Our research is focused on both pre-clinical and aspects basic science of Parkinson's disease research. The preclinical aspect of our research entails the development of a novel optical guidance system for precise targeting of neurosurgical procedures ranging from placement of deep brain stimulating electrodes or infusion catheters to the delivery of stem cell or gene therapy using catheter-based optical coherence tomography (OCT).  The basic science approach takes advantage of our model showing progressive slow dopaminergic degeneration over months in an organotypic nigrostriatal coculture system. 

Neurosurgical guidance

Please click here to see our webpage dedicated to our neuro-imaging projects

For more OCT videos including monitoring of in vivo injections into brain tissue, see "Other Resources" section below.  Manuscript on OCT-guided stereotactic procedures in rodents accepted in August 2008 to Journal of Neuroscience Methods  (see "Publications").

The delivery of therapeutic agents directly to targets deep within the brain is becoming an important tool in the treatment of a variety of neurological disorders.  One of the key factors contributing to the success of gene- or cell-based therapy in the CNS is the ability to precisely and reproducibly deliver the therapy. While the development of therapeutic agents has been advancing for conditions ranging from epilepsy to neurodegenerative disorders such as Parkinson’s disease (PD), there is a continuing need to improve the techniques to deliver them to humans, where precision and reproducibility are essential.

Currently, the standard method to accomplish this is using stereotactic procedures.  While this existing method is adequate for many experimental situations, it has a number of significant drawbacks:

• It is essentially a blind procedure so cannot provide real-time feedback on whether the actual location deviated from the intended location or whether the substance was actually delivered.
• It is impossible to know whether a blood vessel is at risk of becoming lacerated as the probe advances
• To further complicate the procedure, the brain will often shift with respect to the preoperative scan due to leakage of cerebrospinal fluid.
• Even with accurate targeting, delivery of microliter volumes is fraught with complications.  When delivering volumes of a few microliters or less, no method currently exists to verify whether the therapeutic agents actually exited the needle tip.
• Furthermore, it is not currently possible to determine whether the therapeutic agent tracked up along the outside of the needle or dissected into a tissue plane or into the ventricle.

Our research program is a multidisciplinary approach designed to address these issues and bring them to the clinic over a relatively short timeline.

1. We are creating a detailed 3D virtual atlas of the basal ganglion, thalamus, and midbrain regions of the human brain with the following characteristics. A sample of this work can be seen here: 3D reconstruction of human basal ganglia

a. Atlas compiled from of  a large number of human brains, currently n = 3 and increasing
b. Atlas providing more relevant fiber tract information (this is made possible by a novel optical imaging method we have developed, detailed below under lab techniques).
c. Atlas allowing morphing onto the patient's individual low resolution MRI so even in the event of a poor MRI, precise location of the desired target is still possible.
d. Atlas will be useful as new and more specific targets are defined for a variety of procedures.

2. Integrating OCT guidance with existing imaging modalities (MRI, CT).

a. What is OCT? click here to see an OCT pass through human basal ganglia
b. Intra-operative CT provide a certain degree of position feedback. The spatial resolution is very coarse. But it provide information on the degree of brain shift.
c. Intra-operative OCT provide real-time feedback in the ~1 mm spatial domain. We have now completed three live monkey studies using OCT in conjunction with standard stereotactic procedures to approach the GPi. Click here for OCT video of NHP basal ganglia during surgery
d. Once the high resolution 3D atlas is completed it will be possible to directly compare what is observed by OCT with what is expected.

3. Development of forward scanning probe

a. This will likely decrease hemorrhagic complication for all stereotactic procedures.
b. We have just initiated a collaboration with an engineering professor who had invented a clever solution to this technical problem.

OCT video of NHP basal ganglia during surgery

3D reconstruction of human basal ganglia

For more OCT videos, see "Other Resources" section below.