Development of an anthropomorphic breast phantom for combined PET, B-mode ultrasound and elastographic imaging

International audienceCombining the advantages of different imaging modalities leads to improved clinical results. For example, ultrasound provides good real-time structural information without any radiation and PET provides sensitive functional information. For the ongoing ClearPEM-Sonic project combining ultrasound and PET for breast imaging, we developed a dual-modality PET/Ultrasound (US) phantom. The phantom reproduces the acoustic and elastic properties of human breast tissue and allows labeling the different tissues in the phantom with different concentrations of FDG. The phantom was imaged with a whole-body PET/CT and with the Supersonic Imagine Aixplorer system. This system allows both B-mode US and shear wave elastographic imaging. US elastography is a new imaging method for displaying the tissue elasticity distribution. It was shown to be useful in breast imaging. We also tested the phantom with static elastography. A 6D magnetic positioning system allows fusing the images obtained with the two modalities. ClearPEM-Sonic is a project of the Crystal Clear Collaboration and the European Centre for Research on Medical Imaging (CERIMED)

An Experimental and Numerical Study on Tactile Neuroimaging: A Novel Minimally Invasive Technique for Intraoperative Brain Imaging

This is the peer reviewed version of the following article: Moslem Sadeghi-Goughari, Yanjun Qian, Soo Jeon, Sohrab Sadeghi and Hyock-Ju Kwon, “An Experimental and Numerical Study on Tactile Neuroimaging: A Novel Minimally Invasive Technique for Intraoperative Brain Imaging,” accepted to The International Journal of Medical Robotics and Computer Assisted Surgery which has been published in final form at: https://doi.org/10.1002/rcs.1893. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Background The success of tumor neurosurgery is highly dependent on the ability to accurately localize the operative target, which may be shifted during the operation. Performing an intraoperative brain imaging is crucial in minimally invasive neurosurgery to detect the effect of brain shift on the tumor’s location, and to maximize the efficiency of tumor resection. Method The major objective of this research is to introduce the tactile neuroimaging as a novel minimally invasive technique for intraoperative brain imaging. To investigate the feasibility of the proposed method, an experimental and numerical study was first performed on silicone phantoms mimicking the brain tissue with a tumor. Then the study was extended to a clinical model with the meningioma tumor. Results The stress distribution on the brain surface has high potential to intraoperatively localize the tumor. Conclusion Results suggest that tactile neuroimaging can be used to provide a non-invasive, and real-time intraoperative data on tumor’s features.Natural Sciences and Engineering Research Council || RGPIN/2015-05273, RGPIN/2015-04118, RGPAS/354703-201

Novel 3D Ultrasound Elastography Techniques for In Vivo Breast Tumor Imaging and Nonlinear Characterization

Breast cancer comprises about 29% of all types of cancer in women worldwide. This type of cancer caused what is equivalent to 14% of all female deaths due to cancer. Nowadays, tissue biopsy is routinely performed, although about 80% of the performed biopsies yield a benign result. Biopsy is considered the most costly part of breast cancer examination and invasive in nature. To reduce unnecessary biopsy procedures and achieve early diagnosis, ultrasound elastography was proposed.;In this research, tissue displacement fields were estimated using ultrasound waves, and used to infer the elastic properties of tissues. Ultrasound radiofrequency data acquired at consecutive increments of tissue compression were used to compute local tissue strains using a cross correlation method. In vitro and in vivo experiments were conducted on different tissue types to demonstrate the ability to construct 2D and 3D elastography that helps distinguish stiff from soft tissues. Based on the constructed strain volumes, a novel nonlinear classification method for human breast tumors is introduced. Multi-compression elastography imaging is elucidated in this study to differentiate malignant from benign tumors, based on their nonlinear mechanical behavior under compression. A pilot study on ten patients was performed in vivo, and classification results were compared with biopsy diagnosis - the gold standard. Various nonlinear parameters based on different models, were evaluated and compared with two commonly used parameters; relative stiffness and relative tumor size. Moreover, different types of strain components were constructed in 3D for strain imaging, including normal axial, first principal, maximum shear and Von Mises strains. Interactive segmentation algorithms were also evaluated and applied on the constructed volumes, to delineate the stiff tissue by showing its isolated 3D shape.;Elastography 3D imaging results were in good agreement with the biopsy outcomes, where the new classification method showed a degree of discrepancy between benign and malignant tumors better than the commonly used parameters. The results show that the nonlinear parameters were found to be statistically significant with p-value \u3c0.05. Moreover, one parameter; power-law exponent, was highly statistically significant having p-value \u3c 0.001. Additionally, volumetric strain images reconstructed using the maximum shear strains provided an enhanced tumor\u27s boundary from the surrounding soft tissues. This edge enhancement improved the overall segmentation performance, and diminished the boundary leakage effect. 3D segmentation provided an additional reliable means to determine the tumor\u27s size by estimating its volume.;In summary, the proposed elastographic techniques can help predetermine the tumor\u27s type, shape and size that are considered key features helping the physician to decide the sort and extent of the treatment. The methods can also be extended to diagnose other types of tumors, such as prostate and cervical tumors. This research is aimed toward the development of a novel \u27virtual biopsy\u27 method that may reduce the number of unnecessary painful biopsies, and diminish the increasingly risk of cancer

Tomographic measurement of all orthogonal components of three-dimensional displacement fields within scattering materials using wavelength scanning interferometry

Experimental mechanics is currently contemplating tremendous opportunities of further advancements thanks to a combination of powerful computational techniques and also fullfield non-contact methods to measure displacement and strain fields in a wide variety of materials. Identification techniques, aimed to evaluate material mechanical properties given known loads and measured displacement or strain fields, are bound to benefit from increased data availability (both in density and dimensionality) and efficient inversion methods such as finite element updating (FEU) and the virtual fields method (VFM). They work at their best when provided with dense and multicomponent experimental displacement (or strain) data, i.e. when all orthogonal components of displacements (or all components of the strain tensor) are known at points closely spaced within the volume of the material under study. Although a very challenging requirement, an increasing number of techniques are emerging to provide such data. In this Thesis, a novel wavelength scanning interferometry (WSI) system that provides three dimensional (3-D) displacement fields inside the volume of semi-transparent scattering materials is proposed. Sequences of two-dimensional interferograms are recorded whilst tuning the frequency of a laser at a constant rate. A new approach based on frequency multiplexing is used to encode the interference signal corresponding to multiple illumination directions at different spectral bands. Different optical paths along each illumination direction ensure that the signals corresponding to each sensitivity vector do not overlap in the frequency domain. All the information required to reconstruct the location and the 3-D displacement vector of scattering points within the material is thus recorded simultaneously in a single wavelength scan. By comparing phase data volumes obtained for two successive scans, all orthogonal components of the three dimensional displacement field introduced between scans (e.g. by means of loading or moving the sample under study) are readily obtained with high displacement sensitivity. The fundamental principle that describes the technique is presented in detail, including the correspondence between interference signal frequency and its associated depth within the sample, depth range, depth resolution, transverse resolution and displacement sensitivity. Data processing of the interference signal includes Fourier transformation, noise reduction, re-registration of data volumes, measurement of the illumination and sensitivity vectors from experimental data using a datum surface, phase difference evaluation, 3-D phase unwrapping and 3-D displacement field evaluation. Experiments consisting of controlled rigid body rotations and translations of a phantom were performed to validate the results. Both in-plane and the out-of-plane displacement components were measured for each voxel in the resulting data volume, showing an excellent agreement with the expected 3-D displacement

Computational ultrasound tissue characterisation for brain tumour resection

In brain tumour resection, it is vital to know where critical neurovascular structuresand tumours are located to minimise surgical injuries and cancer recurrence. Theaim of this thesis was to improve intraoperative guidance during brain tumourresection by integrating both ultrasound standard imaging and elastography in thesurgical workflow. Brain tumour resection requires surgeons to identify the tumourboundaries to preserve healthy brain tissue and prevent cancer recurrence. Thisthesis proposes to use ultrasound elastography in combination with conventionalultrasound B-mode imaging to better characterise tumour tissue during surgery.Ultrasound elastography comprises a set of techniques that measure tissue stiffness,which is a known biomarker of brain tumours. The objectives of the researchreported in this thesis are to implement novel learning-based methods for ultrasoundelastography and to integrate them in an image-guided intervention framework.Accurate and real-time intraoperative estimation of tissue elasticity can guide towardsbetter delineation of brain tumours and improve the outcome of neurosurgery. We firstinvestigated current challenges in quasi-static elastography, which evaluates tissuedeformation (strain) by estimating the displacement between successive ultrasoundframes, acquired before and after applying manual compression. Recent approachesin ultrasound elastography have demonstrated that convolutional neural networkscan capture ultrasound high-frequency content and produce accurate strain estimates.We proposed a new unsupervised deep learning method for strain prediction, wherethe training of the network is driven by a regularised cost function, composed of asimilarity metric and a regularisation term that preserves displacement continuityby directly optimising the strain smoothness. We further improved the accuracy of our method by proposing a recurrent network architecture with convolutional long-short-term memory decoder blocks to improve displacement estimation and spatio-temporal continuity between time series ultrasound frames. We then demonstrateinitial results towards extending our ultrasound displacement estimation method toshear wave elastography, which provides a quantitative estimation of tissue stiffness.Furthermore, this thesis describes the development of an open-source image-guidedintervention platform, specifically designed to combine intra-operative ultrasoundimaging with a neuronavigation system and perform real-time ultrasound tissuecharacterisation. The integration was conducted using commercial hardware andvalidated on an anatomical phantom. Finally, preliminary results on the feasibilityand safety of the use of a novel intraoperative ultrasound probe designed for pituitarysurgery are presented. Prior to the clinical assessment of our image-guided platform,the ability of the ultrasound probe to be used alongside standard surgical equipmentwas demonstrated in 5 pituitary cases

COMPUTATIONAL ULTRASOUND ELASTOGRAPHY: A FEASIBILITY STUDY

Ultrasound Elastography (UE) is an emerging set of imaging modalities used to assess the biomechanical properties of soft tissues. UE has been applied to numerous clinical applications. Particularly, results from clinical trials of UE in breast lesion differentiation and staging liver fibrosis indicated that there was a lack of confidence in UE measurements or image interpretation. Confidence on UE measurements interpretation is critically important for improving the clinical utility of UE. The primary objective of my thesis is to develop a computational simulation platform based on open-source software packages including Field II, VTK, FEBio and Tetgen. The proposed virtual simulation platform can be used to simulate SE and acoustic radiation force based SWE simulations, including pSWE, SSI and ARFI. To demonstrate its usefulness, in this thesis, examples for breast cancer detections were provided. The simulated results can reproduce what has been reported in the literature. To statistically analyze the intrinsic variations of shear wave speed (SWS) in the fibrotic liver tissues, a probability density function (PDF) of the SWS distribution in conjunction with a lossless stochastic tissue model was derived using the principle of Maximum Entropy (ME). The performance of the proposed PDF was evaluated using Monte-Carlo (MC) simulated shear wave data and against three other commonly used PDFs. We theoretically demonstrated that SWS measurements follow a non-Gaussian distribution for the first time. One advantage of the proposed PDF is its physically meaningful parameters. Also, we conducted a case study of the relationship between shear wave measurements and the microstructure of fibrotic liver tissues. Three different virtual tissue models were used to represent underlying microstructures of fibrotic liver tissues. Furthermore, another innovation of this thesis is the inclusion of “biologically-relevant” fibrotic liver tissue models for simulation of shear wave elastography. To link tissue structure, composition and architecture to the ultrasound measurements directly, a “biologically relevant” tissue model was established using Systems Biology. Our initial results demonstrated that the simulated virtual liver tissues qualitatively could reproduce histological results and wave speed measurements. In conclusions, these computational tools and theoretical analysis can improve the confidence on UE image/measurements interpretation

Multimodal and multiscale imaging of the human placental vasculature

Minimally invasive fetal interventions, such as those used for therapy of twin-to- twin transfusion syndrome (TTTS), require accurate image guidance to optimise patient outcomes. Photoacoustic imaging can provide molecular contrast based on the optical absorption of the haemoglobin, and in this dissertation, it was proposed as a novel technique to image the human placental vasculature. Normal term and in utero TTTS treated placentas were imaged post-partum using two novel photoacoustic imaging systems. With PA imaging, vasculature was resolved to a depth of approximately 7 mm from the chorionic placental surface; the photocoagulated tissue provided a negative contrast and the ablation depth of the scar was visualised. Complementary imaging of the placental vasculature in a microscopic size scale was performed with a handheld incident dark field illumination video microscope in fresh and formalin-fixed term placentas. Real time visualisation of the villus tree down to the terminal villi level was achieved without any contrast injection or extensive tissue preparation. Additionally, the novel application of photoacoustic imaging to guide minimally invasive fetal interventions motivated the development of tissue-mimicking placental phantoms for bench-top system validation and for clinical training. Ideally, phantoms for this modality comprise materials with optical and acoustic properties that can be precisely and independently controlled, which are stable over time, and which are non-toxic and low-cost. Gel wax was proposed as a novel tissue-mimicking material (TMM) that satisfies these criteria, and that it can be used to represent various soft tissues and fabricate heterogeneous phantoms with structures based on patient-specific anatomy. This dissertation sets the stage for the development of miniaturised photoacoustic imaging probes for intraoperative guidance, and new methods of understanding the placental vascular anatomy in health and disease. Gel wax has strong potential to become a next generation TMM for evaluation, and standardisation of imaging systems, and for clinical training

Tissue mimicking materials for imaging and therapy phantoms: a review

Tissue mimicking materials (TMMs), typically contained within phantoms, have been used for many decades in both imaging and therapeutic applications. This review investigates the specifications that are typically being used in development of the latest TMMs. The imaging modalities that have been investigated focus around CT, mammography, SPECT, PET, MRI and ultrasound. Therapeutic applications discussed within the review include radiotherapy, thermal therapy and surgical applications. A number of modalities were not reviewed including optical spectroscopy, optical imaging and planar x-rays. The emergence of image guided interventions and multimodality imaging have placed an increasing demand on the number of specifications on the latest TMMs. Material specification standards are available in some imaging areas such as ultrasound. It is recommended that this should be replicated for other imaging and therapeutic modalities. Materials used within phantoms have been reviewed for a series of imaging and therapeutic applications with the potential to become a testbed for cross-fertilization of materials across modalities. Deformation, texture, multimodality imaging and perfusion are common themes that are currently under development

SMART IMAGE-GUIDED NEEDLE INSERTION FOR TISSUE BIOPSY

M.S

QUANTITATIVE THREE DIMENSIONAL ELASTICITY IMAGING

Neoplastic tissue is typically highly vascularized, contains abnormal concentrations of extracellular proteins (e.g. collagen, proteoglycans) and has a high interstitial fluid pres- sure compared to most normal tissues. These changes result in an overall stiffening typical of most solid tumors. Elasticity Imaging (EI) is a technique which uses imaging systems to measure relative tissue deformation and thus noninvasively infer its mechanical stiffness. Stiffness is recovered from measured deformation by using an appropriate mathematical model and solving an inverse problem. The integration of EI with existing imaging modal- ities can improve their diagnostic and research capabilities. The aim of this work is to develop and evaluate techniques to image and quantify the mechanical properties of soft tissues in three dimensions (3D). To that end, this thesis presents and validates a method by which three dimensional ultrasound images can be used to image and quantify the shear modulus distribution of tissue mimicking phantoms. This work is presented to motivate and justify the use of this elasticity imaging technique in a clinical breast cancer screening study. The imaging methodologies discussed are intended to improve the specificity of mammography practices in general. During the development of these techniques, several issues concerning the accuracy and uniqueness of the result were elucidated. Two new algorithms for 3D EI are designed and characterized in this thesis. The first provides three dimensional motion estimates from ultrasound images of the deforming ma- terial. The novel features include finite element interpolation of the displacement field, inclusion of prior information and the ability to enforce physical constraints. The roles of regularization, mesh resolution and an incompressibility constraint on the accuracy of the measured deformation is quantified. The estimated signal to noise ratio of the measured displacement fields are approximately 1800, 21 and 41 for the axial, lateral and eleva- tional components, respectively. The second algorithm recovers the shear elastic modulus distribution of the deforming material by efficiently solving the three dimensional inverse problem as an optimization problem. This method utilizes finite element interpolations, the adjoint method to evaluate the gradient and a quasi-Newton BFGS method for optimiza- tion. Its novel features include the use of the adjoint method and TVD regularization with piece-wise constant interpolation. A source of non-uniqueness in this inverse problem is identified theoretically, demonstrated computationally, explained physically and overcome practically. Both algorithms were test on ultrasound data of independently characterized tissue mimicking phantoms. The recovered elastic modulus was in all cases within 35% of the reference elastic contrast. Finally, the preliminary application of these techniques to tomosynthesis images showed the feasiblity of imaging an elastic inclusion.CenSSIS, the Center for Subsurface Sensing and Imaging Systems, under the Engineering Research Centers Program of the National Science Foundation (award number EEC-9986821