Biomedical Applications of Nuclear Magnetic Resonance (NMR)

1. Introduction Nuclear Magnetic Resonance (NMR) is a phenomenon discovered about 60 years ago.  Since then it has been used for many biomedical engineering applications from medical imaging to the molecular and tissue structure and function.  Using NMR one can measure NMR spectra, diffusion coefficients, electric current, flow velocity, temperature, blood oxygenation, brain function, muscle metabolism, reaction rates and much much more. The IBBME is the proud owner of a TeachSpin PS1-A NMR spectrometer.  This is a device that can (in its present state) demonstrate many basic features of NMR but little else. BME 1450 Introduction to NMR

2. Problem • Identify a biomedical application of NMR of interest to your group and find out: • What is problem that NMR helps to solve? • How is NMR is used to solve this problem in theory? • How is NMR is used to solve this problem in practice? • What are the specifications and price of the NMR equipment required? • Why are the above specifications important? • Could the TeachSpin PS1-A NMR spectrometer be modified (if necessary) to meet these specifications?  If so how and if not why not. BME 1450 Introduction to NMR

3. www.ecf.utoronto.ca/~joy BME1450 Intro to NMRNovember 2002 The Basics The Details

4. Example of MRI Images of the Head • Bone and air are invisible. • Fat and marrow are bright. • CSF and muscle are dark. • Blood vessels are bright. • Grey matter is darker than white matter. BME 1450 Introduction to NMR

5. MRI Imagers GE 1.5 T Signa Imager • GE 0.2T Profile/i imager BME 1450 Introduction to NMR

6. www.ecf.utoronto.ca/~joy BME1450 Intro to NMRNovember 2002 The Basics The Details

7. The Details J and  Magnetic Resonance (MR) • An object in a magnetic field B0 will become magnetized and develop a net Magnetization, M. • Most of M arises from the orbital electrons but a small part is the Nuclear Magnetization. • The nucleus has a magnetic dipole moment, , and angular momentum,J. • ||/|J| = , the gyromagnetic ratio. • For Hydrogen  = 43 MHz/T.  Magnetization is “magnetic dipole moment per unit volume”. BME 1450 Introduction to NMR

8. The Details Z B0 J or  Y |B0|••t X MR: Precession • The 1.5T magnetic, B0 field of the MR Imager makes the Hydrogen Nuclei precess around it. • The precession rate,, is the Larmor frequency. • fL =  B0 = 43*1.5 = 64MHz for Hydrogen in water • +- 300Hz in other molecules.

9. The Details Receive Coil Z B0 J or  or M Y |B0|••t X Summary • The magnetization,M, is the density of nuclear magnetic dipole moments. • If you tip M away from B0 it will precess, at frequency B0, producing a measurable RF magnetic field. • The precessing M will induce an RF voltage in the receive coil if it is not perpendicular to B0 • This signal is called the FID (free induction decay)

10. The Details Z |B1|••t B0 J or  or M Y |B0|••t B1 |B0|••t X B0 MR Excitation pulse Excitation coils B1 • You can tip M by applying a circularly polarized RF magnetic field pulse, B1, to the sample. • If B1 is at the Larmor frequency, B0you get this. • M is now precessing about two magnetic fields. • B1 is effective because it tracks M.

11. The Details The Rotating Frame • It is much easier to visualize all this if you observe it from a frame of reference which is rotating at the Larmor frequency, fL=B0. • B1 appears motionless in this rotating frame and B0effectively disappears and… • During the excitation pulse, M precesses only about B1 at frequency B1!! Z |B1|••t MZ M Y’ My’ Rotating Frame B1 X’ BME 1450 Introduction to NMR

12. The Details The Rotating Frame • When the excitation pulse is over, M is stationary in the rotating frame. • In the Lab frame, however, it is still precessing. Z MZ M Y’ My’ Rotating Frame X’ BME 1450 Introduction to NMR

13. The Details M M(t) 0 | | t T 2 Magnitisation Relaxation (Decay) • The transverse (M) and longitudinal (M||) components of the magnitization change with time. • Two relaxation times T1 (longitudinal) and T2 (transverse). T1 T2 BME 1450 Introduction to NMR

14. The Details 10ms Rotation by Q degrees Flip angle RF Excitation Time FID 100 ms 5ms << T2 !!! Basic NMR Pulse Sequence What flip angle gives biggest FID???? BME 1450 Introduction to NMR

15. NMR Instrumentation The Main Magnet The sample • Ideally B0 is uniform to 1or 2 ppm • In the teach spin magnet it is not as good • B0 non-uniformity over a sample means that it produces a range of RF frequencies around gBomean • FID decay in T2* < T2 • Spectral lines become blurred Move the sample holder to the most uniform spot BME 1450 Introduction to NMR

16. NMR Instrumentation The CP Spin echo sequence This sequence overcomes the T2*non-uniformity effects allowing T2 to be measured. 90 degrees Flip 180 degrees Flip RF Excitation FID 30 ms BME 1450 Introduction to NMR

17. NMR Instrumentation Why CP Spin echo makes an echo • This animation shows the rotating frame coordinates. • The two RF pulses (p/2 & p) are along the rotating x axis. • The arrows are magnetisation at various points in the sample. • Most arrows precess faster or slower than the rotating frame. http://www.physics.monash.edu.au/~chrisn/espin.html BME 1450 Introduction to NMR

18. NMR Instrumentation The mixer • The FID is amplified and then shifted down in frequency in the “mixer”. mixer Mixer output DC X FID ~15 MHz time RF oscillator 15 MHz

19. NMR Instrumentation An FID and four Echos FID Scope sweep 10ms / div Four Echos BME 1450 Introduction to NMR