UCLA

Purpose

Magnetic resonance imaging (MRI) can non-invasively quantify fat and the transverse relaxation rate (R2*) in the human body. This quantitative information can provide further insight about diseases such as non-alcoholic fatty liver disease (NAFLD), obesity, and ischemic placental disease (IPD). Conventional MRI methods for quantifying fat and R2* require breath-holding, which limits the spatial resolution, volumetric coverage, and signal-to-noise ratio that may be achieved. Moreover, several subject populations, including sick, elderly, and mentally impaired patients, as well as children, infants, and pregnant women, may have difficulty performing a breath-hold or are unable to breath-hold. The purpose of this work is to develop and evaluate a new free-breathing 3D stack-of-radial MRI technique (FB radial) for fat and R2* quantification at 3 Tesla (T) that overcomes the aforementioned limitations of conventional breath-holding MRI.

Methods

To enable free-breathing MRI, a multiecho golden-angle ordered 3D stack-of-radial radiofrequency-spoiled gradient echo sequence with gradient calibration and correction (FB radial) was developed. First, to evaluate FB radial without motion, fat quantification accuracy using FB radial was compared to conventional Cartesian and reference single-voxel magnetic resonance spectroscopy (SVS) sequences using a fat fraction phantom and in the pelvis of five healthy subjects at 3 T. To evaluate FB radial fat quantification accuracy in subjects capable of breath-holding, a population consisting of eleven healthy adults were recruited and imaged at 3 T. The fat quantification accuracy of FB radial was compared to conventional breath-held Cartesian (BH Cartesian) MRI and reference breath-held SVS (BH SVS).

The feasibility and repeatability of FB radial for hepatic fat quantification was evaluated in children, which represents a population that may have limited breath-hold ability or may have difficulty complying with operator instructions. Ten healthy children and nine overweight children with NAFLD, 7-17 years of age, were imaged at 3 T using FB radial, BH Cartesian and BH SVS. Acquisitions were performed twice to assess repeatability. Images and proton-density fat fraction (PDFF) maps were scored for image quality. Liver coverage was measured.

Ten healthy infants aged 2-7 months were recruited to evaluate the feasibility of FB radial for quantifying hepatic fat and body composition in a population incapable of breath-holding. The preparation time and scan time (median ± interquartile range) for each non-sedated MRI exam was recorded. Abdominal and head and chest FB radial scans and abdominal Cartesian scans were performed. Abdominal scans were scored for motion artifacts by a radiologist, masked to the trajectory. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and brown adipose tissue (BAT) (volume and PDFF) and hepatic PDFF were measured using FB radial. Repeatability of FB radial hepatic PDFF was assessed.

To evaluate the quantitative accuracy of FB radial for R2* mapping without motion, FB radial was compared to a conventional Cartesian sequence using a R2* phantom. To evaluate FB radial R2* mapping in the presence of motion, thirty subjects with normal pregnancies and three subjects with ischemic placental disease (IPD) were scanned twice: between 14-18 and 19-23 weeks gestational age (GA). Feasibility and repeatability of FB radial placental R2* mapping was assessed. The mean and spatial coefficient of variation (CV) of placental R2* was determined for all subjects, and separately for anterior and posterior placentas, at each GA range.

For all analyses, quantitative accuracy of fat or R2* quantification was evaluated using linear correlation (Pearson’s correlation coefficient, r; Lin’s concordance correlation coefficient, ρc) and Bland-Altman analyses (mean difference, MD; limits of agreement, LoA = MD ± 1.96 ± standard deviation). The repeatability of FB radial between back-to-back scans for fat or R2* quantification was assessed by calculating the within-technique mean difference (MDwithin) and the coefficient of repeatability (CR). To compare image quality between FB radial and BH Cartesian, differences in the distribution of scores between FB radial and Cartesian were determined using McNemar-Bowker tests. For all statistical analyses, a p-value (P) < 0.05 was considered significant.

Results

In a fat fraction phantom, FB radial demonstrated accuracy with r and ρc > 0.995 (P < 0.001), absolute MD < 2.2 ± 4.9% compared to SVS and absolute MD < 0.6 ± 3.3% compared to Cartesian. In the pelvis of healthy adults, FB radial demonstrated fat quantification accuracy with absolute MD < 1.2 ± 3.2% in low fat fraction regions (< 5% PDFF) and absolute MD < 4.6 ± 5.6% in high fat fraction regions (> 80% PDFF). In the liver and abdomen, PDFF showed significant correlation (ρ > 0.986, ρc > 0.985), and absolute MD < 1.0 ± 10.6% between FB radial and BH SVS, and significant correlation (r > 0.996, ρc > 0.995), and absolute MD < 0.9 ± 5.7% between FB radial and BH Cartesian.

In children with NAFLD, FB radial demonstrated significantly less motion artifacts compared to BH Cartesian (P < 0.05). FB radial PDFF demonstrated a linear relationship (P < 0.001) versus BH SVS PDFF and BH Cartesian PDFF with r = 0.996 and ρc = 0.994, and r = 0.997 and ρc = 0.995, respectively. The absolute MD in PDFF between FB radial, BH Cartesian, and BH SVS was less than 0.7 ± 2.6% Repeated FB radial had MDwithin = 0.25% and CR = 1.53% for PDFF.

Ten infants were enrolled, and nine infants completed the study (90% completion). The preparation time and scan time were 32 ± 7 min and 24 ± 11 min, respectively. FB radial MRI demonstrated significantly higher image quality scores compared to Cartesian MRI (P = 0.01). The measurements using FB radial were VAT = 48.2 ± 16.5 cm3; VAT-PDFF = 41.6 ± 3.8%; SAT = 281.6 ± 104.5 cm3; SAT-PDFF = 86.1 ± 4.8%; BAT = 1.5 ± 0.6 cm3; and BAT-PDFF = 28.9 ± 8.8%. Hepatic PDFF measured using FB radial was 3.5 ± 1.1% and had repeatability of MDwithin < 0.25% and CR < 2.0%.

For R2* mapping, FB radial demonstrated accurate (ρc ≥ 0.996; P < 0.001; absolute MD < 0.2 ± 4 s-1) and repeatable (MDwithin = 0.23 s-1; CR = 3.9 s-1) quantification in a phantom, and repeatable (MDwithin < 0.5 s-1; CR ≤ 4.6 s-1) quantification in thirty subjects with normal pregnancies. At 3T, placental R2* mean ± standard deviation was 12.9 ± 2.7 s-1 for 14-18 and 13.2 ± 1.9 s-1 for 19-23 weeks GA. The CV was significantly greater (P = 0.043) at 14-18 (0.63 ± 0.12) than 19-23 (0.58 ± 0.13) weeks GA. At 19-23 weeks, the CV was significantly lower (P < 0.001) for anterior (0.49 ± 0.08) than posterior (0.67 ± 0.11) placentas. One IPD subject had a lower mean R2* than normal subjects at both GA ranges (Z ̂ < −2).

Conclusion

FB radial demonstrated quantitative accuracy compared to BH techniques in a fat fraction phantom and in the pelvis and liver of healthy volunteers. In healthy children and children with NAFLD, non-sedated free-breathing radial MRI provided accurate and repeatable hepatic PDFF measurements and improved image quality, compared to standard breath-held MR techniques. Finally, in a R2* phantom FB radial provided accurate and repeatable three-dimensional R2* mapping and in pregnant subjects FB radial provided repeatable R2* mapping in the entire placenta at 3T during early GA.