Part VI: Advanced Concepts (Selection)

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1 Part VI: Advanced Concepts (Selection) Contents Cardiovascular magnetic resonance imaging (CMR; cardiac MRI) Diffusion Imaging (diffusion weighted imaging: DWI, diffusion tensor imaging: DTI) BOLD (blood oxygenation level dependent) Imaging (functional MRI: fmri) MR Angiography (MRA) MR Spectroscopy (MRS)

2 Cardiac Imaging Non-invasive assessment of the function and structure of the cardiovascular system. (characterization of heart muscle as normal or abnormal: fat infiltration, oedematous, iron loaded, acutely infarcted or fibrosed). ECG???

3 Cardiac Imaging Initial attempts to image the heart were confounded by respiratory and cardiac motion, solved by using cardiac ECG gating, faster scan techniques and breath hold imaging. ECG-gating ( prospective gating ): multiple phases ECG Segment of k-space phase1 Segment of k-space phase2 Segment of k-space phase3 Segment of k-space phase4 Segment of k-space phase5

4 Cardiac Imaging ECG-gating ( prospective gating ): multiple phases Example: GE-Sequence, TR = 10 ms, imaging matrix 128 x 128, heart beat rate 70/min How long does patient has to hold his breath? ECG 10 ms

5 Molecular Diffusion of Water Diffusion probes for dynamic displacements of water on cellular dimensions and provides a unique insight into tissue structure, microstructure and organization. Spins in motion: Diffusion In 1956, H.C. Torrey mathematically showed how the Bloch equations for magnetization would change with the addition of diffusion. Torrey modified Bloch's original description of transverse magnetization to include diffusion terms and the application of a spatially varying gradient. The Bloch-Torrey equation neglecting relaxation is: Isotropic Diffusion 1 m D D

6 Diffusion Weighted Imaging (DWI) Diffusion-weighted imaging is an MRI method that produces in vivo magnetic resonance images of biological tissues weighted with the local characteristics of water diffusion. DWI is a modification of regular MRI techniques, and is an approach which utilizes the measurement of Brownian motion of molecules. 10 mt/m -10 mt/m t v=0 with random motion (diffusion) Diffusion (random walk) generates a random phase offset after bipolar gradient: Total signal is reduced depending on strength of diffusion ands gradient t

7 Diffusion Weighted Imaging (DWI) Diffusion (random walk) generates a random phase offset after bipolar gradient G [mt/m] b 2 G t G [mt/m] b 1 ( ) G t Signal attenuattion from diffusion: SbD (, ) Me bd 0 Example: G = 10 mt/m, = 30 ms b ~130 s/mm 2 S ~ 0.75 M 0 D: diffusion constant (water = 2.5x10-9 m 2 /s), b: diffusion weighting factor (from gradients)

8 Restricted Diffusion & Anisotropic Diffusion

9 Restricted Diffusion D D D > Deff Deff D eff Large compartements, high diffusion small compartements, low diffusion cell Detection of affected regions after acute stroke

10 Anisotropic Diffusion Nerve bundles: diffusion is higher along than across nerve fibres: Anisotropic diffusion! Diffusion sensitizing gradients (Bx,Gy,Gz) can be applied independently along all three spatial directions (x,y,z) This allows to calculate the direction of highest (lowest) diffusion within each imaging voxel! D D D 3 Calculate eigenvectors!

11 Diffusion Tensor Imaging: Tractography Determine diffusion tensor from at least six measurements with diffusion sensitizing gradients along different directions. fiber tracks in white matter

12 Functional magnetic resonance imaging (fmri)

13 Functional magnetic resonance imaging (fmri) Functional magnetic resonance imaging is a type of specialized MRI scan used to measure the hemodynamic response (change in blood flow) related to neural activity in the brain. It is one of the most recently developed forms of neuroimaging. Since the early 1990s, fmri has come to dominate the brain mapping field due to its relatively low invasiveness, absence of radiation exposure, and relatively wide availability. Red blood cells contain hemoglobine Heme, part of hemoglobine, contains Iron (Fe) Hemoglobine can either be paramagnetic or diamagnetic, depending on oxygenation state hemoglobine Heme group

14 Functional magnetic resonance imaging (fmri) BOLD: blood oxygenation level dependent imaging Hemoglobine can either be paramagnetic or diamagnetic, depending on oxygenation state magnetic moment Fe vein no magnetic moment Deoxyhemoglobin o o Magnetic field flux Fe arterie Oxyhemoglobin

15 Functional magnetic resonance imaging (fmri) BOLD: blood oxygenation level dependent imaging deox 0 frequency TE t ox 0 frequency TE t

16 Functional magnetic resonance imaging (fmri) BOLD: blood oxygenation level dependent imaging Firering nerve cells require energy Energy is provided as oxygen and glucose via capilaries This locally increases blood flow Increase of blood flow exceeds demand of oxygen This locally increases blood oxygenation Resting state Activated state Arterioles Capillaries Venules HbO2 Hbr - normal flow - base level of [Hbr] - base level of CBV CBV = cerebral blood volume - increased flow - reduced level of [Hbr] - increased CBV

17 Functional magnetic resonance imaging (fmri) BOLD: blood oxygenation level dependent imaging T2* (rest) < T2* (activation)

18 MR Angiography (MRA)

19 MRA: Introduction What is MRA used for? Characterization of (Human) Vascular System

20 MRA: Introduction Vascular abnormalities for MRA? Stenosis Aneurysm Arterial Venous Malformation (AVM) Thrombus Plaque Internal bleeding

21 MRA: Properties of Blood Relaxation Times Arterial T1 ~ 1.5T T1 ~ 3.0T T2 ~ 250ms Venous T1 ~ 1.5T T1 ~ 3.0T T2 ~ 30ms Flow Velocity (mean) cm/sec ( km/h) in abdominal aorta cm/sec ( km/h) in peripheral arteries Pulsatile: Peak arterial ms after ventricular contraction

22 MRA: Techniques Contrast Enhanced MRA (CE-MRA) high contrast-to-noise ratio (of course!) fast acquisition dynamic imaging No flow induced dephasing of signal loss Acquisition timing is important (bolus!) Gd related NSF is a concern Non-Enhanced (native) MRA (native-mra) can be quantitative prone to artifacts techniques are region specific

23 CE-MRA became popular during Requirements: High resolution and coverage of large VOI Short acquisition times to allow breath-holding, e.g. for visualization of abdominal vasculature Fast 3D Sequences 3D GRE!

24 CE-MRA: GRE Parameters TE TR TR: Repetition time TE: Echo time : excitation (flip) angle

25 CE-MRA: GRE Contrast What do we expect for a GRE acquisition with short TR/TE (we want to be fast!!!) and a 90 flip angle? TR = 3ms << T1, TE ~ 0 ms, = 90

26 CE-MRA: GRE Contrast TE 0 S S PD E1 (1 ) TR = 6 sec (1 0) Signal of blood for a fast 3D GRE? TR = 3 msec (1 1)

27 MRI: Contrast Agents (CA) revisited Contrast enhanced MRI, cell tracking, SPIOs, USPIOs, Paramagnetic agents: 1/ T 1/ T [ CA] r 1/ T 1/ T [ CA] r 2 2, nativ 2 1 1, nativ 1 Contrast agents accelerate T1 & T2. CA Positive CA: low concentrated Gd-chelates. Predominantly reduction in T1 (electron-proton dipolar coupling). Positive contrast in T1w-image!

28 CE-MRA Gd contrast agents decrease T1 and thereby increase CNR between blood and soft tissue

29 CE-MRA The contrast medium is injected into a vein, and images are acquired during the first pass (bolus) of the agent through the arteries. 4 sec 8 sec 12 sec 16 sec 20 sec 24 sec 28 sec 32 sec RF spoiled SSFP-FID (FLASH, SPRG, T1-FFE) TR = 3.54 ms TE = 1.38 ms Flip = x 1.0 x 0.9 mm heavily T1-weighted This is the most common MRA method Visualization: Images (source is 3D) are displayed as 2D MIPs (screen is 2D)

30 MRA: MIPs Maximum Intensity Projection Courtesy of S. Wetzel, University Hospital Basel The highest intensity signal along each ray of is mapped onto the projection image MIP imaging was invented for use in Nuclear Medicine by Jerold Wallis, MD, in 1988

31 Time-of-Flight (TOF) MRA Remember: This is a native MRA technique! There is no contrast agent slice being imaged

32 TOF-MRA: Principle Remember: This is a native MRA technique! There is no contrast agent Short TR! SATURATION! NO SIGNAL FROM TISSUE!

33 TOF-MRA: Principle The effective T1 is reduced due to inflow flow velocity static slow fast maximum medium minimum saturation

34 TOF-MRA: Principle Inflow of venous blood Elimination of venous signal?

35 TOF-MRA: Principle saturated venous phase! flow velocity static slow fast maximum medium minimum saturation

36 TOF-MRA (2D, 3D) RF spoiled SSFP-FID (FLASH, SPRG, T1-FFE) MIP TR ~ 50 ms TE ~ 10 ms Flip = 25 Inflow (flow-related enhancement) Seqential 2D (native) MR Angiography Saturated background Inflow related transient signal

37 CE-MRA & TOF-MRA: Issues The same sequence (FLASH) is used for TOF and CE-MRA and images rely on high CNR between blood and tissue (hyperintense signal from blood): Thus, the absence or reduction of the blood signal is related to the presence of some disease Artifactual Signal Loss 2D-TOF/3D-TOF In-plane, slow or retrograde flow Intravoxel dephasing (turbulent flow, e.g., after stenosis) CE-MRA Improper bolus timing T2* dephasing

38 Phase Contrast (PC) MRA M variabel stationary = + transverse magnetization = longitudinal magnetization Amplitude Image Signal Amplitude + Signal Phase Phase Image

39 PC-MRA: Principle Gradient waveform over time: v t G () t dt venc z z t G () t dt z z t Phase images measure the velocity! Gradient field strength static flow + φ

40 PC-MRA RF spoiled SSFP-FID (FLASH, SPRG, T1-FFE) 3D PC MRA TR ~ 50 ms TE ~ 10 ms Flip = 25 flow encoding gradients flow encoded (phase contrast) phase contrast MRA flow quantification Courtesy of F. Santini, Radiological Physics,Basel

41 PC-MRA

42 PC-MRA: Issues The strength of the PC- MRA technique is that in addition to imaging the flowing blood, quantitative measurements of blood flow occur at the same time. Courtesy of F. Santini, Radiological Physics,Basel slow method: 1D: 1 flow, 1 reference, 3D: 3 flow, 1 reference long acquisition time (time for PC-MRA >> TOF-MRA) phase wraps & poor SNR: proper venc selection intravoxel dephasing: turbulent flow, diffusion, longer TE from flow-encoding

43 MR Spectroscopy (MRS)

44 Nuclear Magnetic Resonance (NMR) MRS and MRI arise from the same principle, nuclear magnetic resonance NMR, first observed by Bloch and Purcell in In Bloch s classical description of the phenomenon, polarized nuclei precess about the direction of the main magnetic field B 0 with a frequency that is a product of the gyromagnetic ratio of the nucleus and the strength of the magnetic field at the nucleus B: Larmor Equation: : Larmor frequency, i.e., the resonance frequency : gyromagnetic ratio

45 Nuclear Magnetic Resonance (NMR) In principle, all nuclei with show nuclear magnetic resonance. High natural abundance required to result in sufficient NMR signal. Biological tissue: 1 H is most abundant in water and fat.

46 Nuclear Magnetic Resonance (NMR) Changes in the resonant frequency gives rise to the information content of both MRI and MRS! In MRI, the resonant frequency is modified by gradients G imposed on the main magnetic field B 0. The frequency thus becomes a function of the position r and in this way, spatial information is extracted and images are created.

47 Introduction: Spectroscopy (MRS) The origin of MRS dates to 1951 when Albert described small changes in resonant frequency of protons due to the local chemical bonding environment. (protons are shielded from the full applied magnetic field B o by surrounding electrons) The frequency of resonance of a nuclei in a molecule is given by where the shift imparted by the local bonding environment is given the symbol and is called the chemical shift.

48 Introduction: Spectroscopy (MRS) Each type of hydrogen has a unique position of absorption (called the chemical shift) in the NMR spectrum Electronegative atoms such as oxygen (O) or chlorine (Cl) attract electrons and cause deshielding of nearby hydrogen. In MRS, the resonance offset is normalized to the operating frequency of the magnet and further referenced to a standard to minimize confusion when comparing results from laboratories using different field strengths. Resonance positions are then reported in parts per million (ppm)

49 Introduction: Spectroscopy (MRS) For 1 H spectroscopy, the standard is the methyl proton resonance of tetramethyl silane which was chosen to be 0 ppm. Based on this standard, protons in water resonate at 4.8 ppm regardless of magnetic field strength. H 2 O H H O H H H H C C C C H H H H The resonance of the methylene protons in adipose tissue is 1.3 ppm. 3.5 ppm Fat The shift between water and fat remains 3.5 ppm, regardless of field strength, although the frequency difference in hertz changes! ppm = 1.5 T 1 ppm = 3.0 T 1 ppm = 7.0 T 0 [ppm]

50 Theoretical Background: Fourier Transform Water and Fat generate a water: A w fat: A f exp( 2 i w t ) exp( 2 i f t ) time varying signal response S(t): A w exp(2 i w t ) + A f exp(2 i f t )

51 Theoretical Background: Fourier Transform a time varying signal response: S(t)=A w exp(2 i w t ) + A f exp(2 i f t ) and its Fourier transform: 1 2 ivt F() v S() t e dt 2 A w 3.5 ppm A f [ppm] The peak height in the spectrum relates to the amplitude

52 Theoretical Background: Line-Width FFT dirac-delta function ( - 0 ) 0 ppm x Lorentzian function FWHM ~ T 2 FFT = damped decay FFT = 0 ppm Shifted Lorentzian function 0 ppm The area under the peak in the spectrum relates to the amplitude

53 Theoretical Background: Line-Width damped decay FFT FFT phase oscillation damping Go for the real part of the Fourier transform of the signal!

54 Theoretical Background: Phase Shifting However, proper phasing of the FFT signal is required

55 Theoretical Background: Truncation truncated damped decay * i 2 i 0 t tt / 2, e e e t t st ()~ 0, t t 0 0 Be aware: Truncation of the signal may cause Fourier wiggles! A filter (exponential envelope) can be applied to smooth the truncation (which removes the wiggles but not without broadening the line).

56 Theoretical Background: Line Broadening Frequency distribution ( ) ppm 0 ppm causing line-broadening The main magnetic field B 0 is perturbed by local susceptibility changes on the macroscopic (e.g., air/bone tissue interface), mesoscopic (e.g., vessels) and microsopic (e.g., cells) level. For 1.5T (64MHz), macroscopic susceptibility effects induce frequency changes in the range of 30Hz ~ 0.5 ppm. Macroscopic susceptibility effects can be reduced by proper shimming! Proper and accurate shimming of the ROI is elementary!

57 Theoretical Background: J-Coupling H H H C A C B O H With increasing B 0, the dispersion (difference in resonance frequency in Hertz) between singlet resonances increases linearly. H H fully decoupled Closely spaced singlets become thus more distinct with increasing B 0 (although the difference in ppm remains the same. [ppm] However, many of these resonances are not singlets (i.e., a single resonance line), but multiplets coupled [ppm] Nuclei with different chemical shifts may exchange energy through the bonding electron clouds in the molecule (J-coupling, being independent on B 0 ).

58 Theoretical Background: Summary The Fourier transform relates the time-domain with the frequency domain and thus the decay of the signal with T 2 relates to the line-width (Lorentzian with FWHM ~ 1/ T2) Only the real part of the spectrum is used (less line broadening, but requires proper phasing) Truncation of the FID may induce Fourier wiggles (can be removed by filtering, but broadens the line) A dispersion in resonance frequencies, e.g., induced by local susceptibility changes, causes a broadening of the lines. (proper shimming required) Separation of lines improves with increasing field strength (T2 ~ 100ms 1.5T, 3.0T, 7.0T) J-coupling may induce the appearance of multiplets (J-coupling is independent on B 0, thus multiplets appear closer with increasing fields)

59 1 H and X-nuclei Spectroscopy MRS methods can be broadly classified into two categories: 1 H MRS X-nuclei MRS The dominant clinical application is 1 H MRS, since no additional hardware is required. (The same RF coils transmit and receive systems used for MRI are also applicable to 1 H MRS) Imaging (H 2 O) MRS (NAA) [H 2 O] : [NAA] = 72 : 0.03 (Molar) SNR H2O : SNR NAA 13 3 : 1 1 x 1 x 1 mm 3 SNR ~ x 13 x 13 mm 3 SNR ~ 100

60 1 H Spectroscopy: Sensitivity the problem with the water The dispersion of the 1 H spectrum is small, with all the resonances of interest in the human within 5 ppm of the water resonance (0 4.8 ppm). The line shape of the water resonance in vivo yields a large base line signal, overwhelming the resonances of interest. Remember SNR H2O : SNR NAA 13 3 : 1 Water suppression required! Baseline correction required!

61 Sample of a 1 H spectrum High-resolution proton spectroscopy at 9.4 T After: Accurate Shimming Water suppresion Baseline correction Phase correction Cr + PCr NAA Cr PCr PE myo- Ins Glc Glu Gln myo-ins scyllo-ins Tau Cho GSH Asp GSH GABA Glu Gln Glu Gln NAA GABA Ala Lac MM ppm

62 1 H Spectroscopy: Single Voxel Excitation How can we select a small volume (~1 cm 3 )? Localized volume Methods: PRESS = Point-resolved spectroscopy STEAM = Stimulated echo acquisition mode

63 1 H Spectroscopy: Localization Methods Point-resolved spectroscopy: PRESS Achieves localization within a single acquisition A slice-selective 90 o and two slice-selective 180 pulses form a spin echo from a single voxel.

64 1 H Spectroscopy: Localization Methods Stimulated echo acquisition mode: STEAM Achieves localization within a single acquisition RF G x G y G z TE/2 TM TE/2 Three slice-selective 90 o pulses form a stimulated echo from a single voxel. Only half of the available signal is obtained Can achieve shorter TE than PRESS

65 2D- 1 H Spectroscopy: Chemical Shift Imaging Chemical Shift Imaging (CSI) Similar to MRI. The FID of a single voxel (i.e., its 1D- 1 H spectrum) is encoded with a phase (via gradients). This encoding has to be done along every direction. Thus, for a 32x32 imaging matrix 1024 phase-encoded 1D- 1 H-spectra are recorded The same principles apply as with 1D- 1 H MRS

66 1 H Spectroscopy: Summary Energy metabolism: 1: phosphcreatine (PCr) 2: creatine (Cr) 3: glucose (Glc) 4: lactate (Lac) 5: alanine (Ala) 1 12, ,7,18 11, ,15 1, , Neurotransmission: 6: glutamate (Glu) 7: glutamine (Gln) 8: GABA 9: N-acetyl-aspartyl-glutamate (NAAG) 10: aspartate (Asp) 11: glycine (Gly) 12: serine (Ser) ppm Membrane metabolism: 13: phospho-ethanolamine (PE) 14: phosphocholine (PC) 15: glycerophosphocholine (GPC) 16: N-acetyl-aspartate (NAA) Antioxidants/osmolytes: 17: glutathione (GSH) 18: vitamin C (Asc) 19: taurine (Tau) 20: myo-inositol (Ins) 21: scyllo-inositol (s-ins)

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