[Angiogenesis inhibition: review of the activity of sorafenib, sunitinib and bevacizumab]. / Inhibiteurs de l'angiogenèse : revues de l'apport thérapeutique du sorafenib, du sunitinib et du bevacizumab dans le cancer du rein métastatique.

Renal cell carcinoma accounts for approximately 3% of all human malignancies. The use of cytokines in metastatic stage of disease has been the standard until last decades, presenting partial and short duration responses. Research on angiogenesis in renal carcinoma has brought important advances to understand tumor biology and to allow us development of new antiangiogenic drugs. Sunitinib (SUTENT), sorafenib (NEXAVAR) and bevacizumab (AVASTIN) are actually three molecules accepted to use in metastatic renal cell carcinoma (mRCC), with a good tolerability demonstrated in different studies. Clinical evidence shows sunitinib to be reference standard of care for the first-line treatment of mRCC. The use of bevacizumab in combination with interferon alfa (IFN alfa) can also be considered in this setting. Sorafenib is recommended for second-line treatment in cytokine-refractory patients, sunitinib being also accepted in this situation. Other combination of these molecules and their use as neo-adjuvant and adjuvant therapy is being evaluated and should change in the short term the management of the disease.

Analysis of the distribution of MRI contrast agents in the livers of small animals by means of complementary microscopies.

BACKGROUND: Magnetic resonance imaging (MRI) contrast agents contain magnetic molecules such as iron (Fe) or gadolinium (Gd) that are injected in vivo into rats or mice to study their distribution inside the liver. Fluorescent europium (Eu) can be used as a model of Gd to obtain comparable information of this distribution of corresponding contrast agents. In a similar approach, Fe can be attached to Texas Red and used as a model of ferumoxides and be detected by fluorescence. METHODS: To combine and compare the advantages of different microscopic imaging modes, characterization studies were carried out by means of a confocal laser scanning microscope (CLSM), a secondary ion mass spectrometric (SIMS) microscope, and an electron energy loss spectrometric (EELS) microscope. In the case of CLSM, the locations of fluorescent signals inside preparations were determined by factor analysis of biomedical image sequences (FAMIS) and selection of image sequences at emission. RESULTS: By CLSM and FAMIS, we distinguished chelated Eu and Texas Red attached to Fe. By SIMS microscopy, we distinguished Eu and Gd of chlorides and chelates and Fe of a ferumoxide. By EELS microscopy, we distinguished Eu and Gd of chlorides. CONCLUSIONS: Analysis of compounds inside correlative specimens by means of CLSM, SIMS, and EELS microscopes provided complementary results.

Mechanisms of action of liver contrast agents: impact for clinical use.

New contrast agents for magnetic resonance imaging are continually being developed by pharmaceutical companies in order to better image the liver. These agents can be divided into hepatobiliary agents directed to the hepatocytes and nanoparticulate agents directed to the reticulo-endothelial system. After intravenous injection, all these agents concentrate in the liver and induce profound changes in signal intensity. Particulate agents induce predominantly a darkening of the liver parenchyma, while hepatobiliary agents induce a brightening. In both cases, liver-lesion conspicuity is enhanced, leading to a better visualization of the lesion. After a brief description of the principal characteristics of the agents, this paper will attempt to summarize the utility of these agents for the detection and characterization of focal liver disease.

Noninvasive assessment of language dominance in children and adolescents with functional MRI: a preliminary study.

BACKGROUND: Assessment of language organization is crucial in patients considered for epilepsy surgery. In children, the current techniques, intra-carotid amobarbital test (IAT) for language dominance, and cortical electrostimulation mapping (ESM), are invasive and risky. Functional magnetic resonance imaging (fMRI) is an alternative method for noninvasive functional mapping, through the detection of the hemodynamic changes associated with neuronal activation. We used fMRI, to assess language dominance in children with partial epilepsy. METHODS: Eleven right handed children and adolescents performed a word generation task during fMRI acquisition focused on the frontal lobes. Areas where the signal time course correlated with the test paradigm (r = 0.7) were considered activated. Extent and magnitude of signal changes were used to calculate asymmetry indices. Seven patients had IAT, ESM, or surgery outcome available for comparison. RESULTS: fMRI language dominance always agreed with IAT (6 cases) and ESM (1 case), showing left dominance in six and bilateral language in one. fMRI demonstrated left dominance in three additional children, and right dominance in one with early onset of left temporal epilepsy. Four children whose initial studies were equivocal due to noncompliance or motion artifacts were restudied successfully. CONCLUSIONS: fMRI can be used to assess language lateralization noninvasively in children. It has the potential to replace current functional mapping techniques in patients, and to provide important data on brain development.

Measurement of liver blood volume using a macromolecular MRI contrast agent at equilibrium.

Liver regional blood volume (LRBV) is altered by several disease states and various drugs. Preliminary studies in the rat, using research MR imaging instruments at 2T and vascular contrast agents, have suggested that MRI may be used to measure LRBV. Our goal was to develop a technique for measuring LRBV using a clinical machine at 1.5 T. This study was performed in the rabbit, using CarboxyMethylDextran Gd-DTPA, a macromolecular contrast agent with a molecular weight of 158 kDa. MRI was performed at 1.5 T, in the plane of the inferior vena cava, with and without flow compensation, before contrast injection and in the steady state after injection. Accuracy and stability of LRBV measurement, over 2 h and with various doses (0.01-0.05 mmol/kg), was tested against a standard Evan's Blue dye-indicator technique. LRBV was 28 +/- 2 mL/100 g when measured by MRI with flow compensation, which is in good agreement with the literature and with the 26 +/- 6 mL/100 g, measured by the Evan's Blue dilution technique. Measurements varied less than 7% over time and less than 9% over the range of doses. LRBV was overestimated using a sequence without flow compensation especially when large doses of contrast agent were injected. This noninvasive MRI technique provides a simple method for measuring liver LRBV and offers new prospects for future physiological and pathological studies.

Phospholipid abnormalities in early Alzheimer's disease. In vivo phosphorus 31 magnetic resonance spectroscopy.

OBJECTIVE: To determine whether changes in phosphomonoester and phosphodiester levels could be detected in vivo with phosphorus magnetic resonance spectroscopy in the early stage of Alzheimer's disease (AD). DESIGN: Survey-type of case-control study using neuropsychological testing as criterion standard with blinded data analysis. SETTING: Patients were from a neurology clinic in Paris, France. The controls were from the community. Magnetic resonance measurements were performed in the prefrontal region of the brain with a clinical 1.5-T scanner. Blinded data analysis. PARTICIPANTS: Twenty-four patients with mild AD and 15 age-matched healthy volunteers. Subjects were separated into two groups, both composed of patients with AD and healthy volunteers. Two successive acquisition protocols were used in the two groups. RESULTS: A significant increase in the phosphomonoester-total phosphorus ratio was found in patients with AD compared with controls. In this series, use of a ratio above 11% as a threshold to test our sample yielded an 83.3% sensitivity and a 73.3% specificity test for AD. Other metabolite ratios (inorganic phosphate, phosphodiesters, phosphocreatine, and nucleotide phosphates to total phosphorus) were not significantly different between patients and controls. No metabolite ratio correlated with the neuropsychological status as assessed by the Mini-Mental State Examination. CONCLUSION: Changes in phospholipid metabolism can be detected in vivo in the early stage of AD. Discrepancies in the literature may be due to differences in technical setting or in subject population types.

Activation of human primary visual cortex during visual recall: a magnetic resonance imaging study.

The degree to which the process involved in visual perception and visual imagery share a common neuroanatomical substrate is unclear. Physiological evidence for localization of visual imagery early in the visual pathways would have important bearing on current theories of visual processing. A magnetic resonance imaging technique sensitive to regional changes in blood oxygenation was used to obtain functional activation maps in the human visual cortex. During recall of a visual stimulus, focal increases in signal related to changes in blood flow were detected in V1 and V2 cortex in five of seven subjects. These experiments show that the same areas of the early visual cortex that are excited by visual stimulation are also activated during mental representation of the same stimulus. Some of the processes used in topographically mapped cortical areas during visual perception may also be utilized during visual recall.

[Spectroscopy of the liver in vivo using nuclear magnetic resonance. A new approach in hepatic physiopathology]. / La spectroscopie du foie in vivo par résonance magnétique nucléaire. Un nouvel abord de la physiopathologie hépatique.

Nuclear magnetic resonance (NMR) spectroscopy is a non-invasive means of detecting numerous compounds, thus enabling real-time studies to be carried out on such topics as energy metabolism, intracellular pH and main intermediate metabolism pathways. This method has been used for several years to study perfused livers and rat livers in vivo, but its application to man has just begun. We describe some of its principal uses, with emphasis on the possibilities it offers to investigate the metabolic pathways. With the rapid advances made in this field, and particularly spectroscopic imaging, NMR spectroscopy should prove valuable in four main branches of research: understanding of physiological and pathological metabolic mechanisms, diagnosis with the possibility of functional tests, follow-up and assessment of new medical treatments, and pharmacology.