We developed a smart optode to perform time domain diffuse optical tomography at 8 wavelengths in the red and near-infrared spectral range (635-1064 nm). Eight optodes were included in a newly developed multimodal probe, which combines the optical tomography capabilities with US. The probe was integrated in a high-end, commercially available US system built by a SOLUS consortium member.
Each component of the optode had to be specifically designed and developed to ensure state-of-the-art performance at a significantly reduced size: 1) the integrated laser driver to generate picosecond pulses (<200 ps) at 8 selected wavelengths, with suitable pulse shape, high average power (>1 mW) and repetition rate (40 MHz); 2) a wide area time-gated single-photon Silicon PhotoMultiplier (SiPM) detector, where the gated acquisition and the capability to control the extension of the active area (up to 8.6 mm2) are needed to reject superficial reflections and manage detected signals varying over orders of magnitude when the source-detector distance is changed in the mm to cm range to collect tomographic data; 3) dedicated acquisition electronics, including a time-to-digital converter and a histogram builder, with 128 channels, channel width of 72 ps, and dead time <100 ns.
All components were integrated into the single optode for a minimum footprint with high collection efficiency.
The handheld multimodal probe was designed to integrate 8 optodes around the US transducer and include water cooling to guarantee reliable performance of the temperature-sensitive optode components. A position sensor is also present. The lasers are Class 1, enabling a safe use for both the operator and the patient without the discomfort of laser safety counter-measures. A full multimodal imaging system was then developed with dedicated software to control operation with the SOLUS probe and with a conventional US probe. The software is capable of multimodal acquisitions, recording patient data, and carrying out a quick analysis of the optical data in real time.
Algorithms were developed to analyze the optical tomographic data collected at multiple wavelengths inside and outside of the lesion, to estimate tissue composition in terms of oxy- and deoxyhemoglobin, water, lipid and collagen content. Advantage is taken of the morphologic information available from B-mode US imaging to guide optical tomography reconstructions, and improve the accuracy of the estimate of lesion properties.
Any development, from the single components, to the smart optode, up to the multimodal probe and the full system were rigorously tested following protocols recognized at European level for performance assessment in diffuse optics (BIT, Medphot, Neuropt). Furthermore, a new protocol was introduced and applied to characterize the tomographic performances of the system, as no specific protocol was available yet. A full kit of bimodal tissue phantoms, suitable for both US and diffuse optical imaging, was developed and exploited. To mimic breast tissue with a lesion, the kit includes homogeneous and heterogeneous phantoms.
Approval for the clinical validation of the SOLUS system was obtained from the Ethics Committee of Ospedale San Raffaele (OSR) and from the Italian Ministry of Health.
The planned clinical validation is presently ongoing at OSR. It includes: 1) mock sessions to train the physicians on the use of the system and get feedback from them on its usability; 2) an initial test of the diagnostic potential (with data collected from 20 patients with malignant and 20 with benign breast lesions).
Due to the COVID pandemic, the start of the clinical validation was delayed. The SOLUS consortium has agreed to voluntarily continue the validation beyond the official end of the project to fully estimate the diagnostic potential.
