Three‐Dimensional Free‐Breathing Ultrashort Echo Time (UTE) ¹H MRI Regional Ventilation: Comparison With Hyperpolarized ¹²⁹Xe MRI and Pulmonary Function Testing in Healthy Volunteers and People With Cystic Fibrosis

MRI can provide localized assessment of lung function for monitoring people with lung disease. Hyperpolarized ¹²⁹Xe MRI directly images pulmonary gas distribution but requires specialized hardware. Conventional ¹H MRI acquisitions can also provide functional maps using free-breathing approaches. The purpose of this study is to evaluate regional ventilation derived from 3D ultrashort echo-time (UTE) ¹H MRI using Motion-Compensated Low-Rank constrained reconstruction (MoCoLoR), by comparing against ¹²⁹Xe MRI and pulmonary function testing as reference-standard. The study is retrospective in design. The study included 57 participants (25.4 ± 15.8 years, 35 males and 22 females): 12 healthy volunteers, 20 pediatric, and 25 adult people with cystic fibrosis (CF) scanned between January 2022 and February 2023. Field strength/sequence: 3T; ¹²⁹Xe: 2D multislice spoiled gradient-recalled sequence; UTE ¹H: variable-density 3D radial sequence. K-means-based ¹²⁹Xe ventilation defect percent (VDP), forced expiratory volume in 1 s (FEV₁), and lung clearance index (LCI) were evaluated against UTE ¹H VDP from a modified k-means method. The correspondence of ventilation defect maps from ¹²⁹Xe and UTE ¹H was also evaluated. Statistical tests included the Pearson correlation coefficient (r) and t tests, with p < 0.05 considered significant. ¹²⁹Xe and UTE ¹H VDP were significantly correlated (r = 0.64, p = <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:mrow><mml:mn>9.1</mml:mn> <mml:mo>×</mml:mo> <mml:msup><mml:mn>10</mml:mn> <mml:mrow><mml:mo>-</mml:mo> <mml:mn>8</mml:mn></mml:mrow> </mml:msup> </mml:mrow> <mml:annotation>$$ 9.1\times {10}^{-8} $$</mml:annotation></mml:semantics> </mml:math> ). Bland-Altman analysis showed a bias of -0.05 (p = <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:mrow><mml:mn>7.2</mml:mn> <mml:mo>×</mml:mo> <mml:msup><mml:mn>10</mml:mn> <mml:mrow><mml:mo>-</mml:mo> <mml:mn>5</mml:mn></mml:mrow> </mml:msup> </mml:mrow> <mml:annotation>$$ 7.2\times {10}^{-5} $$</mml:annotation></mml:semantics> </mml:math> ) and limits of agreement of (0.07, -0.17). The Dice spatial accuracy of the UTE-based ventilation defect regions using ¹²⁹Xe as reference was 0.64 ± 0.05. UTE ¹H VDP was significantly correlated with FEV₁ (r = -0.54, p = <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:mrow><mml:mn>2.9</mml:mn> <mml:mo>×</mml:mo> <mml:msup><mml:mn>10</mml:mn> <mml:mrow><mml:mo>-</mml:mo> <mml:mn>4</mml:mn></mml:mrow> </mml:msup> </mml:mrow> <mml:annotation>$$ 2.9\times {10}^{-4} $$</mml:annotation></mml:semantics> </mml:math> ) and LCI (r = 0.48, p = <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:mrow><mml:mn>5.9</mml:mn> <mml:mo>×</mml:mo> <mml:msup><mml:mn>10</mml:mn> <mml:mrow><mml:mo>-</mml:mo> <mml:mn>3</mml:mn></mml:mrow> </mml:msup> </mml:mrow> <mml:annotation>$$ 5.9\times {10}^{-3} $$</mml:annotation></mml:semantics> </mml:math> ) and was significantly different between healthy and CF participants (p = 0.017), although the correlations and differences were stronger for ¹²⁹Xe VDP. UTE ¹H VDP correlated with ¹²⁹Xe VDP, FEV₁, and LCI, and demonstrated high, consistent Dice spatial accuracy against ¹²⁹Xe VDP. UTE ¹H VDP captured variations in lung ventilation and has the advantage that it can be widely implemented on any MR system for evaluation and monitoring of patients with lung disease.