Pulse-Wave Velocity Measurement in Patients with Marfan Syndrome: Automated and Non-Invasive Assessment of the Regional Vascular Status for Risk Stratification

Recent publications emphasize the importance of measuring the Pulse-Wave
Velocity (PWV) in the aorta as an indicator of arterial stiffness in vascular
disease. Echo Doppler and intra-vascular pressure measurements are currently
the methods of choice to derive the PWV. However, accurate pressure
measurements require an invasive procedure. Using echo Doppler, the course
along the aorta, which the wave has to propagate (needed for PWV calculation),
is estimated from the distance between two measurement sites (i.e., the carotid
and the iliac artery). This results only in crude estimation of the global PWV.
Reproducibility and accuracy are questionable.
Several studies explored the possibilities of using velocity-encoded (VE) MRI
to determine the PWV. MRI is an accurate and non-invasive modality from which a
3D-velocity vector field in vessels can be determined, without the need of
modeling assumptions.
The availability of a diagnostic and prognostic tool to study areas in the
aorta with regionally impaired wall compliance is very much desired, as these
areas are at risk for dissection or aneurysm development. Such is the case in
patients with Marfan syndrome. Marfan syndrome is an autosonomal dominant
connective tissue disorder concerning many systems, also with cardiovascular
manifestations. The leading cause of premature death in these patients is
aortic dissection due to progressive dilatation of the aortic root. Aortic
stiffness is investigated as a potential predictor of aorta dissection and
aneurysm development.

Main objective of this study is to develop an MRI protocol from which regional
PWV can be assessed. An automated image analysis tool, indispensable for fast,
reproducible and observer-independent data processing will be developed. The
technique will be validated with intra-arterial pressure measurements in a
phantom study and in patients.

This four year study will be performed in four phases:
A. Scan optimization: a multi-directional VE MRI scan protocol with a high
temporal resolution needs to be optimized for tracing the systolic wave front
through the aorta.
B. Software development: the MRI acquisition results in large data sets (i.e.,
1500-2000 images per patient). In order to make the analysis of these images
and the quantification of PWV applicable in clinical routine, segmentation
(contour detection) of the aorta in these VE MR images (needed for constructing
the intra-aortic flow velocity vector field) has to be automated.
C. Validation: the accuracy of PWV MRI measurements will be determined by
comparing MRI with intra-arterial pressure measurements in a phantom study and
in patients selected for cardiac catheterization.
D. Application: the new MRI method will be applied in a patient study to test
the prognostic value of PWV measurement. Fifty patients with Marfan syndrome,
with proven regional impaired aortic wall compliance (i.e., with an implanted
aortic graft), will undergo an MRI examination. A follow-up MRI examination two
years later will provide insight on aortic events (i.e., local dilatation). For
comparison, 25 healthy volunteers (age- and gender-matched with the patients)
will be included.

The risks for the participating 25 patients in the validation part of the study
are minimal. Patients will undergo additional intra-aortic pressure
measurements during the angiographic procedure. During this angiogram, pressure
measurements are already routinely performed in the left ventricle. Aditionally
for this study, during pull back of the catheter, the pressure will be
registered at 8-10 locations in the aorta. No additional catheter will be
inserted, no additional contrast will be administered and no additional x-ray
images will be acquired. One week after catheterization, patients will undergo
an additional MRI examination. For this, no contrast agent will be
administered, and MRI is free from radiation, so this will not result in
additional burden to the patient.
The risks for the participating 25 volunteers in the validation part of the
study are also minimal. Volunteers will only undergo the MRI examination.
Finally, the risks for the participating 50 patients with Marfan syndrome in
the application part of the study are minimal. These patients already routinely
undergo MRI examinations at the AMC. When participating in this study, the
patients will undergo this clinically needed MRI at the LUMC instead. Usually
two weeks before this routine examination, patients will stop using beta
blocker medication. Medication will start again after MRI examination. This
procedure will also be followed for their MRI examination at the LUMC. The only
additional examinations needed for this research study are two scans resulting
in 15-20 minutes longer examination time compared to the routine MRI.