Himanshu Gupta1,2, Ankur Gupta1, and Thomas S Denney3,4
1Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States, 2VA Medical Center, Birmingham, AL, United States, 3Auburn University MRI Research Center, Auburn University, Auburn, AL, United States, 4Electrical and Computer Engineering, Auburn University, Auburn, AL, United States
Synopsis
Pulmonary arterial (PA) impedance accounts for pulsatile
blood flow through elastic pulmonary arteries as compared to static pulmonary
vascular resistance. Increased PA impedance is an early physiological
manifestation of PA remodeling. Currently, PA impedance can only be detected
invasively, is expensive and cumbersome to calculate and not done in routine
clinical practice. Non-invasive assessment of PA impedance can provide insights
in evaluation of patients with normal PA pressures or mild pulmonary
hypertension such as in patients with chronic obstructive lung disease. We
propose a novel non-invasive parameter, the velocity transfer function (VTF), which
is related to PA stiffness and impedance.Introduction
Pulmonary arterial (PA) impedance takes in to account pulsatile
blood flow through elastic pulmonary arteries as compared to static pulmonary
vascular resistance. Increased PA impedance is an early physiological
manifestation of PA remodeling. Currently PA impedance can only be detected
invasively, is expensive and cumbersome to calculate and thus not done in
routine clinical practice. The ability to assess PA impedance non-invasively
can provide fundamental insights in evaluation of patients with normal PA
pressures or mild pulmonary hypertension (PH) such as in patients with chronic
obstructive lung disease. We propose a novel non-invasive parameter, the velocity
transfer function (VTF), which is related to PA stiffness and
impedance.
Theoretical Development
PA pressure measurements are obtained by invasive techniques
for quantification of PA impedance. Velocity and flow, however, can be measured
non-invasively with phase-contrast cardiac MR (CMR) at arbitrary points in the
PA tree. Figure 1 shows the pulsatile velocity profiles measured at the main PA (MPA) (input) and the proximal right PA (RPA) (output) in a normal
human volunteer and a patient with PH.
In a normal volunteer, with a compliant PA, the velocity profile not
only is shifted in the transit time between the two sites, but there are also
complex shape changes across the entire wave.
In a patient with PH, the PA is stiffer and both the time shift and
shape change are reduced. These time
shifts and shape changes are frequency dependent and are related to the
compliance and geometry of the artery between the two points. These
frequency-dependent changes can be compactly described by the transfer function
between the two velocity profiles measured non-invasively with phase-contrast
MRI. A transfer function is a function
that describes the relationship between the frequency spectra of any two
functions that are linearly related. Impedance is a specific case of a transfer
function when the two functions are voltage and current or pressure and flow.
Here, the PA was modeled between two points as a VTF with the velocity measured
at the MPA as the input and the velocity measured at the RPA as the output. Specifically, the VTF
$$$[S_F(f)]$$$ was computed between the two measured velocity profiles by taking
the Fourier transform of each velocity profile and dividing one by other as
follows: $$$S_F(f) = V_{RPA}(f)/V_{MPA}(f)$$$. The VTF is similar to impedance because it
describes predominantly the influence of vessel geometry and
compliance/stiffness to cause frequency-dependent changes in the input velocity
profile as it travels through the artery thereby producing the output velocity
profile.
Methods
The VTF was validated against invasive reference standard
(invasive impedance) measured using pressure data from right heart
catheterization and velocity data from Doppler echocardiography on 20 patients
undergoing clinically indicated right heart catheterization. Each patient also underwent a comprehensive
phase-contrast and cine CMR exam to calculate the VTF. Impedance and VTF were computed as a function
of heart rate harmonic to compensate for heart rate variability.
Results and Discussion
In Figure 2, impedance curves for patients with normal pulmonary
vascular resistance (PVR) £2.5
Woods Units (WU) show a low modulus at zero harmonic, then rapidly descend down
with first minimum modulus occurring at low harmonics (1 or 2). Impedance modulus curves of patients with
high PVR (>2.5 WU) show high modulus at zero harmonic, and then slowly descends
down with first minimum occurring at later harmonics (3 or 4 or higher). This
is the expected behavior of impedance curves [1]. Corresponding VTF curves in
Figure 2 demonstrate that VTF curves start at similar zero harmonic for
patients with normal or high PVR but then shows differentiation at higher
harmonics (5 or 6), when the VTF magnitude increases in patients with high PVR.
For invasive impedance, the pressure and
flow curves have different mean values, which reflects as high impedance moduli
at zero and lower impedance harmonics. In contrast, for VTF, the input
(MPA) and output (RPA) velocity curves have close to the same mean value, so
the zero and lower VTF harmonics are close to 1 before separating at higher
harmonics. Representative phase-contrast velocity curves and corresponding VTF
for patients in the PVR£2.5
and PVR>2.5 groups are shown in Figure 3. Two patients in the study showed signs of early PA remodeling and were removed as outliers (upper left in Figure 4). The average of VTF magnitude harmonics 5 and
6 in the remaining patients were correlated with impedance harmonics 0 and 1 (Pearson
r = 0.75, p=0.002).
Conclusion
The VTF has the potential to assess PA impedance non-invasively and reliably using cMRI with potential to non-invasively detect early PA remodeling.
Acknowledgements
Walter B. Frommeyer, Jr. Fellowship in
Investigative Medicine References
[1] Nichols, W. and M. O’Rourke, McDonald’s Blood Flow in Arteries. 5th ed. 2005, London: Hodder Arnold.