How is it different from conventional MRI? What is MR Spectroscopy? How is it different from conventional MRI? MR Active Nuclei
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1 What is MR Spectroscopy? MR-Spectroscopy (MRS) is a technique to measure the (relative) concentration of certain chemical or biochemical molecules in a target volume. MR-Spectroscopy is an in vivo (in the living) application of traditional laboratory-based NMR techniques. How is it different from conventional MRI? Comparison: How is it different from conventional MRI? In MR-Spectroscopy the signal comes from a selected volume. At least 128 signal averages (NEX, NSA) are required to obtain interpretable spectra within a clinically acceptable time period. Nuclei that are used in spectroscopy have ODD mass numbers. MR Active Nuclei MR Active Nuclei Nuclei that aligns its axis to a magnetic field. They do this because of electromagnetic induction: Angular momentum or spin. Posses an electrical charge (+) If two of these characteristics are present it induces the third - magnetism Called a magnetic moment 1
2 MR Active Nuclei: Naturally occurring nuclei with an odd number of Protons or Neutrons. Precession Precession is the wobble of a top Precessional Frequency is the speed it wobbles. (Mhz) Gyromagnetic ratio is a constant for each type of MR active nuclei. Larmor Frequency: Larmor Equation: The Larmor frequency is also called the Precessional frequency. 2
3 Why do you need to suppress water? Mountain (Water) Since water is the most abundant substance in the human body, the signal from water is significantly higher than the signal from metabolites in the sample of tissue. Pine Tree (Metabolite) What is a Spectrum? In MR-Spectroscopy it is a range of separate frequencies, which coincide with different metabolites in a sample of tissue. It is measured in amplitude and chemical shift. 3
4 Amplitude Number of metabolites Absolute Quantification: MRS method that records a single metabolite. Chemical Shift More than one peak in the spectrum. 4
5 What is Chemical shift and why is it important? Protons within various compounds, such as water and fat, resonate at slightly different frequencies. These small frequency differences are referred to as chemical shift (or field inhomogeneities). The Chemical shift differences between water and fat protons results in the familiar two-peak spectrum commonly seen during the prescan portion of a conventional MRI exam. Field Strength of External Magnet What is ppm (Parts Per Million) The greater the field strength of the external magnet the greater the chemical shift. Could you do MRS on a low field magnet? PPM is a system adopted to measure these slight differences in frequencies. 5
6 Trivia Questions (1.5 T): 1. How far apart are fat and water in Hz (Hertz)? 2. How far apart is that in ppm (parts per million)? 3. What compound resonates at 0 on the ppm scale? Trivia Questions (1.5T)Answers: 1. How far apart are fat and water in Hz (Hertz)? 210 Hz 2. How far apart is that in ppm (parts per million)? 3.3 ppm 3. What compound resonates at 0 on the ppm scale? tetramethylsilane or TMS Bonus question: So if TMS is at 0 on the ppm scale. Where is fat and water? Bonus question answer: On the ppm scale: TMS is at 0 ppm (reference frequency) Fat is at 1.4 ppm Water is at 4.7 ppm Additional Biochemical's on the ppm scale: Choline Creatine N-acetylaspartate Lactate Myo-inositol Glutamine & Glutamate 3.22 ppm 3.03 ppm 2.02 ppm 1.3 ppm 3.6 ppm ppm Aromatic amino acids (tryptophan, histidine, tyrosine) ppm Cholesterol (liver only) ppm Brain and myelin related amino acids (glycine, taurine) ppm 6
7 How does field strength affect Spectroscopy? What is J-Coupling? Provides adequate dispersion of spectral components (Better chemical shift). Better field homogeneity. Better SNR. Smaller volume samples. Ability to sample areas off isocenter. Increase size of spectral peaks. What is J-Coupling? What is J-Coupling? 7
8 What is J-Coupling? What is J-Coupling? What is J-Coupling? Brain Activation Demand for nutrients by the brain to maintain neural metabolism. What is the necessary nutrient for electrical activity in the brain? Glucose. MRS spectrum of a brain differs with age. 8
9 N-acetylaspartate NAA is accepted as a neuronal marker; as such, its concentration will decrease with many insults to the brain (such as neoplasms, infarcts, epilepsy, and dementia). 31P in MR-Spectroscopy: (3 ATP peaks-see supp. reading) 31P Metabolites: Adenosine Triphosphate (ATP) (major carrier of energy to cells) Creatine Phosphate (CrP) Inorganic Phosphate (Pi) Phosphodiesters (PDE) Phosphomonoesters (PME) 31P in MR-Spectroscopy (cont.): Indicators: The 31P chemical shift of Pi is a useful indicator of ph. ATP and CrP resonances provide a measurement of the energetic status of the sample, and are sensitive to pathological or pharmacological stress. PME and PDE resonances are of interest with respect to rapidly growing (i.e. cancerous) tissue. 31P is used to diagnose McArdles disease (an increase build up of glycogen in muscle tissue). 13C in MR-Spectroscopy: Carbon-13 has a wide range of chemical shifts. Used to study glycogen metabolism in the human liver. Not widely used because of low population. 9
10 19F in MR-Spectroscopy: Indicator of intracellular Ca2+ levels using fluorinated indicators. Used to measure intracellular ph in vivo. ph of malignant tissue is lower than normal. Used to asses tumor vascularity. What are the different imaging techniques for Spectroscopy? Single Voxel Techniques: PRESS: (Point Resolved Spectroscopy) Longer relaxation times. Double spin echo technique echo. STEAM: (Stimulated Echo Acquisition) Shorter relaxation times. Three 90 degree pulses echo. Achieves shorter TE s Water suppression is prior to the first 90 degree pulse in both techniques. What are the different imaging techniques for Spectroscopy? Probe-S, Probe-P, and Probe-SV are automated versions of PRESS and STEAM. Probe-P is better for measuring levels of lactate. What are the different imaging techniques for Spectroscopy? Multi-Voxel Techniques: 10
11 Manipulating TE Short Acquisitions (left): Provide higher SNR and allow more compounds to be visualized. Longer Acquisitions (right): Simplified spectrum with reduced residual water and fat signals Manipulating TE (cont.) In choosing the appropriate TE one has to consider what metabolites are expected. Certain metabolites have a short T2-time (for instance glutamine, glutamate, Myo-Inositol), therefore TE needs to be short in order to measure before the transverse magnetization of the metabolite decays. Manipulating TE (cont.) If metabolites exhibit j-coupling, TE needs to be chosen so that the spins are in phase. If lactate is expected, the TE is often chosen as 144 msec. Leading to an inverted peak. Adjusting the magnetic field homogeneity. Shimming This is another element that improves the dispersion of the spectral peaks. Automatic shimming programs have greatly enhanced the quality of spectroscopy over the years. The automatic shim should be done on each individual patient. 11
12 Question: What conditions are going to affect getting a good shim on a patient? Answer: A good shim is dependant upon the patient removing every piece of metal in or on his/her body that realistically can be removed. A homogeneous field maximizes SNR. Magnetic field inhomogeneity (fluctuations) causes peak broadening. What are the medical applications? MRS, particularly in the human brain provides unique information about: ph of CNS fluid. Glucose metabolism. Amount of energy stored in cells. Levels of different chemicals in the brain. What are the medical applications? Using metabolic information Physicians can define the nature and spatial extent of many different pathologies including: Cancer Epilepsy Stroke Multiple Sclerosis Neurodegenerative diseases 12
13 What is fmri? (module: supp. read. #6) Functional MRI is based on the increase in blood flow to the local vasculature that accompanies neural activity in the brain. Microvascular MR signal Microvascular MR signal on T2 and T2* weighted images is strongly influenced by the oxygenation state of the blood. 70% of the brain's blood lies within the microvascular capillaries and venules. Glucose is the necessary nutrient for electrical activity in the brain. Brain activation is the demand for nutrients by the brain to maintain neural metabolism. Hemoglobin Oxyhaemoglobin & Deoxyhaemoglobin Hemoglobin is a molecule that contains iron and transports oxygen in the vascular system as oxygen binds directly to iron. Oxyhemoglobin. Oxygen is bound to hemoglobin and the magnetic properties of iron are suppressed (diamagnetic). Deoxyhemoglobin. Oxygen is not bound to hemoglobin and the magnetic properties of iron are more magnetic (paramagnetic). Hemoglogin (Hgb): - four globin chains - each globin chain contains a heme group - at center of each heme group is an iron atom (Fe) - each heme group can attach an oxygen atom (O 2 ) - oxy-hgb (four O 2 ) is diamagnetic no B effects - deoxy-hgb is paramagnetic if [deoxy-hgb] local B Source: Jorge Jovicich 13
14 Blood Interaction with a Magnet Ferromagnetic strong susceptibility Paramagnetic weak susceptibility Diamagnetic no susceptibility Iron ferromagnetic Oxyhemoglobin diamagnetic (electrons from oxygen shields iron) Deoxyhemoglobin paramagnetic Oxygenated blood volume, leads to in local susceptibility and local magnetic inhomogeneity. Deoxygenated blood volume, leads to in local susceptibility and local magnetic inhomogeneity. Scanning Techniques and Parameters Interleaved Echo-Planer Imaging (EPI) is the most common scanning technique for fmri. Gradient-Recalled Echo (GRE) Spin-Echo (SE). These sequences require longer TE s (~100ms) to maximize blood susceptibility contrast. Lowers image signal and SNR (trade-off). Scanning Techniques and Parameters (cont.) Data acquisition: A spiral acquisition of k-space is the fastest. If using a linear acquisition an interleaved slice acquisition is preferred to reduce cross-talk from adjacent slices. Spatial Resolution in fmri What affects spatial resolution in fmri? SNR Pixel size (matrix) Partial-volume effects FOV Slice Thickness 14
15 SNR in fmri What affects increase SNR in fmri? Larger magnetic field strengths. Decrease TE. RF coils. FOV NEX/NSA BOLD Technique Blood Oxygenation Level Dependent = The ratio of deoxyhemoglobin to oxyhemoglobin in blood. T2* is dependent on the presence of blood deoxygenation T2* effect is larger by factors of 3 to 10 and is the dominant and most widely-studied mechanism employed in fmri. BOLD (cont.) In short, the response to a local increase in metabolic rate is increased delivery of blood (oxygenated) to the activated region. Such a change in hemodynamics produces small alterations in T1, T2 or T2*, which can be visualized as a change in MR image intensity (approx. 1-10%). Oxygenated blood is the source of contrast in bold imaging. Terminology CBV: Cerebral Blood Volume CBF: Cerebral Blood Flow HBr: Deoxy- Hemoglobin HRF: Hemodyanmic Response Function 15
16 BOLD (cont.) Remember? Ferromagnetic strong susceptibility Paramagnetic weak susceptibility Diamagnetic no susceptibility Iron ferromagnetic Oxyhemoglobin diamagnetic (electrons from oxygen shields iron) Deoxyhemoglobin paramagnetic Blood Oxygen Level Dependent Imaging (BOLD) -Theory Right Hand Motor Task Protons near paramagnetic tissue (i.e., more deoxygenated blood) experience a quicker dephasing after a spin excitation. Increase in T 2 * rate reduction in local signal. So, for pulse sequences sensitive to T 2 * contrast, deoxyhemoglobin appears dark, and oxyhemoglobin appears bright. 16
17 Left Hand Motor Task Auditory Task Task presentation systems fmri Projection System Visual presentation Slide projector LCD panel & overhead projector & rear screen projection Large screen LCD MRI projection systems Electronic goggles MRI compatible corrective lenses 17
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