Quantitative Clinical uses of MRI

Question 1

is conventional MRI qualitative or quantitative?

Answer 1

qualitative

Question 2

overview quantitative MRI

Answer 2

an advanced way of imaging- ensures the same patient in different scanners gives the same results- the numbers mean something (can compare between patients or same patient over time). Image intensity is physically meaningful

however, takes longer scan time as repeat scans are required

Question 3

outline an example of how MRI biomarkers have been used

Answer 3

one from:
- studying MS , known to effect WM initially. Quantitative research looking at distribution of WM found there’s a large variation in disease progression

• used to select treatment after acute stroke. A key treatment is the injection of thrombolytics into blood to dissolve clot, it has been shown to be effective in early stroke in penumbra, however if area of tissue is permanently damaged it will worsen the damage. Using diffusion and perfusion scan to compare areas infarcted and penumbra areas (which can be recovered if treated quickly)
• looking at treatment response of radiotherapy to cancer- scanning to measure perfusion in brain to see if angiogenic activity is still in tumor

Question 4

overview qualitative MRI

Answer 4

different scanners produce different images of the same anatomy, only looking at image contrast, not intensity
the majority of clinical MRIs are qualitative

Question 5

compare the use of MRI biomarkers to biofluids (such-as blood or urine)

Answer 5

it gives more primary details of organ (detecting disease/treatment effects in situ) and is not confounded by changes outside of target organ

Question 6

compare the use of MRI biomarkers with biopsy

Answer 6

non-invasive (doesn’t cause damage.disturb the tissue state and is repeatable)
no sampling error (e.g. in heterogenous disease- like different areas of tumor)

Question 7

overview the unique features of MRI biomarkers

Answer 7

comprehensive multi-scale assessment (anatomy/structure/function) and enables the study of organ interactions (e.g. multiorgan post-hospitalisation covid-19 study)

Question 8

overview the history of MRI biomarker development

Answer 8

1972- first biomarker proposed- faster T1 relaxation signal seen in malignant tissues, however qualitative MRI still favoured clinically
early 2000s- renewed interest in quantitative biomarkers when looking at tumor phenotypes quantitative scan numbers were better at decoding tumors than radiologists looking at qualitative scans
2010s- emergence of quantitative radiology
2020s- imaging biomarkers combined with AI- e.g. UoS findings able to detect heart disease

Question 9

what are MR contrast agents

Answer 9

paramagnetic molecules (such as gadopentetate dimeglumine) which alters the magnetic environment in its locale, therefore alters signal

Question 10

how are T1,T2 and T2* signals effected by presence of gadolinium-based contrast agents?

Answer 10

shortens them
T1 weighted images exhibit increased signal
T2* weighted images exhibit decreased signal

Question 11

why can gadolinium not be used alone?

Answer 11

it is toxic so needs to be combined with something to make it inert but retain its magnetic responses

Question 12

what 2 pathologies is gadolinium useful for imaging?

Answer 12

stroke and tumour

Question 13

what is MR perfusion imaging (DSC-MRI) (stands for)

Answer 13

dynamic susceptibility contrast MRI

Question 14

what is perfusion?

Answer 14

local blood flow through a region of brain tissue

Question 15

what are the 3 measurable parameters (quantitative biomarkers) of interest?

Answer 15

• CBF- cerebral blood flow
• CBV- cerebral blood volume
• MTT- mean transit time

Question 16

overview methodology for DSC MRI perfusion imaging

Answer 16

• acquire baseline pre-contrast images
• inject contrast agent (bolus)
• observe signal change during first passage of bolus through brain
• T2* weighted sequence is sensitive to intravascular
  contrast agent (T1 more sensitive extravascularly)
• requires high temporal resolution- multi-slice imaging
• can watch contrast bolus agent in passage films

Question 17

draw perfusion measurement curve and indicate what different aspects mean

Answer 17

see notes

Question 18

outline jet-colour maps of perfusion

Answer 18

often used to indicate contrast agent uptake, however, can fol the eye, providing artificial transitions making it look like there are clear boundaries where there aren’t

Question 19

use of perfusion imaging to look at stroke…

Answer 19

whether/what treatment is required and can often see hyperaemia (increased blood flow compensation for previous flow deficit)

Question 20

use of perfusion imaging to look at tumour…

Answer 20

aggressive tumours tend to have a rim of vasculature and necrotic core, using contrast uptake perfusion imaging can establish how aggressive tumour is (vasculature) and then can be used to check the efficacy on treatment of tumour (post-steroid)

Question 21

arterial spin labelling (ASL)

Answer 21

measures perfusion to invert magnetisation using exogenous contrast agent
blood magnetically labelled in neck as it flows to the brain-difference between labelled and non-labelled images is proportional to cerebral blood flow
the signal change is tiny, so not always clearly seen, especially in WM

Question 22

what does DCE-MRI permeability imaging stand for

Answer 22

dynamic contrast enhanced MRI

Question 23

overview the BBB

Answer 23

normal brain- endothelial cells form tight junctions creating the BBB- allows permeability of essential molecules such as glucose but not toxins
severely impedes drug delivery
breakdown of BBB can occur in various disease states e.g. tumours

Question 24

what is the purpose of permeability imaging?

Answer 24

it attempts to quantity the permeability of the blood vessel endothelial wall
in normal subjects, vessel integrity is maintained and no leakage occurs, however, in disease imperfections in vessel wall are seen and can be measured

Question 25

what are the measurable parameters of interest in permeability imaging?

Answer 25

PS/Vt (Ktrans) - permeability surface areas product per unit volume of tissue

Ve- extravascular extracellular space volume fraction

Question 26

overview methodology of permeability imaging

Answer 26

• acquire baseline pre-contrast images
• inject bolus contrast agent
• observe signal up to 30 mins after injection
• convert signal change into contrast agent concentration
• T10 weighted sequence is sensitive to leakage of contrast agent in to the extravascular extracellular space (EES)

Question 27

what does a single post-contrast time provide?

Answer 27

information on amount of leakage at a specific time

Question 28

discuss contrast agent uptake curves, can use a diagram

Answer 28

using curves of time vs signal enhancement can detect between benign and malignant tissue.

Malignant tumor tissue: large and fast uptake w/o washout
benign/necrotic tumour tissue: large but more progressive uptake
normal tissue: minimal contrast uptake

Question 29

outline signal enhancement vs contrast agent concentration

Answer 29

signal enhancement is not linearly related to contrast agent concentration. It exhibits high-dependency on pre-contrast tissue T1 (T10)

T10 must be measured to enable contrast agent concentration to be calculated from signal enhancement measurements

visually, contrast agent concentration and signal enhancement look very similar

Question 30

what can model BBB permeability?

Answer 30

pharmacokinetic model can be created to describe interaction between blood plasma and extravascular extracellular space (measures leakage)

an equation for this provides reasonable model of the contrast agent uptake observes in human tissues

Question 31

discuss vasculature in regards to tumours

Answer 31

without vasculature, tumours are limited in growth ~1-2mm diameter, in order to grow, cancer cell send signalling molecules that generate angiogenesis
new vessels are often imperfect without tight endothelial junctions (can be up to 2000nm pore as opposed to ~4nm in normal endothelial cell). Higher grade, more aggressive tend to be more vascular (and leaky) hence can be observed using permeability imaging

Question 32

name 3 intracranial tumour types

Answer 32

• Glioblastoma Mutliform (GBM)

-Meningioma

• Low Grade Oligodendroglioma (LGO)

Question 33

what seems to be a good predicter of steroid response (tumour treatment)

Answer 33

regional CBF

Question 34

what are the 5 key imaging techniques used in clinical practice?

Answer 34

• volumetry (VMB)
• fMRI
• DTI
• perfusion
  -spectroscopy

Question 35

outline volumetry use in clinical practice

Answer 35

• used to look at grey matter volume
• good for longitudinal study to monitor atrophy over time
• particularly used in neurodegenerative disease- AD/PD
• fairly simple to do

Question 36

outline fMRI in clinical use

Answer 36

• relies on BOLD contrast
• due to large masses of data provided by EPl it’s only started being used in clinical practice more recently
• useful in understanding which pparts of cortex are recruited for a specific function e.g. to see which hemisphere is dominant in language, as language centres are in the temporal lobe, which can be near regions causing seizures, this ensures surgery won’t remove language centres.
• also used in tumour planning/pre-surgery in order to understand which parts of cortex are being recruited as tumour may change this- ensures preservation of function
• paradigms for visual/motor/language systems are well-established
• the downside is that fMRI is very motion sensitive so if you are looking at a patient who is unable to stay still in machine it may be unviable

Question 37

overview DTI (diffusion tensor imaging) in clinical practice

Answer 37

• one of the most useful methods clinically
  -it measures Brownian motion of water, which produces maps of trace diffusion and diffusion coefficient can be calculated
• can identify disease e.g. stroke leads to vasogenic oedema with larger extracellular space allowing greater fluid diffusion
• whereas tumours tend to show as hypercellular tissues where cells are closely packed, hence reducing diffusion
• DTI allows you to be able to differentiate between more diseases based on the flow of water e.g. a cerebral abscess may be unclear in a standard T1 scan as it could look like a number of things e.g. stroke, however, with Diffusion imaging, reduced diffusion in the tissue indicates tightly packed cells so this could be a cerebral abscess (filled with dead bacterial and WBCs, hence reduced diffusion)
• diffusion along WM tracts is anisotropic, seen in DTI wherby it follows the tracts, clinically this can be used to determine the edges of tumour and gives a better idea of the extent of tumour- useful for tumour planning
• normal DWI uses 3 directions, DTI uses around 30
• also motion sensitive so may be difficult in certain patients

Question 38

Overview Neurite Orientation Dispersion and Density Imaging (NODDI)

Answer 38

an advance version of DTI which can model extra-neurite, intra-neurite and CSF compartments within each voxel, hence we can measure different types of tissue