results suggested that both SI and T2* in lung parenchyma measured with the method represent fractional volume of lung tissue.

Conclusion:

The UTE imaging provided MR signal from the lung parenchyma. Moreover, the UTE sequence was sensitive to emphysematous changes and may provide a direct assessment of lung parenchyma. UTE imaging has the potential to assist detection of localized pathological destruction of lung tissue architecture in emphysema. J. Magn. Reson. Imaging 2010;32:326–333. © 2010 Wiley‐Liss, Inc.     

Ventilation/perfusion imaging of the lung using ultra-short echo time (UTE) MRI in an animal model of pulmonary embolism

Purpose:

To test the feasibility of ultra‐short echo time (UTE) MRI for assessment of regional pulmonary ventilation/perfusion in a standard 3 Tesla clinical MRI system.

Materials and Methods:

MRI of the lungs was conducted with an optimized three‐dimensional UTE sequence in normal rats and in a rat model of pulmonary embolism (PE) induced by a blood clot. Changes in signal intensities (SIs) due to inhalation of molecular oxygen or intravenous (i.v.) injection of Gd, which represents the distribution of ventilation and perfusion, respectively, were assessed in the lung parenchyma.

Results:

The UTE MRI with a TE of 100 μs could detect and map the changes in SI of the lung parenchyma due to the inhalation of 100% oxygen or i.v. injection of Gd in normal rats. Reduced T1 resulting from oxygen inhalation was also quantified. These changes were not observed on the images that were obtained simultaneously with a conventional range of TE (2.3 ms). Furthermore, the method could delineate the embolized lesions where the lung ventilation and perfusion were mismatched in a rat model with PE.

Conclusion:

These results show the feasibility and diagnostic potential of UTE MRI for the assessment of pulmonary ventilation and perfusion which is essential for the evaluation of a variety of lung diseases. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Diffusion‐weighted hyperpolarized 129Xe MRI in healthy volunteers and subjects with chronic obstructive pulmonary disease

Given its greater availability and lower cost, ¹²⁹Xe apparent diffusion coefficient (ADC) MRI offers an alternative to ³He ADC MRI. To demonstrate the feasibility of hyperpolarized ¹²⁹Xe ADC MRI, we present results from healthy volunteers (HV), chronic obstructive pulmonary disease (COPD) subjects, and age‐matched healthy controls (AMC). The mean parenchymal ADC was 0.036 ± 0.003 cm² sec^?1 for HV, 0.043 ± 0.006 cm² sec^?1 for AMC, and 0.056 ± 0.008 cm² sec^?1 for COPD subjects with emphysema. In healthy individuals, but not the COPD group, ADC decreased significantly in the anterior–posterior direction by ～22% (P = 0.006, AMC; 0.0059, HV), likely because of gravity‐induced tissue compression. The COPD group exhibited a significantly larger superior–inferior ADC reduction (～28%) than the healthy groups (～24%) (P = 0.00018, HV; P = 3.45 × 10^?5, AMC), consistent with smoking‐related tissue destruction in the superior lung. Superior–inferior gradients in healthy subjects may result from regional differences in xenon concentration. ADC was significantly correlated with pulmonary function tests (forced expiratory volume in 1 sec, r = ?0.77, P = 0.0002; forced expiratory volume in 1 sec/forced vital capacity, r = ?0.77, P = 0.0002; diffusing capacity of carbon monoxide in the lung/alveolar volume (V_A), r = ?0.77, P = 0.0002). In healthy groups, ADC increased with age by 0.0002 cm² sec^?1 year^?1 (r = 0.56, P = 0.02). This study shows that ¹²⁹Xe ADC MRI is clinically feasible, sufficiently sensitive to distinguish HV from subjects with emphysema, and detects age‐ and posture‐dependent changes. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.