1H MRS and Volumetric MRI Studies of Multiple Sclerosis

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

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.

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

• 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

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

• PRESS sequence

• STEAM sequence90o

90o

TE/2 TM TE/2

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

1H MRSI Studyin Multiple Sclerosis

(TE/TR: 135/1500 ms)

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.

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

1H MRSI Studyin 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

0.5

1.5

2.5

3.5

-2 -1 0 1 2

BRB

RP

PV

NA

A/C

R

r = 0.64p < 0.001

0.5

1

1.5

2

2.5

3

3.5

-2 -1 0 1 2

BRB

RP

PV

NA

A/C

ho

r = 0.56p < 0.001

.00

.20

.40

.60

.80

1.00

1.20

1.40

-2.00 -1.00 .00 1.00 2.00

BRB

CC

SF

r = -0.70p < 0.001

.50

1.00

1.50

2.00

2.50

3.00

3.50

.00 .50 1.00 1.50

CCSF

RP

PV

NA

A/C

r

r = -0.63p < 0.001

Overall Neuropsychological Performance Z Score

2.01.51.0.50.0-.5-1.0-1.5-2.0

Co

mb

ine

d M

R V

ari

able

Pre

dic

ted S

co

re 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)

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

NA

A/H

20

r = 0.59p < 0.05

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%)


• 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


0

200

400

600

800

1000

1200

1400

0 20 40 60 80 100 120 140

Time (Sec)

S


Single-voxel MRS, PRESS(TE/TR 135/2000 ms)


• 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

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.

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

1H MRS for Monitoring Head and Neck Cancer Response to Therapy

Proton Spectra of a Patient with Metastatic Squamous Cell Carcinoma


Localization of Spectroscopic Voxel for a Patient with Squamous Cell Carcinoma


Proton Spectra of a Patient with Squamous Cell Carcinoma


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

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

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) thyroid lesions

0

2

4

6C

ho

/Wat

er (

x 10

E-3

)

* p < 0.001

Neoplasm Non-neoplasm

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-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.

Proton MRS Studies of Pediatric Neurodisorder

1H 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

1H 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 0.83 0.88 0.21

WM initial 1.62 0.91 0.00

WM follow-up 1.38 1.10 0.00

In vivo 1H 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

NA

A/C

r

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

Ch

o/C

r

Control Autistic

p < 0.001

Significant increase of mI/Cr in autistic rats

0

0.5

1

1.5

2

2.5

mI/C

r

Control Autistic

p < 0.02

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



1H Spectra from Healthy Controls

Left Hipp-Amyg Cerebellum

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 0.651.45 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 0.130.51 0.17* 0.20 0.12

mean SD; *: mean in PDD group differs significantly from the control group (unpaired t-test, p < 0.05).

Documents

1H MRS and Volumetric MRI Studies of Multiple Sclerosis