Magnetic Resonance Imaging

B0

Thomas Vosegaard
Laboratory for Biomolecular NMR Spectroscopy Department of Molecular Biology and Interdisciplinary Nanoscience Center University of Aarhus

November 2005

Preface
These Notes intend to give a short introduction to magnetic resonance imaging (MRI). MRI represents a very hot topic within medical sciences as evidenced by the 2003 Nobel Price in medicine awarded to the founders of MRI, Paul Lautherbur and Peter Manseld. The rst Sections summarize basic NMR theory. It may be well-known stuff and serves primarily to present the entire theory needed to understand MRI in the same notation as applied for the following imaging Sections. From Section 6 and onwards the basic concepts of MRI are explained, and pulse sequences routinely applied on MR scanners worldwide are presented. I hope these Notes contribute to your understanding of imaging and that you, after reading them, share my fascination for MRI. I would like to thank Anders Malmendal for many valuable comments on these Notes.

Thomas Vosegaard

CONTENTS

iii

Contents
1 Nuclear Spin Interactions 1.1 1.2 1.3 1.4 Nuclear Magnetic Moment and Nuclear Spin . . . . . The Zeeman Interaction . . . . . . . . . . . . . . . . The Magnetization of the Sample . . . . . . . . . . . . Nuclear Spin Interactions . . . . . . . . . . . . . . . . 1.4.1 1.4.2 Chemical Shift . . . . . . . . . . . . . . . . . Spin-Spin Coupling . . . . . . . . . . . . . . . 1 1 2 3 4 4 4 7 8 9 9

2 Aspects of One-Dimensional NMR 2.1 2.2 2.3 Manipulation of the Nuclear Magnetization . . . . . . 2.1.1 Detection of the Free-Induction Decay . . . . . The Rotating Frame of Reference . . . . . . . . . . . . 2.3.1 2.3.2 3 Relaxation 3.1 3.2

Radio-Frequency Pulses . . . . . . . . . . . . . . . . 11 The Single-Pulse Experiment . . . . . . . . . 13 The Spin-Echo Experiment . . . . . . . . . . . 13 17

Longitudinal Relaxation, T1 . . . . . . . . . . . . . . 17 Transverse Relaxation, T2 and T2 . . . . . . . . . . . 20 22

4 Fourier Transformation 4.1 4.2 4.3

One-Dimensional Fourier Transformation . . . . . . . 22 Discrete Fourier Transformation . . . . . . . . . . . . 24 Two-Dimensional Fourier Transformation . . . . . . . 24 27 27

5 Basic Two-Dimensional NMR 6 Magnetic Field Gradients 6.1

The Gradient Echo . . . . . . . . . . . . . . . . . . . 28

iv

CONTENTS

Principles of Magnetic Resonance Imaging 7.1 7.2

28

Selective Radio-Frequency Irradiation . . . . . . . . . 30 Slice Selection . . . . . . . . . . . . . . . . . . . . . 31 33

k-Space Imaging 8.1 8.2 8.3

Acquiring k-Space Data . . . . . . . . . . . . . . . . 34 Practical Aspects of k-Space Imaging . . . . . . . . . 37 Fast Imaging Techniques . . . . . . . . . . . . . . . . 39 8.3.1 8.3.2 8.3.3 Echo Planar Imaging . . . . . . . . . . . . . . 42 Spiral Imaging . . . . . . . . . . . . . . . . . 42 Comparison of Spiral and Echo-Planar Imaging 44

8.4 8.5 8.6 8.7 9

Image Contrast . . . . . . . . . . . . . . . . . . . . . 47 T1-Weighted Imaging . . . . . . . . . . . . . . . . . . 47 T2- and T2 -Weighted Imaging . . . . . . . . . . . . . 49 Creating Contrast Using Contrast Agents . . . . . . . . 50 51 55

Functional Imaging

10 Magnetic-Resonance Angiography

10.1 Time-of-Flight MRA . . . . . . . . . . . . . . . . . . 55 10.2 Phase-Contrast MRA . . . . . . . . . . . . . . . . . . 56 11 Localized Magnetic Resonance Spectroscopy 56

11.1 Single-Voxel Techniques . . . . . . . . . . . . . . . . 58 11.2 Multi-Voxel Techniques . . . . . . . . . . . . . . . . . 58 12 Instrumentation 60

12.1 MR Scanners . . . . . . . . . . . . . . . . . . . . . . 60 12.2 Gradient System . . . . . . . . . . . . . . . . . . . . . 62

1 NUCLEAR SPIN INTERACTIONS

1 Nuclear Spin Interactions

The physical principle that forms the basis for nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) is the interaction between atomic nuclei with nonzero spin and a magnetic eld. This concept was rst postulated in the 1920s by the Wolfgang Pauli, but was not experimentally demonstrated until 1946 when Felix Bloch and Edward Purcell ran the rst NMR spectra. Bloch and Purcell were awarded the Nobel price in 1952 for their achievements.

1.1 Nuclear Magnetic Moment and Nuclear Spin The atomic nucleus consists of protons and neutrons and is positively charged. If the nucleus spins about its own axis, it will generate a magnetic eld similarly to an electric current owing in the loop of a circular wire. This eld is termed the nuclear magnetic dipole. The magnetic dipole will interact with external magnetic elds just like a compass needle interacts with the magnetic eld of the Earth. The nuclear spin describes the fact that some nuclei interact with external magnetic elds like a rotating top that not only rotates about its own axis but may be perturbed so its rotation axis precesses around the Earths gravitational eld. Thus, the nuclear spin may be represented by a vector aligned along the precession axis. For the nucleus the precession frequency, 0 , is proportional to the external magnetic eld B0 as 0 = B0 (1)

where the constant of proportionality, , is termed the gyromagnetic ratio and is a fundamental property for every isotope. Only atomic nuclei with unpaired protons or neutrons possess a

1.2 The Zeeman Interaction

Table 1: Nuclear spin, natural abundance, and gyromagnetic ratios for some typical isotopes

Atom Spin H C 15 N 19 F 31 P
13 1

1/2 1/2 1/2 1/2 1/2

Natural abundance (%) 99.985 1.108 0.37 100 100

Gyromagn. ratio /2 (MHz/T) 42.58 10.71 4.32 40.07 17.24

Biological density (%) 10 23 2.6 0.04 1.1

nuclear spin. The nuclear spin I is the number of unpaired nuclear particles times 1/2. In this text we will focus on isotopes with nuclear spin I = 1/2, of which some are listed in Table 1. The nuclear spin number, I, is often termed the nuclear spin quantum number and represents the length of the spin vector.

1.2

The Zeeman Interaction

When a nucleus possessing a nuclear spin is placed in a magnetic eld (in NMR and MRI the magnetic eld is normally dened to be parallel to the z axis), the z component of the nuclear spin, Iz , becomes quantitized and only takes discrete values of Iz = I, I + 1, ..., I. (2)

In the case of spin-1/2 nuclei Iz takes the values 1/2 and 1/2, typically referred to as and . The different states arise because of the interaction between the nuclear spin and the external magnetic eld. This interaction was rst characterized by Pieter Zeeman and is therefore dubbed the Zeeman interaction. The energy of the individual levels are given by

1 NUCLEAR SPIN INTERACTIONS

E = 0 Iz . 1.3 The Magnetization of the Sample

(3)

The population of the and spin states of a large number of spins present in a macroscopic sample is determined by the temperature. At very low temperature, all spins will be in the low-energy state while at higher temperatures there will be some thermal excitation to the highenergy state. This was originally described by Ludwig Boltzmann and is normally called the Boltzmann distribution. It states that the macroscopic distribution of particles over the energy levels is exponentially decreasing, N E E = exp N kT 1 0 , kT (4)

with k representing the Boltzmann constant and T being the absolute temperature of the sample. The last approximation is a power expansion1 using the fact that for NMR the energy difference is much smaller than kT . The fact that the and states are differently populated creates a macroscopic magnetization of the sample. At equilibrium, this magnetization will be aligned along the magnetic eld, i.e., it may be represented by a vector, M eq = M z , pointing along the magnetic eld (z). Since the energy difference between two spin states is very small, e.g. as compared to the energies present in vibrational or electronic spectroscopy, the termodynamic preference for the state with lower
1 A power expansion is an approximation where a complicated function, f (x), may be approximated by the function f (x) = f (x0 ) + f (x0 )(x x0 ) + ..., for values of x in the vicinity of x0 .

1.4 Nuclear Spin Interactions

energy is not very large. With the NMR signal being proportional to the population difference (N N ) NMR has a relatively low sensitivity compared to other spectroscopic techniques. For example, the population difference between protons in the and states at 1.5 T is about 105 . 1.4 Nuclear Spin Interactions

A number of different nuclear spin interactions makes NMR spectroscopy a very informative disciplin, capable of providing important structural and dynamic information. Below we will briey summarize two of these interactions and the type of information they may provide.
1.4.1 Chemical Shift

Just like the nucleus creates a small magnetic eld due to its rotation, electrons circling around the nucleus in different orbitals will generate a magnetic eld. This eld is in opposite direction to the external magnetic eld resulting in a diminished effective magnetic eld at the position of the nucleus. This phenomenon, known as chemical shielding, is illustrated in Fig. 1a. Shielding because the electrons diminish the eld and thereby shield the nucleus and chemical because the shielding depends on the chemical environment of the particular atom studied.
1.4.2 Spin-Spin Coupling

As discussed in Section 1.1, a nucleus creates a small magnetic eld which, according to Section 1.2, either is aligned along or against the external magnetic eld. Close to the nuclear spin, the effective magnetic eld will then be either larger or smaller than B0 depending on the spin state ( or ) of the nucleus as illustrated in Fig. 1b. A second

1 NUCLEAR SPIN INTERACTIONS

a
B eff =B 0 (1) B0

B eff = B 0 + B n

Bn

B0

B eff = B 0 B n Bn

Figure 1: Illustration of the effect of chemical shielding and spinspin couplings. (a) Compared to the external magnetic eld B0 , the nucleus will sense a smaller magnetic eld due to the shielding of the surrounding electrons. (b) A nearby spin will create a net magnetization parallel or antiparallel to B0 causing a change in the effective eld at the position of the observed nucleus.

ppm

Figure 2: 1 H NMR spectrum of ethanol.

nucleus placed in the vicinity of the rst nucleus will then have a resonance frequency depending on the spin state of the rst nucleus. This is referred to as a coupling between the nuclei. The most common type of coupling in liquids is the J-coupling that is mediated through covalent bonds.

Since the Boltzmann distribution only causes a marginal difference in the population of the and states, the coupling between two nuclei will make each of their resonance split into two lines of virtually equal intensity corresponding to the two spin states of the neighbouring spin.

2 ASPECTS OF ONE-DIMENSIONAL NMR

2 Aspects of One-Dimensional NMR

The basic art of nuclear magnetic resonance spectroscopy is to measure the difference in energy between the and spin states. This may be - and was originally - done by irradiating the sample with electromagnetic waves of appropriate frequency range and then measure the absorption. As we shall see in the following Sections there are more clever ways of doing NMR experiments, but before proceeding to these, let us have a look at a simple NMR spectrum. The 1 H NMR spectrum of ethanol is displayed in Fig. 2 and shows chemical shifts and J-couplings typical for ethanol. The scale below this spectrum represents the frequency difference () between the resonance () and the 1 H resonance of trimethylsilane (TMS) (0 ). Normally we will measure in parts per million (ppm) relative to 0 0 106 . 0

(ppm) =

(5)

It should be noted that the denition that 0 = 0 (TMS) is arbitrary but routinely used. Likewise NMR spectroscopists have chosen special reference compounds dening the zero-point for the ppm scale for many other isotopes. The spectrum in Fig. 2 shows three sets of resonances located at 1.2, 3.65, and 5.25 ppm. They are the resonances corresponding to the CH3 , CH2 , and OH groups, respectively, and have different frequencies because of the different electronic environment. Moreover, the CH2 and CH3 groups show up as a quartet and a triplet because they are J-coupled to eachother. The OH group shows no coupling because the O-H bond is delocalized due to hydrogen bonding.

2.1 Manipulation of the Nuclear Magnetization

Theory Box 1: The Bloch Equations

The nuclear magnetization may be manipulated by external magnetic elds with orientations perpendicular to the magnetization vector, M. Likewise the magnetic eld will be represented by the vector B, and thus B0 = (0, 0, B0 ). The magnetization vector obeys a differential equation, the socalled Bloch equation, constructed in 1948 by Felix Bloch, dMx dt dMy dt dMz dt If B = B0 (= Bz ), the solution to these differential equations is Mx (t) = 0 0 Mx cos(0 t) My sin(0 t) My (t) = 0 0 My cos(0 t) + Mx sin(0 t) 0 Mz (t) = Mz (T1-2) where 0 = B0 . This shows that if there were initial transverse (x and y) components of the magnetization vector, they would precess around the external magnetic eld with the larmor frequency, while the longitudinal (z) component will remain unaltered.

= = =

(My Bz Mz By ) (Mz Bx Mx Bz ) (Mx By My Bx ) (T1-1)

2.1

Manipulation of the Nuclear Magnetization

Theory Box 1 demonstrates how the macroscopic magnetization of the sample may be manipulated by external magnetic elds, and it is demonstrated that the magnetic eld must be perpendicular to the magnetization to have any effect. Moreover, the concepts of longitudinal and transverse magnetization are introduced in Theory Box 1. These terms represent the magnetization components along z and in the xy plane, respectively. As we shall see later, and as it is also apparent from Eq. T1-2 in Theory Box 1 there is a physical basis for this distinction. We may use the behaviour of the Bloch equations to manipulate the orientation of the magnetization by applying small magnetic elds in other directions. Equation T1-1 in Theory Box 1 states that whenever

2 ASPECTS OF ONE-DIMENSIONAL NMR

the magnetization vector experiences a magnetic eld perpendicular to its orientation, it will start to precess around the axis of the magnetic eld. Suppose we in addition to the B0 eld apply a small eld, B1 , along x. This will just create an effective eld slightly tilted away from z in the xz plane and the magnetization will start to precess around this new effective eld axis. On the other hand, if the B1 eld oscillates in the xy plane with a frequency of 0 , it may be kept perpendicularly to M at all times and tilt the magnetization away from z. This is illustrated in Fig. 3a on page 12 and will be treated more thoroughly in Section 2.3.
2.1.1 Detection of the Free-Induction Decay

It is well-known, e.g. from electrical transformators, that just like an alternating current in a coil will create an alternating magnetic eld, an alternating magnetic eld is able to generate an alternating current in a coil. Thus, the oscillating magnetic eld caused by the precession of the transverse component of the magnetization of the sample may be detected as an alternating current in a coil wrapped around the sample. In practice, we will measure the NMR signal, S, in this manner by measuring both the x and y components of the free-induction decay. This means that the harmonically oscillating signal may be described by the complex function S(t) = exp{it}.2 2.2 The Rotating Frame of Reference You probably nd it much easier to denominate resonance frequencies by e.g., 1 ppm as on the scale in Fig. 2 instead 400.0004, etc. The scale below the spectrum is a ppm scale calculated by Eq. 5.
2 A complex number (c) has a real (x) and an imaginary (y) part, c = x + iy, where i is the complex number i = 1. The complex exponential function is represented by the harmonic oscillators, exp{it} = cos t + i sin t.

10

2.2 The Rotating Frame of Reference

Theory Box 2: The Rotating Frame

As evidenced in Theory Box 1 any transverse magnetization will rotate with the larmor frequency around the z axis. In our normal representation of NMR spectra (see e.g., Fig. 2 we use the ppm scale which represents the actual resonance frequency minus the larmor frequency. Likewise, when observing the evolution of the magnetization in a coordinate system, it is convenient to use a frame where the larmor frequency is subtracted. This corresponds to transferring the description of into a frame rotating at the larmor frequency around z. This frame will be denoted x , y , and z. The relation between the two frames is as follows:

x = x cos 0 t + y sin 0 t y = y cos 0 t x sin 0 t (T2-1)

When depicting the oscillation of the magnetization vector in a three-dimensional coordinate system it is also simpler to omit the larmor frequency and only depict the small variations in the resonance frequencies relative to the larmor frequency. For details on the mathematical way of handling this, see Theory Box 2. In popular terms, the philosophy of the rotating frame is like a carousel in an amusement park. If you want to talk to the people who are on the carousel it is most convenient to step onto the carousel than staying next to it. In the NMR spectrometer or MR imaging scanner, the signal in the rf coil generated by the sample consists of as a high-frequency (0 ) signal with small frequency modulations () due to the nuclear spin interactions. This is in full analogy to the principle of normal FM radios where the signal of interest (audio signal) represents a modulation of a high-frequency carrier of around 100 MHz. In NMR and MRI the signal from the coil is passed through a frequency mixer which creates the difference signal 0 , which exactly corresponds to the description in the rotating frame.

2 ASPECTS OF ONE-DIMENSIONAL NMR

11

The radio frequency of the mixer is often referred to as the carrier frequency and needs not be identical to the Larmor frequency 0 . However, to keep the notation simple in these notes we will also use the term 0 as the carrier frequency. 2.3 Radio-Frequency Pulses As previously mentioned the nuclear magnetization will interact with external magnetic elds. If the additional B1 eld rotates in the xy plane with the resonance frequency (0 ), it appears static in the rotating frame, e.g. along the x axis, and will always be perpendicular to M. Consequently this eld makes the magnetization begin to precess around the B1 (x ) axis. The effect of this is visualized in Fig. 3 as observed in the laboratory (a) and rotating (b) frames. Because 0 lies in the radio-frequency range of the electromagnetic spectrum, the oscillating B1 eld will be a referred to as a radio-frequency (rf) eld. Like large magnetic eld, B0 , the small oscillating eld will make the magnetization vector precess with a frequency of 1 = B1 . For most NMR and MRI experiments 1 will be in the kHz range. If we want to bring the sample from its thermal equilibrium state (Mz ) to a state with transverse magnetization in order to detect the NMR signal, we may apply the B1 eld for exactly the period of time it takes to perform a 90 (/2) rotation of the magnetization vector around x . Such short periods of rf irradiation are referred to as rf pulses and the rotation angle is called the ip-angle. The ip angle of the pulse is given by = 1 t and hence t90 = . 21 (6)

The concept of pulsed NMR spectroscopy was developed by Richard R. Ernst in the 1960s, an effort for which he was awarded the Nobel

12

2.3 Radio-Frequency Pulses

Figure 3: Evolution of the nuclear spin magnetization in the laboratory frame (a) and in the rotating frame (b) in the presence of an external eld, B0 , and a transverse rotating eld, B1 .

3 RELAXATION

13

price in 1991. In the following Sections it will be demonstrated how pulse sequences may be used to manipulate the spin system and to bring it to a desired state.

2.3.1 The Single-Pulse Experiment

The most simple pulsed NMR experiment one may think of consists of a 90 pulse that ips the equilibrium magnetization Mz to an orientation in the transverse plane (e.g. along the x axis) for detection as illustrated in Fig. 4a. If all spins were precessing with exactly 0 there would be no further evolution in the rotating frame and the spin system would stay in the state shown in Fig. 4b (in practice there will be an exponential decay due to relaxation as discussed in Section 3). However, if there are different spins the magnetization vectors for these spins (e.g. as labelled 1-4 in Fig. 4c) will start to precess with frequences determined by the nuclear spin interactions. Upon detection the free-induction decay may be transformed from the time domain into a spectrum like the one in Fig. 2.

2.3.2 The Spin-Echo Experiment

The spin-echo experiment shown in Fig. 5 uses the following sequence of pulses and delays: 90 180 . After the rst pulse and delay, x y the different species will have obtained a x y phase encoding, i = (i 0 ) , due to their different resonance frequencies. The 180 pulse brings magnetization along x to x and z to z, changing the x y phases from i i . Consequently, after a second delay of duration all spins will be refocussed and a socalled spin echo is formed.

14

TR
y

TR

a b

x z

1 2 x

Figure 4: Rotating-frame vector representation of the evolution of the magnetization before and after a pulse using the displayed pulse sequence. (a) Before the 90 pulse the magnetization is at thermal equilibrium aligned along the external magnetic eld. (b) The pulse ips the magnetization from z to x . When being in the transverse plane, the magnetization vectors for different spins start to precess with different frequencies due to their chemical shift. At a certain time, t, the individual species have obtained different x y phases given by i (t) = (i 0 )t. To improve the S/N ratio the experiment will typically be repeated several times with a repetition delay of T R as shown on the top.

3 RELAXATION
TE
y x

15

a b c d
z

x z

1 2 x 3 z

4 3 x 2

Figure 5: Rotating-frame vector representation of the evolution of the magnetization during a spin-echo experiment as displayed by the pulse sequence on the top. (a) An initial 90 pulse ips the magnetization from z to x (b). (c) After a delay the different species have obtained x y phases due to their different chemical shift. (d) A 180 pulse is applied to the spins in (c) and they undergo the x transformation y y , z z. (e) After a second delay all spins are refocussed to lie along x . If no transverse relaxation were present this situation would correspond to the spin state in (a). The time elapsed from the initial pulse to the formation of the echo is called TE.

16

Theory Box 3: The Modied Bloch Equations

The differential equations describing the evolution of the magnetization vector in the presence of an external magnetic eld, the socalled Bloch equations (Eq. T1-1 in Theory Box 1) represents the ideal behaviour of the magnetization vector in the presence of external magnetic elds. However, as we mentioned above the system studied will be inuenced by relaxation, which is a physical phenomenon that makes the system return from an excited state to its equilibrium state. The Bloch equation (Eq. T11) may be extended to include this effect, resulting in a new set of differential equations, normally dubbed the modied Bloch equations dMx dt dMy dt dMz dt = (Mz Bx Mx Bz ) My /T2 (T3-1) = (Mx By My Bx ) +Mz /T1, in which case the solution for the transverse components of the magnetization become Mx (t) = ` 0 0 Mx cos(0 t) My sin(0 t) exp(t/T2). (T3-2) The latter equation in Eq. T3-1 tells us that the longitudinal component of the magnetization vector will return to the equilibrium state via an exponential growth (1 exp(t/T1)), in analogy to the decay of the transverse magnetization.

(My Bz Mz By ) Mx /T2

3 RELAXATION

17

3 Relaxation
Inclusion of relaxation in the description of the time evolution of the magnetization leads to a new set of differential equations, the socalled modied Bloch equations. Theory Box 3 introduces these equations and gives the solutions. Relaxation is characterized by a relaxation time (T) and is separated into longitudinal relaxation along the direction of the external magnetic eld (T1) and transverse relaxation (T2) in the xy plane. The physical meaning of these two different relaxation mechanisms will be explained in the following example: Suppose the magnetization vector of the system has been excited from its equilibrium state along z to an alignment along the x axis. According to Eqs. T1-2 it will start to rotate in the x-y plane with the frequency . The transverse relaxation causes an exponential decay (exp(t/T2)) of the transverse magnetization as shown in Fig. 6b. The longitudinal relaxation causes the magnetization to return to thermal equilibrium with an orientation along the external magnetic eld. 3.1 Longitudinal Relaxation, T1 The longitudinal relaxation provides a mechanism by which the spins may give up their energy to return to their original orientation. This is also referred to as the spin-lattice relaxation time, since the spin needs to transfer energy to the surroundings (lattice) for the process to happen. The longitudinal relaxation may be measured in several different ways. The most common experiment is the inversion-recovery experiment shown in Fig. 7. An initial 180 pulse inverts the magnetization vector, i.e. it inverts the populations of the and states. The spins will then begin to relax back to the equilibrium state. At a time TI,

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3.1 Longitudinal Relaxation, T1

a
Intensity,Mz

Small T1 Large T1

Time

b
Intensity,Mxy

Large T2

Small T2 Time
Figure 6: Graphical representation of the signal intensity as a function of (a) the delay TI in an inversion-recovery experiment, shown in Fig. 7, and (b) the delay TE in a spin-echo experiment. Both relaxation mechanisms are exemplied by species having small and large relaxation times.

3 RELAXATION

19

TI
y y

a b

c d

Figure 7: Inversion-recovery pulse sequence used to measure the longitudinal (T1) relaxation time. The equilibrium magnetization (a) is inverted by a 180 pulse and is then aligned along z (b). The longitudinal relaxation will cause the magnetization to return to its equilibrium state (a). After the time TI (c) a 90 pulse is applied to ip the magnetization vector into the transverse plane (d) so the signal intensity may be measured.

20

3.2 Transverse Relaxation, T2 and T2

the relaxation process is probed by applying a 90 pulse to create detectable transverse magnetization. A plot of the intensity as a function of the waiting time TI in this experiment will give a curve as shown in Fig. 6a. This curve is described by the equation

S(t) =

Mz (t)
0 Mz (1 2 exp{TI/T1}).

(7)

If the spins were not inverted but only saturated (i.e. brought to a state where M = 0) the signal would be described by S(t) 1 exp{TI/T1}. For highly mobile molecules the longitudinal relaxation will typically be slower than for immobilized species. In the latter case T1 will often be dependent on the magnetic eld strength so that T1 increases when B0 increases. 3.2 Transverse Relaxation, T2 and T2

The physical origin of the transverse relaxation is spin-spin interactions that lead to a net energy loss among the spins. The transverse relaxation time may be equal to the longitudinal relaxation time in cases where relaxation simply brings the magnetization back from the transverse to the longitudinal orientation, but generally the transverse relaxation is faster than the longitudinal. Other processes than spin-spin interactions may also play a role in the transverse relaxation. These rely on nonuniformity of the main magnetic eld B0 and come from two sources: 1. Main eld inhomogeneity. There is always some degree of nonunifority to B0 due to imperfections in magnet manufacturing

3 RELAXATION

21

and nearby metal objects. 2. Sample-induced inhomogeneity. Differences in magnetic susceptibility or degree of magnetic polarization within the sample, e.g. for adjacent tissues, will distort the local magnetic eld near the interface between these tissues. The main eld inhomogeneity (m) and magnetic susceptebility (s) add to the spin-spin relaxation time T2 to give the total transverse relaxation time, T2 , 1 1 1 1 + = m + T2 T2 T2 T2s (8)

The transverse relaxation time may be measured by the spin-echo experiment shown in Fig. 5. This is done by measuring the signal intensity as a function of the echo time (TE) as shown in Fig. 6a. Since this experiment uses a 180 refocussing pulse the effect from the two additional components to the total signal dephasing are eliminated, so this experiment measures T2 and not T2 . The signal intensity of the spin-echo experiment has the following exponential decay

S(t)

Mx y (t)
0 = Mx y exp{TE/T2}.

(9)

The magnetic susceptibility effect to T2 relaxation may be changed dramatically in the presence of paramagnetic species in the tissue. The reason is that paramagnetic species have unpaired electrons, which, like nuclei, will be polarized in the strong magnetic eld. Since electrons resonate in the microwave region of the electromagnetic spectrum (e /2 = 28.0 GHz/T) while nuclei resonate in the radio-frequency region, the polarization of electrons will be about three orders

22

of magnitude stronger than proton the polarization. This polarization changes the magnetic susceptibility of the tissue and consequently decreases T2 .

4 Fourier Transformation
4.1 One-Dimensional Fourier Transformation

The free-induction decay acquired as described in the previous Sections, is caused by the oscillations of the magnetization vector. Since many nuclei experiencing different surroundings may be present, it is likely that the total magnetization vector will be composed of several components (due to each type of nuclei) with different oscillation frequencies, dened by the chemical shift of the individual nuclei. In order to determine the resonance frequencies of each type of nuclei, we need to gure out the different frequencies in the free-induction decay. Our way of doing this is to transform the description from the timedomain (free-induction decay) to the frequency domain (spectrum) by a socalled Fourier transformation. Theory Box 4 gives the mathematical tool for performing the Fourier transformation between the time- and frequency-domain. The essential point to remember is that we have a simple analytical tool to transfer the description from one domain to another. It should be noted that the Fourier transformation is not restricted to the t transformations, but may be generally applied to transform between reciprocal spaces. For example, X-ray diffraction uses a Fourier transformation to obtain the electron density from the intensities of the Bragg reections being proportional to the socalled structure factors.

4 FOURIER TRANSFORMATION

23

Theory Box 4: One-Dimensional Fourier Transformation

The free-induction decay acquired as described previously, represents oscillations due to the individual resonances like the 1 H resonances of ethanol (Fig. 2). From this spectrum we could readily calculate the free-induction decay or time evolution of the magnetization, S(t), by superposition of the oscillating terms for each resonance i weighted by its spectral intensity Si : X
i

The back-calculation from the frequency spectrum to the time spectrum expressed by Eq. T4-2 was rst described by Jean Baptiste Joseph Fourier in the late 18th century and is normally referred to as the inverse Fourier transformation. The transformation from time to frequency is referred to as the direct Fourier transformation or just the Fourier transformation. The direct Fourier transformation described by Z

S(t) =

Si exp{ii t}

(T4-1) S() =

S(t) exp{it}dt,

We can also consider a continous frequency distribution, dubbed the frequency spectrum, S(). In this case the summation in Eq. T4-1 is simply replaced by an integration over all frequencies, 1 2 Z

(T4-3) is not as intuitively understandable as the inverse Fourier transformation but represents a tremendously important tool for NMR spectroscopy because it allows us to obtain the frequency spectrum from the free-induction decay.

S(t) =

S() exp{it}d (T4-2)

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4.2 Discrete Fourier Transformation

4.2

Discrete Fourier Transformation

When working with real experimental data it is impossible to accumulate the data in a continous fashion as required to perform the Fourier transformation (see Eq. T4-3). Data will always be accumulated stroboscopically as data points. This means that we need to modify the Fourier transformation to operate on discrete points instead of a continous function. Theory Box 5 presents some issues regarding discrete Fourier transformations, and the essential points are listed below Spectral width: The frequency range covered in a particular experiment. To increase the spectral width, a shorter delay between the time-domain data points is needed. Frequency resolution: The resolution in the frequency domain depends on the sampling time. To increase the frequency resolution, a larger total sampling time T is needed. 4.3 Two-Dimensional Fourier Transformation

An intriguing feature of the Fourier transformation is that it may be performed individually for each dimension in a multidimensional data set. In the next section we shall see how to design multidimensional NMR experiments with two or more different evolution periods. For now, let us just assume that we have a time spectrum composed of two different evolution periods, t1 and t2 , so that we have a twodimensional time spectrum, S(t1 , t2 ). This may be fourier transformed into the frequency spectrum S(1 , 2 ).

4 FOURIER TRANSFORMATION

25

Theory Box 5: Discrete Fourier Transformation

In practice we will never be able to measure a continous dataset, but we will always measure discrete values of e.g. the free-induction decay. This is called sampling or acquisition of the free-induction decay. It should be emphasized that when fourier transforming the discrete dataset the sampling rate and sampling time inuence the appearance of the fourier-transformed frequency spectrum. If points in the dataset are sampled at times 0, dt, 2dt, ..., the sampling rate is 1/dt. This digitization of the time-domain signal implies that the maximum frequency which can be measured is 1/2dt since a frequency of 1/2dt+ will be indistinguishable from a frequency of 1/2dt + . Therefore, we dene the spectral width (sw) as 1 , (T5-1) dt stating that it is only possible to measure frequencies between sw/2 and +sw/2. The theorem describing this effect is called the Nyquist theorem due to the physicist Harry Nyquist. The frequency 1/2dt is often referred to as the Nyquist frequency. sw = The total sampling time determines the resolution in the frequency dimension. This is intuitively clear since species resonating with close frequencies need to evolve for long time before their difference becomes pronounced. If we acquire a signal for a total sampling time of T , we will acquire np (= T /dt) points in the time domain, and hench the resolution in the frequency domain will be sw/np. Some 40 years ago Cooley and Tukey developed a fast computer algorithm for Fourier transformation which needs np ln(np) mathematical operations to accomplish the transformation. This number would otherwise be np2 . The fast Fourier transformation requires the number of points to be a socalled fourier number 2n , where n = 0, 1, 2, 3, .... The reason for mentioning this is that the spectrometers only use fast fourier transformation and for good reasons. If we record a three-dimensional image with 256 256 256 points, the fast fourier transformation may last some seconds while the normal fourier transformation will last roughly the same number of days on the same computer.

26

4.3 Two-Dimensional Fourier Transformation

a b
1 2 3 4 ...

Preparation

(t 1) Evolution

Mixing

(t 2) Acquisition

c
dt 1 2dt 1

t2

t1
3dt 1

d
Prep. 1 t1 Mix. t2

e
H
13 13

Figure 8: Basic principles of 2D NMR spectroscopy. (a) sketch of pulse sequences used in 2D NMR spectroscopy consisting of a preparation period, t1 evolution, mixing, and t2 acquisition. (b) t2 slices are acquired via sequential incrementation of t1 . (c) 2D time-domain dataset. (d) Heteronuclear correlation (HSQC) pulse sequence used for correlation of 13 C (t1 ) with directly bonded 1 H (t2 ) nuclei. The deeper insight into this kind of pulse sequences is beyond the scope of these notes. (e) HSQC spectrum of ethylbromide, CH3 CH2 Br, showing the signals from the protons (horizontal axis) and their correlations with the carbon signals (vertical axis).

6 MAGNETIC FIELD GRADIENTS

27

5 Basic Two-Dimensional NMR

Two-dimensional NMR spectroscopy is typically used to correlate different interactions through various types of connectivities. Examples can be homonuclear 1 H-1 H or heteronuclear 1 H-13 C correlation spectra allowing to determine J-coupling connectivities between neighbouring nuclei. In typical two-dimensional experiments the sample is initially prepared to a state where it evolves under the rst interaction (e.g.
13

C chemical shift) for a time t1 followed by a mixing

where the sample is brought to evolve under the second interaction (e.g. 1 H chemical shift) for which the free-induction decay is acquired (corresponding to t2 ). The two-dimensional free-induction decay is achieved by acquiring a one-dimensional t2 free-induction decays for a series of values for t1 as schematically depicted in Fig. 8.

6 Magnetic Field Gradients

A magnetic eld gradient creates different magnetic elds at different locations in space. In NMR we typically work with linear gradients along x, y, or z. Since the gradient represents the rst derivative of the magnetic eld with respect to its spatial orientation, i.e. an x gradient is represented by B/x = Gx where Gx is the x component of the magnetic eld gradient G. If we create a magnetic eld gradient in addition to the external B0 eld we achieve an effective magnetic eld of B(r) = B0 + G r, where r is a vector describing the position. As previously mentioned the precession of the magnetization will create a signal given by S(t) = exp{it}, which in the presence of a (10)

28

6.1 The Gradient Echo

magnetic eld gradient reads (t, G, r) = 0 + G r (11)

From this equation we see that applying a magnetic eld gradient will create a spatially dependent phase encoding of the signal. 6.1 The Gradient Echo

The gradient-echo experiment consists of an initial 90 pulse which creates transverse magnetization. A magnetic eld gradient, e.g. Gx , is then turned on. This creates a linear variation in the resonance frequencies along the x axis of the sample, implying a dephasing of the magnetization (Fig. 9). After a time the sign of the gradient is changed from Gx to Gx which changes the sign of the resonance frequency along x relative to the rotating frame. Consequently, after an additional time the magnetization is refocussed just like it was the case with the spin-echo experiment. Although the gradient echo acts very similarly to the spin echo there is one important difference between these two sequences. In contrast to the spin-echo sequence, the gradient-echo sequence does not refocus the B0 -eld inhomogeneity. Consequently, the magnetization will relax due to T2 during the gradient-echo sequence and due to T2 during the spin-echo sequence.

7 Principles of Magnetic Resonance Imaging

In 1972 the Australian Paul Lautherbur demonstrated for the rst time that the spatial dependence (Eq. 11) of signals submitted to eld gradients may be used to generate NMR images and was awarded the 2003 Nobel price in medicine for his discovery. This may immediately be

7 PRINCIPLES OF MAGNETIC RESONANCE IMAGING

29

TE
y

e c,d TE/2

a b Gradient

TE/2

x z z

x z

1 2 x 3

1 2 x 3

Figure 9: Rotating-frame vector representation of the evolution of the magnetization during a gradient-echo experiment as displayed by the pulse/gradient sequence on the top. (a) An initial 90 pulse ips the magnetization from z to x (b). (c) After a delay the magnetization will be partially dephased due to the gradient. (d) The sign of the gradient is reversed, making the counterclockwise rotating species rotate in a clockwise orientation and vice versa. (e) After a second delay all spins are refocussed to lie along x . If no transverse relaxation were present this situation would correspond to the spin state in (a). The time elapsed from the initial pulse to the formation of the echo is called TE.

30

7.1 Selective Radio-Frequency Irradiation

a Time

b
d

d
d

f
d

Freq.
0 0 0

Figure 10: Different pulse schemes for frequency-selective excitation (a,c,e) and the corresponding excitation proles (b,d,f). The pulse shapes are (a,b) rectangular pulse, (c,d) gaussian pulse, and (e,f) sinc pulse. The three pulses have different band widths of d = 2/ (b), d = 4/ (d), d = 2/ (f).

applied for 1D imaging, but if one wants to do 2D or 3D imaging it is necessary to be able to select separate slices of the sample. The means for doing this is the frequency-selective rf pulse which will only affects spins with particular resonance frequency range while leaving all other spins untouched. The art of creating frequency selective rf pulses will be discussed in the following Section. 7.1 Selective Radio-Frequency Irradiation

As the free-induction decay of an excited sample has a frequency domain spectrum, so do radio-frequency pulses. Consider a 90 pulse (Fig. 10a) with the resonance frequency 0 and a radio-frequency eld strength of 1 , determining the strength of the oscillating magnetic

7 PRINCIPLES OF MAGNETIC RESONANCE IMAGING

31

eld, B1 (see section 2.3). The Fourier transformation of this pulse shown in Fig. 10b represents the socalled excitation prole of this pulse. We say that the pulse is on resonance with species resonating exactly with a resonance frequency of 0 , while species with other resonance frequencies are off resonance relative to the pulse. The excitation prole for the pulse shows its effect at different frequencies. It is not surprising that the largest effect for this pulse is achieved on resonance (see Fig. 10b). The frequency width of the pulse, , is typically dubbed the band width of the pulse. It is often desirable to have a very band selective rf pulse, i.e. a pulse that has a rectangular excitation prole with well-dened edges. The large number of wiggles for the rectangular pulse in Fig. 10a tells us that this pulse is not particularly good in achieving this. However, by selecting other amplitude proles for the rf pulse, or to be more specic, by choosing the right time-encoding for 1 , we may achieve rf pulses with nicer band-specic excitation proles. For example, the gaussian pulse in Fig. 10c also gives a gaussian excitation prole (Fig. 10d), while the more fancy sinc (sin t/t) pulse in Fig. 10e give a more rectangular excitation prole as shown in Fig. 10f. We will typically use sinc type of pulses for band-specic purposes. 7.2 Slice Selection Consider an experiment where we apply a magnetic eld gradient, Gx , while we apply a frequency-selective rf pulse. Since the resonance frequency of the spins along the x axis varies because of Gx , the pulse will only excite a particular region along the x axis. In this manner we have selectively excited a yz plane/slice at a particular x position depending on the carrier frequency of the selective pulse. This is illustrated in Fig. 11.

7.2 Slice Selection

a
rf

Gx

b
B0
Gx x x x

B0
x1 x2 x3

Figure 11: (a) Selective slice excitation by combining a magnetic eld gradient with a frequency-selective rf pulse. (b) Illustration of the slice-selection process. Due to the magnetic eld gradient along x, only tissue located at position xi will have the right resonance frequency to be excited by the frequency-selective pulse.

32

8 K-SPACE IMAGING

33

Theory Box 6: k-Space Imaging

As described in Section 7.2, magnetic eld gradients may create a spatial distribution of resonance frequencies in order to give information on (r). If we excite the sample uniformly, the freeinduction decay in the rotating frame for a single voxel (v) will be given by If we dene a new vector k given by 1 Gt, (T6-3) 2 Eequation T6-2 may be rewritten to become very similar to Eq. T4-2 k= Z

S(k) = Sv (t, r, G) = (r)dr exp{iG rt} (T6-1) and the detected signal arising from all voxels is obtained by integration over r, Z

(r) exp{i2k r}dr,

(T6-4) and therefore the spin density is obtained by a simple fourier transformation, Z

S(t, G) =

(r) exp{iG rt}dr. (T6-2)

(r) =

S(k) exp{i2k r}dk. (T6-5)

8 k-Space Imaging
In NMR spectroscopy we are interested in identifying different species by their different chemical shift. On the other hand, magnetic resonance imaging normally aims at determining the density, (r), of spins at a particular position in space, r. We can divide the space into small cubes, called voxels, of size dr. The signal intensity for a voxel will be given by (r)dr. As evidenced by Theory Box 6 it is convenient to dene a vector k, k= Gt. 2 (12)

We normally refer to the space spanned by the k vector as the k-space. Equation T6-5 forms a very important basis of magnetic res-

34

8.1 Acquiring k-Space Data

onance imaging since it relates the k-space to the spin density, (r). The spin density is exactly the property that we want to image, since the spin density will vary from tissue to tissue. This implies that we just need to develop a method for acquiring data in k-space in order to obtain magnetic resonance images. 8.1 Acquiring k-Space Data

Most magnetic resonance images are obtained by acquiring a series of 2D images in the xy plane for different locations along z. The initial step in MRI is selection of the desired spatial slice along z as explained in Section 7.2, of which the 2D image should be recorded. Then, the signal is phase encoded by the second gradient along y as the t1 phase encoding of a 2D NMR experiment is achieved (see Section 5). Finally, the third gradient is applied during acquisition. A pulse/gradient sequence accomplishing these three steps is shown in Fig. 12a, and the corresponding k-space trajectory is shown in Fig. 12b. It should be noted that a Gx gradient is applied prior to acquisition under Gx . This moves the initial point to a negative value of kx as illustrated by the dashed arrows in Fig. 12b. Figure 13a on page 36 shows an example of a 2D k-space dataset acquired for a horizontal slice through the head of a patient. The resulting image achieved by fourier transformation of the k-space dataset is shown in Fig. 13b. This image shows well-known features of a persons head and brain. In the following Sections some practical considerations regarding acquisition of k-space data will be discussed, and fast imaging techniques will be presented. Later we shall see how it is possible to change the contrast in images like the one in Fig. 13b either by pulse sequences or by contrast agents.

8 K-SPACE IMAGING

35

a
rf Gz Gy Gx Acq

Slice

Phase

Read

1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000

ky

kx

Figure 12: Two-dimensional imaging pulse sequence (a) and data acquisition scheme (b). The x and y gradients are responsible for phase and frequency encoding, respectively, with the latter being termed the read gradient and the former the phase gradient. The horizontal shading of the phase gradient indicates that it is increased for each experiment. In (b) each row of points is acquired during the read and the strength of the phase gradient determines the vertical position.

36

8.1 Acquiring k-Space Data

ky kx

Figure 13: The k-space data (a) and resulting image (b).

8 K-SPACE IMAGING

37

8.2 Practical Aspects of k-Space Imaging

There are several practical aspects of acquiring k-space data that need be considered before obtaining high-quality images (Fig. 13b). First, we need to know the physical size of the object that we want to make an image of. Just as the spectral width sw (= 1/dt) identies the frequency range of a free-induction decay, we may dene the image size, often dubbed the eld of view (FOV), as

FOV =

1 . dk

(13)

Since k Gt the image size (length and width) is controlled jointly by the sampling rate and gradient eld strengths applied in the experiment. Figure 14 on page 38 gives examples on this. For reference, the good k-space dataset (a) and its corresponding image (b) from Fig. 13 are shown at the top of this gure. Figure 14c is a k-space dataset identical to the central part of that in (a) and may result from a truncated acquisition where the number of sampling points is too low to acquire the full signal. The corresponding image (Fig. 14d) shows that the central part of k-space indeed contains most of the overall image features but also reveals that the missing outer regions of k-space govern the high resolution observed in Fig. 14b. The nal example in Fig. 14e shows a k-space dataset acquired with half as many datapoints as the dataset in Fig. 14a and thereby with the half sampling rate. According to Eq. 13 this should give a two-fold reduction of the FOV in the x and y dimensions as also observed in the image (Fig. 14f). Together these examples demonstrate some of the possibilities and pitfalls one is facing when acquiring k-space data.

38

8.2 Practical Aspects of k-Space Imaging

ky kx

ky kx

ky kx

Figure 14: k-space data (a) and resulting image (b) identical to the data shown in Fig. 13. The effect of not sampling the whole kspace is shown as the reduced dataset in (c) and the corresponding image (d) shows signicantly less resolved features. If the whole kspace is sampled but only with half as many points (e), this reduces the eld-of-view, and only the central part of the patients brain is imaged (f).

8 K-SPACE IMAGING

39

8.3 Fast Imaging Techniques

One of the major problems in the early stages of MRI for clinical applications was the long experiment time for experiments like the one sketched in Fig. 12a. If there are ny increments along the phase direction, acquisition of one image slice lasts roughly ny TR and if we need to acquire nz different slices, the total acquisition time will be approximately ny nz TR. Typical numbers for a MR scanning of a human head may be ny = 128, nz = 40, and TR = 1s which results in a total acquisition time of 85 minutes. This is obviously too much for most practical applications considering that the patient should be immobilized throughout the scanning. This way of acquiring data is schematically represented in Fig. 15 on page 40 and is referred to as single-slice (or single-selection) imaging because it completes one image slice before proceeding to the next. A rst increase in speed may be achieved by realizing that the slice-selection pulse only affects the slice which is excited. This means that it is possible to record a spectrum for several slices during TR while this delay is only necessary between different acquisitions of the same slice. This principle is demonstrated in Fig. 16 on page 41 and allows us to acquire multiple slices at once. Therefore, this method is typically referred to as multi-slice (MS) acquisition. In Fig. 16 four slices are acquired just after one-another giving a four-fold reduction of total acquisition time. In practice more than four slices may be acuired simultaneously, thus adding even more to the time-gain of the method. Still, with this improvement, a scanning employing the sequence in Fig. 12a will last some minutes and still needs to be shortened to be usefull in many diagnostic studies.

40

8.3 Fast Imaging Techniques

Slice acquisition time

Slice 1

Slice 1

Slice 1

Slice 1

TR rf Acq Gy

TR

TR

Frequency of sliceselective pulse is moved

Slice 2

Slice 2

Slice 2

Slice 2

TR rf Acq Gy

TR

TR

Figure 15: Typical sequence of rf, acquisition, and phase-encoding gradient events involved in imaging of a stack of slices using singleslice acquisition. A given slice is excited repeatedly, varying the strength of the phase-encoding gradient (Gy ). After enough echoes have been obtained to complete acquisition of a given slice, the process is repeated for a different slice.

8 K-SPACE IMAGING
< TR

41

Slice 1

Slice 3

Slice 2

Slice 4

TMS

rf TE Acq Gy

TR

Slice 1

Slice 3

Slice 2

Slice 4

TMS

rf TE Acq Gy

Figure 16: Sequence of rf, acquisition, and phase-encoding gradient events involved in imaging of a stack of slices using multi-slice (MS) acquisition. Each section is excited using a giv en phaseencoding gradient (Gy ). After each section has been recorded once, all sections are excited a second time, using a different phase-encoding gradient strength. The attractive issue of this sequence over the one in Fig. 15 is that the multislice repetition time (TMS) is comparable to TE ( 50 ms) which is signicantly shorter than TR ( 1 s).

42 8.3.1 Echo Planar Imaging

8.3 Fast Imaging Techniques

In 1977 Peter Manseld presented a conceptually new technique which acquires a whole k-space plane in one shot. This is one of the reasons why he was awarded the 2003 Nobel price in medicine. A pulse sequence using Manselds idea is shown in Fig. 17a and this kind of experiments are referred to as echo-planar imaging (EPI). In this sequence, negative Gx and Gy gradients applied prior to acquisition move the acquisition starting point to the lower-left corner of k space as illustrated in Fig. 17b by a dashed arrow. The acquisition is carried out in ny steps each acquiring horizontal traces in k-space followed by a short Gy gradient shifting the position along ky to the next row. Reversal of the Gx sign between each row changes the direction of the k space acquisition. With EPI and multislicing the whole 3D imaging time may be reduced to a few seconds. The hardware requirements for an EPI experiment are severe but such experiments are now widely available on commercial scanners. The gradient system must be able to generate very strong gradients with very short raise and fall times to give precise k-space trajectories. Such problems has delayed the practical breakthrough of EPI till the early 1990s, some 15 years after its introduction, but by now EPI has already revolutionized imaging of the brain, allowing for diffusion, perfusion, and functional cortical activation imaging as will be discussed in a later Section of these notes.

8.3.2 Spiral Imaging

Using the basic concept of echo-planar imaging that a whole k-space plane may be recorded at once it is obvious that other gradient sequences may achieve the same. A second method that deserves to be discussed here is spiral imag-

8 K-SPACE IMAGING

43

a
rf Gz

a
rf Gz

Gx
Gx

Gy

Gy

Acq

Acq

ky

ky

kx

kx

Figure 17: (a) An echo-planar imaging (EPI) sequence. In the frequency encoding direction (Gx ) there are rapidly oscillating gradients. In the phase-encoding direction (Gy ) there are multiple short blips. (b) depiction of the echo-planar sequence lling of k-space.

Figure 18: (a) Spiral imaging sequence showing sinusoidal gradients in the Gx and Gy gradients. (b) The resulting spiral trajectory in k-space. The spiral begins in the center of kspace and ends on the edge.

44

8.3 Fast Imaging Techniques

ing. Spiral imaging is performed using two oscillating gradients during the readout period (following the slice-selection period) of the sequence as illustrated in Fig. 18a. To generate spirals in k-space, linearly increasing (in time) sinusoidal gradients are applied along the Gx (cosine) and Gy (sine) axes in such a manner as to follow the spiral through k-space beginning at the center of k-space and ending on the edge (Fig. 18b). Because the spiral begins at the center of k-space, the high-contrast portion of the data is collected at the beginning of the readout before many T2 signal losses. Thus, most errors due to motion and relaxation are minimized compared with other techniques which begin the acquisition on the edge of k-space and reach the center midway through acquisition, as is the case for EPI (Fig. 17). A drawback of spiral imaging is that the data are not located in a rectangular grid required for numerical fourier transformation of the data. This means that the data needs to be interpolated into a rectangular grid prior to processing.
8.3.3 Comparison of Spiral and Echo-Planar Imaging

Both the spiral and echo-planar imaging techniques are extremely powerful and robust, and both allow for the fast scanning which makes certain applications possible. However, there are advantages and disadvantages to both techniques. Availability and image processing Echo-planar imaging is much more widely available on commercial scanners, and vendors already provide EPI sequences which require no ofine processing (i.e., the image reconstruction can be performed on the scanners computers). Performing spiral imaging currently requires a spectroscopist who can program the sequence, al-

8 K-SPACE IMAGING

45

though some commercial vendors are beginning to provide some spiral sequences. Also, because the spiral data are not in rectangular coordinates, ofine processing on a remote computer is usually required to generate images.

Artifacts

EPI suffers from off-resonance problems because there are no refocussing pulses. These off-resonance issues arise from susceptibility artifacts and fat-water separation and lead to well-recognized distortions of the images. With EPI any phase errors are propagated throughout k-space, leading to mismapping and thus distortion on the image. Spiral imaging refocusses periodically in both dimensions leading to less distorted images. However, the artifacts which occur in spiral images exist in both dimensions and manifest as blurring of the image rather than as discrete artifacts as is the case for EPI.

Efciency

Spiral imaging is slightly more efcient than EPI. In EPI, the x gradient is not driven very hard, whereas the y gradient must be driven extremely hard (for the socalled blips). Just like any machine or motor, driving the gradient extremely hard in short bursts requires some small break for rest. Spiral imaging uses both x- and y-gradients and drives both at a high but constant rate. Because there are no sudden changes in the gradients, less of the break is required. This slight increase in efciency means that using a spiral trajectory, one can usually acquire a few more slices than when using EPI at a given temporal and spatial resolution.

46

8.4 Image Contrast

a
Intensity

Small T1 Large T1 Difference 1 Time

b
Small T1 Intensity 1 Large T1

Time

Figure 19: Magnetization/signal recovery after saturation (a) and inversion (b). The times labelled 1 and 2 represent the inversion times yielding maximum intensity difference between the species with small and large T1 relaxation times.

8 K-SPACE IMAGING

47

8.4 Image Contrast In order to distinguish different types of biological tissue in a magnetic resonance imaging experiment there must be a contrast or difference in signal intensity between adjacent tissues. Since the signal intensity is proportional to the number of spins and thereby with the spin density of the voxel, the spin density represents the most pronounced contrast in the image. However, by using special pulse- and gradient-sequences it is possible to obtain T1-, T2-, velocity-, or diffusion-weighted images. How these different contrasts are favoured over oneanother will be discussed in the following sections. Prior to presenting these techniques it should be noted that among radiologists and clinicians, the terms T1- and T2 weighted are very unprecise and typically just refer to experiments using short TR/short TE (T1-weighted), long TR/long TE (T2-weighted), and nally the standard (ideal) experiment with long TR/short TE is referred to as spin-density weighted. A fundamental misconception about a T1 or T2 weighted image is that all tissue contrast in the image is dominated by T1 or T2 effects. Nearly all MR images display contrast primarily related to the proton spin density overlaid by relatively weak effects from relaxation. The following two sections will discuss how to achieve the most pronounced contrast between tissues with different relaxation times.

8.5 T1-Weighted Imaging Apart from having different proton spin density, the relaxation times for different tissue also varies. Representative values are listed in Table 2 and do indeed show signicant variation from tissue to tissue. In the ideal case TR should be so large that all signal is recovered before pulsing the next time, and if TR > T1 there will be at least 99%

48

8.5 T1-Weighted Imaging

180

90

TI

rf Gz

Gx

Gy

Acq
Figure 20: Echo-planar imaging pulse sequence equipped with an initial inversion-recovery block. TI denotes the inversion time (see text).

Table 2: Representative T1 relaxation times.

T1 (ms) 0.5 T 1.5 T Cerebrospinal uid (F) > 4000 > 4000 Skeletal muscle (B/F) 600 870 Gray matter (B/F) 656 920 Liver (B/F) 323 490 Adipose tissue 215 260 a B/F denotes bound and free water, respectively.

Tissuea

8 K-SPACE IMAGING

49

of the signal recovered. If TR is shorter, less signal is recovered, which results in signal loss. However, when tissues with different T1 relaxation times are present, we may have relaxation behaviour as sketched in Fig. 19a for two types of tissue with short and long T1 relaxation times. The two solid curves display how the signals recover as a function of the repetition time, while the dotted line shows the difference in signal between the two tissues. If we want to use the difference in T1 as additional contrast, a simple experiment to achieve this would be a standard MRI experiment employing the repetition time labeled 1 in Fig. 19a. This experiment will partly suppress the tissue with long relaxation time, thus increasing the image contrast. To further improve the T1 weighting one may apply the inversionrecovery pulse sequence shown in Fig. 7 prior to e.g. the echo-planar imaging sequence as shown in Fig. 20. If the inversion time TI is adjusted so that the proton magnetization for one of the tissues exactly crosses zero this tissue will be completely suppressed in the resulting image as illustrated by the inversion times labelled 1 and 2 in Fig. 19b. It should be emphasized that the inversion-recovery experiment provides a much better T1 weight than the standard experiments at the expense of signicantly longer experiment time. If both the 180 and 90 rf pulses are slice selective as shown in Fig. 20 it is still possible to acquire such data using the multi-slice protocol. 8.6 T2- and T2 -Weighted Imaging Just like longitudinal relaxation, transverse relaxation, T2, also varies from tissue to tissue. Figure 21 depicts the signal decay due to T2 relaxation for small and large T2 relaxation times. At the echo time labelled 1 in this gure, the maximum difference between the two

50

8.7 Creating Contrast Using Contrast Agents

Intensity

Small T2 Large T2 1 Time

Figure 21: Signal intensity as a function of the echo time TE. The solid lines represent the signal decay due to small and large T2 relaxation times and the dotted line displays the difference between the two solid curves. The echo time labelled 1 marks the time yielding maximum difference in the two signals.

signals is achieved. While the echo-planar imaging sequence (Fig. 17) is dependent on relaxation under T2 other techniques may refocus the additional magnetic-eld and susceptibility effects discussed in Section 3.2 and display relaxation behaviour according to T2. A very widely used sequence for achieving this is the fast spin-echo (FSE) sequence shown in Fig. 22. Rather than using gradient refocussing the magnetization, this sequence uses a series of 180 pulses to create spin echoes. Thereby the additional T2 effects cancelled.

8.7

Creating Contrast Using Contrast Agents

The beauty of MRI is its ability to create different types of contrast without injecting any radioactive contrast compounds into the veins, as it is necessary for a number of other imaging techniques like PET and CT. MRI normally relies on the intrinsic contrast between tissues. However, MRI will also often benet from using external contrast agents to increase contrast between different tissues.

9 FUNCTIONAL IMAGING
TE
90
o

51

180

rf Gz

Gx

Gy

Acq

Figure 22: Fast spin-echo (FSE) pulse sequence. Each echo is obtained using a different phase-encoding step.

MRI contrast agents are indirect agents that will never be visualized directly in the image, but affect the relaxation times of the water protons in the nearby tissue. Such agents are often paramagnetic and may be categorized in T1 and T2 relaxation agents depending on their actual properties.

9 Functional Imaging
The term functional imaging may have several specic meanings. In all cases the basic idea of functional imaging is, however, to obtain images displaying physiology rather than simple anatomy. In this Section we will focus on the most common use of the term functional imaging, abbreviated fMRI. Specically this technique is used for mapping brain activation. Functional imaging relies on the tight coupling between neuronial activity and blood ow, a coupling that was rst proposed in 1890

52

Brain activity

Oxygen consumption

Cerebral blood flow

Oxyhemoglobin

Deoxyhemoglobin

Magnetic susceptibility

T2 * Increase Decrease MRI signal intensity

Figure 23: Mechanism of blood-oxygenation level dependent (BOLD) imaging. Increased brain activity causes increased oxygen consumption and cerebral blood ow. Hench the oxyhemoglobin level increases and the deoxyhemoglobin level decreases. Since deoxyhemoglobin is paramagnetic the relaxation time increases when the paramagnetic species is removed, leading to an increased MRI signal intensity.

9 FUNCTIONAL IMAGING

53

by Roy and Sherrington. This coupling, although not fully understood, allows for indirect measurement of cerebral activity by monitoring changes in cerebral hemodynamics as illustrated in the ow-chart in Fig. 23. The T2 relaxation rate of blood changes depending on whether or not the hemoglobin is bound with oxygen, a phenomenon rst described by Linus Pauling. When the hemoglobin molecule is bound with oxygen (oxyhemoglobin), blood is slightly diamagnetic. However, when oxygen is removed from the hemoglobin molecule (deoxyhemoglobin), it becomes more paramagnetic due to more unpaired electrons. This increased paramagnetism leads to increased magnetic susceptibility of the tissue. Changes in magnetic susceptibility introduces a change in T2 and may be mapped by T2 -weighted pulse sequences like EPI. Functional imaging takes advantage of the changing signal within blood and surrounding tissue at the ratio of oxyhemoglobin-deoxyhemoglobin changes. When a task or stimulus paradigm is presented to the person in the MR scanner, the cortical neurons in the area responsible for processing the information become active. This activity leads to local increased neuronal metabolism which then leads to increased blood ow. However, the increased blood ow is greater than the metabolic needs of the neurons, thereby resulting in excess oxygen being supplied to the active area. Thus, the oxyhemoglobindeoxyhemoglobin ratio in the capillaries and small veins increases compared to the situation when the neurons are inactive. This increase means less deoxyhemoglobin and thus less signal loss from T2 relaxation. Thereby an increased signal during the neuronally active state compared with the resting state is achieved. It is this slight increase in signal during the active state that is detected in functional imaging. This contrast methanism is referred to as BOLD (Blood Oxygenation Level-Dependent) contrast and is the most commonly used MR tech-

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Figure 24: Three-dimensional, whole brain images of activation during a language task based on word generation from a phoneme. The test persons were presented phonemes and were asked to think of as many English words as they could that contained the phoneme until the presentation of the next phoneme. The dark-gray picture is the anatomical image. In light color is the superimposed functional map. Brain images shown are (a) left hemispheres (b) right hemispheres, and (c) at an angle where the left hemisphere and top of the brain are both partially seen. In (a)-(c), the anatomical images are opaque; consequently only activated regions that lie predominantly on the cortical surface are seen. Image (d) is identical to (c) except that the anatomical image was rendered partially transparent in order to look through and see the activated regions that would normally be blocked from the view by overlapping cortex.

10 MAGNETIC-RESONANCE ANGIOGRAPHY

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nique to evaluate cortical activation. Since the absolute MR signal differences are very small (< 5% with 1.5-T systems), appropriate activation mechanisms must be constructed, to enable precise measurements of activated and nonactivated brain states. Since the signal change is due to T2 relaxation, it is measured by T2 -weighted sequences of which echo-planar imaging is the most widely used. Figure 24 exemplies functional imaging. In this Figure, the test persons were presented phonemes and were asked to think of as many English words as they could that contained the phoneme. The images represent the anatomical image in dark gray overlaid by the functional map in light colors.

10 Magnetic-Resonance Angiography
Angiography is the imaging of owing blood in the arteries and veins of the body. In the past, angiography was only performed by introducing an X-ray opaque dye into the human body and making an X-ray image of the distribution of the dye. This procedure created a picture of the blood vessels in the body. It did not, however, produce an image which distinguished between static and owing blood. Magneticresonance angiography (MRA), on the other hand, produces images showing the blood ow. The intensity in MRA images is proportional to the velocity of the ow. In the following two general types of MRA, time-of-ight and phase-contrast will be described. 10.1 Time-of-Flight MRA Time-of-ight angiography can be performed in several ways. One method uses a spin-echo sequence where the slice-selective 90 and 180 pulses have different frequencies. The 90 pulse excites spins

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10.2 Phase-Contrast MRA

in one plane. The 180 pulse excites spins in another plane. In the absence of ow, no signal is seen because no spins experience both pulses. However, if the ow matches the slice-distance and TE time, blood from the 90 plane ows into the 180 plane and an echo is produced. This principle is illustrated in Fig. 25a. 10.2 Phase-Contrast MRA

Phase-contrast angiography is a little more complicated. Recall the gradient echo which refocusses the magnetization and thus has no net effect on the spins. However, spins moving in the direction of the gradient direction will not be refocussed by the gradient echo. This effect is used to distinguish stationary from moving spins. In practice, two images are acquired, the rst having a gradient echo (e.g. Gx Gx ), and the second has the echo with reversed sign (Gx Gx ). Stationary spins will appear identically in the two images, while moving spins will obtain opposite phases. Thus, the difference between the two images will only contain signal from moving spins while stationary spins disappear. For illustration, Fig. 25 shows a MRA image of the human head. This image clearly shows the blood veins in white while the background signals from stationary tissue are rather weak. For angiography it may also be benecial to use contrast agents to emphasize the blood veins in the images, but it will not be discussed in more detail here, since the beauty of MRI is its ability to achieve MRA images using the intrinsic properties of the different tissues.

11

Localized Magnetic Resonance Spectroscopy

In certain cases the images based on the spin density, as discussed so far, do not provide the desired information. It is often desirable to

90o

180o

11 LOCALIZED MAGNETIC RESONANCE SPECTROSCOPY

Figure 25: (a) Spin-echo sequence using different frequencies for the 90 and 180 pulses. This makes them act on different slices. (b) blood vein in which the 90 pulse excites only the blood contained in the image slice. During the delay between the pulses this blood ows through the vein. The 180 pulse is applied to another slice, and only if the shaded blood volume ows into this slice its magnetization will be refocussed by the 180 pulse. (c) Magnetic-resonance angiograph showing the blood arteries in a human head in white and light gray.

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11.1 Single-Voxel Techniques

monitor the spatial abundance of different metabolites. Signals from such metabolites appear at different resonance frequencies in an NMR spectrum and will thus be distinguishable by NMR. The idea of localized magnetic resonance spectroscopy (MRS) is to acquire an NMR spectrum for a particular spatial location. Unlike MRI where voxel sizes of 1 1 5 mm3 or smaller are available, the voxel size should typically be larger than 1 1 1 cm3 in MRS to obtain an acceptable signal to noise ratio. There are two main techniques for acquiring localized MRS, singlevoxel and multi-voxel techniques. 11.1 Single-Voxel Techniques

Single-voxel techniques acquire spectra from a single small volume element of the tissue. The most common approaches excite only the desired tissue volume through the intersection of three orthogonal sliceselection pulses. A pulse sequence that achieves this is shown in Fig. 26a and is known as point-resolved spectroscopy (PRESS). It uses a 90 excitation pulse and two refocussing 180 pulses, each with different physical gradient as the slice-selection gradient. Only spins located in the intersection of all three slices produce the spin echo and appear in the spectrum. Figure 26c exemplies applications of MRS. It displays point-resolved spectra of the human brain and in addition, two zoomed representative spectra. 11.2 Multi-Voxel Techniques

Multi-voxel techniques are those from which multiple spectra are obtained during a single measurement. The most common of these is known as chemical-shift imaging (CSI). CSI techniques are analogous to standard imaging techniques in that phase encoding gradient tables

11 LOCALIZED MAGNETIC RESONANCE SPECTROSCOPY

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a
rf Gx

90

180

180

b
rf Gx

90

180

Gy

Gy Gz

1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000 1111 0000

Gz Acq

Acq

Figure 26: (a) Point-resolved spectroscopy (PRESS) pulse sequence timing diagram. (b) Multi-voxel volume selective chemicalshift imaging (CSI) pulse sequence. (c) point-resolved spectroscopy of the human brain and zoomed representative spectra from 1) white matter hyperintensities and 2) normal appearing white matter.

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are used for spatial localization. An example of such a sequence is shown in Fig. 26b.

12

Instrumentation

At the end of these Notes it appears relevant to make a few comments on the instrumentation used for MRI experiments. Although the MR scanner is much

12.1

MR Scanners

Figure 27 shows pictures of four different types of scanners. The whole-body scanner (Fig. 27a) is typically used for scanning of the body region of the patient. It has the magnetic eld aligned along the body of the patient. The hole in the scanner is typically between 55 and 60 cm, which may limit the size of the patient entering the scanner, but obviously it is much more difcult to manufacture scanners with larger diameters. The magnetic eld strength may be up to 1.5 T on whole-body scanners. An important application of MRI is imaging of patients heads. Thus, specially designed head scanners have been developed as illustrated in Fig. 27b. Since the hole in these scanners is much narrower than in whole-body scanners, the magnetic eld strength may be as high as 7 T for head scanners. Finally, it is convenient to have scanners where extremities (arms, shoulders, legs) may be scanned. Such scanners typically have a much more open design than the cylindrical head- and whole-body scanners. For such scanners the magnetic eld strength may be up to 3 T.

12 INSTRUMENTATION

Figure 27: MR scanners for different purposes. (a) whole-body-, (b) head-, (c,d) extremety-scanners.

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12.2 Gradient System

12.2

Gradient System

An additional issue that makes MR scanners differ from normal NMR spectrometers is the need for magnetic eld gradients in MR scanners. As mentionned in Section 6 it should be possible to create magnetic eld gradients in all three dimensions. Figure 28 shows the coil design used for generation of z (Fig. 28a) and xy (Fig. 28b) gradients in whole-body and head scanners. The principle is to place two electromagnets (coils with high current through them) with opposite orientation in the direction of the desired gradient. This is relatively simple for the z gradient which is created by two oppositely oriented solenoid coils, while the xy gradients are created by sets of socalled gure-8 saddle coils. Since the spatial resolution depends on the gradient strength, it is desirable to have as strong gradients as possible. In practice this will be a trade off between sensitivity and resolution. Also the current running through the gradient coils may be a severely limiting factor since too high current through the gradient coils will make them heat up and eventually quench the magnet. Typically achievable gradient strengths are on the order of 40 mT/m corresponding to 1.7 MHz/m for 1 H.

12 INSTRUMENTATION

Figure 28: Schematic of gradient coils used to generate z (a) and x or y (b) gradients.

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