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: dynamic MRI with inhalation of molecular oxygen

We have recently demonstrated a non-invasive technique to visualize pulmonary ventilation in humans with inhalation of molecular oxygen as a paramagnetic contrast agent. In the current study, T1 shortening of lung tissue by inhalation of oxygen was observed (P<0.001). The T1 values of lung tissue were also correlated with arterial blood oxygen pressure (PaO(2)) in a pig, resulting in excellent correlation (r(2)=0.997). Dynamic wash-in and wash-out MR ventilation images as well as dynamic wash-in wash-out signal intensity versus time curves were obtained. The mean wash-in decay constants were 26.8+/-10.5 s in the right lung, and 26.3+/-9.5 s in the left lung. The mean wash-out decay constants were 23.3+/-11.3 s in the right lung, and 20.8+/-10.5 s in the left lung. Dynamic assessment of pulmonary ventilation is feasible using oxygen-enhanced MR imaging, which could provide dynamic MR ventilation-perfusion imaging in combination with recently developed MR perfusion imaging technique, and thus a robust tool for the study of pulmonary physiology and pathophysiology.     

Pulmonary embolism: comprehensive evaluation with MR ventilation and perfusion scanning with hyperpolarized helium-3, arterial spin tagging, and contrast-enhanced MRA

PURPOSE: Development of a comprehensive magnetic resonance (MR) examination consisting of MR angiography (MRA) and MR ventilation and perfusion (MR V/Q) scan for the detection of pulmonary emboli (PE) and assessment of the technique in a rabbit model. MATERIALS AND METHODS: Reversible PE was induced by inflating a non-detachable silicon balloon in the left pulmonary artery of five New Zealand White rabbits. MR V/Q scans were obtained prior to, during, and after balloon deflation. MRA was performed during balloon inflation. MR ventilation imaging was performed after the inhalation of hyperpolarized helium-3. MR perfusion imaging was performed with Flow-sensitive Alternating Inversion Recovery with an Extra Radiofrequency pulse technique (FAIRER). High-resolution contrast-enhanced MR pulmonary angiography was used to confirm the occlusion of the pulmonary artery. All imaging was performed on a 1.5-T whole body scanner with broadband capabilities. RESULTS: High-resolution ventilation images of the lungs were obtained. No ventilation defects were detected before, during, or after resolution of simulated PE. FAIRER imaging allowed visualization of pulmonary perfusion. No perfusion defects were detected prior to balloon inflation. During balloon inflation (PE), there was decreased perfusion in the left lower lobe. After reversal of the PE, there was improved perfusion to the left lower lobe. In analogy to nuclear medicine techniques, acute PE produced a mismatched defect in the MR V/Q scan. MRA verified the occlusive filling defect in the left pulmonary artery. CONCLUSION: High-resolution MRA and MR V/Q imaging of the lung is feasible and allows comprehensive assessment of pulmonary embolism in one imaging session.     

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.     

Operating characteristics of hyperpolarized 3He and arterial spin tagging in MR imaging of ventilation and perfusion in healthy subjects

RATIONALE AND OBJECTIVES: The authors tested the feasibility of a magnetic resonance (MR) imaging method combining the use of hyperpolarized helium 3 (3He) for ventilation imaging and an arterial spin-tagging sequence for perfusion imaging in six healthy human subjects. MATERIALS AND METHODS: High-resolution sagittal images depicting 3He distribution were acquired after the subjects' inhalation of 500 mL of laser-hyperpolarized 3He produced by spin-exchange optical pumping. Perfusion MR imaging was performed with a steady-state arterial spin-tagging sequence that enabled the acquisition of three-dimensional images of pulmonary perfusion without the need for subject breath holding. RESULTS: The 3He ventilation images display, with high signal intensity and detailed anatomic localization, the airspace of the lung parenchyma. The signal intensity on the perfusion images decreased by 23.2% with the use of arterial spin tagging. Ventilation and perfusion were matched, as is expected in healthy subjects. CONCLUSION: This method may have important applications in the assessment of lung function, enabling the calculation of regional ventilation-perfusion ratios. It may also aid in the selection of candidates for lung volume-reduction surgery.     

Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch

A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is often needed for accurate differential diagnosis.     

Oxygen-enhanced MR ventilation imaging of the lung: preliminary clinical experience in 25 subjects.

OBJECTIVE: The purpose of this study was to show the feasibility of oxygen-enhanced MR ventilation imaging in a clinical setting with correlation to standard pulmonary function tests, high-resolution CT, and (81m)Kr ventilation scintigraphy. SUBJECTS AND METHODS: Seven healthy volunteers, 10 lung cancer patients, and eight lung cancer patients with pulmonary emphysema were studied. A respiratory synchronized inversion-recovery single-shot turbo-spin-echo sequence (TE, 16; inversion time, 720 msec; interecho spacing, 4 msec) was used for data acquisition. The following paradigm of oxygen inhalation was used: 21% oxygen (room air), 100% oxygen, 21% oxygen. MR imaging data including maximum mean relative enhancement ratio and mean slope of relative enhancement were correlated with forced expiratory volume in 1 sec, diffusing lung capacity, high-resolution CT emphysema score, and mean distribution ratio of (81m)Kr ventilation scintigraphy. RESULTS: Oxygen-enhanced MR ventilation images were obtained in all subjects. Maximum mean relative enhancement ratio and mean slope of relative enhancement of lung cancer patients were significantly decreased compared with those of the healthy volunteers (p < 0.0001, p < 0.0001). The mean slope of relative enhancement in lung cancer patients with pulmonary emphysema was significantly lower than that of lung cancer patients without pulmonary emphysema (p < 0.0001). Maximum mean relative enhancement ratio (r(2) = 0.81) was excellently correlated with diffusing lung capacity. Mean slope of relative enhancement (r(2) = 0.74) was strongly correlated with forced expiratory volume in 1 sec. Maximum mean relative enhancement had good correlation with the high-resolution CT emphysema score (r(2) = 0.38). The maximum mean relative enhancement had a strong correlation with the distribution ratio (r(2) = 0.77). CONCLUSION: Oxygen-enhanced MR ventilation imaging in human subjects showed regional changes in ventilation, thus reflecting regional lung function.     

Contrast-enhanced MRI of the lung

The lung has long been neglected by MR imaging. This is due to unique intrinsic difficulties: (1) signal loss due to cardiac pulsation and respiration; (2) susceptibility artifacts caused by multiple air-tissue interfaces; (3) low proton density. There are many MR strategies to overcome these problems. They consist of breath-hold imaging, respiratory and cardiac gating procedures, use of short repetition and echo times, increase of the relaxivity of existing spins by administration of intravenous contrast agents, and enrichment of spin density by hyperpolarized noble gases or oxygen. Improvements in scanner performance and frequent use of contrast media have increased the interest in MR imaging and MR angiography of the lung. They can be used on a routine basis for the following indications: characterization of pulmonary nodules, staging of bronchogenic carcinoma, in particular assessment of chest wall invasion; evaluation of inflammatory activity in interstitial lung disease; acute pulmonary embolism, chronic thromboembolic pulmonary hypertension, vascular involvement in malignant disease; vascular abnormalities. Future perspectives include perfusion imaging using extracellular or intravascular (blood pool) contrast agents and ventilation imaging using inhalation of hyperpolarized noble gases, of paramagnetic oxygen or of aerosolized contrast agents. These techniques represent new approaches to functional lung imaging. The combination of visualization of morphology and functional assessment of ventilation and perfusion is unequalled by any other technique.     

A diagnostic strategy using ventilation-perfusion studies in patients suspect for pulmonary embolism.

A diagnostic strategy for the assessment of pulmonary embolism was developed using results of scintigraphic examinations in over 100 patients, all of whom had angiographic assessment of their pulmonary vasculature and nearly 50% of whom had combined ventilation-perfusion studies. The highest-probability estimate of pulmonary embolism that could be made in the absence of a ventilation study was 80%. When a ventilation study was added, this probability increased to nearly 100% for patients with multiple large perfusion defects and normal ventilation. For smaller defects with normal ventilation, the probability of pulmonary embolism was only 50%. For perfusion defects corresponding to known radiographic abnormalities, the probability of pulmonary embolism was 25%.     

Oxygen-enhanced magnetic resonance ventilation imaging of the human lung at 0.2 and 1.5 T.

Lung ventilation imaging using inhaled oxygen as a contrast medium was performed using both a 0.2 and a 1.5 T clinical magnetic resonance (MR) scanner in eight volunteers. Signal-to-noise-ratios (SNRs) of the ventilation images as well as T1 values of the lung acquired with inhalation of 100% oxygen and room air were calculated. The SNR was 9.7 +/- 3.0 on the 0.2 T MR system and 69.5 +/- 28.8 on the 1.5 T system (P < 0.001). The mean T1 value on the 0.2 T MR system with subjects breathing room air was 632 +/- 54 msec; with 100% oxygen, it was 586 +/- 41 msec (P < 0.01). At 1.5 T, the mean values were 904 +/- 99 msec and 790 +/- 114 msec, respectively (P < 0.0001). We conclude that MR oxygen-enhanced ventilation imaging of the lung is feasible with an open configured 0.2 T MR system.     

A combined 1H perfusion/3He ventilation NMR study in rat lungs.

The assessment of both pulmonary perfusion and ventilation is of crucial importance for a proper diagnosis of some lung diseases such as pulmonary embolism. In this study, we demonstrate the feasibility of combined magnetic resonance imaging lung ventilation and perfusion performed serially in rat lungs. Lung ventilation function was assessed using hyperpolarized 3He, and lung perfusion proton imaging was demonstrated using contrast agent injection. Both imaging techniques have been implemented using projection-reconstruction sequences with free induction decay signal acquisitions. The study focused on fast three-dimensional (3D) data acquisition. The projection-reconstruction sequences used in this study allowed 3D data set acquisition in several minutes without high-performance gradients. 3D proton perfusion/helium ventilation imaging has been demonstrated on an experimental rat model of pulmonary embolism showing normal lung ventilation associated with lung perfusion defect. Assuming the possibility, still under investigation, of showing lung obstruction pathologies using 3He imaging, these combined perfusion/ventilation methods could play a significant clinical role in the future for diagnosis of several pulmonary diseases.     

99mTc-DTPA aerosol for same-day post-perfusion ventilation imaging: Results of a multicentre study

A multicentre study was performed in an attempt to evaluate a submicronic technetium-99m diethylene triamine penta-acetic acid aerosol generated by a newly developed delivery system, the aerosol production equipment (APE nebulizer), for same-day post-perfusion ventilation imaging in patients with clinically suspected pulmonary embolism. Quantitative comparison between the DTPA aerosol and krypton gas demonstrated a close correlation with respect to regional pulmonary distribution of activity and peripheral lung penetration (n=14,r=0.94,P<0.001 andr=0.75,P<0.0025, respectively). In 169 consecutive patients, DTPA aerosol images performed immediately following perfusion (inhalation scan I) were compared to those carried out on the next day (inhalation scan 11) with respect to image quality and assessment of perfusion-ventilation matches or mismatches. Agreement between inhalation scans I and II with respect to perfusion defects matched or mismatched to ventilation was found in 166/169 (98%) studies. The image quality of inhalation scan I was equal to that of scan II in 72%; inhalation scan I was superior in 11% of cases, while scan 11 was superior in 17%. This submicronic^99mTc-labelled DTPA aerosol is well suited for fast same-day post-perfusion ventilation imaging in patients with clinical suspicion of pulmonary embolism.     

Oxygen-enhanced magnetic resonance ventilation imaging of lung

The oxygen-enhanced magnetic resonance (MR) ventilation imaging is a new technique, and the full extent of its physiological significance has not been elucidated. This review article includes background on (1) respiratory physiology; (2) mechanism and optimization of oxygen-enhanced MR imaging technique; (3) recent applications in animal and human models; and (4) merits and demerits of the technique in comparison with hyperpolarized noble gas MR ventilation imaging. Application of oxygen-enhanced MR ventilation imaging to patients with pulmonary diseases has been very limited. However, we believe that further basic studies, as well as clinical applications of this new technique will define the real significance of oxygen-enhanced MR ventilation imaging in the future of pulmonary functional imaging and its usefulness for diagnostic radiology.     

MR ventilation-perfusion imaging of human lung using oxygen-enhanced and arterial spin labeling techniques.

Magnetic resonance ventilation-perfusion (V/Q) imaging has been demonstrated using oxygen and arterial spin labeling techniques. Inhaled oxygen is used as a paramagnetic contrast agent in ventilation imaging using a multiple inversion recovery (MIR) approach. Pulmonary perfusion imaging is conducted using a flow-sensitive alternating inversion recovery with an extra radiofrequency pulse (FAIRER) technique. A half Fourier single-short turbo spin echo (HASTE) sequence is used for data acquisition in both techniques. V/Q imaging was performed in ten of the twenty volunteers, while either ventilation or perfusion was imaged in the other ten. This V/Q imaging scheme is completely noninvasive, does not involve ionized radiation, and shows promising potential for clinical use in the diagnosis of lung diseases such as pulmonary embolism.     

Improved quantitative dynamic regional oxygen-enhanced pulmonary imaging using image registration.

Oxygen-enhanced MR imaging has been demonstrated in a number of recent studies as a potential method to visualize regional ventilation in the lung. A quantitative pixel-by-pixel analysis is hampered by motion and volume change due to breathing. In this study, image registration via active shape modeling is shown to produce significant improvements in the regional analysis of both static and dynamic oxygen-enhanced pulmonary MRI for five normal volunteers. The method enables the calculation of regional change in relaxation rate between breathing air and 100% oxygen, which is proportional to the change in regional oxygen concentration, and regional oxygen wash-in and wash-out time constants. Registration-corrected mapping of these parameters is likely to provide improved information in the regional assessment of a range of lung diseases.     

Reverse mismatched ventilation-perfusion pulmonary imaging with accumulation of technetium-99m-DTPA in a mucous plug in a main bronchus: a case report

The phenomenon of reverse mismatched ventilation-perfusion on pulmonary scintigraphy is a fairly common occurrence. We present a patient who was experiencing decreasing oxygen saturation and had a reverse mismatched ventilation-perfusion imaging pattern associated with radiotracer retention in a main bronchus. Technetium-99m-DTPA aerosol lung imaging showed tracer retention in the trachea and right main bronchus, absent ventilation in the right lung, and normal ventilation in the left lung. Technetium-99m-MAA perfusion lung images showed normal perfusion of the left lung and some perfusion in the right lung. These findings represented a reverse ventilation-perfusion mismatch. Reverse mismatched ventilation-perfusion, or totally absent ventilation with preservation of some perfusion in the right lung, resulted in functional intrapulmonary shunting, which explained the decreasing oxygen saturation observed in this patient. A concurrent portable chest radiograph showed elevation of the right hemidiaphragm, a shift of the mediastinum to the right, deviation of the endotracheal tube, narrowing of the intercostal space of the right thorax, and collapse of the right lower lobe. The radiographic findings of underventilation of the right lung with atelectasis of the right lower lobe were due to mucous plugging the right main bronchus.     

Perfusion magnetic resonance imaging of the lung: characterization of pneumonia and chronic obstructive pulmonary disease. A feasibility study

Perfusion magnetic resonance (MR) imaging is a promising new method for detection of perfusion defects in the diagnosis of pulmonary embolism. In the present study we evaluated the first-pass characteristics of perfusion MR imaging in patients with pneumonia or chronic obstructive pulmonary disease (COPD), frequent differential diagnoses to pulmonary embolism. Dynamic contrast-enhanced MR images of 12 patients with acute pneumonia and 13 patients with exacerbation of COPD were acquired in both the coronal and transaxial planes (an inversion recovery prepared gradient-echo sequence using 0.05 mmol/kg gadodiamide/injection). The MR images and the signal intensity (SI) versus time curves were characterized for each disease entity and compared with normal lung and the findings in pulmonary embolism from our previous study. The perfusion MR images of pneumonia showed distinct regions of increased contrast enhancement; in COPD with signs of emphysema (11 of the 13 COPD patients), the images showed a coarse pattern of reduced contrast enhancement. The SI versus time curves of pneumonia, COPD with signs of emphysema, and normal lung were statistically different, the respective pooled SI values (+/-95% CI) being as follows: mean baseline SI, 20.7 (1.1), 7.4 (0.4), and 8.5 (0.3); mean peak SI, no peak, 12.9 (1.5), and 27 (4.6); and mean max change of SI in percent, 110 (27), 79 (22), and 205 (52). Perfusion MR imaging of pneumonia and COPD with signs of emphysema showed first-pass that were characteristics promising for diagnostic use. Both the MR images and the SI versus time curves were different from the perfusion characteristics in normal lung and pulmonary embolism shown previously.     

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.     

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.     

Assessment of human pulmonary function using oxygen-enhanced T(1) imaging in patients with cystic fibrosis.

Indirect qualitative MRI of pulmonary function is feasible using the paramagnetic effects of oxygen physically dissolved in blood. In this study, a more quantitative oxygen-enhanced pulmonary function test based on the slope of a plot of R(1) vs. oxygen concentration-the oxygen transfer function (OTF)-was developed and tested in a pool of five healthy volunteers and five patients with cystic fibrosis (CF). The lung T(1) relaxation rate, R(1), under normoxic conditions (room air, 21% O(2)), and the response to various hyperoxic conditions (40%-100% O(2)) were studied. Lung T(1) in healthy volunteers showed a relatively homogeneous distribution while they breathed room air, and a homogeneous decrease under hyperoxic conditions. Lung T(1) in CF patients showed an inhomogeneous distribution while they breathed room air, and the observed lung T(1) decrease under hyperoxia depended on the actual state of the diseased lung tissue. In the selected group of CF patients, areas with reduced OTF also showed reduced perfusion, as confirmed by qualitative contrast-enhanced MR pulmonary perfusion imaging. The results demonstrate that this completely noninvasive oxygen-enhanced pulmonary function test has potential for clinical applications in the serial diagnosis of lung diseases such as CF. .