Effects of gadoxetic acid on liver elasticity measurement by using magnetic resonance elastography

The purpose of this study was to evaluate the effect of gadoxetic acid (Gd-EOB-DTPA) on measurements of liver stiffness by using magnetic resonance elastography (MRE). In this study, 104 consecutive patients (mean age, 67.7±9.4 years) underwent MRE using a 1.5-T MR scanner equipped with a cylindrical passive driver that was placed across the right chest wall for delivering vibrations. Axial gradient-echo images, which were automatically converted to elastograms that represented stiffness (kPa), were acquired using a continuous sinusoidal vibration of 60 Hz. Two raters independently placed a region of interest on the right lobe of the liver on the elastograms obtained before and after Gd-EOB-DTPA was administered. Liver stiffness was measured using these two elastograms and compared using a paired t test and correlation analysis. No significant difference was observed in liver stiffness before and after Gd-EOB-DTPA was administered (Rater 1, P=.1200; Rater 2, P=.3585). The correlation coefficients were 0.986 (Rater 1) and 0.984 (Rater 2), indicating excellent correlation between the stiffness values before and after Gd-EOB-DTPA was administered. Liver stiffness measured by MRE did not differ before and after Gd-EOB-DTPA was administered.     

Correlation of MRI findings to histology of acetaminophen toxicity in the mouse

Acetaminophen (APAP) toxicity is responsible for approximately half of all cases of acute liver failure in the United States. The mouse model of APAP toxicity is widely used to examine mechanisms of APAP toxicity. Noninvasive approaches would allow for serial measurements in a single animal to study the effects of experimental interventions on the development and resolution of hepatocellular necrosis. The following study examined the time course of hepatic necrosis using small animal magnetic resonance imaging (MRI) following the administration of 200 mg/kg ip APAP given to B6C3F1 male mice. Mice treated with saline served as controls (CON). Other mice received treatment with the clinical antidote N-acetylcysteine (APAP+NAC). Mouse liver pathology was characterized using T1- and T2-weighted sequences at 2, 4, 8 and 24 h following APAP administration. Standard assays for APAP toxicity [serum alanine aminotransaminase (ALT) levels and hematoxylin and eosin (H&E) staining of liver sections] were examined relative to MRI findings. Overall, T2 sequences had a greater sensitivity for necrosis and hemorrhage than T1 (FLASH) images. Liver injury severity scoring of MR images demonstrated increased scores in the APAP mice at 4, 8 and 24 h compared to the CON mice. APAP+NAC mice had MRI scores similar to the CON mice. Semiquantitative analysis of hepatic hemorrhage strongly correlated with serum ALT. Small animal MRI can be used to monitor the evolution of APAP toxicity over time and to evaluate the response to therapy.     

Paradoxical uptake of Gd-EOB-DTPA on the hepatobiliary phase in the evaluation of hepatic metastasis from breast cancer: is the “target sign” a common finding?

Purpose

The purpose was to describe magnetic resonance imaging (MRI) findings of breast cancer liver metastasis using gadoxetic acid (Gd-EOB-DTPA) with an emphasis on the added value of the hepatobiliary phase (HBP).

Material and methods

Nine patients with 13 liver metastases were included in the study after the medical records of 29 breast cancer patients who underwent Gd-EOB-DTPA-enhanced MRI between February 2008 and June 2010 were reviewed. The diagnoses of liver metastasis were established by percutaneous liver biopsy or surgery and on the basis of image findings. Two radiologists retrospectively evaluated signal intensity (SI) and sizes of metastases and patterns of enhancement in an HBP. The SI ratio was calculated as the SI of the central hyperintense portion in “target” lesions divided by the SI of nearby normal liver parenchyma on the HBP. We also measured apparent diffusion coefficient (ADC) values from Diffusion Weighted Image (DWI).

Results

Liver metastases were all hypointense [n=13/13 (100%)] on T1-weighted imaging (WI), and many lesions had a “target” appearance with a central high SI and a peripheral low SI rim (47%) on T2WI. Dynamic study showed rim enhancement on the arterial phase (85%) and a “target” appearance, consisting of a central enhancing portion with peripheral washout or hypointense rim, on the HBP (62%). The mean SI ratio was 0.7. The mean ADC value of “target” appearing metastases was 1.25 (×10⁻³ mm²/s; range 1.3–1.6) compared with a mean value of 0.8 (×10⁻³ mm²/s; range 0.8–1.4) in homogeneous defect on the HBP. There was statistically significant difference (P<.05).

Conclusion

Breast cancer liver metastases commonly demonstrated as a peripheral ring enhancement on arterial dominant phase and a target sign with a central round enhancing portion and a peripheral hypointense rim on the HBP.     

Cross-sectional investigation of correlation between hepatic steatosis and IVIM perfusion on MR imaging

The purpose of this study was to investigate the relationship between liver fat fraction (FF) and diffusion parameters derived from the intravoxel incoherent motion (IVIM) model. Thirty-six subjects with suspected nonalcoholic fatty liver disease underwent diffusion-weighted magnetic resonance imaging with 10 b-values and spoiled gradient recalled echo imaging with six echoes for fat quantification. Correlations were measured between FF, transverse relaxivity (R2), diffusivity (D) and perfusion fraction (f). The primary finding was that no significant correlation was obtained for D vs. FF or f vs. FF. Significant correlations were obtained for D vs. R2 (r=-0.490, P=.002) and f vs. D (r=-0.458, P=.005). The conclusion is that hepatic steatosis does not affect measurement of perfusion or diffusion and therefore is unlikely to confound the use of apparent diffusivity to evaluate hepatic fibrosis.     

In vitro evaluation of the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curves

The objective of this study was to assess in vitro the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curves formed from dynamic contrast-enhanced ultrasound image loops. An indicator-dilution experiment was developed with an in vitro flow phantom setup used with SonoVue contrast agent (Bracco SpA, Milan, Italy). Imaging was performed with a Philips iU22 scanner and two transducers (L9-3 linear and C5-1 curvilinear). The following ultrasound scanner settings were investigated, along with contrast bolus volume: contrast-specific nonlinear pulse sequence, gain, mechanical index, focal zone depth, acoustic pulse center frequency and bandwidth. Four parameters (rise time, mean transit time, peak intensity, and area under the curve) were derived from time-intensity curves which were obtained after pixel by pixel linearization of log-compressed data (also referred to as video data) included in a region of interest. Rise time was found to be the parameter least impacted by changes to ultrasound scanner settings and contrast bolus volume; the associated coefficient of variation varied between 0.7% and 6.9% while it varied between 0.8% and 19%, 12% and 71%, and 9.2% and 66%, for mean transit time, peak intensity, and area under the curve, respectively. The present study assessed the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curve analysis. One should be aware of these issues to standardize their technique in each specific organ of interest and to achieve accurate, sensitive, and reproducible data using dynamic contrast-enhanced ultrasound. One way to mitigate the impact of ultrasound scanner settings in longitudinal, multi-center quantitative dynamic contrast-enhanced ultrasound studies may be to prohibit any adjustments to those settings throughout a given study. Further clinical studies are warranted to confirm the reproducibility and diagnostic or prognostic value of time-intensity curve parameters measurements in a particular clinical scenario of interest, for example that of cancer patients undergoing vascular targeting therapies.     

Myofibroblasts are important contributors to human hepatocellular carcinoma: Evidence for tumor promotion by proteome profiling

Liver cancer typically occurs with a background of chronic fibrosis, characterized by the accumulation of myofibroblast‐like cells. We performed 2D‐PAGE‐based comparative analyses with the aim to identify proteins expressed in human hepatocellular carcinoma (HCC) tissue but not in neighboring healthy liver tissue, and to make out which cell types are responsible for the expression of proteins most characteristic for HCC. LC‐MS/MS analysis of the most striking spots identified proteins that were mainly related to myofibroblast‐like cells. To gain more insights into the role of these cells in their contribution to HCC, we isolated myofibroblast‐like cells as well as hepatocytes, both derived from HCC tissues, and subjected them to proteome profiling based on shotgun experiments. Comparative analysis, also referring to proteome profiles of other cell types previously investigated by us, pointed again to a marked contribution of myofibroblast‐like cells to HCC. Intriguingly, secretome analysis of these cells identified several growth factors that may act as tumor promoters and several proteins that have been described as potential biomarkers for HCC including dickkopf‐1, connective tissue growth factor, and CXCL1. Other biomarker candidates presently identified in the secretome of myofibroblasts, including lipocalin‐1 and pappalysin‐1, may be selected for future clinical validation. The identification of myofibroblast‐like cells as important source of tumor‐promoters may open new avenues to therapeutic intervention by targeting these stroma cells in addition to the cancer cells.     

Evaluation of two new gadolinium chelates as contrast agents for MRI

Two new gadolinium chelates were investigated for potential use as tissue-specific contrast agents for magnetic resonance imaging. In vitro measurements of stability constants, octanol/water partition coefficients and relaxation times in solutions of water and human serum albumin (HSA) were performed with each new chelate and compared with gadolinium-diethylenetriamine pentaacetic acid, Gd(DTPA). Biodistribution studies and magnetic resonance imaging in rats were used to evaluate the new chelates in vivo. The stability constants (log K) of gadolinium-N,N″-bis(3-hydroxy-6-methyl-2-pyridylmethyl)diethylenetriamine-N,N′,N″-triacetic acid, Gd(DTTA-HP), and gadolinium-1,7-13-triaza-4,10-16-trioxacyclooctadecane-N,N′,N″-triacetic acid, Gd(TTCT), were determined to be 23.65 and 18.07, respectively. These can be compared to a literature value of 22.46 for Gd(DTPA). Octanol/water partition coefficients for both complexes showed they were more lipophilic than Gd(DTPA). Gd(DTTA-HP) exhibited a smaller relaxivity in water but a larger relaxivity in 4% HSA than Gd(DTPA). Gd(TTCT) exhibited a lower relaxivity than Gd(DTPA) in both water and 4% HSA. Both complexes showed similar biodistributions to Gd(DTPA) no carrier-added concentrations. Gd(DTTA-HP) had a greater percent change in signal intensity than Gd(DTPA) on T₁-weighted spin-echo images in the heart, liver, and kidney. Percent change in signal intensity for Gd(TTCT) was lower than Gd(DTPA) in heart, liver, and kidney.     

A study of T1-weighted 31phosphorus MR-spectroscopy from patients with focal and diffuse liver disease.

³¹P-MR-Spectroscopy was performed in 28 patients with focal (n = 23) and diffuse (n = 5) liver disease and in 18 healthy volunteers. The spectra were obtained with a whole body scanner operating at 1.5 T by using a surface coil. To get T₁-weighted ³¹P-spectra a short TR of 600 msec was taken, because T₁-weighted spectra of focal liver disease were more significantly different from spectra from healthy volunteers than density weighted ones. The VOI from patients with focal superficial alterations showed a mean volume of 172 ml, with diffuse liver disease 196 ml, and from volunteers 158 ml. Focal tumors filled up the VOI on an average of 70%. This investigation demonstrated that PME/β-ATP- and PDE/β-ATP-ratios were sensitive indicators for focal liver disease. As a result of this study we could establish a significant increase of PME/β-ATP- (0.75 ± 0.30) and PDE/β-ATP-ratios (1.68 ± 0.62) in patients with superficial focal liver metastases (n = 19) compared to the control group (PME/β-ATP: 0.49 ± 0.17, PDE/β-ATP: 1.24 ± 0.24; t-test: p < 0.02). Patients with a hemangioma (n = 1), liver infarction (n = 1), empyema of gallbladder (n = 1) and a hepatic involvement by a malignant lymphoma (n = 1) showed a similar increase of PME/β-ATP and/or PDE/β-ATP. Up to now spectral changes seemed to be non-specific. The ratios of ³¹P metabolites of the cirrhoses (n = 4) and the fatty liver (n = 1) did not show any characteristic changes versus the volunteers.     

Study of light propagation in human, rabbit and rat liver tissue by Monte Carlo simulation

Monte Carlo Simulation for light propagation in liver tissues of human and animal was done using Monte Carlo simulation. During the simulation we recorded the photon reflectance, transmittance and absorption of human, rabbit and rat liver tissues. Then their comparative studies were done. Average values of total diffuse reflectance, transmittance and absorption were calculated by the 10 simulations of 100,000 photons for these tissues at 633 nm. We found that diffuse reflectance increases as μ_s increases or g decreases and diffuse transmittance increases as μ_a or μ_s decreases, or as g increases. It is also concluded that the radially resolved diffuse reflectance of the tissues decays exponentially of second order.     

Detection of small intrahepatic metastases of hepatocellular carcinomas using diffusion-weighted imaging: comparison with conventional dynamic MRI

Purpose

The purpose of our study was to compare diffusion-weighted MR imaging (DWI) with conventional dynamic MRI in terms of the assessment of small intrahepatic metastases from hepatocellular carcinoma (HCC).

Materials and Methods

In 24 patients with multifocal, small (≤2 cm) intrahepatic metastatic foci of advanced HCC, a total of 134 lesions (≤1 cm, n=81; >1 cm, n=53) were subjected to a comparative analysis of hepatic MRI including static and gadopentetate dimeglumine-enhanced dynamic imaging, and DWI using a single-shot spin-echo echo-planar MRI (b values=50, 400 and 800 s/mm²), by two independent reviewers.

Results

A larger number of the lesions were detected and diagnosed as intrahepatic metastases on DWI [Reviewer 1, 121 (90%); Reviewer 2, 117 (87%)] than on dynamic imaging [Reviewer 1, 107 (80%); Reviewer 2, 105 (78%)] (P<.05). For the 81 smaller lesions (≤1 cm), DWI was able to detect more lesions than dynamic imaging [Reviewer 1, 68 (84%) vs. 56 (69%), P=.008; Reviewer 2, 65 (80%) vs. 55 (68%), P=.031], but there was no statistically significant difference between the two image sets for larger (>1 cm) lesions.

Conclusion

Due to its higher detection rate of subcentimeter lesions, DWI could be considered complementary to dynamic MRI in the diagnosis of intrahepatic metastases of HCCs.