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Photoacoustic/Ultrasound Mammoscopy for evaluating screening-detected abnormalities in the breast

Periodic Reporting for period 2 - PAMMOTH (Photoacoustic/Ultrasound Mammoscopy for evaluating screening-detected abnormalities in the breast)

Reporting period: 2018-07-01 to 2019-12-31

With Europe’s aging population, its high incidence of breast cancer, its tightening health-care budget [Rechel et al 2013, Ferlay et al 2013, Karanikolos et al 2013, Morgan & Astolfi 2015], and drawbacks in conventional breast imaging modalities [Nass, S.J. et al 2001], there is a need for a technique that can provide images with high specificity, contrast and spatial resolution, all at a sufficiently low cost that it can be made universally available. Photoacoustic (also called optoacoustic) imaging [Wang & Hu 2012, Beard 2011, Ntziachristos & Razansky 2010], in which the contrast is dependent on light absorption and which therefore offers spectroscopic (molecular) specificity, has the potential to be that technique [Heijblom et al 2015a]. However, while the literature of the last 15 years has witnessed technological advances in photoacoustic breast imaging, these have been incremental and conservative steps, fragmented across various groups and companies. The end result is that many possibilities and opportunities have not been exploited or explored, and even after a decade and half following the first application of photoacoustic imaging in the breast [Oraevsky et al 2001], we still describe the method tantalizingly as having potential and promise.

PAMMOTH brings together applied physicists, technology developers, mathematicians, algorithm developers, ultrasound detection experts, laser specialists, epidemiologists and radiologists to work on a new generation system for imaging the breast using both photoacoustics and ultrasound. Academia, Industry and the Clinic from 6 different countries form a strong European consortium in PAMMOTH.

The PAMMOTH consortium’s objective is to develop, validate and begin exploitation of a dedicated breast imaging device for a significant impact in breast cancer diagnosis. The proposed device combines non-invasive 3D photoacoustic imaging and ultrasound imaging. The device will provide full-breast, multimodal images to the radiologist. From the ultrasound mode, the radiologist will visualize anatomical features and extent of tumors, and from multiwavelength photoacoustics, she will see tumor vascularity. Quantitative spectroscopic photoacoustic images will be extracted off-line, providing the radiologist information relating to tumor physiology and function such as angiogenesis and hypoxia.

The choice of the relevant biological targets, and of the functionalities and technical principles applied in the PAMMOTH imager, will provide relevant information to the radiologist to make accurate diagnosis with high specificity.

The consortium aims to make the imaging device for all populations of women, with short time intervals between positive screening and diagnosis. The device has high through-put, possesses no carcinogenic potential and causes no pain and discomfort to patients.
At the 36th month in the project we have together realized the following:
• The clinical prototype PAMMOTH, boasting sub-systems that are technically beyond the state-of-the-art, has been developed and installed in the Medisch Spectrum Twente Hospital, Oldenzaal. The system underwent tests and a risk management report evaluating the risks due to electrical, mechanical, hygienic, ultrasound, and laser control aspects of the imager was developed. This has been submitted to the Medical Ethical Review Committee along with the study protocol. An improved study protocol was re-submitted and approval for the start of the human subject study is awaited.
• The developed ns laser has among the highest energy outputs per ns pulse. The OPO pumped by the laser allows fast tuning and high efficiency. The light is coupled to the PAMMOTH imager using an optical fiber bundle, designed to accept high energy pulses, split in 40 outputs.
• The 512 ultrasound transducers arranged in hemispherical geometry provide a low minimum detectable pressure with a wide fractional frequency bandwidth.
• The 512 multi-channel Data-Acquisition System is also equipped to transmit ultrasound from the same transducers for ultrasound imaging.
• Cups of various sizes to immobilize the breast during measurements have been produced to hold the breast in the imaging bowl.
• A novel algorithm has been developed for the specific task of reconstructing intermediate images on the fly as projections are being acquired.
• Novel algorithms for speed of sound reconstruction from ultrasound data have been developed and tested.
• A photoacoustic image reconstruction (using a priori known speed of sound map) based on an iterative approach has been developed.
• The algorithm for quantitative photoacoustic reconstruction has been developed.
• The framework for automatic planning and execution of the off-line image reconstructions (quantitative photo-acoustics) has been implemented.
• A suite of test and calibration objects has been developed. Further, a novel 3D phantom simulating both acoustic and optical properties of the breast and its abnormalities has been developed for studying the performance of the system. These phantoms also carry blood vessel simulating channels through which blood can be streamed, whose oxygen saturation can be controlled.
• The combination of quantitative photoacoustic and ultrasound imaging makes the PAMMOTH imager unique.
• The laser developed produces pulse energies at the fundamental and second-harmonic which are highest within the same application class of lasers.
• The characteristics of the ultrasound detectors are superior to the state-of-the-art detectors.
• A multi-channel Data-Acquisition System (DAS) shows low noise and also has higher level of complexity compared to devices available. The analog front ends in the PAMMOTH DAQ are also capable of driving ultrasound generation by electrical actuation of transducers.
• The ultrasound simulation codes required for the acoustic inversion were optimized for systems with multiple GPUs reaching almost 10-fold speed-up compared to conventional servers.
• The 3D phantom developed are among the first for photoacoustics which may be described as semi-anthropomorphic as well as physiopathological phantoms.

References
1) Rechel, B., et al, 2013. The Lancet, 381(9874), pp.1312-1322.
2) Ferlay, J., et al, 2013. European Journal of Cancer, 49(6), pp.1374-1403.
3) Karanikolos, M., et al, 2013. The Lancet, 381(9874), pp.1323-1331.
4) Morgan, D. and Astolfi, R., 2015. 10(01), pp.7-19.
5) Nass, S.J. et al, eds., 2001. National Academies Press.
6) Beard, P., 2011. Interface Focus, p.rsfs20110028.
7) Ntziachristos, V. and Razansky, D., 2010. Chemical Reviews, 110(5), pp.2783-2794.
8) Heijblom, M., et al, 2015a. Scientific Reports, 5.
9) Oraevsky, A.A. et al, BiOS 2001 The International Symposium on Biomedical Optics (pp. 6-15).
PAMMOTH concept
PAMMOTH imaging bowl
PAMMOTH emblem