New imaging technique may facilitate surgical precision in removing entire brain tumor

Moritz Kircher, M.D.,Ph.D.

Memorial Sloan-Kettering Cancer Center

Funded in September, 2011: $300000 for 3 years
LAY SUMMARY . ABSTRACT . BIOGRAPHY .

LAY SUMMARY

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New imaging technique may facilitate surgical precision in removing entire brain tumor

This study will validate a new MRI imaging technique in an animal model of brain tumor that could enable surgeons to precisely remove all tumor cells to extend survival and possibly save lives.         

Patients with deadly brain tumors (glioma) rarely live more than two years after the tumor is surgically removed. Current MRI techniques do not enable neurosurgeons to detect residual microscopic cancer cells that have migrated beyond the edges (“margins’) of the tumor mass and infiltrated many other brain areas. Consequently, tumor recurs, and the patient dies. Current MRI techniques simply lack spatial resolution and the ability to detect all cancer cells (sensitivity) and only cancer cells (specificity).  

The Sloan-Kettering investigators have developed a new approach to MRI imaging of brain gliomas that they hypothesize will have adequate sensitivity, specificity and spatial resolution to prevent tumor recurrence. They will undertake studies in animals with transplanted human glioma to validate the technique’s effectiveness. The technique involves a single intravenous injection into the patient of a nanoparticle, a tiny molecular probe that attaches solely to glioma cells. The nanoparticle is highly permeable, so it can get into the brain and into any brain cell that has been infiltrated by tumor. Moreover, it lasts for a week. So, after using this MRI imaging technique preoperatively to map the surgical plan, the surgical team will use a hand-held “Ramon” imaging device during surgery to pick up the nanoparticle’s signal. This will enable the neurosurgeon to identify any and all tumor cells and remove them, while sparing healthy brain tissue. Then the investigators will examine the surgically removed tissue to verify that it contains tumor cells and will examine the remaining autopsied brain tissue to verify that it contains no tumor cells. 

Significance: If successful in the animal model, this imaging technique will be rapidly translated into clinical trials in patients with deadly brain tumors and may ultimately improve outcomes.   

 

ABSTRACT

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Malignant brain tumors remain a therapeutic challenge, partially because of the difficulty of visualizing infiltrative tumor borders during surgical resection. The overall goal of this project is to develop a new molecular approach to brain tumor imaging that allows both preoperative staging and intraoperative high-resolution imaging using a single molecular imaging agent. We propose to accomplish this by using a novel dual-modality MRI-Raman nanoparticle. This nanoparticle consists of a thin Raman active layer adsorbed to an inert gold core protected by a silica shell, and is coated with gadolinium ions. This nanoparticle can be detected by both MRI and Raman spectroscopic imaging with very high sensitivity. It was shown that this nanoparticle allows three-dimensional visualization of brain tumors with MRI, and high-resolution guidance of tumor resection with Raman imaging in mouse glioblastoma models. Because the nanoparticle is retained by the brain tumor for more than a week, it allows performing both preoperative and intraoperative imaging with a single intravenous injection of the nanoparticle.
The nanoparticle approach used here has a significant potential for clinical translation as gold-silica nanoparticles are relatively inert materials and some of these constructs have already entered clinical trials. In addition, hand-held Raman imaging devices that could be used in the operating room have already been developed. The results obtained from this proposal could significantly accelerate the translation of this novel strategy into the clinics. We hope that this approach will ultimately lead to improved brain tumor resection and thus lead to better survival of brain tumor patients.


 

 

 

INVESTIGATOR BIOGRAPHIES

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Moritz Kircher, M.D.,Ph.D.

Moritz Kircher, MD, PhD is a graduate of the Humboldt University Medical School in Berlin, Germany. He underwent radiology residency and MRI fellowship training at Harvard and Stanford University and postdoctoral training at the Center for Molecular Imaging Research at Harvard and the Molecular Imaging Program at Stanford. In 2010, he joined the faculty of Memorial Sloan-Kettering Cancer Center as a physician-scientist, focusing on novel multimodal molecular nanoparticle imaging approaches for combined pre-and intraoperative cancer detection. In particular, this involves novel imaging technologies such as surface-enhanced Raman spectroscopy that enable cancer detection with the highest sensitivity and specificity.


URL of my profile:

http://www.mskcc.org/cancer-care/doctor/moritz-kircher


Key Words:

Central Nervous System
Brain Tumors
Animal Research
Imaging
MRI