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.
1 Introduction MRI: anatomy and structure MRS: metabolism and function
1 1HH
PCr PDE 31 PI P PME a-ATP g-ATP b-ATP
ppm 10 5 0 -5 -10 -15 -20
13C
2 Anatomy MR of the Brain Microvasculature
Microstructure
Cellular function and Conventional metabolism MRI Perfusion imaging DWI/DTI
MRS
3 Cells Neuron
General cellular functions • Turn glucose into energy • Maintain cellular integrity – Ionic balance – Osmotic balance – Membrane structure • Perform cell specific functions, e.g. neurons send/receive electrical signals 4 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) 5 1H Brain Spectroscopy In vivo 1.5T (in vivo)
GE MRS phantom
11T (extract) In vitro solutions … 6 1H Brain Spectra
NAA Cho Cre We’ll start with “late” echo spectra
water
7 N-acetyl Aspartate (NAA) 3 T In vivo 1H Brain Spectrum Biochemical role? NAA
ppm NAA • Largest peak in a 1H- NAA MRS brain spectrum • Neuronal marker • 2.0 ppm • Approx 10 mM NAA
8 Creatine (Cre) Fast reaction to buffer 3 T In vivo 1H Brain energy levels while Spectrum glucose is metabolized often lost with water suppression Biochemical role Cre Cre NAA
ppm
“Cre” peak from both creatine and phosphocreatine (often Cre called referred to as total creatine peak) • Reflects cellular energetics PCr • 3.0 ppm • Cre+PCr=“tCr” • Approx 5-10 mM
9 Choline (Cho) 3 T In vivo 1H Brain Spectrum Biochemical role NAA Cre Cho Cre
ppm Cho
“Cho” peak from several • Largely reflects cell choline containing membrane repair and compounds: synthesis (acetyl- phosphocholine, choline component glycerphophocholine, etc. very small) • 3.2 ppm • Approx 1-2.5 mM
9 protons! 10 Example: Brain Tumor 52 y.o male: MRI #1 - rule out stroke, MRI # - tumor?
choline
choline NAA creatine T2 creatine NAA
TE = 144 ms TE = 144 ms
post-contrast T1
11 Lactate (Lac) 3 T In vivo 1H Brain Spectrum Biochemical role NAA Cre Cho Cre
Lac
ppm Lac • Indicator of anaerobic Lac metabolism • Doublet at 1.3 ppm • Approx 0.4 mM (normal brain tissue) Cerebral infarct Non-selective SE, TE=288 ms (2/J)
12 Kamada, et al, J. N Psych, 70:675, 2001. Short TE 1H-MRS Brain Spectra
some new peaks
ppm 1.5T 1H-MRS In Vivo Brain Spectrum TE = 35 ms
13 myo-Inositol (mI) 1.5 T In vivo 1H Brain Spectrum (TE=35ms) Biochemical role? mI mI • Suggested as a glial marker. • Glial cells provide ppm structural support for neurons in addition to involvement in mI neurotransmitter processes. • Largest peak at 3.6 ppm • Approx 4-8 mM
14 Neurotransmitters
Glutamate is the major excitatory neurotransmitter in the brain
15 Glutamate (Glu) and Glutamine (Gln) 1.5 T In vivo 1H Brain Spectrum (TE=35ms) Glu Gln
Glu
Gln In vivo concentrations 8-10 mM 2-3 mM 16 g-aminobutyric acid (GABA) GABA is the major inhibitory neurotransmitter in the brain (conc: 1-2 mM)
GABA
Example In vivo GABA (3T)
GABA GABA A real neural net + Glu 17 Muscle and Fat
18 Prostate
Normal prostate (1.5 T)
Prostate cancer (1.5 T)
19 Breast
Elevated choline
Breast cancer Noncancerous lesion 2D-J spectrum
20 Sensitivity
γ 2!2B in vivo SNR ∝ ρ 0 4kT 21
€ 31P Spectroscopy
muscle
brain
22 13C Spectroscopy
Note: very wide chemical shift range
13C natural abundance is low, but 13C-labeled glucose or acetate infusions can yield important information regarding metabolic fluxes 23 Example: 13C-glucose Infusion
Gruetter, et al., J. Neurochem., 63:1377-1385, 1994.
24 Other Nuclei • Sodium (23Na, spin=3/2) Involved in ionic balances, – Intracellular 10 mM generation of action potentials, – Extracellular 150 mM regulations of cell volume.
• Fluorine (19F) cell membrane – No endogenous 19F compounds in biological tissue – Lots of fluorinated drugs!
25 Next Lecture: 1H MRS Methods
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