A gated-7T MRI technique for tracking lung tumor development and progression in mice after exposure to low doses of ionizing radiation

Abstract

A gated-7T magnetic resonance imaging (MRI) application is described that can accurately and efficiently measure the size of in vivo mouse lung tumors from ∼0.1 mm(3) to >4 mm(3). This MRI approach fills a void in radiation research because the technique can be used to noninvasively measure the growth rate of lung tumors in large numbers of mice that have been irradiated with low doses (<50 mGy) without the additional radiation exposure associated with planar X ray, CT or PET imaging. High quality, high resolution, reproducible images of the mouse thorax were obtained in ∼20 min using: (1) a Bruker 7T micro-MRI scanner equipped with a 60 mm inner diameter gradient insert capable of generating a maximum gradient of 1000 mT/m; (2) a 35 mm inner diameter quadrature radiofrequency volume coil; and (3) an electrocardiogram and respiratory gated Fast Low Angle Shot (FLASH) pulse sequence. The images had an in-plane image resolution of 98 μm and a 0.5 mm slice thickness. Tumor diameter measured by MRI was highly correlated (R(2) = 0.97) with the tumor diameter measured by electronic calipers. Data generated with an initiation/promotion mouse model of lung carcinogenesis and this MRI technique demonstrated that mice exposed to 4 weekly fractions of 10, 30 or 50 mGy of CT radiation had the same lung tumor growth rate as that measured in sham-irradiated mice. In summary, this high-field, double-gated MRI approach is an efficient way of quantitatively tracking lung tumor development and progression after exposure to low doses of ionizing radiation.

FIG. 1

A representative double-gated 7T MRI image of a bitransgenic mouse thorax illustrating our sub-millimeter spatial resolution. Although the smallest tumor in this image has a measured diameter of 0.33 mm, compact tumors with a diameter of ~0.2 mm could be identified, tracked, and their volume determined over the period from 3–9 months postirradiation.

FIG. 2

Contoured tumors from an MC+BHT mouse 9 months after 4 fractions of 30 mGy. Tumor volume was measured from the MR images or was calculated from the major and minor diameters using the equation 0.5(major axis)(minor axis)² or the equation for the volume of an ellipsoid with all 3 dimensions obtained from the images. Tumor 1: MRI volume = 1.13 mm³; 0.5bc² = 0.64 mm³; ellipsoid = 0.69 mm³. Tumor 2: MRI volume = 2.09 mm³; 0.5bc² = 1.44 mm³; ellipsoid = 1.67 mm³.

FIG. 3

MR lung images from MC+BHT mice demonstrating the capability to longitudinally assess in vivo tumor growth: (a) unirradiated control; (b) irradiated with 4 fractions of 30 mGy; (c) irradiated with 4 fractions of 50 mGy.

FIG. 4

A comparison of lung tumor diameters at 9 months postirradiation measured in vivo using our double-gated 7T MRI technique and ex vivo using electronic calipers after excising the lungs. The data are for tumors from the bitransgenic (closed diamonds) and NNK (open triangles) mouse models.