Biopathologic Characterization and Grade Assessment of Breast Cancer With 3-D Multiparametric Ultrasound Combining Shear Wave Elastography and Backscatter Tensor Imaging.

OBJECTIVE: Despite recent improvements in medical imaging, the final diagnosis and biopathologic characterization of breast cancers currently still requires biopsies. Ultrasound is commonly used for clinical examination of breast masses. B-Mode and shear wave elastography (SWE) are already widely used to detect suspicious masses and differentiate benign lesions from cancers. But additional ultrasound modalities such as backscatter tensor imaging (BTI) could provide relevant biomarkers related to tissue organization. Here we describe a 3-D multiparametric ultrasound approach applied to breast carcinomas in the aims of (i) validating the ability of BTI to reveal the underlying organization of collagen fibers and (ii) assessing the complementarity of SWE and BTI to reveal biopathologic features of diagnostic interest. METHODS: Three-dimensional SWE and BTI were performed ex vivo on 64 human breast carcinoma samples using a linear ultrasound probe moved by a set of motors. Here we describe a 3-D multiparametric representation of the breast masses and quantitative measurements combining B-mode, SWE and BTI. RESULTS: Our results reveal for the first time that BTI can capture the orientation of the collagen fibers around tumors. BTI was found to be a relevant marker for assessing cancer stages, revealing a more tangent tissue orientation for in situ carcinomas than for invasive cancers. In invasive cases, the combination of BTI and SWE parameters allowed for classification of invasive tumors with respect to their grade with an accuracy of 95.7%. CONCLUSION: Our results highlight the potential of 3-D multiparametric ultrasound imaging for biopathologic characterization of breast tumors.

Proof of Concept of 3-D Backscatter Tensor Imaging Tomography for Non-invasive Assessment of Human Breast Cancer Collagen Organization.

Tumor growth, similarly to several other pathologies, tends to change the structural orientation of soft tissue fibers, which can become relevant markers for diagnosis. Current diagnosis protocols may require a biopsy for histological analysis, which is an invasive, painful and stressful procedure with a minimum turnaround time of 2 d. Otherwise, diagnosis may involve the use of complex methods with limited availability such as diffusion tensor imaging (magnetic resonance diffusion tensor imaging), which is not widely used in medical practice. Conversely, advanced methodologies in ultrasound imaging such as backscatter tensor imaging (BTI) might become a routine procedure in clinical practice at a limited cost. This method evaluates the local organization of soft tissues based on the spatial coherence of their backscattered ultrasonic echoes. Previous work has proven that BTI applied with matrix probes enables measurement of the orientation of soft tissue fibers, especially in the myocardium. The aims of the study described here were (i) to present for the first time a methodology for performing BTI in a volume on ex vivo human breast tumors using a linear probe and (ii) to display a first proof of concept of the link between BTI measurements and the orientation of collagen fibers.

Simultaneous positron emission tomography and ultrafast ultrasound for hybrid molecular, anatomical and functional imaging.

Positron emission tomography-computed tomography (PET-CT) is the most sensitive molecular imaging modality, but it does not easily allow for rapid temporal acquisition. Ultrafast ultrasound imaging (UUI)-a recently introduced technology based on ultrasonic holography-leverages frame rates of up to several thousand images per second to quantitatively map, at high resolution, haemodynamic, biomechanical, electrophysiological and structural parameters. Here, we describe a pre-clinical scanner that registers PET-CT and UUI volumes acquired simultaneously and offers multiple combinations for imaging. We demonstrate that PET-CT-UUI allows for simultaneous images of the vasculature and metabolism during tumour growth in mice and rats, as well as for synchronized multi-modal cardiac cine-loops. Combined anatomical, functional and molecular imaging with PET-CT-UUI represents a high-performance and clinically translatable technology for biomedical research.

Development and validation of a prognostic model incorporating texture analysis derived from standardised segmentation of PET in patients with oesophageal cancer.

OBJECTIVES: This retrospective cohort study developed a prognostic model incorporating PET texture analysis in patients with oesophageal cancer (OC). Internal validation of the model was performed. METHODS: Consecutive OC patients (n = 403) were chronologically separated into development (n = 302, September 2010-September 2014, median age = 67.0, males = 227, adenocarcinomas = 237) and validation cohorts (n = 101, September 2014-July 2015, median age = 69.0, males = 78, adenocarcinomas = 79). Texture metrics were obtained using a machine-learning algorithm for automatic PET segmentation. A Cox regression model including age, radiological stage, treatment and 16 texture metrics was developed. Patients were stratified into quartiles according to a prognostic score derived from the model. A p-value < 0.05 was considered statistically significant. Primary outcome was overall survival (OS). RESULTS: Six variables were significantly and independently associated with OS: age [HR =1.02 (95% CI 1.01-1.04), p < 0.001], radiological stage [1.49 (1.20-1.84), p < 0.001], treatment [0.34 (0.24-0.47), p < 0.001], log(TLG) [5.74 (1.44-22.83), p = 0.013], log(Histogram Energy) [0.27 (0.10-0.74), p = 0.011] and Histogram Kurtosis [1.22 (1.04-1.44), p = 0.017]. The prognostic score demonstrated significant differences in OS between quartiles in both the development (X2 143.14, df 3, p < 0.001) and validation cohorts (X2 20.621, df 3, p < 0.001). CONCLUSIONS: This prognostic model can risk stratify patients and demonstrates the additional benefit of PET texture analysis in OC staging. KEY POINTS: • PET texture analysis adds prognostic value to oesophageal cancer staging. • Texture metrics are independently and significantly associated with overall survival. • A prognostic model including texture analysis can help risk stratify patients.

ATLAAS: an automatic decision tree-based learning algorithm for advanced image segmentation in positron emission tomography.

Accurate and reliable tumour delineation on positron emission tomography (PET) is crucial for radiotherapy treatment planning. PET automatic segmentation (PET-AS) eliminates intra- and interobserver variability, but there is currently no consensus on the optimal method to use, as different algorithms appear to perform better for different types of tumours. This work aimed to develop a predictive segmentation model, trained to automatically select and apply the best PET-AS method, according to the tumour characteristics. ATLAAS, the automatic decision tree-based learning algorithm for advanced segmentation is based on supervised machine learning using decision trees. The model includes nine PET-AS methods and was trained on a 100 PET scans with known true contour. A decision tree was built for each PET-AS algorithm to predict its accuracy, quantified using the Dice similarity coefficient (DSC), according to the tumour volume, tumour peak to background SUV ratio and a regional texture metric. The performance of ATLAAS was evaluated for 85 PET scans obtained from fillable and printed subresolution sandwich phantoms. ATLAAS showed excellent accuracy across a wide range of phantom data and predicted the best or near-best segmentation algorithm in 93% of cases. ATLAAS outperformed all single PET-AS methods on fillable phantom data with a DSC of 0.881, while the DSC for H&N phantom data was 0.819. DSCs higher than 0.650 were achieved in all cases. ATLAAS is an advanced automatic image segmentation algorithm based on decision tree predictive modelling, which can be trained on images with known true contour, to predict the best PET-AS method when the true contour is unknown. ATLAAS provides robust and accurate image segmentation with potential applications to radiation oncology.

PETSTEP: Generation of synthetic PET lesions for fast evaluation of segmentation methods.

PURPOSE: This work describes PETSTEP (PET Simulator of Tracers via Emission Projection): a faster and more accessible alternative to Monte Carlo (MC) simulation generating realistic PET images, for studies assessing image features and segmentation techniques. METHODS: PETSTEP was implemented within Matlab as open source software. It allows generating three-dimensional PET images from PET/CT data or synthetic CT and PET maps, with user-drawn lesions and user-set acquisition and reconstruction parameters. PETSTEP was used to reproduce images of the NEMA body phantom acquired on a GE Discovery 690 PET/CT scanner, and simulated with MC for the GE Discovery LS scanner, and to generate realistic Head and Neck scans. Finally the sensitivity (S) and Positive Predictive Value (PPV) of three automatic segmentation methods were compared when applied to the scanner-acquired and PETSTEP-simulated NEMA images. RESULTS: PETSTEP produced 3D phantom and clinical images within 4 and 6 min respectively on a single core 2.7 GHz computer. PETSTEP images of the NEMA phantom had mean intensities within 2% of the scanner-acquired image for both background and largest insert, and 16% larger background Full Width at Half Maximum. Similar results were obtained when comparing PETSTEP images to MC simulated data. The S and PPV obtained with simulated phantom images were statistically significantly lower than for the original images, but led to the same conclusions with respect to the evaluated segmentation methods. CONCLUSIONS: PETSTEP allows fast simulation of synthetic images reproducing scanner-acquired PET data and shows great promise for the evaluation of PET segmentation methods.