Molecular imaging is a type of medical imaging that provides detailed pictures of what is happening inside the body at the molecular and cellular level (SNMMI, 2016) and offers insight into body functioning and biological/chemical processes. The ability to image fine molecular level paves the way for earlier detection and treatment of diseases and basic pharmaceutical development.

Animal molecular imaging is molecular imaging of animals in vivo for research purposes. Multiple imaging modalities, including micro-computed tomography (CT), micro-single photon emission computed tomography (SPECT), micro-positron emission tomography (PET), micro-magnetic resonance imaging (MRI), micro-ultrasonography (US), and various optical techniques using fluorescence and bioluminescence, are available for small animal imaging (Youn & Hong, 2012). Figure 1 (Marketsandmarkets, 2015) illustrates the global preclinical imaging system market, by modality, 2014 vs. 2019 forecast. Molecular imaging is typically multimodal approach using PET/MRI/CT/SPECT to image the molecular activities in vivo.

MRI imaging provides very high spatial resolution and is very adept at morphological imaging and functional imaging (Molecular imaging, 2016). MRI imaging is non-invasive, making it possible for repetitive observations. In some cases, contrast can be used in MRI to provide more information. MRI can be combined with other modalities to identify the specific molecular activity. MRI does have disadvantages. Sensitivity or MRI signal is limiting compared with other modalities due to the small difference in the population of atoms between the high energy state and the low energy state. One way to improve sensitivity of MRI imaging is to increase imaging field strength. Another way is hyperpolarization i.e. increase the intrinsic magnetization of the sample.

The primary role of MRI in Animal Molecular Imaging is to provide high resolution anatomical imaging. SNR varies linearly with field strength (B 0). The higher SNR can be exploited to improve spatial resolution or to reduce imaging time. The performance improvements at higher and higher field strength are not without challenges and limitations. There are other roles that MRI can have in Animal Molecular Imaging. These other applications yield different optimum field strength choices. So a tradeoff is required to determine what field strengths should be chosen for a given pre-clinical imaging site. Specific contrast protocols can have specific optimum field strengths for various reasons. Translational studies from preclinical to clinical applications need to consider the ability to do experiments at FDA approved clinical field strengths.

Higher field and larger bore diameter will increase the system cost and siting footprint greatly. The system cost and siting footprint will also determine the highest realizable field strength, irrespective of other technical issues.

Characterizing MRI imaging field strength:

The definitions of low-field and high field MRI have been changing over the last three decades and there is no official dividing line. In the early days of MRI, field strengths of 0.2T or below were considered low field and high fields were anything greater than or equal to 1.0T (Elster, 2015). The MRI industry has shifted toward higher and higher fields and hence the definition of low field and high field has also changed.

For Clinical MRI imaging, the imaging field strength can be characterized as the following (Elster, 2015):

· Ultra high field -> above 7.0T. Ultra High Frequency (>7T) - Note that the terminology is based on classification of radiofrequency (RF) bands. The frequency range 300 MHz to 3 GHz is defined as ultra high frequency (UHF) (Ultra high frequency, 2016). The hydrogen nucleus resonance frequency at 7 T is ~300 MHz, ie, in the UHF band. Therefore, above 7T and up to 70 T is defined as ultrahigh field (UHF).

· Very high field -> 3.0T to 7.0T

· High field -> 1.0T to 3.0T

· Mid-field -> 0.3T to 1.0T

· Low field -> below 0.3T

Although some might argue, MRI for Animal Molecular Imaging is more advanced and requires higher imaging performance than clinical MRI. The practical reality is that the smaller bore magnets can have higher field strengths more economically. The MR imaging field strength for Animal Molecular Imaging can be characterized as the following:

· High field for Animal Molecular imaging -> above 4.7T. This body of work offered certain advantages and ultimately led to the development of instruments operating at higher and higher magnetic fields, such as 7.0T, 9.4T, 11.7T, 14T, 16.4T, and 17 T.

· Low Field for Animal Molecular Imaging -> 1.5T to 4.7T. Commonly available field strength includes 4.7T, 3.0T, and down to 1.5T.

· Very Low Field for Animal Molecular Imaging -> below 1.5T. For example 1.0T or lower.

Application Dependence: The nature of the research will most likely dictate the field strength.

· The perfect choice for translation of results to clinical applications

· Optimum choice for hyperpolarized MRI research

· Provides adequate imaging performance for full body imaging, musculoskeletal studies, cardiovascular research, cancer research & oncology, angiography, and spectroscopy.

· Less artifacts -> much lower chemical Shift and Susceptibility effects

· Less RF issues-> longer wavelengths are less likely to be on the scale of the animal, avoiding dielectric shading.

· Less noise issues due to longer wavelengths.

· SAR is lower.

· Cost is significantly lower both on the equipment side and site construction side, making it more affordable

· Siting: smaller fringe field, can be Cryogen free technology

· SNR is always better at higher field strengths, but SNR at high fields is generally compromised to reduce artifacts from chemical shift and susceptibility.

· Sequences that are signal starved are better run at higher field strengths. For instance, diffusion weighting becomes much less feasible at field strengths below 1.5T. Higher SNR at higher field also benefits spectroscopic imaging, especially for nuclei other than proton such as sodium and phosphorous due to the inherently low concentrations (Le, 2003).

· The longitudinal or spin-lattice relaxation time (T1) is shorter at lower field strength. The prolonged T1 at high field has been successfully employed for better imaging using the time-of-flight (TOF) technique (Le, 2003).

· Very high magnetic fields have been indispensable for achieving important gains in biological information content in MR imaging and spectroscopy techniques for neurobiology studies. MR systems operating at magnetic fields ranging from ~ 11 to 17 Tesla is expected to advance the field further for animal model experiments (Öz, Tkáč, & Uğurbil, 2015).

· MRI systems with Permanent magnets

o Field instability, temperature dependence;

o Generally lack shielded gradient coils;

o Poorer field homogeneity;

o Not suitable for advanced imaging sequences;

o Generally a simpler system

· MRI systems Superconducting wet magnets

o Requires liquid helium fill and re-fills, adding operation costs.

o Heavier magnet. May require floor reinforcement, adding to site construction cost.

o Magnet is bulky. Requires ceiling height of 2.8m (9.2 feet)

o Requires quench pipe installed for safety. Site construction can be very costly, sometimes the total cost of equipment and site construction doubles the cost of equipment;

o Do not support variable field imaging;

o In the event of magnet quenches, significant interruption to operation. Liquid helium fill after quench could be 100K USD, and wait time for liquid helium could be many months. System could be down for a long period of time.

· MRI systems with Superconducting Cryogen-free magnet technology

o No need for liquid helium ever. Reduced operation cost

o No need for quench pipes. Significantly reduced site construction cost.

o Magnet is light and compact. No need for high ceiling or reinforced floor.

o System has very small footprint (the size of a large desk) and can fit in any ordinary rooms.

o Reduced fringe field.

o More compatible with other imaging modalities.

· MRI systems with Superconducting Cryogen-Free variable field magnet technology

o Same advantages as above for Superconducting Cryogen-Free magnet with the addition of

o Customer can have the freedom to operate at a number of different field strengths to best suit each application

o It takes an hour or so to change imaging field strength to a new one

o Easy operation and user friendly

o Customer can change imaging field strength easily and quickly depends on the needs of the experiments.

o 4.7T system can operate at any field strength between 0.1T to 4.7T. 3.0T system can operate at any field strength between 0.1T to 3.0T. (high field 7.0T Cryogen-Free Variable Field systems can operate at any field strength between 0.1T to 7.0T.)

o Easily support clinical translation studies at 1.5T or 3.0T

o Perfect choice to support contrast agent research for different field strengths

o Capable of supporting hyperpolarized research

o Capable of supporting multinuclear imaging.

o Not get stuck with imaging field strength choice and provide flexibility for future research at different field strengths.