Hyperpolarized 3He MRI in asthma measurements of regional ventilation following allergic sensitization and challenge in mice--preliminary results

RATIONALE AND OBJECTIVES: Quantitative regional measurement of physiological parameters of lung may improve both early detection of asthma and its response to treatment by elucidating the characteristics of airway obstruction. Recent emergence of hyperpolarized helium-3 magnetic resonance imaging as a sensitive pulmonary imaging tool has shown great potential in capturing important structural and functional aspects of normal and diseased lungs. The objective of this study was to investigate regional ventilation changes in the mouse lung following allergen sensitization and challenge. MATERIALS AND METHODS: A murine model of allergic airway inflammation was created in mice following allergen challenge using Af and IgE-mediated asthma. The creation of model was verified using pulmonary function test and histology. Regional fractional ventilation was then measured in the animals using hyperpolarized 3He MRI on a pixel-by-pixel basis with a planar resolution of 0.24 mm. The sensitized and healthy animals were then compared statistically to assess the potential sensitivity of this technique in detection of such pulmonary abnormalities. RESULTS: In this work, we have demonstrated for the first time the quantitative measurement of regional ventilation in normal and asthmatic mice. Results of this study show significant changes in regional ventilation in murine model of allergic airway sensitization compared with that in normal control animals. CONCLUSION: Further development of this technique can potentially serve as a quantitative marker to investigate the physiology of allergen-induced airway hyperresponsiveness and to assist in disease treatment and prevention.     

Pulmonary edema induced by allergen challenge in the rat: noninvasive assessment by magnetic resonance imaging.

The course of pulmonary edema formation after an intratracheal (i.t.) instillation of ovalbumin was followed noninvasively by magnetic resonance imaging (MRI) in actively sensitized Brown Norway (BN) rats. Changes in edema volume assessed by MRI mimicked the results from the analysis of the number and activation of inflammatory cells recovered from the broncho-alveolar lavage (BAL) fluid. Rats treated with budesonide did not develop edema following challenge with ovalbumin, and these animals showed a significant decrease in BAL fluid inflammatory cell numbers and eosinophil peroxidase and myeloperoxidase activities. Thus, following lung edema formation by MRI provides a reliable means of assessing pulmonary inflammation after allergen challenge. Unlike BAL fluid analysis, which requires killing animals at each time point, this method is noninvasive. MRI could be of importance for the noninvasive profiling of anti-inflammatory drugs in animal models of asthma and in the clinic. Magn Reson Med 45:88-95, 2001.     

Evaluation of structure-function relationships in asthma using multidetector CT and hyperpolarized He-3 MRI

RATIONALE AND OBJECTIVES: Although multiple detector computed tomography (MDCT) and hyperpolarized gas magnetic resonance imaging (HP MRI) have demonstrated ability to detect structural and ventilation abnormalities in asthma, few studies have sought to exploit or cross-validate the regional information provided by these techniques. The purpose of this work is to assess regional disease in asthma by evaluating the association of sites of ventilation defect on HP MRI with other regional markers of airway disease, including air trapping on MDCT and inflammatory markers on bronchoscopy. MATERIALS AND METHODS: Both HP MRI using helium-3 and MDCT were acquired in the same patients. Supervised segmentation of the lung lobes on MRI and MDCT facilitated regional comparisons of ventilation abnormalities in the lung parenchyma. The percentage of spatial overlap was evaluated between regions of ventilation defect on HP MRI and hyperlucency on MDCT to determine associations between obstruction and likely regions of gas trapping. Similarly, lung lobes with high defect volume were compared to lobes with low defect volume for differences in inflammatory cell number and percentage using bronchoscopic assessment. RESULTS: There was significant overlap between sites of ventilation defect on HP MRI and hyperlucency on MDCT suggesting that sites of airway obstruction and air trapping are associated in asthma. The percent (r=0.68; P= .0039) and absolute (r=0.61; P= .0125) number of neutrophils on bronchoalveolar lavage for the sampled lung lobe also directly correlated with increased defect volume. CONCLUSIONS: These results show promise for using image guidance to assess specific regions of ventilation defect or air trapping in heterogeneous obstructive lung diseases such as asthma.     

Near-infrared fluorescence imaging and histology confirm anomalous edematous signal distribution detected in the rat lung by MRI after allergen challenge

PURPOSE: To address the issue concerning the predominant location, on the left anatomic side, of edematous signals detected by magnetic resonance imaging (MRI) in the lungs of actively sensitized rats following intratracheal (IT) allergen challenge. MATERIALS AND METHODS: Near-infrared fluorescence (NIRF) imaging was used to detect the lobular distribution in the lungs of normal rats of an IT instilled fluorescent dye, Cy5.5. Actively sensitized Brown Norway rats were examined by MRI 24 hours after IT administration of ovalbumin. The perivascular edema was quantified by histology in the different lobes of lungs removed from the same animals immediately after the MRI acquisitions. RESULTS: An uneven distribution of Cy5.5 was found, predominantly on the left lobe, paralleling the localized development of allergic pulmonary inflammation in the left lobe detected as edematous signal by MRI and confirmed by histology. The patterns of the distributions of the dye between and within the lobes were very similar to those of perivascular edema assessed histologically. CONCLUSION: The data indicate a relationship between the molecular deposition of the dye detected by NIRF in the lungs and the distribution of allergen eliciting the development of pulmonary inflammation in actively rats. The combination of MRI with NIRF imaging may provide important information in preclinical pharmacologic research in the area of airway diseases. While MRI is able to address the effects of compounds on the inflammatory response in models of airways diseases, NIRF imaging may provide important insights on drug distribution and interaction in the lung, being thus suited for molecular imaging studies.     

PET/MRI of the thorax,abdomen and retroperitoneum: Benefits of the breathing-synchronized scanning

Hybrid imaging using various radiopharmaceuticals is currently essential not only in detection and therapy response monitoring of tumors, but also in assessment of inflammatory or systemic diseases. Combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) is still relatively new method with great prospects of comprehensive assessment using anatomical and multiple functional information. However, benefits of PET/MRI in thorax, abdomen and retroperitoneum are not completely defined. Breathing movements affect imaging of thoracic, abdominal and retroperitoneal organs and pathological structures using PET and MRI. Fast MRI sequences are performed using breath-hold technique; however, acquisition of longer sequences and PET scanning need to be breathing-synchronized. Review article summarizes concrete PET/MRI protocols and importance of concrete MRI sequences and radiopharmaceuticals in different pathological lesions with focus on benefit of breathing-synchronized techniques.     

晚期帕金森病患者脑内18F-FDG摄取变化及其异常脑内环路机制的探讨

目的　用1 8F 脱氧葡萄糖 (FDG)PET显像显示晚期帕金森病患者异常的脑内环路。方法　对 10例双侧症状的晚期帕金森病患者和 10例正常人分别行静息状态下1 8F FDGPET显像 ,用统计参数图 (SPM)方法对晚期帕金森病患者和正常人的PET图像进行组间t检验分析 ,比较 2组间脑内葡萄糖代谢的差异。结果　与正常人相比 ,帕金森病患者双侧丘脑、海马、中央前回皮质 (Brodmann6区 ,BA6 )及豆状核代谢增加 (P <0 0 0 1) ;前额叶运动区 (BA4 6、BA4 7)及顶叶 (BA7、BA39)代谢减低(P <0 0 0 1)。结论　帕金森病脑内异常代谢环路的显示有助于帕金森病的辅助诊断及其发病机理的探讨。     

Pulmonary CT and MRI phenotypes that help explain chronic pulmonary obstruction disease pathophysiology and outcomes

Pulmonary x‐ray computed tomographic (CT) and magnetic resonance imaging (MRI) research and development has been motivated, in part, by the quest to subphenotype common chronic lung diseases such as chronic obstructive pulmonary disease (COPD). For thoracic CT and MRI, the main COPD research tools, disease biomarkers are being validated that go beyond anatomy and structure to include pulmonary functional measurements such as regional ventilation, perfusion, and inflammation. In addition, there has also been a drive to improve spatial and contrast resolution while at the same time reducing or eliminating radiation exposure. Therefore, this review focuses on our evolving understanding of patient‐relevant and clinically important COPD endpoints and how current and emerging MRI and CT tools and measurements may be exploited for their identification, quantification, and utilization. Since reviews of the imaging physics of pulmonary CT and MRI and reviews of other COPD imaging methods were previously published and well‐summarized, we focus on the current clinical challenges in COPD and the potential of newly emerging MR and CT imaging measurements to address them. Here we summarize MRI and CT imaging methods and their clinical translation for generating reproducible and sensitive measurements of COPD related to pulmonary ventilation and perfusion as well as parenchyma morphology. The key clinical problems in COPD provide an important framework in which pulmonary imaging needs to rapidly move in order to address the staggering burden, costs, as well as the mortality and morbidity associated with COPD. J. MAGN. RESON. IMAGING 2016;43:544–557.     

轻度认知障碍患者海马的影像学研究进展

海马是学习记忆相关的重要脑区,其结构、功能的异常与轻度认知障碍（MCI）的发生发展密切相关。MRI、PET等影像学检查手段能提供海马的结构、功能与葡萄糖代谢等指标,能对早期筛查和诊断MCI提供更多的影像学支持。笔者主要综述了遗忘型MCI患者海马结构、海马的功能连接及海马葡萄糖代谢的影像学研究进展,以期发现更加敏感的影像学指标用于MCI的诊断。     

Adrenoleukodystrophy: imaging with CT, MRI, and PET

A patient with adrenoleukodystrophy (ALD) was tested with a series of CT scans, magnetic resonance imaging (MRI), and positron emission tomographic (PET) images. The computed tomographic (CT) scan revealed the classical pattern described in ALD but showed little relation to the clinical presentation and the evolution of the disease. The MRI showed a larger area of abnormality than the one detected with the CT scan and was more sensitive to progression of the disease process. The PET scan done for cerebral blood flow and glucose metabolism showed derangements on gray matter that were not detected with either of the previous tests.     

Utility of positron emission tomography-magnetic resonance imaging in musculoskeletal imaging

Differentiation between neoplastic and nonneoplastic conditions magnetic resonance imaging (MRI) has established itself as one of the key clinical tools in evaluation of musculoskeletal pathology. However, MRI still has several key limitations which require supplemental information from additional modalities to complete evaluation of various disorders. This has led to the development hybrid positron emission tomography (PET)-MRI which is rapidly evolving to address key clinical questions by using the morphological strengths of MRI and functional information of PET imaging. In this article, we aim to review physical principles and techniques of PET-MRI and discuss clinical utility of functional information obtained from PET imaging and structural information obtained from MRI imaging for the evaluation of musculoskeletal pathology. More specifically, this review highlights the role of PET-MRI in musculoskeletal oncology including initial diagnosis and staging, treatment planning and post-treatment follow-up. Also we will review utility of PET-MRI in evaluating musculoskeletal infections (especially in the immunocompromised and diabetics) and inflammatory condition. Additionally, common pitfalls of PET-MRI will be addressed.     

PET/MRI在肺癌中的潜在临床应用价值

PET/MRI作为新出现的融合影像技术,其临床应用价值尚未得到充分证实。与CT相比,MRI具有软组织对比分辨力高、无辐射、多参数成像、能够提供更多功能信息的优势,PET与MRI的融合对于肺癌的潜在应用价值可能要优于PET/CT。简述不同的PET/MRI系统的设计,并从肺结节的检出、鉴别诊断、TNM分期、预后/早期疗效评价/肿瘤复发4个方面介绍PET/MRI在肺癌中的潜在临床价值。     

Clinical use of cardiac PET/MRI: current state-of-the-art and potential future applications

Combined PET/MRI is a novel imaging method integrating the advances of functional and morphological MR imaging with PET applications that include assessment of myocardial viability, perfusion, metabolism of inflammatory tissue and tumors, as well as amyloid deposition imaging. As such, PET/MRI is a promising tool to detect and characterize ischemic and non-ischemic cardiomyopathies. To date, the greatest benefit may be expected for diagnostic evaluation of systemic diseases and cardiac masses that remain unclear in cardiac MRI, as well as for clinical and scientific studies in the setting of ischemic cardiomyopathies. Diagnosis and therapeutic monitoring of cardiac sarcoidosis has the potential of a possible ‘killer-application’ for combined cardiac PET/MRI. In this article, we review the current evidence and discuss current and potential future applications of cardiac PET/MRI.     

The role of hyperpolarized 129xenon in MR imaging of pulmonary function

In the last two decades, functional imaging of the lungs using hyperpolarized noble gases has entered the clinical stage. Both helium (³He) and xenon (¹²⁹Xe) gas have been thoroughly investigated for their ability to assess both the global and regional patterns of lung ventilation. With advances in polarizer technology and the current transition towards the widely available ¹²⁹Xe gas, this method is ready for translation to the clinic. Currently, hyperpolarized (HP) noble gas lung MRI is limited to selected academic institutions; yet, the promising results from initial clinical trials have drawn the attention of the pulmonary medicine community. HP ¹²⁹Xe MRI provides not only 3-dimensional ventilation imaging, but also unique capabilities for probing regional lung physiology. In this review article, we aim to (1) provide a brief overview of current ventilation MR imaging techniques, (2) emphasize the role of HP ¹²⁹Xe MRI within the array of different imaging strategies, (3) discuss the unique imaging possibilities with HP ¹²⁹Xe MRI, and (4) propose clinical applications.     

Assessment of hyperpolarized 3He lung MRI for regional evaluation of interventional therapy: A pilot study in pediatric cystic fibrosis

Purpose:

To determine whether regional changes in lung ventilation in a group of pediatric cystic fibrosis (CF) patients following a course of chest physiotherapy could be detected with ³He MRI.

Materials and Methods:

The reproducibility of lung ventilation volume measurements obtained with ³He lung magnetic resonance imaging (MRI) was established in a group of five children with CF age 6–15 years. The same methodology was then used to evaluate whether standard chest physiotherapy (percussion and drainage) had any immediate effect on regional ventilated lung volumes in a further group of nine age‐matched CF children (5–15 years).

Results:

Global lung ventilation volumes remained the same within the limits of sensitivity derived from the reproducibility study; however, regional lung ventilation was observed to change in most patients after therapy.

Conclusion:

³He MRI can be successfully used in children with CF, and has the sensitivity to detect regional quantitative changes in lung ventilation following chest physiotherapy. J. Magn. Reson. Imaging 2009;30:981–988. © 2009 Wiley‐Liss, Inc.     

Fluorine-18 deoxyglucose and false-positive results: a major problem in the diagnostics of oncological patients

Fluorine-18 deoxyglucose (FDG) is not a very tumour-specific substance, and its accumulation in benign lesions with increased glucose metabolism may give rise to false-positive results and hence cause FDG positron emission tomography (PET) to display relatively low specificity (frequently below 85%). Correct interpretation of FDG PET studies is predicated upon detailed knowledge of morphological abnormalities, and the importance of the correlation of functional and morphological information, as derived from computed tomography or magnetic resonance imaging, is discussed. It is emphasized that image fusion programs cannot substitute for understanding of functional and morphological methods. The reconstruction of PET cross-sections is considered, and it is concluded that an iterative image reconstruction method is to be favoured, given its advantages in reducing image artefacts and improving quantification of radioactivity concentrations. The differentiation of malignant and benign lesions when using FDG PET is then reviewed; false-positive findings may be obtained, for example, in patients with acute inflammatory lesions, chronic pancretitis, retroperitoneal fibrosis or salivary gland tumours. It is suggested that these problems may be alleviated by means of multitracer studies, e.g. using carbon-11 labelled aminoisobutyric acid for quantification of A-type amino acid transport. Finally, the effects of radiotherapy and chemotherapy on FDG uptake and the problems that accrue from these effects are reviewed. Both radiotherapy and chemotherapy can cause increased FDG uptake, complicating diagnosis and evaluation. Knowledge of the effects of different treatment procedures on regional FDG metabolism is therefore necessary for correct interpretation of the PET data.     

多模态MRI对乳腺癌化疗相关认知功能障碍的研究进展

乳腺癌病人化疗相关认知功能障碍（CRCI）发生的重要神经基础是化疗引起的脑结构、代谢、灌注和功能的改变。多模态MRI可以通过基于体素的形态学测量、扩散张量成像、磁共振波谱、磁敏感加权成像、动脉自旋标记灌注成像和基于血氧水平依赖的功能MRI等技术从局部或全局显示脑灰质体积和密度改变、脑白质纤维损伤、脑代谢改变、脑血流灌注以及脑区激活和功能连接变化等,从而为进一步探索乳腺癌CRCI的发病机制、早期诊断和症状研究提供依据。就多模态MRI在乳腺癌CRCI中的研究进展予以综述。     

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.     

Two cases of pulmonary paragonimiasis on FDG-PET CT imaging

Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) is useful in cancer diagnosis owing to its sensitivity to the differences in glucose metabolic rate between benign and malignant diseases, especially in the lung. One pitfall in PET imaging of lung disease, however, is the overlap in metabolic rate of inflammatory and neoplastic entities. Paragonimiasis is a food-borne parasitic disease that causes the pulmonary and pleural inflammation. We present two cases of pulmonary paragonimiasis that showed high uptake suggestive of tumor on FDG-PET CT images, both confirmed on histopathology by visualization of Paragonimus westermani eggs in the involved tissues.     

MR imaging of lung cancer

Since publication of the Radiologic Diagnostic Oncology Group Report in 1991, the clinical application of pulmonary magnetic resonance (MR) imaging to patients with lung cancer has been limited. Computed tomography has been much more widely available for staging of lung cancer in clinical situations. Currently, ventilation and perfusion scintigraphy is the only modality that demonstrates pulmonary function while 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography is the only modality that reveals biological glucose metabolism of lung cancer. However, recent advancements in MR imaging have made it possible to evaluate morphological and functional information in lung cancer patients more accurately and quantitatively. Pulmonary MR imaging may hold significant potential to substitute for nuclear medicine examinations. In this review, we describe recent advances in MR imaging of lung cancer, focusing on (1) characterization of solitary pulmonary nodules; (2) differentiation from secondary change; evaluation of (3) medastinal invasion, (4) chest wall invasion, (5) lymph node metastasis, and (6) distant metastasis; and (7) pulmonary functional imaging. We believe that further basic studies, as well as clinical applications of newer MR techniques, will play an important role in the management of patients with lung cancer.     

Proton magnetic resonance imaging for assessment of lung function and respiratory dynamics

Since many pulmonary diseases present with a variable regional involvement, modalities for assessment of regional lung function gained increasing attention over the last years. Together with lung perfusion and gas exchange, ventilation, as a result of the interaction of the respiratory pump and the lungs, is an indispensable component of lung function. So far, this complex mechanism is still mainly assessed indirectly and globally. A differentiation between the individual determining factors of ventilation would be crucial for precise diagnostics and adequate treatment. By dynamic imaging of the respiratory pump, the mechanical components of ventilation can be assessed regionally. Amongst imaging modalities applicable to this topic, magnetic resonance imaging (MRI), as a tool not relying on ionising radiation, is the most attractive. Recent advances in MRI technology have made it possible to assess diaphragmatic and chest wall motion, static and dynamic lung volumes, as well as regional lung function. Even though existing studies show large heterogeneity in design and applied methods, it becomes evident that MRI is capable to visualise pulmonary function as well as diaphragmatic and thoracic wall movement, providing new insights into lung physiology. Partly contradictory results and conclusions are most likely caused by technical limitations, limited number of studies and small sample size. Existing studies mainly evaluate possible imaging techniques and concentrate on normal physiology. The few studies in patients with lung cancer and emphysema already give a promising outlook for these techniques from which an increasing impact on improved and quantitative disease characterization as well as better patient management can be expected.