Quantitative Susceptibility Mapping: Concepts and Applications.

PURPOSE: To review the fundamental principles of susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM), and to discuss recent clinical developments. METHODS: SWI is a magnetic resonance imaging method that takes advantage of magnitude signal loss and phase information to reveal anatomic and physiologic information about tissue and venous vasculature. The method enhances image contrast qualitatively, relying on phase shifts due to differences in magnetic susceptibility between tissues. QSM, extending SWI in an elegant way, is a new sophisticated postprocessing technique that numerically solves the inverse source-effect problem to derive local tissue magnetic susceptibility (source) from the measured magnetic field distribution (effect) as it is reflected in the phase images of gradient-echo sequences. RESULTS: SWI has meanwhile been established in numerous clinical as well as basic biomedical applications due to its ability to highlight tissue structures and compounds that are difficult to detect by conventional magnetic resonance imaging (MRI), including iron, calcifications, small veins, blood, and bones. The field of QSM has also progressed rapidly, both in terms of optimizing the post-processing strategies and algorithms as well as in gaining ground for new clinical applications that take advantage of its quantitative nature and improved specificity to identify the magnetic signature of lesions. CONCLUSIONS: Though magnetic susceptibility may be a major nuisance producing image artifacts in MRI, recent work has transformed it into a useful source of image contrast. Both SWI and QSM are gaining increasing acceptance in clinical practice. In particular, QSM provides new insights into tissue composition and organization due to its more direct relation to the actual physical tissue magnetic properties.

Acquisition and interactive 3D exploration of the internal structure of a dissected specimen.

We present a system to keep track of a destructive process such as a medical specimen dissection, from data acquisition to interactive and immersive visualization, in order to build ground truth models. Acquisition is a two-step process, first involving a 3D laser scanner to get a 3D surface, and then a high resolution camera for capturing the texture. This acquisition process is repeated at each step of the dissection, depending on the expected accuracy and the specific objects to be studied. Thanks to fiducial markers, surfaces are registered on each others. Experts can then explore data using interaction hardware in an immersive 3D visualization. An interactive labeling tool is provided to the anatomist, in order to identify regions of interest on each acquired surface. 3D objects can then be reconstructed according to the selected surfaces. We aim to produce ground truths which for instance can be used to validate data acquired with MRI. The system is applied to the specific case of white fibers reconstruction in the human brain.

Retrovirus-mediated transfer of a suicide gene into lens epithelial cells in vitro and in an experimental model of posterior capsule opacification.

PURPOSE: The most common complication of cataract surgery is the development of posterior capsule opacification (PCO). Hyperplasia of the lens epithelium is one of the main cellular events following phacoemulsification and was found to be an important feature contributing to opacification of the posterior capsule. We investigated the feasibility of killing the residual lens epithelial cells by retroviral-mediated transfer of the herpes simplex virus-thymidine kinase (HSV-tk) gene, a well-studied suicide gene, into rabbit lens epithelial cells followed by ganciclovir (GCV) treatment. METHODS: The capacity of retroviral vectors to transfer genes into rabbit lens epithelial cells was determined either in vitro (culture of rabbit lens epithelial cells) or in vivo (experimental model of PCO in rabbits) using cDNA encoding the beta-galactosidase (LacZ) reporter gene. To evaluate the efficiency of suicide gene therapy (infection with retroviral vectors encoding the HSV-tk gene followed by GCV treatment) we determined the sensitivity of HSV-tk infected lens epithelial cells to different concentrations of GCV in vitro. Then, in an experimental model of PCO, rabbits were treated with HSV-tk retroviral vectors at the end of the surgery and they received repeated intracameral and intravitreal injections of GCV at the concentration determined by the in vitro experiments. RESULTS: Infection efficiency using LacZ retroviral vectors was about 29% in vitro and 10% in vivo. After infection of the HSV-tk cDNA in vitro, the cell killing effect of GCV was evaluated. A significant enhancement (four- to five-fold) of the cell sensitivity to GCV was shown in FLY-DFGtk as compared with mock infected (P < 0.01) cells even without selection of the HSV-tk positive cells. The GCV concentration leading to 50% reduction in cell number (IC50) was 50 microg/ml. In vivo infection with a HSV-tk vector led to the tk gene transfer into lens epithelial cells. Despite this local HSV-tk gene expression, we could not prevent capsule opacification. CONCLUSIONS: Lens epithelial cells were successfully infected both in vitro and in vivo by beta-galactosidase and HSV-tk genes via retroviral vectors. In vitro infected lens epithelial cells displayed a strong sensitivity to GCV treatment. In vivo, we could not prevent capsule opacification in the rabbit model, very likely due to the limited level of the HSV-tk gene expression. However, our results suggest that virus-mediated suicide gene therapy might be a feasible treatment strategy to prevent capsule opacification with a more powerful vector.

Adenovirus-mediated suicide gene transduction: feasibility in lens epithelium and in prevention of posterior capsule opacification in rabbits.

The most common complication of cataract surgery is the development of posterior capsule opacification (PCO). Hyperplasia of the lens epithelium is one of the main cellular events following phacoemulsification, and has been found to be an important feature contributing to opacification of the posterior capsule. Adenoviral vector-mediated transfer is a suitable method for transducing the herpes simplex virus thymidine kinase gene (HSV-tk) into proliferating cells, allowing for the selective killing of these cells by ganciclovir (GCV) treatment. To determine the potential of gene transduction for lens epithelial cells, we studied the transduction of rabbit lens epithelial cells with adenoviral vectors containing either the Escherichia coli beta-galactosidase (lacZ) gene or the HSV-tk gene in vitro and in vivo in an experimental model of PCO. The efficiency of lacZ gene transfer in rabbit lens epithelial cells was at least 95% both in vitro and in vivo. In vivo transduction with HSV-tk adenoviral vector followed by GCV treatment significantly inhibited the development of PCO (p<0.001). These results suggest that adenoviral vector-mediated transfer of HSV-tk into the proliferating lens epithelial cells is feasible and may provide a novel therapeutic strategy for PCO.