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Central nervous system (CNS) demyelination represents the pathological hallmark of multiple sclerosis (MS) and contributes to other neurological conditions. Quantitative and specific imaging of demyelination would thus provide critical clinical insight. Here, we investigated the possibility of targeting axonal potassium channels to image demyelination by positron emission tomography (PET). These channels, which normally reside beneath the myelin sheath, become exposed upon demyelination and are the target of the MS drug, 4-aminopyridine (4-AP). We demonstrate using autoradiography that 4-AP has higher binding in non-myelinated and demyelinated versus well-myelinated CNS regions, and describe a fluorine-containing derivative, 3-F-4-AP, that has similar pharmacological properties and can be labeled with 18F for PET imaging. Additionally, we demonstrate that [18F]3-F-4-AP can be used to detect demyelination in rodents by PET. Further evaluation in Rhesus macaques shows higher binding in non-myelinated versus myelinated areas and excellent properties for brain imaging. Together, these data indicate that [18F]3-F-4-AP may be a valuable PET tracer for detecting CNS demyelination noninvasively.

There is strong clinical interest in using neural stem cells (NSCs) as carriers for targeted delivery of therapeutics to glioblastoma. Multimodal dynamic in vivo imaging of NSC behaviors in the brain is necessary for developing such tailored therapies; however, such technology is lacking. Here we report a novel strategy for mesoporous silica nanoparticle (MSN)–facilitated NSC tracking in the brain via SPECT. Methods 111In was conjugated to MSNs, taking advantage of the large surface area of their unique porous feature. A series of nanomaterial characterization assays was performed to assess the modified MSN. Loading efficiency and viability of NSCs with 111In-MSN complex were optimized. Radiolabeled NSCs were administered to glioma-bearing mice via either intracranial or systemic injection. SPECT imaging and bioluminescence imaging were performed daily up to 48 h after NSC injection. Histology and immunocytochemistry were used to confirm the findings. Results 111In-MSN complexes show minimal toxicity to NSCs and robust in vitro and in vivo stability. Phantom studies demonstrate feasibility of this platform for NSC imaging. Of significance, we discovered that decayed 111In-MSN complexes exhibit strong fluorescent profiles in preloaded NSCs, allowing for ex vivo validation of the in vivo data. In vivo, SPECT visualizes actively migrating NSCs toward glioma xenografts in real time after both intracranial and systemic administrations. This is in agreement with bioluminescence live imaging, confocal microscopy, and histology. Conclusion These advancements warrant further development and integration of this technology with MRI for multimodal noninvasive tracking of therapeutic NSCs toward various brain malignancies.

Tissue-like materials are required in many robotic systems to improve human-machine interactions.However, the mechanical properties of living tissues are difficult to replicate. Synthetic materials are not usually capable of simultaneously displaying the behaviors of the cellular ensemble and the extracellular matrix. A particular challenge is identification of a cell-like synthetic component which is tightly integrated with its matrix and also responsive to external stimuli at the population level. Here, we demonstrate that cellular-scale hydrated starch granules, an underexplored component in materials science, can turn conventional hydrogels into tissue-like materials when composites are formed. Using several synchrotron-based X-ray techniques, we reveal the mechanically-induced motion and training dynamics of the starch granules in the hydrogel matrix.These dynamic behaviors enable multiple tissue-like properties such as strain-stiffening, anisotropy, mechanical heterogeneity, programmability, mechanochemistry, impact absorption, and self-healability. The starch-hydrogel composites can be processed as robotic skins that maintain these tissue-like characteristics. One-sentence SummaryMechanically programmable granular materials in hydrogels enable tissue-like materials for robotic skins. ACKNOWLEDGMENTS Funding:We thank Karen Watters for scientific editing of the manuscript.