Multi-probe robotic positioner for cryoablation in MRI

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2012.Cataloged from PDF version of thesis.Includes bibliographical references (p. 116-118).This thesis describes the design of a guidance device for faster and more accurate targeting of multiple probes during cryoablation and other percutaneous interventions performed in closed bore magnetic resonance (MR) imaging systems. The device is intended to be mounted onto a Siemens 110 mm MR loop coil that rests on the patient and contains a cable driven two-degree-of- freedom spherical mechanism that orientates the intervention probes about a remote center of motion located 15 mm above the skin entry point. A carriage, pulled by strong and low stretch cables, can position up to three intervention probes as it travels on a rotating hoop. Its motion is constrained by a custom designed roller bearing to minimize friction. A thumbscrew fastened latch allows a probe to be engaged in a guide that constrains the probe along a specific trajectory. The probe can also be disengaged from its track, freeing it to move with respiration and enabling the guide to be repositioned for another probe to be inserted. Compact MR compatible piezoelectric motors are used to actuate the system. A prototype was built from 3D printed ABS plastic as a proof of concept. Bench level evaluation demonstrated that each component of the device performs according to the design specifications. The device performance was characterized by analyzing still images taken before and after movement, which yielded sub-degree accuracy, sub-degree repeatability near vertical position, and an incremental step resolution of at least 0.5 degree. Upon further developments of the registration and calibration modules in 3D slicer to interface the robot with image data, evaluation of the device in MRI will be performed.by Faye Y. Wu.S.M

Ultra-High Field Strength MR Image-Guided Robotic Needle Delivery Device for In-Bore Small Animal Interventions

Current methods of accurate soft tissue injections in small animals are prone to many sources of error. Although efforts have been made to improve the accuracy of needle deliveries, none of the efforts have provided accurate soft tissue references. An MR image-guided robot was designed to function inside the bore of a 9.4T MR scanner to accurately deliver needles to locations within the mouse brain. The robot was designed to have no noticeable negative effects on the image quality and was localized in the MR images through the use of an MR image visible fiducial. The robot was mechanically calibrated and subsequently validated in an image-guided phantom experiment, where the mean needle targeting accuracy and needle trajectory accuracy were calculated to be 178 ± 54µm and 0.27 ± 0.65º, respectively. Finally, the device successfully demonstrated an image-guided needle targeting procedure in situ

Microgel Suspensions for Tissue Engineering and Tumor Models

Human tissues are complex materials with hierarchical organizations of a variety of different cell types and matrix properties. Capturing these properties in vitro has been a chief goal of tissue engineering since its inception. However, full recapitulation of native tissue structures and functions remains unresolved. This thesis explores a new methodology to capture native tissue’s complexity using hydrogel matrices composed of microgel suspensions. In this thesis, I developed a new microgel particle using a water in oil emulsion technique with methacrylated gelatin. The mechanics and size of individual microgels are readily tunable. Packing particles tight enough forms jammed suspensions that enable direct extrusion of the particles as a 3D printing ink. And exposure to purple light photocrosslinks microgels together into annealed cell-laden matrices for long term culture. When jammed, microgels also function as a support bath for 3D printing. To demonstrate the utility of a microgel support bath, I created a model tumor microenvironment to study cancer metastasis. Direct writing of a Pluronic sacrificial ink into a stromal cell-microgel suspension was used to form endothelialized vessel structures. Further 3D printing of melanoma cancers enabled freeform spatial control over tumor architectures and relative distances to vessel structures. Tumor cells were found to migrate into the prototype vessels as a function of distance. I next explored microgel suspensions as a platform for stem cell differentiation. Current efforts to recapitulate native tissue structures using stem cells lack tight spatial control over cell locations and matrix architectures. To address this issue, I first demonstrate how modifications to microgel properties can direct stem cell differentiation. By combining varied microgels together, I created gradients of microgel sizes and stiffness to spatially direct cell lineage using adipose derived stromal cells (ADSCs) as a model stem cell system. Further optimizations of cell printing enabled high spatial control over cell location and differentiation outcomes. As a final demonstration, I created heterogenous matrices of microgels with interspersed or directly printed functional microcapsules. The novel capsule design enabled the highest recorded loading of protein in a microscale volume, accommodating up to 40 mg/mL of biologically active species within a single microcapsule. By adding in enzymes, gas releasing hydrogels, and nanoparticles, I successfully perturbed the local gas concentrations within the matrix. I demonstrate the capsules capacity as a 3D printable ink, enabling spatial control over gradients of gas release to direct secondary messenger signals. The modularity of the system was demonstrated through several potential applications including attenuation of peroxide activity to combat radiation damage, and creating hypoxic cell culture conditions for wound healing and tumor microenvironment mimicry Together, these findings demonstrate the versatility of GelMa microgel suspensions as a tool with unique advantages for biofabrication and scaffolding for tissue engineering. This work has scope across the fields of material science, bioengineering, regenerative medicine, and cancer modeling

Neurological Disease Diagnosis and Treatment via Precise Robotic Intervention

This work focuses on the development and application of mechatronic systems for measurement, diagnosis and treatment of acute and chronic neurological conditions. The development of an automated tendon reflex stimulation device, as well as analysis and classification methods for both automated and manual stimulus delivery will provide the groundwork for improvements to both diagnosis and treatment of neurological injuries. In a similar vein, development of a variable resonance actuator for Magnetic Resonance Elastography imaging enables tissue property measurement of the intervertebral discs, hopefully providing an early marker and better understanding of degeneration. In addition to MRI based spinal tissue property measurements, an MRI guided high precision robot is developed for direct injection into the spinal cord, along with an accompanying image guided control scheme. The novel parallel plane mechanism enables control of 4 degrees of freedom, while the linear piezoelectric actuators in a direct drive configuration enables superior accuracy. Taken together, these robotic device developments constitute contributions to the field of precision medical robotics with applications to physiological understanding of the human body.Ph.D

Radiolabeled Compounds for Diagnosis and Treatment of Cancer

Radiopharmaceuticals are used in the diagnosis and treatment of various diseases, especially cancer. In general, radiopharmaceuticals are either salts of radionuclides or radionuclides bound to biologically active molecules, drugs, or cells. Tremendous progress has been made in discovering, developing, and commercializing numerous radiopharmaceuticals for the imaging and therapy of cancer. Significant research is ongoing in academia and the pharmaceutical industry to develop more novel radiolabeled compounds as potential radiopharmaceuticals for unmet needs. This Special Issue aims to focus on all aspects of the design, characterization, evaluation, and development of novel radiolabeled compounds for the diagnosis and treatment of cancer and the application of new radiochemistry and methodologies for the development of novel radiolabeled compounds. Outstanding contributions presented in this Special Issue will significantly add to the field of radiopharmaceuticals