With great interest, our independent groups of scientists located in Korea and Germany recognized the use of a very similar methodologic approach to quantify the uptake of radioactive glucose ( 18 F-FDG) at the cellular level. The focus of our investigations was to disentangle microglial 18 F-FDG uptake. To do so, CD11b immunomagnetic cell sorting was applied to isolate microglia cells after in vivo 18 F-FDG injection, to allow simple quantification via a g-counter. Importantly, this technique reveals a snapshot of cellular glucose uptake in living mice at the time of injection since 18 F-FDG is trapped by hexokinase phosphorylation without a further opportunity to be metabolized. Both studies indicated high 18 F-FDG uptake of single CD11b-positive microglia cells and a significant increase in microglial 18 F-FDG uptake when this cell type is activated in the presence of amyloid pathology. Furthermore, another study noticed that immunomagnetic cell sorting after tracer injection facilitated determination of high 18 F-FDG uptake in myeloid cells in a range of tumor models. Here, we aim to discuss the rationale for singlecell radiotracer allocation via immunomagnetic cell sorting (scRadiotracing) by providing examples of promising applications of this innovative technology in neuroscience, oncology, and radiochemistry.

Unraveling the spatial configuration of the tumor microenvironment (TME) is key to understanding tumor-immune interactions to translate them into immuno-oncology. With the advent of spatially resolved transcriptomics (SRT), the TME could be dissected for whole cell types across numerous RNAs. We suggest a novel approach, STopover, which performs topological analysis to compute the colocalization patterns between cell types and map the location of cell-cell interactions. While gradually lowering the threshold for the feature, the connected components (CCs) were extracted based on the spatial distance between the unit tissue region and the persistence of the CCs. Local and global Jaccard indices were calculated between the CCs of a feature pair to measure the extent of spatial overlap. The STopover was applied to various lung cancer data obtained from SRT platforms, both barcode and image-based SRT, and could explain the infiltration patterns of immune and stromal cells in the TME. Moreover, the method predicted the top cell-cell communication based on the ligand-receptor database and highlighted the main region of the interaction. STopover is a tool to decipher spatial interaction in the tissue and shed light on the pathophysiology underlying the microenvironment.

k-core percolation on the scale-free static brain connectivity revealed hierarchical structure of inter-voxel correlations, which was successfully visualized by hyperbolic disc embedding on resting-state fMRI. In static study, flagplots and brain rendered kmax-core display showed the changes of hierarchical structures of voxels belonging to functional independent components (IC). In this dynamic sliding-window study, temporal progress of hierarchical structure of voxels were investigated in individuals and in sessions of an individual. kmax-core and coreness k values characterizing time-varying core voxels were visualized on animated stacked-histogram/flagplots and animated brain-rendered images. Resting-state fMRI of Human Connectome Project and of Kirby weekly revealed the slow progress and multiple abrupt state transitions of the voxels of coreness k and at the uppermost hierarchy, representing their correlative time-varying mental states in individuals and in sessions. We suggest this characteristic core voxels-IC compositions on dynamic study fingerprint the time-varying resting states of human minds.

Age–related cognitive decline is associated with dysfunctional lymphatic efflux of cerebrospinal fluid (CSF) through meningeal lymphatic vessels. Intrathecal [64Cu]Cu–albumin positron emission tomography (PET) was applied in mice for the evaluation of lymphatic efflux of CSF and its age–related variation. [64Cu]Cu–albumin PET was done at multiple time points after intrathecal injection of [64Cu]Cu–albumin with the infusion speed of 700 nl/min in the adult and aged mice of 15–25 months old age. CSF clearance and paravertebral lymph nodes were quantified after injection and at later stationary phase. Representing perturbed state by 6 μl (1/7 of CSF volume with twice the production rate for 9 minutes of intrathecal injection) and at the next day of stationary return of CSF dynamics in mice, CSF clearance half–time from the subarachnoid space was 93.4 ± 19.7 in adult and 123.3 ± 15.6 minutes in aged mice (p = 0.01). The % injected dose at 4, 6 and 24 hours were higher in aged mice than in the adult mice (p < 0.05) and the visualized paravertebral lymph node activity tended to be lower in the aged, which was different from [64Cu]Cu-NOTA or [64Cu]Cu-ESION PET. [64Cu]Cu-albumin PET enabled quantification of CSF–lymphatic efflux over all the levels of brain spinal cords and visualization with quantifiability of lymph node activity. [64Cu]Cu-albumin PET revealed an age-related decrease in CSF–lymphatic efflux due to less efflux from the subarachnoid space, especially at stationary phase in the aged mice.