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

Subarachnoid Hemorrhage Clinical Trial

Official title:

Contrast Enhanced Ultrasound Imaging for Cerebral Perfusion Measurement in Cerebral Vasospasm After Subarachnoid Hemorrhage

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02907879
• Other study ID #: SONO SAB
• Status: Terminated
• Start date: July 2013
• Est. completion date: April 2021

Study information

• Verified date: April 2021
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 54
• Est. completion date: April 2021
• Est. primary completion date: January 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemorrhage
• Subarachnoid Hemorrhage
• Vasospasm, Intracranial

Locations

Country	Name	City	State
Switzerland	Department of Neurosurgery, University Hospital Bern	Bern

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne

Country where clinical trial is conducted

Switzerland, 

References & Publications (12)

Aaslid R, Huber P, Nornes H. Evaluation of cerebrovascular spasm with transcranial Doppler ultrasound. J Neurosurg. 1984 Jan;60(1):37-41. — View Citation

Beck J, Raabe A, Lanfermann H, Seifert V, Weidauer S. Perfusion-weighted magnetic resonance imaging in patients with vasospasm: a useful new tool in the management of patients with subarachnoid hemorrhage. Neurosurgery. 2006 Mar;58(3):E590; author reply E590. — View Citation

Beck J, Raabe A, Lanfermann H, Seifert V, Weidauer S. Tissue at risk concept for endovascular treatment of severe vasospasm after aneurysmal subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 2004 Dec;75(12):1779-81. — View Citation

de Rooij NK, Linn FH, van der Plas JA, Algra A, Rinkel GJ. Incidence of subarachnoid haemorrhage: a systematic review with emphasis on region, age, gender and time trends. J Neurol Neurosurg Psychiatry. 2007 Dec;78(12):1365-72. Epub 2007 Apr 30. Review. — View Citation

Eyding J, Krogias C, Schöllhammer M, Eyding D, Wilkening W, Meves S, Schröder A, Przuntek H, Postert T. Contrast-enhanced ultrasonic parametric perfusion imaging detects dysfunctional tissue at risk in acute MCA stroke. J Cereb Blood Flow Metab. 2006 Apr;26(4):576-82. — View Citation

Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL, Parag V. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol. 2009 Apr;8(4):355-69. doi: 10.1016/S1474-4422(09)70025-0. Epub 2009 Feb 21. Review. — View Citation

Johnston SC, Selvin S, Gress DR. The burden, trends, and demographics of mortality from subarachnoid hemorrhage. Neurology. 1998 May;50(5):1413-8. — View Citation

Raabe A, Beck J, Keller M, Vatter H, Zimmermann M, Seifert V. Relative importance of hypertension compared with hypervolemia for increasing cerebral oxygenation in patients with cerebral vasospasm after subarachnoid hemorrhage. J Neurosurg. 2005 Dec;103(6):974-81. — View Citation

Reitmeir R, Eyding J, Oertel MF, Wiest R, Gralla J, Fischer U, Giquel PY, Weber S, Raabe A, Mattle HP, Z'Graggen WJ, Beck J. Is ultrasound perfusion imaging capable of detecting mismatch? A proof-of-concept study in acute stroke patients. J Cereb Blood Flow Metab. 2017 Apr;37(4):1517-1526. doi: 10.1177/0271678X16657574. Epub 2016 Jan 1. — View Citation

Seidel G, Meyer-Wiethe K, Berdien G, Hollstein D, Toth D, Aach T. Ultrasound perfusion imaging in acute middle cerebral artery infarction predicts outcome. Stroke. 2004 May;35(5):1107-11. Epub 2004 Mar 18. — View Citation

Vergouwen MD, Vermeulen M, Roos YB. Effect of nimodipine on outcome in patients with traumatic subarachnoid haemorrhage: a systematic review. Lancet Neurol. 2006 Dec;5(12):1029-32. Review. — View Citation

Weidauer S, Lanfermann H, Raabe A, Zanella F, Seifert V, Beck J. Impairment of cerebral perfusion and infarct patterns attributable to vasospasm after aneurysmal subarachnoid hemorrhage: a prospective MRI and DSA study. Stroke. 2007 Jun;38(6):1831-6. Epub 2007 Apr 19. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Detection of cerebral hypoperfusion leading to either infarcts, neurological deficits, or initiation of rescue therapy	(1) normal, i.e. with a perfusion delay < 2 sec, (2) hypoperfusion, i.e. with a perfusion delay = 2sec and < 6 sec, and (3) no perfusion, i.e. with a perfusion delay = 6 sec as compared with the average of the 2 thalamic territories of the unaffected side	14 days after ictus
Secondary	Correlation between UPI parameters and cerebral perfusion as assessed by CT-perfusion		Within 14 days after ictus
Secondary	Correlation between UPI parameters and cerebral perfusion as assessed by MRI-perfusion		Within 14 days after ictus
Secondary	Correlation between UPI parameters and flow velocities in the middle cerebral artery as measured by TCD		Within 14 days after ictus
Secondary	Correlation between UPI parameters with vessel diameters of the MCA as assessed by DSA		Within 14 days after ictus