Introduction lecture (Monday 31th Oct)

Question 1

What is the purpose of imaging biomarkers and for what can these imaging biomarkers be used in regard to research?

Answer 1

Imaging biomarkers:
- should reflect disease activity
- are used to study the natural course of disease and to study interventions for treatment such as medication

Question 2

Name four requirements of imaging biomarkers.

Answer 2

1. Should truly reflect disease activity
2. Should have an excellent reproducibillity (rigid quality control)
3. Should be sensitive enough to detect (small) changes in disease activity (power of studies)
4. Should be validated to be accepted by regulatory agencies (FDA accepted)

Question 3

For what can imaging biomarkers used for?

Answer 3

Imaging biomarkers are used to assess:
- eligibility of patients for a specific trial (inclusion and exclusion criteria)
- disease acitivity
- adverse events

Question 4

Name two reasons why imaging biomarkers are not always easy to assess.

Answer 4

• There can be many important issues concerning the methodology used to read or measure the imaging data.
• The technique should be robust, and this robustness should be challenged before using it in clinical drug trials.

Question 5

Name examples of diseases where imaging biomarkers are/can be used for drug efficacy studies?

Answer 5

• RA-scores in rheumatoid arthritis
• Vertebral morphometry in osteoporosis
• Arthritis-scores in degenrative joint disease
• MS-scores in Multiple Sclerosis
• MTA-scores in Alzheimer’s disease
• Recist criteria in oncology studies

Question 6

There is a need to understand heterogeneity of disease activity better than we do currently.
What can be a reason why currently some patient do not respond to treatment?

Answer 6

Current therapy regimens are ‘shock and awe’ and not personalized.
- Shock and awe → a military strategy based on the use of overwhelming power and spectacular displays of force to paralyze the enemy’s perception of the battlefield and destroy their will to fight.

Question 7

• What is the problem with currently validated imaging biomarkers?
• What should be different to new imaging biomarkers that could solve the problem of currently validated imaging biomarkers?

Answer 7

• Currently, validated imaging biomarkers mainly reflect morphological features on images (i.e. parameters that can be quantified e.g. erosions, joint space narrowing, dimensions of size). These parameters are static features of disease that need follow-up measurements and thus the assessment of delta-change to give information about disease activity.
• New imaging biomarkers should be physiologic or metabolic and should reflect acutal disease activity at the time of imaging.

Question 8

So new imaging biomarkers should be physiologic or metabolic and should reflect actual disease activity at the time of imaging.
What others things can you name that can/should be taken into account with the development of new imaging biomarkers?

Answer 8

New imaging biomarkers:
- should take into account the problem of heterogeneity.

This means that there is quite some biological variability in disease activity and severy between patients. Therefore heterogeneity in disease expression and sensitivity to certain treatments should be studied and taken into account with the development of new imaging biomarkers.