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Proton Density and R2* Estimation of Neonatal Lung Parenchyma During Free Breathing with UTE MRI

Andrew Hahn¹, Nara Higano^2,3, Jean Tkach⁴, Laura Walkup², Robert Thomen², Xuefeng Cao^2,5, Stephanie Merhar⁶, Jason Woods^2,3, and Sean Fain¹

¹Medical Physics, University of Wisconsin - Madison, Madison, WI, United States, ²Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States, ³Department of Physics, Washington University in St. Louis, St. Louis, MO, United States, ⁴Imaging Research Center, Department of Radiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, ⁵Department of Physics, University of Cincinnati, Cincinnati, OH, United States, ⁶Perinatal Institute, Division of Neonatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States

Synopsis

The majority of patients in the neonatal intensive care unit (NICU) have pulmonary morbidities, yet little is known about the underlying parenchymal structure. We quantify parenchymal proton density and R₂^* in the lungs of quiet breathing, non-sedated neonates in the NICU using a multi-echo 3D radial UTE MRI. Results indicate that lung proton density decreases as expected with lung inflation, while R₂^* increases. A positive relationship between gravitational dependence and tissue density is also apparent, while R₂^* decreases in more gravitationally dependent regions. Overall, our findings support a negative relationship between tissue density and R₂^* in the neonatal lung.

Purpose

Recent work has demonstrated the feasibility for ultrashort echo time (UTE) MRI of the lung in quiet breathing, non-sedated, neonatal intensive care unit (NICU) patients¹, which is of particular interest due to the elevated risk in this population of exposure to ionizing radiation from x-ray computed tomography (CT). Parenchymal density and R₂^* are biophysical parameters which are important for designing optimal neonatal lung MRI techniques, and may potentially contain clinically useful information for diagnosing and monitoring pathology such as microstructural abnormalities including alveolar simplification due to bronchopulmonary dysplasia (BPD). Here, multi-echo 3D UTE MRI is used to quantify parenchymal tissue density and R₂^* in the lungs of NICU patients during quiet tidal breathing, utilizing the self-navigation properties of the acquisition sequence to retrospectively reconstruct separate images at end-tidal inspiration and expiration².

Methods

All studies were approved by our institutional review board, were HIPAA compliant, and were conducted with parental consent. 11 neonatal patients underwent MRI in the NICU (post-menstrual ages 36-43 weeks at date of imaging) on a 1.5T MRI scanner³ designed specifically for neonatal imaging, using a body coil. A 3-D radial UTE MRI sequence¹, was modified to acquire each radial view at 4 different echo times (TE = 0.20ms, 0.95ms, 1.70ms, 2.45ms, 50,000-75,000 projections per TE, 1.4mm isotropic image resolution). 2 adults also underwent MRI on a conventional 1.5T scanner using the same imaging sequence with an 8-channel coil and slightly different parameters (TE = 0.09ms, 0.59ms, 1.09ms, 1.59ms, 25,000 projections per TE, 2.0mm isotropic image resolution). The center of k-space acquired with each view was used for self-navigated retrospective respiratory gating², and end-tidal inspiration and expiration images (50% acceptance windows) were reconstructed at each TE. Least squares estimates of R₂^* and spin density (M₀) were estimated at both respiratory phases from

$$S_k(r)=M_0e^{TE_k(2\pi i\Delta B_0(r)-R_2^*(r))}, \space\space\space k=1,2,3,4$$

, where S_k and TE_k are the measured signal and echo times at the k^th echo, ΔB₀ is the field off-resonance and r varies over all voxels. Parenchymal spin density was estimated by normalizing M₀ to adjacent muscle tissue signal (expressed as % of muscle), motivated by the assumption that lung and muscle tissues are expected to be similarly T₁-weighted^1,4. Average whole lung estimates of tissue density and R₂^* are compared between inspiration and expiration, using a paired t-test to evaluate statistical significance. Additionally, anterior-posterior (AP) relationships in these parameters are explored by dividing the segmented lung volumes into thirds along the AP axis (anterior/middle/posterior regions). Due to the coil sensitivity variations, proton density was not analyzed in adult data.

Results

Representative images of lung tissue density and parametric maps of R₂^* are shown at both inspiration and expiration in Figure 1 and Figure 2 for a neonatal and adult subject, respectively. The larger R₂^* values at inspiration relative to expiration are generally apparent from these images in both subjects, along with a negative AP gradient in R₂^* in the neonate, particularly at end-expiration. This latter relationship is not as clear in the adult images. The plots in Figure 3 demonstrate whole lung tissue density and R₂^* at expiration and inspiration in the neonatal cohort. As expected, tissue density decreases as the lung inflates (p = 1.8x10-4). However, R₂^* shows the opposite trend, increasing with lung inflation (p = 2.5x10-5). Regional AP trends in the estimated parameters at end-expiration, along with the differences between end-tidal inspiration and expiration, are shown in Figure 4 for neonates. Figure 4 demonstrates that proton density tends to increase in posterior lung regions at end-expiration, and decrease at end-inspiration as expected due to gravity dependence. Figure 4 also supports the finding that R₂^* increases as proton density decreases especially in the posterior, gravity-dependent region. Mean regional R₂^* estimates are presented in Table 1 for both adults and neonates. These neonatal trends are also seen in adults; however, R₂^* in adults is consistently larger.

Discussion and Conclusion

We present initial results of proton density and R₂^* measures in the lungs of free breathing neonates, and compare these data to similar estimates in adults. These results support a negative relationship between proton density and R₂^* that is maintained for both end-tidal and end inspiratory lung inflation. R₂^* also appears to be smaller in the lungs of neonates relative to adults, although more adult data is required to verify this finding. There is a wide range of measured baseline tissue densities and R₂^* values in this neonatal cohort. Determination of the source of these differences may have a clinically useful physiologic basis and is an important topic for further research.

Acknowledgements

The authors would like to acknowledge financial support from The Hartwell Foundation, GE Healthcare, The Perinatal Institute at Cincinnati Children’s Hospital Medical Center, and NIH P01 HL070831.

References

1. Hahn AD, Higano NS, Walkup LL, Thomen RP, Cao X, Merhar SL, Tkach JA, Woods JC, Fain SB. (2016) Pulmonary MRI of neonates in the intensive care unit using 3D ultrashort echo time and a small footprint MRI system. J Magn Reson Imaging. doi: 10.1002/jmri.25394

2. Higano NS, Hahn AD, Tkach JA, Cao X, Walkup LL, Thomen RP, Merhar SL, Fain SB, Woods JC (2016) Retrospective respiratory self-gating and removal of bulk motion in pulmonary UTE MRI of neonates and adults. Magn Reson Med. doi: 10.1002/mrm.26212

3. Tkach JA, Merhar SL, Kline-Fath BM, Pratt RG, Loew WM, Daniels BR, Giaquinto RO, Rattan MS, Jones BV, Taylor MD, Tiefermann JM, Tully LM, Murphy EC, Wolf-Severs RN, LaRuffa AA, Dumoulin CL (2014) AJR Am J Roentgenol. 202(1):W95-W105. doi: 10.2214/AJR.13.10613.

4. Gold GE, Han E, Stainsby J, Wright G, Brittain J, Beaulieu C (2004) Musculoskeletal MRI at 3.0T: relaxation times and image contrast. Am J Roentgenol 183:343–351. doi: 10.2214/ajr.183.2.1830343

Figures

Figure 1: Axial plane images of proton spin density (top row) and R₂^* (bottom row) at end-tidal expiration (left column) and inspiration (right column) in a neonatal subject. Note the apparent decrease in parenchymal spin density and increase in R₂^* at inhale vs. exhale. A negative anterior-to-posterior gradient in R₂^* is apparent at end-expiration.

Figure 2: Axial plane images of proton spin density (top row) and R₂^* (bottom row) at end-tidal expiration (left column) and inspiration (right column) in an adult subject. R₂^* is apparently increased at inhale vs. exhale, as in neonates. An anterior-to-posterior gradient in R₂^* is not as apparent as in neonates, however.

Figure 3: Neonatal whole lung averages of normalized lung tissue density (left) and R₂^* (right) at exhalation and inhalation during tidal breathing. Plots indicate that tissue density decreases with inhalation, as expected, while R₂^* increases with inhalation.

Figure 4: Neonatal regional averages of normalized tissue density (top) and R₂^* (bottom) along the anterior-posterior axis at end-tidal expiration (left) and average change in tissue density and R₂^* between inhalation and exhalation (right). Tissue density and change in tissue density generally increase with regional gravitational dependence and increases overall at exhalation relative to inhalation, as expected, due to lung deflation. End-expiration R₂^* decreases with gravitational dependence (i.e. decreases as tissue density increases), while the magnitude of R₂^* change increases with gravitational dependence. R₂^* decreases at exhalation relative to inhalation, consistent with an inverse relationship between tissue density and R₂^*.

Table 1: Mean regional R₂^* estimates in adult and neonatal subjects. Mean adult R₂^* values are consistently larger, but trends are otherwise generally similar between adult and neonates (lowest R₂^* and greatest change in R₂^* in posterior, increase in R₂^* at inhale vs. exhale).

Proc. Intl. Soc. Mag. Reson. Med. 25 (2017)

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