Contrast Enhanced Ultrasound Imaging for Cerebral Perfusion Measurement in Cerebral Vasospasm After SAH

The objective of the study is to assess brain tissue perfusion by ultrasound perfusion imaging. Specifically

* to diagnose brain tissue hypoperfusion due to CVS with contrast enhanced UPI and to assess specificity and sensitivity, and predictive values for detection of brain tissue hypoperfusion leading to infarction
* to test whether treatment-effects by induced hypertension, balloon-dilatation, or intra-arterial nimodipine infusion can be detected and quantified by UPI

The aim of the study is to assess brain tissue perfusion by ultrasound perfusion imaging (UPI).

The specific aim is to diagnose brain tissue hypoperfusion leading to infarction due to CVS with ultrasound perfusion imaging (UPI) and to correlate it with the gold standard of diagnosis of brain infarcts, i.e. with MRI and CT. According to contrast enhanced UPI brain tissue will be classified as (1) normal, i.e. not leading to tissue infarction, (2) as hypoperfused, i.e. functionally impaired and prone to DIND and to infarction, or (3) non-perfused. Thus, temporary hypoperfusion that may be resolved by therapy or spontaneously, not leading to tissue infarction shall be assessed. This strategy will lead to guiding therapy by UPI.

Questionnaire:

* to assess cerebral perfusion in patients with SAH by contrast enhanced UPI
* to assess specificity and sensitivity, as well as positive and negative predictive values of contrast enhanced UPI for detection of brain tissue misery perfusion leading to infarction
* to evaluate feasibility and practicability of repeated bed-side assessments of UPI
* to test whether treatment-effects like induced hypertension, balloon-dilation, or intra-arterial nimodipine infusion can be detected and quantified by contrast enhanced UPI
* to analyze whether TCD or contrast enhanced UPI is superior for screening of CVS and detection of cerebral infarcts (vessel vs. tissue assessment)
* to correlate contrast enhanced UPI with perfusion measurements by CT-perfusion imaging

Ultrasound perfusion imaging (UPI) is able to detect cerebral hypoperfusion that can result in cerebral infarction in a clinical setting. As reference the incidence of cerebral infarcts is assessed by CT- and MR-imaging and cerebral perfusion is analyzed by CT-perfusion (CTP) imaging.

The day of the ictus (SAH) is defined as day 0. The ultrasound examinations will be performed at

* Day 0-4: one baseline UPI study will be performed. This time period (0-4) is set as baseline, because this baseline investigation will be performed before vasospasm develops. The current policy of early aneurysm treatment results in clipping or coiling of patients within 24-48 hours. The relevant phase of CVS, however, starts on day 4 to 5 after the ictus. The already established routine protocol with early CT and CTP imaging after aneurysm treatment allows differentiation between infarcts due to the procedure of aneurysm clipping or coiling, bleeding, edema, or surgical contusions from cerebral infarcts due to CVS that develop later on. This early routine CT imaging includes a CT-perfusion study on post-op day 1, serving as reference for the ultrasound perfusion measurements.
* Day 5-14: during the term with the highest risk for CVS, a UPI study will be performed every second day.
* Several events trigger additional UPI studies:

  * angiography (scheduled or emergency)
  * endovascular intervention (angioplasty or intraarterial nimodipine infusion)
  * CT or MRI study with new infarcts
  * Development of DIND or reversal of DIND
  * in case of placement of an intracerebral microprobe (rCBF or ptiO2) an UPI study will be performed when significant changes (rCBF drop below 20ml/100g/min or below 60% of baseline, ptiO2 drop below 10mmHg or below 60% of baseline) occur.

Currently all patients are scanned by MRI and or CT several times in the course of the disease. Each imaging study serves as reference for UPI.

During day 5-14 high risk patients (Fisher grade 3, or TCD \> 150 cm/sec, or new deficit) receive one CT-perfusion study between day 7 and 11 (period of highest risk).

During day 5-14 patients with proven CVS (angiography) will receive two CT-perfusion studies, one at day 7, and one at day 11, or at the time when new deficits or infarcts evolve. Additional about 20% of patients will get MRI including perfusion weighted imaging (PWI). In these patients misery perfusion as detected by PWI serves as reference for UPI.

The actual UPI measurement takes place at the bedside, is performed by the study physician, and takes about 15 -30 minutes.

The trial duration per patient is 14 days during the initial hospitalization.

Eligibility Criteria:
Inclusion Criteria:

* Proven SAH (CT or lumbar puncture)
* Proven aneurysm (digital subtraction angiography or CT-angiography)
* Age \>18
* Informed consent of patient or relative

Exclusion Criteria:

* Pregnancy and breast feeding
* Acute coronary syndromes, severe ischemic heart disease (requiring revascularisation), severe aortic and mitral valve disease, severe congestive heart failure (NYHA \>III/IV)
* Severe pulmonary or renal dysfunction
* Known allergy or adverse reaction to contrast material