posters 5th Asia-Pacific NMR Symposium 2013

Towards Early Detection of Pancreatic Cancers & Brain Tumors by Active-Feedback MR Imaging (#135)

Chaohsiung Hsu 1 2 , Zhao Li 3 , Dueng-Yuan Hueng 4 , Dennis Hwang 5 , Lian-Pin Hwang 6 , Yung-Ya Lin 3
  1. Department of Chemistry, National Tsing-Hua University, Hsinchu, Taiwan
  2. Molecular Science and Technology Taiwan International Graduate Program, Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, Taiwan
  3. Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA
  4. Department of Neurological Surgery, Tri-Service General Hospital, Taipei, Taiwan
  5. Department of Chemistry and Biochemistry, National Chung-Cheng University, Chiayi, Taiwan
  6. Department of Chemistry, National Taiwan University, Taipei, Taiwan
Objectives.  Early detection of high-grade malignancy, such as pancreatic cancers and glioblastoma multiforme (GBM), significantly increases patients’ survival rate. For this purpose, a new approach, termed “Active-Feedback MR”, was developed. An active-feedback electronic device was homebuilt to implement active-feedback pulse sequences to generate “avalanching spin amplification” effect, which enhances the weak magnetic-field perturbations from magnetic nanoparticles in targeted pancreatic cancers or malignant physiological conditions in GBM.
Methods.
  The general principles of the “Active-Feedback MR” were detailed in our publications1-4. Here, its specific applications to early tumor detection were developed and demonstrated. (i) An active-feedback electronic device was home-built. It filters, phase-shifts, and amplifies the signals from the receiver coils and then re-transmits the modified signals into the RF transmission-coil with adjustable and programmable feedback phases and gains, allowing us utilize the active-feedback fields in novel ways. (ii) Active-feedback pulse sequences were developed for early tumor detection and was statistically tested on in vivo orthotopic mice tumor models.

Results: Early
Pancreatic Cancers Detection.  Anti-CA19-9 antibodies were conjugated to NH2-PEG-coated magnetic nanoparticles. The antigen binding capacity to CA19-9 over-expressing cell lines (BxPC3) was confirmed by in vitro MR cellular images. In vivo images of orthotopic pancreatic cancers (PANC-1) mouse models show that the active-feedback images successfully highlight the magnetic nanoparticles distribution with close correlation with iron-stained histopathology.

Results: Early GBM Detection.  
Orthotopic GBM mouse models infected with human U87 cell-line were imaged. Our active-feedback images and decay constant mapping provide 4-5 times of improvements in GBM tumor contrast through sensitively imaging the susceptibility variations due to irregular water contents and deoxyhemoglobin.

Conclusion.  
In vivo pancreatic cancers and GBM mouse models validated the superior contrast/sensitivity and robustness of the “Active-Feedback MR” for early tumor detection. Statistical results at various cancer stages and alternative active-feedback pulse sequences with improved performance will also be presented.
  1. Science 290, 118 (2001)
  2. Magn. Reson. Med. 56, 776 (2006)
  3. Magn. Reson. Med. 61, 925 (2009)
  4. J. Phys. Chem. B 110, 22071 (2006)