Radiologic-pathologic correlation of lesions in resected liver specimens with an ex vivo MRI-compatible localization device.

OBJECTIVE: Liver lesion characterization is limited by the lack of an established gold standard for precise correlation of radiologic characteristics with their histologic features. The objective of this study was to demonstrate the feasibility of using an ex vivo MRI-compatible sectioning device for radiologic-pathologic co-localization of lesions in resected liver specimens. METHODS: In this prospective feasibility study, adults undergoing curative partial hepatectomy from February 2018 to January 2019 were enrolled. Gadoxetic acid was administered intraoperatively prior to hepatic vascular inflow ligation. Liver specimens were stabilized in an MRI-compatible acrylic lesion localization device (27 × 14 × 14 cm3) featuring slicing channels and a silicone gel 3D matrix. High-resolution 3D T1-weighted fast spoiled gradient echo and 3D T2-weighted fast-spin-echo images were acquired using a single channel quadrature head coil. Radiologic lesion coordinates guided pathologic sectioning. A final histopathologic diagnosis was prepared for all lesions. The proportion of successfully co-localized lesions was determined. RESULTS: A total of 57 lesions were identified radiologically and sectioned in liver specimens from 10 participants with liver metastases (n = 8), primary biliary mucinous cystic neoplasm (n = 1), and hepatic adenomatosis (n = 1). Of these, 38 lesions (67%) were < 1 cm. Overall, 52/57 (91%) of radiologically identified lesions were identified pathologically using the device. Of these, 5 lesions (10%) were not initially identified on gross examination but were confirmed histologically using MRI-guided localization. One lesion was identified grossly but not on MRI. CONCLUSIONS: We successfully demonstrated the feasibility of a clinical method for image-guided co-localization and histological characterization of liver lesions using an ex vivo MRI-compatible sectioning device. KEY POINTS: • The ex vivo MRI-compatible sectioning device provides a reliable method for radiologic-pathologic correlation of small (< 1 cm) liver lesions in human liver specimens. • The sectioning method can be feasibly implemented within a clinical practice setting and used in future efforts to study liver lesion characterization. • Intraoperative administration of gadoxetic acid results in enhancement in ex vivo MRI images of liver specimens hours later with excellent image quality.

Improved free-breathing liver fat and iron quantification using a 2D chemical shift-encoded MRI with flip angle modulation and motion-corrected averaging.

OBJECTIVES: 3D chemical shift-encoded (CSE) MRI enables accurate and precise quantification of proton density fat fraction (PDFF) and R2*, biomarkers of hepatic fat and iron deposition. Unfortunately, 3D CSE-MRI requires reliable breath-holding. Free-breathing 2D CSE-MRI with sequential radiofrequency excitation is a motion-robust alternative but suffers from low signal-to-noise-ratio (SNR). To overcome this limitation, this work explores the combination of flip angle-modulated (FAM) 2D CSE imaging with a non-local means (NLM) motion-corrected averaging technique. METHODS: In this prospective study, 35 healthy subjects (27 children/8 adults) were imaged on a 3T MRI-system. Multi-echo 3D CSE ("3D") and 2D CSE FAM ("FAM") images were acquired during breath-hold and free-breathing, respectively, to obtain PDFF and R2* maps of the liver. Multi-repetition FAM was postprocessed with direct averaging (DA)- and NLM-based averaging and compared to 3D CSE using Bland-Altmann and regression analysis. Image qualities of PDFF and R2* maps were reviewed by two radiologists using a Likert-like scale (score 1-5, 5 = best). RESULTS: Compared to 3D CSE, multi-repetition FAM-NLM showed excellent agreement (regression slope = 1.0, R2 = 0.996) for PDFF and good agreement (regression slope 1.08-1.15, R2 ≥ 0.899) for R2*. Further, multi-repetition FAM-NLM PDFF and R2* maps had fewer artifacts (score 3.8 vs. 3.2, p < 0.0001 for PDFF; score 3.2 vs. 2.6, p < 0.001 for R2*) and better overall image quality (score 4.0 vs. 3.5, p < 0.0001 for PDFF; score 3.4 vs. 2.7, p < 0.0001 for R2*). CONCLUSIONS: Free-breathing FAM-NLM provides superior image quality of the liver compared to the conventional breath-hold 3D CSE-MRI, while minimizing bias for PDFF and R2* quantification. KEY POINTS: • 2D CSE FAM-NLM is a free-breathing method for liver fat and iron quantification and viable alternative for patients unable to hold their breath. • 2D CSE FAM-NLM is a feasible alternative to breath-hold 3D CSE methods, with low bias in proton density fat fraction (PDFF) and no clinically significant bias in R2*. • Quantitatively, multiple repetitions in 2D CSE FAM-NLM lead to improved SNR.

Limits of Fat Quantification in the Presence of Iron Overload.

BACKGROUND: Chemical shift encoded magnetic resonance imaging (CSE-MRI)-based tissue fat quantification is confounded by increased R2* signal decay rate caused by the presence of excess iron deposition. PURPOSE: To determine the upper limit of R2* above which it is no longer feasible to quantify proton density fat fraction (PDFF) reliably, using CSE-MRI. STUDY TYPE: Prospective. POPULATION: Cramér-Rao lower bound (CRLB) calculations, Monte Carlo simulations, phantom experiments, and a prospective study in 26 patients with known or suspected liver iron overload. FIELD STRENGTH/SEQUENCE: Multiecho gradient echo at 1.5 T and 3.0 T. ASSESSMENT: CRLB calculations were used to develop an empirical relationship between the maximum R2* value above which PDFF estimation will achieve a desired number of effective signal averages. A single voxel multi-TR, multi-TE stimulated echo acquisition mode magnetic resonance spectroscopy acquisition was used as a reference standard to estimate PDFF. Reconstructed PDFF and R2* maps were analyzed by one analyst using multiple regions of interest drawn in all nine Couinaud segments. STATISTICAL TESTS: None. RESULTS: Simulations, phantom experiments, and in vivo measurements demonstrated unreliable PDFF estimates with increased R2*, with PDFF errors as large as 20% at an R2* of 1000 s-1 . For typical optimized Cartesian acquisitions (TE1 = 0.75 msec, ΔTE = 0.67 msec at 1.5 T, TE1 = 0.65 msec, ΔTE = 0.58 msec at 3.0 T), an empirical relationship between PDFF estimation errors and acquisition parameters was developed that suggests PDFF estimates are unreliable above an R2* of ~538 s-1 and ~779 s-1 at 1.5 T and 3 T, respectively. This empirical relationship was further investigated with phantom experiments and in vivo measurements, with PDFF errors at an R2* of 1000 s-1 at 3.0 T as large as 10% with TE1 = 1.24 msec, ΔTE = 1.01 msec compared to 3% with TE1 = 0.65 msec, ΔTE = 0.58 msec. DATA CONCLUSION: We successfully developed a theoretically-based empirical formula that may provide an easily calculable guideline to identify R2* values above which PDFF is not reliable in research and clinical applications using CSE-MRI to quantify PDFF in the presence of iron overload. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Free-breathing R2∗ mapping of hepatic iron overload in children using 3D multi-echo UTE cones MRI.

PURPOSE: To enable motion-robust, ungated, free-breathing R2∗ mapping of hepatic iron overload in children with 3D multi-echo UTE cones MRI. METHODS: A golden-ratio re-ordered 3D multi-echo UTE cones acquisition was developed with chemical-shift encoding (CSE). Multi-echo complex-valued source images were reconstructed via gridding and coil combination, followed by confounder-corrected R2∗ (=1/ T2∗ ) mapping. A phantom containing 15 different concentrations of gadolinium solution (0-300 mM) was imaged at 3T. 3D multi-echo UTE cones with an initial TE of 0.036 ms and Cartesian CSE-MRI (IDEAL-IQ) sequences were performed. With institutional review board approval, 85 subjects (81 pediatric patients with iron overload + 4 healthy volunteers) were imaged at 3T using 3D multi-echo UTE cones with free breathing (FB cones), IDEAL-IQ with breath holding (BH Cartesian), and free breathing (FB Cartesian). Overall image quality of R2∗ maps was scored by 2 blinded experts and compared by a Wilcoxon rank-sum test. For each pediatric subject, the paired R2∗ maps were assessed to determine if a corresponding artifact-free 15 mm region-of-interest (ROI) could be identified at a mid-liver level on both images. Agreement between resulting R2∗ quantification from FB cones and BH/FB Cartesian was assessed with Bland-Altman and linear correlation analyses. RESULTS: ROI-based regression analysis showed a linear relationship between gadolinium concentration and R2∗ in IDEAL-IQ (y = 8.83x - 52.10, R2 = 0.995) as well as in cones (y = 9.19x - 64.16, R2 = 0.992). ROI-based Bland-Altman analysis showed that the mean difference (MD) was 0.15% and the SD was 5.78%. However, IDEAL-IQ R2∗ measurements beyond 200 mM substantially deviated from a linear relationship for IDEAL-IQ (y = 5.85x + 127.61, R2 = 0.827), as opposed to cones (y = 10.87x - 166.96, R2 = 0.984). In vivo, FB cones R2∗ had similar image quality with BH and FB Cartesian in 15 and 42 cases, respectively. FB cones R2∗ had better image quality scores than BH and FB Cartesian in 3 and 21 cases, respectively, where BH/FB Cartesian exhibited severe ghosting artifacts. ROI-based Bland-Altman analyses were 2.23% (MD) and 6.59% (SD) between FB cones and BH Cartesian and were 0.21% (MD) and 7.02% (SD) between FB cones and FB Cartesian, suggesting a good agreement between FB cones and BH (FB) Cartesian R2∗ . Strong linear relationships were observed between BH Cartesian and FB cones (y = 1.00x + 1.07, R2 = 0.996) and FB Cartesian and FB cones (y = 0.98x + 1.68, R2 = 0.999). CONCLUSION: Golden-ratio re-ordered 3D multi-echo UTE Cones MRI enabled motion-robust, ungated, and free-breathing R2∗ mapping of hepatic iron overload, with comparable R2∗ measurements and image quality to BH Cartesian, and better image quality than FB Cartesian.

Sensitivity of quantitative relaxometry and susceptibility mapping to microscopic iron distribution.

PURPOSE: Determine the impact of the microscopic spatial distribution of iron on relaxometry and susceptibility-based estimates of iron concentration. METHODS: Monte Carlo simulations and in vitro experiments of erythrocytes were used to create different microscopic distributions of iron. Measuring iron with intact erythrocyte cells created a heterogeneous distribution of iron, whereas lysing erythrocytes was used to create a homogeneous distribution of iron. Multi-echo spin echo and spoiled gradient echo acquisitions were then used to estimate relaxation parameters ( R2 and R2* ) and susceptibility. RESULTS: Simulations demonstrate that R2 and R2* measurements depend on the spatial distribution of iron even for the same iron concentration and volume susceptibility. Similarly, in vitro experiments demonstrate that R2 and R2* measurements depend on the microscopic spatial distribution of iron whereas the quantitative susceptibility mapping (QSM) susceptibility estimates reflect iron concentration without sensitivity to spatial distribution. CONCLUSIONS: R2 and R2* for iron quantification depend on the spatial distribution or iron. QSM-based estimation of iron concentration is insensitive to the microscopic spatial distribution of iron, potentially providing a distribution independent measure of iron concentration.