Structural Defect‐Enabled Magnetic Neutrality Nanoprobes for Ultra‐High‐Field Magnetic Resonance Imaging of Isolated Tumor Cells in Vivo

Abstract The identification of metastasis “seeds,” isolated tumor cells (ITCs), is of paramount importance for the prognosis and tailored treatment of metastatic diseases. The conventional approach to clinical ITCs diagnosis through invasive biopsies is encumbered by the inherent risks of overdiagnosis and overtreatment. This underscores the pressing need for noninvasive ITCs detection methods that provide histopathological‐level insights. Recent advancements in ultra‐high‐field (UHF) magnetic resonance imaging (MRI) have ignited hope for the revelation of minute lesions, including the elusive ITCs. Nevertheless, currently available MRI contrast agents are susceptible to magnetization‐induced strong T 2 ‐decaying effects under UHF conditions, which compromises T 1 MRI capability and further impedes the precise imaging of small lesions. Herein, this study reports a structural defect‐enabled magnetic neutrality nanoprobe (MNN) distinguished by its paramagnetic properties featuring an exceptionally low magnetic susceptibility through atomic modulation, rendering it almost nonmagnetic. This unique characteristic effectively mitigates T 2 ‐decaying effect while concurrently enhancing UHF T 1 contrast. Under 9 T MRI, the MNN demonstrates an unprecedentedly low r 2 / r 1 value (≈1.06), enabling noninvasive visualization of ITCs with an exceptional detection threshold of ≈0.16 mm. These high‐performance MNNs unveil the domain of hitherto undetectable minute lesions, representing a significant advancement in UHF‐MRI for diagnostic purposes and fostering comprehensive metastasis research.