Prognostic Value of [18F]FDG PET Radiomics to Detect Peritoneal and Distant Metastases in Locally Advanced Gastric Cancer-A Side Study of the Prospective Multicentre PLASTIC Study.

AIM: To improve identification of peritoneal and distant metastases in locally advanced gastric cancer using [18F]FDG-PET radiomics. METHODS: [18F]FDG-PET scans of 206 patients acquired in 16 different Dutch hospitals in the prospective multicentre PLASTIC-study were analysed. Tumours were delineated and 105 radiomic features were extracted. Three classification models were developed to identify peritoneal and distant metastases (incidence: 21%): a model with clinical variables, a model with radiomic features, and a clinicoradiomic model, combining clinical variables and radiomic features. A least absolute shrinkage and selection operator (LASSO) regression classifier was trained and evaluated in a 100-times repeated random split, stratified for the presence of peritoneal and distant metastases. To exclude features with high mutual correlations, redundancy filtering of the Pearson correlation matrix was performed (r = 0.9). Model performances were expressed by the area under the receiver operating characteristic curve (AUC). In addition, subgroup analyses based on Lauren classification were performed. RESULTS: None of the models could identify metastases with low AUCs of 0.59, 0.51, and 0.56, for the clinical, radiomic, and clinicoradiomic model, respectively. Subgroup analysis of intestinal and mixed-type tumours resulted in low AUCs of 0.67 and 0.60 for the clinical and radiomic models, and a moderate AUC of 0.71 in the clinicoradiomic model. Subgroup analysis of diffuse-type tumours did not improve the classification performance. CONCLUSION: Overall, [18F]FDG-PET-based radiomics did not contribute to the preoperative identification of peritoneal and distant metastases in patients with locally advanced gastric carcinoma. In intestinal and mixed-type tumours, the classification performance of the clinical model slightly improved with the addition of radiomic features, but this slight improvement does not outweigh the laborious radiomic analysis.

Suite of 3D test objects for performance assessment of hybrid photoacoustic-ultrasound breast imaging systems.

SIGNIFICANCE: During the development and early testing phases of new photoacoustic (PA) breast imaging systems, several choices need to be made in aspects of system design and measurement sequences. Decision-making can be complex for state-of-the-art systems such as 3D hybrid photoacoustic-ultrasound (PA-US) breast imagers intended for multispectral quantitative imaging. These systems have a large set of design choices and system settings that affect imaging performance in different ways and often require trade-offs. Decisions have to be made carefully as they can strongly influence the imaging performance. AIM: A systematic approach to assess the influence of various choices on the imaging performance in carefully controlled laboratory situations is crucial before starting with human studies. Test objects and phantoms are used for first imaging studies, but most reported structures have a 2D geometry and are not suitable to assess all the image quality characteristics (IQCs) of 3D hybrid PA-US systems. APPROACH: Our work introduces a suite of five test objects designed for hybrid PA-US systems with a 3D detection aperture. We present the test object designs and production protocols and explain how they can be used to study various performance measures. To demonstrate the utility of the developed objects, measurements are made with an existing tomographic PA system. RESULTS: Two test objects were developed for measurements of the US detectors' impulse responses and light distribution on the breast surface. Three others were developed to assess image quality and quantitative accuracy of the PA and US modes. Three of the five objects were imaged to demonstrate their use. CONCLUSIONS: The developed test objects allow one to study influences of various choices in design and system settings. With this, IQCs can be assessed as a function of measurement sequence settings for the PA and US modes in a controlled way. Systematic studies and measurements using these objects will help to optimize various system settings and measurement protocols in laboratory situations before embarking on human studies.

Tunable blood oxygenation in the vascular anatomy of a semi-anthropomorphic photoacoustic breast phantom.

SIGNIFICANCE: Recovering accurate oxygenation estimations in the breast with quantitative photoacoustic tomography (QPAT) is not straightforward. Accurate light fluence models are required, but the unknown ground truth of the breast makes it difficult to validate them. Phantoms are often used for the validation, but most reported phantoms have a simple architecture. Fluence models developed in these simplistic objects are not accurate for application on the complex tissues of the breast. AIM: We present a sophisticated breast phantom platform for photoacoustic (PA) and ultrasound (US) imaging in general, and specifically for QPAT. The breast phantom is semi-anthropomorphic in distribution of optical and acoustic properties and contains wall-less channels with blood. APPROACH: 3D printing approaches are used to develop the solid 3D breast phantom from custom polyvinyl chloride plastisol formulations and additives for replicating the tissue optical and acoustic properties. A flow circuit was developed to flush the channels with bovine blood with a controlled oxygen saturation level. To showcase the phantom's functionality, PA measurements were performed on the phantom with two oxygenation levels. Image reconstructions with and without fluence compensation from Monte Carlo simulations were analyzed for the accuracy of oxygen saturation estimations. RESULTS: We present design aspects of the phantom, demonstrate how it is developed, and present its breast-like appearance in PA and US imaging. The oxygen saturations were estimated in two regions of interest with and without using the fluence models. The fluence compensation positively influenced the SO2 estimations in all cases and confirmed that highly accurate fluence models are required to minimize estimation errors. CONCLUSIONS: This phantom allows studies to be performed in PA in carefully controlled laboratory settings to validate approaches to recover both qualitative and quantitative features sought after in in-vivo studies. We believe that testing with phantoms of this complexity can streamline the transition of new PA technologies from the laboratory to studies in the clinic.

Tomographic imaging with an ultrasound and LED-based photoacoustic system.

Pulsed lasers in photoacoustic tomography systems are expensive, which limit their use to a few clinics and small animal labs. We present a method to realize tomographic ultrasound and photoacoustic imaging using a commercial LED-based photoacoustic and ultrasound system. We present two illumination configurations using LED array units and an optimal number of angular views for tomographic reconstruction. The proposed method can be a cost-effective solution for applications demanding tomographic imaging and can be easily integrated into conventional linear array-based ultrasound systems. We present a potential application for finger joint imaging in vivo, which can be used for point-of-care rheumatoid arthritis diagnosis and monitoring.

Current and future trends in photoacoustic breast imaging.

Non-invasive detection of breast cancer has been regarded as the holy grail of applications for photoacoustic (optoacoustic) imaging right from the early days of re-discovery of the method. Two-and-a-half decades later we report on the state-of-the-art in photoacoustic breast imaging technology and clinical studies. Even within the single application of breast imaging, we find imagers with various measurement geometries, ultrasound detection characteristics, illumination schemes, and image reconstruction strategies. We first analyze the implications on performance of a few of these design choices in a generic imaging system, before going into detailed descriptions of the imagers. Per imaging system we present highlights of patient studies, which barring a couple are mostly in the nature of technology demonstrations and proof-of-principle studies. We close this work with a discussion on several aspects that may turn out to be crucial for the future clinical translation of the method.

Semi-anthropomorphic photoacoustic breast phantom.

Imaging parameters of photoacoustic breast imaging systems such as the spatial resolution and imaging depth are often characterized with phantoms. These objects usually contain simple structures in homogeneous media such as absorbing wires or spherical objects in scattering gels. While these kinds of basic phantoms are uncluttered and useful, they do not challenge the system as much as a breast does, and can thereby overestimate the system's performance. The female breast is a complex collection of tissue types, and the acoustic and optical attenuation of these tissues limit the imaging depth, the resolution and the ability to extract quantitative information. For testing and challenging photoacoustic breast imaging systems to the full extent before moving to in vivo studies, a complex breast phantom which simulates the breast's most prevalent tissues is required. In this work we present the first three dimensional multi-layered semi-anthropomorphic photoacoustic breast phantom. The phantom aims to simulate skin, fat, fibroglandular tissue and blood vessels. The latter three are made from custom polyvinyl chloride plastisol (PVCP) formulations and are appropriately doped with additives to obtain tissue realistic acoustic and optical properties. Two tumors are embedded, which are modeled as clusters of small blood vessels. The PVCP materials are surrounded by a silicon layer mimicking the skin. The tissue mimicking materials were cast into the shapes and sizes expected in the breast using 3D-printed moulds developed from a magnetic resonance imaging segmented numerical breast model. The various structures and layers were assembled to obtain a realistic breast morphology. We demonstrate the phantom's appearance in both ultrasound imaging as photoacoustic tomography and make a comparison with a photoacoustic image of a real breast. A good correspondence is observed, which confirms the phantom's usefulness.

Opening the "White Box" in Tissue Engineering: Visualization of Cell Aggregates in Optically Scattering Scaffolds.

The noninvasive and longitudinal imaging of cells or cell aggregates in large optically scattering scaffolds is still a largely unresolved problem in tissue engineering. In this work, we investigated the potential of near-infrared (NIR) photoacoustic (PA) tomography imaging to address this issue. We used clinically relevant sizes of highly light scattering polyethersulfone multibore(®) hollow fiber scaffolds seeded with cells. Since cells have little optical absorption at NIR wavelengths, we studied labeling of cells with absorbers. Four NIR labels were examined for their suitability based on absorption characteristics, resistance to bleaching, and influence on cell viability. On the basis of these criteria, carbon nanoparticles proved most suitable in a variety of cells. For PA imaging, we used a research setup, based on computed tomography geometry. As proof of principle, using this imager we monitored the distribution and clustering of labeled rat insulinoma beta cell aggregates in the scaffolds. This was performed for the duration of 1 week in a nondestructive manner. The results were validated using fluorescence imaging, histology, and light microscopy imaging. Based on our findings, we conclude that PA tomography is a powerful tool for the nondestructive imaging of cells in optically scattering tissue-engineered scaffolds.