Effect of lesion morphology on microwave signature in 2-D ultra-wideband breast imaging

This paper studies the possibility of distinguishing between benign and malignant masses by exploiting the morphology-dependent temporal and spectral characteristics of their microwave backscatter response in ultra-wideband breast cancer detection. The spiculated border profiles of 2-D breast masses are generated by modifying the baseline elliptical rings based upon the irregularity of their peripheries. Furthermore, the single- and multilayer lesion models are used to characterize a distinct mass region followed by a sharp transition to background, and a blurred mass border exhibiting a gradual transition to background, respectively. Subsequently, the complex natural resonances (CNRs) of the backscatter microwave signature can be derived from the late-time target response and reveal diagnostically useful information. The fractional sequence CLEAN algorithm is proposed to estimate the lesions' delay intervals and identify the late-time responses. Finally, it is shown through numerical examples that the locations of dominant CNRs are dependent on the lesion morphologies, where 2-D computational breast phantoms with single and multiple lesions are investigated. The analysis is of potential use for discrimination between benign and malignant lesions, where the former usually possesses a better-defined, more compact shape as opposed to the latter.

Three-dimensional, in-silico breast phantom for multimodality image simulations

We report on the construction of anatomically realistic three-dimensional in-silico breast phantoms with adjustable sizes, shapes and morphologic features. The concept of multiscale spatial resolution is implemented for generating breast tissue images from multiple modalities. Breast epidermal boundary and subcutaneous fat layer is generated by fitting an ellipsoid and 2nd degree polynomials to reconstructive surgical data and ultrasound imaging data. Intraglandular fat is simulated by randomly distributing and orienting adipose ellipsoids within a fibrous region immediately within the dermal layer. Cooper’s ligaments are simulated as fibrous ellipsoidal shells distributed within the subcutaneous fat layer. Individual ductal lobes are simulated following a random binary tree model which is generated based upon probabilistic branching conditions described by ramification matrices, as originally proposed by Bakic et al [3, 4]. The complete ductal structure of the breast is simulated from multiple lobes that extend from the base of the nipple and branch towards the chest wall. As lobe branching progresses, branches are reduced in height and radius and terminal branches are capped with spherical lobular clusters. Biophysical parameters are mapped onto the complete anatomical model and synthetic multimodal images (Mammography, Ultrasound, CT) are generated for phantoms of different adipose percentages (40%, 50%, 60%, and 70%) and are analytically compared with clinical examples. Results demonstrate that the in-silico breast phantom has applications in imaging performance evaluation and, specifically, great utility for solving image registration issues in multimodality imaging.

Planification de traitements de curiethérapie du sein à l’aide de l’imagerie par résonance magnétique

Ce mémoire présente l’étude de la faisabilité de la planification de traitements pour la curiethérapie interstitielle du sein en utilisant l’imagerie par résonance magnétique (IRM) seule au lieu de l’imagerie par tomodensitométrie (CT). L'imagerie CT étant la référence, la mesure des différences observables sur la distribution de doses provenant des deux types d’imagerie a été effectuée. Des fantômes de seins ont été fabriqués et utilisés, ainsi que l’imagerie de patients. La taille des fantômes en fonction du positionnement dans l’appareil d’IRM et la longueur reconstruite des cathéters ont été analysées. Les différences dans les distributions de doses de fantômes et de patients ont été calculées en s’assurant que la reconstruction des cathéters provenant des images CT et IRM est la seule variable. La différence dans les critères de doses à respecter est plus grande lorsque la taille du fantôme et/ou un déplacement latéral dans l’IRM sont plus grands. La longueur reconstruite des cathéters est comparable entre les deux techniques d’imagerie. Pour le petit fantôme des différences <2% ont été observées pour tous les critères de dose. Pour le grand fantôme et pour les patients, une valeur maximale de 5% est observée pour les critères sur la cible, mais peut atteindre 19% pour le critère Externe V150%/V100% pour le grand fantôme et 33% pour les patients. Par contre, le seuil clinique de ce critére est toujours respecté. Ceci nous indique que pour la plupart des patients, la zone à traiter serait bien couverte en utilisant les images IRM uniquement pour planifier.

Development of active microwave imaging techniques for applications in mammography

Breast cancer is the most common non - skin malignancy in women and a leading cause of female morality. A potentially important strategy for reducing this menace is the detection at an early stage . The invention of non-invasive and non-ionizing microwave technique, to reveal the internal structure of biological objects was a break through in the field of medical diagnostics. Electrical properties of biological tissues and their interaction with electromagmetic waves have direct impact on human life. This thesis focuses on theoretical and experimental investigations of active microwave imaging techniques for breast cancer detection.

Simulador radiográfico antropomórfico de mama humana

Mammography is a diagnostic imaging method in which interpretation depends on knowledge of radiological aspects as well as the clinical exam and pathophysiology of breast diseases. In this work a mammography phantom was developed to be used for training in the operation of mammographic x-ray equipment, image quality evaluation, self-examination and clinical examination of palpation. Polyurethane was used for the production of the phantoms for its physical and chemical properties and because it is one of the components normally used in prostheses. According to the range of flexibility of the polyurethane, it was possible to simulate breasts with higher or lower amount of adipose tissue. Pathologies such as areolar necrosis and tissue rejection due to surgery reconstruction after partial mastectomy were also simulated. Calcifications and nodules were simulated using the following materials: polyethylene, poly (methyl methacrylate), polyamide, polyurethane and poly (dimethyl silicone). Among these, polyethylene was able to simulate characteristics of calcification as well as breast nodules. The results from mammographic techniques used in this paper for the evaluation of the phantoms are in agreement with data found in the literature. The image analyses of four phantoms indicated significant similarities with the human skin texture and the female breast parenchyma. It was possible to detect in the radiographic images produced regions of high and low radiographic optical density, which are characteristic of breasts with regions of different amount of adipose tissue. The stiffnesses of breast phantoms were adjusted according to the formulation of the polyurethane which enabled the production of phantoms with distinct radiographic features and texture similar to human female breast parenchyma. Clinical palpation exam of the phantoms developed in this work indicated characteristics similar to human breast in skin texture, areolar region and parenchyma

Simulador radiográfico antropomórfico de mama humana

Mammography is a diagnostic imaging method in which interpretation depends on knowledge of radiological aspects as well as the clinical exam and pathophysiology of breast diseases. In this work a mammography phantom was developed to be used for training in the operation of mammographic x-ray equipment, image quality evaluation, self-examination and clinical examination of palpation. Polyurethane was used for the production of the phantoms for its physical and chemical properties and because it is one of the components normally used in prostheses. According to the range of flexibility of the polyurethane, it was possible to simulate breasts with higher or lower amount of adipose tissue. Pathologies such as areolar necrosis and tissue rejection due to surgery reconstruction after partial mastectomy were also simulated. Calcifications and nodules were simulated using the following materials: polyethylene, poly (methyl methacrylate), polyamide, polyurethane and poly (dimethyl silicone). Among these, polyethylene was able to simulate characteristics of calcification as well as breast nodules. The results from mammographic techniques used in this paper for the evaluation of the phantoms are in agreement with data found in the literature. The image analyses of four phantoms indicated significant similarities with the human skin texture and the female breast parenchyma. It was possible to detect in the radiographic images produced regions of high and low radiographic optical density, which are characteristic of breasts with regions of different amount of adipose tissue. The stiffnesses of breast phantoms were adjusted according to the formulation of the polyurethane which enabled the production of phantoms with distinct radiographic features and texture similar to human female breast parenchyma. Clinical palpation exam of the phantoms developed in this work indicated characteristics similar to human breast in skin texture, areolar region and parenchyma

Performance metrics of an optical spectral imaging system for intra-operative assessment of breast tumor margins.

As many as 20-70% of patients undergoing breast conserving surgery require repeat surgeries due to a close or positive surgical margin diagnosed post-operatively [1]. Currently there are no widely accepted tools for intra-operative margin assessment which is a significant unmet clinical need. Our group has developed a first-generation optical visible spectral imaging platform to image the molecular composition of breast tumor margins and has tested it clinically in 48 patients in a previously published study [2]. The goal of this paper is to report on the performance metrics of the system and compare it to clinical criteria for intra-operative tumor margin assessment. The system was found to have an average signal to noise ratio (SNR) >100 and <15% error in the extraction of optical properties indicating that there is sufficient SNR to leverage the differences in optical properties between negative and close/positive margins. The probe had a sensing depth of 0.5-2.2 mm over the wavelength range of 450-600 nm which is consistent with the pathologic criterion for clear margins of 0-2 mm. There was <1% cross-talk between adjacent channels of the multi-channel probe which shows that multiple sites can be measured simultaneously with negligible cross-talk between adjacent sites. Lastly, the system and measurement procedure were found to be reproducible when evaluated with repeated measures, with a low coefficient of variation (<0.11). The only aspect of the system not optimized for intra-operative use was the imaging time. The manuscript includes a discussion of how the speed of the system can be improved to work within the time constraints of an intra-operative setting.

Investigation and Development of a Fully 3D Tilt Capable Hybrid SPECT - CT System for Dedicated Breast Imaging

X-ray mammography has been the gold standard for breast imaging for decades, despite the significant limitations posed by the two dimensional (2D) image acquisitions. Difficulty in diagnosing lesions close to the chest wall and axilla, high amount of structural overlap and patient discomfort due to compression are only some of these limitations. To overcome these drawbacks, three dimensional (3D) breast imaging modalities have been developed including dual modality single photon emission computed tomography (SPECT) and computed tomography (CT) systems. This thesis focuses on the development and integration of the next generation of such a device for dedicated breast imaging. The goals of this dissertation work are to: [1] understand and characterize any effects of fully 3-D trajectories on reconstructed image scatter correction, absorbed dose and Hounsifeld Unit accuracy, and [2] design, develop and implement the fully flexible, third generation hybrid SPECT-CT system capable of traversing complex 3D orbits about a pendant breast volume, without interference from the other. Such a system would overcome artifacts resulting from incompletely sampled divergent cone beam imaging schemes and allow imaging closer to the chest wall, which other systems currently under research and development elsewhere cannot achieve.

The dependence of x-ray scatter radiation on object shape, size, material composition and the CT acquisition trajectory, was investigated with a well-established beam stop array (BSA) scatter correction method. While the 2D scatter to primary ratio (SPR) was the main metric used to characterize total system scatter, a new metric called ‘normalized scatter contribution’ was developed to compare the results of scatter correction on 3D reconstructed volumes. Scatter estimation studies were undertaken with a sinusoidal saddle (±15° polar tilt) orbit and a traditional circular (AZOR) orbit. Clinical studies to acquire data for scatter correction were used to evaluate the 2D SPR on a small set of patients scanned with the AZOR orbit. Clinical SPR results showed clear dependence of scatter on breast composition and glandular tissue distribution, otherwise consistent with the overall phantom-based size and density measurements. Additionally, SPR dependence was also observed on the acquisition trajectory where 2D scatter increased with an increase in the polar tilt angle of the system.

The dose delivered by any imaging system is of primary importance from the patient’s point of view, and therefore trajectory related differences in the dose distribution in a target volume were evaluated. Monte Carlo simulations as well as physical measurements using radiochromic film were undertaken using saddle and AZOR orbits. Results illustrated that both orbits deliver comparable dose to the target volume, and only slightly differ in distribution within the volume. Simulations and measurements showed similar results, and all measured dose values were within the standard screening mammography-specific, 6 mGy dose limit, which is used as a benchmark for dose comparisons.

Hounsfield Units (HU) are used clinically in differentiating tissue types in a reconstructed CT image, and therefore the HU accuracy of a system is very important, especially when using non-traditional trajectories. Uniform phantoms filled with various uniform density fluids were used to investigate differences in HU accuracy between saddle and AZOR orbits. Results illustrate the considerably better performance of the saddle orbit, especially close to the chest and nipple region of what would clinically be a pedant breast volume. The AZOR orbit causes shading artifacts near the nipple, due to insufficient sampling, rendering a major portion of the scanned phantom unusable, whereas the saddle orbit performs exceptionally well and provides a tighter distribution of HU values in reconstructed volumes.

Finally, the third generation, fully-suspended SPECT-CT system was designed in and developed in our lab. A novel mechanical method using a linear motor was developed for tilting the CT system. A new x-ray source and a custom made 40 x 30 cm2 detector were integrated on to this system. The SPECT system was nested, in the center of the gantry, orthogonal to the CT source-detector pair. The SPECT system tilts on a goniometer, and the newly developed CT tilting mechanism allows ±15° maximum polar tilting of the CT system. The entire gantry is mounted on a rotation stage, allowing complex arbitrary trajectories for each system, without interference from the other, while having a common field of view. This hybrid system shows potential to be used clinically as a diagnostic tool for dedicated breast imaging.

Quantitative ultrasound imaging during shear wave propagation for application related to breast cancer diagnosis

Dans le contexte de la caractérisation des tissus mammaires, on peut se demander ce que l’examen d’un attribut en échographie quantitative (« quantitative ultrasound » - QUS) d’un milieu diffusant (tel un tissu biologique mou) pendant la propagation d’une onde de cisaillement ajoute à son pouvoir discriminant. Ce travail présente une étude du comportement variable temporel de trois paramètres statistiques (l’intensité moyenne, le paramètre de structure et le paramètre de regroupement des diffuseurs) d’un modèle général pour l’enveloppe écho de l’onde ultrasonore rétrodiffusée (c.-à-d., la K-distribution homodyne) sous la propagation des ondes de cisaillement. Des ondes de cisaillement transitoires ont été générés en utilisant la mèthode d’ imagerie de cisaillement supersonique ( «supersonic shear imaging » - SSI) dans trois fantômes in-vitro macroscopiquement homogènes imitant le sein avec des propriétés mécaniques différentes, et deux fantômes ex-vivo hétérogénes avec tumeurs de souris incluses dans un milieu environnant d’agargélatine. Une comparaison de l’étendue des trois paramètres de la K-distribution homodyne avec et sans propagation d’ondes de cisaillement a montré que les paramètres étaient significativement (p < 0,001) affectès par la propagation d’ondes de cisaillement dans les expériences in-vitro et ex-vivo. Les résultats ont également démontré que la plage dynamique des paramétres statistiques au cours de la propagation des ondes de cisaillement peut aider à discriminer (avec p < 0,001) les trois fantômes homogènes in-vitro les uns des autres, ainsi que les tumeurs de souris de leur milieu environnant dans les fantômes hétérogénes ex-vivo. De plus, un modéle de régression linéaire a été appliqué pour corréler la plage de l’intensité moyenne sous la propagation des ondes de cisaillement avec l’amplitude maximale de déplacement du « speckle » ultrasonore. La régression linéaire obtenue a été significative : fantômes in vitro : R2 = 0.98, p < 0,001 ; tumeurs ex-vivo : R2 = 0,56, p = 0,013 ; milieu environnant ex-vivo : R2 = 0,59, p = 0,009. En revanche, la régression linéaire n’a pas été aussi significative entre l’intensité moyenne sans propagation d’ondes de cisaillement et les propriétés mécaniques du milieu : fantômes in vitro : R2 = 0,07, p = 0,328, tumeurs ex-vivo : R2 = 0,55, p = 0,022 ; milieu environnant ex-vivo : R2 = 0,45, p = 0,047. Cette nouvelle approche peut fournir des informations supplémentaires à l’échographie quantitative statistique traditionnellement réalisée dans un cadre statique (c.-à-d., sans propagation d’ondes de cisaillement), par exemple, dans le contexte de l’imagerie ultrasonore en vue de la classification du cancer du sein.

Fluorescence-enhanced optical imaging on three-dimensional phantoms using a hand-held probe based frequency-domain intensified charge coupled device (ICCD) optical imager

Fluorescence-enhanced optical imaging is an emerging non-invasive and non-ionizing modality towards breast cancer diagnosis. Various optical imaging systems are currently available, although most of them are limited by bulky instrumentation, or their inability to flexibly image different tissue volumes and shapes. Hand-held based optical imaging systems are a recent development for its improved portability, but are currently limited only to surface mapping. Herein, a novel optical imager, consisting primarily of a hand-held probe and a gain-modulated intensified charge coupled device (ICCD) detector, is developed towards both surface and tomographic breast imaging. The unique features of this hand-held probe based optical imager are its ability to; (i) image large tissue areas (5×10 sq. cm) in a single scan, (ii) reduce overall imaging time using a unique measurement geometry, and (iii) perform tomographic imaging for tumor three-dimensional (3-D) localization. Frequency-domain based experimental phantom studies have been performed on slab geometries (650 ml) under different target depths (1-2.5 cm), target volumes (0.45, 0.23 and 0.10 cc), fluorescence absorption contrast ratios (1:0, 1000:1 to 5:1), and number of targets (up to 3), using Indocyanine Green (ICG) as fluorescence contrast agents. An approximate extended Kalman filter based inverse algorithm has been adapted towards 3-D tomographic reconstructions. Single fluorescence target(s) was reconstructed when located: (i) up to 2.5 cm deep (at 1:0 contrast ratio) and 1.5 cm deep (up to 10:1 contrast ratio) for 0.45 cc-target; and (ii) 1.5 cm deep for target as small as 0.10 cc at 1:0 contrast ratio. In the case of multiple targets, two targets as close as 0.7 cm were tomographically resolved when located 1.5 cm deep. It was observed that performing multi-projection (here dual) based tomographic imaging using a priori target information from surface images, improved the target depth recovery over using single projection based imaging. From a total of 98 experimental phantom studies, the sensitivity and specificity of the imager was estimated as 81-86% and 43-50%, respectively. With 3-D tomographic imaging successfully demonstrated for the first time using a hand-held based optical imager, the clinical translation of this technology is promising upon further experimental validation from in-vitro and in-vivo studies.

Clinical translation of a hand-held optical imager for breast cancer diagnostics: In vitro and in vivo tomography studies

Optical imaging is an emerging technology towards non-invasive breast cancer diagnostics. In recent years, portable and patient comfortable hand-held optical imagers are developed towards two-dimensional (2D) tumor detections. However, these imagers are not capable of three-dimensional (3D) tomography because they cannot register the positional information of the hand-held probe onto the imaged tissue. A hand-held optical imager has been developed in our Optical Imaging Laboratory with 3D tomography capabilities, as demonstrated from tissue phantom studies. The overall goal of my dissertation is towards the translation of our imager to the clinical setting for 3D tomographic imaging in human breast tissues. A systematic experimental approach was designed and executed as follows: (i) fast 2D imaging, (ii) coregistered imaging, and (iii) 3D tomographic imaging studies. (i) Fast 2D imaging was initially demonstrated in tissue phantoms (1% Liposyn solution) and in vitro (minced chicken breast and 1% Liposyn). A 0.45 cm3 fluorescent target at 1:0 contrast ratio was detectable up to 2.5 cm deep. Fast 2D imaging experiments performed in vivo with healthy female subjects also detected a 0.45 cm3 fluorescent target superficially placed ∼2.5 cm under the breast tissue. (ii) Coregistered imaging was automated and validated in phantoms with ∼0.19 cm error in the probe’s positional information. Coregistration also improved the target depth detection to 3.5 cm, from multi-location imaging approach. Coregistered imaging was further validated in-vivo , although the error in probe’s positional information increased to ∼0.9 cm (subject to soft tissue deformation and movement). (iii) Three-dimensional tomography studies were successfully demonstrated in vitro using 0.45 cm3 fluorescence targets. The feasibility of 3D tomography was demonstrated for the first time in breast tissues using the hand-held optical imager, wherein a 0.45 cm3 fluorescent target (superficially placed) was recovered along with artifacts. Diffuse optical imaging studies were performed in two breast cancer patients with invasive ductal carcinoma. The images showed greater absorption at the tumor cites (as observed from x-ray mammography, ultrasound, and/or MRI). In summary, my dissertation demonstrated the potential of a hand-held optical imager towards 2D breast tumor detection and 3D breast tomography, holding a promise for extensive clinical translational efforts.

Multi-modal ultrasound imaging for breast cancer detection

This work describes preliminary results of a two-modality imaging system aimed at the early detection of breast cancer. The first technique is based on compounding conventional echographic images taken at regular angular intervals around the imaged breast. The other modality obtains tomographic images of propagation velocity using the same circular geometry. For this study, a low-cost prototype has been built. It is based on a pair of opposed 128-element, 3.2 MHz array transducers that are mechanically moved around tissue mimicking phantoms. Compounded images around 360 degrees provide improved resolution, clutter reduction, artifact suppression and reinforce the visualization of internal structures. However, refraction at the skin interface must be corrected for an accurate image compounding process. This is achieved by estimation of the interface geometry followed by computing the internal ray paths. On the other hand, sound velocity tomographic images from time of flight projections have been also obtained. Two reconstruction methods, Filtered Back Projection (FBP) and 2D Ordered Subset Expectation Maximization (2D OSEM), were used as a first attempt towards tomographic reconstruction. These methods yield useable images in short computational times that can be considered as initial estimates in subsequent more complex methods of ultrasound image reconstruction. These images may be effective to differentiate malignant and benign masses and are very promising for breast cancer screening. (C) 2015 The Authors. Published by Elsevier B.V.