Neuroimaging Biomarkers

Biomarkers and Surrogate End Points

CNS drugs

A biomarker is “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention” (Biomarkers Definitions Working Group. 2001).

In clinical trials, biomarkers can be used (Butz & Hilton. 2013):

  • to select and to stratify the patients to include (diagnosic, prognostic and predictive applications),
  • to monitor the response to treatment (pharmacodynamic, theragnostic and surrogate end points applications).

The use as a surrogate end point, i.e. "a laboratory measurement or physical sign that is used in therapeutic trials as a substitute for a clinically meaningful end point that is a direct measure of how a patient feels, functions or survives and is expected to predict the effect of therapy" (Temple. 1999), is particularly useful, as the true clinical outcome (e.g., recovery, disability or death) usually occurs late after the end of the clinical trial. However, this use is only meaningful if the surrogate end point reliably predicts the true clinical outcome, independently of other factors which may be not be measured by the biomarker. This approach has therefore limitations, which should be taken into account (Fleming & DeMets. 1996).

Neuroimaging Biomarkers

Neuroimaging biomarkers use brain imaging techniques in order to image the morphology (e.g., MRI), the function (e.g. fMRI), the microenvironment (e.g., perfusion MRI), the metabolism (e.g., PET-FDG), or the molecular content (e.g., MR spectroscopy) of the brain and its lesions (Boland. 2014).

Neuroimaging biomarkers of Alzheimer's Disease include measurement of beta-amyloid deposition with amyloid PET, of brain metabolism with FDG-PET, of brain and hippocampal atrophy with MRI (Bateman et al. 2012). Read more about neuroimaging biomarkers for Alzheimer's disease.

Neuroimaging biomarkers of multiple sclerosis (MS) include counting and volume of T2 lesions, enhancing lesions, and black holes. Brain morphometry can be used to measure the brain's atrophy, a biomarker of the degenerative aspect of the disease. Read more about neuroimaging biomarkers in multiple sclerosis (MS).

Neuroimaging biomarkers of ischemic stroke include, at the acute phase, the volume of the ischemic core, as measured on apparent diffusion coefficient (ADC) maps, the volume of the ischemic penumbra, as estimated by the MR perfusion-based TMAX parameters, and, at the chronic stage, the lesion of the ischemic lesions, as measured on the FLAIR images. Read more about neuroimaging biomarkers in ischemic stroke.

Other Biomarkers in the CNS

Although imaging biomarkers play a key role in the central nervous system, they should be used in conjunction with other biomarkers, such as blood-based, CSF-based, genetic, and electrophysiological biomarkers. Their description is outside the scope of this review.

Related Topics


  • Bateman et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012, 367:795-804.
  • Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001, 69:89-95.
  • Boland. The role of imaging in the era of personalized / precision medicine. Imaging Biomarkers in Clinical Trials: Current Practice & Future Trends. Harvard Medical School 2014.
  • Budz & Hilton. Precision medicine: Using biomarkers to accelerate clinical development. White Paper, PPD 2013.
  • Fleming & DeMets. Surrogate end points in clinical trials: Are we being misled? Ann. Intern. Med. 1996, 125:605-613.
  • Temple. Are Surrogate Markers Adequate to Assess Cardiovascular Disease Drugs? JAMA 1999, 282:790-795.

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