Intraoperative Molecular Imaging for Cancer Detection

Intraoperative molecular imaging (IMI) has emerged as a transformative strategy to enhance the precision of cancer surgery by providing real-time visualisation of tumour tissue and margins. By administering targeted or non-targeted fluorescent contrast agents prior to or during surgery, surgeons can distinguish neoplastic from healthy tissue with improved sensitivity and specificity. Key modalities include near-infrared (NIR) fluorescence imaging, multispectral imaging and fluorescence molecular tomography. These techniques exploit the preferential accumulation of fluorophores in hyperpermeable or receptor-expressing tumour microenvironments, yielding high signal-to-background ratios that guide resection. IMI addresses critical challenges in oncological surgery: localising occult lesions, ensuring negative margins, detecting residual disease in the wound bed and identifying metastatic lymph nodes. Practical considerations encompass depth of penetration, agent safety and the trade-off between sensitivity and field of view. Recent advances in probe chemistry, imaging hardware and data analysis have propelled IMI towards routine clinical adoption, with potential to reduce recurrence rates and improve patient outcomes across diverse solid tumours.

Research from Nature Portfolio

Recent instrumental studies have scrutinised methods to quantify and compare tumour fluorescence in surgical settings. One foundational investigation evaluated three imaging platforms—spectroscopy, luminometry and digital imaging—across in vitro models, murine xenografts and clinical specimens. The work demonstrated that fibre-optic spectroscopy exhibited superior sensitivity for incremental changes in fluorescence, while digital imaging afforded the broadest field of view and operational practicality. This comparative framework informs selection of optimal systems for specific surgical applications. Another seminal study elucidated the mechanism by which indocyanine green (ICG) accumulates in necrotic tissue via lipoprotein and phospholipid interactions. Preclinical models across multiple organ systems showed that submillimetre zones of necrosis could be detected with precise boundary delineation. This discovery underscores the potential of repurposing established fluorophores to target pathophysiological hallmarks of tumours and enhance intraoperative guidance.

Intraoperative Molecular Imaging for Cancer Detection publication trend

The graph below shows the total number of articles in intraoperative molecular imaging for cancer detection across all publications each year (not limited to Nature Index journals).

Technical terms

Fluorophore: A molecule that absorbs light at one wavelength and emits it at another, used as a contrast agent in imaging.

Near-infrared (NIR) imaging: Optical imaging technique using light in the 700–900 nm range for deep tissue visualisation.

Signal-to-background ratio (SBR): The intensity of fluorescence from target tissue relative to surrounding normal tissue, indicating imaging contrast.

Indocyanine green (ICG): An FDA-approved NIR dye that accumulates in hyperpermeable tissues and is widely used for intraoperative imaging.

Fluorescence molecular imaging (FMI): A modality that employs fluorescent probes to visualise specific molecular targets or physiological states in tissues during surgery.

References

1. Quantification of tumor fluorescence during intraoperative optical cancer imaging. Scientific Reports (2015).
2. Illuminating necrosis: From mechanistic exploration to preclinical application using fluorescence molecular imaging with indocyanine green. Scientific Reports (2016).
3. Intraoperative near infrared functional imaging of rectal cancer using artificial intelligence methods - now and near future state of the art. European Journal of Nuclear Medicine and Molecular Imaging (2024).
4. Progression in Near-Infrared Fluorescence Imaging Technology for Lung Cancer Management. Biosensors (2024).
5. Tumor-selective dye-based histological electrophoresis enables intraoperative tumor diagnosis via tumor-specific enhancement. Theranostics (2025).