lecture #14 in vivo mrs-detectable metabolites · 1 lecture #14! in vivo mrs-detectable metabolites...
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Lecture #14��� In Vivo MRS-detectable Metabolites
• Topics– 1H-MRS– 31P-MRS– 13C-MRS– Other nuclei
• Handouts and Reading assignments– de Graaf, Chapter 2.– de Graaf, Chapter 3, 158-171.
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IntroductionMRI: anatomy and structure MRS: metabolism and function
13C
β-ATPα-ATP
γ-ATP
PCrPDE
PIPME
10 5 0 -5 -10 -15 -20ppm
31P
1H 1H
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MR of the Brain
Conventional MRI
Anatomy
Microvasculature
Perfusion imaging
Microstructure
DWI/DTI
Cellular function and metabolism
MRS
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CellsNeuron
General cellular functions• Turn glucose into energy
• Perform cell specific functions, e.g. neurons send/receive electrical signals
• Maintain cellular integrity– Ionic balance– Osmotic balance– Membrane structure
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1H Brain Spectroscopy
Some general rules of thumb• In vivo MRS does not see everything! Maudsley paper is rather optimistic.
• Concentration limit (of protons) around 1 mM for NMR-detection
• Macromolecules are non-detectable (T2s too short)
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GE MRS phantom
1H Brain Spectroscopy1.5T
(in vivo)
11T(extract) In vitro
solutions
…
In vivo
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1H Brain Spectra
We’ll start with “late” echo spectra
NAACreCho
water
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N-acetyl Aspartate (NAA)
ppm
3 T In vivo 1H Brain Spectrum
NAA• Largest peak in a 1H-
MRS brain spectrum
• Neuronal marker
• 2.0 ppm
• Approx 10 mM
NAA
NAA
NAA Biochemical role?
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Creatine (Cre)
“Cre” peak from both creatine and
phosphocreatine (often called referred to as total
creatine peak) PCr
ppm
3 T In vivo 1H Brain Spectrum
NAA Biochemical role
Cre• Reflects cellular
energetics• 3.0 ppm• Cre+PCr=“tCr”• Approx 5-10 mM
CreCreoften lost with water
suppression
Fast reaction to buffer energy levels while
glucose is metabolized
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Choline (Cho)
“Cho” peak from several choline containing
compounds: phosphocholine,
glycerphophocholine, etc.
Biochemical role
Cho• Largely reflects cell
membrane repair and synthesis (acetyl-choline component very small)
• 3.2 ppm
• Approx 1-2.5 mM
ppm
3 T In vivo 1H Brain Spectrum
CreCre NAACho
9 protons!
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Example: Brain Tumor52 y.o male: MRI #1 - rule out stroke, MRI # - tumor?
NAA
creatine
choline
TE = 144 ms
T2
post-contrast T1
NAAcreatine
choline
TE = 144 ms
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Biochemical role
Lactate (Lac)
Kamada, et al, J. N Psych, 70:675, 2001.
Cerebral infarctNon-selective SE, TE=288 ms (2/J)
Lac• Indicator of anaerobic
metabolism• Doublet at 1.3 ppm• Approx 0.4 mM
(normal brain tissue)
Lacppm
3 T In vivo 1H Brain Spectrum
CreCre Cho NAA
Lac
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13
ppm
Short TE 1H-MRS Brain Spectra
1.5T 1H-MRS In Vivo Brain SpectrumTE = 35 ms
some new peaks
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1.5 T In vivo 1H Brain Spectrum (TE=35ms)
ppm
myo-Inositol (mI)Biochemical role?
mI• Suggested as a glial
marker.
• Glial cells provide structural support for neurons in addition to involvement in neurotransmitter processes.
• Largest peak at 3.6 ppm
• Approx 4-8 mM
mI
mI
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Neurotransmitters
Glutamate is the major excitatory neurotransmitter in the brain
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Glutamate (Glu) and Glutamine (Gln)1.5 T In vivo 1H Brain Spectrum (TE=35ms)
Glu
Gln
8-10 mMIn vivo concentrations
2-3 mM
Glu Gln
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γ-aminobutyric acid (GABA)
A real neural net
GABA is the major inhibitory neurotransmitter in the brain
(conc: 1-2 mM)
GABA GABA+ Glu
Example In vivo GABA (3T)
GABA
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Muscle and Fat
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Prostate
Normal prostate (1.5 T)
Prostate cancer (1.5 T)
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Breast cancer2D-J spectrum
BreastElevated choline
Noncancerous lesion
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Sensitivity
€
in vivo SNR∝ργ 2!2B0
4kT
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brain
muscle
liver
31P Spectroscopy
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13C Spectroscopy
13C natural abundance is low, but 13C-labeled glucose or acetate infusions can yield important information regarding metabolic fluxes
Note: very wide chemical
shift range
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Example: 13C-glucose Infusion
Gruetter, et al., J. Neurochem., 63:1377-1385, 1994.
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Other Nuclei• Sodium (23Na, spin=3/2)
– Intracellular 10 mM– Extracellular 150 mM
Involved in ionic balances, generation of action potentials,
regulations of cell volume.
cell membrane• Fluorine (19F)– No endogenous 19F compounds in biological tissue– Lots of fluorinated drugs!
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Next Lecture: 1H MRS Methods