The aim of this work is to develop a remotely controlled manipulator to perform minimally invasive diagnostic and therapeutic interventions in the abdominal and thoracic cavities, with real-time magnetic resonance imaging (MRI) guidance inside clinical cylindrical MR scanners. The manipulator is composed of a three degree of freedom Cartesian motion system, which resides outside the gantry of the scanner, and serves as the holder and global positioner of a three degree of freedom arm which extends inside the gantry of the scanner At its distal end, the arm's end-effector can carry an interventional tool such as a biopsy needle, which can be advanced to a desired depth by means of a seventh degree of freedom. These seven degrees of freedom, provided by the entire assembly, offer extended manipulability to the device and a wide envelope of operation to the user, who can select a trajectory suitable for the procedure. The device is constructed of nonmagnetic and nonconductive fiberglass, and carbon fiber composite materials, to minimize artifacts and distortion on the MR images as well as eliminate effects on its operation from the high magnetic field and the fast switching magnetic field gradients used in MR imaging. A user interface was developed for man-in-the-loop control of the device using real-time MR images. The user interface fuses all sensor signals (MR and manipulator information) in a visualization, planning, and control command environment. Path planning is performed with graphical tools for setting the trajectory of insertion of the interventional tool using multislice and/or three dimensional MR images which are refreshed in real time. The device control is performed with an embedded computer which runs real-time control software. The manipulator compatibility with the MR environment and image-guided operation was tested on a 1.5 T MR scanner.

No abstract

It has been demonstrated previously that water diffusion anisotropy in vivo is equivalent to that observed ex vivo after perfusion fixation in the mouse brain. This finding supports the practice of ex vivo diffusion tensor imaging (DTI) measurement on perfusion-fixed tissues. However, the validity of extrapolating ex vivo DTI measurements from immersion-fixed autopsy specimens to the in vivo state is questionable because of variable postmortem delays often encountered before fixation. In this study, we investigated the effect of postmortem delay on the water diffusion anisotropy of ventrolateral spinal cord white matter from mice. Mouse spinal cords, each from the same animal, were examined using DTI in vivo, in situ after death before fixation, and ex vivo immersion fixed 10 h after death. Our results suggest that diffusion anisotropy in mouse spinal cord is preserved up to 10 h after death. Regional characteristics of diffusion anisotropy in mouse spinal cord white matter are equivalent in vivo, in situ after death (up to 10 h before fixation), and ex vivo 15 weeks after immersion fixation.

The development of new small molecule-based therapeutic drugs requires accurate quantification of drug bioavailability, biological activity and treatment efficacy. Rapidly measuring these endpoints is often hampered by the lack of efficient assay platforms with high sensitivity and specificity. Using an in vivo model system, we report a simple and sensitive liquid chromatography-tandem mass spectrometry assay to quantify the bioavailability of a recently developed novel cyclin-dependent kinase inhibitor VMY-1-103, a purvalanol B-based analog whose biological activity is enhanced via dansylation. We developed a rapid organic phase extraction technique and validated wide and functional VMY-1-103 distribution in various mouse tissues, consistent with its enhanced potency previously observed in a variety of human cancer cell lines. More importantly, in vivo MRI and single voxel proton MR-Spectroscopy further established that VMY-1-103 inhibited disease progression and affected key metabolites in a mouse model of hedgehog-driven medulloblastoma.

For obtaining a complete model the diffusion tensor imaging (DTI) method is derived in a new linear algebraic framework in order to include the effect of all of the magnetic field gradients on the MRI signal. In the framework, the coefficient matrix of the estimation equations consists of the sum of three matrices corresponding to diffusion gradients, imaging gradients and the cross–terms between them. The derivations demonstrate that there exists modeling incongruities originating from the choice of phase–encoding gradient magnitude and the read–out gradient affecting the entirety of the signal sample points. These reflect on the cross–terms and the imaging gradient coefficient matrix, revealing the DTI's inadequacy for the inclusion of imaging gradients. The linear algebraic framework mitigates the inadequacy by the utilization of center–symmetric gradient schemes. The observations are verified by the experimental results obtained from an isotropic phantom using several existing diffusion gradient schemes.