The Noninvasive Diagnosis of Central Nervous System Leukemia by Specifically Enhanced Magnetic Resonance Imaging

Central nervous system (CNS) infiltration in acute lymphoblastic leukemia (ALL) frequently serves as a critical indicator of disease relapse. However, there is currently a lack of early, noninvasive, effective, and straightforward diagnostic methods. Magnetic resonance imaging (MRI) plays a pivotal role in the diagnosis of CNS disease due to its exceptional soft tissue resolution and multidimensional imaging capabilities. However, conventional MRI techniques are ineffective in the diagnosis of CNS leukemia (CNS-L) because there was a lack of an MRI contrast agent with high selectivity to tumor cells in the early stage. In this study, inactivated NALM6 cells, a type of acute lymphoblastic B cell, were used as carriers loaded with gadolinium (Gd) ions to develop a novel MRI contrast agent, named Gd-INC, which targets leukemic metastatic leptomeninges. The T₁-weighted imaging (T₁WI) relaxation rate of Gd-INC reached 8.818 mM^-1 s^-1, more than double that of clinically used Gd-DOTA (3.195 mM^-1 s^-1). Due to its high relaxation rate and selective accumulation in the lesion, after in vivo injection, the Gd-INC could specifically enhance the MRI contrast of the thickened meninges. This innovative strategy not only paves the way for noninvasive diagnosis of CNS-L but also holds transformative potential to redefine precision imaging paradigms for hematological malignancies.