Objectives: To understand 1 Basic physics of magnetic moments, macroscopic magnetization, precession,rotating reference frame 2 Relaxation and the Bloch equations 3 Free induction decay 4 The spin echo pulse sequence 5 Basic MRI apparatus, quadrature detection 6 Slice selection 7 Gradient Compensation 8 Spatial encoding 9 Spin warp imaging 10 Stimulated echos 11 Inversion recovery 12 Fast Imaging 13 Flow and Angiography--Phase contrast and time-of-flight 14 Maximum intensity projection 15 Qualitiative difference between angiographic methods Nuclear magnetic resonance was discovered by Bloch and coworkers and by Purcell and coworkers in 1946 and has been an important tool for spectroscopic analysis of molecular structure ever since. Bloch and Purcell received Nobel Prizes for their work. The use of magnetic resonance for imaging purposes began in the early seventies with perhaps the most important contributions made by Lauterbur who suggested the use of gradient fields to encode spatial position of the nuclear spins. Commercial introduction of MR imagers began in the early 1980's and since then MRI has become the greatest innovation in medical imaging since computed tomography, which it has come to outperform in several areas. As we will see, in addition to directly competing in areas where CT is used, MRI has far broader potential, for example in generating quantitative flow information and for spectroscopic identification of specific molecules taking part in physiological processes. The force exerted on a particle with charge Q by an electric field E is given by Fe= QE. If there were magnetic monopoles Maxwells equations would be symmetric with respect to interchange of electric and magnetic fields and we would have a force relationship like Fm = mB. Fortunately, for patients sitting inside MRI magnets, magnetic poles always come in pairs so that there is no net magnetic force on static objects. Figure 1 illustrates that for the case of a magnetic dipole, which does exist, a torque T can be exerted on the dipole. B mB +m d -m - mB The torque is given by T = mdB = B where is the magnetic dipole moment = md (1) A similar torque is exerted on a current carrying loop situated in a magnetic field as indicated in Figures 2A and 2B Figure 2A Figure 2B B B F = idl x B • A x i µ = iA Torque out of page = µ x B The magnetic moment of this current loop can be shown to be =iA The origin of the magnetic resonance signal is the nuclear magnetic moment produced by the nuclear spin. The relationship between angular momentum and the magnetic moment can be understood qualitatively by considering the magnetic moment of a current loop of area A, carrying current i, such as that shown in Figure 3. Assuming that the current is due to a charge q of mass m traveling in a circle at radius r as shown in Figure 3 we can write = iA = (q) / (2 r/v ) (r 2 ) = (q/2) vr = (q/2m) mvr = ( q / 2 m) J (2) where J = mvr is the angular momentum of the particle. For a nucleus, we can consider that there is a distribution of rotating charge analogous to that in the example. The differences between the nucleus and the current loop are reflected in the factor multiplying the angular momentum. In the case of the nuclear magnetic moment the relationship is written as J (3) where is called the gyromagnetic ratio and the magnitude of J is related to the nuclear spin quantum number I by J = (I ( I+1 )) 1/2 h / 2 where h is Plank's constant. Although MRI in general deals with any nucleus having non zero spin, protons are by far the easiest to image because they are most abundant. For the purposes of this course we will limit our attention to proton imaging. However, keep in mind that specialized applications including sodium, phosphorus and other nuclei are possible, although usually more difficult. In the absence of an external magnetic field the proton spins in the body would be randomly oriented giving rise to no measurable magnetic moment in a volume the size of a typical imaging volume element (voxel). However when placed in a magnetic field the proton energy is quantized into two quantum levels which depend on whether their spin is up or down relative to the magnetic field. The higher energy level is associated with the spin down state since the natural tendency is for spins to align with the field and work is required to twist the spin around to the spin-down position. The energy of the magnetic moment in the magnetic field is given by E = - For protons = ((1/2(1/2 +1))1/2 h/2and the two possible energy states shown in Figure 4 are E+ = + (1/2) (h/2 and E- = - (1/2) (h/2 B0 Spin up E + Spin down N+ Spin down E - Spin up N- Transitions from the low energy state to the high energy state may be induced by radiation of frequency where h= E and E = (E+ - E-) = (h/2) B0 (7) (8) This yields =( / 2)B0 (9) or an angular frequency of = 2 B0 ~ 64 MHz at 1.5 Tesla. (10) Photons with energy equal to the difference in energy between two states are said to be in resonance with these states. This is the origin of the "resonance " part of nuclear magnetic resonance. In the original applications of NMR, samples were irradiated with radiofrequency radiation and the absorption of the radiation by the sample was measured as the frequency was swept. This produced a spectrum of absorption lines at various frequencies. Because the protons in various molecules see slightly different magnetic fields because of contributions from neighboring charges, it is possible to identify the absorption lines associated with various molecules by the so called "chemical shift " in their resonant absorption. When protons are placed in an external field B0 at temperature T there will be an excess population of protons N- aligned with the field and a somewhat smaller number N+ antiparallel to the field, where the + and - refer to relative energy. The ratio of the number of protons in the two energy states is given by the Boltzmann relation N- / N+ = e E/kT where k is Boltzmann's constant. (11) To calculate the ratio in the exponential we need / 2 = 42.58 * 106 Hz/Tesla h / 2 Joules/Hz and k = 1.38 * 10-23 Joules / degree Kelvin Assuming B=1.5T and a temperature of 300K, we obtainE =4.2* 10 - 26 Joules and kT = 4.14 * 10 - 21 joules. This gives E / kT = 10 - 5. Therefore we can expand the exponential obtaining or (N-) - (N+) = N+ N/N =E / 2kT = 5 10 -6 (12) Where we have used the fact that N = N + N and N ~ N . + + So N+ ~ N/2 Therefore, there is an excess of only about 5 protons in 10 6 which are aligned with the applied magnetic field. These excess protons combine to produce a net magnetic moment per unit volume M. Since there is no other defined direction except that of B0, the expectation values of the components of the individual proton magnetic moments along the x and y directions are zero. Therefore the net magnetic moment ( or magnetization ) produced by the excess protons points directly along the applied magnetic field. Suppose that by some means the magnetization is tipped away from its equilibrium direction along B0 as shown in Figure 5. B0 T M Figure 5 A torque given by T = M x B0 (13) will be exerted on the magnetization causing a precession around B0 with angular frequency prec . The equation of motion of the magnetization is written by recalling the angular form of Newton's second law, namely that torque equals change in angular momentum. Therefore, since the angular momentum per unit volume Jv is given by Jv = M / Newton’s second law bcomes dJv / dt = d( M / ) / dt = M x B0 (15) It can also be shown that for a vector M precessing at angular velocity wprec dM / dt = wprec x M (16) comparing equations 15 and 16 we see that wprec = - B0 (17) which corresponds to a clockwise rotation with an angular velocity equal in magnitude to the angular frequency of the photons required to induce transitions between the proton energy levels. The precessing transverse component of the magnetization produces a time varying magnetic field which can induce a voltage signal in a receiver coil according to Faraday's law of magnetic induction, which states that the induced EMF is equal to the time rate of change of the magnetic flux through the receiver loop. Recall that the flux is the integral of the normal component of the magnetic field over the surface of the coil as shown in Figure 6. B0 M Receiver coil Mxy Induced voltage Optional reading Ch. 14 and 15 Bushberg et al The Essential Physics of Medical Imaging Ch 28 Christensen It is convenient to look at the behavior of the magnetization in a reference frame rotating at an angular frequency equal to the resonant frequency. It can be shown that in a reference frame rotating at angular velocity f there is an effective magnetic field given by Beff = B0 -f / This can be seen by arguing that in the rotating frame the effective rotational frequency is eff =B0 - fBeff which can be solved for Beff . For f = 0 = B0 the effective field of the NMR magnet goes to zero in the rotating frame. As the frequency is increased from below resonance to above resonance the z component of Beff decreases from B0, goes through zero and then becomes negative. In order for there to be precession, which is required before an observable signal can be induced in the detector coil, we must tip the magnetization into the transverse plane. This is done by applying a radiofrequency field, usually called B1. The total effective field in the rotating frame is given by B' = B0 - + B1 (19) In the rotating frame precession takes place around the effective field B'. If a linearly polarized B1 field of frequency = 0 is applied it can be shown that this can be decomposed into two circularly polarized fields, one which rotates with the precessing magnetization in the laboratory frame, and one which rotates at resonant frequency but in the opposite (counterclockwise) direction from the magnetization as shown in Figure 7. Figure 7 B0 M Laboratory frame B1 cw B1 B1 ccw Any torques exerted on the magnetization by the counterclockwise field cancel over time and produce no effect. In the rotating frame neither the clockwise rf field nor the magnetization precess and the clockwise component ,which we will call B1 from now on, can cause the magnetization to precess toward the transverse plane as shown in Figure 8. z M M x B1 Rotating frame y x B1 By analogy with our previous discussion of the torque exerted on M by B0 , we can immediately write that the angular precession frequencytip is given by tip = B1 (20) =wtip t (21) and the tip angle is given by where t is the duration of the radiofrequency pulse. As an example, let us calculate the size of the rf field needed to produce a tip angle of 90 degrees in a time of 1 millisecond. B1 =/ ( t ) = (( / 2 ) / ( 2 * 42 MHz/T * 10- 3 secs) = 6 * 10- 6 T * (1 gauss /10- 4 T ) = .06 gauss We should mention that if a linear excitation field is used, only one half of the rf power is effective in tipping the magnetization. The other half can still contribute to heating the patient. Therefore it is more efficient to produce circularly polarized rf fields so that all of the rf power is used for imaging purposes. This can be done using so-called quadrature excitation using rf fields of sinusoidally varying amplitude. Suppose we apply a 180 degree rf pulse to a sample. The longitudinal magnetization will be inverted and will point in a direction opposite B0. The longitudinal magnetization will then undergo an exponential return to equilibrium with a time constant T1 introduced by Bloch and called the spin-lattice or longitudinal relaxation constant. Following excitation, the longitudinal magnetization Mz will be given by Mz = M0 - 2M0e - t / T1 as shown in Figure 9. (22) Longitudinal Magnetization Following Inversion T1=1000 ms Time Seconds Notice that after four or five T1 intervals the system has nearly returned to equilibrium. T1 is a phenomenological descriptor of the rate at which various interactions between the proton and its environment induce energy transitions which slowly result in the reestablishment of the spin up and spin down level populations predicted by the Boltzmann equation. The importance of the T1 constant for medical imaging is that different types of tissues have different T1 values. Depending on the sequence of rf excitation and signal readout used to form the MR image, these T1 differences produce differences in tissue contrast which may readily be seen as pixel intensity differences on the image. Bloch also introduced another time constant T2 which he ascribed to the exponential attenuation of the transverse magnetization following an excitation pulse. This time constant includes those interactions which contribute to T1 but also those which involve only phase changes as opposed to energy transitions. The effect of T2 decay following a 90 degree pulse is shown in Figure 10. A homogeneous B0 field is assumed for the present discussion. Relaxation Following 90 Degree Pulse Bloch introduced some phenomenological equations to describe the sort of time dependent behavior of the magnetization described above. The Bloch Equation is an extension of the basic Newton's second law equation with the addition of terms describing the relaxation effects and is given in vector form as dM / dt = M x B - ( Mx i + My j ) / T2 - ( Mz - M0 ) k /T1 where i, j, and k are unit vectors along x, y, and z. (23) In the rotating frame, the first term, which produces precession, is absent and the solutions reduce to Mz = Mz0 e- t / T1 + M0 ( 1- e- t = M0 - (M0-Mz0)e- t/T1 Mxy = Mxy0 e -t / T2 / T1 ) (24) (25) where Mz0 is the initial longitudinal magnetization, M0 is the equilibrium magnetization, and Mxy0 is the initial transverse magnetization following the excitation pulse. Remember that for any nuclear state the Heisenberg uncertainty principle says that E = h / t (26) recalling that E= hf, and w = 2f, we get w=2/t (27) where t is the lifetime of the state. This band of frequencies causes interference(dephasing) which causes the signal decay as shown in Figure 12. The frequencies which are present can be obtained from the Fourier transform of the detected signal which is shown in Figure 13. Narrow resonances are characterized by large T2 values. Wide resonances are associated with short T2 values. ( FID ) In a Real Magnet When an excitation pulse is given in a real imaging magnet, it is found that the signal decays more rapidly than predicted by the transverse decay constant T2 as shown in Figure 14. Figure 14 The detected signal decays faster than expected, with a decay constant called T2* associated with the combined effects of T2 and magnetic field inhomogeneities which produce a spectrum of detected frequencies. The oscillations inside the envelope imposed by T2* decay occur near the resonant frequency. The interference between several nearby frequencies associated with the variations in the magnetic field lead to a rate of dephasing which is faster than that predicted by T2 decay alone. The Fourier transform of the detected signal gives the distribution of proton precession frequencies present in the detected signal. The faster the falloff in the transverse magnetization, the broader will be the width of the observed proton line. This rapid falloff in signal is a problem in imaging but is a disaster for spectroscopic applications where one hopes to separate the peaks from protons in biological molecules. Because of the line broadening produced by field inhomogeneity, careful shimming of the magnet is done by tweaking small currents in correction coils or by placing metal shims in the magnet to perturb the field so as to achieve greater uniformity. Some typical values for T1 and T2 are given in Table 1 in milliseconds. Table 1 B0 = .15 T TISSUE Grey matter White matter Fat Cerebrospinal fluid (csf) T1 520 380 170 2000 T2 95 85 100 1000 Table 1 continued B0 = 1.5 T T1 T2 Grey matter 950 100 White matter 780 92 Muscle 869 47 Blood 1200 100 Some general remarks can be made regarding T1 and T2. T1 increases at higher field strength, whereas T2 is fairly independent of field strength. From the table above note that fat has a very short T1, while csf has a very long T1. Solids have long T1 but very short T2. See page 52 of Smith and Ranallo. There are a variety of rf pulse sequences which can be used to generate solutions of the Bloch equations which emphasize either proton density, T1, T2, or combinations of these parameters. A frequently sequence for MR imaging is the spin echo sequence. This sequence has the property that the effects of magnet inhomogeneities which lead to rapid decay of the MR signal are greatly reduced. Consider the sequence of Rf pulses shown in Figure 15. TR TE/2 TE/2 90x RF a b 90x 180y c d signal FID ECHO (data acquisition) At time a, a 90 degree pulse is applied along the x axis in order to tip the magnetization into the transverse plane. Because of field inhomogeneities and T2 effects the spins will precess at different angular velocities. In the rotating frame those spins precessing faster than the resonant frequency will go clockwise, while those going slower will precess in a counterclockwise fashion as shown at time b. b a slower y x dephasing faster At time c, a 180 degree pulse is applied along the y axis in order to place the fast spins at the phase angle formerly occupied by the slow spins and vice versa. Since the fast spins are still faster because their local environment has not changed, they will catch up with the slow spins which are now precessing toward them. c d faster rephasing slower Rotating frame Note that the rephased amplitude is not as large as the amplitude of the original FID since the effects of T2 decay may not be rephased. If a series of 180 degree pulses are applied at equal intervals the signal may be repeatedly rephased. The envelope of all the rephased signals represents the T2 decay for the sample. In this way the spin echo sequence permits improved measurement of T2 in the presence of field inhomogeneities. From an imaging point of view it also removes so called susceptibility artifacts which can arise at interfaces of dissimilar materials. The time between excitations is called TR and plays an important role in the determination of T1 contrast since it determines the extent to which the longitudinal magnetization recovers. For very long TR the longitudinal magnetization of all tissues will have recovered producing no contrast. High T1 contrast between two tissues is obtained by choosing TR approximately equal to the average T1 of the two tissues. Now that we have some idea how spins may be manipulated to produce signal we will move on to MR imaging (MRI). We will need to learn more about how pulse sequences can be manipulated to produce various contrasts as different combinations of spin density, T1, and T2 contrast are generated. But first we need to review the basic imaging apparatus. Figures 16 and 17 ( From General Electric Signa product literature ) illustrate the basis components. Figure 16 CONTROL COMPUTER SCANNING Shim Supply Image Disc Tape Data Disc Magnet Gradient Coils Array Processor MAIN COMPUTER Gradient Amplifiers Pulse Control Module Image Processor Operator’s Console Image Processor Image Transceiver Patient Transport RF Amplifier Remote Console A simplified schematic of the Signa System’s components and their interrelationships Figure 17 Magnet and cryogens Shim coils Gradient Coils RF Coils The Z Gradient Coil Z axis RF Coils Gradient Coils Shim coils Magnet and cryogens A coil flux lines A cross sectional representation of the Signa Magnet B coil flux lines The Z gradient coil varies the magnetic field along the longitudinal plane Nitrogen X Helium Vacuum X gradient coil Cryogens surrounded by vacuum are used to to maintain low temperatures Y Status Display Panel Button Controls Trolley Bridge The Face of the Signa Magnet Y gradient coil Z Relative orientation of X and Y gradient coils The main magnet can be permanent, resistive or superconducting. The latter is commonly used for high field applications typically above 1 T. Because uniformity is essential for decreasing T2* signal decay and to prevent spectral broadening from the same mechanism in spectroscopic applications shim coils are used to tweak the magnetic field. Superconducting magnets are operated at liquid helium temperatures, about 4 degrees K. Both liquid helium and liquid nitrogen are employed to ensure that the coils remain in the superconducting range. Maintenance of cryogens is a major expense for MR scanning with a superconducting magnet.The coils consist of superconducting niobium-titanium wire embedded in a protective copper matrix. The main magnet provides the B0 field which determines the resonant frequency of the precessing protons. The gradient coils provide linear variations of the local magnetic field for the purpose of spatially encoding the positions of the protons by creating spatial variations in their precession frequencies. The x,y, and z gradient coils are all concentric with the z axis of the magnet (patient cranio-caudal axis). The coils are formed by wrapping conducting wire around a fiberglass cylinder. The z coils are wrapped at the two ends of the magnet opening and produce linear variations from B0 as distance increases from the magnet isocenter. The x and y coils are saddle shaped and are identical to each other except that the are oriented at 90 degrees to each other. . For the x and y coils it is important to realize that the effect is to increase or decrease the magnitude of the z component of the field in the x or y directions, not to introduce x or y field components The main or so-called body rf coil is also enclosed within the magnet cover and is usually of a birdcage resonator design. Additional specialized coils which can be situated closer to the patient to increase the detected signal are also used. Head, extremity, neck and various surface coils are used in an attempt to improve signal to noise ratio. For some applications where the uniformity of deposition of rf energy is better with the body coil, than with the specialized coils, the body coil may be used to deliver a uniform tip angle while the specialized coils are used for receiving only. Because the received signal is thousands of times smaller than the rf excitation pulse, it is important to detune the receiver coil during rf pulse transmission. The received signal is sent to a quadrature phase detector. The purpose of this circuit is to strip off the resonant frequency so that audio frequency signals can be used for signal processing. This amounts to analyzing the data in the rotating frame. Quadrature detection is also necessary in order to distinguish between signals which are equally displaced in frequency from the resonant frequency in the positive and negative directions( since cos w= cos (-w) ) The processing is shown in Figure 18 and relies on the fact that cos( + )t cos t = [ cos(t) + cos(2 + ) t ] / 2 (29) and cos( + )t (- sint) = [ sin t - sin(2 + ) t] / 2 (30) cos ( + )t Multiply by cos t Multiply by - sin t sin (t) + - Sin (2 + )t Cos (t) + cos (2 + )t Low pass filter Low pass filter sin (t) Cos (t) M real imaginary M imaginary t real Because the imaginary signal is available ( the signal that has been set up so that it is known to lag the real signal by 90 degrees ) it is possible to distinguish between + and - values of w. This scheme is referred to as quadrature detection. This is illustrated in Figure 19 which shows how the availability of the imaginary component can distinguish between the signals associated with points at +x and -x. These signals have equal real parts but opposite imaginary parts due to the fact that they are rotating in opposite directions in the rotating reference frame. imaginary -x • -x • 0 • +x + t - t +x real Since the resonant frequency has been stripped from the detected signal, further amplification and A/D conversion of the signal can take place at audio frequencies ( kHz instead of mHz ). The real and imaginary parts of the signal are separately digitized and are separately stored in the computer so that phase images as well as magnitude images can be formed. In most MRI applications it is desirable to excite spins in specific planes within the patient so that tomographic images analogous to CT slices can be obtained. This is done by temporally modulating the rf excitation pulse so that it contains a predetermined band of frequencies. This rf pulse is delivered while a slice select gradient is applied in the desired direction. This gradient creates a linear variation in resonant frequency. Only those spins having resonant frequencies within the bandwidth of the rf pulse are excited. For example, suppose a gradient is applied along the z direction as shown in Figure 20. frequency ∆ rf bandwidth Excited Slice ∆Z 0 Z=0 Variation in resonant frequency vs Z due to Z gradient Z Since the resonant frequency is given by f B/2 in the presence of the Z gradient, which has a value Gz T/cm, the resonant frequency as a function of Z becomes f (Z) = (Z) / 2=(B0 + Gz Z) / 2 and the slice thicknessZ is related to the rf bandwidth by f = Gz Z / 2 For a 1.5 T system with = 42 mHz/T and Gz = .5 G/cm, with 1G = 10- 4 T, a 2 cm slice requires f = 4200 Hz If we desire to place this slice around the position Z = +10 cm then the center frequency shift f0 for the rf excitation should be f0 = ( Gz Z ) / 2kHz The rf excitation pulse is arranged to be circularly polarized with the form Bxy = e it The desired rf bandwidth is obtained by temporally modulating the rf with a waveform S(t) as shown in Figure 21. xy The overall waveform then becomes Bxy(t) = e i wt S(t) (33) The Fourier transform of this is given by the convolution theorem as xy(w') ('-) where is the FT of S. In order to form a well defined slice profile a sinc function sin (t / t ) / (tt) as shown in Figure 22 is used. This produces a rectangular profile in frequency (and in the slice select direction) as shown in Figure 23. ∆ f = 1/ ∆t Thus, for 1 millisecond t we obtain a bandwidth of 1000 Hz. For Gz = 0.5 G/cm this produces a selected slice of Z =f / (GZ/2 = 1000Hz / [ (42*106 Hz/T)*0.5*10- 4T ] = 0.5 cm During the slice selection process the rf pulse is applied while the slice select gradient is turned on. The presence of the gradient will act to dephase the transverse component of the magnetization. This would reduce the amount of signal available at readout since, even if a spin echo sequence is used, the effects of the dephasing due to different amounts of precession at various spatial positions along the gradient would not be refocused. Therefore it is necessary to apply a negative lobe of the slice select gradient which is equal and opposite to that which is present while the rf is applied. This is shown in Figure 24. RF Slice select Compensation lobe Although it is not obvious that the compensation lobe duration should be half that of the slice select gradient, it can be shown that this is a good approximation to the solutions of the Bloch equations. ( Bailes and Bryant ,Contemp. Physics,1984,vol.25. N0. 5, 441-475) We should mention that since it takes several T1 periods for the longitudinal magnetization to recover before the slice may be reexcited, it is possible to jump to other slices while the first slice is recovering. In this way multi-slice techniques considerably decrease the scan time which would be required for sequential single slice techniques. This is a less important issue when very short TR sequences are used. Thursday- Thanksgiving no class Tues Nov 3 RSNA no class Thursday Nov 5 more MR Tuesday Nov 10 MR applications Thursday Nov 12 Review session Tuesday Nov 17 Final exam CSC G5/113 10am-noon Now that we have a slice selected in the z direction, we need to determine the x and y coordinates within the slice. Spatial encoding is done using gradients in the x and y directions, applied separately. We will consider a one dimensional problem first. Suppose in the slab shown in Figure 25 that there are two objects at x1 and x2. X Y • • x2 Z ∆Z x1 Bz x B0 If we apply a gradient in the x direction, the objects will resonate at frequencies relative to isocenter ( the point where the gradient amplitude is zero ) of 1= Gx x1 and 2 =Gx x2. (35) By Faraday’s law, the detected signal in the receiver coil will be proportional to the time derivative of the magnetic field and therefore proportional to the rate of change of the transverse magnetization. Assuming a 90 degree tip has been done we get s2(t) = D1 1 e i1t + D2 2 e i2t (36) where e.g. D1 represents the density of protons at x1 multiplied by a geometrical factor describing the coil sensitivity at x1. Since the changes in w caused by the gradient are much smaller than w0, we can replace the multiplicative (x) terms by 0 and write s1(t)=s2(t) / 0 = ( D(x) e iw(x) t dx) (37) In the present example D(x) would just be the sum of two functions. Note that it is important to keep the (x) terms in the phase factor. The signal with0 stripped off can be expressed in terms of the 's as s(t)= ( D(x) e i(x) t dx) (38) This describes a superposition of signals at different frequencies which vary with x position and which are weighted by the signal strength at each position. This would be equivalent to listening to all of the radio stations on the dial at the same time. This can also be written as s(t) = D(x) eiGxxt dx (39) We can describe the spatial distribution of spins in the x direction as a Fourier integral over spatial frequency kx as D(x) = (1/2 D (kx) e ikx x dkx (40) where D (kx) represents the k space weightings of the spatial frequencies needed to reproduce D(x). Taking the FT of equation 40 we get D(kx) = (1/2 D(x) e - ikx x dx (41) Now if we make the substitution in equation 39 s(t) = D(x) eiGxxt dx (39) that Kx =-Gxt we obtain s(t) = ( D(x) e -iKxx dx) (42) (43) Comparing equations 41 and 43 D(kx) = (1/2 D(x) e - ikx x dx (41) s(t) = ( D(x) e -iKxx dx) (43) we see that the two expressions are equivalent if and kx = Kx = -Gx t (44) This means that the MR signal at each t provides the k space expansion coefficients for kx = Gx t . To summarize, when we write the equation for the temporal signal s(t), which contains several temporal frequencies, the fact that these frequencies are linearly related to the x position enables us to write an expression for s(t) which is identical to that for the Fourier expansion coefficients D(kx) which describe the weightings of the various spatial frequencies needed to describe D(x). Let's use these equations to examine the imaging situation involving the two point objects at x1 and x2 shown in Figure 25. Since there is a direct relationship between the x axis and frequency, there will be two frequencies superimposed in the detected signal as shown in Figure 26 giving, according to equation 38, s(t)= D(x1) e i (x1) t +D(x2) e i (x2) t (45) As a function of temporal frequency w(x) this waveform obviously contains two temporal frequencies as shown in Figure 27. X Y • • x2 x1 ∆x Signal strength 2 1 However we can obtain the same result using the previous equations which, in a more complicated situation, would be the best method. Using equation 40, 44,and 45, D(x) = (1/2 D (kx) e ikx x dkx (40) (44) s(t)= D(x1) e i (x1) t +D(x2) e i (x2) t (45) we get D(x) = ( (D(x1) e i (x1) t +D(x2) e i (x2) t) e ikxx dkx) /2 which , when we substitute kxx = -(x) t becomes D(x) = ( (D(x1) e - i kxx1 +D(x2) e -i kxx2 ) e -i kxxdkx)/2 or, D(x) = D(x1) ( e ikx(x-x1) dkx)/2 + D(x2) ( e ikx(x-x2) dkx)/2 or, recognizing the integral form of the delta function, we get e ikx(x-xi)dkx = 2(x-xi) D(x) = D(x1) (x-x1) + D(x2) (x-x2) which represents two delta functions at x1 and x2 in the x domain as shown in Figure 28. Figure 28 At this point we should emphasize that and x are linearly related by Gxx and that time and spatial frequency are linearly related by kx = -Gxt. Time and temporal frequency form one set of conjugate Fourier variables, and x and spatial frequency in the x direction form another as shown in Figure 29. Generally, everything is done by converting all values to the x,kx pair. x FT kx FT x t The MR signal is typically sampled 256-512 times during the echo or FID. The relationship between the bandwidth w , desired field of view in the x direction, FOVx, and the required x gradient is given by (kHZ) = Gx FOVx (46) The temporal bandwidth filter is used to prevent higher frequency information outside the field of view from aliasing into the image. This would occur because of undersampling of the temporal information. Aliasing can still occur in the directions perpendicular to the xreadout since, as we will, see there is no temporal bandwidth filter available in those directions. We will defer our discussion of spatial encoding in the y direction, which is done somewhat differently. Eventually we will map out 128 (typically) lines in k space obtaining a continuous set of D (kx) values as in Figure 26 for 128 fixed values of Ky. This method is called SPIN WARP imaging. But first let's see how we could make a 2D projection imaging just with the x space ( Figure 28 ) encoding that we have done. If we apply a linear combination of x and y gradients simultaneously we can repeat the above analysis along several different x' axes. The D(x) values we obtain can then be back projected using the same methods we have discussed for x-ray CT as shown in Figure 30. Basically the D(x) values will reinforce where they overlap. As in the x-ray case avoidance of the star artifact would require filtering before back projection. Figure 30 Recall that in our discussions of x-ray imaging we said that we could represent any one dimensional image as a superposition of images formed by sticking an appropriate series of sinusoidally transmitting grids in the beam as shown in Figure 31. The mathematical description of this is Image(x) = ai sin kix + bi cos kix where the ai and bi are real numbers. (47) If we have a set of grids of continuously varying spatial frequency we can write this as Image(x) = 1/(2) D(kx) eikx x dkx (48) where D(kx) is the weighting of the transmission contribution per unit frequency interval from the grids. D(kx) is a complex number which introduces whatever necessary phase is needed to ensure that the proper admixture of sine grids and cosine grids are used. To make a 2 dimensional x - ray image we would need some grids oriented in the y direction. The transmission through these grids would multiply the transmissions produced by the x grids. The grid equation in pictorial form would be as shown in Figure 32. Figure 32 Image (x,y)= where it is assumed that each of the grids is multiplied by an appropriate complex weighting factor which determines its transmission and its lateral shift. In general the weightings of the x grids may change depending on which y grid is in. This gives us a 2 dimensional matrix or space of weighting coefficients for the various spatial frequency grids present as shown in Figure 33. ky kx This space is called (spatial) frequency or k space. The above example illustrates the construction of an image in k space using a series of grids with weightings which vary at each point shown in this space. Knowing that it is possible to construct a 2 dimensional image by a series of sinusoidal waves as we did above, the next question is to ask how we can determine the weightings of the sinusoidal construction functions at each point in frequency space. The procedure is very similar to what we would do in a one dimensional case. For example, suppose we want to expand the square wave x=0 - a/2 shown above into a cosine series as + a/2 square(x) = a0 +an cos kn x. where kn = (2n-1)/a and n goes from 1 to infinity ( in practical systems the highest frequency is always limited by apparatus or image processing constraints). The way we determine the weighting of the various cosine functions is to multiply the function of interest by each cosine function one by one. On the right side the products of all unlike cosine terms integrate to zero (orthogonality). The cosine2 integrates to a constant giving an = constant * square(x) cosknx dx (49) As we will see, in spin warp magnetic resonance imaging, the determination of the k space weighting coefficients along lines in the kx direction is also carried out by multiplying the proton distribution by one sinusoidal function of spatial frequency ky at a time in the y direction and then multiplying by a series of sinusoidal functions of frequency kx in the x direction. Let us now consider the MRI case. A two dimensional distribution of protons can be represented by a superposition of waves in two dimensions as D(x,y) = 1/2 D(kx,ky) e ikx x e iky y dkx dky ) (50) Suppose that following excitation and before readout with the x gradient as discussed earlier, we apply a y gradient for a short period of time . While the y gradient is on, the precession frequency will depend on y according to y = Gy y (51) and the MR signal following application of the y gradient will have acquired a phase factor equal to y = Gy y During the x readout the signal will be modified from our previous signal equation as s(t,)= ( D(x,y) e i(x) t ei Gy y dxdy ) (53) Notice that this equation is analogous to equation 49 an = constant * square(x) cosknx dx (49) for the solution of the Fourier expansion coefficient for the square wave. In this case the image, in addition to being multiplied by the xwaves, is also multiplied by a sinusoidal wave of fixed frequency in the y direction. Setting ky = - Gy and recalling that (x)t= -kxx , equation 53 becomes s(t,)/2= 1/2 ( D(x,y) e -i kxx e- i ky y dxdy ) (54) Taking the 2D Fourier Transform we obtain D(x,y) =1/4 ( s(t,) e i kxx ei ky y dkx dky ) (55) Comparing equations 50 D(x,y) = 1/2 D(kx,ky) e ikx x e iky y dkx dky ) (50) and 55 we see that s(t,) = 2D(kx,ky) (56) So, equation 54 which reminded us of the solution for the coefficient of the square wave expansion functions is also a solution for the 2D k space weighting coefficients in the MR case. In the MR case the multiplication of the image (proton signal distribution) is accomplished by applying a y gradient for a short timeand producing a continuously changing sinusoidal multiplication factor in the x direction by means of the x gradientsSince kx = -Gxt and ky = -Gy depend linearly on t and respectively, the signal obtained during x readout following the imposed y gradient gives us a line of k space weighting coefficients along a line of constant ky. The variable is usually held constant while the y gradient is incremented evenly, usually for 128 separate lines in k space.The effect is the same as if the y gradient were held constant and were allowed to increase linearly. This process is called phase encoding but is better understood as solving for D(kx,ky) at fixed ky. The temporal progression of the MR signal as the phase encoding is increased is said to occur in pseudotime, a time variable which increases a little bit at a time. The y direction is called the phase encoding direction and the x direction is called the frequency encoding direction. Each line in k space, shown in Figure 35 is called a "view". View 128 Ky View 1 kx The phase encoding gradient is usually represented on the pulse timing diagram as shown in Figure 36. Gy The figure is meant to indicate that the y gradient is stepped so as to cover all the necessary y spatial frequencies in k space. Notice that negative as well as positive frequencies are obtained. Remember the existence of "negative frequencies" really just means that in order to have a complete Fourier representation of an object, for example in the x direction, terms of the form e- ikx as well as terms of the form eikx are required. The extension of the 2D case discussed to 3D is straightforward. As you might guess, an additional phase encoding operation is performed by stepping the z gradient. In this way the Fourier coefficients D(kx,ky,kz) are obtained, once again by fixing ky and kz and then reading out the time varying signal during the x gradient. The advantages of 3D imaging include the possibility of voxels of equal size in all three dimensions and certain SNR gains derived from processing the signal from the entire volume at all times during the data acquisition. The relationship between the field of view in the y direction, FOVy, the spatial resolution in the y direction y and the k space resolution ky are determined by the requirements of the Nyquist sampling theorem which states that there must be two samples per cycle. This means that since k = 2f, kymax= 2/2y (57) The k space resolution ky is then given by, since the region from -kymax to + kymax is spanned ky = 2kymax/Ny = 2 / Nyy (58) where Ny is the number of phase encoding steps. It can be shown that the number of pixels is equal to the number of phase encoding steps. Therefore FOVy = Nyy=2/ky (59) Therefore the field of view in the y direction is inversely proportional to the k space resolution. For a given field of view the size of the pixel in the y dimension is inversely proportional to the number of phase encodes. The size of the phase encoding gradient is determined by equations (42) and (57). At the highest spatial frequency (and therefore the highest Gy) there should be one cycle, or a 360 degree phase change every 2 pixels as shown in Figure 37. The progressive wrapping of the spins in the y direction in this diagram is the origin of the term " Spin Warp ". The Nyquist criterion leads to a phase shift per pixel of r max = Gymax y = Gymax= FOVy / Ny)= Ny / FOVy (61) Therefore, if the desired FOVy and the number of phase encode steps are known a can be chosen and Gymax is determined. Just as we multiplied the square box function by the particular cosine function to determine its weighting coefficient, in the case of MR imaging we also multiply through by a factor which causes sinusoidal variation in the y direction. The sinusoidal variation in detected intensity from protons situated along the y direction is due to the progressive twist in the spins in that direction. This twist is due to the linearly increasing resonant frequency created by the y gradient. Recall that since kyy=-t , the twist created by the linear gradient causes the same sort of sinusoidal signal variation as the sinusoidal xray grid we discussed at the beginning of this section. In the 2D MR case, multiplication by this sinusoidal variation in the y direction not only gives us a single solution, but a series of weighting coefficients at fixed ky and continuously variable kx (= -Gxt ) as the signal is read out in time as shown by the solution machine in Figure 38. In this machine we put in coins, first a ky coin and then a series of kx coins to get out a series of D(kx, ky) solutions for the k-space coefficients along one k-space view. Then we put in another ky coin and start the kx coins over again. The ky coin corresponds to a phase wrap in the y direction. As time goes on, the linearly increasing frequency along the x direction multiplies the proton signal distribution by sinusoidal functions of increasing frequency in the x direction. The proton phases are wrapped in the y and the x directions.The y wrap is applied and held constant for each progression of x wraps. At each point in time the detected signal is the solution for the weighting function D(kx, ky) which multiplies the two dimensional spatial frequency function which modulates the signal distribution at that time. In general there is a different set of x weighting coefficients for each value of the applied sinusoidal y function ( i.e. for each phase encoding). MR Scanner Acting As An Analog Computer s(t,)/ 2 = D(kx,ky)= 1/2 ( D(x,y) e -i kxx e- i ky y dxdy ) (54) B0 Receiver coil M D(kx,ky) Mxy y phase encoding twist ky multiplies proton signal by fixed eiky Gx early later performs integral to produce k-space data D(kx,ky) kx=-Gt x multiplies proton signal by eikx There are a number of variations in the way that the spins may be excited and read out. These various pulse sequences are designed to create different contrast dependencies on T1, T2, spin density, spin velocity, etc. Clinically it has been found that certain sequences are best for certain applications. The radiologist must become familiar with all of the available sequences in order to intelligently order the sequence of scans which will lead to the most diagnostic image for each case. We will now review some of the most commonly used sequences including the spin echo sequence described briefly earlier. The pulse sequence for the spin echo sequence is shown in Figure 39. TR TE/2 RF a b TE/2 c 180y d 90x 90x signal ECHO FID (data acquisition) Gz Slice select readout Gx Rephase in x Dephase in x Phase encode Notice that the dephasing lobe of the x readout gradient which has been placed before the 180 degree pulse has the same sign as that of the rephasing portion. This is because the 180 degree pulse reverses the relative positions of the phase shifts caused by the dephasing gradient. Therefore the x dependent phase shifts are all refocused at the peak of the echo. The signal amplitude for the spin echo sequence may be derived by considering the solutions of the Bloch equations and is given by (62) s =D(H) [1- e-TR/T1] e-TE/T2 where D(H) is the density of protons (with a coil sensitivity factor lumped in) and T1 and T2 are the local relaxation values. By varying TE and TR images emphasizing differences in each of these parameters may be generated. For large TR the term in brackets is close to one and T1 contrast will be suppressed. This is because all substances regardless of their T1 values will have time to return to equilibrium value of longitudinal magnetization. If, at the same time, TE is made short, the last term will also generate little dependence on T2. Therefore the combination of long TR and short TE produces an image with signal proportional to the local density of protons. These images usually have fairly low contrast. Short TE combined with short TR produces T1 weighted images since the first exponential term will be highly T1 dependent. The combination of long TR and long TE will generate primarily T2 contrast. Which combination is chosen depends on the clinical situation. From the equation for the spin echo signal amplitude s =D(H) [1- e-TR/T1] e-TE/T2 it can be seen that a tissue with longer T1 will appear darker than one of shorter T1, since the term in brackets decreases for large T1. On the other hand, longer T2 increases the image brightness as can be seen from the last exponential term. Therefore T1 and T2 contrast are of opposite sign. Since tissues with longer T1 usually have a longer T2, this effect can produce a cancellation of contrast making it more difficult to distinguish two different types of tissue. That is why it is important to use images with different amounts of T1 and T2 weightings. Sometimes in a spin echo sequence two different 180 degree pulses are used after the rf excitation so that the first generates a short TE and the second generates a long TE. In this way from a single rf excitation two echoes can be recorded, the first containing little T2 contrast and the second containing significant T2 contrast. Figure 40 illustrates the use of multiple 180 degree pulses to repeatedly refocus the spins while they are in the transverse plane. This permits the acquisition of images with different T2 weighting within the same 90 degree excitation sequence. Notice that the refocused echoes have an amplitude falling on the T2 decay curve. The individual echoes decay at the T2* decay rate. 90 180 180 90 Excitation )) TI TE Detected Signal TE T2 decay T2* decay TR Figure 41 (From Wehrli et al. Parameters Determining the Appearance of NMR Images-General Electric) illustrates the wide variation in image contrast that may be obtained with a spin-echo sequence depending on the parameters chosen. Figure 41 shows two sets of four echo acquisitions. Set A was obtained at TR = 0.5 seconds. Set B was obtained with TR =2.0 seconds. Within each set the amount of T2 decay which occurs increases from left to right. Figure 41 Note that in A1 the cerebrospinal fluid (arrows), which has a long T1 and a long T2 is suppressed by the short TR which has prevented full recovery before the application of the 90 degree pulse. In B4 which corresponds to long T2 decay, the cerebrospinal fluid has a greater relative image brightness than the rest of the brain because of its long T2. The images have been individually rescaled to show relative brightness. It is possible to show that any two rf pulses will result in a spin echo signal. In Figure 1 of Hahn "Spin Echoes",Physical Review, Vol. 80, no.4 page 583, it is demonstrated how two ninety degree pulses lead to the formation of a spin echo at a time equal to twice the separation of the two pulses. Basically after being rotated to the transverse plane, the spins fan out uniformly into a circular figure. This figure is then rotated into the vertical plane by the second ninety degree pulse. Then the spins, because of their different precession rates refocus into a figure eight on the surface of a sphere and form the peak echo signal. (You have to look at the figure). Since any two rf pulses will have components in the transverse plane, these 90 degree components will also form a spin echo regardless of the rf tip angle. In Hahn's paper he shows that three 90 pulses will also form an echo which is called a stimulated echo and involves a rather complicated set of illustrations. Foo (UW-1990) used the stimulated echo pulse sequence related to the sequence shown in Figure 42 to image blood flow. TE 90 TE TE 90 90 spin echo Simulated echo A spatially selective 90 pulse is applied in the upstream region of the vessels of interest. These are allowed to fan out. Then a nonselective 90 is applied. This places all of the spins into the longitudinal plane where no T2 decay is experienced. After a suitable travel time, another spatially selective 90 is applied in the downstream region of the vessels producing a stimulated echo for those spins which saw all three 90 pulses. Since the two selective 90 pulses do not overlap spatially, the static tissue does not see all three 90 pulses and does not experience the stimulated echo. Therefore this method represents a potential, although not often used, non-subtractive approach to MR angiography, which we will discuss in more detail later. Notice in the diagram that a spin echo is formed due to the first two 90 pulses. Another spin echo would be formed from the second and third 90 pulses. It is important to choose the time parameters so that this echo does not overlap the stimulated echo. There are also FID signals following application of the first and third 90 pulses. The last one must also be over before the stimulated echo occurs or signal from static tissue will be seen in the image. The stimulated echo is also used in a spectroscopic technique called STEAM in which three selective 90 pulses are used to excite a small cubical region over which excellent field uniformity leads to narrower spectral lines. This technique provides the opportunity to examine a small selected region of the body where questions related to tissue viability may be studied based on the presence of spectral lines associated with various metabolites such as ATP. spectroscopic voxel excite three orthogonal planes A pulse sequence called inversion recovery is used to provide maximal T1 contrast. In this sequence the longitudinal magnetization is inverted using a 180 pulse and is then read out with a 90 pulse after a time TI called the inversion time. The magnetization recovers according to the equation Mz = Mz0 ( 1 - 2 e-t / T1 ) (63) where Mz0 is the equilibrium magnetization at the time of the 180 pulse. This value depends on the repetition rate TR. The recovery curves for two tissues with T1 values of 1000 and 2000 are shown in Figure 43. By choosing the inversion time so that one of the tissues is passing through zero, this tissue will provide zero signal upon readout with the 90 pulse. The maximum signal difference is obtained by choosing TI to be approximately equal to the average of the two T1 values. Following application of the 90 degree readout pulse, magnetization which had passed through zero and was pointing upwards will be 180 degrees out phase in the transverse plane with magnetization which was still negative at the time of the 90 degree pulse. This fact can be used to distinguish between magnetization of equal magnitude but opposite sign. Such phase corrected inversion recovery displays preserve all of the contrast provided by the recovery of the longitudinal magnetization. The inversion recovery sequence may be combined with a spin echo sequence as shown in Figure 44. TR TE/2 T1 180 90 FID TE/2 180 180 SPIN ECHO In this case the 180 degree pulses refocuses the dephasing caused by T2* effects as in normal spin echo imaging. Additionally data can be collected in negative as well as positive areas of frequency (k) space. A special case of the inversion recovery spin echo sequence is the so called Short TI Inversion Recovery (STIR) sequence. We mentioned above that T1 and T2 effects produce opposing contrast leading to possible cancellation of contrast. In the STIR sequence the inversion time is kept short enough so that all of the longitudinal magnetization is still negative. In this case tissues with smaller T1 will produce less signal following the 90 pulse. Once in the transverse plane, the magnetization associated with tissues having short T2 will decay faster leading to diminished signal. Therefore the effects of T1 and T2, which are correlated within a given tissue ( since T1 interactions also contribute to T2) will be additive, removing the possibility of contrast cancellation. Following a few years of heavy reliance on spin echo imaging, interest was focused on techniques for faster imaging. These techniques utilize gradient echo imaging with small tip angles. The advantages of using small tip angles is illustrated in the Figure 45. z Mz0 .86 Mz0 30o .5 Mz0 Mz0 M For a 30 degree tip angle, half of the transverse magnetization is realized while the longitudinal magnetization is only decreased by 13 percent. This permits rapid restoration of the longitudinal magnetization so that short TR values may be used, thus reducing scan time. A gradient echo pulse sequence is shown in Figure 46 . RF a a signal Readout gradient Phase encode spoiler The dephasing lobe of the readout gradient dephases the FID. The size of the gradient echo signal is the same as the FID would have been at the same time if it had not been disturbed. Because there is no 180 pulse, the decay of the signals proceeds according to T2* and field nonuniformity effects are not refocused. In very short TR sequences it is possible for a so-called steady state transverse magnetization to be set up. The alpha pulses (analogous to the 90 degree pulses in a spin echo sequence) can cause spin echoes which build up to produce a steady state signal separate from the gradient echo which is formed from the FID . The contrast produced by the steady state signal has a different dependence on T1 and T2* than the gradient echo. In some cases it is desirable to suppress the steady state signal. In the sequence shown, the "spoiler gradient" on the phase encode axis has been used to dephase the transverse magnetization. The steady state can also be destroyed by randomly changing the phase of the alpha pulses so that no steady state coherence is built up. This is called "RF spoiling". Gradient echo sequences are especially useful in MR angiography where short TR sequences are used to suppress static tissues. In conventional MR imaging, which typically uses spin echo sequences, flow manifests itself as a signal void( dark region ) in the slice images. This happens simply because in order for a spin echo to be formed, the spins must see both the selective 90 and the selective 180 pulses. Thus, the cross sections of blood vessels are routinely seen in axial spin echo images. The use of pulse sequences designed to generate signal from flowing spins is called MR Angiography (MRA). In the discussion below we will look at some of the basic concepts of MRA. There are three major types of MRA methods, Phase Contrast Time-of-Flight., and Contrast Enhanced. Phase contrast angiography relies on the fact that spins moving in a gradient with velocity v, for example in the x direction, will experience a phase shift given by = (t)dt = Gx vt dt (64) Consider the effect of placing a bipolar gradient in the x direction prior to the x readout pulse as shown in Figure 47 . RF readout x It can be shown that the phase shift acquired by the moving spin as a result of the bipolar gradient is + - = - G v t2 (65) where t is the width of one of the bipolar lobes and G is the size of the bipolar gradient. = B(t) dt = G xdt = G vt dt 0 t 2t = Gv/2 {t2 =-Gvt2 t 0 -t2 2t t =Gv/2 {t2-0 –4t2-t2} For static spins the effects of the two lobes cancel and the net phases shift is zero. This is shown in Figure 48. Static Spins Moving Spins net phase Basically the static spins see equal and opposite magnetic fields during the two lobes. Therefore, the phase shift caused by the positive lobe is cancelled by that produced by the negative lobe. However, for the moving spin, a greater magnetic field is seen during the negative lobe, since it has moved along the gradient into regions of higher field. Because of this the phase shift during the negative lobe is larger than that during the positive lobe leading to the net result calculated. Now suppose that a bipolar gradient of opposite sign is used. This will produce a phase shift of - + = + G v t2 (66) The complex difference between the signal readout following each of these bipolar gradients will be proportional to (67) Therefore, for G v t2 less than or equal to about 1 radian, the angiographic difference signal is approximately linearly related to velocity. The vector diagram associated with the formation of the complex difference image is shown in Figure 49. Complex Difference Signal sinGvt2 The phase contrast data acquisition usually must be done using separate bipolar sensitization gradients in all three directions. The results from these three scans are added vectorially by taking the square root of the sum of the magnitude images from the three scans. It is important to set the size of the bipolar gradient carefully so that velocities which are too high do not go over the top of the sine function and provide incorrect or even zero signal. This is a problem in areas of high vessel pulsatility in which the velocity varies greatly within the cardiac cycle. Even in the absence of pulsatility there is a distribution of velocities within vessels. For parabolic flow in a circular vessel the peak flow velocity in the center of the vessel is twice the average velocity and the velocity at the edges of the vessel is near zero. VENC sinGvt2 velocity aliasing v The phase contrast method can be implemented in a phase difference display mode in which phase difference images are used instead of magnitude images. In this mode images display flow direction rather than just speed. In this mode only one direction of flow sensitization can be used at a time. This mode is most useful in vessels with flow in one dominant direction. The phase difference image is calculated as arctan I R arctan I (68) R where, for example, R+ and I + are the real and imaginary components of the signal obtained with the bipolar gradient of positive (up-down) polarity. Velocity-Resolved PC 1 2 11:12 P 3 2563 4 Sum of S/I Velocity Images 5 6 Sum of flows Vel FOV = +/- 60cm/s Vres =17cm/s A 4 x 2 enc steps 7 8 Sc =22 Speed Image It is important to obtain a phase difference in order to eliminate any non-zero phase which might be associated with the static background tissues, which, even though they are not moving, typically have nonzero phase. The size of the velocity sensitization gradient is usually chosen so that the fastest velocities present will provide a phase difference of . The velocity corresponding to this maximum phase difference is called VENC. Velocities greater than VENC will be aliased to lower velocities. This can be a problem in clinical imaging where the velocity spectrum present is unpredictable and changes throughout the cardiac cycle. It should be noted that although the static tissue cancels in the complex difference image, its presence leads to an underestimation of phase and therefore of velocity. This is a so-called partial volume effect. When phase difference images are used to calculate flow, the product of velocity and area, the presence of the static tissues in the pixel also leads to an overestimation of vessel area which tends to lead to an overestimation of flow. Although the two effects tend to compensate, the net effect is usually an overestimation of flow, at least in small vessels. Typical phase contrast angiograms are shown in Figure 50. These are sagittal views (lateral view looking through the ears) taken at two different VENC values. The image on the right was taken at a lower VENC to emphasize the slow flow in the arterio-venous malformation seen in the upper right hand side of each image. We have already discussed the fact that flowing blood gives a signal void in spin echo sequences because the spins do not see both RF pulses. We also mentioned the method of Foo in which the stimulated echo sequence involving three 90 pulses was used to selectively image flowing spins. The latter method is called a "tagging" method and is one example of a time of flight technique. Most current clinically used time of flight angiography relies on another effect called "flow related enhancement". This effect relies on the fact that if static spins see a series of RF pulses with short TR interval they will not have time for their longitudinal magnetization to recover. Soon the longitudinal magnetization becomes "saturated" and tends toward a small equilibrium value. Conversely, spins which are flowing into the field of view have full longitudinal magnetization and will produce far greater signal and pass out of the imaging slice before seeing too many rf pulses. RF Saturation 1.0 RF Pulses Longitudinal Magnetization (along B0) 0.5 Regrowth Equilibrium magnetization TR 0 Time Flow Related Enhancement Imaging Slice Flow 0 1 2 Mz Static Tissue Time Flow Related Enhancement Vessels Static Tissue Image from Anderson, Edelman and Turski Clinical MRA Many of the angiographic techniques provide 3D data sets, including the sequential 2D TOF technique described above. In order to produce projection angiograms which look like their x-ray counterpart, it is necessary to trace rays through the 3D volume at some angle of interest. Several algorithms exist for dealing with the information encountered along the various paths through the data set. The most frequently used technique is called the "Maximum Intensity Pixel (MIP) " method. In this technique only the value of the most intense pixel is projected onto the image plane. This method is robust and provides attractive vessel images. Its primary disadvantages are that it underestimates vessel diameters and that vessel overlap is not adequately represented. Maximum Intensity Projection 1 Images from Anderson, Edelman and Turski Clinical MRA 5 2 10 6 2 7 3 10 Underestimation of vessel diameter is due to the fact that the small vessel signal at the edge of the vessel does not compete favorably with the more numerous maximum pixel signal candidates residing in the static spin background pixels. Because these may be chosen more often than the vessel signal, the edge of the vessel merges with the background resulting in decreased apparent width. Nevertheless, this technique often produces satisfactory images and is the most widely used algorithm for generating projection images from 3D MR angiographic data sets. MIP Images from 3D Volume Data axial coronal sagittal left carotid sagittal right carotid source image F. Korosec PhD Thesis U. of Wisconsin 1991 Examples of Signal Saturation 2D TOF 3D TOF 3D Slab Keller and Saloner, TOF Flow Imaging, in MRA Concepts and Applications, Potchen et al. eds. The dependence of the signal on the number of RF pulses is shown in Figure 51 for 10, 30, and 50 degree tip angles. Notice that the larger the tip angle, the more rapidly the static tissue is suppressed. The size of the tip angle must be chosen in accordance with the expected blood velocity and slice thickness so that adequate saturation of static spins is achieved but flowing blood signal does not become saturated. The geometry for a 2D sequential slice time of flight technique is shown in Figure 53. The data is acquired one slice at a time. Therefore, in order to acquire 128 phase encodings, 128 RF pulses are applied to the same slice. This is more than adequate to saturate the static spins. The number of RF pulses seen by the flowing spins depends on slice thickness and velocity. The signal produced by spins of various velocities are shown in Figure 54 for various tip angles in the case of a 5 mm slice. Note that for spins traveling at 1 cm/sec, a small tip angle is optimal in order to reduce saturation. As the velocity increases, the optimal tip angle increases. In the 2D TOF geometry it is possible to apply a 90 pulse and a spoiler gradient above the slice in order to dephase flow coming from the direction opposite from that of the vessels of interest. This "SAT" technique is useful for separation of arterial from venous flow signals. Time of flight (and phase contrast) techniques are presently implemented in 2D and 3D acquisition geometries. In the 3D techniques, because larger volumes are used, rf saturation becomes a more important consideration than in 2D geometries. The spatial resolution of an MR angiogram is determined by the voxel size. The voxel sizes for several geometries are shown in Figure 57. As can be seen from the diagrams, the 3D data acquisition sequences provide the smallest voxels. The direct projection techniques have voxels which extend all the way through the region of interest. In these applications it is customary to apply a mild dephasing gradient in the projection direction in order to partially dephase large objects while leaving small objects like vessels relatively unaffected. This results in a smaller overall detected signal, which means that the signal representing the vessels can occupy a larger fraction of the dynamic range of the A/D converter. Increased spatial resolution is not the only advantage of smaller voxels. As we mentioned before, there can be a distribution of velocities within a vessel. The accumulated phase of the flowing spins within a vessel can destructively interfere, leading to signal loss. This is generally referred to as "intravoxel dephasing" and is another reason why it is important to keep voxels as small as possible. There are three things which may be done to minimize intravoxel dephasing. Aside from keeping the distribution of velocities small by using small voxels, it is important to use the smallest possible TE time so that dephasing has less time to occur. Another method is called "gradient moment nulling". It is possible to design gradient waveforms which refocus moving as well as static spins. The phase acquired by a by a moving spin is given by =Gr r(t) dt (69) The position variable r(t) can be expanded into a series of terms representing velocity, acceleration, jerk, and higher order terms as r(t) = r0 + vt + 1/2 at2 + ... (70) It can be shown that if only velocity is present, the phase shift produced by a gradient of amplitude 1,-2,1 as shown in Figure 58, will refocus all spins moving with constant velocity in the direction of the gradient, independent of the magnitude of this velocity. Flow compensated gradient G t It is also possible to design gradients which refocus acceleration as well as velocity induced phase shifts. However these gradient require longer TE times and lead to possible problems with higher order motion terms which depend on the third and higher powers of t. Generally velocity compensated gradients are worthwhile, but the use of acceleration compensation is not worth the additional increase in the required TE. Contrast Enhanced MRA Effect of Gadolinium on MRA Signal 1 Through Plane 0.8 0 Gado 60 T1 = 50 0.6 Signal 0.4 In-Plane 15 0.2 0 0 T1 = 1000 60 0 0 5 10 A 15 Number of RF Pulses 20 Comparison of 2D TOF with 3D Contrast-Enhanced MRA Prince, Grist and Debatin, 3D Contrast MR Angiography, 1997 Some Current MRI Contrast Agents Knopp et al, J Magnetic Resonance Imaging, 1999 Artifacts due to Uneven Weighting of Acquired Data Injected contrast signal Time Overlap of Arteries and Veins Fast Imaging Data acquisition in k-space (the spatial frequency domain) ky kx The Mona Lisa in k-space ky kx Low frequency Mona k - space ky kx High frequency Mona k - space Image k-space space k-space Image space k-Space Flight Plans Cartesian Undersampled Projections PR HyperTRICKS VIPR PR TRICKS HyperVIPR Keyhole Imaging* Spock in k-space Dynamic Static * Van Vaals et al. J. Magn. Reson. Imaging, 3,671-675 (1993) Keyhole Acquisition c(t) Artery Vein Time AAAAAAAAAAAAAAA B B A K-Space A B Keyhole k-space Keyhole Imaging Low Resolution Time frames Keyhole Time frames 3D TRICKS* * Time Resolved Imaging of Contrast KineticS Korosec F, Frayne R, Grist T, Mistretta C. Time-resolved contrast-enhanced 3D MR angiography. Magn Reson Med 1996; 36:345-351. C B A K-Space Segments for 3D TRICKS B C ky Vein Artery ••• A ••• Temporal Aperture Keyhole Frame Time B A C A C A B C A B TRICKS 7.5-10 s B C 3D TRICKS Selected MIP images from a 27 frame series. Frame time Contrast dose 5.6 seconds 35 ml Gadodiamide. 3D TRICKS 512 x 128 x16 Frame Time 5.6 s “We are using 3D TRICKS” 3D Muppet Show Disney’s California Adventure Theme Park High Resolution Time Resolved MRA Objectives • Dynamic time series • High spatial resolution HyperTRICKS Acquisition Artery Vein c(t) Time Dynamic Phase Steady-State A B A C AB A CA ... D kx ky kz A BC D VTRAC - Vessel Segmentation Vessel Segmentation using Time-Resolved ACquistion Mazaheri, Du, Carroll, et al., Proc. 7th ISMRM, p. 2181 (1999). ROI Selection time 2D Cross Correlation Coefficients Formed from Arterial and Venous Reference Curves ccA cc(x,y,z) = ccV S (x, y,z) S (x, y, z)R i i i i R S (x, y,z) S (x, y,z) R R 2 1/2 2 i i i original 6 segmented HyperTRICKS* with Low Frequency Vein Suppression * 2 minute dynamic followed by 10 minute steady state* 4 4.6 s time frame 12 min MF Vein suppressed MF 3 3 2.05 mm 0.19 mm * using Gadomer 17- long lasting intravascular contrast agent How Would We Do MRA If We Could Start all Over? Cartesian MRA Limitations of Cartesian Acquisitions For Cartesian acquisition the number of pixels in y or z is directly proportional to imaging time. This is a serious limitation in the presence of motion or dynamic contrast variations as in contrastenhanced MRA UW CME Imaging Course Wollaston Lake Saskatchewan August 1996 Dr. Reichelderfer “How could we do virtual real time endoscopy with MR”? Cartesian vs. PR trajectories ky ky kx kx FT (Spin-warp) PR Caution Undersampled Projection Holes! Fully Sampled k-space Image space Undersampled k-space Image space Comparison of Conventional and PR Methods Imaging Time 1 Cartesian 512 x 128 D. Peters PhD Thesis UW 1999 1 PR 512 x 128 4 Cartesian 512 x 512 PR TRICKS 72 projections 8x undersampling 2.6 s frames 384 x 256 x 18 3 times more resolution / time than previous 3D TRICKS movie K Vigen et al PR HyperTRICKS D C B C B A A B C B C D ABACABAC Contrast Arrival D Steady State PR HyperTRICKS PR TRICKS Sagittal Coronal J. Du et al PR HyperTRICKS 1mm slices Calfs from 2 station exam 0.94 mm pixels 4.1 sec frames 2.5 min exam J. Du et al PR-hyperTRICKS: Run-off Study 45 sec 59 sec 81 sec Asymmetric enhancement: A-V transit time T. Carroll, J. Du et al Vastly Undersampled Isotropic PRojection Imaging ( VIPR ) A full 3D projection sampling trajectory Barger, Block et al. Relative VIPR Noise vs Speedup Factor 22 11 5.5 2.7 256 x 256 x 256 Relative noise g 49 6 Speedup factors R relative to Cartesian 49 5 4 22 3 11 5.5 2 2.7 1 5000 10000 15000 20000 25000 Number of projections angles Preliminary Results 2 3 4 4 sec time frames 256 x 256 x256 1.6 x 1.6 x 1.6 mm 6 7 8 Speedup relative to Cartesian = 33 Undersampled by 100x W. Block et al Arterial Time Frame W. Block et al Time Resolved VIPR 2 sec time frame intervals 40 x 24 x 40 elliptical FOV 256 x 256 x 256 1.6 x 0.94 x 1.6 mm 40 ml Gado at 3ml/s 24 s BH Speedup relative to Cartesian = 33 Undersampled by 100x E. Brodsky and W. Block Time Resolved VIPR 2 sec time frame intervals 256 x 256 x256 1.6 x 1.6 x 1.6 mm 24s BH Speedup relative to Cartesian = 33 Undersampled by 100x E. Brodsky and W. Block Jiang Du VIPR + Bolus-Chase initial results Abdomen & calf: Bolus-chasing + timeresolved Thigh: separate injection 400 X 400 X 400 FOV 256 X 256 X 256 matrix 1.56 X 1.56 X 1.56 mm All the stations are time-resolved 15 s acq. 22 ml dose 2.0 ml/sec 56 s acq. 16 ml dose 2.0 ml/sec 56 s acq. M.S. VIPR+Bolus-Chase 4D imaging MIP 3D Jiang Du Time series M.S. Phase Contrast VIPR Provides signal proportional to velocity TL GU et al Basic VIPR PC vs 3D TOF voxelsize = 0.24 mm3 4:48 voxelsize = 1 mm3 VIPR 10 minutes post contrast 384 x 384 x 384 10x speed gain relative to 3D TOF 3D TOF 5:40 No contrast TL Gu et al Basic VIPR PC vs Conventional PC 10X Advantage 4:35 Voxel Size 0.83mm3 2.5mm3 7:11 TL Gu et al Pulsatile Flow Phantom Cartesian PC PC VIPR 30cm/sec VENC =50 Flow pump waveform 72 bpm Images Courtesy of Sean Fain PC VIPR 10-15 m post contrast 12 24 1.0 *24*24*12*5:48 = 12 S= 0.24*22*16* 8*4:48 .63 24 .63 .24 mm3 .63 Need to repeat at higher BW and with eddy current correction 4:48 3843 3D TOF 8 22 .86 16 5:40 256 x 224 2 slabs 1.6 mm slices 1.0 mm3 .74 1.6 Questions Regarding 3D TOF vs PC VIPR Image Quality • Will longer PC VIPR TE’s, typically 5-6 ms cause dephasing or will 0.25mm3 voxels reduce velocity dispersion enough? • Can we use contrast to go to higher BW for VIPR PC. Velocity and Speed Resolved PC VIPR Motivation: It is the goal of PC VIPR to image all vessels in the FOV with good SNR When a single Venc is used, some vessels may alias while others may be imaged with low SNR. Fourier velocity encoding permits the use of the large gradients required for good low velocity SNR without aliasing. All applied gradient encodings contribute to the SNR in each velocity bin. Velocity-Resolved VIPR PC 1 2 11:12 P 3 2563 4 Sum of S/I Velocity Images 5 6 Sum of flows Vel FOV = +/- 60cm/s Vres =17cm/s A 4 x 2 enc steps 7 8 Sc =22 Speed Image Formation of Anatomical Image from Speed Images S1 S2 S3 S4 Sx X Y Sy Z Sz SMIP, Sum or Matched Filter Sum of Squares Tian-Liang Gu M.S. Cine’ VIPR PC: Introduction Motivation: One isotropic 3D scan to retrospectively measure all the blood vessel waveforms in the image volume. VIPR trajectories are acquired for each cardiac phase using retrospective ECG gating.* *Wieben O, PhD thesis UW-Madison, 2002 1 2 3 4 5 6 7 8 9 Cine’ PC VIPR 9 cardiac phases 2563 10 min scan Venc = 30 time series Sum of all projections Sum of All Projections Acquired During Time Series Time Series Motion Correction Using VIPR Projections as Navigators O. Wieben et al. Motion Motion with correction No motion Undersampled Projection Reconstruction Spatial Resolution SNR X Imaging Time D. Peters - Thesis Undersampled Projection MRA Imaging of Coronary Artery Plaque Fayad, ZA et al. 500 µm in-plane resolution Circ. 2000 (in press) 16 heart-beats imaging X-ray angiogram mild LAD disease Concentric Thickened Wall LAD Wall LAD RVOT LV RV Fayad, ZA et al. Circ. 2000 (In press) ~ 670X500 µm resolution 4 mm slice ~ 4 mm max wall thickness Sign-Up Here for Wine/Grape Juice Study •High fat diet •Unlimited wine/juice •Active sex life •Free housing •Free medical care J. 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