Double Diffusion Encoding for Probing Radiation-Induced Microstructural Changes in a Tumor Model: A Proof-of-Concept Study With Comparison to the Apparent Diffusion Coefficient and Histology.

Background: Microstructure analyses are gaining interest in cancer MRI as an alternative to the conventional apparent diffusion coefficient (ADC), of which the determinants remain unclear.

Purpose: To assess the sensitivity of parameters calculated from a double diffusion encoding (DDE) sequence to changes in a tumor's microstructure early after radiotherapy and to compare them with ADC and histology.

Study Type: Cohort study on experimental tumors.

Insights into tissue microstructure using a double diffusion encoding sequence on a clinical scanner: Validation and application to experimental tumor models.

Purpose: To present a double diffusion encoding MRI sequence on a clinical scanner to analyze micro-structure and micro-vasculature of tumors.

Methods: The sequence was tested on phantoms, asparaguses, and 2 tumors allografts in a rodent. Results were analyzed using an adapted VERDICT model to estimate microstructural parameters.

Effect of curcumin on the cell surface markers CD44 and CD24 in breast cancer.

Human breast cell lines are often characterized based on the expression of the cell surface markers CD44 and CD24. CD44 is a type I transmembrane glycoprotein that regulates cell adhesion and cell-cell, as well as cell-extracellular matrix interactions. CD24 is expressed in benign and malignant solid tumors and is also involved in cell adhesion and metastasis.

Ras protein expression as a marker for breast cancer.

Breast cancer, the most common neoplasm in women of all ages, is the leading cause of cancer-related mortality in women worldwide. Markers to help to predict the risk of progression and ultimately provide non-surgical treatment options would be of great benefit. At present, there are no available molecular markers to predict the risk of carcinoma progression to invasive cancer; therefore, all women diagnosed with this type of malignancy must undergo surgery.

Relevance of activated hepatic stellate cells in predicting the development of pediatric liver allograft fibrosis.

Activated hepatic stellate cells (HSCs) are the main collagen-producing cells in liver fibrogenesis. With the purpose of analyzing their presence and relevance in predicting liver allograft fibrosis development, 162 liver biopsies of 54 pediatric liver transplantation (LT) recipients were assessed at 6 months, 3 years, and 7 years after LT. The proportion of activated HSCs, identified by α-smooth muscle actin (ASMA) immunostaining, and the amount of fibrosis, identified by picrosirius red (PSR%) staining, were determined by computer-based morphometric analysis.

Vimentin and Notch as biomarkers for breast cancer progression.

Breast cancer, the most common spontaneous malignancy diagnosed in women, is a classical model of hormone dependency as it is associated with prolonged exposure to female hormones. Different cytoplasmic proteins are important in the transformation of a normal cell to an invasive tumor cell, and these include vimentin and Notch. To investigate the importance of these two genes and proteins in breast carcinogenesis, we used an breast cancer model system, in which an immortalized human breast epithelial cell line, MCF-10F, was malignantly transformed by exposure to low doses of high linear energy transfer α particle (150 keV/μm) radiation and subsequent growth in the presence or absence of 17β-estradiol.

Enhanced choline metabolism in a rodent rhabdomyosarcoma model: correlation between RT-PCR and translational 3 T H-MRS.

Purpose: To investigate which transmembrane choline transporters and intracellular choline kinases play a prominent role at gene expression level in the rise of the total choline (tCho) peak at proton MR spectra in a rodent rhabdomyosarcoma model.

Materials And Methods: Twenty-two rats bearing grafted bilateral syngenic rhabdomyosarcoma were examined on a clinical 3 T MR system. Total choline concentration was measured from proton MR spectra using cubic centimeter volumes of interest (VOIs) located contiguously along the greater axis of the tumour.

Multiparametric magnetic resonance imaging to differentiate high-grade gliomas and brain metastases.

Purpose: To assess the performance of parameters used in conventional magnetic resonance imaging (MRI), perfusion-weighted MR imaging (PWI) and visual texture analysis, alone and in combination, to differentiate a single brain metastasis (MET) from glioblastoma multiforme (GBM).

Patients And Methods: In a retrospective study of 50 patients (41 GBM and 14 MET) who underwent T2/FLAIR/T1(post-contrast) imaging and PWI, morphological (circularity, surface area), perfusion (rCBV in the ring-like tumor area, rCBV in the peritumoral area, percentage of signal intensity recovery at the end of first pass) and texture parameters in the peritumoral area were estimated. Statistical differences and performances were assessed using Wilcoxon's test and receiver operating characteristic curves, respectively.

Early (72-hour) detection of radiotherapy-induced changes in an experimental tumor model using diffusion-weighted imaging, diffusion tensor imaging, and Q-space imaging parameters: a comparative study.

Purpose: To assess and compare the potential of various diffusion-related magnetic resonance imaging (MRI) parameters to detect early radiotherapy (RT)-induced changes in tumors.

Materials And Methods: Nineteen tumors in a rat model were imaged on a clinical 3T system before and 72 hours after a single RT session. Diffusion imaging was performed using an echo planar sequence containing 16 b-factors and six gradient directions.

Participation of liver progenitor cells in liver regeneration: lack of evidence in the AAF/PH rat model.

When hepatocyte proliferation is impaired, liver progenitor cells (LPC) are activated to participate in liver regeneration. We used the 2-acetaminofluorene/partial hepatectomy (AAF/PH) model to evaluate the contribution of LPC to liver cell replacement and function restoration. Fischer rats subjected to AAF/PH (or PH alone) were investigated 7, 10 and 14 days post-hepatectomy.

Kupffer cells influence parenchymal invasion and phenotypic orientation, but not the proliferation, of liver progenitor cells in a murine model of liver injury.

Activation of myofibroblasts (MF) and extracellular matrix (ECM) deposition predispose the expansion and differentiation of liver progenitor cells (LPC) during chronic liver injury. Because Kupffer cells (KC) are active modulators of tissue response and fibrosis, we analyzed their role in a model of LPC proliferation. A choline-deficient diet, supplemented by ethionine (CDE) was administrated to C57Bl/6J mice that were depleted of KC by repeated injections of clodronate (CLO) and compared to PBS-injected mice.

MRI of iron-oxide labelled transplanted hepatocytes in mice: effect of treatment with cyclophosphamide.

Purpose: To assess if 1.5T MRI can be used to study the transport to the liver, the intrahepatic distribution and engraftment of iron-oxide labelled hepatocytes in cyclophosphamide-treated and untreated mice.

Materials And Methods: Hepatocytes were isolated from C57bl/6 mice and were labelled with 1.

Early monitoring of external radiation therapy by [18F]-fluoromethylcholine positron emission tomography and 3-T proton magnetic resonance spectroscopy: an experimental study in a rodent rhabdomyosarcoma model.

Purpose: To assess early radiation therapy (RT)-induced variations in total choline (tCho) concentration measured by proton magnetic resonance spectroscopy (H-MRS) and in (18)F-labelled fluoromethylcholine (FCH) uptake measured by PET in a rodent tumour model.

Methods: Nine rats bearing syngenic rhabdomyosarcoma grafts in both thighs were irradiated (13 Gy, one fraction). H-MRS data and FCH-PET were acquired in the same imaging session prior to and 3, 9 and 16 days after external RT.

Rodent rhabdomyosarcoma: comparison between total choline concentration at H-MRS and [18F]-fluoromethylcholine uptake at PET using accurate methods for collecting data.

Purpose: To compare choline concentration/amount at proton magnetic resonance spectroscopy (H-MRS) and [18F]-fluoromethylcholine (FCH) uptake at positron emission tomography (PET) in a tumour animal model.

Procedures: Twenty-two rats bearing grafted syngenic rhabdomyosarcoma in both thighs were examined on a 3T MR system and on a small animal PET system. Total choline concentration was measured on proton MR spectra using a so-called 'best internal fitting' volume of interest.

Efficacy of lanreotide in preventing the occurrence of chemically induced hepatocellular carcinoma in rats.

Hepatocellular carcinoma (HCC) is increasing worldwide and is the third cause of cancer-related death. HCC develops in a pre-neoplastic organ, the cirrhotic liver. Therefore, chemoprevention could play a role in the management of HCC.

Development of hepatic fibrosis occurs normally in AMPK-deficient mice.

Inhibition or blockade of HSCs (hepatic stellate cells), the main matrix-producing cells involved in the wound-healing response, represents an attractive strategy for the treatment of liver fibrosis. In vitro studies have shown that activation of AMPK (AMP-activated protein kinase), a key player in the regulation of cellular energy homoeostasis, inhibits proliferation of myofibroblasts derived from HSCs. If AMPK is a true regulator of fibrogenesis then defective AMPK activity would enhance fibrogenesis and hepatic fibrosis.

Early detection of steatohepatitis in fatty rat liver by using MR elastography.

Purpose: To assess the potential value of magnetic resonance (MR) elastographic imaging to help detect nonalcoholic steatohepatitis in the fatty rat liver.

Materials And Methods: This study was approved by the regional ethics committee. Fifty-four rats were imaged after being fed either a standard diet, a choline-deficient diet for up to 8 weeks to induce steatohepatitis, or a 2-week orotic acid diet to induce steatosis; or were imaged 48 hours after carbon tetrachloride injection to model acute liver injury.

Enhanced expression of the high affinity glutamate transporter GLT-1 in C6 glioma cells delays tumour progression in rat.

High grade gliomas are known to release excitotoxic concentrations of glutamate, a process thought to contribute to their malignant phenotype through enhanced autocrine stimulation of their proliferation and destruction of the surrounding nervous tissue. A model of C6 glioma cells in which expression of the high affinity glutamate transporter GLT-1 can be manipulated both in vivo and in vitro was used in order to investigate the consequences of increasing glutamate clearance on tumour progression. These cells were grafted in the striatum of Wistar rats and doxycycline was administered after validation of tumour development by magnetic resonance imaging.

Relation between liver progenitor cell expansion and extracellular matrix deposition in a CDE-induced murine model of chronic liver injury.

Unlabelled: In chronic liver injury, liver progenitor cells (LPCs) proliferate in the periportal area, migrate inside the lobule, and undergo further differentiation. This process is associated with extracellular matrix (ECM) remodeling. We analyzed LPC expansion and matrix accumulation in a choline-deficient, ethionine-supplemented (CDE) model of LPC proliferation.

Prevention of steatohepatitis by pioglitazone: implication of adiponectin-dependent inhibition of SREBP-1c and inflammation.

Background/aims: Peroxisome proliferator-activated receptor gamma (PPARgamma) agonist drugs, like pioglitazone (PGZ), are proposed as treatments for steatohepatitis. Their mechanisms of action remain ill-clarified.

Methods: To test the hypothesis that PGZ improves steatohepatitis through adiponectin-dependent stimulation of AMPK and/or PPARalpha, mice lacking adiponectin (Adipo(-/-)) or the AMPKalpha1 catalytic subunit (AMPKalpha1(-/-)) or wild-type (Wt) mice were fed the methionine and choline deficient (MCD) diet, supplemented or not with PGZ.

Transvascular and interstitial transport in rat hepatocellular carcinomas: dynamic contrast-enhanced MRI assessment with low- and high-molecular weight agents.

Purpose: To assess which MRI-derived kinetic parameters reflect decreased transvascular and interstitial transport when low- and high-molecular-weight agents are used in rat hepatocellular carcinomas.

Materials And Methods: Dynamic MRI after injection of a low-molecular-weight contrast agent of 0.56 kDa (Gd-DOTA, gadoterate) and two high-molecular-weight contrast agents of 6.

Alginate moulding: an empirical method for magnetic resonance imaging/positron emission tomography co-registration in a tumor rat model.

Background And Purpose: In the experimental field of animal models, co-registration between positron emission tomography (PET) and magnetic resonance imaging (MRI) data still relies on non-automated post-processing using sophisticated algorithms and software developments. We assessed the value of an empirical method using alginate moulding for PET-MR co-registration in a tumor rat model.

Methods: Male WAG/RijHsd rats bearing grafted syngenic rhabdomyosarcoma were examined under general anesthesia by MRI using a clinical whole-body 3-T system equipped with a sensitivity-encoding four-channel wrist coil and by a small animal PET system using labelled [(18)F]-fluorocholine as tracer.

Inhibition of early preneoplastic events in the rat liver by the somatostatin analog lanreotide.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death, and its incidence is increasing worldwide. Due to the known risk factors (mainly hepatitis B and C viruses), we believe there is a rationale for a chemopreventive approach to treat HCC. Here, based on described in vitro data, we evaluated the preventive effects of lanreotide, a somatostatin analog, on the induction of early carcinogenic events.

Hepatic viscoelastic parameters measured with MR elastography: correlations with quantitative analysis of liver fibrosis in the rat.

Purpose: To determine the correlations between the viscoelastic parameters of the liver measured with in vivo MR elastography and quantitative analysis of liver fibrosis.

Materials And Methods: MR elastography of the liver was performed in 10 rats with hepatic fibrosis induced by intraperitoneal carbon tetrachloride (CCl(4)) injections and five normal rats. Longitudinal waves of 200 MHz were transmitted into the liver with a mechanical transducer.

Assessment of diffusion-weighted MR imaging in liver fibrosis.

Purpose: To assess whether hepatic fibrosis is associated with a restriction in the diffusion of water that can be analyzed with diffusion-weighted MR imaging (DWI) of the liver.

Materials And Methods: DWI was performed in 10 normal rats and 15 rats with liver fibrosis. Echo-planar DWI was performed in the living rats at 1.