Hand-held Spectroscopic Device for In Vivo and Intraoperative Tumor Detection: Contrast Enhancement, Detection Sensitivity, and Tissue Penetration

摘要

Surgery is one of the most effective and widely usednprocedures in treating human cancers, but a majornproblem is that the surgeon often fails to remove the entirentumor, leaving behind tumor-positive margins, metastaticnlymph nodes, and/or satellite tumor nodules. Here wenreport the use of a hand-held spectroscopic pen devicen(termed SpectroPen) and near-infrared contrast agents fornintraoperative detection of malignant tumors, based onnwavelength-resolved measurements of fluorescence andnsurface-enhanced Raman scattering (SERS) signals. ThenSpectroPen utilizes a near-infrared diode laser (emittingnat 785 nm) coupled to a compact head unit for lightnexcitation and collection. This pen-shaped device effectivelynremoves silica Raman peaks from the fiber opticsnand attenuates the reflected excitation light, allowingnsensitive analysis of both fluorescence and Raman signals.nIts overall performance has been evaluated by using anfluorescent contrast agent (indocyanine green, or ICG) asnwell as a surface-enhanced Raman scattering (SERS)ncontrast agent (pegylated colloidal gold). Under in vitronconditions, the detection limits are approximately 2-5 ×n10-11 M for the indocyanine dye and 0.5-1 × 10-13nM for the SERS contrast agent. Ex vivo tissue penetrationndata show attenuated but resolvable fluorescencenand Raman signals when the contrast agents are buriedn5-10 mm deep in fresh animal tissues. In vivo studiesnusing mice bearing bioluminescent 4T1 breast tumorsnfurther demonstrate that the tumor borders can benprecisely detected preoperatively and intraoperatively,nand that the contrast signals are strongly correlatednwith tumor bioluminescence. After surgery, the Spectro-nPen device permits further evaluation of both positivenand negative tumor margins around the surgical cavity,nraising new possibilities for real-time tumor detectionnand image-guided surgery.