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
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.
- Science 290, 118 (2001)
- Magn. Reson. Med. 56, 776 (2006)
- Magn. Reson. Med. 61, 925 (2009)
- J. Phys. Chem. B 110, 22071 (2006)