This research plan represents the first combination of photoacoustic imaging with polymeric nanosensor technology. This approach couples the imaging depth and resolution of photoacoustics with the tunable sensor response and modular sensor design of nanosensors, enabling continuous monitoring of lithium concentrations in vivo. Bipolar disorder affects approximately 2.6% of the population and lithium is one of the most commonly used management treatments as it drastically reduces suicide risk. Unfortunately, lithium has a narrow therapeutic window and a low toxic dose. The proposed research is to develop lithium selective nanosensors which can be used for continuous monitoring of lithium concentrations in vivo as well as coupling these nanosensors with both fluorescent and photoacoustic imaging. This research will enable improved study of individualized pharmacokinetics and personalized medicine. Additionally, this research will set the groundwork for a wide range of future investigations utilizing the combination of photoacoustics and nanosensors. These include: monitoring metabolic profiles in tumors which are too deep to measure with fluorescence or drug concentration profiling in the brain and other organs.
The specific aims of this research are: 1) Develop and characterize absorbance and fluorescence based nanosensors for lithium detection and characterize in vitro 2) Demonstrate in vivo application of nanosensors using fluorescence imaging for monitoring subcutaneous lithium concentrations 3) Couple lithium nanosensors with photoacoustic microscopy to monitor blood lithium concentrations. This research couples together the Clark laboratory's experience with nanosensor development and testing with the photoacoustic microscopy experience of Lihong Wang's laboratory. The proposed research and training plan enable improve study of individualized pharmacokinetics and personalized medicine will provide ample training in both research techniques as well as career development which will leave me well placed for a future as an independent investigator in biomedical research.

Public Health Relevance

This research plan represents the first combination of photoacoustic imaging with polymeric nanosensor technology. This combination will be used to monitor lithium concentration continuously in vivo to enable improve study of individualized pharmacokinetics and personalized medicine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32EB015270-02
Application #
8458783
Study Section
Special Emphasis Panel (ZRG1-F15-P (20))
Program Officer
Erim, Zeynep
Project Start
2012-04-01
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2013
Total Cost
$53,942
Indirect Cost
Name
Northeastern University
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
001423631
City
Boston
State
MA
Country
United States
Zip Code
02115