Hyperpolarized HHe 3 MRI of the lung in cystic fibrosis: assessment at baseline and after bronchodilator and airway clearance treatment

RATIONALE AND OBJECTIVES: The purpose of this study is to determine hyperpolarized helium 3 (HHe) magnetic resonance (MR) findings of the lung in patients with cystic fibrosis (CF) compared with healthy subjects and determine whether HHe MR can detect changes after bronchodilator therapy or mechanical airway mucus clearance treatment. MATERIALS AND METHODS: Thirty-one subjects, 16 healthy volunteers and 15 patients with CF, underwent HHe lung ventilation MR imaging and spirometry at baseline. Eight patients with CF then were treated with nebulized albuterol, after which a follow-up HHe MR scan was obtained. Subsequently, recombinant human deoxyribonuclease (DNase) treatment and chest physical therapy were performed in these eight subjects, followed by a third HHe MR scan. For each MR study, the number of ventilation defects was scored by a human reader. RESULTS: Patients with CF had significantly more HHe MR ventilation defects per image than healthy subjects (mean, 8.2 defects in patients with CF vs 1.6 defects in healthy subjects; P < .05). Even the four subjects with CF with a normal forced expiratory volume in 1 second had significantly more ventilation defects than healthy subjects (mean, 6.5 defects in these patients with CF; P = .0002). After treatment with albuterol, there was a small, but statistically significant, decrease in number of ventilation defects (mean, 9.6-8.0 defects; P = .025). After DNase and chest physical therapy, there was a trend toward increasing ventilation defects (mean, 8.3 defects; P = .096), but with a residual net improvement relative to baseline. CONCLUSION: In patients with CF, HHe MR ventilation defects correlate with spirometry, change with treatment, and are elevated in number in patients with CF with normal spirometry results. Thus, HHe MR appears to possess many of the characteristics required of a biomarker for pulmonary CF and may be useful in the evaluation of CF pulmonary disease severity or progression.     

Comparison of Xe-133 washout and single-breath imaging for the detection of ventilation abnormalities

The Xe-133 ventilation studies of 115 patients were analyzed to determine the relative abilities of the single-breath and washout phases to detect regional ventilation abnormalities. All Xe-133 images were obtained in the posterior projection before 6-view perfusion studies with Tc-99m human albumin microspheres. There were 275 regions with matching V-P abnormalities in the patients. The washout portion of the study detected 258 of these regions (94%) and the single breath detected 175 (64%) (p less than 0.01). The discrepancies were confined to regions with nonsegmental perfusion defects, where the single breath detected 139 matches and the washout 216. The discrimination ratio between normal areas and areas of obstructive lung disease improved from 2 to 1 after 1 min washout to 30 to 1 after 5 min. The late phases of Xe-133 washout are useful in detecting ventilation abnormalities, especially those associated with nonsegmental perfusion defects.     

Assessment of lung development using hyperpolarized helium-3 diffusion MR imaging

PURPOSE: To determine whether hyperpolarized helium-3 (HHe) diffusion MR can detect the expected enlargement of alveoli that occurs with lung growth during childhood. MATERIALS AND METHODS: A total of 29 normal subjects aged four to 30 years underwent HHe diffusion MR imaging with the b-value pair 0, 1.6 second/cm(2). A second acquisition during a separate breathhold was performed using the b-value pair 0, 4 second/cm(2) to evaluate the dependence on b-value. The mean apparent diffusion coefficient (ADC) and lung volume for each acquisition and each subject was determined. RESULTS: Subjects as young as four years of age were able to cooperate with the imaging procedure. The mean ADC increased with increasing subject age (r = 0.8; P < 0.001), with a 55% increase in mean ADC from the youngest to oldest subject. Lung volumes measured on MR were highly repeatable for the two HHe MR acquisitions (r = 0.980, P < 0.001). The mean ADC values measured with the two different b-value pairs were highly correlated (r = 0.975; P < 0.001), but the higher b-value pair resulted in slightly lower mean ADCs (P < 0.001). CONCLUSION: HHe diffusion MR appears to detect the expected increase in alveolar size during childhood, and thus HHe MR may be a noninvasive method to assess development of the lung microstructure.     

Neue Entwicklungen in der MRT des Thorax

MRI was not used often for lung imaging due to technical and physical limitations. Recent developments have considerably improved anatomical MR imaging, and at the same time new perspectives for functional imaging emerged. They consist of functional investigations of pulmonary perfusion (contrast agents, MR angiography) and ventilation (inhaled contrast aerosols, oxygen, hyperpolarized noble gases [He-3, Xe-129] and fluorinated gases [SF6]). New parameters can be measured: homogeneity of ventilation, lung volumes, airspace size, intrapulmonary oxygen partial pressure, dynamic ventilation distribution and ventilation/perfusion ratios. MRI-inherent advantages are: lack of radiation, high spatial and temporal resolution, and a broad range of functional information. MRI of lung ventilation seems to be more sensitive in the detection of ventilation defects than scintigraphy, CT or pulmonary function tests. By combining the new strategies the radiologist will be capable to improve specificity of the investigations and to characterize lung function impairments. The joint assessment of ventilation and perfusion will play a major role in this development.     

Functional lung imaging using hyperpolarized gas MRI

The noninvasive assessment of lung function using imaging is increasingly of interest for the study of lung diseases, including chronic obstructive pulmonary disease (COPD) and asthma. Hyperpolarized gas MRI (HP MRI) has demonstrated the ability to detect changes in ventilation, perfusion, and lung microstructure that appear to be associated with both normal lung development and disease progression. The physical characteristics of HP gases and their application to MRI are presented with an emphasis on current applications. Clinical investigations using HP MRI to study asthma, COPD, cystic fibrosis, pediatric chronic lung disease, and lung transplant are reviewed. Recent advances in polarization, pulse sequence development for imaging with Xe-129, and prototype low magnetic field systems dedicated to lung imaging are highlighted as areas of future development for this rapidly evolving technology.     

Lung ventilation‐ and perfusion‐weighted Fourier decomposition magnetic resonance imaging: In vivo validation with hyperpolarized 3He and dynamic contrast‐enhanced MRI

The purpose of this work was to validate ventilation‐weighted (VW) and perfusion‐weighted (QW) Fourier decomposition (FD) magnetic resonance imaging (MRI) with hyperpolarized ³He MRI and dynamic contrast‐enhanced perfusion (DCE) MRI in a controlled animal experiment. Three healthy pigs were studied on 1.5‐T MR scanner. For FD MRI, the VW and QW images were obtained by postprocessing of time‐resolved lung image sets. DCE acquisitions were performed immediately after contrast agent injection. ³He MRI data were acquired following the administration of hyperpolarized helium and nitrogen mixture. After baseline MR scans, pulmonary embolism was artificially produced. FD MRI and DCE MRI perfusion measurements were repeated. Subsequently, atelectasis and air trapping were induced, which followed with FD MRI and ³He MRI ventilation measurements. Distributions of signal intensities in healthy and pathologic lung tissue were compared by statistical analysis. Images acquired using FD, ³He, and DCE MRI in all animals before the interventional procedure showed homogeneous ventilation and perfusion. Functional defects were detected by all MRI techniques at identical anatomical locations. Signal intensity in VW and QW images was significantly lower in pathological than in healthy lung parenchyma. The study has shown usefulness of FD MRI as an alternative, noninvasive, and easily implementable technique for the assessment of acute changes in lung function. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Accuracy and feasibility of dynamic contrast-enhanced 3D MR imaging in the assessment of lung perfusion: comparison with Tc-99 MAA perfusion scintigraphy

AIM: The aim of this study was to correlate findings of perfusion magnetic resonance imaging (MRI) and perfusion scintigraphy in cases where there was a suspicion of abnormal pulmonary vasculature, and to evaluate the usefulness of MRI in the detection of perfusion deficits of the lung. METHODS: In all, 17 patients with suspected abnormality of the pulmonary vasculature underwent dynamic contrast-enhanced MRI. T1-weighted 3D fast-field echo pulse sequences were obtained (TR/TE 3.3/1.58 ms; flip angle 30 degrees; slice thickness 12 to 15 mm). The dynamic study was acquired in the coronal plane following administration of 0.1 mmol/kg gadopentetate dimeglumine. A total of 8 to 10 sections repeated 20 to 25 times at intervals of 1s were performed. Perfusion lung scintigraphy was carried out a maximum of 48 h before the MR examination in all cases. Two radiologists, who were blinded to the clinical data and results of other imaging methods, reviewed all coronal sections. MR perfusion images were independently assessed in terms of segmental or lobar perfusion defects in the 85 lobes of the 17 individuals, and the findings were compared with the results of scintigraphy. RESULTS: Of the 17 patients, 8 were found to have pulmonary emboli, 2 chronic obstructive pulmonary disease with emphysema, 2 bullous emphysema, 2 Takayasu arteritis and 1 had a hypoplastic pulmonary artery. Pulmonary perfusion was completely normal in 2 cases. In 35 lobes, perfusion defects were detected using both methods, in 4 with MR alone and in 9 only with scintigraphy. There was good agreement between MRI and scintigraphy findings (kappa=0.695). CONCLUSION: Pulmonary perfusion MRI is a new alternative to scintigraphy in the evaluation of pulmonary perfusion for various lung disorders. In addition, this technique allows measurement and quantification of pulmonary perfusion abnormalities.     

Noninvasive mapping of regional response to segmental allergen challenge using magnetic resonance imaging and [F-18]fluorodeoxyglucose positron emission tomography.

Magnetic resonance (MR) and positron emission tomography (PET) imaging techniques were coregistered to demonstrate regional ventilation and inflammation in the lung for in vivo, noninvasive evaluation of regional lung function associated with allergic inflammation. Four Brown Norway rats were imaged pre- and post segmental allergen challenge using respiratory-gated He-3 magnetic resonance imaging (MRI) to visualize ventilation, T(1)-weighted proton MRI to depict inflammatory infiltrate, and [F-18]fluorodeoxyglucose-PET to detect regional glucose metabolism by inflammatory cells. Segmental allergen challenges were delivered and the pre- and postchallenge lung as well as the contralateral lung were compared. Coregistration of the imaging results demonstrated that regions of ventilation defects, inflammatory infiltrate, and increased glucose metabolism correlated well with the site of allergen challenge delivery and inflammatory cell recruitment, as confirmed by histology. This method demonstrates that fusion of functional and anatomic PET and MRI image data may be useful to elucidate the functional correlates of inflammatory processes in the lungs.     

Radiocolloid liver imaging in hepatic steatosis

In a review of 60 patients with fatty infiltration of the liver documented by Xe-133 imaging, 43% had normal radiocolloid liver images, and 57% had abnormal images with various combinations of hepatomegaly, mottling, splenomegaly, and splenic shift of radioactivity. None, however, showed focal defects. Fatty infiltrates do not simulate mass lesions on the radiocolloid study of the liver, and an area of photon deficiency in the presence of hepatic steatosis points to an additional pathologic process. The interpretation of the radiocolloid liver image is unhindered by fatty infiltration when searching for discrete space-occupying lesions.     

正常胃的MRI表现与扫描技术

目的：研究正常胃的MRI表现和扫描技术。方法：在胃不同充盈状态下，采用单次屏气快速扫描序列，共进行72人次MRI平扫和7次增强检查，分析正常胃的MRI表现和图像质量。结果：按充盈程度不同，胃壁形态可分为扩张不良，适度扩张、充分扩张3型表现。MRI能较好显示胃及其与邻近器官的关系。胃壁厚度平均值在适度扩张下为2．7mm，在充分扩张下为2.4.T2WI图像均无运动伪影，79％的T1WI图像在使用解痉剂后无运动伪影。结论：采用单次屏气快速扫描序列，MRI能获得满意的胃部图像，较好显示胃及其与邻近解剖关系。     

Prospective comparison of MR lung perfusion and lung scintigraphy

This study attempted to assess the accuracy and potential of lung magnetic resonance (MR) perfusion imaging compared with perfusion scintigraphy in the evaluation of patients with suspected lung perfusion defects. The technique, which uses an inversion recovery turbo-FLASH sequence with ultra-short TE (1.4 msec), was tested in 24 patients suspected clinically of having acute pulmonary embolism (n = 19) and in patients with severe pulmonary emphysema (n = 5). Perfusion lung scintigraphy was performed within 48 hours prior to the MRI examination in both groups of patients. The dynamic study was acquired in the coronal plane and consisted of 10 images of 6 slices (a total of 60 images per series). Gadopentetate dimeglumine (0.1 mmol/kg) was manually injected as a compact bolus during the acquisition of the first image. Three senior radiologists reviewed all unprocessed two-dimensional coronal sections. They were blinded to clinical data and other imaging modalities. For the three observers, the average sensitivity and specificity of MR were 69% and 91%, respectively. The overall agreement between MR and scintigraphy appears to be good, with a good correlation between the two modalities (kappa = 0.63). However, the data showed variability depending on the location of the perfusion defect, with higher accuracy in the upper lobes. The agreement between MR perfusion and scintigraphy appears to be moderate in the left inferior lobe (kappa = 0.48). The data showed an overall good interobserver agreement (kappa = 0.66). MR perfusion of the lung is a promising technique in detecting lung perfusion defects.     

Oxygen-enhanced MR imaging of mice lungs.

Inhaled molecular oxygen has been widely used in humans to evaluate pulmonary ventilation using MRI. MR imaging has recently played a greater role in examining the morphologic and physiologic characteristics of mouse models of lung disease where structural changes are highly correlated to abnormalities in respiratory function. The motivation of this work is to develop oxygen-enhanced MR imaging for mice. Conventional human MR techniques cannot be directly applied to mouse imaging due to smaller dimensions and faster cardiac and respiratory physiology. This study examines the development of oxygen-enhanced MR as a noninvasive tool to assess regional ventilation in spontaneously breathing mice. An optimized cardiac-triggered, respiratory-gated fast spin-echo imaging sequence was developed to address demands of attaining adequate signal from the parenchyma, maintaining practical acquisition times, and compensating for rapid physiological motion. On average, a 20% T1-shortening effect was observed in mice breathing 100% oxygen as compared to air. The effect of ventilation was shown as a significant signal intensity increase of 11% to 16% in the mouse parenchyma with 100% oxygen inhalation. This work demonstrates that adequate contrast and resolution can be achieved using oxygen-enhanced MR to visualize ventilation, providing an effective technique to study ventilation defects in mice.     

MR肺通气联合灌注成像的动物模型研究

目的 探讨氧增强MR肺通气成像联合肺灌注成像诊断气道阻塞和肺栓塞(PE)病变的可行性和价值。方法 对8只犬通过肺段动脉水平注入凝胶海绵颗粒复制周围型PE模型，其中5只经自制球囊导管插入二级气道又建立气道阻塞模型。通过吸纯氧前后的图像减影可获得氧增强MR肺通气图像。利用对比剂首次通过法可进行MR肺灌注成像。观察MR肺通气和灌注成像的表现，并与大体病理解剖、核素肺通气-灌注成像和肺血管造影进行对照。结果 MR肺通气和灌注成像在气道阻塞区的表现相匹配，但在肺栓塞区不匹配。气道阻塞区在MR肺通气成像中的缺损区域小于核素肺通气成像。根据信号强度随时间变化曲线，肺灌注异常区可分为灌注缺损和减低区。MR肺通气联合灌注成像诊断肺栓塞的敏感度和特异度分别为75．0％和98．1％；其诊断结果与核素肺通气一灌注成像和肺血管造影的一致性较好(K=0．743、0．899)。结论 氧增强MR肺通气成像联合肺灌注成像可用来诊断肺内气道和血管异常，该方法与核素肺通气-灌注成像类似，并能提供量化的功能信息和更高的时间、空间分辨率，具有临床应用价值。     

Pulmonary ventilation-perfusion MR imaging in clinical patients

The purpose of this study was to evaluate the feasibility of comprehensive magnetic resonance (MR) assessment of pulmonary perfusion and ventilation in patients. Both oxygen-enhanced ventilation MR images and first-pass contrast-enhanced perfusion MR images were obtained in 16 patients with lung diseases, including pulmonary embolism, lung malignancy, and bulla. Inversion recovery single-shot fast spin-echo images were acquired before and after inhalation of 100% oxygen. The overall success rate of perfusion MR imaging and oxygen-enhanced MR imaging was 94% and 80%, respectively. All patients with pulmonary embolism showed regional perfusion deficits without ventilation abnormality on ventilation-perfusion MR imaging. The results of the current study indicate that ventilation-perfusion MR imaging using oxygen inhalation and bolus injection of MR contrast medium is feasible for comprehensive assessment of pulmonary ventilation-perfusion abnormalities in patients with lung diseases.     

Assessment of lung ventilation by MR imaging: current status and future perspectives

The aim of this paper is to review the present status of novel MRI techniques as a new important instrument for functional ventilation imaging. The current status and future perspectives in research and clinical applications are summarized. Morphological lung imaging is based on chest radiography and computed tomography, whereas scintigraphy is used for ventilation imaging. During recent years, MRI has emerged as a new means for functional imaging of ventilation. Aerosolized contrast agents and oxygen are used in proton imaging, whereas non-proton imaging relies on fluorine compounds, such as sulfur hexafluoride and perfluorcarbons, or on hyperpolarized noble gases, such as helium-3 or xenon-129. All the gases are administered as inhaled "contrast agents" for imaging of the airways and airspaces. In general, straightforward images demonstrate the homogeneity of ventilation in a breath-hold and allow for determination of ventilated lung. The different properties of the different compounds enable the measurement of additional functional parameters. They comprise airspace size, regional oxygen partial pressure, and analysis of ventilation distribution, ventilation/perfusion ratios, and gas exchange, including oxygen uptake. Novel MRI techniques provide the potential for functional imaging of ventilation. The next steps include definition of the value and the potential of the different contrast mechanisms as well as determination of the significance of the functional information with regard to physiological research and patient management in chronic obstructive pulmonary disease and others.     

Combined helium-3/proton magnetic resonance imaging measurement of ventilated lung volumes in smokers compared to never-smokers

PURPOSE: To use a combination of helium-3 (3-He) magnetic resonance imaging (MRI) and proton single-shot fast spin echo (SSFSE) to compare ventilated lung volumes in groups of "healthy" smokers, smokers diagnosed with moderate chronic obstructive pulmonary disease (COPD), and never-smokers. MATERIALS AND METHODS: All study participants were assessed with spirometry prior to imaging. 3-He images were collected during an arrested breath hold, after inhaling a mixture of 200 mL of hyperpolarized 3-He/800 mL of N2. Proton SSFSE images were acquired after inhaling 1 liter of room air. The ventilated volume for each study participant was calculated from the 3-He images, and a ratio was calculated to give a percentage ventilated lung volume. RESULTS: Never-smokers exhibited a 90% mean ventilated volume. The mean ventilated lung volumes for healthy smokers and smokers diagnosed with COPD were 75.2% and 67.6%, respectively. No correlation with spirometry was demonstrated for either of the smoking groups. CONCLUSION: Combined 3-He/Proton SSFSE MRI of the lungs is a noninvasive method, using nonionizing radiation, which demonstrates ventilated airspaces and enables the calculation of ventilated lung volumes. This method appears to be sensitive to early obstructive changes in the lungs of smokers.     

The pelvis: T2-weighted fast spin-echo MR imaging.

Fast spin-echo (SE) T2-weighted magnetic resonance (MR) imaging provides images with highly T2-weighted contrast in substantially reduced imaging times. In a prospective evaluation, fast SE T2-weighted imaging of the pelvis was compared with conventional SE T2-weighted imaging in 30 consecutive patients in whom pelvic pathologic conditions were suspected. Three reviewers independently analyzed the images for (a) overall image quality, (b) pelvic organ definition, (c) conspicuity of pelvic fluid, and (d) conspicuity of pelvic pathologic conditions. Fast SE images were rated superior to conventional SE T2-weighted images in 60% (54 of 90) of the case reviews for overall image quality, in 69% (62 of 90) for pelvic organ definition, in 63% (57 of 90) for conspicuity of pelvic fluid, and in 68% (43 of 63) for conspicuity of pelvic pathologic conditions. The fast SE examinations were typically three to four times faster than conventional SE T2-weighted examinations. No pathologic findings seen on conventional SE T2-weighted images were undetected on fast SE images. Fast SE images may replace conventional SE T2-weighted images in MR imaging of the pelvis.     

Non‐contrast‐enhanced perfusion and ventilation assessment of the human lung by means of fourier decomposition in proton MRI

Assessment of regional lung perfusion and ventilation has significant clinical value for the diagnosis and follow‐up of pulmonary diseases. In this work a new method of non‐contrast‐enhanced functional lung MRI (not dependent on intravenous or inhalative contrast agents) is proposed. A two‐dimensional (2D) true fast imaging with steady precession (TrueFISP) pulse sequence (TR/TE = 1.9 ms/0.8 ms, acquisition time [TA] = 112 ms/image) was implemented on a 1.5T whole‐body MR scanner. The imaging protocol comprised sets of 198 lung images acquired with an imaging rate of 3.33 images/s in coronal and sagittal view. No electrocardiogram (ECG) or respiratory triggering was used. A nonrigid image registration algorithm was applied to compensate for respiratory motion. Rapid data acquisition allowed observing intensity changes in corresponding lung areas with respect to the cardiac and respiratory frequencies. After a Fourier analysis along the time domain, two spectral lines corresponding to both frequencies were used to calculate the perfusion‐ and ventilation‐weighted images. The described method was applied in preliminary studies on volunteers and patients showing clinical relevance to obtain non‐contrast‐enhanced perfusion and ventilation data. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Ventilation imaging with Kr-81m

Sixty-five patients with suspected pulmonary embolism were studied prospectively with both Kr-81 m and Xe-133 ventilation imaging and Tc-99m MAA perfusion imaging. The krypton images, perfusion scintigrams and chest radiographs were read independently of the xenon images, perfusion scintigrams and chest radiographs by three observers. The studies of 53 patients were interpreted as normal or as indicative of a low or intermediate probability for pulmonary embolism with both gases. One study indicated intermediate probability with Xe-133 due to diffuse, severe xenon retention but low probability with Kr-81 m because of close ventilation-perfusion correspondence. The studies of 9 patients indicated a high probability of embolism with both gases, while those of two additional patients (one with emboli at angiography) indicated a high probability only with Kr-81m. While essential agreement between Xe-133 and Kr-81m ventilation imaging was found in most patients, the significant difference in interpretation in 2 of 11 patients with probable pulmonary embolism suggests that a controlled, prospective trial with pulmonary angiography is warranted before Kr-81m is employed for routine clinical use.     

Tc-99m-DTPA aerosol and radioactive gases compared as adjuncts to perfusion scintigraphy in patients with suspected pulmonary embolism

To evaluate the clinical utility of improved methods for radioaerosol inhalation imaging, we obtained preperfusion radioaerosol images in 107 patients (mean age = 62 years), who were referred for evaluation of suspected pulmonary embolism (PE). For each patient, we compared six-view aerosol images with accompanying perfusion scans and chest radiographs and with Xenon-133 (Xe-133) or Krypton-81m (Kr-81m) studies. Four observers at four different institutions independently evaluated aerosol-perfusion and gas-perfusion pairs, classifying the probability of PE as low, high, or indeterminate. The radioaerosol images were good to excellent in quality; excessive central deposition of activity was infrequent and did not interfere with image interpretation. The aerosol-perfusion studies showed 86% agreement with Xe-133 perfusion interpretations (n = 299) and 80% agreement with Kr-81m perfusion interpretations (n = 99). These rates of agreement were comparable with those of intraobserver agreement for gas-to-gas and aerosol-to-aerosol comparisons, and higher than interobserver agreement rates. In a limited number (n = 9) of angiographically documented cases, aerosol-perfusion and gas-perfusion studies provided accurate and equivalent diagnoses. The results suggest that radioaerosol inhalation studies, performed with improved nebulizers, are diagnostically equivalent to ventilation imaging as an adjunct to perfusion scintigraphy in evaluating patients with suspected PE.