The realization of medical devices for precision surgery – development and implementation of ‘stop-and-go’ imaging technologies

Figures & data

Table 1. Typical characteristics of the most common molecular imaging modalities for surgical guidance.

Modality	Signature	Tissue penetration	Resolution	Measurement time	Suitable for noninvasive preoperative imaging	Suitable for intraoperative imaging	Suitable for back-table imaging	Suitable for pathological imaging
Gamma Radioguidance [8]	25–300 keV or 511 keV gamma rays	>100 mm	2–5 mm	-Real-time (tracing) −10-30s (imaging)	Yes (scintigraphy, SPECT and PET)	Both in-depth and superficial detection	yes	no
Beta+ Radioguidance [9,10]	600–2000 keV positrons	<3 mm	2–5 mm	Real-time (tracing)	Yes (PET)	Superficial detection	yes	no
Beta+ Cerenkov imaging [11]	250–1300 nm (Max in UV (<400 nm))	<3 mm	1–2 mm	>5 minutes (imaging)	Yes (PET)	Superficial detection	yes	no
Fluorescence imaging [12,13]	450–900 nm	<10 mm	0.02–1 mm	Real-time (Imaging)	No	Superficial detection	yes	yes
Magnetic particle tracing [14,15]	20–100 emu/g (saturation magnetization)	<20 mm	6 mm	Real-time (tracing)	Yes (negative contrast on MRI)	Superficial detection	yes	yes

SPECT/CT = Single Photon Emission Computed Tomography/x-ray Computed Tomography, PET/CT = Positron Emission Tomography/x-ray Computed Tomography, MRI = Magnetic Resonance Imaging.

Table 2. Most common surgical applications of molecular imaging, summarizing surgical targets, the anatomies and molecular targets.

Surgical targets	Anatomies	Molecular targets (under investigation)
Perfusion	e.g., bowel anastomosis, ureters, lymphatics [17–20]	e.g., ICG clearance, fluorescein clearance
Primary tumor margins	e.g., prostate, lung, head-and-nek, colon [21–25]	e.g. PSMA, Folate, VEGF, EGFR, C-Met, CEA, Somatostatin
Local metastatic disease spread to lymph nodes	e.g., Breast, melanoma, penis, vulva, prostate [26–29]	e.g., Sentinel nodes tracers, PSMA-receptors
(Local) metastatic disease spread	e.g., Liver [30]	e.g., Impaired ICG clearance

ICG = indocyanine green, PSMA = prostate specific membrane antigen, VEGF = vascular endothelial growth factor, EGFR = Epidermal growth factor receptors, C-Met = c-mesenchymal-epithelial transition, CEA = Carcinoembryonic antigen.

Figure 1. Decision making stages in a typical intraoperative molecular imaging surgery workflow and how these relate to red- (stop), orange- (slow down and approach with caution), and green- (go) light image guidance.

Figure 2. Examples of molecular image guidance technologies at different stages of the procedure. Stage 1, showing PET imaging (top and middle) and SPECT imaging (bottom) for planning of the intervention; Stage 2, showing freehand SPECT navigation (top), DROP-IN gamma probe and gamma camera guidance (middle) and fluorescence flow analysis [38] and optical guidance, for in vivo guidance during the intervention; Stage 3, showing DROP-IN beta probe analysis (top) and PET specimen imager [39] (bottom), for ex vivo back-table analysis during the intervention. Non referenced images originate from authors personal collection. No changes have been made to the referenced images, which are licensed under CC by 4.0 (https://creativecommons.org/licenses/by/4.0/).

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