Mark Flashcards
Basis of magnetic resonance
RF applied in the X/y plane
B1 rotates at the Lamor frequency
Transfer from B1 to u
Flips from alpha to beta
Each isotope has a unique RF
By tuning the magnetic and gyromagnetic ration, can be tuned for an isotope
Spin populations at rest
E = hyBo
NB/NA = exp -E/kbT
Means that to get a high ratio, need big energy and magnetic field
Difference between T1 and T2
T1 = Z recovery. Spin lattice relaxation T2 = X/y decay. Spin-spin relaxation, energy lost between pairs of spins
NMR raw data transformation
Collected in time domain Converted to frequency domain Time domain is induced current detected as magnetisation decays Known as the FID Fourier transformation
Lamor frequency equation
V = y Bo /2pi
Where y is the gyromagnetic ration and Bo is the magnetic field
Difference between fat and CSF
Fat-fast t1 and t2
CSF- slow T1 and medium T2
3 main methods of water suppression
Pre saturation
Water gate, 1ppm lost
Excitation sculpting, 0.5ppm lost
Positive markers in lung cancer
Negative markers
LDL, VLDL, lipids, pyruvate
HDL, glucose, methanol, citrate, choline, acetate
Prostate cancer
In a healthy peripheral zone, ZIPI uptake of Zn inhibits isomerisation of citrate by m-aconitase
Result is high Zn and citrate
In cancer, there is no Zn in, which promotes citrate through the TCA cycle
High levels of lactate
Alanine due to proteolysis (end of anaerobic metabolism)
Metabolic markers used in cancer
Metabolic rampage
Glycolysis elevated, but lack of oxidative metabolism
Warburg effect
More acetyl coa promotes fatty acid synthesis
More nucleotides made by the pentose phosphate pathway
How can NMR be used for cancer?
Single and combination therapies
Toxicology
Drug dosage
Resistance
FATE NMR
Uses glucose with either carbon 2 or 4 C13 carbons
‘Spin labelled’
Carbon. 2- glycolytic and PPP fluxes because DHAP becomes labelled in multiple positions
Carbon4- sole labelled carbon can only reach the first carbon of DHAP
Both follow the fate of pyruvate- but 2 follows citrate and 4 follows malic acid
Most popular label is 1,2 as can cover the glycolysis pathway and remainder
31P metabolomics using MRS
Tumour has higher phosphomonoesters
Higher PDE
Lower phopshocreatine
PME used as a marker for neonatal liver-infiltrating neoblastoma
Magic angle spinning
Spun at 1-80 kHz
Tilted at 54.74 degrees
Half width = 1/PI T2
Increases T2 so narrows lines
Solids have nuclear dipole coupling, when spun at angle =0
Hd u 3cos^2 theta-1, where at the Magic angle 3cos^2 theta-1 =0
And as the Hd is proportional to 1/T2, this means that when Hd is small that the T2 increases
Zirconium used
HR MAS in metabolism
4-6 kHz
Otherwise disrupt cells
Standard NMR
Other MAS methods
CRAMPS- combined rotation and multiple-pulse. Polymers and inorganic
DD-MAS- dipole decoupling
CP-MAS- cross polarisation. Non H, membrane proteins and lipids
HR MAS sample prep
12-65 uL
Zirconium oxide rotor
HR MAS and genomics
An aplastic gangliogliomas
Analyser by gene expression and hr MAS
Microarray
Agreed, multiomics technology
Brain tumour and Kennedy pathway
Produces phosphatidylcholine and phsophatidyethanolamine
Choline kinase up regulation increases flux
HR MAS for pathogen study
Drug sugar interactions
Mycobacterium smegmatis, c.jejuni and neisseria meningitidis
Drug ethambutol
Showed that emb separates the sugar from the cell wall but can be resigned in mutant
HR MAS and chemotherapy
Tumours had increases glutathione, creatine and phospholipids
Lower AAs
Tested the therapies docetaxel and fotemustine
Decreases in hypotaurine and GSH shows drug efflux activated
Can be used to measure drug resistance
Intrinsic contrast parameters
Cannot be changed
T1 and T2
Protein density
Flow
Extrinsic contrast parameters
TR time, changes both TE time, changes T2 Flip angle TI changes T1 Turbo factor, as echo train increases the signal decreases B value (gradient duration and interval)
Water and fat weighting
T1- water is larger, so the fat will recover quicker and give more signal. Fat will be brighter
T2- water is larger, so fat will decay quicker.
3 things that influence contrast
Energy of tissue- tissues that absorb energy have smaller T1 as are quick relaxing
Molecular packing- relaxation is more efficient when tissues are together. Higher density means short T2. Good contrast
Tumbling rate- optimal energy exchange at Lamor freq. t1 is minimum here, so recovery is optimum.
T1 weighting MRI
Large angle to saturate
Short TR to maximise sat
Short TE to minimise T2