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1
Q

Basis of magnetic resonance

A

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

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2
Q

Spin populations at rest

A

E = hyBo

NB/NA = exp -E/kbT

Means that to get a high ratio, need big energy and magnetic field

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3
Q

Difference between T1 and T2

A 
T1 = Z recovery. Spin lattice relaxation
T2 = X/y decay. Spin-spin relaxation, energy lost between pairs of spins
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4
Q

NMR raw data transformation

A 
Collected in time domain
Converted to frequency domain
Time domain is induced current detected as magnetisation decays
Known as the FID
Fourier transformation
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5
Q

Lamor frequency equation

A

V = y Bo /2pi

Where y is the gyromagnetic ration and Bo is the magnetic field

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6
Q

Difference between fat and CSF

A

Fat-fast t1 and t2

CSF- slow T1 and medium T2

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7
Q

3 main methods of water suppression

A

Pre saturation
Water gate, 1ppm lost
Excitation sculpting, 0.5ppm lost

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8
Q

Positive markers in lung cancer

Negative markers

A

LDL, VLDL, lipids, pyruvate

HDL, glucose, methanol, citrate, choline, acetate

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9
Q

Prostate cancer

A

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)

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10
Q

Metabolic markers used in cancer

A

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

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11
Q

How can NMR be used for cancer?

A

Single and combination therapies
Toxicology
Drug dosage
Resistance

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12
Q

FATE NMR

A

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

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13
Q

31P metabolomics using MRS

A

Tumour has higher phosphomonoesters
Higher PDE
Lower phopshocreatine

PME used as a marker for neonatal liver-infiltrating neoblastoma

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14
Q

Magic angle spinning

A

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

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15
Q

HR MAS in metabolism

A

4-6 kHz
Otherwise disrupt cells
Standard NMR

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16
Q

Other MAS methods

A

CRAMPS- combined rotation and multiple-pulse. Polymers and inorganic

DD-MAS- dipole decoupling

CP-MAS- cross polarisation. Non H, membrane proteins and lipids

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17
Q

HR MAS sample prep

A

12-65 uL

Zirconium oxide rotor

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18
Q

HR MAS and genomics

A

An aplastic gangliogliomas
Analyser by gene expression and hr MAS
Microarray
Agreed, multiomics technology

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19
Q

Brain tumour and Kennedy pathway

A

Produces phosphatidylcholine and phsophatidyethanolamine

Choline kinase up regulation increases flux

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20
Q

HR MAS for pathogen study

A

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

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21
Q

HR MAS and chemotherapy

A

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

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22
Q

Intrinsic contrast parameters

A

Cannot be changed
T1 and T2
Protein density
Flow

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23
Q

Extrinsic contrast parameters

A 
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)
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24
Q

Water and fat weighting

A

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.

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25
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.
26
T1 weighting MRI
Large angle to saturate Short TR to maximise sat Short TE to minimise T2
27
T2 weighting MRI
Short angle Long Tr Long TE
28
PD contrast MRI
Short angle Long tr Short TE
29
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
30
Factors that affect black blood imaging
``` Velocity of flow Slice thicknes TE Slice orientation Pre saturation of signal ```
31
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
32
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 ```
33
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
34
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
35
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
36
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
37
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
38
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
39
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
40
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
41
Centric K space filling
Central lines first More scan to increase SN ratio Shared peripheral E.g. TWIST
42
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 ```
43
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
44
How to avoid phase mismapping
Swap the phase and frequency encoded axis Respiratory compensation Bellows attached and transducer picks up air movement
45
Imaging planes for cardiac MRI
Two chamber- parallel to the inter-ventricular septum | Four chamber- perpendicular to
46
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
47
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 ```
48
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
49
What is fMRI?
Spotting proton changes in oxygenated and deoxygenated blood Needs: Activity At rest
50
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
51
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
52
BOLD brain regions study
Faces- visual cortex Houses- frontal lobes Also applied to coma patients
53
fMRI chronic stroke
Finger rolling Showed that the brain could be retaught Increased brain activity
54
fMRI for brain injury
Indicate recovery | Looks for focal adhesions for repair and memory
55
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
56
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
57
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
58
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
59
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
60
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
61
Age profiling of children
Metabolic fingerprint from urine Creatine increases with age H NMR Creatinine as a disease biomarker
62
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
63
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
64
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
65
Role of fMRI in cognitive neuroscience | Ethical issues
Lie detection | Uncommitted voters showed anxiety in the amygdala

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