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Intraoperative molecular imaging; Fluorescence-guided surgery; PET; Intraoperative MRI; Cancer surgery

Cancer surgery, especially tumor resection, has traditionally relied on visual inspection, tactile feedback, and preoperative imaging. While these methods are effective to some extent, they often fall short when it comes to identifying small or hidden cancerous tissue. Incomplete resections can lead to recurrence, metastasis, or poor prognoses for patients. Intraoperative molecular imaging (IMI) offers a promising solution by providing real-time, molecular-level information about the tumor and surrounding tissues, enhancing the surgeon's ability to make precise decisions during surgery. IMI technologies leverage molecular markers and imaging agents to highlight cancer cells, making them visible to the surgeon during the procedure [1][2].

Intraoperative Molecular Imaging

Intraoperative molecular imaging refers to imaging techniques that provide real-time, molecular-specific data during surgery. These technologies utilize molecular probes or contrast agents that selectively bind to tumor-specific biomarkers, allowing for the visualization of cancer cells in situ. The goal is to guide the surgeon in distinguishing malignant tissue from normal tissue, ensuring complete tumor resection and minimizing damage to healthy structures. Common modalities used in IMI include fluorescence-guided surgery (FGS), which uses fluorescent dyes, and nuclear medicine-based imaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) [3][4].

Fluorescence Guided Surgery (FGS)

Fluorescence-guided surgery (FGS) has emerged as one of the most widely used techniques in intraoperative molecular imaging. By using specific fluorescent dyes that bind to cancerous tissues, FGS enables the surgeon to visualize tumors that may not be apparent using traditional visualization methods. One of the most common fluorescent agents is indocyanine green (ICG), which is often used for detecting tumors in the gastrointestinal tract, liver, and brain. ICG binds to tumor cells and emits fluorescence when exposed to near-infrared light, allowing the surgeon to distinguish tumor tissue from healthy tissue. This technique has shown promise in improving surgical outcomes, reducing the likelihood of incomplete tumor resections, and minimizing postoperative complications [5]. Another important aspect of FGS is its potential to be used in combination with other imaging modalities, such as MRI or CT, to provide a more comprehensive view of the tumor and its relationship with surrounding structures. For instance, in colorectal cancer surgery, fluorescence imaging has been successfully integrated into laparoscopic and robotic surgery platforms, enabling better visualization of the tumor's boundaries and improving the accuracy of resection [6].

Positron Emission Tomography (PET) in Surgery

Positron emission tomography (PET) is a nuclear imaging technique that provides high-resolution images based on the metabolic activity of tissues. It is most commonly used to detect areas of high glucose metabolism, a hallmark of many cancer cells. Intraoperative PET, when combined with surgery, can offer a highly detailed map of the tumor's location, helping surgeons identify cancerous tissue that may not be visible with traditional imaging methods. PET is particularly useful in the resection of tumors in organs such as the brain, lungs, and pancreas, where precise delineation of tumor boundaries is critical [7]. One of the challenges with PET in surgery, however, is its spatial resolution. Although it offers excellent sensitivity, the resolution is often limited compared to other imaging techniques like MRI or CT. To address this, hybrid imaging systems that combine PET with other modalities, such as MRI-PET or CT-PET, have been developed to improve both resolution and accuracy during surgery [8].

Intraoperative Magnetic Resonance Imaging (iMRI)

Intraoperative magnetic resonance imaging (iMRI) is another valuable tool in precision cancer surgery. iMRI provides high-resolution, real-time imaging during the surgical procedure, enabling surgeons to accurately visualize tumors, adjacent structures, and the extent of resection. iMRI is especially useful for brain and spinal cord tumors, where tumor margins can be difficult to define. The ability to obtain real-time images during surgery ensures that any residual tumor is detected and removed before closing the surgical site [9]. The major challenge with iMRI is the need for specialized equipment, as well as the cost and technical difficulties associated with operating an MRI system in the sterile operating room environment. Despite these challenges, studies have shown that iMRI significantly improves the completeness of tumor resections, particularly in neurosurgery, and can reduce the need for repeat surgeries due to residual tumor tissue [10].

Benefits of Intraoperative Molecular Imaging

The primary benefit of intraoperative molecular imaging is its ability to enhance the surgeon’s accuracy in tumor resection. By providing real-time molecular information, IMI helps ensure that the tumor is completely removed while minimizing damage to surrounding healthy tissue. This is particularly important in surgeries involving tumors located near critical structures, such as in the brain, liver, or pancreas. The use of IMI can reduce the likelihood of incomplete resections, which can otherwise lead to recurrence or metastasis. IMI also contributes to more personalized cancer treatments. By incorporating molecular markers that are specific to the patient’s cancer, surgeons can tailor their approach to individual tumors. This personalized treatment strategy improves the likelihood of positive surgical outcomes and minimizes postoperative complications. Additionally, the integration of IMI into minimally invasive surgery techniques, such as laparoscopy or robotic surgery, allows for smaller incisions, reduced blood loss, faster recovery times, and a lower risk of infection. As a result, patients experience less trauma and faster postoperative recovery, which is particularly important for those undergoing complex oncological procedures.

Challenges and Limitations

While intraoperative molecular imaging offers numerous advantages, there are several challenges that need to be addressed. One of the primary limitations is the cost and complexity of the technologies involved. Advanced imaging systems such as iMRI, PET, and hybrid imaging platforms are expensive and require specialized training for both the surgical and radiology teams. The infrastructure required to support these technologies, such as the installation of MRI machines in operating rooms, can be financially burdensome. Furthermore, the resolution and sensitivity of some imaging techniques may not be sufficient to detect very small tumor deposits or subtle tissue changes. For example, although PET is highly sensitive, its spatial resolution is often not as fine as that of MRI or ultrasound. This limits its application in certain types of tumors or in situations where precise localization is critical.

Conclusion

Intraoperative molecular imaging is revolutionizing cancer surgery by offering real-time, molecular-level visualization of tumors during surgery. The integration of imaging modalities like fluorescence-guided surgery, PET, and iMRI into surgical practice has the potential to significantly improve the accuracy of tumor resections, reduce the risk of recurrence, and enhance patient outcomes. While challenges such as cost, equipment limitations, and technical expertise remain, the future of IMI in oncology looks promising, with ongoing advancements likely to make these technologies more accessible and effective in clinical practice. As research progresses, intraoperative molecular imaging will continue to play a pivotal role in the precision treatment of cancer.

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