Presentation on theme: "Spatial Localization and Multinuclear MR Spectroscopy Techniques"— Presentation transcript:
1 Spatial Localization and Multinuclear MR Spectroscopy Techniques Navin Bansal, Ph.D.Associate Professor and Director of MR Research
2 Proton MR ImageMR images contain anatomical information based on the distribution of protons and the relative proton relaxation rates in various tissuesMR images are based on proton signals from water and fat
3 MR SpectrumMR spectroscopy determines the presence of certain chemical compoundsStress, functional disorders, or diseases can cause the metabolite concentration to varyMetabolite concentrations are low, generating ~10,000 times less signal intensity than the water signal
4 Chemical Shift 1H MR spectra The electron cloud around each nuclei shields the external magnetic fieldBecause of differences in electron shielding, identical nuclei resonate at different frequenciesThe resonance frequency in the presence of shielding is expressed as:= (1- )BoWhere is the gyromagnetic ratio and Bo is the external magnetic field strength1H MR spectra-CH3-OH, ppm21
5 = (water - fat) 106/Bo, in ppm units Chemical ShiftThe frequency shift increases with field strength. For example, shift difference between water and fat(water - fat) at 1.5 T is 255 Hz at 3.0 T is 510 Hz = (water - fat) 106/Bo, in ppm unitswater-fat is 3.5 ppm independent of field strengthBy conventionSignals of weakly shielded nuclei with higher frequency are on the leftSignals of more heavily shielded nuclei with lower frequency are on the rightChemical shift of water is set to 4.7 ppm at body temperature
9 Surface Coil Acquisition A simple loop of wire and associated circuit tuned to the desired frequency are placed directly over the tissue of interest to obtain spectraA surface coilAdvantagesEasy to build and does not require specialized pulse sequenceSuperb SNR and filling factorDisadvantagesMust be close to region of interestChanging ROI is difficultInhomogeneous RF fieldRFPulse-acquire sequence
11 Depth Resolved Surface Coil Spectroscopy, DRESSA disk-shaped slice is excited parallel to the surface coil with a frequency selective RF pulse in the presence of a gradient.AdvantagesRelatively simpleSuppresses signal from superficial tissueMulti-slice acquisition, SLIT-DRESSDisadvantagesT2 lossPartial LocalizationRFGslice
12 Single Volume Localization RFGxGyGzLocalized spectra is obtained from a single volume of interest (VOI)Localization is achieved by sequential selection of three orthogonal slicesThe size and location of VOI can be easily controlledAnatomic 1H images are used for localizing the VOI
13 Single Volume Localization Image selected in vivo spectroscopy, ISISPoint resolved spectroscopy, PRESSStimulated echo acquisition mode, STEAM
14 Image Selected In Vivo Spectroscopy ISIS One DimensionalSlice inversionNo inversionSubtraction180o90oRFGsliceTwo acquisitions with and without inversion of a selected slice are obtained and subtracted
15 3D ISIST1Gxyz180°190°324576RF8+-A set of eight pulse sequences with one, two, or three slice selective inversion pulses are usedThe signal is localized to a VOI by adding signals from sequences 1, 5, 6, and 7 and subtracting signals from 2, 3, 4, and 8.
16 Image Selected In Vivo Spectroscopy, ISIS AdvantagesNo T2 loss – 31P MRSLess sensitive to gradient imperfectionsCan be used with a surface coilDisadvantagesDynamic rangeSubtraction error due to motion
17 Point Resolved Spectroscopy, PRESS 180°180°90°RFGxGyGzTE1/2(TE1+TE2)/2TE2/2A slice-selective 90o pulse is followed by two slice-selective 180o refocusing pulsesAchieves localization within a single acquisitionSuitable for signals with long T2 – 1H MRS
18 Stimulated Echo Acquisition Mode, STEAM 90°TMRFGxyzThree slice-selective 90o pulses form a stimulated echo from a single voxel.Achieves localization within a single acquisitionOnly half of the available signal is obtainedCan achieve shorter TE than PRESS
19 Effects of MR Parameters on PRESS spectraRepetition Time, TRNumber of Signal AveragesEcho Time, TEVoxel Size
20 Effect of Repetition Time (TR) TR = 1500 msTR = 5000 msNAACr/PCrCho
21 Effect of Signal Averaging 8 Averages64 Averages256 Averages
24 Short TE 1H Brain Spectrum Healthy volunteerAdditional PeaksGlx ppmppmmI ppmGlucose ppmppmAnd more
25 The Lactate DoubletTumor spectra: showing no NAA, Cho, mI, lactateLipids andlactateInvertedlactateUprightlactate
26 Single Voxel Spectroscopy: Overview SimplicityFlexibility in voxel size and positionAccurate definition of VOIExcellent shim and spectral resolutionMany voxels within the same dataset
27 Chemical Shift Imaging Multiple localized spectra are obtained simultaneously from a set of voxels spanning the region of interestUses same phase-encoding principles as imagingNo gradient is applied during data collection, so spectral information is preservedRFGsliceyz90°
28 CSI Spectral Map Display of all spectra Underlying reference image shows voxel positionIndividual spectra can be displayed enlargedSpectral map can be archived together with the reference image and the CSI grid
29 CSI Data AnalysisImage showing voxel positionSpectrum from a voxel
31 CSI: Overview Advantages Acquisition of multiple voxels Metabolite images, spectral maps, peak information maps, and results tableMany voxels within the same datasetDisadvantagesLarge volume – more difficult to shimVoxel bleedingLarge datasets
33 Important Nuclei for Biomedical MR NucleusSpin, MHz/TNatural AbundanceRelative Sensitivity1H1/242.57699.9851002H16.5360.0150.963He32.433.000134413C10.7051.1081.617O3/25.7720.0372.919F40.05583.423Na11.2629.331P17.2366.639K1.98793.08.05
34 Important Nuclei for Biomedical MR 1H – Neurotransmitters, amino acids, membrane constituents2H – Perfusion, drug metabolism, tissue and cartilage structure.13C – Glycogen, metabolic rates, substrate preference, drug metabolism, etc.19F – Drug metabolism, pH, Ca2+ and other metal ion concentration, pO2, temperature, etc23Na – Transmembrane Na+ gradient, tissue and cartilage structure.31P – Cellular energetics, membrane constituents, pHi, [Mg2+], kinetics of creatine kinase and ATP hydrolysis.
36 1H MR Spectra of the Brain Short TENAACrChoGlxInsGlxLipidsCr1.04.52.53.02.01.53.50.5ppm
37 Important 1H Signals N-Acetyl aspartate (NAA) NAA is a neuronal marker and indicates density and viability of neurons.It is decreased in glioma, ischemia and degenerative diseases.CH3-C-NH-CH-CH2-COOHOCH2-COOH2.02, CH32.52, CH22.70, CH24.40, CHCreatine (Cr), phosphocreatine (PCr)Cr is a marker of aerobic energy metabolismCr signal is constant even with pathologic changes and may be used as a control valueHowever, isolated cases of Cr deficiency may occur in childrenNH2-C-N-CH2-COOHCH3NH3.04, CH33.93, CH2
38 Important 1H Signals Choline (Cho), choline compounds Cho compounds are involved in phospholipid metabolism of cell membrane.Increase Cho mark tumor tissue or multiple sclerosis plaques3.24, CH33.56, CH24.07, CH2CH3-N-CH2-CH2-OHCH3Glutamate (Glu), glutamine (Gln)Glu is a neurotransmitter, Gln a regulator of Glu metabolismIt is hardly possible to detect their signals sepratly. The signals are jointly designated “Glx”.HOOC-CH2-CH2-CH-COOHNH2NH2-CH2-CH2-CH-COOH2.1, CH22.4, CH23.7, CH
39 Important 1H Signals Lactate (Lac) Lactate is the final product of glycolysisIt can be detected in ischemic/hypoxic tissue and tumors indicating lack of oxygenCH3-CH-COOHOH1.33, CH34.12, CHTaurine (Tau)Cells examination indicates taurine synthesis in astrocytes3.27, NCH23.44, SCH2NH2-CH2-CH2-S-OHMyo-inositol (Ins)Ins marks glia cells in brainIt is decreased in hepatic encephalopathy and elevated in Alzheimer’s disease.PO4-3.56, CH
41 31P MR Spectra of Normal Tissue 43261MuscleHeartLiverKidneyBrain-ATP-ATP-ATPPCrPDEPiPME4263175362741653241765432110-10-20ppm
42 Important 31P Signals Adenosine triphosphate (ATP) ATP is the energy currency in living systems- and -ATP have contributions from ADP, NAD and NADH-ATP is uncontaminated and used for quantification-ATP-7.8 -ATP-2.7 -ATPPhosphocreatine (PCr)PCr is used for storing energy and converting ADP to ATPIt is absent in liver, kideny and red cellsIt is used as an internal reference for chemical shift0 PCr
43 Important 31P Signals Inorganic Phosphate (Pi) Phosphomonoester (PME) Pi is generated from hydrolysis of ATP and increased in compromised tissueIts chemical shift is sensitive to pH3.7 to 5.7 PiPhosphomonoester (PME)PME signal contains contribution from membrane constituents and glucose-6-phosphate and glycerol-3 phosphate.It is elevated in tumors5.6 to 8.1 PMEPhosphodiester (PDE)PME signal contains contribution from membrane constituents0.6 to 3.7 PDE
44 Measurement of pH by 31P MRS Shift, ppm302010-10-20PCrATPPiPMEH2PO4- HPO42- + H+ pKa = 6.75é-ùêobsHPO-pH=apk+úlog24ê-úëûHPO2-obs4
46 Detection of myocardial infarctions by 31P-MR spectroscopyBeer et al., J Magn Reson Imaging. 2004;20:
47 A Lesson from 31P MRS Tumor Microenvironment Tumors are expected Poor Vascularizationand PerfusionTumors are expectedto be acidicHypoxiaAnaerobic GlycolysisAerobic GlycolysisIncreased Acid Production
48 ü ý þ pH of Tumors and Normal Tissue Electrode Measurements Normal 5.66.06.46.87.27.6A:pHPOTüýþSkeletal MuscleNormalBrainTissueSkinGlioblastomasAstrocytomasMeningiomasBrain MetastasesMalignant MelanomasSarcomasMammary Ca.AdenocarcenomasSquamousCell Ca.
49 pH of Tumors and Normal Tissue MRS MeasurementspH5.66.06.46.87.27.6B:pHNMRSkeletal MuscleüýþBrainNormalSkinTissueHeartSarcomasSquamous Cell Ca.Mammary Ca.Brain TumorsNon-Hodgkin Lymp.Misc TumorsBansal, et al.
50 Spectroscopy and Imaging 23Na MRSpectroscopy and Imaging
51 Biological Importance of Sodium Sodium and other ions are inhomogeneously distributed across the cell membrane.A transmembrane sodium gradient reflects a dynamic equilibrium between Na+-K+ ATPase versus passive or mediated flux.The sodium gradient may be altered in certain diseased states.Normal cells maintain an intracellular concentration of approximately 5-35 mM against an extracellular concentration of approximately mM.This sodium concentration gradent is maintained by Na+-K+ ATPase and is essential to drive many physiologic function such as transport of other ions and substrats, maintenance of normal cell volume, muscle contractile function and transmission of nervous impulse, etc.In many diseased states such as hypertension, manic depressive disease, oncogensis and sepsis, alteration in intracellular concentration may occur due to abnormalities in ion transport and exchange process across the cell membrane.Therefore, noninvasive observation of intracellular Na+ may be useful in understanding the mechanism of diseased state and may also have important diagnostic utility.Bansal, et al.
52 Biomedical 23Na NMR23Na is the second most sensitive nucleus for biomedical NMR.Intra- and extracellular sodium resonate at the same frequency.Two approaches to distinguish between different sodium pools:Paramagnetic Shift ReagentsMultiple Quantum Filters23Na is the second most sensitive NMR nuclei in tissue and has been the focus of numerous recent imaging studies in humans.However, standard NMR techniques alone are unable to separate intra- and extracellular Na+ because, Na+ exists in only one chemical form is tissue and the 23Na signals from intra- and extracellular compartments are coincident.Our current research involves developing and evaluating two techniques for discriminating between intra- and extracellular sodium. The first technique is based on the use of paramagnetic shift reagents. The second technique, multiple quantum filters, does not require any exogenous reagent and can be applied to humans.Bansal, et al.
53 23Na Shift ReagentsSRs are membrane impermeable negatively charged chelates of a lanthanide metal ion. They interact with extracellular Na+, causing its signal to be shifted away from intracellular Na+.Na+eNa+eNa+eNa+iNa+iNa+eNa+eNa+eSRNa+eSRSR
54 Action of a Typical Shift Reagent With SRNaeNai10ppmWithout SRNai + Nae10ppmBansal, et al.
56 In Vivo 23Na Spectra after TmDOTP5- Infusion MuscleHeartLiverBrainKidneyExtIntx 5Urine9L Glioma40302010-10ppmBansal, et al.
57 Nai in Perfused RIF-1 Tumor Cells Significance: ** p < 0.01 (with vs without EIPA)20037 oC45 oC37 oCHyperthermia produced a 60-70% increase in Nai+.The increase in Nai+ is mainly due to an increase Na+/H+ antiporter activity**180**w/o EIPA**160with EIPARelative Nai Signal Intensity140120EIPA10080-10-20-101020304050607080Time, minBansal, et al.
58 Multiple-Quantum Filters MQFs depend only on the relaxation properties of 23Na. Thus, they do not produce any known physiological perturbation to the biological system and cab be applied to humans.DisadvantagesLow signal-to-noise ratioSome Nae+ contributionBansal, et al.
59 MQ Filtered 23Na NMR“Transiently bound” Na+ can pass through a MQ filter.|-3/2>SQ outer|-1/2>SQ innerTQDQ|1/2>SQ outerDQ|3/2>“Free” Na+“Transiently Bound” Na+Concentration of macromolecules within the cytoplasm is relatively high while the extracellular milieu is largely aqueous.
60 SQ and TQ Filtered 23Na Spectra of a Phantom AqueousAgarose40 mMTmDOTP5-10%AgaroseSQTQAgaroseppm50-50ppm50-50Bansal, et al.