Hyperpolarized ³He MRI of mouse lung

Abstract

Hyperpolarized 3 He images of mouse lung are presented. Ventilation images and measurements of 3 He apparent diffusion coefficient (ADC) are reported in healthy mice, and preliminary studies of emphysema and lung cancer in mice are described using these techniques. The design and operation of an electronically controlled small-animal ventilator to deliver the hyperpolarized gas and control animal respiration are described. Images are acquired using an asymmetric gradient echo imaging method to enhance the signal-to-noise ratio of the rapidly diffusing 3 He. In mice with elastase-induced emphysema, the whole-lung average ADC is greater by approximately 25%, a statistically significant difference, compared to healthy animals. By contrast, mice exposed to cigarette smoke for up to 12 months reveal no statistically relevant increases in ADC, although emphysema was not confirmed in these mice. Conventional magnetic resonance imaging (MRI), which detects the 1 H resonance signal from tissue water, is a powerful imaging modality for characterizing a wide variety of organs. However, lungs present a unique challenge for MRI and 1 H studies of lung suffer from a number of factors, including low water content within the lung and short T 2 and T 2 * relaxation times caused by variations in magnetic susceptibility associated with the many air-tissue interfaces of the alveoli and bronchioles that reduce sensitivity and can limit available information. By contrast, hyperpolarized (HP) 3 He MRI detects helium gas introduced directly into the gas-exchange spaces of the lung. The imaging of hyperpolarized gas enables studies of both lung structure and function that are not possible with other methods. Previous studies of human and animal lungs have demonstrated the utility of hyperpolarized 3 He magnetic resonance lung imaging techniques and have proven particularly effective at detecting and tracking ventilation defects. These techniques can, therefore, be extremely useful in studying diseases of the lung that are characterized by such defects (1-7). In addition, in vivo measurements of the 3 He apparent diffusion coefficient (ADC) in emphysema have effectively quantified lung structure by measuring its restrictive effects on the motion of 3 He gas atoms (1), providing detection and longitudinal tracking of changes in microarchitecture resulting from disease destruction of alveolar walls. HP 3 He lung MRI studies of emphysema in humans (1-5) and a variety of animals, including pigs, dogs, guinea pigs, and rats, have produced very promising results (6 -10). However, no applications of hyperpolarized 3 He magnetic resonance imaging to the mouse have been reported.Mouse models of disease are widely used in the medical research community and the availability of transgenic mouse models has greatly expanded the role of the mouse in preclinical research. HP 3 He MR imaging methods offer a potential means for studying a variety of lung disease models, including emphysema and lung cancer in the mouse. However, the small size of the mouse...

3He MRI in mouse models of asthma

“…Compared to the ϳ2-ml tidal volume of the rat, its ϳ200-l tidal volume makes the mouse challenging to ventilate and image with HP 3 He. The first HP 3 He MRI of a mouse was demonstrated by Dugas et al (9), who used an asymmetric readout gradient recalled echo (GRE) multislice sequence with 1.2 ms echo time to achieve a resolution of 0.25 ϫ 0.25 ϫ 3 mm 3 . 3 He imaging of mice was subsequently demonstrated by Haczku et al (10), who employed a conventional single-slice GRE sequence with TE ϭ 3.4 ms to achieve similar (0.24 ϫ 0.24 ϫ 3 mm 3 ) resolution images in a mouse model of asthma.…”

Small Animal Imaging with Hyperpolarized 129Xe Magnetic Resonance

“…Mouse models of pulmonary diseases, such as emphysema, 33,34 asthma, 35,36 inflammation, 37 and cancer, 33,38 have been employed to assess functional or structural changes using HP 3 He MRI, where the ventilation property and apparent diffusion coefficient are measured. On the other hand, the application of HP 129 Xe to mouse models has been limited to our studies of emphysema 30,32,[39][40][41] and cancer.…”

Achieving high spatial resolution and high SNR in low-field MRI of hyperpolarised gases with Slow Low Angle SHot

“…Similar resolutions can be obtained in the read directions as well, provided that ultra-fast (sub-ms) acquisition is performed (Eq. 10), but this is not normally done except in lung MRI of small animals where high resolution is mandatory [25]. For a set read time, the achievable resolution in the image reconstructed from the second echo is indeed coarser, by an amount of order √ 3 (Eq.…”