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.     

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.     

Basics concepts and clinical applications of oxygen-enhanced MR imaging

Oxygen-enhanced MR imaging is a new technique, and its physiological significance has not yet been fully elucidated. This review article covers (1) the theory of oxygen enhancement and its relationship with respiratory physiology; (2) design for oxygen-enhanced MR imaging sequencing; (3) a basic study of oxygen-enhanced MR imaging in animal models and humans; (4) a clinical study of oxygen-enhanced MR imaging; and (5) a comparison of advantages and disadvantages of this technique with those of hyperpolarized noble gas MR ventilation imaging.Oxygen-enhanced MR imaging provides not only the ventilation-related, but also respiration-related information. Oxygen-enhanced MR imaging has the potential to replace nuclear medicine studies for the identification of regional pulmonary function, and many investigators are now attempting to adapt this technique for routine clinical studies.We believe that further basic studies as well as clinical applications of this new technique will define the real significance of oxygen-enhanced MR imaging for the future of pulmonary functional imaging and its usefulness for diagnostic radiology and pulmonary medicine.     

Basics concepts and clinical applications of oxygen-enhanced MR imaging

Oxygen-enhanced MR imaging is a new technique, and its physiological significance has not yet been fully elucidated. This review article covers (1) the theory of oxygen enhancement and its relationship with respiratory physiology; (2) design for oxygen-enhanced MR imaging sequencing; (3) a basic study of oxygen-enhanced MR imaging in animal models and humans; (4) a clinical study of oxygen-enhanced MR imaging; and (5) a comparison of advantages and disadvantages of this technique with those of hyperpolarized noble gas MR ventilation imaging. Oxygen-enhanced MR imaging provides not only the ventilation-related, but also respiration-related information. Oxygen-enhanced MR imaging has the potential to replace nuclear medicine studies for the identification of regional pulmonary function, and many investigators are now attempting to adapt this technique for routine clinical studies. We believe that further basic studies as well as clinical applications of this new technique will define the real significance of oxygen-enhanced MR imaging for the future of pulmonary functional imaging and its usefulness for diagnostic radiology and pulmonary medicine.     

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。     

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.     

The use of ECG and respiratory triggering to improve the sensitivity of oxygen-enhanced proton MRI of lung ventilation

Changes in lung signal between normal breathing and breathing pure oxygen is the basis for oxygen-enhanced ventilation MRI. An optimal technique guarantees a significant response to pure oxygen in well-ventilated lung tissue. To improve the sensitivity, we investigated the effect of ECG and respiratory triggering. Centric reordered single-shot rapid acquisition relaxation enhancement sequences (TE 4.2 ms, echo spacing 4.2 ms, bandwidth 650 Hz/pixel), with an inversion recovery preparation pulse (TI 700 ms), were used. Series of 20 measurements were performed with and without ECG and respiratory triggering in five young volunteers. Subsequently, series of 100 images were acquired during breathing normal air and pure oxygen (as "stimulus"). Ventilation maps showed by means of the z-score how far the response deviates from the signal intensities during the normal air condition. The standard deviation of the lung signal intensities was lowest for the cardiac-triggered series. In the ventilation maps, on the other hand, signal changes were statistically more significant in the respiratory than in the cardiac-triggered series. The average z-scores in the right (left) cranial part of the lung were 12.4 (13.0) and 9.2 (9.7) for respiratory and ECG-triggered acquisitions. We propose to use respiratory triggering as a means to improve the sensitivity of MR ventilation studies. Electronic Publication     

MR lung imaging at 0.2 T with T1-weighted true FISP: native and oxygen-enhanced

An inversion recovery true fast imaging with steady precession (FISP) pulse sequence was developed to carry out fast imaging of the lungs at 0.2 T. Using this sequence, oxygen-enhanced magnetic resonance (MR) lung imaging was performed on healthy volunteers. The lungs showed signal enhancement (11.7% +/- 3.8%) when breathing 100% oxygen. Using inversion recovery, true FISP at low field may prove promising for MR lung imaging.     

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.     

Influence of oxygen flow rate on signal and T(1) changes in oxygen-enhanced ventilation imaging

PURPOSE: To investigate the optimal oxygen flow rate for oxygen-enhanced MR ventilation imaging. MATERIALS AND METHODS: Using a cardiac-triggered nonselective inversion recovery (IR) half Fourier single-shot fast spin echo sequence, series of images were acquired with the subject alternately inhaling room air and 100% oxygen. Oxygen flow rates of 5 L/min, 10 L/min, 15 L/min, 20 L/min, and 25 L/min were studied, and signal intensity from the oxygen-enhanced ventilation images and T(1) of the lung were measured. RESULTS: The average signal intensity was 63.0 +/- 21.0 for 5 L/min, 98.7 +/- 26.8 for 10 L/min, 133.8 +/- 20.0 for 15 L/min, 138.7 +/- 19.7 for 20 L/min, and 139.2 +/- 37.9 for 25 L/min. The average T(1)'s of the lung were 1399 msec +/- 130 msec for room air, 1314 msec +/- 101 msec for 5 L/min, 1276 msec +/- 105 msec for 10 L/min, 1207 msec +/- 71 msec for 15 L/min, 1206 msec +/- 90 msec for 20 L/min, and 1207 msec +/- 42 msec for 25 L/min. CONCLUSION: The optimal flow rate is 15 L/min for oxygen-enhanced ventilation imaging.     

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.     

Multiple inversion recovery MR subtraction imaging of human ventilation from inhalation of room air and pure oxygen.

The feasibility of MR subtraction imaging of lung ventilation using air against oxygen using a multiple inversion recovery half-Fourier single-shot turbo spin echo (MIR-HASTE) sequence was investigated. Eight healthy, nonsmoking volunteers (3 males, 5 females; from 27 to 48 years of age) were studied on a 1.5 T MR unit. The ventilation image was obtained from the subtraction of the images acquired with the subject inhaling room air and 100% oxygen. By suppressing the signal from subcutaneous fat and thoracic muscle, MIR-HASTE improved the subtraction of signal arising from background tissues. Lung parenchyma, pulmonary veins, descending aorta, spleen, and kidney showed high signal difference, but pulmonary arteries exhibited minimal signal difference. Because of minimal signal change in the pulmonary arteries after inhalation of 100% oxygen, the average signal decreases in the left and right lungs including hilus and periphery amounted to only 19.4+/-4.5 and 20.2+/-3.4%, respectively, compared with regional averages of 23.6+/-5.4 and 24.1+/-3.1% for both lung peripheries alone. Magn Reson Med 43:913-916, 2000.     

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.     

Pulmonary diffusing capacity: assessment with oxygen-enhanced lung MR imaging preliminary findings

PURPOSE: To determine differences in the signal intensity (SI) time courses at oxygen-enhanced magnetic resonance (MR) lung imaging in healthy volunteers and patients with pulmonary diseases and to correlate these differences with pulmonary diffusing capacity. MATERIALS AND METHODS: Seventeen patients with pulmonary diseases and 11 healthy volunteers underwent oxygen-enhanced MR imaging while they breathed room air and 100% oxygen. A turbo spin-echo sequence with global or section-selective inversion pulses was used. For postprocessing, SI slope maps during the breathing of 100% oxygen were calculated. Mean SI slope and SI change values were compared with the diffusing capacity of the lung for carbon monoxide (DLCO). RESULTS: The SI slopes were significantly different for patients and volunteers (P < or = .05, Mann-Whitney U test). Linear correlations were detected between the DLCO and SI slopes for the section-selective inversion pulse (r(2) = 0.81) and the global inversion pulse (r(2) = 0.74). A lower correlation was associated with the SI change for the section-selective pulse (r(2) = 0.04; global pulse, r(2) = 0.81). Regional differences were seen in the SI slope and SI change maps. These differences correlated with findings on radiographs and computed tomographic scans. CONCLUSION: The SI slope during the breathing of 100% oxygen allows spatially resolved assessment of the pulmonary diffusion capacity.     

Centrically reordered inversion recovery half-Fourier single-shot turbo spin-echo sequence: improvement of the image quality of oxygen-enhanced MRI

PURPOSE: The purpose of the study presented here was to determine the improvement in image quality of oxygen-enhanced magnetic resonance (MR) subtraction imaging obtained with a centrically reordered inversion recovery half-Fourier single-shot turbo spin-echo (c-IR-HASTE) sequence compared with that obtained with a conventional sequentially reordered inversion recovery single-shot HASTE (s-IR-HASTE) sequence for pulmonary imaging. MATERIALS AND METHODS: Oxygen-enhanced MR imaging using a 1.5 T whole body scanner was performed on 12 healthy, non-smoking volunteers. Oxygen-enhanced MR images were obtained with the coronal two-dimensional (2D) c-IR-HASTE sequence and 2D s-IR-HASTE sequence combined with respiratory triggering. For a 256x256 matrix, 132 phase-encoding steps were acquired including four steps for phase correction. Inter-echo spacing for each sequence was 4.0 ms. The effective echo time (TE) for c-IR-HASTE was 4.0 ms, and 16 ms for s-IR-HASTE. The inversion time (TI) was 900 ms. To determine the improvement in oxygen-enhanced MR subtraction imaging by c-IR-HASTE, CNRs of subtraction image, overall image quality, and image degradation of the c-IR-HASTE and s-IR-HASTE techniques were statistically compared. RESULTS: CNR, overall image quality, and image degradation of c-IR-HASTE images showed significant improvement compared to those s-IR-HASTE images (P<0.05). CONCLUSION: Centrically reordered inversion recovery half-Fourier single-shot turbo spin-echo (c-IR-HASTE) sequence enhanced the signal from the lung and improved the image quality of oxygen-enhanced MR subtraction imaging.     

Supplemental oxygen causes increased signal intensity in subarachnoid cerebrospinal fluid on brain FLAIR MR images obtained in children during general anesthesia

PURPOSE: To prospectively test the hypothesis that high levels of the fraction of inspired oxygen (Fio(2)) during general anesthesia cause subarachnoid cerebrospinal fluid (CSF) hyperintensity during fluid-attenuated inversion-recovery (FLAIR) magnetic resonance (MR) imaging. MATERIALS AND METHODS: At brain MR imaging during general anesthesia with propofol, two FLAIR sequences were performed in 20 children with American Society of Anesthesiologists physical status classification system grades of 3 or lower. The first FLAIR sequence was performed with the child breathing 100% oxygen; the second was performed with the child breathing 30% oxygen. CSF signal intensity was quantified on a three-point ordinal scale (0 = hypointense to brain parenchyma, 1 = isointense to brain parenchyma, 2 = hyperintense to brain parenchyma) by a pediatric neuroradiologist who was blinded to the Fio(2) level. The Wilcoxon signed rank test was used to determine if CSF hyperintensity was correlated with Fio(2). RESULTS: CSF hyperintensity was present in all 20 children (age range, 1.9-16.7 years; 12 children were boys) when the Fio(2) was 100%. The hyperintensity partially or completely disappeared in the basilar cisterns (P <.001) and cerebral sulcal subarachnoid space (P <.001) after Fio(2) was reduced from 100% to 30%. CONCLUSION: These findings are consistent with the hypothesis that increased arterial oxygen tension and consequently increased CSF Po(2) resulting from administration of high Fio(2) during general anesthesia are responsible for the increased CSF signal intensity noted on brain FLAIR MR images.     

Simultaneous cardiac and respiratory synchronization in oxygen-enhanced magnetic resonance imaging of the lung using a pneumotachograph for respiratory monitoring

OBJECTIVES: We sought to evaluate an optimized method for oxygen-enhanced magnetic resonance imaging of the lung, using electrocardiogram-trigger and a pneumotachograph for simultaneous cardiac and respiratory synchronization. MATERIALS AND METHODS: Five series of IR-SSFSE images (echo time = 28.2 milliseconds; inversion time = 1,200 milliseconds) were obtained in 6 volunteers during the ventilation-paradigm room-air/oxygen/room-air: series 1, respiratory-triggered; series 2, cardiac-triggered; series 3, cardiac-triggered and respiratory-synchronized using the signal of the pneumatic belt; series 4, cardiac-triggered and respiratory-synchronized using the external signal of the pneumotachograph; and series 5, not cardiac-triggered and respiratory-synchronized using the signal of the pneumotachograph. Standard deviations of the lung (SI(var)) and diaphragm mismatch (DM) were measured. The relative SI change (DeltaSI) was computed from room-air and oxygen-enhanced images. Parametric maps were obtained from cross-correlation analysis of the ventilation paradigm. Mean correlation coefficients (cc) and the percentage of activated pixels over the lung (Act%) were calculated from these maps. All 5 parameters were compared among the 5 series (Friedman-analysis of variance, Dunn's posthoc test). RESULTS: In series 4, DM and SI(var) were significantly lower than in respiratory and cardiac-triggered series (DM = 4.7 vs. 14.3 and 18.4; SI(var) = 4.9 vs. 10 and 11). In the same series cc and Act% also were significantly higher than in series 1 and 2 (cc = 0.86 vs. 0.7 and 0.6; Act% = 71.3 vs. 44.7 and 41.2). DeltaSI was not significantly different among all series. CONCLUSIONS: Effective respiratory and cardiac synchronization can be achieved in oxygen-enhanced magnetic resonance imaging of the lung, using a pneumotachograph for real-time targeting of end-expiration.     

Functional MR imaging of pulmonary ventilation using hyperpolarized noble gases

The current status of experimental and clinical applications for functional MR imaging of pulmonary ventilation using hyperpolarized noble gases are reviewed. 3-helium (3He) and 129-xenon (129Xe) can be hyperpolarized by optical pumping techniques such as spin exchange or metastability exchange in sufficient amounts. This process leads to an artificial, non-equilibrium increase of the density of excited nuclei which represents the source of the MR signal. Those hyperpolarized gases are administered mostly via inhalation, and will fill airways and airspaces allowing for ventilation imaging. Recent human studies concentrate on imaging the airways and airspaces with high spatial resolution. Normal ventilation is reflected by an almost complete and homogeneous distribution of the hyperpolarized gas represented by the signal detected. Loss of signal or inhomogeneous signal distribution represent mass effects and ventilatory abnormalities. Even healthy subjects with seasonal allergies without pulmonary symptoms have been observed to exhibit transient ventilation defects. Real-time imaging of ventilation has become feasible for 3He MR imaging and allows for assessment of ventilation-distribution. Furthermore, functional oxygen-sensitive 3He MR imaging opens the field of non-invasive assessment of regional intrapulmonary oxygen concentrations in vivo. Knowing that the diffusion of gas is affected by the geometry and nature of its environment, diffusion measurements are under investigation as a sensitive marker of diseases that involve structural changes of lung parenchyma, such as emphysema and fibrosis. Whereas 3He is not absorbed and is restricted to the airspaces, 129Xe is soluble in blood and lipid-rich tissue. This presents the opportunity for additional dissolved-phase imaging, providing a step towards simultaneous ventilation-perfusion studies.     

Measurement of MR signal and T2* in lung to characterize a tight skin mouse model of emphysema using single-point imaging

PURPOSE: To evaluate whether MRI signal and T2* measurements of lung tissue acquired at ultrashort detection times (tds) can detect emphysematous changes in lungs. MATERIALS AND METHODS: MR signal intensity of in vivo mouse lungs was measured at 4.7 T at tds of 0.2 and 0.4 msec using single-point imaging (SPI). T2* was calculated from the measurements obtained at the two tds. Two groups of 8- and 30-week-old Tight Skin (TS) and aged-matched CB57BL/6 mice were examined. The TS mice spontaneously developed emphysema-like alveolar enlargement. In vivo micro-computed tomography (microCT) scanning and histology were used as reference methods. RESULTS: MR signal and T2* were significantly lower in the lungs of TS mice than in controls. There were no significant differences between the different age groups. MR signal in lung parenchyma correlated linearly (P < 0.0001, r = 0.89) with microCT mass density, and T2* correlated linearly (P < 0.0001, r = -0.91) with the alveoli size (mean linear intercept [MLI]). CONCLUSION: The MR signal intensity and T2* measured at short tds can be used as imaging biomarkers to characterize parenchyma density and alveolar size, respectively.     

Computing oxygen-enhanced ventilation maps using correlation analysis.

Correlation maps of oxygen-enhanced ventilation were obtained in nine healthy volunteers using complete and selected image series. The complete series included all images acquired with the subjects alternately inhaling room air and 100% oxygen. The selected series were the subsets of the complete series and included only co-registered images that showed matched diaphragmatic position at maximal expiration. Cross-correlation was computed between the time response function of each pixel and the input function representing the alternation between periods of room air and 100% oxygen inhalation. The confidence level for the correlation analysis was set to 0.01. Pulmonary parenchymal anatomy was consistently reproduced throughout the lung, even in anterior slices where published data have reported correlation problems. The overall average correlation coefficient was 0.66 +/- 0.07 for the complete series and 0.75 +/- 0.08 for the selected series. It was concluded that correlation analysis could be used to reconstruct qualitative oxygen-enhanced ventilation maps.