Magnetic Resonance Imaging (MRI) is unique on its ability to provide exquisite images of the human anatomy within acceptable imaging times, without the use of ionizing radiation and in vivo. Since its inception in ca. 1973, MRI has continuously made tremendous strides towards providing metabolic and physiological information that could be used for better diagnose and monitor disease. There are, however, some inherent limitations for conventional, proton-based, MRI where the information provided by other NMR-active nuclei could be of tremendous and unique value. Specifically, conversion of water-based MRI signal into physiologically relevant parameters is indirect and often not specific to a given pathology. As a result, assessment of pathological conditions in a quantitative fashion using water-based MRI requires the use of multiple pulse sequences, which eventually leads to workflow complexity and long examination times. Several, physiologically important, nuclei are NMR active and are, therefore, conceptually suitable for MRI. Capitalizing on such potential, however, requires close scrutiny of the methodological challenges imposed by the NMR properties for the nuclei of interest. Most NMR active nuclei have physiological concentrations that are several orders of magnitude lower than water. In addition, their NMR sensitivity is also lower and, more often than not, their relaxation properties pose challenges that cannot be easily overcome using conventional pulse sequence schemes. Fortunately, in recent years, many efficient approaches have been developed for the sole purpose of imaging non-proton nuclei (1-3). Sodium MRI, in particular, has received a lot of attention because of the unique role of the sodium ion in mammalian physiology and its relatively high NMR sensitivity (relative to other NMR active nuclei). In this presentation, the challenges and solutions associated with providing non-proton MRI images of adequate resolution and signal-to-noise ratio (SNR) for a variety of NMR-active nuclei of high physiological relevance will be presented. Implementations of the corresponding methodologies, on different scanner platforms, will be discussed and their use on clinically relevant applications illustrated (4-9).

The overall outline of the presentation is as follows:

1. General Considerations: The Curie Law.

2. Equilibrium Magnetization.

3. The sodium nucleus.

4. Quadrupolar dynamics.

5. Relaxation constraints.

6. Data acquisition requirements.

7. Efficient data acquisition schemes: acquisition and reconstruction.

8. The role of the readout time.

9. Sample density and corrections.

10. Multiple quantum sodium MRI.

11. Examples: Ischemia, Neoplasia, Bipolar Disorder.

12. The Fluorine (19F) Nucleus.

13. Relaxation properties.

14. Imaging constraints.

15. 19F Existing agents.

16. Examples.

After completion of this course the attendees should be able to:

1.- Identify the conditions that must be met to successfully implement data acquisition techniques for physiologically-relevant, non-water-based, nuclei.

2.- Identify the techniques that can be deployed to address the data acquisition constraints imposed by the NMR properties of several nuclei.

3.- Recognize the advantages of different hardware platforms during the implementation of non-proton MRI sequences. This includes RF coil designs as well as high field strength scanners.

4.- Have a conceptual understanding of the required steps for image reconstruction of non-proton MRI data sets, including sample density correction, off-resonance correction and B1 correction.

5.- Identify the clinical scenarios where non-proton MRI could provide clinically relevant information that cannot be obtained with conventional MRI.

6.- Recognize the limitations and potential interpretation confounds of non-proton MRI applications such as sodium MRI and 19F MRI in the context of important pathological conditions.

1. Shen GX, Boada FE, Thulborn KR. Dual-frequency, dual-quadrature, birdcage RF coil design with identical B1 pattern for sodium and proton imaging of the human brain at 1.5 T. Magn Reson Med. 1997;38(5):717-25. Epub 1997/11/14. PubMed PMID: 9358445.

2. Boada FE, Shen GX, Chang SY, Thulborn KR. Spectrally weighted twisted projection imaging: reducing T2 signal attenuation effects in fast three-dimensional sodium imaging. Magn Reson Med. 1997;38(6):1022-8. Epub 1997/12/24. PubMed PMID: 9402205.

3. Boada FE, Gillen JS, Shen GX, Chang SY, Thulborn KR. Fast three dimensional sodium imaging. Magn Reson Med. 1997;37(5):706-15. Epub 1997/05/01. PubMed PMID: 9126944.

4. Boada FE, Tanase C, Davis D, Walter K, Torres-Trejo A, Couce M, Hamilton R, Kondziolka D, Bartynski W, Lieberman F. Non-invasive assessment of tumor proliferation using triple quantum filtered 23/Na MRI: technical challenges and solutions. Conf Proc IEEE Eng Med Biol Soc. 2004;7:5238-41. Epub 2007/02/03. doi: 10.1109/IEMBS.2004.1404464. PubMed PMID: 17271521.

5. LaVerde G, Nemoto E, Jungreis CA, Tanase C, Boada FE. Serial triple quantum sodium MRI during non-human primate focal brain ischemia. Magn Reson Med. 2007;57(1):201-5. Epub 2006/12/28. doi: 10.1002/mrm.21087. PubMed PMID: 17191243.

6. Hancu I, Boada FE, Shen GX. Three-dimensional triple-quantum-filtered (23)Na imaging of in vivo human brain. Magn Reson Med. 1999;42(6):1146-54. Epub 1999/11/26. doi: 10.1002/(SICI)1522-2594(199912)42:6<1146::AID-MRM20>3.0.CO;2-S [pii]. PubMed PMID: 10571937.

7. Constantinides CD, Kraitchman DL, O'Brien KO, Boada FE, Gillen J, Bottomley PA. Noninvasive quantification of total sodium concentrations in acute reperfused myocardial infarction using 23Na MRI. Magn Reson Med. 2001;46(6):1144-51. Epub 2001/12/18. doi: 10.1002/mrm.1311 [pii]. PubMed PMID: 11746581.

8. Constantinides CD, Gillen JS, Boada FE, Pomper MG, Bottomley PA. Human skeletal muscle: sodium MR imaging and quantification-potential applications in exercise and disease. Radiology. 2000;216(2):559-68. Epub 2000/08/05. PubMed PMID: 10924586.

9. Jones SC, Kharlamov A, Yanovski B, Kim DK, Easley KA, Yushmanov VE, Ziolko SK, Boada FE. Stroke onset time using sodium MRI in rat focal cerebral ischemia. Stroke. 2006;37(3):883-8. Epub 2006/01/21. doi: 01.STR.0000198845.79254.0f [pii]10.1161/01.STR.0000198845.79254.0f. PubMed PMID: 16424376.