A clinical trial that uses real-time intraoperative MRI (RT-iMRI) to deliver stem cell therapy into the brain for treating Parkinson's disease (PD) has gained approval from U.S. regulatory agencies. Foundational research on the method was published in the Journal of Neurosurgery.
PD is a neurodegenerative disorder that primarily affects dopamine-producing neurons in the brain, which leads to motor impairment. Traditional treatments rely on medication to manage symptoms but do not repair neural damage. Stem cell transplantation has emerged as a possible route to replacing lost cells, and in that approach the accuracy of the injection site is decisive for transplant survival and for whether the graft connects to host circuitry. The putamen is the usual target, since it receives the dopaminergic input that is lost as the substantia nigra degenerates, and a graft placed outside it survives without restoring the circuit.
RT-iMRI generates high-resolution 3D images in real time, which gives dynamic monitoring during surgery and lets the surgeon confirm the placement of instruments and therapeutic agents while the procedure is running. Studies show that using RT-iMRI to guide stem cell transplantation in cynomolgus monkeys improves motor function and neural recovery compared with traditional methods.
The research used dopaminergic neuroprogenitor cells (DANPCs) derived from human-induced pluripotent stem cells (iPSCs), delivering these cells to the putamen region of cynomolgus monkeys under RT-iMRI guidance.
Experimental Design and Methods
Researchers immunosuppressed nine cynomolgus monkeys to simulate clinical conditions. RT-iMRI was used to monitor each step of the brain injection in real time, so that cells were placed in the targeted striatum under direct observation rather than by coordinates alone. Immunosuppression is a standard requirement in this design: human cells grafted into a macaque brain are rejected within days unless the host response is suppressed, and the regimen has to be tolerated for the full observation period.
Cell Preparation and Injection
Dopaminergic neuroprogenitor cells were suspended in a carrier solution containing an MRI contrast agent (gadoteridol). Each hemisphere of the monkeys' brains received two needle tracks for the injection, with catheters along both dorsal and ventral pathways delivering varying doses of the cell suspension. The contrast agent is what makes the deposit visible on the scan, and it is the reason the injection can be judged while it happens.
Real-Time Monitoring and Injection Strategy
RT-iMRI allowed researchers to confirm the positioning of the catheter and the distribution of injected cells, which limits the risk of cell leakage or damage from misalignment, a problem common with traditional techniques. A slow injection rate (2.5 µL/min) reduced fluid reflux and kept the cells in the target area.
Key Findings and Results
All cynomolgus monkeys successfully received bilateral striatal cell injections, and RT-iMRI confirmed precise targeting. Tissue analysis at 7 and 30 days post-injection revealed the survival and differentiation of dopaminergic neuroprogenitor cells in the striatum, with signs of integration and neural fiber extension. Immunohistochemical staining confirmed positive expression of the human cell marker STEM121, indicating that the transplanted cells survived and dispersed along the injection tracks.
Innovation and Significance
The study shows what RT-iMRI can do in preclinical central nervous system (CNS) research. With precise targeting, stem cells can be implanted into the intended brain region more reliably, and the therapeutic outcome follows from that. The precision and safety demonstrated in stem cell transplantation point to a role for RT-iMRI in studying diseases such as Parkinson's, in developing new treatment strategies, and in shortening the path to clinical translation.
Prisys Biotechnologies is the first in Asia to introduce the RT-iMRI, integrated with the Orchestral Head Frame for non-human primates and SmartFlow catheters, which apply Convection-Enhanced Delivery (CED) Technology to bypass the blood-brain barrier. CED maintains a pressure gradient at the catheter tip so that infusate moves through tissue by bulk flow instead of diffusion, which is why reflux control and a steady rate decide how far the deposit spreads.
Prisys Biotechnologies' CNS platform integrates RT-iMRI, CT, DSA, and ultrasound into one navigation and delivery system, which raises the success rate of brain-targeted therapies and improves the precision and safety of neurosurgical procedures. Applied to cynomolgus monkey models, the platform supports closer disease simulation and more precise delivery of candidate therapies.
**Prisys Biotech's Intrastriatal Drug Injection Procedure with Simultaneous Scanning**
Prisys Biotechnologies has established cynomolgus monkey models for several CNS diseases, including Parkinson's disease (PD), cerebral ischemia (MCAO), epilepsy, and pain. Using RT-iMRI, researchers can deliver drugs and interventions to defined targets in these models. In the PD model, medications can be delivered directly to the target brain region to evaluate efficacy and mechanism of action; in the ischemia model, real-time monitoring of ischemic region changes supports assessment of neuroprotective drug efficacy.
Prisys Biotechnologies continues to develop RT-iMRI applications in CNS disease research and treatment, working with research groups on delivery questions that coordinates alone cannot answer, and on the imaging evidence needed to show where a deposit actually landed.
Reference:
Emborg, M.E., Mancinelli, A., Colwell, J.C., et al. (2024). Preclinical evaluation of transaxial intraputaminal trajectory for enhanced distribution of grafted cells in Parkinson's disease. Journal of Neurosurgery, 1(aop), 1-13.
