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
T2 weighting MRI
Short angle
Long Tr
Long TE
PD contrast MRI
Short angle
Long tr
Short TE
Black blood imaging
Must be in the slice to be both 90 and 180
Flow phenomenon is called time of flight
After excitation with 90, signals depend on T2
Stationary tissue appears bright
Factors that affect black blood imaging
Velocity of flow Slice thicknes TE Slice orientation Pre saturation of signal
Pre saturation
90 pulse before imaging
The first proper 90 then saturates the blood into the -z
180 pulse will put it into +z
Already hypointense in T1 weighting as have a long T1
Bright blood imaging
Gradient rephrasing instead of spin echo Entire imaging volume Surrounding tissue needs to be saturated Imaging techniques are known as MRA 3 types: TOF-MRA PC-MRA CE-MRA
TOF-MRA
Determining blood direction
Entry slice phenomenon
60 degrees, short repetition
Stationary spins are saturated whereas in flow nuclei are not
Sensitivity best when perddendicular to blood flow
Nuclei entering the slice can be selectively saturated, so the presaturated will appear dark
Allows to determine the flow direction
3D or 2D TOF MRA?
3D:
Higher signal to noise
Higher res
More tolerant of movement
2D:
Slow blood flow
Wider area coverage
MOTSA- multiple overlapping thin section angiography
Number of small scans to get a wider area, as volume limited by saturation
TOF MRA disadvantages
Haemorrhaging lesions may mimic vessels
Conversion of oxyhemoglobin to methaemoglobin shorts the T1 time of nearby scans
Area limited by saturation, especially in plane flow
Presentation of MRA images
3
Maximum intensity projection
Numberical value to each
Brightest pixel in each column
Viewed from two orthogonal directions
Shaded surface display
Treats boundaries between high and low signal as a surface
Solid and 3D
Radial MRA
Rotated and viewed from angle
Phase contrast MRA
Two bipolar pulses
Stationary are returned to z
Moving pulses will be at the opposite end of the second gradient
Will not be returned to zero so will give signal
Phase advanced again
Applied in 3 axis
Too steep- only slow blood near to the vessels
Too shallow- only fast blood in centre
PC MRA flow direction
2D and 3D MRA
Advantages
Disadvantages
Advance phase white
Retarded black
3D has better resolution and higher S/N
But does take a lot longer
Sensitive to flow direction and velocity
Good background suppression
Long time for 3D imaging
Sensitive
CE-MRA
Gd reduces T1 of blood
Allows short can times, breath hold and short angle to saturate non blood T1s
Insensitive to turbulence and in plane flow
Digital subtraction
Gd reduces T1
Administering contrast agent
Antecubital vein
30ml
RH -> lung -> LH -> arterial -> arterial venous
Could pass through aorta quicker than acquisition
In renal failure causes nephrogenic systemic fibrosis
Centric K space filling
Central lines first
More scan to increase SN ratio
Shared peripheral
E.g. TWIST
Spiral/elliptical k-space filling
Single shot method One excitation pulse Train of gradient echoes (echo planar imaging) Poor SNR but improved by data averaging Large strain on gradients
Optimisation of scan timing
3
Best guess- travel time + (injection time/2) - (imaging time/2)
Places scan at central arterial phase
Needs accurate estimate of travel time dependent on patient
Test bolus
3-4ml
Rapid low scans TWIST
Increases background
Automatic triggering
Simple pulse to detect leading edge
6s between leading edge and arterial phase for breath hold
Centric filling
How to avoid phase mismapping
Swap the phase and frequency encoded axis
Respiratory compensation
Bellows attached and transducer picks up air movement
Imaging planes for cardiac MRI
Two chamber- parallel to the inter-ventricular septum
Four chamber- perpendicular to
Cardiac gating
Collection timed from ECG
Prospective gating- triggered by R wave
Single phase prospective- same phase of heart, static image
Trigger window- waits for next cycle
Trigger delay- length of time after R wave before start
Dark and bright blood
Averaging scans for arrythmias
Multiphase imaging
Heart physiology and function Several stages of cardiac cycle Played as loop Prospective or retrospective gating 15-25 phases per heart beat to give 40-60 ms temporal resolutions
Myocardial tagging
Spatial modulation of magnetisation (SPAMM)
Gradients used to null signal from stripes
Movement of grid is used to monitor the ventricular contraction
Measurements of boxes can be used to quantify function of systole
What is fMRI?
Spotting proton changes in oxygenated and deoxygenated blood
Needs:
Activity
At rest
How does fMRI work?
Oxygen-haemoglobin - diamagnetic, paired electron, T2 not influenced
Deoxygenated- paramagnetic (unpaired) -> T2 reduced
Observe paramagnetic broadening as the T2 changes
No oxygen -> broad peak
BOLD
Blood oxygen level dependent
Blood with short T2 gives signal loss or retention
Long TE values (40-70) with echo trains to differentiate broad parts from narrow
BOLD brain regions study
Faces- visual cortex
Houses- frontal lobes
Also applied to coma patients
fMRI chronic stroke
Finger rolling
Showed that the brain could be retaught
Increased brain activity
fMRI for brain injury
Indicate recovery
Looks for focal adhesions for repair and memory
Doggy fMRI
In humans the same region is used for dogs and humans
Dogs have different areas for dogs and humans
And a. Much wider area
So that although initially they thought the brain was similar, more in depth it is not. So suggests there may be parallel evolution not divergent
What is MRS?
MRI -> NMR signals
Used for cancer and heart attacks, shows chemicals without biopsies
Can compare normal and abonormal tissue identified by MRI
MRS for Alzheimer’s
Biochemical changes associated with loss of neuronal integrity
A screen for dementia?
Creatine, choline, NAA. GABA, MI
Predicted by low NAA/Cr and high Cho/Cr and MI/Cr
NAA/Cr indicates mild cognitive impairment -> dementia
MRS and magnetic fields
Runs 4-7 where MRI is 1-3
Improves resolution
Better to do high res, as GABA peaks can change at low tesla
MRS and cancer
Metabolites
Diagnostic and monitoring
Choline- increased cellular activity and glial cell proliferation.
Glial cells -> neoplasm
Creatine- increased metabolism
Lactate- anaerobic glycolysis, Warburg effect
Myoinositol- glial hyper trophy and proliferation
N acetylaspartate- reduced suggests brain damage
Foetal MRI
Planning of surgery
Cerebellum haemorrhage- T1 weighted
Peri ventricular modular heterotopia- fatal
Congenital diaphragmatic hernia- 50% mortality, surgery after birth
Hole in heart
Age profiling of children
Metabolic fingerprint from urine
Creatine increases with age
H NMR
Creatinine as a disease biomarker
Cold shock in CHO cells
Lower alanine levels
Lactate levels depend on cell line
Allows to identify rate limiting steps to improve flux
Antibody creation
HR MAS biomarkers to grade tumours
New MRS for prostate cancer
Can observe by HR MAS for metabolites
Then Gleason score using microscope
GpCho/PCho correlates with % cancer in sample
New MRS can calculate volume and stage without invasion
High choline and low citrate
Cardiac MRS study
PCr used for energy before ATP is
Means that the PCR/ATP ration drops rapidly in ischemia
Long term low PCR indicative of heart failure
Role of fMRI in cognitive neuroscience
Ethical issues
Lie detection
Uncommitted voters showed anxiety in the amygdala
