Early detection of high-grade malignancy, such as brain tumor glioblastoma multiforme (GBM), using enhanced chemical imaging techniques significantly increases not only the treatment options available, but also the patients’ survival rate. For this purpose, we have developed a new chemical imaging method to detect GBM at early stages based on two key findings: (i) Deoxyhemoglobin can serve as a chemical biomarker for early GBM. Pathologically, GBM is associated with anemia and edema. As GBM cells grow very rapidly, there are usually regional anemia in the brain tumor. GBM cells also increase the vascular endothelial growth factor secretion, weaken the blood brain barrier junctions, and therefore cause excess accumulation of water. Regional anemia and excess accumulation of water cause a local lower concentration of deoxyhemoglobin. Since anemia and edema usually emerge even at the early stage of tumor growth, we take advantage of the slightly lower concentration of deoxyhemoglobin at the tumor and develop new imaging techniques to sensitively detect GBM at early stage. (ii) Paramagnetic deoxyhemoglobin can be sensitively imaged by MRI. The MRI contrast originated from local magnetic-field gradient variations due to lower paramagnetic deoxyhemoglobin concentration in early GBM can be significantly enhanced by our invented “Active-Feedback MRI” [1-7]. An active feedback electronic device was homebuilt to implement active-feedback pulse sequences to generate avalanching spin amplification, which enhances the weak field perturbations from paramagnetic deoxyhemoglobin in GBM. Stage-1 orthotopic GBM mouse models infected with human U87MG cell line were imaged. Representative results from 4 mice were shown below. Statistical results (N=22) show that this new approach provides 5-6 times of improvements in GBM tumor contrast. [1] Science 290, 118 (2001) [2] Magn Reson Med 56, 776 (2006) [3] J Phys Chem B 110, 22071 (2006) [4] Magn Reson Med 61, 925 (2009) [5] Biomaterials 37, 436 (2015) [6] Curr Pharm Des 21, 1 (2015) [7] Magn Reson Med 74, 33 (2015)

Early brain tumor detection by chemical imaging of deoxyhemoglobin

251st National Meeting (2016)

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