The value of the signal intensity of peritumoral tissue on Gd-EOB-DTPA dynamic enhanced MRI in assessment of microvascular invasion and pathological grade of hepatocellular carcinoma.

ABSTRACT: The aim of the study was to assess the potential role of preoperative gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) dynamic enhanced MR imaging for diagnosing microvascular invasion (MVI) and pathological grade of hepatocellular carcinoma (HCC).A total of 113 consecutive HCC patients confirmed by histopathology underwent preoperative Gd-EOB-DTPA dynamic enhanced MRI were included. Signal intensity (SI) of peritumoral, normal liver tissue and tumor parenchyma during arterial phase and hepatobiliary phase (HBP) were analyzed. The receiver operating characteristic (ROC) curves were performed to assess the potential diagnostic capability for MVI and pathological grade of HCC. Kaplan-Meier method was performed to estimate the recurrence-free survival rate and compared using the log rank test.SI ratio of peritumoral tissue to normal liver in arterial phase (SIAp/Al) was independently associated with MVI [odds ratio (OR) = 3.115, 95% confidence interval (CI): 1.867-5.198] and pathological grades (OR = 1.437, 95% CI: 1.042-1.981). The area under the curve (AUC) of SIAp/Al was equivalent to the SI of tumor parenchyma on arterial phase (SIAt) in distinguishing low and high pathological grades. However, the AUC of SIAp/Al (0.851) was larger than peritumoral hypointensity on HBP (0.668) for distinguishing MVI. The recurrence-free survival rate of HCC patients with SIAp/Al<1.1 was higher than HCC with SIAp/Al≥1.1(P = .025).The SIAp/Al in preoperative Gd-EOB-DTPA dynamic enhanced MR imaging is a potential diagnosis marker for MVI and pathological grade of HCC noninvasively. The higher SIAp/Al may predict the poor prognosis of HCC after surgery.

Noninvasive Assessment of Liver Fibrosis in Patients with Chronic Hepatitis B or C by Contrast-Enhanced Magnetic Resonance Imaging.

Background and Aim. To develop a noninvasive magnetic resonance imaging (MRI) method for evaluation of liver fibrosis. We evaluate the utility of hepatocyte-phase Gadoxetate disodium-enhanced magnetic resonance (MR) imaging in staging hepatic fibrosis and compare it with histological analysis as the reference standard (liver biopsy). Methods. Prospective cohort of 78 patients, who received Gadoxetate disodium dynamic contrast-enhanced MRI (DCE-MRI), were divided into three groups. The first group (n=19) was a control group of healthy individuals without liver injury and remaining 59 subjects were chronic hepatitis B and C patients who underwent liver biopsy. These patients were divided into the mild fibrosis F1-F2 (n=32) and advanced fibrosis F3-F4 (n=27) groups. Patients were examined by generated DCE-MRI in 20th minute. Variables such as liver surface changes, homogeneities, and quantitative contrast liver/spleen ratio-Q-LSCR were evaluated and these results were consequently compared between the three groups. Results. Gd-EOB-DTPA contrast-enhanced dynamic liver MRI examination (DCE-MRI) can in the 20th minute differentiate mild stage of liver fibrosis (F1-F2) from severe stage of liver fibrosis (F3-F4) on the basis of liver surface changes, homogeneities, and quantitative contrast liver/spleen ratio-Q-LSCR. Diagnostic MRI criteria were created and named MRI Triple test. This test correctly identified 96% of patients with F3-F4 fibrosis and 91% of patients with the F1-F2 fibrosis in the liver biopsy. This test correctly identified 42,1% of patients in the control group (presumed F0 fibrosis without liver disease). Spearman's rank correlation coefficient (r = 0,86, P < .001) confirmed high agreement of biopsy and MR Triple test. MR Triple test's sensitivity was 96.30% (95%CI 81.03% to 99.91%), specificity 90.62% (95%CI 74.98% to 98.02%), positive predictive value 89.66% (95%CI 74.64% to 96.23%), and negative predictive value 96.67% (95%CI 80.86% to 99.50%) for discrimination between F3-4 and F1-2 fibrosis on liver biopsy. Conclusions. Gd-EOB-DTPA contrast-enhanced MRI liver examination in 20th minute is able to reliably differentiate mild stage of liver fibrosis (F1-F2) from severe stage fibrosis (F3-F4) on the basis of Triple test (liver surface changes, homogeneities, and quantitative contrast liver/spleen ratio-Q-LSCR).

Assessment of liver fibrosis with gadoxetic acid-enhanced MRI: comparisons with transient elastography, ElastPQ, and serologic fibrosis markers.

OBJECTIVES: To compare the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging (MRI), ultrasonography (US)-based elastography, and serologic fibrosis markers in assessing the stage of liver fibrosis. MATERIALS AND METHODS: This retrospective study included 67 patients (55 male and 12 female; mean age 62.5 years) who underwent gadoxetic acid-enhanced MRI and liver stiffness measurements before liver biopsy or surgery between January 2014 and January 2018. Measurements were performed using transient elastography (TE), ultrasound shear wave elastography point quantification (ElastPQ), and blood tests. The following MRI-based fibrosis markers were assessed: contrast enhancement index (CEI), liver-spleen contrast ratio (LSC), liver-portal vein contrast ratio (LPC), and signal intensity ratio (SIR). The diagnostic performances of fibrosis markers were compared using the area under the receiver operating characteristic curve (AUC), with histopathologic fibrosis stage as the reference standard. RESULTS: The fibrosis stages were F0-F1 (n = 17), F2 (n = 7), F3 (n = 20), and F4 (n = 23). MRI-based fibrosis markers negatively correlated with histologic stage: CEI (r = -0.786); LSC (r = - 0.718); LPC (r = - 0.448); and SIR (r = - 0.617; all P < 0.001). For diagnosis of either significant liver fibrosis (≥ F2) or cirrhosis (F4), the CEI provided better diagnostic accuracy (AUC = 0.898 and 0.881) than the aspartate aminotransferase-to-platelet ratio index (APRI) (AUC = 0.699 and 0.715; all P < 0.05). The CEI displayed similar diagnostic accuracy for ≥ F2 or F4 when using TE (AUC = 0.866 and 0.884, both P > 0.05) or ElastPQ [AUC = 0.751 (P = 0.021) and AUC = 0.786 (P = 0.234)]. CONCLUSIONS: The CEI measured by gadoxetic acid-enhanced MRI allows the staging of liver fibrosis, with a diagnostic accuracy comparable to that of TE and superior to that of ElastPQ or APRI.

Incremental value of extracellular volume assessment by cardiovascular magnetic resonance imaging in risk stratifying patients with suspected myocarditis.

Cardiovascular magnetic resonance imaging (CMR) has become a key investigative tool in patients with suspected myocarditis. However, the prognostic implications of T1 mapping, including extracellular volume (ECV) calculation, is less clear. Patients with suspected myocarditis who underwent CMR evaluation, including T1 mapping at our institution were included. CMR findings including late gadolinium enhancement (LGE), left ventricular ejection fraction (LVEF), native T1 mapping, and ECV calculation were associated with first major adverse cardiac events (MACE). MACE included a composite of all-cause death, heart failure hospitalization, heart transplantation, documented sustained ventricular arrhythmia, and recurrent myocarditis. One hundred seventy-nine patients with a mean age of 49 ± 15 years were identified. Seventy nine individuals (44%) were female. Mean LVEF was 48 ± 16. At a median follow-up of 4.1 [interquartile-range (IQR) 2.2-6.1] years, 22 (12%) patients experienced a MACE. Mean ECV (per 10%) was significantly associated with MACE (HR 2.09, 95% CI 1.07-4.08, p = 0.031). Presence of ECV ≥ 35% demonstrated significant univariable association with MACE (HR 3.3, 95% CI 1.43-7.97, p = 0.005) and such association was maintained when adjusted to LVEF (HR 3.42, 95% CI 1.42-7.94, p = 0.006). ECV ≥ 35% portended a greater than threefold increased hazards to MACE adjusted to LGE presence (HR 3.14, 95% CI 1.29-7.36, p = 0.012). In patients without LGE, ECV ≥ 35% portended a greater than sixfold increased hazards (HR 6.6, p = 0.010). In the multivariable model including age, LVEF and LGE size, only ECV ≥ 35% maintained its significant association with outcome. ECV calculation by CMR is a useful tool in the risk stratification of patients with clinically suspected myocarditis, incremental to LGE and LVEF.

Feasibility of gadoxetate disodium enhanced 3D T1 MR cholangiography (MRC) with a specific inversion recovery prepulse for the assessment of the hepatobiliary system.

AIM: To compare the potential of a gadoxetate disodium enhanced navigator-triggered 3D T1 magnetic-resonance cholangiography (MRC) sequence with a specific inversion recovery prepulse to T2-weighted MRCP for assessment of the hepatobiliary system. MATERIALS AND METHODS: 30 patients (12 male, 18 female) prospectively underwent conventional navigator-triggered 3D turbo spin-echo T2-weighted MRCP and 3D T1 MRC with a specific inversion pulse to minimise signal from the liver 30 minutes after administration of gadoxetate disodium on a 1.5 T MRI system. For qualitative evaluation, biliary duct depiction was assessed segmentally following a 5-point Likert scale. Visualisation of hilar structures as well as image quality was recorded. Additionally, the extrahepatic bile ducts were assessed quantitatively by calculation of signal-to-noise ratios (SNR). RESULTS: The advantages of T1 3D MRC include reduced affection of image quality by bowel movement and robust depiction of the relative position of the extrahepatic bile ducts in relation to the portal vein and the duodenum compared to T2 MRCP. However, overall T1 3D MRC did not significantly (p > 0.05) improve the biliary duct depiction compared to T2 MRCP in all segments: Common bile duct 4.1 vs. 4.4, right hepatic duct 3.6 vs. 4.2, left hepatic duct 3.5 vs. 4.1. Image quality did not differ significantly (p > 0.05) between both sequences (3.6 vs. 3.5). SNR measurements for the hepatobiliary system did not differ significantly (p > 0.05) between navigator-triggered T1 3D MRC and T2 MRCP. CONCLUSIONS: This preliminary study demonstrates that T1 3D MRC of a specific inversion recovery prepulse has potential to complement T2 MRCP, especially for the evaluation of liver structures close to the hilum in the diagnostic work-up of the biliary system in patients receiving gadoxetate disodium.

Quantitative assessment of hepatic fibrosis in chronic hepatitis B and C: T1 mapping on Gd-EOB-DTPA-enhanced liver magnetic resonance imaging.

AIM: To assess the accuracy of Look-Locker on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for staging liver fibrosis in chronic hepatitis B/C (CHB/C). METHODS: We prospectively included 109 patients with CHB or CHC who underwent a 3.0-Tesla MRI examination, including T1-weighted and Look-Locker sequences for T1 mapping. Hepatocyte fractions (HeF) and relaxation time reduction rate (RE) were measured for staging liver fibrosis. A receiver operating characteristic analysis using the area under the receiver operating characteristic curve (AUC) was used to compare the diagnostic performance in predicting liver fibrosis between HeF and RE. RESULTS: A total of 73 patients had both pathological results and MRI information. The number of patients in each fibrosis stage was evaluated semiquantitatively according to the METAVIR scoring system: F0, n = 23 (31.5%); F1, n = 19 (26.0%); F2, n = 13 (17.8%); F3, n = 6 (8.2%), and F4, n = 12 (16.4%). HeF by EOB enhancement imaging was significantly correlated with fibrosis stage (r = -0.808, P < 0.05). AUC values for diagnosis of any (≥ F1), significant (≥ F2) or advanced (≥ F3) fibrosis, and cirrhosis (F4) using HeF were 0.837 (0.733-0.913), 0.890 (0.795-0.951), 0.957 (0.881-0.990), and 0.957 (0.882-0.991), respectively. HeF measurement was more accurate than use of RE in establishing liver fibrosis staging, suggesting that calculation of HeF is a superior noninvasive liver fibrosis staging method. CONCLUSION: A T1 mapping-based HeF method is an efficient diagnostic tool for the staging of liver fibrosis.

Assessment of myocardial fibrosis by late gadolinium enhancement imaging and biomarkers of collagen metabolism in chronic rheumatic mitral regurgitation.

BACKGROUND: In chronic rheumatic mitral regurgitation (CRMR), involvement of the myocardium in the rheumatic process has been controversial. Therefore, we sought to study the presence of fibrosis using late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) and biomarkers of collagen turnover in CRMR. METHODS: Twenty-two patients with CRMR underwent CMR and echocardiography. Serum concentrations of matrix metalloproteinase- 1 (MMP-1), tissue inhibitor of MMP-1 (TIMP- 1), MMP-1-to-TIMP-1 ratio, procollagen III N-terminal pro-peptide (PIIINP) and procollagen type IC peptide (PIP) were measured. RESULTS: Four patients had fibrosis on LGE-CMR. PICP and PIIINP concentrations were similar to those of the controls, however MMP-1 concentration was increased compared to that of the controls (log MMP-1 3.5 ± 0.7 vs 2.7 ± 0.9, p = 0.02). There was increased MMP-1 activity as the MMP-1-to- TIMP-1 ratio was higher in CRMR patients compared to the controls ( -1.2 ± 0.6 vs -2.1 ± 0.89, p = 0.002). CONCLUSIONS: Myocardial fibrosis was rare in CRMR patients. CRMR is likely a disease characterised by the predominance of collagen degradation rather than increased synthesis and myocardial fibrosis.

Characterization of Severe Arterial Phase Respiratory Motion Artifact on Gadoxetate Disodium-Enhanced MRI - Assessment of Interrater Agreement and Reliability.

PURPOSE: To assess the interrater agreement and reliability of experienced abdominal radiologists in the characterization and grading of arterial phase gadoxetate disodium-related respiratory motion artifact on liver MRI. MATERIALS AND METHODS: This prospective multicenter study was initiated by the working group for abdominal imaging within the German Roentgen Society (DRG), and approved by the local IRB of each participating center. 11 board-certified radiologists independently reviewed 40 gadoxetate disodium-enhanced liver MRI datasets. Motion artifacts in the arterial phase were assessed on a 5-point scale. Interrater agreement and reliability were calculated using the intraclass correlation coefficient (ICC) and Kendall coefficient of concordance (W), with p < 0.05 deemed significant. RESULTS: The ICC for interrater agreement and reliability were 0.983 (CI 0.973 - 0.990) and 0.985 (CI 0.978 - 0.991), respectively (both p < 0.0001), indicating excellent agreement and reliability. Kendall's W for interrater agreement was 0.865. A severe motion artifact, defined as a mean motion score ≥ 4 in the arterial phase was observed in 12 patients. In these specific cases, a motion score ≥ 4 was assigned by all readers in 75 % (n = 9/12 cases). CONCLUSION: Differentiation and grading of arterial phase respiratory motion artifact is possible with a high level of inter-/intrarater agreement and interrater reliability, which is crucial for assessing the incidence of this phenomenon in larger multicenter studies. KEY POINTS: · Inter- and intrarater agreement for motion artifact scoring is excellent among experienced readers.. · Interrater reliability for motion artifact scoring is excellent among experienced readers.. · Characterization of severe motion artifacts proved feasible in this multicenter study.. CITATION FORMAT: · Ringe KI, Luetkens JA, Fimmers R et al. Characterization of Severe Arterial Phase Respiratory Motion Artifact on Gadoxetate Disodium-Enhanced MRI - Assessment of Interrater Agreement and Reliability. Fortschr Röntgenstr 2017; 190: 341 - 347.

CMR assessment and clinical outcomes of hypertrophic cardiomyopathy with or without ventricular remodeling in the end-stage phase.

End-stage phase of hypertrophic cardiomyopathy (ES-HCM) is a recognized part of HCM disease spectrum. Information on cardiac magnetic resonance (CMR) studies for ES-HCM especially for those without ventricular remodeling has been limited. We aimed to evaluate the morpho-functional and tissue features of ES-HCM with or without ventricular remodeling and to explore CMR prognostic value in these patients. We analysed CMR scans of sixty-three ES-HCM patients and divided them into those with ventricular dilatation (D-ES, n = 41) and those with normal ventricular size (N-ES, n = 22). Cox proportional hazards models were used to assess the association between CMR parameters and outcomes. Patients in D-ES showed hypokinetic-dilated HCM phenotype, while patients in N-ES showed hypokinetic-restrictive HCM phenotype. LGE extent was significantly larger in D-ES (34.7% ± 15.4% vs. 22.8% ± 7.7%; P < 0.01). Atrial fibrillation and edema of lower extremity were more common in N-ES (72.7 vs. 29.3% and 54.5 vs. 24.4%, respectively; P < 0.05). Log-rank test found no significant difference between 2 groups in combined end point of cardiovascular events (χ2 = 0.66, P = 0.418). In multivariate analysis, LGE (HR 1.57-1.83 per 10% LGE increase, P < 0.01) and indexed left atrial volume (LAVI) (HR 1.14-1.21 per 20 mL/m2 increase, P < 0.05) remained independently associated with combined end point when adjusted by other risk factors. The CMR features of HCM in end-stage span between two extremes. LGE is more extensive in those with ventricular remodeling and LAVI is larger in those with normal ventricular size. Both LGE and LAVI are significant predictors of poor outcomes.

Gadolinium-enhanced 7.0 T magnetic resonance imaging assessment of the aqueous inflow in rat eyes in vivo.

The goal of this study was to calculate the anterior chamber volume and assess aqueous inflow in rat eyes in vivo, under anesthetic condition. Gadolinium-contrast agent (Gd-DTPA, 234.5 mg/ml) was administered to Sprague-Dawley rat eyes via anterior chamber injection or instillation of 234.5 or 117.25 mg/ml Gd-DTPA in 0.2% azone as eye drops, and changes of Gd signal visualized by 7.0 T magnetic resonance imaging (MRI). The safety of local application of Gd-DTPA and azone were performed after MRI scanning. The anterior chamber injection of Gd-DTPA (234.5 mg/ml) group was used for anterior chamber volume and aqueous inflow calculating. Serial changes in Gd-DTPA relative concentration in the anterior chamber was determined based on the initial Gd signal gray values and the initial relative concentration of Gd-DTPA after anterior chamber Gd-DTPA injection. The mean aqueous inflow in rat eyes in vivo was assessed based on changes in Gd-DTPA relative concentration and the anterior chamber volume. Eye drops of Gd-DTPA (234.5 mg/ml) in 0.2% azone readily allowed safe assessment of the aqueous inflow by 7.0 T MRI. Under anesthetic condition in vivo, the mean anterior chamber volume (ACV) in rats was 8493.6 ± 657.4 µm3, no differences were observed in the aqueous inflow measured by topical instillation of 234.5 mg/ml Gd-DTPA in 0.2% azone (0.182 ± 0.011 µl/min) between that measured by anterior chamber injection (0.165 ± 0.041 µl/min, P > 0.05), Timolol reduced aqueous inflow to 0.124 ± 0.020 µl/min (P < 0.05). Our results indicated that Gd-enhanced 7.0 T MRI allows evaluation of the Gd signal variation and anterior chamber volume in rats in vivo. The aqueous inflow calculation via non-invasive local application of 234.5 mg/ml Gd-DTPA can be assessed by the variability of relative concentration of Gd-DTPA in anterior chamber and ACV in vivo, under anesthetic condition.

Comparison of 10- and 20-min hepatobiliary phase images on Gd-EOB-DTPA-enhanced MRI T1 mapping for liver function assessment in clinic.

PURPOSE: To compare hepatobiliary phase (HBP) images obtained 10 and 20 min after Gd-EOB-DTPA-enhanced MRI for liver function assessment in clinic on 3.0 T MR imaging. METHODS: 103 patients were separated into four groups: 38 patients for the normal liver function (NLF) group, 33 patients for the liver cirrhosis with Child-Pugh A (LCA) group, 21 patients for the liver cirrhosis with Child-Pugh B group, and 11 patients for a liver cirrhosis with Child-Pugh C group. T1 relaxation times (T1rt) were measured on T1 mapping and reduction rates of T1rt (rrT1rt) were calculated. HBP images were obtained at the 10- and 20-min mark after Gd-EOB-DTPA enhancement. RESULTS: T1rt on pre-enhancement imaging showed no significant difference (p > 0.05) among all four groups. T1rt for both the 10-min HBP and the 20-min HBP showed a significant difference (p < 0.05) among all groups, but showed no significant difference (p > 0.05) between the NLF group and the LCA group. T1rt and rrT1rt showed no significant difference (p > 0.05) between 10-min HBP and 20-min HBP among all groups. The ROC analysis on 10-min HBP and 20-min HBP showed a lower diagnostic performance between NLF group and LCA group (AUC from 0.532 to 0.582), but high diagnostic performance (AUC from 0.788 to 1.000) among others group. CONCLUSIONS: In comparing 10-min HBP and 20-min HBP T1 mapping after Gd-EOB-DTPA enhancement, our results suggest that 10-min HBP T1 mapping is a feasible option for quantitatively assessing liver function.

Radiation-induced Liver Injury after 3D-conformal Radiotherapy for Hepatocellular Carcinoma: Quantitative Assessment Using Gd-EOB-DTPA-enhanced MRI.

Focal liver reaction (FLR) appears in the hepatobiliary-phase images of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) following radiotherapy (RT). We investigated the threshold dose (TD) for FLR development in 13 patients with hepatocellular carcinoma (HCC) who underwent three-dimensional conformal radiotherapy (3D-CRT) with 45 Gy in 15 fractions. FLR volumes (FLRVs) were calculated based on planning CT images by referring to fused hepatobiliary- phase images. We also calculated the TD and the irradiated volumes (IVs) of the liver parenchyma at a given dose of every 5 Gy (IVdose) based on a dose-volume histogram (DVH). The median TD was 35.2 Gy. The median IV20, IV25, IV30, IV35, IV40, and IV45 values were 371.1, 274.8, 233.4, 188.6, 145.8, and 31.0 ml, respectively. The median FLRV was 144.9 ml. There was a significant difference between the FLRV and IV20, IV25, and IV45 (p<0.05), but no significant differences between the FLRV and IV30, IV35, or IV40. These results suggest that the threshold dose of the FLR is approx. 35 Gy in HCC patients who undergo 3D-CRT in 15 fractions. The percentage of the whole liver volume receiving a dose of more than 30-40 Gy (V30-40) is a potential candidate optimal DVH parameter for this fractionation schedule.

Quantification and Assessment of the Chemical Form of Residual Gadolinium in the Brain After Repeated Administration of Gadolinium-Based Contrast Agents: Comparative Study in Rats.

OBJECTIVE: Multiple clinical and preclinical studies have reported a signal intensity increase and the presence of gadolinium (Gd) in the brain after repeated administration of Gd-based contrast agents (GBCAs). This bioanalytical study in rat brain tissue was initiated to investigate whether the residual Gd is present as intact GBCA or in other chemical forms by using tissue fractionation and chromatography. MATERIALS AND METHODS: Rats were divided randomly in 6 groups of 10 animals each. They received 10 daily injections of 2.5 mmol/kg bodyweight of 1 of 5 different GBCAs: linear GBCAs such as gadodiamide (Omniscan; GE Healthcare), gadopentetate dimeglumine (Gd-DTPA, Magnevist; Bayer), or gadobenate dimeglumine (Multihance; Bracco) and macrocyclic GBCAs such as gadobutrol (Gadovist; Bayer) and gadoterate meglumine (Gd-DOTA, Dotarem; Guerbet) or saline. On days 3 and 24 after the last injection (p.i.), 5 randomly chosen animals of each group were killed by exsanguination, and their brains were excised and divided into cerebrum, pons, and cerebellum. The brain sections were homogenized by sonication in ice-cold buffer at pH 7.4. Soluble and insoluble fractions were separated by centrifugation, and the soluble fractions were further separated by gel permeation chromatography (GPC). The Gd concentration in all tissue fractions and in the GPC eluate was measured by inductively coupled plasma-mass spectrometry. In a recovery control experiment, all GBCAs were spiked to blank brain tissue and more than 94% recovery of Gd in the tissue fractions was demonstrated. RESULTS: Only traces of the administered Gd were found in the rat brain tissue on day 3 and day 24 p.i. In the animals treated with macrocyclic GBCAs, Gd was found only in the soluble brain fraction and was present solely as low molecular weight molecules, most likely the intact GBCA. In the animals treated with linear GBCAs Gd was found to a large extent in the insoluble tissue fraction. The Gd concentration in the soluble fraction was comparable to the macrocyclic agents. According to GPC, a smaller portion of the Gd in the soluble fraction of the linear GBCAs groups was bound to macromolecules larger than 250 to 300 kDa. The nature of the Gd-containing macromolecules and the insoluble species were not determined, but they appeared to be saturable with Gd. The excretion of the soluble Gd species in the linear and macrocyclic GBCA groups was still ongoing between days 3 and 24 p.i. This was also observed for the macromolecular Gd species in the linear GBCA groups, but at a slower rate. CONCLUSIONS: The residual Gd found in the rat brain after repeated administration of all 3 linear GBCAs was present in at least 3 distinctive forms-soluble small molecules, including the intact GBCA, soluble macromolecules, and to a large extent in insoluble form. The latter 2 are most likely responsible for the prolonged signal intensity enhancement in brain structures observed in magnetic resonance imaging. No relevant differences between the 3 linear GBCAs were observed. The Gd concentrations in the brain after administration of macrocyclic GBCAs are lower, and the Gd is only present in soluble small molecules, which were slowly excreted. This underlines the crucial importance of the kinetic inertness of macrocyclic agents in the prevention of potential retention of Gd in the brain compared with the 3 linear, kinetically less restricted GBCAs.

Assessment of Cochlea Endolymphatic Hydrops Using 3-D FLAIR and 3-D Real IR Sequence in Guinea Pigs via 3T MRI After Intratympanic Gadolinium: A Histopathological Comparison.

OBJECTIVE: We assessed whether the three-dimensional fluid-attenuated inversion-recovery (3-D FLAIR) and three-dimensional inversion-recovery with real reconstruction (3-D real IR) sequences can be used to detect cochlea endolymphatic hydrops (EHs) in guinea pigs using 3 Tesla magnetic resonance imaging (3T MRI). The results of 3-D real IR imaging were compared with histopathological outcomes. MATERIALS AND METHODS: Fourteen healthy men and women albino guinea pigs were used in this study. Their right ears received procedures that promoted EHs, and their left ears were used as untreated controls. High-resolution 3T MRI, combined with the intratympanic injection of gadolinium (Gd) in both ears, was performed 8 to 12 weeks after surgery. Both sides of the cochlea midmodiolar sections were observed under a light microscope and saved as the histopathological images. The signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) between the T2-weighted 3-D FLAIR and T2-weighted 3-D real IR sequences were compared. The appearance of EHs in the basal, second, third, and apical turns of the cochlea was further evaluated using 3-D FLAIR, 3-D real IR, and the histopathological images. Moreover, the maximum scala media area ratios (SMRs) on the histopathological sections were compared with the grading of the EHs on the 3-D real IR sequence with regard to each turn of the cochlea. RESULTS: Significant differences were found between the 3-D FLAIR and 3-D-real IR sequences with regard to the SNRs and CNRs (p < 0.05): the 3-D FLAIR sequence exhibited higher SNRs (SNRROI: 347.95 ±â€Š105.01; SNRB: 103.28 ±â€Š17.61) compared with the 3-D real IR sequence (SNRROI: 86.71 ±â€Š30.11; SNRB: 11.11 ±â€Š3.45), whereas the 3-D real IR sequence showed higher CNRs (2.78 ±â€Š0.58) compared with the 3-D FLAIR sequence (2.18 ±â€Š0.55). Various degrees of EHs were observed in each turn of the cochlea in the experimental ears on the basis of the histopathological images. Thirteen, 10, 4, and 0 EHs were observed in the basal, second, third, and apical turns of the cochlear using 3-D FLAIR images, respectively, whereas 14, 14, 14, and 13 EHs were found using 3-D real IR images, respectively. Significant differences were found between the two sequences when evaluating the second, third, and apical turns of the cochlear but not with regard to the basal turn (p < 0.05). The SMRs were proportional to the extent of the EHs on 3-D real IR imaging in each turn of the cochlea. CONCLUSIONS: 3-D real IR images are clearer than 3-D FLAIR images, and they can display cochlea EHs more precisely using 3T MRI in guinea pigs. The extent of the EHs on 3-D real IR imaging was more consistent with the histopathological observations in each turn of the cochlea.

Combining hyperpolarized 13 C MRI with a liver-specific gadolinium contrast agent for selective assessment of hepatocyte metabolism.

PURPOSE: Hyperpolarized 13 C MRI is a powerful tool for studying metabolism, but can lack tissue specificity. Gadoxetate is a gadolinium-based MRI contrast agent that is selectively taken into hepatocytes. The goal of this project was to investigate whether gadoxetate can be used to selectively suppress the hyperpolarized signal arising from hepatocytes, which could in future studies be applied to generate specificity for signal from abnormal cell types. METHODS: Baseline gadoxetate uptake kinetics were measured using T1 -weighted contrast enhanced imaging. Relaxivity of gadoxetate was measured for [1-13 C]pyruvate, [1-13 C]lactate, and [1-13 C]alanine. Four healthy rats were imaged with hyperpolarized [1-13 C]pyruvate using a three-dimensional (3D) MRSI sequence prior to and 15 min following administration of gadoxetate. The lactate:pyruvate ratio and alanine:pyruvate ratios were measured in liver and kidney. RESULTS: Overall, the hyperpolarized signal decreased approximately 60% as a result of pre-injection of gadoxetate. In liver, the lactate:pyruvate and alanine:pyruvate ratios decreased 42% and 78%, respectively (P < 0.05) following gadoxetate administration. In kidneys, these ratios did not change significantly. Relaxivity of gadoxetate for [1-13 C]alanine was 12.6 times higher than relaxivity of gadoxetate for [1-13 C]pyruvate, explaining the greater selective relaxation effect on alanine. CONCLUSIONS: The liver-specific gadolinium contrast-agent gadoxetate can selectively suppress normal hepatocyte contributions to hyperpolarized 13 C MRI signals. Magn Reson Med 77:2356-2363, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

An echo-planar imaging sequence is superior to a steady-state free precession sequence for visual as well as quantitative assessment of cardiac magnetic resonance stress perfusion.

BACKGROUND: To assess myocardial perfusion, steady-state free precession cardiac magnetic resonance (SSFP, CMR) was compared with gradient-echo-echo-planar imaging (GRE-EPI) using myocardial perfusion scintigraphy (MPS) as reference. METHODS: Cardiac magnetic resonance perfusion was recorded in 30 patients with SSFP and in another 30 patients with GRE-EPI. Timing and extent of inflow delay to the myocardium was visually assessed. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated. Myocardial scar was visualized with a phase-sensitive inversion recovery sequence (PSIR). All scar positive segments were considered pathologic. In MPS, stress and rest images were used as in clinical reporting. The CMR contrast wash-in slope was calculated and compared with the stress score from the MPS examination. CMR scar, CMR perfusion and MPS were assessed separately by one expert for each method who was blinded to other aspects of the study. RESULTS: Visual assessment of CMR had a sensitivity for the detection of an abnormal MPS at 78% (SSFP) versus 91% (GRE-EPI) and a specificity of 58% (SSFP) versus 84% (GRE-EPI). Kappa statistics for SSFP and MPS was 0·29, for GRE-EPI and MPS 0·72. The ANOVA of CMR perfusion slopes for all segments versus MPS score (four levels based on MPS) had correlation r = 0·64 (SSFP) and r = 0·96 (GRE-EPI). SNR was for normal segments 35·63 ± 11·80 (SSFP) and 17·98 ± 8·31 (GRE-EPI), while CNR was 28·79 ± 10·43 (SSFP) and 13·06 ± 7·61 (GRE-EPI). CONCLUSION: GRE-EPI displayed higher agreement with the MPS results than SSFP despite significantly lower signal intensity, SNR and CNR.

Evaluación de la intensidad de señal en núcleo dentado, puente, globus pallidus y tálamo en pacientes con esclerosis múltiple: valoración de la retención de gadolinio / Evaluation of signal intensity in dentate nucleus, pons, globus pallidus and thalamus in patients with multiple sclerosis: assessment of gadolinium retention

Introduction: Recently, some studies have reported accumulation of gadolinium in the brain of patients with multiple administrations of gadolinium-based contrast. Patients with multiple sclerosis are subjected to multiple contrasting resonances and could become a population at risk. Objective: To determine whether repeated intravenous exposure to gadolinium is associated with more intensity in the thalamus, dentate nucleus, pons and the globus pallidus. Methods: A retrospective study of 60 patients with MS who had undergone two or more contrasted MRs between 2007 and 2015, was performed. The ratios calculated were: dentate nuclei-to-pons (DNP), thalamus-to-pons (TP), caudate nuclei-to-pons (CNP), globus pallidus-to-thalamus (GPT), globus pallidus-to-pons (GPP), by reviewing simple T1 axial sequences. Relative changes were calculated and compared with the number of contrasted MRs. The concordance between observers and the intraclass correlation coefficient was evaluated. Results: There was no evidence of increased signal intensity in T1 sequences (DNP 0.524, GPT 0.466, GPP 0.684, TP 0.771, CNP 0.352). As there were no differences, the Spearman coefficient showed no correlation between relative changes and the number of resonances performed. Inter-observer agreement was almost perfect (0.982) for all structures. Conclusion: Our study did not find a statistically significant increase in the T1 signal intensity in patients with multiple sclerosis. However, there are factors to consider, such as the type of gadolinium and the time lapse between administrations.

Introducción: Recientemente, algunos estudios han informado acumulación de gadolinio en el cerebro de los pacientes con múltiples administraciones de contraste basado en gadolinio. Los pacientes con esclerosis múltiple son sometidos a múltiples resonancias contrastadas y podrían convertirse en una población de riesgo. Objetivo: Determinar si la exposición repetida por vía intravenosa a gadolino se asocia con mayor intensidad en el tálamo, el dentado, el puente y el globo pálido. Métodos: Se realizó un estudio retrospectivo núcleo de 60 pacientes con EM que habían sido sometidos a dos o más RM contrastadas entre 2007 - 2015. Se calcularon las razones núcleo dentado - puente (DNP), tálamo-puente (TP), núcleo caudado- puente (CNP), globus pallidus - tálamo (GPT), globus pallidos - puente (GPP), revisando secuencias T1 axiales simples. Se calcularon los cambios relativos y se compararon con el número de RM contrastadas. Se evaluó la concordancia entre observadores con el coeficiente de correlación intraclase. Resultados: No hubo evidencia de aumento de la intensidad de la señal en secuencias T1 (DNP 0,524, 0,446 GPT, GPP 0,684, 0,771 PT, CNP 0.352). Al no existir diferencias, el coeficiente de Spearman no mostró correlación entre los cambios relativos y el número de resonancias realizadas. La concordancia interobservador fue casi perfecta (0.982) para todas las estructuras. Conclusión: Nuestro estudio no encontró un aumento estadísticamente significativo en la intensidad de la señal T1 en pacientes con esclerosis múltiple. Sin embargo, hay factores a considerar, tales como el tipo de gadolinio y el lapso de tiempo entre las administraciones.

Comprehensive Cardiovascular Magnetic Resonance Assessment in Patients With Sarcoidosis and Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Cardiac sarcoidosis (CS) may manifest as arrhythmia or even sudden cardiac death. Because patients with CS often present with nonspecific symptoms, normal electrocardiography, and preserved left ventricular ejection fraction, a reliable diagnostic tool for the work-up of CS is needed. Late gadolinium enhancement-cardiovascular magnetic resonance has proven diagnostic value in CS but has some limitations that may be overcome by adding newer cardiovascular magnetic resonance mapping techniques. The aim of our study was to evaluate a comprehensive cardiovascular magnetic resonance protocol, including late gadolinium enhancement and mapping sequences in sarcoid patients with no symptoms or unspecific symptoms and preserved left ventricular ejection fraction. METHODS AND RESULTS: Sixty-one sarcoid patients were prospectively enrolled and underwent comprehensive cardiovascular magnetic resonance imaging. Twenty-six healthy volunteers served as control group. Mean left ventricular ejection fraction was 65%; late gadolinium enhancement was only present in sarcoid patients (n=15). Sarcoid patients had a higher median native T1 (994 versus 960 ms; P<0.001), lower post contrast T1 (491 versus 526 ms; P=0.001), expanded extracellular volume (28 versus 25%; P=0.001), and higher T2 values (52 versus 49 ms; P<0.001) compared with controls. Among patients with values higher than the 95% percentile of healthy controls, most significant differences were observed for native T1 and T2 values. Most of these patients were late gadolinium enhancement negative. CONCLUSIONS: Patients with sarcoidosis demonstrate higher T1, extracellular volume, and T2 values compared with healthy controls, with most significant differences for native T1 and T2. While promising, the clinical significance of the newer mapping techniques with respect to early diagnosis and therapy of CS will have to be determined in future studies.

Evaluation of Magnetic Resonance (MR) Biomarkers for Assessment of Response With Response Evaluation Criteria in Solid Tumors: Comparison of the Measurements of Neuroendocrine Tumor Liver Metastases (NETLM) With Various MR Sequences and at Multiple Phases of Contrast Administration.

PURPOSE: Our aim was to compare the interobserver and intraobserver variability for the measurement of the size of liver metastases in patients with carcinoid tumors with various magnetic resonance (MR) series. MATERIALS AND METHODS: In this retrospective institutional review board-approved study, 30 patients with liver metastases from a carcinoid primary had a complete MR examination of the abdomen at 1.5 T with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA). The complete MR examination included T1 (in-phase [IP]/out-of-phase [OOP], T2, diffusion-weighted imaging, pre-Gd-EOB-DTPA and post-Gd-EOB-DTPA 3D gradient echo (4 phases plus 20-minute hepatobiliary phase [HBP] Gd]). Four readers reviewed each series independently. The measurement for each lesion was compared to HBP-Gd images. The sensitivity for detection of each lesion was compared to HBP-Gd. Variance component analysis was used to estimate variance due to patient, lesion within patient, and reader by sequence. Linear mixed model was used to compare lesion size between sequences. RESULTS: The HBP-Gd had the smallest interreader variability. There was no significant difference between series with respect to interreader variability. Lesion sizes measured in diffusion-weighted imaging was significantly higher. T2-weighted imaging was the closest to HBP-Gd. Lesion sizes measured with the other sequences were significantly smaller. There was significant difference in sensitivity of lesion detection of some series when compared to HBP-Gd. CONCLUSION: The HBP-Gd series had the smallest interreader variability and is the recommended series to measure lesion size for evaluation of response to treatment.

Quantitative diffusion-weighted magnetic resonance imaging in the assessment of myocardial fibrosis in hypertrophic cardiomyopathy compared with T1 mapping.

To identify myocardial fibrosis in hypertrophic cardiomyopathy (HCM) subjects using quantitative cardiac diffusion-weighted imaging (DWI) and to compare its performance with native T1 mapping and extracellular volume (ECV). Thirty-eight HCM subjects (mean age, 53 ± 9 years) and 14 normal controls (mean age, 51 ± 8 years) underwent cardiac magnetic resonance imaging (CMRI) on a 3.0T magnetic resonance (MR) machine with DWI, T1 mapping and late gadolinium enhancement (LGE) imaging as the reference standard. The mean apparent diffusion coefficient (ADC), native T1 value and ECV were determined for each subject. Overall, the HCM subjects exhibited an increased native T1 value (1241.04 ± 78.50 ms), ECV (0.31 ± 0.03) and ADC (2.36 ± 0.34 s/mm(2)) compared with the normal controls (1114.60 ± 37.99 ms, 0.24 ± 0.04, and 1.62 ± 0.38 s/mm(2), respectively) (p < 0.05). DWI differentiated healthy and fibrotic myocardia with an area under the curve (AUC) of 0.93, while the AUCs of the native T1 values (0.93), (p > 0.05) and ECV (0.94), (p > 0.05) exhibited an equal differentiation ability. Both HCM LGE+ and HCM LGE- subjects had an increased native T1 value, ECV and ADC compared to the normal controls (p < 0.05). HCM LGE+ subjects exhibited an increased ECV (0.31 ± 0.04) and ADC (2.43 ± 0.36 s/mm(2)) compared to HCM LGE- subjects (p < 0.05). HCM LGE+ and HCM LGE- subjects had similar native T1 values (1250 ± 76.36 ms vs. 1213.98 ± 92.30 ms, respectively) (p > 0.05). ADC values were linearly associated with increased ECV (R(2) = 0.36) and native T1 values (R(2) = 0.40) among all subjects. DWI is a feasible alternative to native T1 mapping and ECV for the identification of myocardial fibrosis in patients with HCM. DWI and ECV can quantitatively characterize the extent of fibrosis in HCM LGE+ and HCM LGE- patients.