MRI spectroscopy- Its Application, Principle & Techniques

MRI spectroscopy- Its Application, Principle & Techniques

1. MAGNETIC RESONANCE SPECTROSCOPY (MRS)

2. Introduction Physics Interpretation Indications Cases Summary

3. Magnetic resonance spectroscopy (MRS) is a means of noninvasive physiologic imaging of the brain that measures relative levels of various tissue metabolites Purcell and Bloch (1952) first detected NMR signals from magnetic dipoles of nuclei when placed in an external magnetic field. Initial in vivo brain spectroscopy studies were done in the early 1980s. Today MRS-in particular, IH MRS-has become a valuable physiologic imaging tool with wide clinical applicability.

4. PRINCIPL E S: The radiation produced by any substance is dependent on its atomic composition. Spectroscopy is the determination of this chemical composition of a substance by observing the spectrum of electromagnetic energy emerging from or through it. NMR is based on the principle that some nuclei have associated magnetic spin properties that allow them to behave like small magnet. In the presence of an externally applied magnetic field, the magnetic nuclei interact with that field and distribute themselves to different energy levels. These energy states correspond to the proton nuclear spins, either aligned in the direction of (low-energy spin state) or against the applied magnetic field (high-energy spin state).

5. MR Spectroscopy  Noninvasive means of assessing the biochemical and metabolic processes in intracranial tissues without ionizing radiation.  For the brain in particular, MRS has been a powerful research tool and provide additional clinical information for several disease such as brain tumors, metabolic disorders, and systemic diseases

6. There are numerous metabolites found in the human brain. Fortunately, only several of them are useful in spectroscopic studies. There is evidence that the normal metabolites in the brain vary with according to the patient's age. T he changes are most noticeable during the first three years of life.

7. If energy is applied to the system in the form of a radiofrequency (RF) pulse that exactly matches the energy between both states. a condition of resonance occurs. Chemical elements having different atomic numbers such as hydrogen ('H) and phosphorus (31P) resonate at different Larmor RFs.

8. N-ACETYLASPARTATE (NAA) NAA is the marker of neuronal density and viability. It is present in both gray and white matter and the difference in concentration is not clinically significant. • • NAA is detected by the its N-acetyl methyl group. Its concentration appears to decrease with any brain insults such as infection, ischemic injury, neoplasm, and demyelination process. NAA is not in found in tumors outside the central nervous system ( CNS ) such as meningioma. NAA is the tallest peak in the proton MR spectrum and it is assigned at 2.0ppm. Additional smaller peaks may be seen at 2.6 and 2.5 ppm. • •

9. C h o l ine The choline peak receives contribution from glycerophosphocholine, phosphocholine, and phosphatidylcholine. It is the precursor of acetyl choline and phosphatidylcholine. Acetylcholine is an important neurotransmitter and the latter is an integral part of cell membrane synthesis. Disease processes affecting the cell membrane and myelin can lead to the release of phosphatidylcholine. Thus, elevation of choline can be seen during ischemic injury, neoplasm or acute demyelination diseases. Choline is the second largest peak and assigned to 3.2 ppm.

10. Creatine (Cr)  The Cr peak receives contribution mainly from creatine, and creatine phosphate.  The phospocreatine supplies phosphate to adenosine diphosphate (ADP) to form adenosine triphosphate (ATP) with the release of creatine. The overall level of total creatine in normal brain is fairly constant. Reduced Cr level may be seen in pathologic processes such as neoplasm, ischemic injury, infection or some systemic diseases. Most metastatic tumors to the brain do not produce creatine since they do not possess creatine kinase. Cr is the third highest peak and is assigned to 3.03 ppm. It is usually seen next to the right of choline .

11. La c tate Lactate has a molecular structure of CH3-COH2-CO2. Lactate levels in the brain are normally are very low or absent. When oxygen supply is depleted, the brain switches to anaerobic respiration (Not from O2) for which one end product is lactate. Therefore, elevated lactate peak is a sign of hypoxic tissue. Low oxygen supply can result from decreased oxygen supply or increased oxygen requirement. The former may be seen in vascular insults, or hypoventilation and the latter may be seen in neoplastic tissue.

12.  Lactate peak occurs at two different locations.  The lower field peak (a doublet) occurs at approximately 1.32 ppm.  The other peak (a quartet) is seen at 4.1 ppm and this is very close to the water peak (4.7 ppm) . – usually suppressed during data processing.

13. Myo-Inositol (mI) Myo-Inositol is a glucose-like metabolite and it involves primarily in hormone-sensitive neuroreception. It is found mainly in astrocytes and helps to regulate cell volume. Elevated level of mI would be seen where there is glial cell proliferation as in gliosis. The main mI peak is assigned to 3.56 ppm and additional peak may be seen at 4.06 ppm

14. Lipids Lipids are composition of triglycerides, phospholipids, and fatty acids. These substances are incorporated into cell membranes and myelin. Lipid peak should not be seen unless there is destructive process of the brain including necrosis, inflammation or infection. Lipids have a very short T1 relaxation time and are normally not seen unless short TEs are utilized. Lipid resonance at 1.2 ppm can sometimes obscure the lactate peak at 1.32 ppm. Fat in the cranium can contaminate the true disease process if the voxels are placed too close the cranium.

15. G l u t amat e an d Glutam i n e ( G l x ) Glutamate is an excitatory n euro transmitter in mitochondrial metabolism. Glutamine and glutamate resonate closely together. Their sum is often designated as Glx and is assigned between 2.1 and 2.5 ppm.

16. SINGLE-VOXEL MR SPECTROSCOPY  Less advance.  Volume averaging Small area of coverage. acquires spectra from single small voxel. short acquisition times. Histologically simpler lesions . MR SPECTROSCOPIC IMAGING/ MULTI-VOXEL . more technically advanced technique. small voxel size  dec. volume averaging large volume of coverage acquires spectra from numerous small voxels. long acquisition times. For complex lesions

17. MULTI VOXEL SPE C T RO S CO PY Multivoxel spectroscopy can be used to obtained one, two or three dimensional localization. The major engine behind multi voxel is CHEMICAL SHIFT IMAGING (CSI). This technique is developed to obtain separate images from water and fat bound protons. It is referred as Magnetic Resonance Spectroscopic Imaging(MRSI).

18. It obtains simultaneously many voxels and spatial distrubution of the metabolities in a single sequence. Large volume of coverage. It is used for complex lesions. Long acquisition time (6-12 min). Time of echo:35 and 144 ms.

19. Ec h o -T i me As in MR imaging, the echo time affects the information obtained with MRS. Short TE refers to a study in which it varies from 20 to 40 ms. It has a higher SNR and less signal loss due to T2 and T1 weighting than long TE. These short TE properties result in a spectrum with more metabolites peaks, such as myoinositol and glutamine-glutamate which are not detected with long TE .

20. MRS spectra may also be obtained with long TEs, from 135 to 288 ms. With a long TE of 270 msec, only metabolites with a long T2 are seen, producing a spectrum with primarily NAA, creatine, and choline. One other helpful TE is 144 msec because it inverts lactate at 1.3 ppm. With TE of 270-288 ms there is a lower SNR and the lactate peak is not inverted

21. Plannin g of MRS The ROI will be placed at the center of the enhancing tumor covering the lesion and the normal brain as much as possible but excluding the subcutaneous fat and sinuses.

22. Normal MRS

23. L y m p homa

24. Anaplastic Astrocytoma

25. Gl i o m a

26. MRS T ECHNIQUES Single Volume MRS STEAM (Stimulated Echo Acquisition Mode) PRESS (Point Resolved Spectroscopy) Short TE can be used to detect glutamate, glutamine, myoinositol Not possible Chemical shift selective pulse used to suppress water signal can be given throughout volume localisation phase Can be given only at preparation phase Factor of 2 loss in signal intensity Factor of 2 gain in signal intensity Susceptible to motion Not affected by motion Multivolume MRS- multiple adjacent volume over a large region of interest can be assessed in a single measurement. Acquisition time is 6-12 min.

27. TE CHN IQ U E :     Single volume and Multivolume MRS. 1) Single volume : Stimulated echo acquisition mode (STEAM) Point-resolved spectroscopy (PRESS) It gives a better signal-to noise ratio 2) Multivolume MRS: chemical shift imaging (CSI) or spectroscopic imaging (SI) Much larger area can be covered, eliminating the sampling error to an extent but significant weakening in the signal-to-noise ratio and a longer scan time. Time of echo : 35 ms and 144ms. Resonance frequencies on the x-axis and amplitude (concentration) on the y-axis.

28. N ORMAL MRS C H OLINE NAA CR E A TINE

29. MRS of white matter in a normal brain. (A) Long TE spectra have less baseline distortion and are easy to process and analyze but show fewer metabolites than short TE spectra. Also, the lactate peaks are inverted, which makes them easier to differentiate them from lipids. (B) Short TE demonstrates peaks attributable to more metabolites, including lipids, glutamine and glutamate, and myo-inositol

30. M ULTI V OXEL MRS

31. Metabolite O BSE R V L o c a ti o n ppm ABLE M ETAB Normal function OLITES Increased Lipids 0.9 & 1.3 Cell membrane Hypoxia, trauma, high grade component neoplasia. Lactate 1.3 Denotes anaerobic Hypoxia, stroke, necrosis, TE=272 glycolysis mitochondrial diseases, (upright) neoplasia, seizure TE=136 (inverted) Alanine 1.5 Amino acid Meningioma Acetate 1.9 Anabolic precursor Abscess , Neoplasia,

32. P RIN C IPLE ME T A B OLITES Metabolite Location ppm Normal fu n ction In c r e ase d Decreased N A A 2 Nonspecific neuronal marker (Reference for chemical shift) C a n a va n ’ s disease Neuronal loss, stroke, dementia, AD, hypoxia, neoplasia, abscess Glutamate , glutamine, GABA 2.1- 2.4 N e ur o tra n smitt er Hypoxia, HE H y p o n a tremia Succinate 2.4 Part of TCA cycle Bra i n a b scess C r e a ti n e 3. 3 Cell energy marker (Reference for metabolite ratio) Trauma, h y p e rosm o l a r state Stroke, hypoxia, n e o p l a sia

33. Metabolite Location ppm Normal f un ct i o n In c r e ase d Decreased Ch ol i ne 3.2 Marker of cell memb turnover Neoplasia, d e m y e l i n ati o n (MS) H y p o m y e l i n atio n Myoinositol 3.5 & 4 Astrocyte marker AD D e m y e l i n ati n g diseases

34. M ETABOLITE RATIOS : Normal abnormal NAA/ Cr 2.0 <1.6 NAA/ Cho 1.6 <1.2 Cho/Cr 1.2 >1.5 Cho/NAA 0.8 >0.9 Myo/NAA 0.5 >0.8

35. MRS Dec NAA/Cr Inc acetate, succinate, amino acid, lactate Neuodegener ati v e Alzheimer Dec NAA/Cr Dec NAA/ Cho Inc Myo/NAA Slightly inc Cho/ Cr Cho/NAA Normal Myo/NAA ± lipid/lactate Inc Cho/Cr Myo/NAA Cho/NAA Dec NAA/Cr ± lipid/lactate Mali g nancy D e m y e linating disease P y o g enic abscess

36. C LINICAL A PPLICATIONS OF MRS:        Class A MRS Applications: Useful in Individual Patients MRS of brain masses: Distinguish neoplastic from non neoplastic masses Primary from metastatic masses. Tumor recurrence vs radiation necrosis Prognostication of the disease Mark region for stereotactic biopsy. Monitoring response to treatment. Research tool MRS of Inborn Errors of Metabolism Include the leukodystrophies, mitochondrial disorders, and enzyme defects that cause an absence or accumulation of metabolites

37. C LASS B MRS A PPLICATIONS : O CCASIONALLY U SEFUL IN I NDIVIDUAL P ATIENTS 1 ) Ischemia, Hypoxia, and Related Brain Injuries Ischemic stroke Hypoxic ischemic encephalopathy. 2)Epilepsy Class C Applications : Useful Primarily in Groups of Patients (Research) HIV disease and the brain Neurodegenerative disorders Amyotrophic lateral sclerosis Multiple sclerosis Hepatic encephalopathy Psychiatric disorders

38. A 50 yr M with fever, headache and Lt hemiparesis B , Axial T2-weighted image showing ring lesion with surrounding hyperintensity and mass effect. C , Axial contrast-enhanced T1W image shows a ring-shaped cystic lesion and surrounding edema. D , DWI shows marked hyperintensity in the cavity and slight iso- to hypointensity surrounding the edema. E , ADC map reveals hypointensity in the cavity, representing restricted diffusion, and hyperintense areas surrounding the edema. DDx- ?abscess, ?tumor F ,G. MRS from the abscess cavity show peaks of acetate ( Ac ), alanine ( Ala ), lactate ( Lac ), and amino acids ( AA ). At a TE of 135 ( G ), the phase reversal resonances are well depicted at 1.5, 1.3, and 0.9 ppm, which confirms the assignment to alanine, lactate, and amino acids, respectively. Dx- Pyogenic abscess

39. A 67 YR M WITH POSTERIOR FOSSA SOL B. Axial T2WI showing hyperintense mass lesion in Rt cerebellum . Box in the center of the lesion represents the 1 H-MRS volume of interest. C , Axial contrast-enhanced T1W image shows a ring-enhanced lesion in the right cerebellum. D , DWI shows markedly low signal intensity in the necrotic part of the tumor. E , ADC map reveals high signal intensity in the necrotic part of the tumor that is similar to that of CSF, reflecting marked diffusion. DDX- ?tumor F , G. MRS from the necrotic center of the tumor show a lactate ( Lac ) peak at 1.3 ppm that is inverted at a TE of 135. No amino acid or lipid peaks seen Dx- tumor Biopsy revealed metastasis from primary lung adenocarcinoma

40. Serial magnetic resonance spectroscopic data from a 25-year-old lady who was under 6-monthly imaging follow-up for a low-grade glioma. A. Voxel (open square) is situated in the bulk of the tumour, which is appreciated as an ill-defined area of T2-weighted hyperintensity within the cingulate gyrus of the right frontal lobe. B. Initial spectra at presentation demonstrates abnormal Cho/NAA area ratio of 1.4. Note the absence of lactate at 1.33ppm. C. Spectroscopy 6-months later demonstrates deterioration in the Cho/NAA area ratio (now 2.21) and the new presence of an inverted lactate peak

41. A 48 Y F WITH HEADACHE AND LEFT HEMIPARESIS A, Coronal contrast-enhanced T1-weighted MR image shows a large right temporal mass with rich contrast uptake with extensive midline shift. B, Spectrum of the lesion shows increased Cho/Cr ratio and an absence of NAA . There is an alanine (Ala) doublet at 1.45 ppm and lipid (lip) signals at 0.8 to 1.2 ppm Dx- Meningioma

42. A 27 Y M WITH MULTIPLE NODULAR LESIONS IN BRAIN A.T1WE at midbrain level shows nothing remarkable B. Contrast enhanced T1 W image revealed multiple small nodular areas of enhancement predominantly located at gray white junction. DDx- ?Multiple tuberculoma, ?Multiple NCC C. MR spectroscopy ( A ; TE = 35ms). peaks A and B at 0.9 and 1.33 ppm, respectively, represent typical long-chain lipids (lipid/lactate). NAA and Cr are barely detectable. A small Cho peak, C , is seen to resonate at 3.2 ppm. ( B ; TE = 144ms) Long TE MRS depicts persistence of predominant lipid peak at 1.33 ppm. Dx- Multiple tuberculoma

43. A 14 Y M WITH REFRACTORY CPS PLANNED FOR SURGERY Conventional MRI revealed no apparent abnormality. MRS of Left anterior hippocampus showed smaller NAA peak (33% less) compared to Right indicating a left temporal seizure focus L e ft R i g h t

44. MRS in hippocampal sclerosis Short TE (35msec) spectra at 3T obtained in the left and right hippocampal formation from a patient with right HS using single-voxel technique. The decreased NAA signal and the increased mI at the affected region (A) are shown when compared with the contralateral normal hippocampal formation

45. FUC OF A 48 YR F WITH PROVEN GLIOBLASTOMA MULTIFORME TREATED WITH SURGERY , EXTERNAL BEAM RADIATION AND INTERSTITIAL BRACHYTHERAPY . A, Axial T1-weighted MR image reveals enhancement of a right frontal lobe/insular lesion that has both solid and cavitary components. The spectroscopy voxel includes the medial margin of enhancement. DDx- ?Recurrent tumor, ?Radiation necrosis B, MR spectrum shows a prominent lipid/lactate peak with minimal residual Cho and Cr; NAA is absent . Dx -radiation necrosis Diagnosis was confirmed at resection. This patient had subsequent follow-up spectroscopy studies at 1, 3, and 4 months that were unchanged (not shown). L i p Lac Cho Cr NAA

46. 76 YRS MALE PRESENTED WITH RECENT MEMORY LOSS T1W image shows reduction in the volume of the hippocampus. Proton MRS in hippocampal region shows MI pe a k, decreased N A A a nd elevated MI/Cr ratio Dx - Alzheimer’s Disease

47. Canavan disease , or spongiform leukodystrophy, results from a deficiency of aspartocylase, an enzyme that hydrolyzes NAA to acetate and aspartate. In its absence, NAA accumulates in the brain. MRS is diagnostic for this condition because the abnormally high NAA peak is almost exclusively seen in Canavan disease.

48. Patient with known diagnosis of MELAS with new onset of visual symptoms. (Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) presenting 1.5T brain MRI demonstrates areas of T2 hyperintensity and abnormal restricted diffusion, likely related to stroke-like areas of cytotoxic edema. MR spectroscopy (TE=144 ms) from the right occipital abnormality shows an inverted doublet at 1.3 ppm (arrows) consistent with a lactate peak.

49. MRS IN OTHER CONDITIONS Ischemic stroke- appearance of lactate peak within minutes of ischemia. In chronic phase NAA is suppressed AIDS dementia- increased MI and Gln detected. MRS may help in detection of subclinical disease, opportunistic infections and monitoring ART Multiple sclerosis- Increased Cho due to active demylination. Lipid and Lac may also rise. Presence of MI suggests severe demylination

50. F UNCTIONAL MRS It is a promising new technique still in research phase Fast spectroscopic imaging technique is used to detect transient rise in metabolites during language or visual tasks Increase in Lac and Cr have been noted in left temporal lobe during language task May complement fMRI and PET

51. 7 MONTH INFANT WITH DELAYED MILESTONES & SPASTICITY T 1W– diffuse hypointensity of supratentorial white matter. T2W -diffuse hyperintensity of supratentorial white matter MRS s h ow markedly raised N AA p eak as compared to control subject. Dx – Canavan’s disease.

52. 5 YRS CHILD WITH SEIZURES & 2 A – T 2 W- hyperintense left occipital region. B- MRS obtained from rt & lt occipital cortices. - i n vert ed d ou b l e t lacta t e pe a k from rt occipital cortex at 1.3 ppm -reduced all peaks from old lt lesion. Dx – MELAS STROKE LIKE EPISODES

53. A LZHEIMER ’ S D ISEASE T1W image shows reduction in the volume of the hippocampus of the patient with AD Proton MRS in hippocampal region shows MI peak,decreased NAA and elevated MI/Cr ratio

54. P A TIENT WITH REFRACTORY CPS PLANNED FOR SURGERY Conventional MRI revealed no apparent abnormality. MRS of Left anterior hippocampus showed smaller NAA peak (33% less) compared to Right indicating a left temporal seizure focus L e ft R i g h t

55. L OCALISED 1 H-MR SPECTROSCOPY FOR METABOLIC CHARACTERISATION OF DIFFUSE AND FOCAL BRAIN LESIONS IN PATIENTS INFECTED WITH HIV I L S IMONEA ET AL A significant decrease in NAA/Cr and NAA/Cho ratios were found in all HIV diagnostic groups in comparison with neurological controls (p<0.003), The NAA/Cr ratio was significantly lower in PML and lymphomas than in HIV encephalopathies (p<0.02) and toxoplasmosis (p<0.05). HIV encephalopathies, lymphomas, and toxoplasmosis showed a significant increase in the Cho/Cr ratio in comparison with neurological controls (p<0.03) The presence of a lipid signal was more frequent in lymphomas (71%) than in other HIV groups CONCLUSION 1 H-MRS shows a high sensitivity in detecting brain involvement in HIV related diseases, but a poor specificity in differential diagnosis of HIV brain lesions.

56. O THER CONDITIONS : Hepatic encephalopathy: increased glutamate, decreased myoinositol Phenylketonuria: increased Phenylalanine peak at 7.3ppm Parkinson’s disease Motor neuron disease Psychiatric disease

57. Proton magnetic resonance spectroscopy of the brain is useful whenever biochemical or metabolic assessment may be necessary, such as in differential diagnosis of focal brain lesions (neoplastic and non-neoplastic diseases) Diagnosis , grading of tumors and response to treatment NAA marker of neuronal viability Tumors – increased Cho/Cr, Cho/NAA, lipid lactate, decreased NAA/Cr Abscess: increased Cho/Cr, lactate, acetate, succinate peaks Demyelinating disease: slightly increased Cho/Cr, Cho/NAA, lipid , decreased NAA/Cr It is non invasive, radiation free, time saving, cost effective, very sensitive and specific

58. The MR spectra do not come labeled with diagnoses. They require interpretation and should always be correlated with the MR images before making a final diagnosis

59. Conclusion There are two methods of proton magnetic resonance spectroscopy: single voxel and multivoxel, with or without spectroscopic imaging. Single voxel proton magnetic resonance spectroscopy provides a rapid biochemical profile of a localized volume within a region of interest that may be determined, especially in brain studies. Spectroscopic imaging provides biochemical information about multiple, small and contiguous volumes focalized on a particular region of interest that may allow the mapping of metabolic tissue distribution. By using this method, the data obtained may be manipulated by computer and superimposed on the image of an abnormality, thereby illustrating the distribution of such metabolites within that area.

60. Interpretation of the spectroscopic curve The spectrum represents radiofrequency signals emitted from the proton nuclei of the different metabolites into the region of interest. Specific metabolites always appear at the same frequencies, expressed as parts per million, and are represented on the horizontal axis of the graph. The vertical axis shows the heights of the metabolite peaks, represented on an arbitrary intensity scale

61. Bradley’s Neurology in clinical practice 7 th edition Neuroradiology in clinical Practice : 1 st edition Clinical MR Neuroimaging : Diffusion, Perfusion & Spectroscopy : MRI Brain and spine : Scott W. Atlas: 4 th edition Reference

62. Thank You Nitish Virmani Lecturer Department of Radio-Imaging Technology Faculty of Allied Health Sciences SGT University Email- [email protected]