John P. Mugler

The Alzheimer's Disease Neuroimaging Initiative (ADNI): MRI methods

The Alzheimers Disease Neuroimaging Initiative (ADNI) is a longitudinal multisite observational study of healthy elders, mild cognitive impairment (MCI), and Alzheimers disease. Magnetic resonance imaging (MRI), (18F)‐fluorodeoxyglucose positron emission tomography (FDG PET), urine serum, and cerebrospinal fluid (CSF) biomarkers, as well as clinical/psychometric assessments are acquiredat multiple time points. All data will be cross‐linked and made available to the general scientific community. The purpose of this report is to describe the MRI methods employed in ADNI. The ADNI MRI core established specifications thatguided protocol development. A major effort was devoted toevaluating 3D T1‐weighted sequences for morphometric analyses. Several options for this sequence were optimized for the relevant manufacturer platforms and then compared in a reduced‐scale clinical trial. The protocol selected for the ADNI study includes: back‐to‐back 3D magnetization prepared rapid gradient echo (MP‐RAGE) scans; B1‐calibration scans when applicable; and an axial proton density‐T2 dual contrast (i.e., echo) fast spin echo/turbo spin echo (FSE/TSE) for pathology detection. ADNI MRI methods seek to maximize scientific utility while minimizing the burden placed on participants. The approach taken in ADNI to standardization across sites and platforms of the MRI protocol, postacquisition corrections, and phantom‐based monitoring of all scanners could be used as a model for other multisite trials. J. Magn. Reson. Imaging 2008.

Hyperpolarized 3He MR lung ventilation imaging in asthmatics: Preliminary findings

Asthma is a disease characterized by chronic inflammation and reversible obstruction of the small airways resulting in impaired pulmonary ventilation. Hyperpolarized 3He magnetic resonance (MR) lung imaging is a new technology that provides a detailed image of lung ventilation. Hyperpolarized 3He lung imaging was performed in 10 asthmatics and 10 healthy subjects. Seven asthmatics had ventilation defects distributed throughout the lungs compared with none of the normal subjects. These ventilation defects were more numerous and larger in the two symptomatic asthmatics who had abnormal spirometry. Ventilation defects studied over time demonstrated no change in appearance over 30–60 minutes. One asthmatic subject was studied twice in a three‐week period and had ventilation defects which resolved and appeared in that time. This same subject was studied before and after bronchodilator therapy, and all ventilation defects resolved after therapy. Hyperpolarized 3He lung imaging can detect the small, reversible ventilation defects that characterize asthma. The ability to visualize lung ventilation offers a direct method of assessing asthmatics and their response to therapy. J. Magn. Reson. Imaging 2001;13:378–384.

Functional MRI of the lung using hyperpolarized 3‐helium gas

Lung imaging has traditionally relied on x‐ray methods, since proton MRI is limited to some extent by low proton density in the lung parenchyma and static field inhomogeneities in the chest. The relatively recent introduction of MRI of hyperpolarized noble gases has led to a rapidly evolving field of pulmonary MRI, revealing functional information of the lungs, which were hitherto unattainable. This review article briefly describes the physical background of the technology, and subsequently focuses on its clinical applications. Four different techniques that have been used in various human investigations are discussed: ventilation distribution, ventilation dynamics, and small airway evaluation using diffusion imaging and oxygen uptake assessment. J. Magn. Reson. Imaging 2004;20:540–554.

Dynamic spiral MRI of pulmonary gas flow using hyperpolarized 3He: Preliminary studies in healthy and diseased lungs

An optimized interleaved‐spiral pulse sequence, providing high spatial and temporal resolution, was developed for dynamic imaging of pulmonary ventilation with hyperpolarized 3He, and tested in healthy volunteers and patients with lung disease. Off‐resonance artifacts were minimized by using a short data‐sampling period per interleaf, and gradient‐fidelity errors were compensated for by using measured k‐space trajectories for image reconstruction. A nonsequential acquisition order was implemented to improve image quality during periods of rapid signal change, such as early inspiration. Using a sliding‐window reconstruction, cine‐movies with a frame rate of 100 images per second were generated. Dynamic images demonstrating minimal susceptibility‐ and motion‐induced artifacts were obtained in sagittal, coronal, and axial orientations. The pulse sequence had the flexibility to image multiple slices almost simultaneously. Our initial experience in healthy volunteers and subjects with lung pathology demonstrated the potential of this new tool for capturing the features of lung gas‐flow dynamics. Magn Reson Med 4:667–677, 2001.

Noninvasive medical imaging system and method for the identification and 3-D display of atherosclerosis and the like

There is disclosed an image processing, pattern recognition and computer graphics system and method for the noninvasive identification and evaluation of atheroscelerosis using multidimensional Magnetic Resonance Imaging (MRI). Functional information, such as plaque tissue type, is combined with structure information, represented by the 3-D vessel and plaque structure, into a single composite 3-D display. The system and method is performed with the application of unsupervised pattern recognition techniques and rapid 3-D display methods appropriate to the simultaneous display of multiple data classes. The results are a high information content display which aids in the diagnosis and analysis of the atherosclerotic disease process, and permits detailed and quantitative studies to assess the effectiveness of therapies, such as drug, exercise and dietary regimens.

White matter abnormalities in mobility-impaired older persons

Objective: To investigate the relationship between white matter abnormalities and impairment of gait and balance in older persons. Methods: Quantitative MRI was used to evaluate the brain tissue compartments of 28 older individuals separated into normal and impaired groups on the basis of mobility performance testing using the Short Physical Performance Battery. In addition, individuals were tested on six indices of gait and balance. For imaging data, segmentation of intracranial volume into four tissue classes was performed using template-driven segmentation, in which signal-intensity–based statistical tissue classification is refined using a digital brain atlas as anatomic template. Results: Both decreased white matter volume, which was age-related, and increased white matter signal abnormalities, which were not age-related, were observed in the mobility-impaired group compared with the control subjects. The average volume of white matter signal abnormalities for impaired individuals was nearly double that of control subjects. Conclusions: This cross-sectional study suggests that decreased white matter volume is age-related, whereas increased white matter signal abnormalities are most likely to occur as a result of disease. Both of these changes are independently associated with impaired mobility in older persons and therefore likely to be additive factors of motor disability.

Magnetic resonance imaging of the body trunk using a single-slab, 3-dimensional, T2-weighted turbo-spin-echo sequence with high sampling efficiency (SPACE) for high spatial resolution imaging: Initial clinical experiences

Purpose:The authors conducted a clinical evaluation of single-slab, 3-dimensional, T2-weighted turbo-spin-echo (TSE) with high sampling efficiency (SPACE) for high isotropic body imaging with large field-of-view (FoV). Materials and Methods:Fifty patients were examined in clinical routine with SPACE (regions of interest: pelvis n = 30, lower spine n = 12, upper spine n = 6, extremities n = 4) at 1.5 T. For achieving a high sampling efficiency, parallel imaging, high turbofactor, and magnetization restore pulses were used. In contrast to a conventional TSE imaging technique with constant flip angle refocusing, the refocusing pulse train of the SPACE sequence consists of variable flip angle radiofrequency pulses along the echo train. Results:Signal-to-noise ratio and contrast-to-noise ratio of SPACE images were of sufficient diagnostic value. The possibility of image reconstruction in multiple planes was of clinical relevance in all cases and simplified data analysis. Conclusion:The achievement of 3-dimensional, T2-weighted TSE magnetic resonance imaging with isotropic and high spatial resolution and interactive 3-dimensional visualization essentially improve the diagnostic potential of magnetic resonance imaging.

Hyperpolarized 129Xe MRI of the human lung

By permitting direct visualization of the airspaces of the lung, magnetic resonance imaging (MRI) using hyperpolarized gases provides unique strategies for evaluating pulmonary structure and function. Although the vast majority of research in humans has been performed using hyperpolarized 3He, recent contraction in the supply of 3He and consequent increases in price have turned attention to the alternative agent, hyperpolarized 129Xe. Compared to 3He, 129Xe yields reduced signal due to its smaller magnetic moment. Nonetheless, taking advantage of advances in gas‐polarization technology, recent studies in humans using techniques for measuring ventilation, diffusion, and partial pressure of oxygen have demonstrated results for hyperpolarized 129Xe comparable to those previously demonstrated using hyperpolarized 3He. In addition, xenon has the advantage of readily dissolving in lung tissue and blood following inhalation, which makes hyperpolarized 129Xe particularly attractive for exploring certain characteristics of lung function, such as gas exchange and uptake, which cannot be accessed using 3He. Preliminary results from methods for imaging 129Xe dissolved in the human lung suggest that these approaches will provide new opportunities for quantifying relationships among gas delivery, exchange, and transport, and thus show substantial potential to broaden our understanding of lung disease. Finally, recent changes in the commercial landscape of the hyperpolarized‐gas field now make it possible for this innovative technology to move beyond the research laboratory. J. Magn. Reson. Imaging 2013;37:313–331.

Simultaneous magnetic resonance imaging of ventilation distribution and gas uptake in the human lung using hyperpolarized xenon-129

Despite a myriad of technical advances in medical imaging, as well as the growing need to address the global impact of pulmonary diseases, such as asthma and chronic obstructive pulmonary disease, on health and quality of life, it remains challenging to obtain in vivo regional depiction and quantification of the most basic physiological functions of the lung—gas delivery to the airspaces and gas uptake by the lung parenchyma and blood—in a manner suitable for routine application in humans. We report a method based on MRI of hyperpolarized xenon-129 that permits simultaneous observation of the 3D distributions of ventilation (gas delivery) and gas uptake, as well as quantification of regional gas uptake based on the associated ventilation. Subjects with lung disease showed variations in gas uptake that differed from those in ventilation in many regions, suggesting that gas uptake as measured by this technique reflects such features as underlying pathological alterations of lung tissue or of local blood flow. Furthermore, the ratio of the signal associated with gas uptake to that associated with ventilation was substantially altered in subjects with lung disease compared with healthy subjects. This MRI-based method provides a way to quantify relationships among gas delivery, exchange, and transport, and appears to have significant potential to provide more insight into lung disease.

Probing lung physiology with xenon polarization transfer contrast (XTC)

One of the major goals of hyperpolarized‐gas MRI has been to obtain 129Xe dissolved‐phase images in humans. So far, this goal has remained elusive, mainly due to the low concentration of xenon that dissolves in tissue. A method is proposed and demonstrated in dogs that allows information about the dissolved phase to be obtained by imaging the gas phase following the application of a series of RF pulses that selectively destroy the longitudinal magnetization of xenon dissolved in the lung parenchyma. During the delay time between consecutive RF pulses, the depolarized xenon rapidly exchanges with the gas phase, thus lowering the gas polarization. It is demonstrated that the resulting contrast in the 129Xe gas image provides information about the local tissue density. It is further argued that minor pulse‐sequence modifications may provide information about the alveolar surface area or lung perfusion. Magn Reson Med 44:349–357, 2000.