On-belt Tomosynthesis: 3D Imaging of Baggage for Security Inspection

This thesis describes the design, testing and evaluation of `On-belt Tomosynthesis' (ObT): a cost-e ective baggage screening system based on limited angle digital x-ray tomosynthesis and close-range photogrammetry. It is designed to be retro tted to existing airport conveyor-belt systems and to overcome the limitations of current systems creating a pseudo-3D imaging system by combining x-ray and optical imaging to form digital tomograms. The ObT design and set-up consists of a con guration of two x-ray sources illuminating 12 strip detectors around a conveyor belt curve forming an 180 arc. Investigating the acquired ObT x-ray images' noise sources and distortions, improvements were demonstrated using developed image correction methods. An increase of 45% in image uniformity was shown as a result, in the postcorrection images. Simulation image reconstruction of objects with lower attenuation coe cients showed the potential of ObT to clearly distinguish between them. Reconstruction of real data showed that objects of bigger attenuation di erences (copper versus perspex, rather than air versus perspex) could be observed better. The main conclusion from the reconstruction results was that the current imaging method needed further re nements, regarding the geometry registration and the image reconstruction. The simulation results con rmed that advancing the experimental method could produce better results than the ones which can currently be achieved. For the current state of ObT, a standard deviation of 2 mm in (a) the source coordinates, and 2 in (b) the detector angles does not a ect the image reconstruction results. Therefore, a low-cost single camera coordination and tracking solution was developed to replace the previously used manual measurements. Results obtained by the developed solution showed that the necessary prerequisites for the ObT image reconstruction could be addressed. The resulting standard deviation was of an average of 0.4 mm and 1 degree for (a) and (b) respectively

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

STATIONARY DIGITAL TOMOSYNTHESIS: IMPLEMENTATION, CHARACTERIZATION, AND IMAGE PROCESSING TECHNIQUES

The use of carbon nanotube cathodes for x-ray generation was pioneered and perfected by our team in the Applied Nanotechnology Laboratory at the University of North Carolina at Chapel Hill. Over the past decade, carbon nanotube (CNT) field emission x-ray source technology has matured and translated into multiple pre-clinical and clinical devices. One of the most prominent implementations of CNT x-ray technology is a limited angle tomography method called tomosynthesis, which is rapidly emerging in clinical radiography. The purpose of this project is two-fold, to develop and characterize to the latest iteration, stationary intraoral tomosynthesis, and develop a low-dose, effective scatter reduction technique for breast and chest tomosynthesis. The first portion of this project was to develop and evaluate a new quasi-3D imaging modality for dental imaging. My work consists of experiments which dictated the design parameters and subsequent system evaluation of the dedicated s-IOT clinical prototype system currently installed in the UNC Department of Oral and Maxillofacial Radiology clinic in the School of Dentistry. Experiments were performed in our lab to determine optimal source array geometry and system configuration. The system was fabricated by our commercial partner then housed in our research lab where I performed initial characterization and assisted with software development. After installation in the SOD, I performed additional system characterization, including source output validation, dosimetry, and quantification of resolution. The system components and software were refined through a rapid feedback loop with the engineers involved. Four pre-clinical imaging studies have been performed in collaboration with several dentists using phantoms, extracted teeth, and cadaveric dentition. I have generated an operating manual and trained four dental radiologists in the use of the s-IOT device. The system has now been vetted and is ready for patient use. The second portion of this project consists of hardware development and implementation of an image processing technique for scatter correction. The primary sampling scatter correction (PSSC) is a beam pass technique to measure the primary transmission through the patient and calculate the scatter profile for subtraction. Though developed for breast and chest tomosynthesis, utilization in mammography and chest radiography are also demonstrated in this project. This dissertation is composed of five chapters. Chapters one and two provide the basics of x-ray generation and a brief history of the evolution of carbon nanotube x-ray source technology in our lab at UNC. Chapter three focuses on stationary intraoral tomosynthesis. The first section provides background information on dental radiology and project motivation. Sections 3.2 and 3.3 detail my work in benchtop feasibility and optimization studies, as well as characterization and evaluation of the clinical prototype. Chapter four introduces scatter in imaging, providing motivation for my work on primary sampling scatter correction (PSSC) image processing method, detailed in chapter five.Doctor of Philosoph

MAMMOGRAM AND TOMOSYNTHESIS CLASSIFICATION USING CONVOLUTIONAL NEURAL NETWORKS

Mammography is the most widely used method of screening for breast cancer. Traditional mammography produces two-dimensional X-ray images, while advanced tomosynthesis mammography produces reconstructed three-dimensional images. Due to high variability in tumor size and shape, and the low signal-to-noise ratio inherent to mammography, manual classification yields a significant number of false positives, thereby contributing to an unnecessarily large number of biopsies performed to reduce the risk of misdiagnosis. Achieving high diagnostic accuracy requires expertise acquired over many years of experience as a radiologist. The convolutional neural network (CNN) is a popular deep-learning construct used in image classification. The convolutional process involves simplifying an image containing millions of pixels to a set of small feature maps, thereby reducing the input dimension while retaining the features that distinguish different classes of images. This technique has achieved significant advancements in large-set image-classification challenges in recent years. In this study, high-quality original mammograms and tomosynthesis were obtained with approval from an institutional review board. Different classifiers based on convolutional neural networks were built to classify the 2-D mammograms and 3-D tomosynthesis, and each classifier was evaluated based on its performance relative to truth values generated by a board of expert radiologists. The results show that CNNs have great potential for automatic breast cancer detection using mammograms and tomosynthesis

Advancing the Clinical Potential of Carbon Nanotube-enabled stationary 3D Mammography

Scope and purpose. 3D imaging has revolutionized medicine. Digital breast tomosynthesis (DBT), also recognized as 3D mammography, is a relatively recent example. stationary DBT (sDBT) is an experimental technology in which the single moving x-ray source of conventional DBT has been replaced by a fixed array of carbon nanotube (CNT)-enabled sources. Given the potential for a higher spatial and temporal resolution compared to commercially-available, moving-source DBT devices, it was hypothesized that sDBT would provide a valuable tool for breast imaging. As such, the purpose of this work was to explore the clinical potential of sDBT. To accomplish this purpose, three broad Aims were set forth: (1) study the challenges of scatter and artifact with sDBT, (2) assess the performance of sDBT relative to standard mammographic screening approaches, and (3) develop a synthetic mammography capability for sDBT. Throughout the work, developing image processing approaches to maximize the diagnostic value of the information presented to readers remained a specific goal. Data sources and methodology. Sitting at the intersection of development and clinical application, this work involved both basic experimentation and human study. Quantitative measures of image quality as well as reader preference and accuracy were used to assess the performance of sDBT. These studies imaged breast-mimicking phantoms, lumpectomy specimens, and human subjects on IRB-approved study protocols, often using standard 2D and conventional 3D mammography for reference. Key findings. Characterizing scatter and artifact allowed the development of new processing approaches to improve image quality. Additionally, comparing the performance of sDBT to standard breast imaging technologies helped identify opportunities for improvement through processing. This line of research culminated in the incorporation of a synthetic mammography capability into sDBT, yielding images that have the potential to improve the diagnostic value of sDBT. Implications. This work advanced the evolution of CNT-enabled sDBT toward a viable clinical tool by incorporating key image processing functionality and characterizing the performance of sDBT relative to standard breast imaging techniques. The findings confirmed the clinical utility of sDBT while also suggesting promising paths for future research and development with this unique approach to breast imaging.Doctor of Philosoph

Iterative CT reconstruction from few projections for the nondestructive post irradiation examination of nuclear fuel assemblies

The core components (e.g. fuel assemblies, spacer grids, control rods) of the nuclear reactors encounter harsh environment due to high temperature, physical stress, and a tremendous level of radiation. The integrity of these elements is crucial for safe operation of the nuclear power plants. The Post Irradiation Examination (PIE) can reveal information about the integrity of the elements during normal operations and off‐normal events. Computed tomography (CT) is a tool for evaluating the structural integrity of elements non-destructively. CT requires many projections to be acquired from different view angles after which a mathematical algorithm is adopted for reconstruction. Obtaining many projections is laborious and expensive in nuclear industries. Reconstructions from a small number of projections are explored to achieve faster and cost-efficient PIE. Classical reconstruction algorithms (e.g. filtered back projection) cannot offer stable reconstructions from few projections and create severe streaking artifacts. In this thesis, conventional algorithms are reviewed, and new algorithms are developed for reconstructions of the nuclear fuel assemblies using few projections. CT reconstruction from few projections falls into two categories: the sparse-view CT and the limited-angle CT or tomosynthesis. Iterative reconstruction algorithms are developed for both cases in the field of compressed sensing (CS). The performance of the algorithms is assessed using simulated projections and validated through real projections. The thesis also describes the systematic strategy towards establishing the conditions of reconstructions and finds the optimal imaging parameters for reconstructions of the fuel assemblies from few projections. --Abstract, page iii

System Characterizations and Optimized Reconstruction Methods for Novel X-ray Imaging

In the past decade there have been many new emerging X-ray based imaging technologies developed for different diagnostic purposes or imaging tasks. However, there exist one or more specific problems that prevent them from being effectively or efficiently employed. In this dissertation, four different novel X-ray based imaging technologies are discussed, including propagation-based phase-contrast (PB-XPC) tomosynthesis, differential X-ray phase-contrast tomography (D-XPCT), projection-based dual-energy computed radiography (DECR), and tetrahedron beam computed tomography (TBCT). System characteristics are analyzed or optimized reconstruction methods are proposed for these imaging modalities. In the first part, we investigated the unique properties of propagation-based phase-contrast imaging technique when combined with the X-ray tomosynthesis. Fourier slice theorem implies that the high frequency components collected in the tomosynthesis data can be more reliably reconstructed. It is observed that the fringes or boundary enhancement introduced by the phase-contrast effects can serve as an accurate indicator of the true depth position in the tomosynthesis in-plane image. In the second part, we derived a sub-space framework to reconstruct images from few-view D-XPCT data set. By introducing a proper mask, the high frequency contents of the image can be theoretically preserved in a certain region of interest. A two-step reconstruction strategy is developed to mitigate the risk of subtle structures being oversmoothed when the commonly used total-variation regularization is employed in the conventional iterative framework. In the thirt part, we proposed a practical method to improve the quantitative accuracy of the projection-based dual-energy material decomposition. It is demonstrated that applying a total-projection-length constraint along with the dual-energy measurements can achieve a stabilized numerical solution of the decomposition problem, thus overcoming the disadvantages of the conventional approach that was extremely sensitive to noise corruption. In the final part, we described the modified filtered backprojection and iterative image reconstruction algorithms specifically developed for TBCT. Special parallelization strategies are designed to facilitate the use of GPU computing, showing demonstrated capability of producing high quality reconstructed volumetric images with a super fast computational speed. For all the investigations mentioned above, both simulation and experimental studies have been conducted to demonstrate the feasibility and effectiveness of the proposed methodologies

Modeling and Development of Iterative Reconstruction Algorithms in Emerging X-ray Imaging Technologies

Many new promising X-ray-based biomedical imaging technologies have emerged over the last two decades. Five different novel X-ray based imaging technologies are discussed in this dissertation: differential phase-contrast tomography (DPCT), grating-based phase-contrast tomography (GB-PCT), spectral-CT (K-edge imaging), cone-beam computed tomography (CBCT), and in-line X-ray phase contrast (XPC) tomosynthesis. For each imaging modality, one or more specific problems prevent them being effectively or efficiently employed in clinical applications have been discussed. Firstly, to mitigate the long data-acquisition times and large radiation doses associated with use of analytic reconstruction methods in DPCT, we analyze the numerical and statistical properties of two classes of discrete imaging models that form the basis for iterative image reconstruction. Secondly, to improve image quality in grating-based phase-contrast tomography, we incorporate 2nd order statistical properties of the object property sinograms, including correlations between them, into the formulation of an advanced multi-channel (MC) image reconstruction algorithm, which reconstructs three object properties simultaneously. We developed an advanced algorithm based on the proximal point algorithm and the augmented Lagrangian method to rapidly solve the MC reconstruction problem. Thirdly, to mitigate image artifacts that arise from reduced-view and/or noisy decomposed sinogram data in K-edge imaging, we exploited the inherent sparseness of typical K-edge objects and incorporated the statistical properties of the decomposed sinograms to formulate two penalized weighted least square problems with a total variation (TV) penalty and a weighted sum of a TV penalty and an l1-norm penalty with a wavelet sparsifying transform. We employed a fast iterative shrinkage/thresholding algorithm (FISTA) and splitting-based FISTA algorithm to solve these two PWLS problems. Fourthly, to enable advanced iterative algorithms to obtain better diagnostic images and accurate patient positioning information in image-guided radiation therapy for CBCT in a few minutes, two accelerated variants of the FISTA for PLS-based image reconstruction are proposed. The algorithm acceleration is obtained by replacing the original gradient-descent step by a sub-problem that is solved by use of the ordered subset concept (OS-SART). In addition, we also present efficient numerical implementations of the proposed algorithms that exploit the massive data parallelism of multiple graphics processing units (GPUs). Finally, we employed our developed accelerated version of FISTA for dealing with the incomplete (and often noisy) data inherent to in-line XPC tomosynthesis which combines the concepts of tomosynthesis and in-line XPC imaging to utilize the advantages of both for biological imaging applications. We also investigate the depth resolution properties of XPC tomosynthesis and demonstrate that the z-resolution properties of XPC tomosynthesis is superior to that of conventional absorption-based tomosynthesis. To investigate all these proposed novel strategies and new algorithms in these different imaging modalities, we conducted computer simulation studies and real experimental data studies. The proposed reconstruction methods will facilitate the clinical or preclinical translation of these emerging imaging methods