1
H Magnetic Resonance Spectroscopy (MRS)
• Introduction
– commonly detectable metabolites
– commonly used 1
H MRS data ac...
Introduction
• useful and important as an additional evaluation tool for
various neurodisorders, such as brain cancer, str...
Commonly detectable Brain Metabolites at low field
strength (≤ 1.5T)
• N-acetylaspartate (NAA)
– neuronal marker
– 2.02 pp...
• Myo-inositol (mI)
– glial marker
– precursor of molecules for cellular signal transduction
– 3.56 ppm
• Higher filed str...
Common 1
H MRS data acquisition
• PRESS (Point RESolved Spectroscopy, 90o
-180o
-180o
)
– stronger signal, long TE applica...
• PRESS sequence
• STEAM sequence
90o
90o
TE/2 TM TE/2
Single-Voxel MRS Studies of Alzheimer’s Disease
(Neurology 2001; 57: 626-632)
1
H MRSI Study
in Multiple Sclerosis
(TE/TR: 135/1500 ms)
Common 1
H MRS data quantitation
• Metabolite ratio (ratio of peak areas): NAA/Cr, Cho/Cr
• Absolute quantitation: mmol/ti...
Single-Voxel MRS Studies of Alzheimer’s Disease
(Neurology 2001; 57: 626-632)
Single-Voxel MRS Studies of Alzheimer’s Disease
Single-Voxel MRS Studies of Alzheimer’s Disease
Single-Voxel MRS Studies of Down Syndrome
( Am J Psychiatry 1999; 156: 1879-1886)
Single-Voxel MRS Studies of Ts65Dn Mouse
---Down Syndrome Model
(NeuroReport 2000; 11: 445-448)
Single-Voxel MRS Studies of Ts65Dn Mouse
---Down Syndrome Model
• mI mI-1- phosphate
Li
1
H MRSI Study
in Multiple Sclerosis
(TE/TR: 135/1500 ms)
Significant correlations between NAA/Cho, NAA/Cr, CCSF volume
fraction (of the total brain and CSF volume), and BRB scores...
Overall Neuropsychological Performance Z Score
2.01.51.0.50.0-.5-1.0-1.5-2.0
CombinedMRVariablePredictedScore
3
2
1
0
-1
-...
NAA quantification using CSF water as internal reference
• Reference MRSI scan without water suppression, 1 scan
average, ...
1
H MRS Study of Breast Cancer
• High false positive rate (60-80%) in conventional
mammography, resulting unnecessary biop...
1
H MRS Study of Breast Cancer
• Promising tools for improving specificity in detection of
breast malignancy:
– 1
H MRS
– ...
1
H MRS Study of Breast Cancer
0
200
400
600
800
1000
1200
1400
0 20 40 60 80 100 120 140
Time (Sec)
S
1
H MRS Study of Breast Cancer
Single-voxel MRS, PRESS
(TE/TR 135/2000 ms)
1
H MRS Study of Breast Cancer
• DCE MRI:
– 100% sensitivity, no false negative
– 9 out of 39 positive turned out benign b...
1
H MRS Study of Brain Cancer
• In recent years, in addition to conventional pre- and post-
contrast MRI, several other MR...
Monitoring tumor response to intracarotid therapy using MRS
Post-contrast T1 Images and Proton Spectra
of a Patient with CNS Lymphoma
Pre - ICC Post - 1st ICC Post - 4th ICC
ADC and rCBV Maps of a Patient with
CNS Lymphoma
Pre - ICC Post - 1st ICC Post - 4th ICC
Localization of Spectroscopic Voxel for a Patient with Metastatic
Squamous Cell Carcinoma
Pre-therapy Post-therapy
1
H MRS...
Proton Spectra of a Patient with Metastatic
Squamous Cell Carcinoma
Pre-therapy Post-therapy
Localization of Spectroscopic Voxel for a
Patient with Squamous Cell Carcinoma
Pre-therapy Post-therapy
Proton Spectra of a Patient with Squamous
Cell Carcinoma
Pre-therapy Post-therapy
Changes of Cho/Water Ratio for Head and
Neck Tumor Patients
Discriminating Neoplastic and Non-neoplastic Thyroid
Lesions Using 1
H MRS
• 29 patients with thyroid lesion
• 1
H MRS exa...
Proton spectra from neoplastic thyroid lesion and
normal-appearing contralateral region
Non-neoplastic thyroid lesion Normal healthy control
Cho
Lip/Lac
Significant difference in Cho/Water ratio between
neoplastic (3.36 ± 2.55, n=22) and non-neoplastic (0.16 ±
0.11, n=7) thy...
Results
• Thyroid neoplasm
Cho/water > 1.0 x 10-3
• Thyroid non-neoplasm
Cho/water < 0.4 x 10-3
Conclusion
• Strong correlation between MRS and pathology results
• It’s difficult to distinguish neoplastic from non-neop...
Proton MRS Studies of Pediatric Neurodisorder
1
H MRS Study of a child with NKH
(Non Ketotic Hyperglycinemia)
(J Neuroimaging 2001; 11: 209-212)
WM proton spectra at 10 and 13 months
(TE/TR 270/2000)
Correlation of plasma and brain glycine levels
1
H MRS Study of a child with ADEM
(Acute Disseminated Encephalomyelitis)
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...
In vivo 1
H MRS study of a rat model of autism
(Physiol Behav 2002; 75: 403-410)
PRESS (TE/TR 40/2000), 0.2 cc voxel size
Significant decrease of NAA/Cr in autistic rats
0.2
0.4
0.6
0.8
1
1.2
1.4
NAA/Cr
Control Autistic
p < 0.01
Significant increase of Cho/Cr in autistic rats
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
Cho/Cr
Control Autistic
p < 0.001
Significant increase of mI/Cr in autistic rats
0
0.5
1
1.5
2
2.5
mI/Cr
Control Autistic
p < 0.02
1
H MRS study of autistic human subjects
(PRESS, TE/TR 40/2000)
1
H MRS study of autistic human subjects
(PRESS, TE/TR 40/2000)
1
H MRS study of autistic human subjects
(PRESS, TE/TR 40/2000)
1
H Spectra from Healthy Controls
Left Hipp-Amyg Cerebellum
1
H MRS study of autistic human subjects
Metabolite Ratios in Children with PDD (N = 10) and Healthy Controls (N = 6)
LHA ...
1H MRS and Volumetric MRI Studies of Multiple Sclerosis ...
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1H MRS and Volumetric MRI Studies of Multiple Sclerosis ...

  1. 1. 1 H Magnetic Resonance Spectroscopy (MRS) • Introduction – commonly detectable metabolites – commonly used 1 H MRS data acquisition methods – examples of 1 H MRS applications in studies of neurodisorders and breast cancer
  2. 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 1 H MRS scans reimbursable. • Research beyond neuro-applications – breast cancer – prostate cancer, etc.
  3. 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. 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 – 13 C MRS --- glucose metabolism – 31 P MRS --- energy metabolism
  5. 5. Common 1 H 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. 6. • PRESS sequence
  7. 7. • STEAM sequence 90o 90o TE/2 TM TE/2
  8. 8. Single-Voxel MRS Studies of Alzheimer’s Disease (Neurology 2001; 57: 626-632)
  9. 9. 1 H MRSI Study in Multiple Sclerosis (TE/TR: 135/1500 ms)
  10. 10. Common 1 H 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 T1and T2-weighted, corrections for differences in T1 and T2between in vivo tissue and aqueous solution environments.
  11. 11. Single-Voxel MRS Studies of Alzheimer’s Disease (Neurology 2001; 57: 626-632)
  12. 12. Single-Voxel MRS Studies of Alzheimer’s Disease
  13. 13. Single-Voxel MRS Studies of Alzheimer’s Disease
  14. 14. Single-Voxel MRS Studies of Down Syndrome ( Am J Psychiatry 1999; 156: 1879-1886)
  15. 15. Single-Voxel MRS Studies of Ts65Dn Mouse ---Down Syndrome Model (NeuroReport 2000; 11: 445-448)
  16. 16. Single-Voxel MRS Studies of Ts65Dn Mouse ---Down Syndrome Model • mI mI-1- phosphate Li
  17. 17. 1 H MRSI Study in Multiple Sclerosis (TE/TR: 135/1500 ms)
  18. 18. Significant correlations between NAA/Cho, NAA/Cr, CCSF volume fraction (of the total brain and CSF volume), and BRB scores 0.5 1.5 2.5 3.5 -2 -1 0 1 2 BRB RPPVNAA/CR r = 0.64 p < 0.001 0.5 1 1.5 2 2.5 3 3.5 -2 -1 0 1 2 BRB RPPVNAA/Cho r = 0.56 p < 0.001 .00 .20 .40 .60 .80 1.00 1.20 1.40 -2.00 -1.00 .00 1.00 2.00 BRB CCSF r = -0.70 p < 0.001 .50 1.00 1.50 2.00 2.50 3.00 3.50 .00 .50 1.00 1.50 CCSF RPPVNAA/Cr r = -0.63 p < 0.001
  19. 19. Overall Neuropsychological Performance Z Score 2.01.51.0.50.0-.5-1.0-1.5-2.0 CombinedMRVariablePredictedScore 3 2 1 0 -1 -2 -3 Relation between overall neuropsychological performance and standardized predicted score from a multiple regression model including: central cerebral atrophy, lesion volume, and RPPV NAA/Cho (R = - 0.785 p < .001)
  20. 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. 0 0.004 0.008 0.012 0.016 -1.5 -0.5 0.5 1.5 BRB NAA/H20 r = 0.59 p < 0.05
  21. 21. 1 H 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. 22. 1 H MRS Study of Breast Cancer • Promising tools for improving specificity in detection of breast malignancy: – 1 H MRS – Perfusion T2*-weighted MRI • 1 H MRS measurement – detection of enhancing Cho signal, marker of active tumor
  23. 23. 1 H MRS Study of Breast Cancer 0 200 400 600 800 1000 1200 1400 0 20 40 60 80 100 120 140 Time (Sec) S
  24. 24. 1 H MRS Study of Breast Cancer Single-voxel MRS, PRESS (TE/TR 135/2000 ms)
  25. 25. 1 H 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. 26. 1 H 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. • 1 H 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.
  27. 27. Monitoring tumor response to intracarotid therapy using MRS
  28. 28. Post-contrast T1 Images and Proton Spectra of a Patient with CNS Lymphoma Pre - ICC Post - 1st ICC Post - 4th ICC
  29. 29. ADC and rCBV Maps of a Patient with CNS Lymphoma Pre - ICC Post - 1st ICC Post - 4th ICC
  30. 30. Localization of Spectroscopic Voxel for a Patient with Metastatic Squamous Cell Carcinoma Pre-therapy Post-therapy 1 H MRS for Monitoring Head and Neck Cancer Response to Therapy
  31. 31. Proton Spectra of a Patient with Metastatic Squamous Cell Carcinoma Pre-therapy Post-therapy
  32. 32. Localization of Spectroscopic Voxel for a Patient with Squamous Cell Carcinoma Pre-therapy Post-therapy
  33. 33. Proton Spectra of a Patient with Squamous Cell Carcinoma Pre-therapy Post-therapy
  34. 34. Changes of Cho/Water Ratio for Head and Neck Tumor Patients
  35. 35. Discriminating Neoplastic and Non-neoplastic Thyroid Lesions Using 1 H MRS • 29 patients with thyroid lesion • 1 H 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
  36. 36. Proton spectra from neoplastic thyroid lesion and normal-appearing contralateral region
  37. 37. Non-neoplastic thyroid lesion Normal healthy control Cho Lip/Lac
  38. 38. 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 0 2 4 6Cho/Water(x10E-3) * p < 0.001 Neoplasm Non-neoplasm
  39. 39. Results • Thyroid neoplasm Cho/water > 1.0 x 10-3 • Thyroid non-neoplasm Cho/water < 0.4 x 10-3
  40. 40. 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. • 1 H 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.
  41. 41. Proton MRS Studies of Pediatric Neurodisorder
  42. 42. 1 H MRS Study of a child with NKH (Non Ketotic Hyperglycinemia) (J Neuroimaging 2001; 11: 209-212)
  43. 43. WM proton spectra at 10 and 13 months (TE/TR 270/2000)
  44. 44. Correlation of plasma and brain glycine levels
  45. 45. 1 H MRS Study of a child with ADEM (Acute Disseminated Encephalomyelitis)
  46. 46. 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
  47. 47. In vivo 1 H MRS study of a rat model of autism (Physiol Behav 2002; 75: 403-410)
  48. 48. PRESS (TE/TR 40/2000), 0.2 cc voxel size
  49. 49. Significant decrease of NAA/Cr in autistic rats 0.2 0.4 0.6 0.8 1 1.2 1.4 NAA/Cr Control Autistic p < 0.01
  50. 50. Significant increase of Cho/Cr in autistic rats 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 Cho/Cr Control Autistic p < 0.001
  51. 51. Significant increase of mI/Cr in autistic rats 0 0.5 1 1.5 2 2.5 mI/Cr Control Autistic p < 0.02
  52. 52. 1 H MRS study of autistic human subjects (PRESS, TE/TR 40/2000)
  53. 53. 1 H MRS study of autistic human subjects (PRESS, TE/TR 40/2000)
  54. 54. 1 H MRS study of autistic human subjects (PRESS, TE/TR 40/2000)
  55. 55. 1 H Spectra from Healthy Controls Left Hipp-Amyg Cerebellum
  56. 56. 1 H 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).

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