gms | German Medical Science

Objective: Visualizing the tumor border intraoperatively remains a major obstacle during oncological surgery. Various optical modalities such as fluorescence imaging face drawbacks like low sensitivity, low specificity, limited resolution and/or imaging depth. We opted to exploit the potential of emerging multispectral optoacoustic tomography (MSOT) to contribute to the surgeon’s success by providing an intrinsic and extrinsic contrast-enhanced imaging technique in near real-time.

Methods: First, we tested the sensitivity and specificity of the technique in brain tissue mimicking phantoms and preclinical cancer models based on the intrinsic MSOT signal in a static imaging approach. We then studied the translatability of the MSOT by exploiting the imaging geometry of 2D vs. 3D handheld probes in preclinical melanoma brain metastasis. Finally, we studied the contrast-enhanced visualization of glioblastoma margins using MSOT suitable nanoprobes in a genetic preclinical glioblastoma model.

Results: In vitro, the intrinsic MSOT limit of detection was found to be approximately five melanoma cells per μl. MSOT was able to detect melanoma lymph micro-metastases in vivo, an ability far superior to positron emission tomography as the gold standard. In translation, both 2D and 3D handheld approaches were capable of imaging the brain metastases at all time points qualitatively. Quantitatively, the 2D approach allowed closer anatomical resemblance of the tumor compared to the 3D. The test-retest reliability was significantly higher for the 2D than the 3D approach while the 3D-image acquisition was less time consuming. Extrinsically, nanoprobe contrast-enhanced MSOT could provide a limit of detection of the contrast agent up to the picomolar range and was able to well depict the glioblastoma up to a centimeter of brain tissue with high specificity in vivo.

Conclusion: The novel MSOT technique for surgical guidance shows excellent specificity and sensitivity of tumor detection. This novel imaging strategy allowed for the sensitive and specific detection of glioblastoma up to a centimeter in tissue depth at high resolution in real time, far beyond the limits of fluorescence imaging. In potential translation, the handheld 2D approach proved to be more suitable than the 3D device for tissue targets at greater depths.