Elemental and phase composition of breast calcifications

Despite the importance of calcifications in early detection of breast cancer, and their proposed association with tumour growth, remarkably little detail is known about their chemical composition, or how this relates to pathology. One reason for this gap is the difficulty of systematically and precisely locating calcifications for analysis, particularly in sections taken from diagnostic archives. Two simple methods were developed which can achieve this in sections cut from wax embedded breast tissue. These are based on micro-CT and x-ray fluoroscopy mapping, and were used to locate calcifications for further study. The elemental composition of calcifications in histological sections was measured using energy-dispersive x-ray spectroscopy in an environmental scanning electron microscope. Variations in Ca:P ratio could in principle be detected non-invasively by dual energy absorptiometry, as demonstrated in a proof of principle experiment. However, the Ca:P ratio was found to lie in a narrow range similar to bone, with no significant difference between benign and malignant. In contrast, a substantial and significant difference in Na:Ca ratio was found between benign and malignant specimens. This has potential for revealing malignant changes in the vicinity of a core needle biopsy. The phase composition and crystallographic parameters within calcifications was measured using synchrotron x-ray diffraction. This is the first time crystallite size and lattice parameters have been measured in breast calcifications, and it was found that these both parallel closely the changes in these parameters with age observed in foetal bone. It was also discovered that these calcifications contain a small proportion of magnesium whitlockite, and that this proportion increases from benign, to carcinoma in-situ, to invasive cancer. When combined with other recent evidence on the effect of magnesium on hydroxyapatite precipitation, this suggests a mechanism explaining observations that carbonate levels within breast calcifications are lower in malignant specimens

Hand X-ray absorptiometry for measurement of bone mineral density on a slot-scanning X-ray imaging system

Includes bibliographical references.Bone mineral density (BMD) is an indicator of bone strength. While femoral and spinal BMDs are traditionally used in the management of osteoporosis, BMD at peripheral sites such as the hand has been shown to be useful in evaluating fracture risk for axial sites. These peripheral locations have been suggested as alternatives to the traditional sites for BMD measurement. Dual-energy X-ray absorptiometry (DXA) is the gold standard for measuring BMD due to low radiation dose, high accuracy and proven ability to evaluate fracture risk. Computed digital absorptiometry (CDA) has also been shown to be very effective at measuring the bone mass in hand bones using an aluminium step wedge as a calibration reference. In this project, the aim was to develop algorithm s for accurate measurement of BMD in hand bones on a slot - scanning digital radiography system. The project assess e d the feasibility of measuring bone mineral mass in hand bones using CDA on the current system. Images for CDA - based measurement were acquired using the default settings on the system for a medium sized patient. A method for automatic processing of the hand images to detect the aluminium step wedge, included in the scan for calibration, was developed and the calibration accuracy of the step wedge was evaluated. The CDA method was used for computation of bone mass with units of equivalent aluminium thickness (mmA1). The precision of the method was determined by taking three measurements in each of 1 6 volunteering subjects and computing the root - mean - square coefficient of variation (CV) of the measurements. The utility of the method was assessed by taking measurements of excised bones and assessing the correlation between the measured bone mass and ash weight obtained by incinerating the bones. The project also assessed the feasibility of implementing a DXA technique using two detectors in a slot-scanning digital radiography system to acquire dual-energy X-ray images for measuring areal and volumetric BMD of the middle phalanx of the middle finger. The dual-energy images were captured in two consecutive scans. The first scan captured the low- energy image using the detector in its normal set-up. The second scan captured the high- energy image with the detector modified to include an additional scintillator to simulate the presence of a second detector that would capture the low-energy image in a two-detector system. Scan parameters for acquisition of the dual-energy images were chosen to optimise spectral separation, entrance dose and image quality. Simulations were carried out to evaluate the spectral separation of the low- and high-energy spectra

Mammographic density. Measurement of mammographic density

Mammographic density has been strongly associated with increased risk of breast cancer. Furthermore, density is inversely correlated with the accuracy of mammography and, therefore, a measurement of density conveys information about the difficulty of detecting cancer in a mammogram. Initial methods for assessing mammographic density were entirely subjective and qualitative; however, in the past few years methods have been developed to provide more objective and quantitative density measurements. Research is now underway to create and validate techniques for volumetric measurement of density. It is also possible to measure breast density with other imaging modalities, such as ultrasound and MRI, which do not require the use of ionizing radiation and may, therefore, be more suitable for use in young women or where it is desirable to perform measurements more frequently. In this article, the techniques for measurement of density are reviewed and some consideration is given to their strengths and limitations

energy-resolved X-ray detectors: the future of diagnostic imaging

Danilo Pacella ENEA-Frascati, Rome, Italy Abstract: This paper presents recent progress in the field of X-ray detectors, which could play a role in medical imaging in the near future, with special attention to the new generation of complementary metal-oxide semiconductor (C-MOS) imagers, working in photon counting, that opened the way to the energy-resolved X-ray imaging. A brief description of the detectors used so far in medical imaging (photographic films, imaging plates, flat panel detectors), together with the most relevant imaging quality parameters, shows differences between, and advantages of these new C-MOS imagers. X-ray energy-resolved imaging is very attractive not only for the increase of contrast but even for the capability of detecting the nature and composition of the material or tissue to be investigated. Since the X-ray absorption coefficients of the different parts or organs of the patient (object) are strongly dependent on the X-ray photon energy, this multienergy ("colored") X-ray imaging could increase enormously the probing capabilities. While dual-energy imaging is now a reality in medical practice, multienergy is still in its early stage, but a promising research activity. Based on this new technique of color X-ray imaging, the entire scheme of source–object–detector could be revised in the future, optimizing spectrum and detector to the nature and composition of the target to be investigated. In this view, a transition to a set of monoenergetic X-ray lines, suitably chosen in energy and intensity, could be envisaged, instead of the present continuous spectra. Keywords: X-ray detectors, X-ray medical imaging, C-MOS imagers, dual and multienergy C

Advanced capabilities for planar X-ray systems

Mención Internacional en el título de doctorThe past decades have seen a rapid evolution towards the use of digital detectors in radiology and a more flexible robotized movement of the system components, X-ray tube and detector. This evolution opened the possibility for incorporating advanced capabilities in these planar X-ray systems, and for providing new valuable diagnostic information compared to the previous technology. Some of the current challenges for radiography are to obtain more quantitative images and to reduce the inherent superposition of tissues because of the 2D nature of the technique. Dual energy radiography, based on the acquisition of two images at different source voltages, enables a separate characterization of soft tissue and bone structures. Its benefits over conventional radiography have been proven in different applications, since it improves information content without adding significant extra acquisition time or radiation dose. In a different direction, a really disruptive advance would be to obtain 3D imaging with systems designed just for planar images. The incorporation of tomographic capabilities into these systems would have to deal with the acquisition of a limited number of projections, with non-standard geometrical configurations. This thesis presents original contributions in these two directions: dual energy radiography and 3D imaging with X-ray systems designed for planar imaging. The work is framed in a line of research of the Biomedical Imaging and Instrumentation Group from the Bioengineering and Aerospace Department of University Carlos III de Madrid working jointly with the University Hospital Gregorio Marañón, focused on the advance of radiology systems. This research line is carried out in collaboration with the group of Computer Architecture, Communications and Systems (ARCOS), from the same university, the Imaging Research Laboratory (IRL) of the University of Washington and the research center CREATIS, France. The research has a clear focus on technology transfer to the industry through the company Sedecal, a Spanish multinational among the 10 best world companies in the medical imaging field. The first contribution of this thesis is a complete novel protocol to incorporate dual energy capabilities that enable quantitative planar studies. The proposal is based on the use of a preliminary calibration with a very simple and low-cost phantom formed by two parts that represent soft tissue and bone equivalent materials. This calibration is performed automatically with no strict placement requirements. Compared to current Dual-energy X-ray Absorptiometry (DXA) systems, 1) it provides real mass-thickness values directly, enabling quantitative planar studies instead of relative comparisons, and 2) it is based on an automatic preliminary calibration without the need of interaction of an experienced technician. The second contribution is a novel protocol for the incorporation of tomographic capabilities into X-ray systems originally intended for planar imaging. For this purpose, we faced three main challenges. First, the geometrical trajectory of equipment follows non-standard circular orbits, thus posing severe difficulties for reconstruction. To handle this, the proposed protocol comprises a new geometrical calibration procedure that estimates all the system parameters per-projection. Second, the reconstruction of a limited number of projections from a reduced angular span leads to severe artifacts when using conventional reconstruction methods. To deal with these limited-view data, the protocol includes a novel advanced reconstruction method that incorporates the surface information of the sample, which can be extracted with a 3D light surface scanner. These data are introduced as an imposed constraint following the Split Bregman formulation. The restriction of the search space by exploiting the surface-based support becomes crucial for a complete recovery of the external contour of the sample and surroundings when the angular span is extremely reduced. The modular, efficient and flexible design followed for its implementation allows for the reconstruction of limited-view data with non-standard trajectories. Third, the optimization of the acquisition protocols has not yet explored with these systems. This thesis includes a study of the optimum acquisition protocols that allowed us to identify the possibilities and limitations of these planar systems. Using the surface-constrained method, it is possible to reduce the total number of projections up to 33% and the angular span down to 60 degrees. The contributions of this thesis open the way to provide depth and quantitative information very valuable for the improvement of radiological diagnosis. This could impact considerably the clinical practice, where conventional radiology is still the imaging modality most used, accounting for 80-90% of the total medical imaging exams. These advances open the possibility of new clinical applications in scenarios where 1) the reduction of the radiation dose is key, such as lung cancer screening or Pediatrics, according to the ALARA criteria (As Low As Reasonably Achievable), 2) a CT system is not usable due to movement limitations, such as during surgery or in an ICU and 3) where costs issues complicate the availability of CT systems, such as rural areas or underdeveloped countries. The results of this thesis has a clear application in the industry, since it is part of a proof of concept of the new generation of planar X-ray systems that will be commercialized worldwide by the company SEDECAL (Madrid, Spain).Los últimos años están viendo un rápido avance de los sistemas de radiología hacia el uso de detectores digitales y a una mayor flexibilidad de movimientos de los principales componentes del sistema, el tubo de rayos X y el detector. Esta evolución abre la posibilidad de incorporar capacidades avanzadas en sistemas de imagen plana por rayos X proporcionando nueva información valiosa para el diagnóstico. Dos retos en radiografía son obtener imágenes cuantitativas y reducir la superposición de tejidos debida a la naturaleza proyectiva de la técnica. La radiografía de energía dual, basada en la adquisición de dos imágenes a diferente kilovoltaje, permite obtener imágenes de tejido blando y hueso por separado. Los beneficios de esta técnica que aumenta la cantidad de información sin añadir un tiempo de adquisición o de dosis de radiación extra significativos frente al uso de radiografía convencional, han sido demostrados en diferentes aplicaciones. En otra dirección, un avance realmente disruptivo sería la obtención de imagen 3D con sistemas diseñados únicamente para imagen plana. La incorporación de capacidades tomográficas en estos sistemas tendría que lidiar con la adquisición de un número limitado de proyecciones siguiendo trayectorias no estándar. Esta tesis presenta contribuciones originales en esas dos direcciones: radiografía de energía dual e imagen 3D con sistemas de rayos X diseñados para imagen plana. El trabajo se encuadra en una línea de investigación del grupo de Imagen Biomédica e Instrumentación del Departamento de Bioingeniería e Ingeniería Aerospacial de la Universidad Carlos III de Madrid junto con el Hospital Universitario Gregorio Marañon, centrada en el avance de sistemas de radiología. Esta línea de investigación se desarollada en colaboración con el grupo Computer Architecture, Communications and Systems (ARCOS), de la misma universidad, el grupo Imaging Research Laboratory (IRL) de la Universidad de Washington y el centro de investigación CREATIS, de Francia. Se trata de una línea de investigación con un claro enfoque de transferencia tecnológica a la industria a través de la compañía SEDECAL, una multinacional española de entre las 10 líderes del mundo en el campo de la radiología. La primera contribución de esta tesis es un protocolo completo para incorporar capacidades de energía dual que permitan estudios cuantitativos de imagen plana. La propuesta se basa en una calibración previa con un maniquí simple y de bajo coste formado por dos materiales equivalentes de tejido blando y hueso respectivamente. Comparado con los sistemas actuales DXA (Dual-energy X-ray Absorptiometry), 1) proporciona valores reales de tejido atravesado, 2) se basa en una calibración automática que no requiere la interacción de un técnico con gran experiencia. La segunda contribución es un protocolo nuevo para la incorporación de capacidades tomográficas en sistemas de rayos X originariamente diseñados para imagen plana. Para ello, nos enfrentamos a tres principales dificultades. En primer lugar, las trayectorias que pueden seguir la fuente y el detector en estos sistemas no constituyen órbitas circulares estándares, lo que plantea retos importantes en la caracterización geométrica. Para solventarlo, el protocolo propuesto incluye una calibración geométrica que estima todos los parámetros geométricos del sistema para cada proyección. En segundo lugar, la reconstrucción de un número limitado de proyecciones adquiridas en un rango angular reducido da lugar a artefactos graves cuando se reconstruye con algoritmos convencionales. Para lidiar con estos datos de ángulo limitado, el protocolo incluye un nuevo método avanzado de reconstrucción que incorpora la información de superficie de la muestra, que se puede se obtener con un escáner 3D. Esta información se impone como una restricción siguiendo la formulación de Split Bregman, para compensar la falta de datos. La restricción del espacio de búsqueda a través de la explotación del soporte basado en superficie, es crucial para una recuperación completa del contorno externo de la muestra cuando el rango angular es extremadamente pequeño. El diseño modular, eficiente y flexible de la implementación propuesta permite reconstruir datos de ángulo limitado obtenidos con posiciones de fuente y detector no estándar. En tercer lugar, hasta la fecha, no se ha explorado la optimización del protocolo de adquisición con estos sistemas. Esta tesis incluye un estudio de los protocolos óptimos de adquisición que permitió identificar las posibilidades y limitaciones de estos sistemas de imagen plana. Gracias al método de reconstrucción basado en superficie, es posible reducir el número total de proyecciones hasta el 33% y el rango angular hasta 60 grados. Las contribuciones de esta tesis abren la posibilidad de proporcionar información de profundidad y cuantitativa muy valiosa para la mejora del diagnóstico radiológico. Esto podría impactar considerablemente en la práctica clínica, donde la radiología convencional es todavía la modalidad de imagen más utilizada, abarcando el 80- 90% del total de los exámenes de imagen médica. Estos avances abren la posibilidad de nuevas aplicaciones clínicas en escenarios donde 1) la reducción de la dosis de radiación es clave, como en screening de cáncer de pulmón, de acuerdo con el criterio ALARA (As Low As Reasonably Achievable), 2) no se puede usar un sistema TAC por limitaciones de movimiento como en cirugía o UCI, o 3) el coste limita la disponibilidad de sistemas TAC, como en zonas rurales o en países subdesarrollados. Los resultados de esta tesis presentan una clara aplicación industrial, ya que son parte de un prototipo de la nueva generación de sistemas planos de rayos X que serán distribuidos mundialmente por la compañía SEDECAL.This thesis has been developed as part of several research projects with public funding: - DPI2016-79075-R. ”Nuevos escenarios de tomografía por rayos X”, IP: Mónica Abella García, Ministerio de Economía y Competitividad, 01/01/2017-31/12/2019, 147.620 e. - ”Nuevos escenarios de tomografía por rayos X (NEXT) DPI2016-79075-R. Ministerio de Economía”, Industria y Competitividad. (Universidad Carlos III de Madrid). 30/12/2016-29/12/2019. 147.620 e. (…) - FP7-IMI-2012 (GA-115337), ”PreDict-TB: Model-based preclinical development of anti-tuberculosis drug combinations”. FP7-IMI - Seventh Framework Programme (EC-EFPIA). Unión Europea. (Universidad Carlos III de Madrid). 01/05/2012-31/10/2017. (…) - TEC2013-47270-R, ”Avances en Imagen Radiológica (AIR)”, Ministerio de Economía y Competitividad”, 01/01/2014-31/12/2016. IP: Mónica Abella Garcia and Manuel Desco Menéndez. 160.204 e (…) - RTC-2014-3028-1, ”Nuevos Escenarios Clínicos con Radiología Avanzada (NECRA)”, Ministerio de Economía y Competitividad, 01/06/2014-31/12/2016 IP: Mónica Abella García. 2014-2016. 219.458,96 e - IDI-20130301, ”Nuevo sistema integral de radiografía (INNPROVE: INNovative image PROcessing in medicine and VEterinary)”, IP: Mónica Abella García and Manuel Desco Menéndez. Ministerio de Economía y Competitividad. Subcontratación CDTI, 14/01/2013-31/03/2015. Total: 1.860.629e (UC3M: 325.000e). (Art. 83) - IPT-2012-0401-300000 INNPACTO 2012, ”Tecnologías para Procedimientos Intraoperatorios Seguros y Precisos. XIORT. MINECO. (Universidad Carlos III de Madrid). 01/01/2013-31/12/2015.Programa Oficial de Doctorado en Ingeniería MatemáticaPresidente: Doménec Ros Puig.- Secretario: Cyril Riddell.- Vocal: Yannick Boursie

The Role Of Tissue Sound Speed As A Surrogate Marker Of Breast Density

Breast density is one of the strongest predictors of breast cancer risk as women with the densest breasts have a three- to five-fold increase in risk compared to women with the least dense breasts. Breast density is currently measured by using mammography, the current gold standard for breast imaging. There are many shortcomings to using mammography to measure breast density, including the use of ionizing radiation. Ultrasound tomography (UST) does not use ionizing radiation and can create tomographic breast sound speed images. These sound speed images are useful because breast density is proportional to sound speed. The purpose of this work was to assess the ability of UST to measure breast density and its ability to measure changes in breast density over short periods of time. A cohort of 251 patients was examined using both UST and mammography. Many different associations were found between the UST density measurement, the volume averaged sound speed, and the mammographic percent density. Additional associations were found between many other UST and mammographic imaging characteristics. UST density was found to correlate with various patient characteristics in a similar manner to mammographic density. Additionally, UST was used to examine the effects of tamoxifen on breast density. Tamoxifen has been shown to reduce mammographic density and breast cancer risk for some women. Preliminary data for 52 patients has shown promising results so far. UST density has decreased for approximately a similar percentage of patients as has been measured for mammographic density. These changes have been measured over short time frames that could not be achieved using mammography. These results show that UST\u27s ability to measure breast density is consistent with mammography, the current standard of care. UST has the potential to become a safe and effective device that can be used to reliably assess breast density and serial changes in breast density

Exploring the visualisation of the cervicothoracic junction in lateral spine radiography using high dynamic range techniques

The C7/T1 junction is an important landmark for spinal injuries. It is traditionally difficult to visualise in a lateral X-ray image due to the rapid change in the bodys anatomy at the level of the junction, where the shoulders cause a large increase in attenuation. To explore methods of enhancing the appearance of this important area, lateral radiographs of a shoulder girdle phantom were subjected to high dynamic range (HDR) processing and tone mapping. A shoulder girdle phantom was constructed using Perspex, shoulder girdle and vertebral bones and water to reproduce the attenuation caused by soft tissue. The design allowed for the removal of the shoulder girdle in order for the cervical vertebrae to be imaged separately. HDR was explored for single and dual-energy X-ray images of the phantom. In the case of single-image HDR, the HDR image of the phantom without water was constructed by combining images created with varying contrast windows throughout the contrast range of an X-ray image. It was found that an overlap of larger contrast windows with a lower number of images performed better than smaller contrast windows and more images when creating an HDR to be tone mapped. Poor results on the phantom without water precluded further testing of single-image HDR on images of the phantom with water, which would have higher attenuation. Dual energy HDR image construction explored images of the phantom both with and without water. A set of images acquired at lower attenuation (phantom without water) was used to evaluate the performance of the various tone mapping algorithms. The tone mapping was then performed on the phantom images containing water. These results showed how each tone mapping algorithm differs and the effects of global vs. local processing. The results revealed that the built-in MatLab algorithm, based on an improved Ward histogram adjustment approach, produces the most desirable result. None of the HDR tone mapped images produced were diagnostically useful. Signal to noise ratio (SNR) analysis was performed on the cervical region of the HDR tone mapped image. It used the scan of the phantom without the shoulder girdle obstruction (imaged under the same conditions) as a reference image. The SNR results quantitatively show that the selection of exposure values affects the visualisation of the tone mapped image. The highest SNR was produced for the 100 - 120 kV dual energy X-ray image pair. The study was limited by the range of HDR image construction techniques employed and the tone mapping algorithms explored. Future studies could explore other HDR image construction techniques and the combination of global and local tone mapping algorithms. Furthermore, the phantom can be replaced by a cadaver for algorithm testing under more realistic conditions

DETECTION OF PHYSICAL HAZARDS IN BONELESS POULTRY PRODUCT USING COMBINED X-RAY AND LASER RANGE IMAGING TECHNOLOGIES

Detection of bone fragments and other physical contaminations in deboned poultry meat has become increasingly important to ensure food quality and safety. Traditional X-ray imaging detection technologies have significant difficulties detecting contaminations because of the meat tissue thickness variation. In order to address the thickness variation problem, in this study, a novel vision system with combined X-ray and laser 3D imaging technology has been developed for accurate physical contamination detection. The X-ray part of the combined system captures high resolution X-ray images in real-time, and the laser 3D part provides an accurate thickness profile for each piece of meat. In the combined system, the 3D thickness information is used to cancel the thickness variation in the X-ray image, thus the process of physical contamination detection is significantly simplified. The combined vision system is capable of detecting calcified bones (rib bones and pulley bones) at a 95% detection rate, and partially calcified bones (fan bones) at a 90% detection rate. In order to handle the inspection tasks in real-time, a multithread architecture is used in this vision system. Various threads work simultaneously in the system, synchronized with each other, taking full advantage of system resources. It is shown that real-time capability is achieved due to the multithread framework. The result of this study has the potential to promote food safety and quality by providing advanced and automated detection techniques to the poultry and food industries

Synchrotron radiation applications in medical research at Brookhaven National Laboratory

In the relatively short time that synchrotrons have been available to the scientific community, their characteristic beams of UV and X-ray radiation have been applied to virtually all areas of medical science which use ionizing radiation. The ability to tune intense monochromatic beams over wide energy ranges clearly differentiates these sources from standard clinical and research tools. The tunable spectrum, high intrinsic collimation of the beams, polarization and intensity of the beams make possible in-vitro and in-vivo research and therapeutic programs not otherwise possible. From the beginning of research operation at the National Synchrotron Light Source (NSLS), many programs have been carrying out basic biomedical research. At first, the research was limited to in-vitro programs such as the x-ray microscope, circular dichroism, XAFS, protein crystallography, micro-tomography and fluorescence analysis. Later, as the coronary angiography program made plans to move its experimental phase from SSRL to the NSLS, it became clear that other in-vivo projects could also be carried out at the synchrotron. The development of SMERF (Synchrotron Medical Research Facility) on beamline X17 became the home not only for angiography but also for the MECT (Multiple Energy Computed Tomography) project for cerebral and vascular imaging. The high energy spectrum on X17 is necessary for the MRT (Microplanar Radiation Therapy) experiments. Experience with these programs and the existence of the Medical Programs Group at the NSLS led to the development of a program in synchrotron based mammography. A recent adaptation of the angiography hardware has made it possible to image human lungs (bronchography). Fig. 1 schematically depicts the broad range of active programs at the NSLS