MRI brain imaging in spontaneous intracerebral haemorrhage; pinpointing the underlying vascular disease

Intracerebral haemorrhage (ICH) is the deadliest subtype of stroke. ICH not
caused by trauma, vascular malformations, tumor or coagulopathy is lumped
together as *primary* or spontaneous ICH. This umbrella term suggests that
affected patients have the same disease, do not require further investigations
to search for the underlying vascular disease and should be treated similarly.
This simplification has slowed down progress in the field of ICH. Many
questions regarding the underlying mechanism in ICH remain wide open. An
initial step to unravel ICH etiology has been to try to attribute deeply
located (non-lobar) ICH to hypertension and lobar ICH in elderly patients to
cerebral amyloid angiopathy (CAA). This dichotomy is still an overtly
insufficient simplification as many patients with non-lobar ICH do not have
hypertension and cerebral amyloid angiopathy is found in at most one-third of
patients with lobar haemorrhage. Recent studies indicate that the mechanisms
involved in the deleterious effect of ICH may not be the same in all patients.
Effective treatments for ICH can only be developed when we can better
characterize the underlying vessel disease in patients with ICH and know the
different mechanisms in the sequence of pathologic events triggered by the
haemorrhage. The knowledge gained with this project will lead to new insights
that will allow development of new and specific treatment targets for patients
with ICH.

The overall aims of the proposed project are
1) to establish biomarkers for identification of the underlying vascular
disease in patients with ICH and
2) to characterize whether disruption of the blood-brain barrier, a key factor
in secondary brain injury after ICH, varies according to the underlying cause.
3) to determine whether timing invariant CT angiography (TI-CTA) can identify
patients at risk of haematoma expansion (HE) and poor outcome more accurately
than conventional CTA
With this knowledge we will be able to develop new targeted treatments and
design targeted randomized clinical trials for patients with ICH.

The study proposed here is a prospective multicenter cohort study.

The extent of burden and risks for this study are minimal. Gadolinium enhanced
3T MRI is performed in patients with ICH in routine clinical practice as part
of the workup to find an underlying cause of the ICH such as a tumor or an
arteriovenous malformation, fistula, or a cavernous malformation, according to
the guidelines by the American Heart Association 2010 and the European Stroke
Organisation 2006. For substudy C, patients will recieve a low dose of extra
radiation.. There is a very small maximum increased risk 0,006% a patient
develops cancer as result of this study. This follow up scan is performed in
routine clinical care in a subset of patients.

For the study all patients will undergo a 3T MRI, with a duration of
approximately 30 minutes.Scanning with 7 Tesla (7T) MRI is not yet routine, but
strict application of contra-indications minimizes the risk of complications. A
7T gadolinium enhanced MRI will take approximately 45 minutes.

A person who is close to the patient (partner, family member or friend) will be
asked to complete the Informant Questionnaire on Cognitive Decline in the
Elderly (IQCODE), which will take approximately 15 minutes. The patient or a
person close to the patients will be asked to fill in a questionaire regarding
possible triggers of intracerebral hemorrhage, which will take 30-45 minutes.

Clinical follow up will be done at 3 months and 12 months by visits to the
outpatient clinic or through standardized telephone interviews, including the
TICS-M cognitive assessment. With this follow up information we will be able to
study whether presence and severity of the MR markers are associated with poor
outcome (modified Rankin score >3) at 3, 12, 24 and 48 months. Total time
involved in participating in this study is between 105 and 210 minutes.