Application of the magnetic resonance 3D multiecho Dixon sequence for quantifying hepatic iron overload and steatosis in patients with thalassemia.

OBJECTIVE: To investigate the feasibility and diagnostic efficacy of a 3D multiecho Dixon (qDixon) research application for simultaneously quantifying the liver iron concentration (LIC) and steatosis in thalassemia patients. MATERIALS AND METHODS: This prospective study enrolled participants with thalassemia who underwent 3 T MRI of the liver for the evaluation of hepatic iron overload. The imaging protocol including qDixon and conventional T2* mapping based on 2D multiecho gradient echo (ME GRE) sequences respectively. Regions of interest (ROIs) were drawn in the liver on the qDixon maps to obtain R2* and proton density fat fraction (PDFF). The reference R2* value was measured and calculated on conventional T2* mapping using the CMRtools software. Correlation analysis, Linear regression analysis, and Bland-Altman analysis were performed. RESULTS: 84 patients were finally included in this study. The median R2*-ME-GRE was 366.97 (1/s), range [206.68 (1/s), 522.20 (1/s)]. 8 patients had normal hepatic iron deposition, 16 had Insignificant, 42 had mild, 18 had moderate. The median of R2*-qDixon was 376.88 (1/s) [219.33 (1/s), 491.75 (1/s)]. A strong correlation was found between the liver R2*-qDixon and the R2*-ME-GRE (r = 0.959, P < 0.001). The median value of PDFF was 1.76% (1.10%, 2.95%). 8 patients had mild fatty liver, and 1 had severe fatty liver. CONCLUSION: MR qDixon research sequence can rapidly and accurately quantify liver iron overload, that highly consistent with the measured via conventional GRE sequence, and it can also simultaneously detect hepatic steatosis, this has great potential for clinical evaluation of thalassemia patients.

Segmental quantification of hepatic lipid content based on volumetric MRI data in patients with suspected iron overload.

PURPOSE: To investigate the segmental distribution of hepatic fat fraction, determined with MRI (MR proton density fat fraction, short MR-PDFF) in patients suspected of having liver iron overload. METHODS: The liver of 44 patients examined with MRI using a 3D multi-echo gradient-echo sequence was segmented semiautomatically and subdivided into nine segments (segment 4 divided in 4a and 4b). Segmental fat content was determined on MR-PDFF maps. Whole-liver steatosis grades were compared to those found in individual segments. Segmental MR-PDFF differences were tested for statistical significance. RESULTS: The most common diseases were thalassemia, various forms of anemia, and hereditary hemochromatosis. No patients suffered from fat metabolism disease. Iron overload was present in 37/44 (84 %) patients. For the whole liver, 22 patients showed a steatosis grade of 0, 21 patients were graded S1, and one patient had a steatosis grade of 2. The grade of steatosis was underestimated in 5 of 21 patients (24 %) in segment 8 and in 8 of 21 patients (38 %) in segment 7. Highly significant segmental MR-PDFF differences were detected with p < 0.00 001, e. g., comparing segment 2 to 5. Segments 1 to 3 had the highest fat content, segments 7 and 8 had the lowest. CONCLUSION: Our results suggest that the storage of fat in the liver is inhomogeneous, so that segment-wise differing fat concentrations were found. Fat distribution in patients with suspected hepatic iron overload was similar to living liver donors. However, it showed significant differences compared with the values published for NAFLD patients, which were less pronounced in the group with high average hepatic MR-PDFF values than in the group with normal lipid content. In patients suspected of having iron overload, segment 8, which is mainly targeted for biopsy, and segment 7 may underestimate steatosis grade. KEY POINTS: · A volumetric analysis of 3D MRI data of patients with suspected hepatic iron overload yielded a markedly elevated MR proton density fat fraction (MR-PDFF) in hepatic segments 1 to 3.. · This hepatic fat distribution, observed for the whole patient cohort, is similar to healthy living liver donors.. · The subgroup of patients with a high average MR-PDFF ≥ 6.5 % shows this effect with lower segmental deviations.. · In patients without fat metabolic disorders, the steatosis grade may be underestimated when taking biopsies in segment 8 or 7..

Preliminary Study of Confounder-Corrected Fat Fraction and R2* Mapping of Bone Marrow in Children With Acute Leukemia.

BACKGROUND: The bone marrow (BM) evaluation of acute leukemia (AL) mainly depends on invasive BM puncture biopsy. Noninvasive and accurate MR examination technology has potential clinical application value in the BM evaluation of AL patients. Multi-gradient-echo (MGRE) has been found useful to evaluate changes in BM fat and iron content, but has not yet been applied in AL. PURPOSE: To explore the diagnostic capability of BM infiltration of quantitative BM fat fraction (FF) and R2* values obtained from a 3D MGRE sequence in children with primary AL. STUDY TYPE: Prospective. POPULATION/SUBJECTS: Sixty-two pediatric patients with untreated AL and 68 healthy volunteers. AL patients were divided into acute lymphoblastic leukemia (ALL) (n = 39) and acute myeloid leukemia (AML) (n = 23) groups. FIELD STRENGTH/SEQUENCE: 3T, 3D chemical-shift-encoded multi-gradient-echo, T1WI, T2WI, T2_STIR. ASSESSMENT: BM FF and R2* values were assessed by manually drawing regions of interest at the L3, L4, ilium, and 1 cm below the bilateral trochanter of the femur (upper femur). STATISTICAL TESTS: Independent sample t-tests, variance analysis, Spearman correlation. RESULTS: BM FF and R2* at L3, L4, ilium, and upper femur, FFtotal and R2*total were significantly lower in the AL than control group. BM FF did not significantly differ between ALL and AML groups (PL3 = 0.060, PL4 = 0.086, Pilium = 0.179, Pupper femur = 0.149, and Ptotle = 0.097, respectively). The R2* was significantly lower in ALL group than AML group for L3, L4, and R2*total . BM FF was moderately positively correlated with R2* in ALL group, and strongly positively correlated in AML group. Area under the receiver operating characteristic curves showed that BM FF had higher AUC in AL, ALL, and AML (all AUC = 1.000) than R2* (0.976, 0.996, and 0.941, respectively). DATA CONCLUSION: MGRE-MRI mapping can be applied to measure BM FF and R2* values, and help evaluate BM infiltration and iron storage in children with AL. EVIDENCE LEVEL: 1 Technical Efficacy: 2.

Chemical Shift MRI Monitoring of Chemoembolization Delivery for Hepatocellular Carcinoma: Multicenter Feasibility of Initial Clinical Translation.

Purpose To demonstrate the feasibility of using chemical shift fat-water MRI methods to visualize and measure intrahepatic delivery of ethiodized oil to liver tumors following conventional transarterial chemoembolization (cTACE). Materials and Methods Twenty-eight participants (mean age, 66 years ± 8 [SD]; 22 men) with hepatocellular carcinoma (HCC) treated with cTACE were evaluated with follow-up chemical shift MRI in this Health Insurance Portability and Accountability Act-compliant prospective, institutional review board-approved study. Uptake of ethiodized oil was evaluated at 1-month follow-up chemical shift MRI. Measurements of tumor size (MRI and CT), attenuation and enhancement (CT), fat content percentage, and tumor:normal ratio (MRI) were compared by lesion for responders versus nonresponders, as assessed with modified Response Evaluation Criteria in Solid Tumors and European Association for the Study of the Liver (EASL) criteria. Adverse events and overall survival by the Kaplan-Meier method were secondary end points. Results Focal tumor ethiodized oil retention was 46% (12 of 26 tumors) at 24 hours and 47% (18 of 38 tumors) at 1 month after cTACE. Tumor volume at CT did not differ between EASL-defined responders and nonresponders (P = .06). Tumor ethiodized oil volume measured with chemical shift MRI was statistically significantly higher for EASL-defined nonresponders (P = .02). Doxorubicin dosing (P = .53), presence of focal fat (P = .83), and a combined end point of focal fat and low doxorubicin dosing (P = .97) did not stratify overall survival after cTACE. Conclusion Chemical shift MRI allowed for assessment of tumor delivery of ethiodized oil out to 1 month after cTACE in participants with HCC and demonstrated tumor ethiodized oil volume as a potential tool for stratification of tumor response by EASL criteria. Keywords: MRI, Chemical Shift Imaging, CT, Hepatic Chemoembolization, Ethiodized Oil Clinicaltrials.gov registration no.: NCT02173119 Supplemental material is available for this article. © RSNA, 2023.

A Faster Prostate MRI: Comparing a Novel Denoised, Single-Average T2 Sequence to the Conventional Multiaverage T2 Sequence Regarding Lesion Detection and PI-RADS Score Assessment.

BACKGROUND: The T2 w sequence is a standard component of a prostate MRI examination; however, it is time-consuming, requiring multiple signal averages to achieve acceptable image quality. PURPOSE/HYPOTHESIS: To determine whether a denoised, single-average T2 sequence (T2 -R) is noninferior to the standard multiaverage T2 sequence (T2 -S) in terms of lesion detection and PI-RADS score assessment. STUDY TYPE: Retrospective. POPULATION: A total of 45 males (age range 60-75 years) who underwent clinically indicated prostate MRI examinations, 21 of whom had pathologically proven prostate cancer. FIELD STRENGTH/SEQUENCE: A 3 T; T2 w FSE, DWI with ADC maps, and dynamic contrast-enhanced images with color-coded perfusion maps. T2 -R images were created from the raw data utilizing a single "average" with iterative denoising. ASSESSMENT: Nine readers randomly assessed complete exams including T2 -R and T2 -S images in separate sessions. PI-RADS version 2.1 was used. All readers then compared the T2 -R and T2 -S images side by side to evaluate subjective preference. An additional detailed image quality assessment was performed by three senior level readers. STATISTICAL TESTS: Generalized linear mixed effects models for differences in lesion detection, image quality features, and overall preference between T2 -R and T2 -S sequences. Intraclass correlation coefficients (ICC) were used to assess reader agreement for all comparisons. A significance threshold of P = 0.05 was used for all statistical tests. RESULTS: There was no significant difference between sequences regarding identification of lesions with PI-RADS ≥3 (P = 0.10) or PI-RADS score (P = 0.77). Reader agreement was excellent for lesion identification (ICC = 0.84). There was no significant overall preference between the two sequences regarding image quality (P = 0.07, 95% CI: [-0.23, 0.01]). Reader agreement was good regarding sequence preference (ICC = 0.62). DATA CONCLUSION: Use of single-average, denoised T2 -weighted images was noninferior in prostate lesion detection or PI-RADS scoring when compared to standard multiaverage T2 -weighted images. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.

Volumetric Evaluation of 3D Multi-Gradient-Echo MRI Data to Assess Whole Liver Iron Distribution by Segmental R2* Analysis: First Experience.

PURPOSE: MR transverse relaxation rate R2* has been shown to be useful for monitoring liver iron overload. A sequence enabling acquisition of the whole liver in a single breath hold is now available, thus allowing volumetric hepatic R2* distribution studies. We evaluated the feasibility of computer-assisted whole liver segmentation of 3 D multi-gradient-echo MRI data, and compared whole liver R2* determination to analyzing only a single slice. Also, segmental R2* differences were studied. MATERIALS AND METHODS: The liver of 44 patients, investigated by multi-gradient echo MRI at 1.5 T, was segmented and divided into nine segments. Segmental R2* values were examined for all patients together and with respect to two criteria: average R2* values, and reason for iron overload. Correlation of single-slice and volumetric data was tested with Spearman's rank test, segmental and group differences were evaluated by analysis of variance. RESULTS: Whole-liver R2* values correlated excellent to single slice data (p < 0.001). The lowest R2* occurred in segment 1 (S1), differences of S1 with regard to other segments were significant in five cases and highly significant in two cases. Patients with high average R2* showed significant differences between S1 and segments 2, 6, and 7. Disease-related differences with respect to S1 were significant in segments 3 to 5 and 7. CONCLUSION: Our results suggest inhomogeneous hepatic iron distribution. Low R2* in S1 may be explained by its special vascularization. KEY POINTS: · Hepatic R2* distribution is not as homogeneous as previously thought.. · Liver segments might have a functional relevance.. · Segmental and total liver R2* values coincide best in segment 8.. CITATION FORMAT: · Wunderlich AP, Cario H, Kannengießer S et al. Volumetric Evaluation of 3D Multi-Gradient-Echo MRI Data to Assess Whole Liver Iron Distribution by Segmental R2* Analysis: First Experience. Fortschr Röntgenstr 2023; 195: 224 - 233.

Hepatic Iron Quantification Using a Free-Breathing 3D Radial Gradient Echo Technique and Validation With a 2D Biopsy-Calibrated R2* Relaxometry Method.

BACKGROUND: Hepatic iron content (HIC) is an important parameter for the management of iron overload. Non-invasive HIC assessment is often performed using biopsy-calibrated two-dimensional breath-hold Cartesian gradient echo (2D BH GRE) R2* -MRI. However, breath-holding is not possible in most pediatric patients or those with respiratory problems, and three-dimensional free-breathing radial GRE (3D FB rGRE) has emerged as a viable alternative. PURPOSE: To evaluate the performance of a 3D FB rGRE and validate its R2* and fat fraction (FF) quantification with 3D breath-hold Cartesian GRE (3D BH cGRE) and biopsy-calibrated 2D BH GRE across a wide range of HICs. STUDY TYPE: Retrospective. SUBJECTS: Twenty-nine patients with hepatic iron overload (22 females, median age: 15 [5-25] years). FIELD STRENGTH/SEQUENCE: Three-dimensional radial and 2D and 3D Cartesian multi-echo GRE at 1.5 T. ASSESSMENT: R2* and FF maps were computed for 3D GREs using a multi-spectral fat model and 2D GRE R2* maps were calculated using a mono-exponential model. Mean R2* and FF values were calculated via whole-liver contouring and T2* -thresholding by three operators. STATISTICAL TESTS: Inter- and intra-observer reproducibility was assessed using Bland-Altman and intraclass correlation coefficient (ICC). Linear regression and Bland-Altman analysis were performed to compare R2* and FF values among the three acquisitions. One-way repeated-measures ANOVA and Wilcoxon signed-rank tests, respectively, were used to test for significant differences between R2* and FF values obtained with different acquisitions. Statistical significance was assumed at P < 0.05. RESULTS: The mean biases and ICC for inter- and intra-observer reproducibility were close to 0% and >0.99, respectively for both R2* and FF. The 3D FB rGRE R2* and FF values were not significantly different (P > 0.44) and highly correlated (R2 ≥ 0.98) with breath-hold Cartesian GREs, with mean biases ≤ ±2.5% and slopes 0.90-1.12. In non-breath-holding patients, Cartesian GREs showed motion artifacts, whereas 3D FB rGRE exhibited only minimal streaking artifacts. DATA CONCLUSION: Free-breathing 3D radial GRE is a viable alternative in non-breath-hold patients for accurate HIC estimation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Magnetic Resonance Elastography for Assessing Fibrosis in Patients with Crohn's Disease: A Pilot Study.

BACKGROUND: Patients with Crohn's disease can develop intestinal strictures, containing various degrees of inflammation and fibrosis. Differentiation of the main component of a stricturing lesion is the key for defining the therapeutic management. AIMS: We assessed for the first time the accuracy of magnetic resonance elastography in detecting intestinal fibrosis and predicting clinical course in patients with Crohn's disease. METHODS: This was a prospective study of adult patients with Crohn's disease and magnetic resonance imaging examination, including magnetic resonance elastography, between April 2019 and February 2020. The association between the bowel stiffness value and the degree of fibrosis was evaluated. The relationship between the stiffness value and the occurrence of clinical events was also investigated. RESULTS: A total of 69 patients were included. The stiffness value measured by magnetic resonance elastography was correlated with the degree of fibrosis (p < 0.001). A bowel stiffness ≥ 3.57 kPa predicted the occurrence of clinical events with an area under the curve of 0.82 (95% CI 0.71-0.93). Bowel stiffness ≥ 3.57 kPa was associated with an increased risk of clinical events (p < 0.0001). CONCLUSION: In Crohn's disease, magnetic resonance elastography is a reliable tool for detecting intestinal fibrosis and predicting a worse disease outcome.

Iterative denoising accelerated 3D SPACE FLAIR sequence for brain MR imaging at 3T.

PURPOSE: The purpose of this study was to prospectively evaluate image quality of three-dimensional fluid attenuated inversion recovery (3D-FLAIR) sequence acquired with a high acceleration factor and reconstructed with iterative denoising (ID) for brain magnetic resonance imaging (MRI) at 3-T. MATERIAL AND METHODS: Patients with brain tumor who underwent brain MRI were consecutively included. Two 3D-FLAIR sequences were successively performed for each patient. A first conventional FLAIR acquisition (conv-FLAIR) was performed with an acceleration factor of 6. The second acquisition was performed with an increased acceleration factor of 9. Two series one without ID (acc-FLAIR) and one with ID (acc-FLAIR-ID) were reconstructed. Two neuroradiologists independently assessed image quality, deep brain nuclei visualization and white matter/gray matter (WM/GM) differentiation on a 4-point scale. RESULTS: Thirty patients with brain tumor were consecutively included in this study. There were 16 women and 14 men with a mean age of 54 ± 17 (SD) years (range: 22-78 years). Scanning time of Acc-FLAIR-ID and Acc-FLAIR (4 min 40 sec) was 37% shorter than that of conv-FLAIR (2 min 50 sec) (P < 0.01). Improved image quality score was significantly different for both conv-FLAIR and acc-FLAIR-ID compared to acc-FLAIR (P < 0.01 for both). WM/GM differentiation score of conv-FLAIR was not significantly different compared to acc-FLAIR-ID (P = 0.10). Improved WM/GM differentiation score was different for both sequences compared to acc-FLAIR (P = 0.017 and P < 0.001). Deep brain nuclei visualization score was not different between conv-FLAIR and acc-FLAIR-ID (P = 0.71). However, the improved deep brain nuclei visualization score was significantly different for both sequences compared to acc-FLAIR (P < 0.001 for both). CONCLUSION: Scanning time of 3D-FLAIR sequence using a high acceleration factor reconstructed with ID algorithm can be reduced by 37% while preserving image quality for brain MRI.

T2-weighted Imaging of the Breast at 1.5T Using Simultaneous Multi-slice Acceleration.

AIM: To evaluate the image quality and time saving using simultaneous multi-slice (SMS)-accelerated T2-weighted turbo spin echo (TSE) sequences compared to standard T2 TSE sequences in breast magnetic resonance imaging (MRI). PATIENTS AND METHODS: Thirty patients were examined with an SMS-accelerated T2 TSE sequence and a standard T2 TSE sequence as part of a breast MRI protocol at 1.5T. Image quality, signal homogeneity and tissue delineation were evaluated. For quantitative assessment, the signal-to-noise ratio (SNR) was measured from representative SNR maps. RESULTS: There were no significant differences regarding tissue delineation and signal homogeneity. Image quality was rated equal at the chest wall and the breasts but decreased in the axilla on SMS-T2 TSE (p=0.01) with a simultaneous decrease of SNR (p=0.03). This did not significantly impact the overall image quality (p=0.2). The acquisition time for SMS-T2 TSE was 48% shorter compared to standard T2 TSE. CONCLUSION: SMS-acceleration for T2-weighted imaging of the breast at 1.5T substantially reduces acquisition time while maintaining comparable quantitative and qualitative image quality. This may pave the way for protocol abbreviation especially in a high-throughput clinical workspace.

Comparison of Inline R2* MRI versus FerriScan for liver iron quantification in patients on chelation therapy for iron overload: preliminary results.

OBJECTIVES: MRI quantification of liver iron concentration (LIC) using R2 or R2* relaxometry requires offline post-processing causing reporting delays, administrative overhead, and added costs. A prototype 3D multi-gradient-echo pulse sequence, with inline post-processing, allows immediate calculation of LIC from an R2* map (inline R2*-LIC) without offline processing. We compared inline R2*-LIC to FerriScan and offline R2* calibration methods. METHODS: Forty patients (25 women, 15 men; age 18-82 years), prospectively underwent FerriScan and the prototype sequence, which produces two R2* maps, with and without fat modeling, as well as an inline R2*-LIC map derived from the R2* map with fat modeling, with informed consent. For each map, the following contours were drawn: ROIs, whole-axial-liver contour, and an exact copy of contour utilized by FerriScan. LIC values from the FerriScan report and those calculated using an alternative R2 calibration were the reference standards. Results were compared using Pearson and interclass correlation coefficients (PCC, ICC), linear regression, Bland-Altman analysis, and estimation of area under the receiver operator curve (ROC-AUC). RESULTS: Inline R2*-LIC demonstrated good agreement with the reference standards. Compared to FerriScan, inline R2*-LIC with whole-axial-liver contour, ROIs, and FerriScan contour demonstrated PCC of 94.8%, 94.8%, and 92%; ICC 93%, 92.7%, and 90.2%; regression slopes 1.004, 0.974, and 1.031; mean bias 5.54%, 10.91%, and 0.36%; and ROC-AUC estimates 0.903, 0.906, and 0.890 respectively. Agreement was maintained when adjusted for sex, age, diagnosis, liver fat content, and fat-water swap. CONCLUSION: Inline R2*-LIC provides robust and comparable quantification of LIC compared to FerriScan, without the need for offline post-processing. KEY POINTS: • In patients being treated for iron overload with chelation therapy, liver iron concentration (LIC) is regularly assessed in order to monitor and adjust therapy. • Magnetic resonance imaging (MRI) is commonly used to quantify LIC. Several R2 and R2* methods are available, all of which require offline post-processing. • A novel R2* MRI method allows for immediate calculation of LIC and provides comparable quantification of LIC to the FerriScan and recently published alternative R2* methods.

Performance of different Dixon-based methods for MR liver iron assessment in comparison to a biopsy-validated R2* relaxometry method.

OBJECTIVES: To prospectively evaluate a 3D-multiecho-Dixon sequence with inline calculation of proton density fat fraction (PDFF) and R2* (qDixon), and an improved version of it (qDixon-WIP), for the MR-quantification of hepatic iron in a clinical setting. METHODS: Patients with increased serum ferritin underwent 1.5-T MRI of the liver for the evaluation of hepatic iron overload. The imaging protocol for R2* quantification included as follows: (1) a validated, 2D multigradient-echo sequence (initial TE 0.99 ms, R2*-ME-GRE), (2) a 3D-multiecho-Dixon sequence with inline calculation of PDFF and R2* (initial TE 2.38 ms, R2*-qDixon), and optionally (3) a prototype (works-in-progress, WIP) version of the latter (initial TE 1.04 ms, R2*-qDixon-WIP) with improved water/fat separation and noise-corrected parameter fitting. For all sequences, three manually co-registered regions of interest (ROIs) were placed in the liver. R2* values were compared and linear regression analysis and Bland-Altman plots calculated. RESULTS: Forty-six out of 415 patients showed fat-water (F/W) swap with qDixon and were excluded. A total of 369 patients (mean age 52 years) were included; in 203/369, the optional qDixon-WIP was acquired, which showed no F/W swaps. A strong correlation was found between R2*-ME-GRE and R2*-qDixon (r2 = 0.92, p < 0.001) with Bland-Altman revealing a mean difference of - 3.82 1/s (SD = 21.26 1/s). Correlation between R2*-GRE-ME and R2*-qDixon-WIP was r2 = 0.95 (p < 0.001) with Bland-Altman showing a mean difference of - 0.125 1/s (SD = 30.667 1/s). CONCLUSIONS: The 3D-multiecho-Dixon sequence is a reliable tool to quantify hepatic iron. Results are comparable with established relaxometry methods. Improvements to the original implementation eliminate occasional F/W swaps and limitations regarding maximum R2* values. KEY POINTS: • The 3D-multiecho-Dixon sequence for 1.5 T is a reliable tool to quantify hepatic iron. • Results of the 3D-multiecho-Dixon sequence are comparable with established relaxometry methods. • An improved version of the 3D-multiecho-Dixon sequence eliminates minor drawbacks.

Liver Iron Content Determination Using a Volumetric Breath-Hold Gradient-Echo Sequence With In-Line R2 * Calculation.

BACKGROUND: Liver iron overload is a serious condition occurring in patients requiring blood transfusions (eg, in thalassemia and different forms of anemia) or with dysfunctional iron resorption, since there is no physiological mechanism to excrete iron. Above a certain level of iron concentration, chelation therapy is indicated. To monitor therapy success, liver iron content should be assessed regularly. A noninvasive method is important for patient management. Existing MRI methods suffer from long acquisition times and cost. PURPOSE: To study the correlation of liver iron content (LIC) reference values to liver R2 * determined using a 3D breath-hold multigradient echo (GRE) MRI sequence, employing accelerated acquisition by parallel imaging and in-line R2 * calculation. STUDY TYPE: Prospective. POPULATION: In all, 117 patients (22.1 ± 14.1 years, 66 men) suspected of iron overload. SEQUENCE: GRE. FIELD STRENGTH: 1.5T. ASSESSMENT: For comparison, a regulatory-approved method with a considerably longer scan time was used, providing LIC reference values. Participants were divided into a calibration group (65 participants), analyzed independently by two observers, and a validation group (52 participants). STATISTICAL TESTS: Linear correlation parameters were evaluated for R2 * values with LIC reference values, and for LIC determined from R2 * for validation group participants with LIC reference values. Sensitivity/specificity for clinical relevant LIC thresholds were analyzed. Interobserver variability was determined by intraclass correlation coefficient (ICC). RESULTS: Interobserver agreement was excellent, with an ICC of 0.99, P < 0.001. Good correlation (R2 = 0.89) and congruence of LIC values obtained with our method to LIC reference values was found, and almost identical diagnostic accuracy. Sensitivity/specificity were 0.98/0.67 for the diagnostic relevant LIC threshold of 4.5 mg/g and 1.0/0.95 for the threshold of 7 mg/g. DATA CONCLUSION: MRI acquisition times for determination of LIC can be significantly reduced by the use of comprehensive in-line R2 * map generation without compromising diagnostic accuracy. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Non-invasive tumor decoding and phenotyping of cerebral gliomas utilizing multiparametric 18F-FET PET-MRI and MR Fingerprinting.

OBJECTIVES: The introduction of the 2016 WHO classification of CNS tumors has made the combined molecular and histopathological characterization of tumors a pivotal part of glioma patient management. Recent publications on radiogenomics-based prediction of the mutational status have demonstrated the predictive potential of imaging-based, non-invasive tissue characterization algorithms. Hence, the aim of this study was to assess the potential of multiparametric 18F-FET PET-MRI including MR fingerprinting accelerated with machine learning and radiomic algorithms to predict tumor grading and mutational status of patients with cerebral gliomas. MATERIALS AND METHODS: 42 patients with suspected primary brain tumor without prior surgical or systemic treatment or biopsy underwent an 18F-FET PET-MRI examination. To differentiate the mutational status and the WHO grade of the cerebral tumors, support vector machine and random forest were trained with the radiomics signature of the multiparametric PET-MRI data including MR fingerprinting. Surgical sampling served as a gold standard for histopathological reference and assessment of mutational status. RESULTS: The 5-fold cross-validated area under the curve in predicting the ATRX mutation was 85.1%, MGMT mutation was 75.7%, IDH1 was 88.7%, and 1p19q was 97.8%. The area under the curve of differentiating low-grade glioma vs. high-grade glioma was 85.2%. CONCLUSION: 18F-FET PET-MRI and MR fingerprinting enable high-quality imaging-based tumor decoding and phenotyping for differentiation of low-grade vs. high-grade gliomas and for prediction of the mutational status of ATRX, IDH1, and 1p19q. These initial results underline the potential of 18F-FET PET-MRI to serve as an alternative to invasive tissue characterization.

Glucose dysregulation in patients with iron overload: is there a relationship with quantitative pancreas and liver iron and fat content measured by MRI?

OBJECTIVES: The aim was to investigate the relationship between pancreatic and hepatic iron and fat to glucose metabolism in patients with iron overload and address conflicting results in literature as regards the relationship between pancreas iron and glucose dysregulation. METHODS: We retrospectively evaluated pancreatic and hepatic R2*, fat fraction (FF), liver iron concentration (LIC), and glucose metabolism in 105 patients with iron overload obtained with a multi-echo gradient echo R2* technique and assessed the correlation between pancreatic R2* and FF to glucose dysregulation. RESULTS: There were no significant differences in pancreatic R2*, liver R2*, and FF in patients with iron overload and glucose dysregulation compared to those with normoglycemia (p = 0.435, p = 0.674, and p = 0.976), whereas pancreatic FF was significantly higher, 23.5% vs 16.7% respectively (p = 0.011). Pancreatic FF and R2* demonstrated an area under the curve of 0.666 and 0.571 for discriminating glucose dysregulation. Pancreatic FF of 26.2% yielded specificity and sensitivity of 80% and 45% for prediction of glucose dysregulation. Pancreatic R2* weakly correlated with pancreatic FF, r = 0.388 (p < 0.001), and liver R2*, r = 0.201 (p = 0.033), and showed no correlation with hepatic FF r = -0.013 (p = 0.892) or LIC categories (p = 0.493). CONCLUSION: Pancreatic FF but not pancreatic R2* was associated with glucose dysregulation in patients with iron overload. Prior studies reporting correlation of pancreatic R2* to glucose dysregulation likely relate from inadequate MRI technique or analysis employed, which unlike our study did not perform simultaneous measurements of fat and iron essential to avoid their confounding effects during quantitative analysis. KEY POINTS: • Pancreatic fat fraction, unlike iron, is associated with glucose dysregulation in iron overload. • Simultaneous measurement of pancreatic iron and fat content with MRI is essential to avoid confounding effects of one another during quantitative analysis. • Pancreatic fat fraction could be utilized to predict glucose dysregulation in iron overload states.

Detection of hepatic steatosis and iron content at 3 Tesla: comparison of two-point Dixon, quantitative multi-echo Dixon, and MR spectroscopy.

PURPOSE: To compare qualitative results obtained from computer-aided dual-ratio analysis on T1-weighted two-point Dixon, with T2*-corrected multi-echo Dixon and T2-corrected multi-echo single-voxel MR spectroscopy sequence (MRS) for evaluation of liver fat and iron at 3T. METHODS AND MATERIALS: This retrospective, HIPAA-compliant, IRB-approved study included 479 patients with known or suspected liver disease. Two-point Dixon, multi-echo Dixon, and MR spectroscopy sequences were performed for each patient at 3T. A receiver-operating characteristic analysis was performed to compare the diagnostic performance in 80 patients using biopsy as the standard. Sensitivity, specificity, PPV, and NPV of qualitative two-point Dixon results, multi-echo Dixon (PDFF and R2*), and MRS (fat fraction and R2 water) for detection of hepatic steatosis and siderosis were assessed. RESULTS: Fat fractions obtained from MRS and multi-echo Dixon have equivalent accuracy for detection of hepatic steatosis (AUC, sensitivity and specificity: 0.90 vs 0.88, 0.77 vs. 0.82, and 0.90 vs. 0.82), but the optimal cutoff value is higher for MRS (6.05% vs. 3.4%). The dual-ratio Dixon discrimination technique showed high negative predictive value for detection of hepatic steatosis and siderosis (0.90 and 0.94, respectively). R2* from multi-echo Dixon and R2water from MRS have equivalent accuracy for detection of iron overload at 3T (AUC 0.89 vs. 0.88). The optimal cutoff for R2* and R2water are 60.5 s-1 and 40.85 s-1, respectively. CONCLUSION: The computer-aided dual-ratio discrimination with two-point Dixon is a useful qualitative screening tool with high negative predictive value for hepatic steatosis and iron overload. Multi-echo Dixon and MRS have similar accuracy for detection of hepatic steatosis and iron overload at 3 Tesla.

Improved accuracy of apparent diffusion coefficient quantification using a fully automatic noise bias compensation method: Preliminary evaluation in prostate diffusion weighted imaging.

Noise in diffusion magnetic resonance imaging can introduce bias in apparent diffusion coefficient (ADC) quantification. Previous studies proposed methods that are site-specific techniques as research tools with limited availability and typically require manual intervention, not completely ready to use in the clinical environment. The purpose of this study was to develop a fully automatic computational method to correct noise bias in ADC quantification and perform a preliminary evaluation in the clinical prostate diffusion weighted imaging (DWI). Using a pseudo replica approach for the noise map calculation as well as a direct mapping and a stepwise Chebychev polynomial modelling approach for the ADC fitting, a fully automatic noise-bias-compensated ADC calculation method was proposed and implemented both on the scanner and offline. The proposed method was validated in a computer simulation and a standardized diffusion phantom with ground-truth values. Two in vivo studies were performed to evaluate the proposed method in the clinical environment. The first in vivo study performed acquisitions using a clinically routine prostate DWI protocol on 29 subjects to evaluate the consistency between simulated and empirical results. In the second in vivo study, prostate ADC values of 14 subjects were compared between data acquired with external coils only and reconstructed with the proposed method vs. acquired with external combined with endorectal coils and reconstructed with the conventional method. In statistical analyses, p < 0.05 was regarded as significantly different. In the computer simulation, the proposed method showed smaller error percentage than the other methods and was significantly different (p < 2.2 × 10-16). With low signal-to-noise ratio (SNR), the conventional method underestimated ADC values compared to the ground truth values of the diffusion phantom, while the results of the proposed method were more consistent with the ground truth values. Statistical analyses showed no significant differences between measured and simulated results in the first in vivo study (p = 0.5618). Data from the second in vivo study showed that agreement between ADC measured with external coils only and combined coils was improved for the proposed method (mean bias: 0.04 × 10-3 mm2/s, 95% confidence interval (CI) = [-0.01, 0.09] × 10-3 mm2/s, p = 0.187), compared to the conventional method (mean bias: -0.12 × 10-3 mm2/s, 95% CI = [-0.17, -0.06] × 10-3 mm2/s, p < 0.0001). The proposed method compensates noise bias in low-SNR diffusion-weighted acquisitions and results show improved ADC quantification accuracy in the prostate. This method may be suitable for both clinical imaging and research utilizing ADC quantification.

MR elastography of liver at 3 Tesla: comparison of gradient-recalled echo (GRE) and spin-echo (SE) echo-planar imaging (EPI) sequences and agreement across stiffness measurements.

PURPOSE: To compare 2D gradient-recalled echo (GRE) and 2D spin-echo (SE) echo-planar imaging (EPI) MR elastography (MRE) for measurement of hepatic stiffness in adult patients with known or suspected liver disease at 3 Tesla. MATERIALS AND METHODS: Three hundred and eighty-seven consecutive patients underwent MRE of the liver at 3 Tesla with 2D-GRE and 2D-SE-EPI sequences. 'Mean liver stiffness (LS)' calculated by averaging 3 ROIs in the right lobe, 'Maximum LS' calculated by an ROI in the right lobe; and 'Freehand LS' calculated by an ROI in the entire liver were measured by two independent readers. Inter-observer and inter-class variability in stiffness measurements were assessed. Stiffness values were correlated with degree of liver fibrosis (METAVIR scores) in 97 patients who underwent biopsy. The diagnostic performance was compared by a receiver-operating characteristic analysis. RESULTS: The technical failure rate was 2.8% for 2D-SE-EPI (11/387) and 4.1% for 2D-GRE (16/387, 9 had R2* > 80 s-1 indicating iron overload). There is high reproducibility for both GRE and SE-EPI variants (ICC = 0.84-0.94 for both GRE and SE-EPI MRE). The highest sensitivity, specificity, and accuracy of differentiating mild fibrosis (F0-F2) from advanced fibrosis (F3-F4) are 0.84 (GRE Freehand measurement), 0.92 (GRE Maximum stiffness measurement), and 0.88 (GRE Freehand measurement), respectively. CONCLUSIONS: High intra-class correlation and intra-reader correlation are seen on measured hepatic stiffness for both 2D-GRE and 2D-SE-EPI MRE. 2D-SE-EPI has lower failure rate. Diagnostic performance of both sequences is equivalent, with highest sensitivity for 2D-GRE Freehand stiffness measurement, and highest specificity 2D-GRE Maximum stiffness measurement.

Prospective Evaluation of an R2* Method for Assessing Liver Iron Concentration (LIC) Against FerriScan: Derivation of the Calibration Curve and Characterization of the Nature and Source of Uncertainty in the Relationship.

BACKGROUND: FerriScan is the method-of-choice for noninvasive liver iron concentration (LIC) quantification. However, it has a number of drawbacks including cost and expediency. PURPOSE/HYPOTHESIS: To characterize an R2*-based MRI technique that may potentially be used as an alternative to FerriScan. This was accomplished through the derivation of a calibration curve that characterized the relationship between FerriScan-derived LIC and R2*. The nature and source of uncertainty in this curve were investigated. It was hypothesized that the source of uncertainty is heterogeneity of LIC across the liver. STUDY TYPE: Prospective. SUBJECTS: In all, 125 patients (69 women, 56 men) undergoing chelation treatment for iron overload prospectively underwent FerriScan and R2* MRI during the same exam. FIELD STRENGTH/SEQUENCE: Pulse sequences included 2D multislice spin-echo pulse for FerriScan, and a prototype 3D 6-echo gradient echo acquisition for R2* mapping at 1.5T. ASSESSMENT: A linear calibration curve was derived from the relationship between FerriScan-derived LIC estimates and R2* through least-squares fitting. STATISTICAL TESTS: The nature of the uncertainty in the curve was characterized through tests of normality and homoscedasticity. The source of uncertainty was tested by comparing the magnitude of LIC variation over the FerriScan ROI to the observed uncertainty in the R2*-derived LIC estimates. RESULTS: A linear relationship between logarithmically transformed FerriScan-derived LIC and R2* (log{FerriScan-derived LIC} = 1.029 log{R2*} - 3.822) was confirmed. Uncertainty was random, with a behaviour that was normal and homoscedastic. The source of uncertainty was confirmed as iron heterogeneity across the liver. The nontransformed calibration curve was: FerriScan-derived LIC = 0.0266⋅R2*, with a constant coefficient-of-variation of 0.32. DATA CONCLUSION: FerriScan and R2* techniques were found to provide equivalent quantification of LIC in this study. Any difference in accuracy or precision was at a level lower than the uncertainty caused by variation in LIC over the liver. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1467-1474.

Quantitative analysis of hepatic iron in patients suspected of coexisting iron overload and steatosis using multi-echo single-voxel magnetic resonance spectroscopy: Comparison with fat-saturated multi-echo gradient echo sequence.

BACKGROUND: The coexistence of hepatic iron and fat is common in patients with hyperferritinemia, which plays an interactive and aggressive role in the progression of diseases (fibrosis, cirrhosis, and hepatocellular carcinomas). PURPOSE: To evaluate a modified high-speed T2 -corrected multi-echo, single voxel spectroscopy sequence (HISTOV) for liver iron concentration (LIC) quantification in patients with hyperferritinemia, with simultaneous fat fraction (FF) estimation. STUDY TYPE: Retrospective cohort study. POPULATION: Thirty-eight patients with hyperferritinemia were enrolled. FIELD STRENGTH/SEQUENCE: HISTOV, a fat-saturated multi-echo gradient echo (GRE) sequence, and a spin echo sequence (FerriScan) were performed at 1.5T. ASSESSMENT: R2 of the water signal and FF were calculated with HISTOV, and R2* values were derived from the GRE sequence, with R2 and LIC from FerriScan serving as the references. STATISTICAL TESTS: Linear regression, correlation analyses, receiver operating characteristic analyses, and Bland-Altman analyses were conducted. RESULTS: Abnormal hepatic iron load was detected in 32/38 patients, of whom 10/32 had coexisting steatosis. Strong correlation was found between R2* and FerriScan-LIC (R2 = 0.861), and between HISTOV-R2_ water and FerriScan-R2 (R2 = 0.889). Furthermore, HISTOV-R2_ water was not correlated with HISTOV-FF. The area under the curve (AUC) for HISTOV-R2_ water was 0.974, 0.971, and 1, corresponding to clinical FerriScan-LIC thresholds of 1.8, 3.2, and 7.0 mg/g dw, respectively. No significant difference in the AUC was found between HISTOV-R2_ water and R2* at any of the LIC thresholds, with P-values of 0.42, 0.37, and 1, respectively. HISTOV-LIC showed excellent agreement with FerriScan-LIC, with a mean bias of 0.00 ± 1.18 mg/g dw, whereas the mean bias between GRE-LIC and FerriScan-LIC was 0.53 ± 1.49 mg/g dw. DATA CONCLUSION: HISTOV is useful for the quantification and grading of liver iron overload in patients with hyperferritinemia, particularly in cases with coexisting steatosis. HISTOV-LIC showed no systematic bias compared with FerriScan-LIC, making it a promising alternative for iron quantification. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2018.