Alpay Özcan

A Prototype Manipulator for Magnetic Resonance-Guided Interventions Inside Standard Cylindrical Magnetic Resonance Imaging Scanners

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 arms 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.

Design and Testing of a Robotic System for mr Image-guided Interventions

The effective integration of robotics together with magnetic resonance (mr) technology is expected to facilitate the real-time guidance of various diagnostic and therapeutic interventions. Specially designed robotic manipulators are required for this purpose, the development of which is a challenging task given the strong magnetic fields and the space limitations that characterize the mr scanning environment. A prototype mr-compatible manipulator is presented, designed to operate inside cylindrical mr scanners. It was developed for the study of minimally invasive diagnostic and therapeutic interventions in the abdominal and thoracic area with real-time mr image guidance. Initial tests were performed inside a high-field clinical mr scanner and included mr-compatibility tests and phantom studies on image-guided targeting.

Characterization of imaging gradients in diffusion tensor imaging.

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 DTIs 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.

Manipulator for magnetic resonance imaging guided interventions: design, prototype and feasibility

The aim of this work is to develop a seven degree of freedom (DOF) remotely controlled manipulator to perform minimally invasive interventions with real-time magnetic resonance imaging (MRI) guidance inside clinical cylindrical scanners. Control of the device is based on MR images collected pre-operatively and in real-time during the procedure. A user interface fuses all sensor information for man-in-the-loop control. Stereotactic guidance uses multislice and/or three-dimensional MR images to set a trajectory of insertion. Free-handed (or manual) guidance uses a master/slave control device, which replicates the kinematics structure of the arm, to control its movement. The control software checks any motion of the manipulator whether it is within an allowable volume extracted from MR images. The device control is performed with a host/target computer configuration. The system is connected to the MR scanner to receive the MR images and send the coordinates of the end-effector for dynamic control of the imaged plane. The manipulator compatibility with the MR environment and image-guided maneuvering was tested on a 1.5 Tesla MR scanner

Quantifying the CDK inhibitor VMY-1-103’s activity and tissue levels in an in vivo tumor model by LC-MS/MS and by MRI

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.

Fast and efficient radiological interventions via a graphical user interface commanded magnetic resonance compatible robotic device.

The graphical user interface for an MR compatible robotic device has the capability of displaying oblique MR slices in 2D and a 3D virtual environment along with the representation of the robotic arm in order to swiftly complete the intervention. Using the advantages of the MR modality the device saves time and effort, is safer for the medical staff and is more comfortable for the patient

A new model for diffusion weighted MRI: Complete Fourier direct MRI

The diffusion weighted MR signal is modeled using particle methods. The model shows that the signal is the Fourier transform of the distribution function of the number of spins at the initial time at a given position with a given displacement integral value. The distribution function is computed via Fourier transform steps that keep the Hermitian property of the signal in order to guarantee that the distribution function is real valued. The function, which depicts the tissue microstructure ‘as it is’ without being tied to any expansions, transformations and assumptions such as Markovian property or symmetry about the spin motions, is displayed using isosurfaces overlayed on the spin density map for a fixed baboon brain sample.

The Interconnection of MRI Scanner and MR-Compatible Robotic Device: Synergistic Graphical User Interface to Form a Mechatronic System

MRI scanner and magnetic resonance (MR)-compatible robotic devices are mechatronic systems. Without an interconnecting component, these two devices cannot be operated synergetically for medical interventions. In this paper, the design and properties of a graphical user interface (GUI) that accomplishes the task is presented. The GUI interconnects the two devices to obtain a larger mechatronic system by providing command and control of the robotic device based on the visual information obtained from the MRI scanner. Ideally, the GUI should also control imaging parameters of the MRI scanner. Its main goal is to facilitate image-guided interventions by acting as the synergistic component between the physician, the robotic device, the scanner, and the patient.

Theoretical and experimental analysis of imaging gradients in DTI

A comprehensive, analytical framework for MR- DTI is constructed in a linear algebra setup. The expressions describing the effects of imaging gradients show formulation ambiguities. Center-symmetric gradient schemes use no cross terms (NoCroT) in the calculations resulting, at least in theory, in the alleviation of the issue. When three estimation methods, all gradients, NoCroT and diffusion gradients only are compared based on experimental results it is observed that the full inclusion of imaging gradients can be detrimental and there is slight improvement with NoCroT over diffusion gradients only. It is concluded that design of new diffusion gradient schemes via optimization is necessary to decouple to the maximum extent the effects of imaging gradients.

Robot-facilitated scanning and co-registration of multi-modal and multi-level sensing: Demonstration with magnetic resonance imaging and spectroscopy

Robotic manipulators have emerged and are continuously evolving as a valuable tool in medical applications. This work introduces a new biomedical application for robotics: multimodality imaging by facilitating scanning of spatially localized bio-sensing and co-registration. Established or currently emerging molecular and near cellular modalities, such as optical and magnetic resonance spectroscopy, offer new opportunities for assessing tissue pathophysiology in situ. The limited tissue penetration of those modalities can be addressed by locally placing the sensor, i.e. with a minimally invasive trans-needle or trans-catheter approach. Herein, we describe the use of a robotic manipulator to scan the area of interest by carrying such a sensor for generating 1-D scans while registering them to a guiding modality. The approach is demonstrated by using a miniature RF coil for collecting proton MR spectra (MRS) and scanning an area of interest on phantoms with the manipulator. MRI is used to guide this procedure as well as co-register MR imaging and spectroscopy. LineScans on two compartment phantoms demonstrated a clear spatial distribution of the resonances originating from those compartments in agreement with the scout guiding MR images. The system described herein, is a generalized platform for performing MR-guided multimodality and multilevel sensing.