Three- and four-dimensional computed tomographic angiography and venography for imaging of the microvascular anatomy of perforator flaps

Two-dimensional (2D) contrast radiography utilising the intravascular injection of lead oxide or barium sulphate mixtures is the current gold-standard for investigating the vascular anatomy of surgical flaps. The vascular anatomies of surgical flaps, however, are three-dimensional (3D), and their evaluation is conceptually limited by evaluation in 2D. Static 3D computed tomographic (CT) angiography enables vascular anatomy to be evaluated in the coronal, axial, and sagittal plane, and dynamic fourdimensional (4D) CT angiography (CTA) allows the vascular filling of a surgical flap to be visualized over short time intervals in three dimensions. These methods are also capable of elucidating the vascular anatomy and perfusion of the integument in general. The tissues of the body are perfused by source arteries in 3D blocks. The perforating vessels that provide blood supply to the skin may be dissected from between or through the underlying muscle, and flaps based on these vessels are termed perforator flaps. These flaps have the advantages of reduced donor site morbidity due to preservation of the underlying muscle, versatility to accurately replace the components required at the recipient site, and freedom from orientation of the pedicle. Their development has followed our understanding of the blood supply from a source artery to the skin, which has been achieved due to landmark studies by Manchot, Salmon, Cormack and Lamberty, Taylor, and others. Many articles now attest to the safety and reliability of perforator flaps. The arterial and venous anatomies of the workhorse perforator flaps, which include the anterolateral thigh (LCFAP-v/), the thoracodorsal artery perforator (TAP), and deep inferior epigastric artery perforator (DIEAP) flaps, remain poorly understood, and better understanding may improve the reliability of these flaps, aid in optimal flap design with regards to the vascular anatomy, and may aid in the development of new perforator flapsTo elucidate the 3D and 4D arterial and venous anatomies and perfusion of perforator flaps, this thesis studied the vascular anatomies of the workhorse perforator regions in fresh adult cadavers acquired through the Willed Body Program at the University of Texas Southwestern Medical Center in Dallas using novel 3D imaging techniques. These regions included the thigh, the abdomen, and the back. The techniques consisted of cannulation of the vessels at the level of perforators and their accompanying venae comitantes, followed by either injection of a lead oxide or barium sulphate and gelatin mixture, or by iodinated CT contrast medium injected using a precision pump prior to acquisition of CT images and three-dimensional volume-rendered reconstructions. CT contrast medium has a viscosity similar to that of blood and enabled better physiological modelling of perforator flap perfusion than had been achievable previously.In conclusion this thesis studied novel techniques for acquiring both static and dynamic three-dimensional images of microvascular perforator flap anatomy using CTA and venography (CTV). The information gained has provided a better understanding of how perforator flaps and the integument in general are perfused

Imaging intact human organs with local resolution of cellular structures using hierarchical phase-contrast tomography

Imaging intact human organs from the organ to the cellular scale in three dimensions is a goal of biomedical imaging. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique using the European Synchrotron Radiation Facility (ESRF)’s Extremely Brilliant Source (EBS). The spatial coherence of the ESRF-EBS combined with our beamline equipment, sample preparation and scanning developments enabled us to perform non-destructive, three-dimensional (3D) scans with hierarchically increasing resolution at any location in whole human organs. We applied HiP-CT to image five intact human organ types: brain, lung, heart, kidney and spleen. HiP-CT provided a structural overview of each whole organ followed by multiple higher-resolution volumes of interest, capturing organotypic functional units and certain individual specialized cells within intact human organs. We demonstrate the potential applications of HiP-CT through quantification and morphometry of glomeruli in an intact human kidney and identification of regional changes in the tissue architecture in a lung from a deceased donor with coronavirus disease 2019 (COVID-19)

UNDERSTANDING ANATOMICAL PERFUSION AND STRATEGIES TO OPTIMIZE VASCULARITY IN FREE TISSUE TRANSFER FOR AUTOLOGOUS BREAST RECONSTRUCTION USING THE DEEP INFERIOR EPIGASTRIC ARTERY PERFORATOR (DIEP) FLAP

Breast cancer is the commonest cancer that affects women in the United Kingdom (UK). Autologous free tissue transfer using abdominal tissue remains an excellent option for breast reconstruction following mastectomy, given greater availability of tissue and lower donor site morbidity associated with muscle-sparing approaches (perforator-based). This research evaluated microvascular anatomy of Deep Inferior Epigastric Artery Perforator (DIEP) flaps, the role of linking vessels on dynamic perfusion in bilateral breast reconstruction and strategies to augment flap vascularity. For the ex-vivo anatomical studies, three and four-dimensional computed tomographic angiography (CTA) were used to evaluate patterns of the microvascular blood supply of individual perforators and corresponding perfusion patterns in the hemi-abdomen. This was combined with an in-vivo clinical study of women undergoing bilateral DIEP breast reconstruction following mastectomy, where both preoperative CTA and intra-operative Laser-Assisted Indocyanine Green Fluorescence Angiography (LA-ICGFA) were used to evaluate perforator anatomy and dynamic perfusion zones of individual perforators. Finally, an experimental in-vivo animal model was used to investigate strategies of pretreatment of perforator flaps with negative pressure wound therapy to augment vascularity of perforator flaps prior to flap harvest. The vascular territories of individual perforator within hemi-DIEP flaps demonstrated variable patterns with unique patterns of perfusion. Concepts including early capture of large calibre direct linking vessels to adjacent perforators or the superficial inferior epigastric artery (SIEA) territories, mostly found in the supra-scarpa’s and subdermal layers of the flap, played a key role in defining overall perfusion area and dynamic perfusion patterns not previously described. In conclusion, this work reported the characterization of the microvasculature within abdominal based perforator flaps to better understand the variation in dynamic perfusion. It also explored the potential role of non-invasive negative pressure treatment to augment flap perfusion that may be translated into the clinical setting.Royal College of Surgeons of England Blond Research Fellowship Restoration of Appearance and Function Trust (RAFT) U

Advancing combined radiological and optical scanning for breast-conserving surgery margin guidance

Breast cancer is one of the most common types of cancer worldwide, and standard-of-care for early-stage disease typically involves a lumpectomy or breast-conserving surgery (BCS). BCS involves the local resection of cancerous tissue, while sparring as much healthy tissue as possible. State-of-the-art methods for intraoperatively evaluating BCS margins are limited. Approximately 20% of BCS cases result in a tissue resection with cancer at or near the resection surface (i.e., a positive margin). A two-fold increase in ipsilateral breast cancer recurrence is associated with the presence of one or more positive margins. Consequently, positive margins often necessitate costly re-excision procedures to achieve a curative outcome. X-ray micro-computed tomography (CT) is emerging as a powerful ex vivo specimen imaging technology, as it provides robust three-dimensional sensing of tumor morphology rapidly. However, X-ray attenuation lacks contrast between soft tissues that are important for surgical decision making during BCS. Optical structured light imaging, including spatial frequency domain imaging and active line scan imaging, can act as adjuvant tools to complement micro-CT, providing wide field-of-view, non-contact sensing of relevant breast tissue subtypes on resection margins that cannot be differentiated by micro-CT alone. This thesis is dedicated to multimodal imaging of BCS tissues to ultimately improve intraoperative BCS margin assessment, reducing the number of positive margins after initial surgeries and thereby reducing the need for costly follow-up procedures. Volumetric sensing of micro-CT is combined with surface-weighted, sub-diffuse optical reflectance derived from high spatial frequency structured light imaging. Sub-diffuse reflectance plays the key role of providing enhanced contrast to a suite of normal, abnormal benign, and malignant breast tissue subtypes. This finding is corroborated through clinical studies imaging BCS specimen slices post-operatively and is further investigated through an observational clinical trial focused on combined, intraoperative micro-CT and optical imaging of whole, freshly resected BCS tumors. The central thesis of this work is that combining volumetric X-ray imaging and sub-diffuse optical scanning provides a synergistic multimodal imaging solution to margin assessment, one that can be readily implemented or retrofitted in X-ray specimen imaging systems and that could meaningfully improve surgical guidance during initial BCS procedures

Diseases of the Chest, Breast, Heart and Vessels 2019-2022

This open access book focuses on diagnostic and interventional imaging of the chest, breast, heart, and vessels. It consists of a remarkable collection of contributions authored by internationally respected experts, featuring the most recent diagnostic developments and technological advances with a highly didactical approach. The chapters are disease-oriented and cover all the relevant imaging modalities, including standard radiography, CT, nuclear medicine with PET, ultrasound and magnetic resonance imaging, as well as imaging-guided interventions. As such, it presents a comprehensive review of current knowledge on imaging of the heart and chest, as well as thoracic interventions and a selection of "hot topics". The book is intended for radiologists, however, it is also of interest to clinicians in oncology, cardiology, and pulmonology

Diseases of the Chest, Breast, Heart and Vessels 2019-2022

This open access book focuses on diagnostic and interventional imaging of the chest, breast, heart, and vessels. It consists of a remarkable collection of contributions authored by internationally respected experts, featuring the most recent diagnostic developments and technological advances with a highly didactical approach. The chapters are disease-oriented and cover all the relevant imaging modalities, including standard radiography, CT, nuclear medicine with PET, ultrasound and magnetic resonance imaging, as well as imaging-guided interventions. As such, it presents a comprehensive review of current knowledge on imaging of the heart and chest, as well as thoracic interventions and a selection of "hot topics". The book is intended for radiologists, however, it is also of interest to clinicians in oncology, cardiology, and pulmonology

Efficient sampling strategies for x-ray micro computed tomography with an intensity-modulated beam

The term "cycloidal CT" refers to a family of efficient sampling strategies that can be applied to x-ray micro-computed tomography (CT) systems which operate with an intensity-modulated beam. Such a beam can be employed to provide access to a phase contrast channel and high spatial resolutions (a few um). Phase contrast can offer better image contrast of samples which have traditionally been "invisible” to x-rays due to their weak attenuation, and high resolutions help view crucial details in samples. Cycloidal sampling strategies provide images more quickly than the gold standard in the field ("dithering”). I conceived and compared four practical implementation strategies for cycloidal CT, three of which are "flyscans” (the sample moves continuously). Flyscans acquire images of similar resolution to dithering with no overheads, reducing acquisition time to exposure time. I also developed a "knife-edge” position tracking method which tracks subpixel motions of the sample stage. This information can be used to facilitate, automate, and improve the reconstruction of cycloidal data. I analysed the effects of different levels of dose on the signal-to-noise ratio (SNR) of an image acquired with cycloidal CT. The results show that cycloidal images yield the same SNR as dithered images with less dose, although a more extensive study is required. Finally, I explored the potential of using cycloidal CT for intraoperative specimen imaging and tissue engineering. My results are encouraging for tissue engineering; for intraoperative imaging, the cycloidal images did not show comparable resolution to the dithered images, although that is possibly linked to issues with the dataset. Overall, my work has provided a benchmark for the implementation and application of cycloidal CT for the first time. Besides a summary of my research, this thesis is meant to be a comprehensive guide for facilitating uptake of cycloidal CT within the scientific community and beyond

Registration of histology and magnetic resonance imaging of the brain

Combining histology and non-invasive imaging has been attracting the attention of the medical imaging community for a long time, due to its potential to correlate macroscopic information with the underlying microscopic properties of tissues. Histology is an invasive procedure that disrupts the spatial arrangement of the tissue components but enables visualisation and characterisation at a cellular level. In contrast, macroscopic imaging allows non-invasive acquisition of volumetric information but does not provide any microscopic details. Through the establishment of spatial correspondences obtained via image registration, it is possible to compare micro- and macroscopic information and to recover the original histological arrangement in three dimensions. In this thesis, I present: (i) a survey of the literature relative to methods for histology reconstruction with and without the help of 3D medical imaging; (ii) a graph-theoretic method for histology volume reconstruction from sets of 2D sections, without external information; (iii) a method for multimodal 2D linear registration between histology and MRI based on partial matching of shape-informative boundaries

Patterns of injury and violence in Yaoundé Cameroon: an analysis of hospital data.

BackgroundInjuries are quickly becoming a leading cause of death globally, disproportionately affecting sub-Saharan Africa, where reports on the epidemiology of injuries are extremely limited. Reports on the patterns and frequency of injuries are available from Cameroon are also scarce. This study explores the patterns of trauma seen at the emergency ward of the busiest trauma center in Cameroon's capital city.Materials and methodsAdministrative records from January 1, 2007, through December 31, 2007, were retrospectively reviewed; information on age, gender, mechanism of injury, and outcome was abstracted for all trauma patients presenting to the emergency ward. Univariate analysis was performed to assess patterns of injuries in terms of mechanism, date, age, and gender. Bivariate analysis was used to explore potential relationships between demographic variables and mechanism of injury.ResultsA total of 6,234 injured people were seen at the Central Hospital of Yaoundé's emergency ward during the year 2007. Males comprised 71% of those injured, and the mean age of injured patients was 29 years (SD = 14.9). Nearly 60% of the injuries were due to road traffic accidents, 46% of which involved a pedestrian. Intentional injuries were the second most common mechanism of injury (22.5%), 55% of which involved unarmed assault. Patients injured in falls were more likely to be admitted to the hospital (p < 0.001), whereas patients suffering intentional injuries and bites were less likely to be hospitalized (p < 0.001). Males were significantly more likely to be admitted than females (p < 0.001)DiscussionPatterns in terms of age, gender, and mechanism of injury are similar to reports from other countries from the same geographic region, but the magnitude of cases reported is high for a single institution in an African city the size of Yaoundé. As the burden of disease is predicted to increase dramatically in sub-Saharan Africa, immediate efforts in prevention and treatment in Cameroon are strongly warranted