Biomarkers

Question 1

What is quantitative MRI?

Answer 1

Commonly used in clinical practice

The most common quantitative measurements are size/volume of an object or region and the distance between structures of interest

Question 2

What are we looking for in conventional quantitative MRI?

Answer 2

Is there inflammation or not and how big is it?

Question 3

What is an issue with MRI?

Answer 3

There are differences e.g. in contrast between vendors #

-We are trying to minimise these differences

Question 4

What colour is commonly used to represent normal brain matter?

Answer 4

Purple

Question 5

Why dont we always use quantiative MRI in routine MRI?

Answer 5

Because to quantify you have to repeat the scans many times and modulate the imaging parameters each time

this is costly in time and expense

Question 6

What do we do with the repeated scans?

Answer 6

Model the changes and apply them to the data to apply more complicated analyses after

• this filters out information that is relavant to the vendor or machines

Question 7

What is a limitation of this type of MRI for the patient?

Answer 7

Spend a long time in the scanner

But if we reduce the number of scans to reduce time patient spends in the scanner then the images become less accurate

Its a trade off between time and accuracy

Question 8

When can we compromise on accuracy?

Answer 8

Depends on purpose of the scan

e.g. to assess brain mestastises in cancer- we dont need a high quality scan so we can compromise

Question 9

When might detail be important?

Answer 9

When we assess inflammation- is there inflammation, how much/how big is the inflammation

Make comparisons between previous visits

Does it require dedicated interventions

Question 10

What is normal appearing white matter?

Answer 10

Visually on a quantitative scan it appears normal but actually it isnt

Question 11

What is important to know clinically?

Answer 11

Whether patients are on a fast path of decline e.g. need aggressive inteventions or on a slow path of design e.g. less intense intervention

Question 12

What is a biomarker ?

Answer 12

A quantitative measurement plus something that allows you to interpret it

A quantitative imaging biomarker can be defined as an imaged characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or a response to a therapeutic intervention

Question 13

What can perfusion scans tell us?

Answer 13

Measure how long it takes for contrast agent to get somewhere in the brain

• could be an indicator of stroke e.g. shows the area in danager of becoming infarct because the arrival time will be greater than 6 seconds

this can be effective at improving the outcomes of patients

Question 14

What area can quantitative MRI be useful for looking at treatment outcomes?

Answer 14

Radiotherapy

Question 15

What is the aim of quantiative MRI in radiology?

Answer 15

Find out whether treatment killed everything or whether there is reoccurance that could spread again after treatment

distinguish areas with damage caused by the cancer to areas still with cancer

Question 16

What are qualitative biomarkers?

Answer 16

Different scanners produce different images of the same anatomy

Only image contrast can be meaningfully interpreted

The vast majority of all MRIs taken in clinical practice

Question 17

What are quantitative biomarkers?

Answer 17

Produces the same results on any scanner anywhere in the world

Image intensity is physically meaningful (has units)

Requires additional scans (scan time) and more complex analysis

Trade off between scan time and accuracy

Question 18

What are MRI biomarkers used for?

Answer 18

Can be used to study biology & disease

Can be used to inform patient management.

Must be accurate & cost effective

Question 19

Why are biomarkers useful?

Answer 19

Typically we take histories, blood, urine samples, biopsies and ultrasounds but there is a gap in thne diagnostic spectrum

• none of these look in detail at the actual organs and this is where MRI fits in as a technique- none of them inform about the level of scale that you can get from an MRI scan

Question 20

What can we compare MRI to, to get an understanding of disease in practice?

Answer 20

Biofluids

Question 21

What is an issue with trying to track diseases with biofluids (blood and urine)

Answer 21

Traces of disease will be within biofluids but this is convoluted by other bodily activity and is also diluted so will be in small quantities

Question 22

How is MRI better than biofluid assessment?

Answer 22

Detect disease or treatment effects in situ

Not confounded by changes outside of target organ

Question 23

What are the limitations of biopsies

Answer 23

Biopsy- goes to the source of the problem, extracts a piece of tisses
- in the brain this is very invasive and dangerous- high risk for only a small piece of tissues

e.g. in cancer there is hetrogeinity- some areas of cancer may be dormant and some other areas may be very aggressive- taking the wrong part could lead to over or under- estimation of the cancer severity - none of this same sampling error in MRI

Don’t observe tissue in its natural state- often frozen, squashed between plates, not the same as seeing the tissue in the organ, MRI doesnt disturb tissue state

Question 24

What is a strength of MRI?

Answer 24

Versatility

Morphology, size, thicker/thinner than normal, can use relaxation times and diffusion to look at microstructure, levels of oxygen, perfusion of tissue, blood flow, inflammation, and we can also see function

All non-invasively

Question 25

What was a recent finding?

Answer 25

Gut-brain interactions that can directly affect diseases

No other techniques allow us to look at several organs in such depth and specificity

Question 26

What are the unique features of MRI?

Answer 26

Comprehensive multi-scale assessment
(anatomy/structure/function)

Enables study of organ interactions

Question 27

What what the first MRI biomarker than was proposed by Raymond Damadion?

Answer 27

Tumor detection by nuclear magnetic resonance in 1972

Led to the development of the MRI scanner

Question 28

What did Aerts et al. (2003) find?

Answer 28

Found an automatic system to find better and more accurate predictions of biological state

Question 29

What gave tise to the emergence of quantitative radiology?

Question 30

How are imaging biomarkers linked to AI?

Answer 30

E.g. Validation of AI Cardiac MRI Measurements

Moving MRI’s
Detection of cardiac contours
Extraction of MRI biomarkers
Prediction of clinical outcomes
Autogenerate reports

Can automatically extract the moving heart from scans of a moving heart - this has important information for patient outcomes and generate reports that can be generated by a physician, important for medical imaging

Question 31

How does this translate to research and clinics?

Answer 31

Imaging biomarker suppliers

• e.g. neurologist treating a patient with MS, use a form of things you would like to assess and you get a report sent back providing numbers and scales of normality or abnormality which you can base future decisions on

Question 32

Are MRI biomarkers useful for clinical practice?

Answer 32

Increasing body of evidence for clinical utility

Now computational technologies & big data enabling
growth

Synergies with AI – both relies on biomarkers and
simplifies extraction

Question 33

What is the practical deployment of MRI?

Answer 33

Increasing number of companies providing biomarker
services

Mostly centralised service model: accreditation of
local labs + central QA

Clinician’s perspective – very similar to blood/urine
test

Question 34

What are the two translational gaps to cross for MRI biomarker development?

Answer 34

Still a time-consuming and costly process

Requires technical, biological and clinical validation + cost-effectiveness