1 (D) Pulsed NMR: D_I Inversion Recovery and T1 Relaxation How can T1 be measured experimentally? (Spin Dynamics p.315-318 (1st) p. 295-298 (2nd)) PX388 Magnetic Resonance: Section D: Pulsed NMR 2 D_II Spin Echoes and T2 Relaxation What is the difference between T2 and T2*? (Spin Dynamics p.318-320 (1st) p.298-299 (2nd)) PX388 Magnetic Resonance: Section D: Pulsed NMR 3 How can T2 be measured? (Spin Dynamics p.320-325 (1st edn.) p. 299-303 (2nd edn.)) PX388 Magnetic Resonance: Section D: Pulsed NMR 4 PX388 Magnetic Resonance: Section D: Pulsed NMR 5 PX388 Magnetic Resonance: Section D: Pulsed NMR 6 D_III Fourier Transformation and Frequency-Domain Spectra How is the sign of the resonance offset determined? (Spin Dynamics p.81-82(1), p.73-75 (2)) PX388 Magnetic Resonance: Section D: Pulsed NMR 7 How is a time-domain NMR signal converted into a frequency-domain spectrum? (Spin Dynamics p.101-107 (1st edn.), p.93-102 (2nd edn.)) S() = s(t) exp(i t) dt 0 PX388 Magnetic Resonance: Section D: Pulsed NMR [D7] 8 D_IV Sensitivity What parameters determine the size of a NMR signal? Why does adding together individual FIDs improve the signal to noise? (Spin Dynamics p.9093 (1st edn.), p.86-89 (2nd edn.)) PX388 Magnetic Resonance: Section D: Pulsed NMR 9 D_IV Magnetic Resonance Imaging (MRI) How can a magnetic-field gradient be used to generate a one-dimensional frequency-encoded image? (Spin Dynamics p.325-329 (1st edn.) p. 309-312 (2nd edn.)) PX388 Magnetic Resonance: Section D: Pulsed NMR 10 Btotal = B0 + Bxgrad = ( )k 0 = Bz 0(x) = ( = [D16] [A9] ) [D17] 0 = 0 rf [B2] Set rf = 0(x = 0) 0(x) = [D18] PX388 Magnetic Resonance: Section D: Pulsed NMR 11 How can the imaging technique be extended beyond one dimension? PX388 Magnetic Resonance: Section D: Pulsed NMR 12 How does phase-encoding work? PX388 Magnetic Resonance: Section D: Pulsed NMR 13 How are frequency- and phase-encoding combined to generate a two-dimensional image? (Spin Dynamics p.330-334 (1st edn.) p. 312-315 (2nd edn.)) PX388 Magnetic Resonance: Section D: Pulsed NMR 14 How are two-dimensional slices taken from a three-dimensional object? (Spin Dynamics p.307-309 (2nd edn.)) PX388 Magnetic Resonance: Section D: Pulsed NMR 15 How is a gradient-echo generated? (Spin Dynamics p.306-307 (2nd edn.)) How are differences in relaxation times used to obtain image contrast? PX388 Magnetic Resonance: Section D: Pulsed NMR 16 What is a typical imaging pulse sequence? How can fast MRI experiments (for functional MRI, fMRI) be performed? PX388 Magnetic Resonance: Section D: Pulsed NMR 17 (D) Pulsed NMR: Key Facts Measurement of the longitudinal relaxation time, T1 The signal, a(), in an inversion-recovery pulse sequence: x /2x tacq a() [1 2 exp(/T1)] [D1] For derivation of eq. [D1] see question 1 below. The first zero crossing occurs when zero-crossing = T1 ln{2} [D2] T2 and T2* In an inhomogeneous B0 magnetic field, nuclei in different parts of the sample have different Larmor frequencies, 0. Hence, during time periods of free precession (i.e., when no B1 magnetic field is applied), they evolve at different resonance offsets, 0. The loss of transverse magnetisation for the nuclei in different parts of the sample is characterised by a common transverse relaxation time, T2, according to exp{t / T2}. However, the superposition of signals evolving at different resonance offsets, 0, causes the total signal to be characterised by a faster apparent decay, exp{t / T2*}, corresponding to an apparent transverse relaxation time, T2*, where T2* < T2. Measurement of the transverse relaxation time, T2 For a spin-echo pulse sequence: /2x /2 y /2 tacq The sandwiching of two time periods of free precession between a pulse that inverts the magnetisation has the consequence that evolution under a resonance offset, 0, is refocused, i.e., the signal, a(), is independent of 0, and hence a() is the same for all nuclei in an inhomogeneous B0 magnetic field. (For derivation, see question 2 below) a() exp( / T2) PX388 Magnetic Resonance: Section D: Pulsed NMR [D3] 18 Quadrature detection (determination of the sign of the resonance offset, 0) Experimentally, two NMR signals that are 90 degrees out of phase with respect to each other are obtained by mixing down the one NMR signal from the probe with two rf waveforms with the same rf, but with relative phases, 0 and 90 (see section B). These two NMR signals (free induction decay, FID) FIDcos(t) cos{0 t} exp{t / T2} [D4] FIDsin(t) sin{0 t} exp{t / T2} [D5] constitute the real and imaginary parts of a complex time-domain signal: s(t) = FIDcos(t) + i FIDsin(t) [cos{0 t} + i sin{0 t}] exp{t / T2} s(t) exp([i 0 (1/T2)] t) [D6] Fourier transformation S() = s(t) exp(i t) dt [D7] 0 Fourier transformation of a complex time-domain signal an oscillating and decaying signal that is characterised by a precession frequency (in the rotating frame), 0, and a transverse relaxation time, T2 gives a complex frequency-domain signal, namely an absorptive-mode (real part) and a dispersive-mode (imaginary part) Lorentzian lineshape (see HO_D11) centred at the frequency, 0. The full-width at half-maximum height (FWHMH) of the absorptive-mode Lorentzian lineshape is inversely proportional to T2 (see question 4 below): FWHMH in Hz = 1 / T2 PX388 Magnetic Resonance: Section D: Pulsed NMR [D10] 19 NMR signal strength From Faraday's law, the induced voltage (i.e., the NMR signal) is proportional to the rate of change of the magnetisation with respect to time. Using eq. [A20] NMR Signal N 3 B02 / T [D12] Importantly, NMR is quantitative, i.e., the intensity of a given resonance is proportional to the number of spins in the sample. Improving signal to noise The signal-to-noise (S/N) in a NMR experiment can be improved by repeating the experiment n times and adding the FIDs together. Since the signal is proportional to n, whereas the noise is proportional to √n: S/N n [D13] The repetition time between experiments is determined by T1, since the thermal equilibrium bulk magnetisation must re-establish. Imaging and Spectroscopy Distinction: spatial information is obtained in an imaging experiment by the use of additional applied magnetic field gradients. Most MRI (magnetic resonance imaging) experiments look at 1H (near 100 % natural abundance, and the highest of all NMR isotopes – remember that the NMR signal 3 [D12]) in water and other biofluids. One-Dimensional Imaging In addition to B0 (due to the strong, static superconducting magnet), a magnetic field gradient is applied (NB: x refers to the x position, and is not a multiply sign): Bxgrad = Gx x k [D14] Gx = dBz / dx [D15] PX388 Magnetic Resonance: Section D: Pulsed NMR 20 NB: The additional magnetic field due to a gradient coil is always in the k direction (i.e., the same direction as B0). It is the gradient of the additional magnetic field that can be in any direction – eq. [D15] is for an x gradient. In a one-dimensional imaging experiment, where rf = 0(x = 0) 0(x) = Gx x [D18] i.e., the precession frequency depends on the x position – this is referred to as frequency encoding. Therefore, the signal intensity at a given resonance offset, S(), is proportional to the density of spins at a particular x position, i.e., the one-dimensional frequency-domain spectrum corresponds to the projection of the spin density onto the x axis: S() (x) [D19] Two-Dimensional Imaging A two-dimensional imaging experiment combines frequency encoding under one magnetic field gradient (e.g., Gx) during the acquisition of the NMR signal (during a time period, t2) with phase encoding under an orthogonal field gradient (e.g., Gy) during a time period, , of free evolution that precedes the acquisition of the NMR signal: S(Gx, t2) = exp{i Gy y exp{i Gx x t2 [D24] A two-dimensional data set is obtained by recording a series of NMR signals for different values of the phase-encoding magnetic field gradient (Gy in eq. [D24]). In MRI-speak, this recorded data set is termed k space. 2D Fourier transformation gives a 2D image. Slice selection 2D images are obtained from 3D objects by creating transverse magnetisation by the simultaneous application of a weak (i.e., low nutation frequency 1) rf pulse and a magnetic field gradient (orthogonal to the two gradients in the 2D imaging experiment). PX388 Magnetic Resonance: Section D: Pulsed NMR 21 e.g., under Bzgrad 0(z) = Gz z [D26] The rf pulse only creates transverse magnetisation for those spins on (or close to) resonance, i.e., only a narrow slice in the z direction. The width of the selected slice depends on 1 (magnetisation is excited for |0| ~ |1|). Different slices can be selected by changing rf. Gradient echoes In analogy to a spin-echo experiment, evolution under a resonance offset can be refocused by reversing the sign of the magnetic field gradient: G1 1 = G2 2 [D27] NB: It is not necessary for the two evolution periods, 1 and 2, to be of equal duration Image contrast By exciting transverse magnetisation by a 90x TR 90x TE pulse sequence, a T1 weighted, T2 weighted, or proton density weighted can be obtained (for derivation, see qu. 3 below): Myr(TR, TE) = M0 [1 exp(TR / T1)] exp(TE / T2) [D28] Conventional and fast imaging In a conventional image (duration ~10 minutes), the imaging sequence incorporates a time period after the acquisition of each NMR signal (FID) (corresponding to one value of the phase-encoding magnetic field gradient) in order for the thermal equilibrium bulk magnetisation to re-establish (depending on the T1 relaxation time) before the experiment is repeated. In a fast imaging experiment, time is not left for the thermal equilibrium bulk magnetisation to re-establish, but rather the residual transverse magnetisation is used to obtain all the slices of the two-dimensional data set sequentially as a series of gradient echoes in a "one-shot" experiment. Fast images are used in functional MRI (fMRI), e.g., to identify specific brain activity associated with a different activity or stimulus. PX388 Magnetic Resonance: Section D: Pulsed NMR 22 (D) Pulsed NMR: Questions In questions 1 to 3, use the Bloch Eqs. [C55-C57]. For rf pulses, phase x means = 0 and phase y means = 90. Assume that the rf pulse durations are sufficiently short such that relaxation can be neglected during the pulses (set 1/T1 = 1/T2 = 0). Assume thermal equilibrium bulk magnetisation at time, t = 0, i.e., Mr(t = 0) = +M0 k 1. Consider the inversion-recovery pulse sequence: x /2x tacq (i) What is Mr after the x pulse? (ii) What is Mr after the time (consider T1 relaxation during this time)? (iii) What is Mr after the /2x pulse? (iv) If signal, a(), is detected in the j direction, show that a() [1 2 exp(/T1)] (eq. [D1]). 2. Consider the spin-echo pulse sequence: /2x /2 y /2 tacq Consider the evolution under a resonance offset 0 and relaxation due to T2 during the two periods. (i) What is Mr after the /2x pulse? (ii) What is Mr after the first time /2? (iii) What is Mr after the y pulse? (iv) What is Mr after the second time /2? (v) If signal, a() is detected in the j direction, show that a() doesn't depend on 0, i.e., a() exp(/T2) (eq. [D3]). PX388 Magnetic Resonance: Section D: Pulsed NMR 23 3. Consider the following pulse sequence used in 1H NMR imaging: 90x TR 90x TE Use the Bloch equations to show that: (a) immediately before the application of the second 90x pulse: Mzr(t = TR) = M0 [1 exp(TR / T1)] (b) Consider the application of the second 90x pulse on this Mzr(t = TR) state. Show that (for 0 = 0) at the end of the TE time period: Myr(t = TE) = M0 [1 exp(TR / T1)] exp(TE / T2) (c) The 1H T1 and T2 of various brain tissues and fluids are shown below: Grey matter White Matter CSF Fat T1 / ms 825 690 3000 130 T2 / ms 110 100 1500 105 (CSF = cerebrospinal fluid) Determine Mzr(t = TR) and Myr(t = TE) for grey matter, white matter, CSF and fat for the following three experiments: (i) TR = 2300 ms & TE = 200 ms (ii) TR = 5000 ms & TE = 20 ms (iii) TR = 500 ms & TE = 20 ms Classify the three cases as to whether the images are T1, T2 or proton density weighted. PX388 Magnetic Resonance: Section D: Pulsed NMR 24 4. A time-domain NMR signal in the rotating frame is described mathematically by: s(t) = exp{i 0 t} exp{t / T2} (i) t0 Perform a complex Fourier transformation: S() = s(t) exp(i t) dt 0 to show that the real and imaginary parts of the corresponding frequency-domain spectrum are given by: real{S()} = (1 / T2) / (1 / T2)2 + ( 0)2] imaginary{S()} = ( 0) / (1 / T2)2 + ( 0)2] 5. (ii) Sketch the form of these real and imaginary parts of the spectrum. (iii) What is the full-width at half-maximum height of the real lineshape? A NMR spectrum recorded in an inhomogeneous magnetic field exhibits a single line whose full-width at half-maximum height equals 1 kHz. In a spin-echo experiment, the signal intensity for = 200 ms is reduced by 80 % as compared to an experiment performed for = 0. The spectroscopist then sets out to improve the homogeneity of the NMR magnet. What is the maximum possible line-narrowing factor that can be achieved? (Assume that the decay of transverse magnetisation is characterised by a decaying mono-exponential function.) 6. The T1 of a certain sample decreases with increasing temperature. At 20 C, it is necessary to leave 10 seconds between transients, while at 40 C only 5 seconds are required. Suppose that 3 hours of NMR spectrometer time is available, and that the instrument is already set up for operation at 20 C. It takes 1 hour to warm up the sample to 40 C and to stabilise the temperature. Assume that the NMR signals are identical at the two temperatures. What is the best strategy for acquiring the signals – running for 3 hours at 20 C, or warming the sample and running for 2 hours at 40 C? PX388 Magnetic Resonance: Section D: Pulsed NMR