1H Magnetic Resonance Spectroscopy MRS

1. 1H Magnetic Resonance Spectroscopy (MRS) Introduction commonly detectable metabolites commonly used 1H MRS data acquisition methods examples of 1H MRS applications in studies of neurodisorders and breast cancer

2. Introduction useful and important as an additional evaluation tool for various neurodisorders, such as brain cancer, stroke, epilepsy, Alzheimer’s disease, multiple sclerosis, etc. Neuro 1H MRS scans reimbursable. Research beyond neuro-applications breast cancer prostate cancer, etc.

3. Commonly detectable Brain Metabolites at low field strength (? 1.5T) N-acetylaspartate (NAA) neuronal marker 2.02 ppm Total creatine (Cr: creatine and phosphocreatine) Energy storage molecules in tissue Stable concentration, as internal reference in MRS studies 3.03 ppm Choline compounds (Cho: phosphocholine, glycero- phosphocholine) cell membrane turnover precursor of molecules for cellular signal transduction 3.23 ppm Lactate (Lac) anaerobic glycolysis 1.33 ppm

4. Myo-inositol (mI) glial marker precursor of molecules for cellular signal transduction 3.56 ppm Higher filed strength (? 3 T) improved S/N, spectral resolution more detectable metabolites, such as Gaba separating glutamate and glutamine 13C MRS --- glucose metabolism 31P MRS --- energy metabolism

5. Common 1H MRS data acquisition PRESS (Point RESolved Spectroscopy, 90o-180o-180o) stronger signal, long TE application STEAM (STimulated Echo Acquisition Mode, 90o-90o-90o) weaker signal, short TE application Water suppression (H2O ~ 50 M, metabolites ~ 1-10 mM) CHESS (chemical shift selective) pulses for saturation Single voxel Multi-voxel (CSI, MRSI) 2D, multi-slice 3D

6. PRESS sequence

7. STEAM sequence

10. Common 1H MRS data quantitation Metabolite ratio (ratio of peak areas): NAA/Cr, Cho/Cr Absolute quantitation: mmol/tissue volume Internal reference: Cr, H2O Phantom replacement method --- correction for coil load External reference --- correction for B1 inhomogeneity * MRS signals are both T1 and T2-weighted, corrections for differences in T1 and T2 between in vivo tissue and aqueous solution environments.

11. Single-Voxel MRS Studies of Alzheimer’s Disease(Neurology 2001; 57: 626-632)

12. Single-Voxel MRS Studies of Alzheimer’s Disease

13. Single-Voxel MRS Studies of Alzheimer’s Disease

14. Single-Voxel MRS Studies of Down Syndrome ( Am J Psychiatry 1999; 156: 1879-1886)

15. Single-Voxel MRS Studies of Ts65Dn Mouse---Down Syndrome Model (NeuroReport 2000; 11: 445-448)

16. Single-Voxel MRS Studies of Ts65Dn Mouse---Down Syndrome Model mI mI-1- phosphate

18. Significant correlations between NAA/Cho, NAA/Cr, CCSF volume fraction (of the total brain and CSF volume), and BRB scores

20. NAA quantification using CSF water as internal reference Reference MRSI scan without water suppression, 1 scan average, other parameters kept the same Water signal from CSF voxel as internal reference NAA/H2O ratio corrected for CSF volume fraction in the MRS voxel.

21. 1H MRS Study of Breast Cancer High false positive rate (60-80%) in conventional mammography, resulting unnecessary biopsy. Recently, dynamic contrast enhancement (DCE) T1-weighted MRI ---- an integral part of a standard breast cancer diagnostic protocol. Excellent sensitivity (88-100%) Specificity rather variable (37-97%)

22. 1H MRS Study of Breast Cancer Promising tools for improving specificity in detection of breast malignancy: 1H MRS Perfusion T2*-weighted MRI 1H MRS measurement detection of enhancing Cho signal, marker of active tumor

23. 1H MRS Study of Breast Cancer

24. 1H MRS Study of Breast Cancer

25. 1H MRS Study of Breast Cancer DCE MRI: 100% sensitivity, no false negative 9 out of 39 positive turned out benign by biopsy ------ 77% specificity. DCE MRI + MRS: no false negative 3 out of 26 MRS cases turned out false positive ------ 88% specificity

26. 1H MRS Study of Brain Cancer In recent years, in addition to conventional pre- and post-contrast MRI, several other MR techniques have been used for the diagnosis and evaluation of brain tumors. 1H MRS: diagnosis, clinical evaluation of tumor response to therapy, differentiate tumor recurrence and radiation necrosis. Elevated Cho signal is a marker of viable tumor Diffusion Weighted Imaging (DWI): differentiate necrosis, edema, and viable tumor regions. Perfusion Imaging: evaluate tumor vascularity, assess tumor grade.

28. Post-contrast T1 Images and Proton Spectra of a Patient with CNS Lymphoma Pre - ICC Post - 1st ICC Post - 4th ICC

29. ADC and rCBV Maps of a Patient with CNS Lymphoma Pre - ICC Post - 1st ICC Post - 4th ICC

31. Localization of Spectroscopic Voxel for a Patient with Metastatic Squamous Cell Carcinoma Pre-therapy Post-therapy

32. Proton Spectra of a Patient with Metastatic Squamous Cell Carcinoma Pre-therapy Post-therapy

33. Localization of Spectroscopic Voxel for a Patient with Squamous Cell Carcinoma Pre-therapy Post-therapy

34. Proton Spectra of a Patient with Squamous Cell Carcinoma Pre-therapy Post-therapy

35. Changes of Cho/Water Ratio for Head and Neck Tumor Patients

36. Discriminating Neoplastic and Non-neoplastic Thyroid Lesions Using 1H MRS 29 patients with thyroid lesion 1H MRS examination PRESS single-voxel (TE/TR 135/2000) at lesion (n = 29) and at normal contralateral side (n=5) from healthy control (n=2) Resection of thyroid mass within one week

37. Proton spectra from neoplastic thyroid lesion and normal-appearing contralateral region

38. Non-neoplastic thyroid lesion Normal healthy control

39. Significant difference in Cho/Water ratio between neoplastic (3.36 ? 2.55, n=22) and non-neoplastic (0.16 ? 0.11, n=7) thyroid lesions

40. Results Thyroid neoplasm Cho/water > 1.0 x 10-3 Thyroid non-neoplasm Cho/water < 0.4 x 10-3

41. Conclusion Strong correlation between MRS and pathology results It’s difficult to distinguish neoplastic from non-neoplastic thyroid lesions based on conventional post-contrast T1-weighted images, as both are usually enhanced. 1H MRS can be a valuable screening tool with high sensitivity in detection of thyroid neoplasm. Aid in treatment planning and evaluation of post-operation recurrence and node/metastasis.

43. 1H MRS Study of a child with NKH(Non Ketotic Hyperglycinemia)(J Neuroimaging 2001; 11: 209-212)

44. WM proton spectra at 10 and 13 months(TE/TR 270/2000)

45. Correlation of plasma and brain glycine levels

46. 1H MRS Study of a child with ADEM(Acute Disseminated Encephalomyelitis)

47. Brain Metabolite Ratios in a Child with ADEM MRS Study NAA/Cr Cho/Cr Lac/Cr Voxel BG initial 0.71 0.76 0.51 BG follow-up 0.83 0.88 0.21 WM initial 1.62 0.91 0.00 WM follow-up 1.38 1.10 0.00

48. In vivo 1H MRS study of a rat model of autism(Physiol Behav 2002; 75: 403-410)

49. PRESS (TE/TR 40/2000), 0.2 cc voxel size

50. Significant decrease of NAA/Cr in autistic rats

51. Significant increase of Cho/Cr in autistic rats

52. Significant increase of mI/Cr in autistic rats

53. 1H MRS study of autistic human subjects(PRESS, TE/TR 40/2000)

54. 1H MRS study of autistic human subjects(PRESS, TE/TR 40/2000)

55. 1H MRS study of autistic human subjects(PRESS, TE/TR 40/2000)

56. 1H Spectra from Healthy Controls Left Hipp-Amyg Cerebellum

57. 1H MRS study of autistic human subjects Metabolite Ratios in Children with PDD (N = 10) and Healthy Controls (N = 6) LHA RHA Cerebellum PDD Control PDD Control PDD Control NAA/Cr 1.97 ? 0.32* 2.42 ? 0.32 1.94 ? 0.51* 2.88 ? 0.65 1.45 ? 0.23 1.38 ? 0.12 Cho/Cr 0.72 ? 0.21* 0.47 ? 0.17 0.68 ? 0.22 0.54 ? 0.28 0.75 ? 0.24* 0.46 ? 0.11 mI/Cr 0.78 ? 0.26* 0.50 ? 0.17 0.72 ? 0.31* 0.39 ? 0.13 0.51 ? 0.17* 0.20 ? 0.12 mean ? SD; *: mean in PDD group differs significantly from the control group (unpaired t-test, p < 0.05).