Jean A Tkach1, Ryan A Moore2, Nara S Higano1,3,4, Laura L Walkup1,3, Mantosh S Rattan5, Paul S Kingma6, Michael D Taylor2, and Jason C Woods1,3,4
1Imaging Research Center, Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, 2The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, 3Center for Pulmonary Imaging Research, Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, 4Department of Physics, Washington University, St. Louis, MO, United States, 5Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, 6Division of Neonatology and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
Synopsis
Pulmonary arterial hypertension (PAH) is common in
congenital diaphragmatic hernia (CDH) and is a major contributor to morbidity
and mortality. Echocardiography and cardiac catheterization are the current standards
for evaluating pulmonary hemodynamics in CDH infants, but both have significant
limitations and/or risks. Phase contrast (PC) MRI can provide quantitative
information about velocity and flow longitudinally, with minimal risk. We demonstrate the feasibility of applying PC
MRI in the neonatal ICU (NICU) to obtain a quantitative assessment of pulmonary
blood flow in CDH infants with the long-term goal to establish imaging
biomarkers to predict PAH and assess therapeutic response. Purpose:
Congenital diaphragmatic hernia (CDH) is a defect
of the diaphragm in utero which allows the abdominal organs to herniate into
the thoracic cavity. Compression of the developing lungs leads to pulmonary
hypoplasia and altered pulmonary vascular development. Pulmonary arterial hypertension (PAH) is very common
in CDH and is a major contributor to morbidity and mortality in these infants. Echocardiography
and cardiac catheterization are the current standard for evaluating pulmonary
hemodynamics in CDH infants, but these modalities have significant limitations
and/or risks. Phase contrast (PC) MRI can provide quantitative information
about velocity and flow; however, application of MRI in the Neonatal Intensive
Care Unit (NICU) patient population is limited to date, primarily due to the
medical risks and logistical challenges of transporting the infants out of the
unit for the exam. These challenges have been mitigated at our institution by
the installation of a unique, neonatal-sized 1.5T MRI scanner within our NICU
1, 2. Furthermore, using the “feed
and swaddle” approach, the NICU MR exams can be performed without sedation
2.
The objective of the present study was to evaluate the feasibility of PC MRI
within the NICU in free-breathing, non-sedated infants with CDH, with the
long-term goal to establish imaging biomarkers to predict PAH and assess
response to therapies.
Methods:
IRB approval and written informed consent was
obtained from the parents prior to imaging on a unique small footprint 1.5T MR
system installed within the NICU at our institution1,2. 8 (5M/3F)
infants with left-sided CDH, ranging from mild to moderate in severity, 3wks±2wks post-surgical
repair were imaged free breathing without sedation (via feed and swaddle) or
intravenous contrast. One CDH patient was also imaged pre-surgical repair, in
addition to one control infant. The
infants were imaged at an average age of 40±4wks adjusted gestational age with
weight and heart rate 3.1±0.5kg and 158.8±12.5bpm respectively. 2D
black blood imaging was used to localize the aorta, main and branch pulmonary arteries.
Retrospective ECG gated 2D PC images were acquired in planes perpendicular to
each of these vessels (TR=12.0-12.8ms; TE=4.5-5.1msec; FA=20°; in plane
resolution 0.9375x1.875mm2; slice thickness=5mm, velocity encoding (VENC)=150-200cm/sec;
2 views per segment; receiver BW = 122Hz/pixel). Standard commercially
available software (QFlow; Medis Medical Imaging Systems; Leiden, the Netherlands)
was used to analyze the PC data to obtain quantitative flow measurements for
the main (MPA), right (RPA) and left (LPA) pulmonary arteries. 3D Fast Gradient Recalled Echo (FGRE)
(TR/TE/FA=6.3ms/1.8ms/4°; FOV=18-20cm; matrix=256x256; 28-32 3mm partitions)
and 2D Time-of-Flight (TOF) (TR/TE/FA= 6.6-10.5ms/3.5-4.6ms/45-60°; FOV=16-17cm;
matrix=192x320; 1.5 - 3mm thick slices; acquired sequentially inferior to
superior; 2 averages) data sets were also obtained to provide an overview of
the pulmonary anatomy and vasculature respectively. To quantify the impact of
CDH on the vascular development in the affected lung, the number of vessels identified
at 50% of the maximum diameter of the left lung was determined from axial
maximum intensity projections (MIP’s) of the 2D TOF data.
Results and Discussion:
PC, 3D FGRE, and 2D TOF data were obtained during free
breathing and without sedation in all 10 infants (Table 1). Hypoplasia and reduced vascularization (Table
1) of the left lung were well visualized in the 3D FGRE and 2D TOF MIP images
of the CDH infants (Figure 1). The
values for total pulmonary flow were
361.6 mL/kg/min for the control infant, 207.3mL/kg/min for the pre-surgical
repair CDH infant, and 344.7±110.6 mL/kg/min [range 208.5-526.3 mL/kg/min] for
the post-surgical repair CDH infants --well within the expected range
3.
As expected, the flow from the MPA was
fairly evenly distributed between the RPA and LPA (%LPA/MPA = 42.5%; %RPA/MPA =54.8%)
in the control infant; however the relative proportion of MPA flow directed to
the LPA versus the RPA was reduced in the CDH infants. In the pre-surgical repair CDH infant, the %
LPA/MPA flow ratio was 12.7%. Similarly, in the post-surgical repair CDH
infants, the %LPA/MPA flow ratio was 31.6±15.5%. This is consistent with what
has been reported for older pediatric patients with a history of left sided CDH
repair
4.
Conclusions:
PC MRI is a viable method to quantitatively assess
pulmonary blood flow in CDH infants within the NICU during free-breathing and
without sedation, with the potential to safely and longitudinally provide information
about PAH and response to therapies.
Acknowledgements
The authors thank the Perinatal Institute at CCHMC and the Center for Translational Science and Training at CCHMC and UC for their financial support. References
1. Tkach JA, et al., Pediatr Radiol 42:1347-1356
(2012).
2. Tkach JA,
et al., Amer J Roentgen 202:W95-W105 (2014).
3. Kluckow M and Evans N . J of Pediatr
137(1):68-72 (2000).
4. Abolmaali et al. Eur Radiol 20:1580-1589 (2010).