Work Package 2: Intraoperative sensing

Professor Paul Beard, Professor Adrien Desjardins, Professor Simon Arridge 

About this work package

Minimally invasive fetal interventions require accurate imaging from inside the uterus. This work package has developed technology to show that superficial and subsurface branching blood vessels could be visualised to depths of approximately 7 mm, and that ablated tissue yielded negative image contrast.  

Twin-to-twin transfusion syndrome (TTTS)

The human placenta is the interface between the mother and the developing fetus, delivering the nutrients and oxygen vital for normal growth and development. In monochorionic twin pregnancies, conditions such as selective fetal growth restriction and twin‐to‐twin transfusion syndrome (TTTS) are associated with specific placental vessel patterns.

Twin‐to‐twin transfusion syndrome (TTTS) occurs from abnormal vascular anastomoses in the placenta that allow blood to flow unevenly between the fetuses

Current clinical practice in the treatment of TTTS

Currently, TTTS is treated fetoscopically by identifying the anastomosing vessels, and then performing laser photocoagulation. Two imaging modalities are used during the intervention: B‐mode ultrasound (US) imaging to guide instruments from outside the mother into the uterus to the placenta, and white light fetoscopy within the uterus to identify vascular anastomoses on the chorionic (fetal) placental surface for photocoagulation. However, both of these modalities provide insufficient contrast to visualise small anastomosing vessels beneath the chorionic placental surface. Missed anastomoses or incomplete photocoagulation are associated with an increased risk of recurrent TTTS, intrauterine fetal death and twin anemia polycythaemia sequence. The “Solomon technique” involves photocoagulation of the entire vascular equator.  In one randomised control trial, this significantly reduced postoperative fetal morbidity, as compared with selective occlusion. However, residual anastomoses remained in around 20% of placentas; therefore, there is room for refinement.

Photoacoustic (PA) imaging

Advances in methods for imaging placental vasculature in vivo could lead to significant improvements in the treatment of TTTS.  Photoacoustic (PA) imaging is an emerging imaging modality that provides molecular contrast from the optical absorption of excitation light. With PA imaging, contrast from vasculature can be particularly prominent due to optical absorption by hemoglobin. PA imaging has already been used to measure in vivo placental oxygenation under conditions of maternal hypoxia and hyperoxygenation and preeclampsia in rats, and in pregnancies associated with hypertension and fetal growth restriction in mice.  

This work extends previously developed 2D technology to perform three‐dimensional (3D) PA imaging. The motivations for our investigations were twofold: first, to explore the potential of PA imaging of postpartum placentas for improving our understanding of TTTS and the effects of photocoagulation; second, to appreciate what information may be available from intraoperative PA imaging, with future probes that would be suitable for intrauterine imaging. 

Work package tasks

Photoacoustic and ultrasound endoscopic imaging probe

The aim of this task is to develop miniature endoscopic imaging probes for internal ultrasound (US) and photoacoustic (PA) imaging. The team has developed two probes: a miniature PA fibre-bundle flexible probe and a PA/US probe. The PA probe comprises a small-diameter optical fibre bundle with a novel optical ultrasound sensor at the distal end that is based on a novel Fabry Perot (FP) etalon sensor. This fibre bundle can be operated in two modes to allow for all-optical implementations of both PA and US imaging. For PA imaging, the fibre bundle delivers nanosecond laser pulses to the tissue ahead of the probe; the resulting PA waves are detected by the sensor and used to reconstruct a 3D image. For US imaging, laser pulses are absorbed by a dichroic absorbing film that is deposited on the FP etalon. This results in the generation of ultrasound waves that propagate through tissue ahead of the fibre bundle. The reflected waves are detected with the sensor, enabling 3D pulseecho ultrasound images to be acquired. Since the same sensor is used to detect the PA and US ultrasound waves, the two images are inherently co-registered with each other. This approach provides high resolution (50-100 µm) images for detailed localised inspection of the fetus and placenta. Real-time imaging is achieved by employing compressed sensing and dynamic imaging techniques. 

Wide-field photoacoustic-ultrasound imaging system

The aim of this task is to develop a free-space rigid PA probe that can provide co-registered wide-field endoscopic images. The system uses a multi-beam scanner for fast acquisition of fully sampled images, and illumination fibres are integrated in the probe walls for white light endoscopy. Real-time 3D image reconstruction is achieved using sub-sampling and a fast learned reconstruction algorithm.

Success stories

Our research on Photoacoustic imaging of the human placental vasculature was on the front cover of the Journal of Biophotonics in April 2020.

Key publications

Approximate k-Space Models and Deep Learning for Fast Photoacoustic Reconstruction. Hauptmann, A., Cox, B., Lucka, F., Huynh, N., Betcke, M., Beard, P., & Arridge, S. (2018). In: Knoll, F., Maier, A., Rueckert, D. (eds) Machine Learning for Medical Image Reconstruction. MLMIR 2018. Lecture Notes in Computer Science, vol 11074. Springer, Cham (Vol. 11074, pp. 103–111). Springer International Publishing. doi: 10.1007/978-3-030-00129-2_12 

Enhancing photoacoustic visualization of medical devices with elastomeric nanocomposite coatings. Xia, W., Noimark, S., Maneas, E., Montana Brown, N, Singh, M. K. A., Ourselin, S., West, S. J., Desjardins, A. E. (2019). Proc. SPIE 10878, Photons Plus Ultrasound: Imaging and Sensing 2019, 108783G. doi: 10.1117/12.2508658 

Photoacoustic imaging of the human placental vasculature. Maneas, E., Aughwane, R., Huynh, N., Xia, W., Ansari, R., Singh, M. K. A., Hutchinson, C. J., Sebire, N. J., Arthurs, O. J., Deprest, J., Ourselin, S., Beard, P. C., Melbourne, A., Vercauteren, T., Desjardins, A. E. (2019). Journal of Biophotonics. doi: 10.1002/jbio.201900167

Polydimethylsiloxane Composites for Optical Ultrasound Generation and Multimodality Imaging. Noimark, S., Colchester, R. J., Poduval, R. K., Maneas, E., Alles, E. J., Zhao, T., Zhang, E. Z., Ashworth, M., Tsolaki, E., Chester, A. H., Latif, N., Bertazzo, S., David, A. L., Ourselin, S., Beard, P. C., Parkin, I. P., Papakonstantinou, I., Desjardins, A. E. (2018). Advanced Functional Materials, 28, 1704919. doi: 10.1002/adfm.201704919 

Miniature all-optical flexible forward-viewing photoacoustic endoscopy probe for surgical guidance. Ansari, R., Zhang, E. Z., Desjardins, A. E., Beard, P. C. (2020). Optics Letters45, 6238-6241. doi: 10.1364/OL.400295