Multicolor^(19)F magnetic resonance imaging:A promising medical technique for in vivo visualization of multiple biological targets

Driven by the needs of precision medicine,current imaging techniques are under continuous development to offer more accurate and comprehensive information beyond traditional macroscopic anatomical images.Multispectral color-coded(multicolor)^(19)F magnetic resonance imaging(MRI)is receiving increasing attention owing to its capability for visualizing quantitative and multiplexed molecular information during various biological processes.The chemical design and preparation of^(19)F probes lie at the core of multicolor^(19)F MRI since their performance dominates the accomplishment of this technique.Herein,the working principles of multicolor^(19)F MRI are briefly introduced.Recent progress on multicolor^(19)F MRI probes for simultaneous in vivo visualization of multiple biological targets is summarized.Finally,current challenges and potential solutions in this fast-developing field are discussed.

Multiplexed Five-Color Molecular Imaging of Cancer Cells and Tumor Tissues with Carbon Nanotube Raman Tags in the Near-Infrared

Single-walled carbon nanotubes(SWNTs)with five different C13/C12 isotope compositions and well-separated Raman peaks have been synthesized and conjugated to five targeting ligands in order to impart molecular specificity.Multiplexed Raman imaging of live cells has been carried out by highly specific staining of cells with a five-color mixture of SWNTs.Ex vivo multiplexed Raman imaging of tumor samples uncovers a surprising up-regulation of epidermal growth factor receptor(EGFR)on LS174T colon cancer cells from cell culture to in vivo tumor growth.This is the first time five-color multiplexed molecular imaging has been performed in the near-infrared(NIR)region under a single laser excitation.Near zero interfering background of imaging is achieved due to the sharp Raman peaks unique to nanotubes over the low,smooth autofluorescence background of biological species.

A novel range-Doppler imaging algorithm with OFDM radar

Traditional pulse Doppler radar estimates the Doppler frequency by taking advantage of Doppler modulation over different pulses and usually it requires a few pulses to estimate the Dop- pler frequency. In this paper, a novel range-Doppler imaging algorithm based on single pulse with orthogonal frequency division multiplexing （OFDM） radar is proposed, where the OFDM pulse is composed of phase coded symbols. The Doppler frequency is estimated using one single pulse by utilizing Doppler modulation over different symbols, which remarkably increases the data update rate. Besides, it is shown that the range and Doppler estimations are completely independent and the well-known range-Doppler coupling effect does not exist. The effects of target movement on the performances of the proposed algorithm are also discussed and the results show that the algo- rithm is not sensitive to velocity. Performances of the proposed algorithm as well as comparisons with other range-Doppler algorithms are demonstrated via simulation experiments.

Multiplexed bioluminescence imaging of cancer cell response to hypoxia and inflammation in the caudal-artery injection model of bone metastasis during zoledronic acid treatment

Aim:Therapeutic agents suppressing bone remodeling have been clinically approved to delay metastatic progression and skeletal-related events in patients with bone metastasis.However,therapeutic agents including zoledronic acid(ZA)are insufficient to regress established bone metastasis.Therefore,new treatment strategies are desired,and unraveling the status of cancer cells during bone metastatic progression will help develop therapeutic strategies.Methods:We developed a unique multiplexed reporter system for bioluminescent imaging(MRS-BLI)using three luciferase reporter genes.This system allows for the noninvasive and quantitative monitoring of tumor growth and activities of nuclear factor-kappa B(NF-κB)and hypoxia-inducible factor(HIF),which are the key transcriptional factors in response to inflammation and hypoxia,respectively.PC-3/MRS-BLI,a human prostate cancer cell line that stably retains the MRS-BLI reporter genes,was applied to the caudal-artery injection model of bone metastasis to observe the status of cancer cells during bone metastasis development and ZA treatment(<1 month).Results:MRS-BLI reveals key events during the bone metastasis development:NF-κB and HIF are activated in cancer cells after migration to the bone marrow and are transiently reduced,followed by rapid activation before proliferation begins.ZA treatment suppresses the growth of metastasized cancer cells by suppressing NF-κB and HIF activities that may be indirectly induced by osteoclast activation.Conclusion:By visualizing the NF-κB and HIF activities of PC-3/MRS-BLI in bone,MRS-BLI has enabled new discoveries regarding the regulation of bone metastases.Further analysis of the progression of bone metastases using MRS-BLI may provide important information for developing new therapeutic strategies.