Mri

The ability to obtain images with resolutions approaching that of a single cell (< 50 ^m) makes MRI particularly well suited for noninvasive studies of stem cell transplants. MRI has become a well-established clinical tool for the noninvasive imaging of anatomical changes in many organ systems. Similarly, highresolution magnetic resonance microscopy (MRM) has also made tremendous strides forward due to advances in magnet technology. MRM images can now be achieved routinely with resolutions well below 100 microns (Benveniste and Blackband, 2006; Maronpot et al., 2004; Ciobanu and Pennington, 2004; Ciobanu et al., 2002). MRM brings not only new capabilities, but also technical challenges to the field of MRI (Tyszka et al., 2005; Pirko et al., 2005). It is rare that MR images are acquired with isotropic resolutions less than 10 ^m and it has been previously estimated that the fundamental limitation to spatial resolution is on the order of 1 ^m (Tyszka et al., 2005). In practice, the achievable imaging resolution will be limited by available gradient strength and sensitivity that is achievable in a given amount of time.

A number of strategies have been employed to improve MR sensitivity by increasing signal to noise. This can be achieved by increasing the magnitude of the induced nuclear magnetism or the efficiency of signal detection (Beck et al., 2002). With the advent of high-field, whole body magnets (3-9.4 T) and ultrahigh field animal imagers (11-21 T) equipped with high performance gradients and phase array RF capabilities, the potential for increased sensitivity can be realized in vivo, but it is still unknown as to whether these technological improvements directly translate into an enhanced ability to perform molecular and cellular imaging. Furthermore, it is widely recognized that numerous MR contrast mechanisms are dependent upon magnetic field strength, offering opportunities for enhanced and emergent contrast mechanisms that could be exploited at high fields for cellular imaging. Figure 6.2 illustrates the great potential of MR microscopy at high fields, namely 21.1 T. In this example, the magnetic field-dependent, susceptibility-weighted contrast afforded by a gradient-recall echo acquisition provides excellent delineation of neuroanatomical structures in an excised, perfusion-fixed C57BL/6J mouse brain while also providing a high spatial resolution of 18 x 18 x 35 ^m3 (Fu et al., 2005). To achieve this level of detail, it is usually necessary to image samples ex vivo using optimized MRM coils and to acquire data over a long acquisition period. On the other hand, in vivo imaging is complicated by the need to image internal structures and by limitations in the total imaging time available. For instance, the achievable resolution in an animal experiment is constrained by the need to maintain a physiologically relevant status, which limits the imaging time, methods of restraint, and exposure to anesthesia.

Working at higher fields also does not come without significant technological challenges. Proton relaxation times (T\, T2, and T2) change in a direction that is not favorable (longer Tu shorter T2s) for tissue imaging. RF penetration decreases, and both macroscopic and microscopic magnetic susceptibility variations in tissue cause intrinsic T2* values to be much lower. These alternations in

Figure 6.2. A Gradient-recall echo images of an excised, perfusion-fixed C57BL/6J mouse brain in a 10 mm linear birdcage recorded at 21.1 T. A true 3D gradient-recall echo dataset was acquired at a resolution of 18 x 18 x 35 |xm in 29 h using the following imaging parameters: matrix = 1024 x 512 x 256; TE/TR = 12.5/100 ms; averages = 8; FOV = 1.9 x 0.92 x 0.8 cm; bandwidth = 100 kHz; 50° tip angle = 25 |xs hard pulse. A series of 2D multi-slice gradient-recall echo images (40 x 40 x 250 |xm resolution) were acquired to sample using the following parameters: matrix = 230 x 200; TE = 4.5-24.5 ms; TR = 1.5 s; averages = 2; FOV = 9.2 x 8.0 mm; slice thickness = 250 |xm; number of slices = 17; 90° pulse = 2 ms three-lobe sinc pulse; and imaging time per dataset = 10 min. B The ultra-wide bore 900 MHz superconducting NMR magnet at the National High Magnetic Field Laboratory in Tallahassee, Florida. This cryostat stands 4.9 m tall, weighs over 13,600 kg and has a stored energy of 38 MJ containing 2,400 L liquid helium at atmospheric pressure. With the room temperature shim set in place the inner diameter is 89 mm. Reprinted from Fu et al. (2005) with permission from Elsevier.

Figure 6.2. A Gradient-recall echo images of an excised, perfusion-fixed C57BL/6J mouse brain in a 10 mm linear birdcage recorded at 21.1 T. A true 3D gradient-recall echo dataset was acquired at a resolution of 18 x 18 x 35 |xm in 29 h using the following imaging parameters: matrix = 1024 x 512 x 256; TE/TR = 12.5/100 ms; averages = 8; FOV = 1.9 x 0.92 x 0.8 cm; bandwidth = 100 kHz; 50° tip angle = 25 |xs hard pulse. A series of 2D multi-slice gradient-recall echo images (40 x 40 x 250 |xm resolution) were acquired to sample using the following parameters: matrix = 230 x 200; TE = 4.5-24.5 ms; TR = 1.5 s; averages = 2; FOV = 9.2 x 8.0 mm; slice thickness = 250 |xm; number of slices = 17; 90° pulse = 2 ms three-lobe sinc pulse; and imaging time per dataset = 10 min. B The ultra-wide bore 900 MHz superconducting NMR magnet at the National High Magnetic Field Laboratory in Tallahassee, Florida. This cryostat stands 4.9 m tall, weighs over 13,600 kg and has a stored energy of 38 MJ containing 2,400 L liquid helium at atmospheric pressure. With the room temperature shim set in place the inner diameter is 89 mm. Reprinted from Fu et al. (2005) with permission from Elsevier.

contrast mechanisms and RF performance can be utilized to provide increased image information at high fields, but they require optimized acquisition parameters, pulse sequence design, and coil technology to take full advantage of this information while maintaining accurate anatomical representations.

Stem cells located within their niche do not have endogenous MR contrast. For stem cells to be visualized by MR, stem cells need to be labeled by either

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