Intermolecular Multiple Quantum Coherences Enable Accurate Thermal Imaging of Red Bone Marrow During Thermal Therapy of Bone Metastases

Prostate and breast cancers are two of the most common types of cancer in the United States, and those cancers metastasize to bone in more than two thirds of patients. Recent evidence suggests that thermal therapy is effective at treating metastatic bone cancer. For example, thermal therapy enables targeted drug delivery to bone, ablation of cancer cells in bone marrow, and palliation of bone pain. Thermal therapy of bone metastases would be greatly improved if it were possible to image the temperature of the tissue surrounding the disease, which is usually red bone marrow (RBM). Unfortunately, current thermal imaging techniques are inaccurate in RBM.

This dissertation shows that many of the difficulties with thermal imaging of RBM can be overcome using a magnetic resonance phenomenon called an intermolecular multiple quantum coherence (iMQC). Herein, iMQCs are detected with a magnetic resonance imaging (MRI) pulse sequence called multi-spin-echo HOMOGENIZED with off resonance transfer (MSE-HOT). Compared to traditional methods, MSE-HOT provided ten-fold more accurate images of temperature change. Furthermore, MSE-HOT was translated to a human MRI scanner, which enabled imaging of RBM temperature during heating with a clinical focused ultrasound applicator. In summary, this dissertation develops a MRI technique that enables thermal imaging of RBM during thermal therapy of bone metastases.

Local examination of skin diffusion using FTIR spectroscopic imaging and multivariate target factor analysis

In the context of trans-dermal drug delivery it is very important to have mechanistic insight into the barrier function of the skin's stratum corneum and the diffusion mechanisms of topically applied drugs. Currently spectroscopic imaging techniques are evolving which enable a spatial examination of various types of samples in a dynamic way. ATR-FTIR imaging opens up the possibility to monitor spatial diffusion profiles across the stratum corneum of a skin sample. Multivariate data analyses methods based on factor analysis are able to provide insight into the large amount of spectroscopically complex and highly overlapping signals generated. Multivariate target factor analysis was used for spectral resolution and local diffusion profiles with time through stratum corneum. A model drug, 4-cyanophenol in polyethylene glycol 600 and water was studied. Results indicate that the average diffusion profiles between spatially different locations show similar profiles despite the heterogeneous nature of the biological sample and the challenging experimental set-up.

Assessing the occupational risk of dust particles in the Kenyan tanning industry using rapid image processing and microscopy techniques

The purpose of this study was to investigate the occupational hazards within the tanning industry caused by contaminated dust. A qualitative assessment of the risk of human exposure to dust was made throughout a commercial Kenyan tannery. Using this information, high-risk points in the processing line were identified and dust sampling regimes developed. An optical set-up using microscopy and digital imaging techniques was used to determine dust particle numbers and size distributions. The results showed that chemical handling was the most hazardous (12 mg m(-3)). A Monte Carlo method was used to estimate the concentration of the dust in the air throughout the tannery during an 8 h working day. This showed that the high-risk area of the tannery was associated with mean concentrations of dust greater than the UK Statutory Instrument 2002 No. 2677. stipulated limits (exceeding 10 mg m(-3) (Inhalable dust limits) and 4 mg m(-3) (Respirable dust limits). This therefore has implications in terms of provision of personal protective equipment (PPE) to the tannery workers for the mitigation of occupational risk.

Imaging intracellular and systemic in vivo gold nanoparticles to enhance radiotherapy

Nanoparticles offer alternative options in cancer therapy both as drug delivery carriers and as direct therapeutic agents for cancer cell inactivation. More recently, gold nanoparticles (AuNPs) have emerged as promising radiosensitizers achieving significantly elevated radiation dose enhancement factors when irradiated with both kilo-electron-volt and mega-electronvolt X-rays. Use of AuNPs in radiobiology is now being intensely driven by the desire to achieve precise energy deposition in tumours. As a consequence, there is a growing demand for efficient and simple techniques for detection, imaging and characterization of AuNPs in both biological and tumour samples. Spatially accurate imaging on the nanoscale poses a serious challenge requiring high- or super-resolution imaging techniques. In this mini review, we discuss the challenges in using AuNPs as radiosensitizers as well as various current and novel imaging techniques designed to validate the uptake, distribution and localization in mammalian cells. In our own work, we have used multiphoton excited plasmon resonance imaging to map the AuNP intracellular distribution. The benefits and limitations of this approach will also be discussed in some detail. In some cases, the same "excitation" mechanism as is used in an imaging modality can be harnessed tomake it also a part of therapymodality (e.g. phototherapy)-such examples are discussed in passing as extensions to the imaging modality concerned.

Stem cell transplantation in brain tumors: a new field for molecular imaging?

Neural stem cells have been proposed as a new and promising treatment modality in various pathologies of the central nervous system, including malignant brain tumors. However, the underlying mechanism by which neural stem cells target tumor areas remains elusive. Monitoring of these cells is currently done by use of various modes of molecular imaging, such as optical imaging, magnetic resonance imaging and positron emission tomography, which is a novel technology for visualizing metabolism and signal transduction to gene expression. In this new context, the microenvironment of (malignant) brain tumors and the blood-brain barrier gains increased interest. The authors of this review give a unique overview of the current molecular-imaging techniques used in different therapeutic experimental brain tumor models in relation to neural stem cells. Such methods for molecular imaging of gene-engineered neural stem/progenitor cells are currently used to trace the location and temporal level of expression of therapeutic and endogenous genes in malignant brain tumors, closing the gap between in vitro and in vivo integrative biology of disease in neural stem cell transplantation.

Application of contrast media in post-mortem imaging (CT and MRI).

The application of contrast media in post-mortem radiology differs from clinical approaches in living patients. Post-mortem changes in the vascular system and the absence of blood flow lead to specific problems that have to be considered for the performance of post-mortem angiography. In addition, interpreting the images is challenging due to technique-related and post-mortem artefacts that have to be known and that are specific for each applied technique. Although the idea of injecting contrast media is old, classic methods are not simply transferable to modern radiological techniques in forensic medicine, as they are mostly dedicated to single-organ studies or applicable only shortly after death. With the introduction of modern imaging techniques, such as post-mortem computed tomography (PMCT) and post-mortem magnetic resonance (PMMR), to forensic death investigations, intensive research started to explore their advantages and limitations compared to conventional autopsy. PMCT has already become a routine investigation in several centres, and different techniques have been developed to better visualise the vascular system and organ parenchyma in PMCT. In contrast, the use of PMMR is still limited due to practical issues, and research is now starting in the field of PMMR angiography. This article gives an overview of the problems in post-mortem contrast media application, the various classic and modern techniques, and the issues to consider by using different media.

Characterization of Carotid Plaques with Ultrasound Non-Invasive Vascular Elastography (NIVE) : Feasibility and Correlation with High-Resolution Magnetic Resonance Imaging

L’accident vasculaire cérébral (AVC) est une cause principale de décès et de morbidité dans le monde; une bonne partie des AVC est causée par la plaque d’athérosclérose carotidienne. La prévention de l’AVC chez les patients ayant une plaque carotidienne demeure controversée, vu les risques et bénéfices ambigus associés au traitement chirurgical ou médical. Plusieurs méthodes d’imagerie ont été développées afin d’étudier la plaque vulnérable (dont le risque est élevé), mais aucune n’est suffisamment validée ou accessible pour permettre une utilisation comme outil de dépistage. L’élastographie non-invasive vasculaire (NIVE) est une technique nouvelle qui cartographie les déformations (élasticité) de la plaque afin de détecter les plaque vulnérables; cette technique n’est pas encore validée cliniquement. Le but de ce projet est d’évaluer la capacité de NIVE de caractériser la composition de la plaque et sa vulnérabilité in vivo chez des patients ayant des plaques sévères carotidiennes, en utilisant comme étalon de référence, l’imagerie par résonance magnétique (IRM) à haute-résolution. Afin de poursuivre cette étude, une connaissance accrue de l’AVC, l’athérosclérose, la plaque vulnérable, ainsi que des techniques actuelles d’imagerie de la plaque carotidienne, est requise. Trente-et-un sujets ont été examinés par NIVE par ultrasonographie et IRM à haute-résolution. Sur 31 plaques, 9 étaient symptomatiques, 17 contenaient des lipides, et 7 étaient vulnérables selon l’IRM. Les déformations étaient significativement plus petites chez les plaques contenant des lipides, avec une sensibilité élevée et une spécificité modérée. Une association quadratique entre la déformation et la quantité de lipide a été trouvée. Les déformations ne pouvaient pas distinguer les plaques vulnérables ou symptomatiques. En conclusion, NIVE par ultrasonographie est faisable chez des patients ayant des sténoses carotidiennes significatives et peut détecter la présence d’un coeur lipidique. Des études supplémentaires de progression de la plaque avec NIVE sont requises afin d’identifier les plaques vulnérables.

Predatory vision : 3D imaging and the transformation of screen-space

Despite Wheatstone’s academic interests in the device, the stereoscope languished somewhat as an optical toy. Yet the advent of 3D screen-spaces for home and mass entertainment suggests today’s consumers and practitioners of screen culture hold the view that screen culture will be ‘improved’ through 3D imaging technologies. Like cinema and photography, stereoscopic 3D imaging has the potential to transform visual culture. But what is transformed, as optics and electronic imaging techniques deliver Alice in Wonderland in 3D? This paper links the advent of 3D cinema and TV to the notion that vision is itself a ‘technology of the visual’. As such, our innate binocular stereoacuity is ripe for exploitation by developers of 3D imaging technologies. I argue that contemporary 3D imaging marks an epistemological visual-perceptual shift: toward screenspaces becoming spaces for potential action. Such a shift entails seeing as doing rather than seeing as thinking. 3D imaging exploits binocular vision’s spatial acuity (stereopsis), but is effective only for objects within near distal space. The 3D effect tapers off dramatically for objects only some metres away, because the two retinal images lack significant lateral disparity (difference) to trigger stereopsis: the imagery flattens out and becomes ‘monoscopic’. Information available from conventional 2D media entails a peculiarly unspecified spatiality. Perceptually, the contents of a conventional cinematic screen are like those of a painting: they are situated neither near nor far, and constitute a shared and ambiguous visual space. Our own eyes are like those of a cat: frontally placed for predatory action. The visuality of 3D screen-spaces assumes a perceptuality of the near-by and close at hand, since this is the structure of the visible information to which stereopsis is adapted to respond. Noting the binocular acuity of predatory animals, as well as some etymological links, this paper examines the implications of perceptually ‘capturing’ the sensation of visually solid objects in one’s immediate space. Stereopsis is about decisive action within an immediate environment: but it also presupposes the single viewpoint of an active observer toward which the 3D imagery is targeted.

New molecular targets for PET and SPECT imaging in neurodegenerative diseases

The pathophysiology of neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD) has not yet been completely elucidated. However, in the past few years, there have been great knowledge advances about intra-and extracellular proteins that may display impaired function or expression in AD, PD and other ND, such as amyloid beta (AB), alpha-synuclein, tau protein and neuroinfiammatory markers. Recent developments in the imaging techniques of positron emission tomography (PET) and single photon emission computed tomography (SPECT) now allow the non-invasive tracking of such molecular targets of known relevance to ND in vivo. This article summarizes recent findings of PET and SPECT studies using these novel methods, and discusses their potential role in the field of drug development for ND as well as future clinical applications in regard to differential diagnosis of ND and monitoring of disease progression.

Very Long Baseline Interferometry in Italy Wide-field VLBI imaging and astrometry and prospects for an Italian VLBI network including the Sardinia Radio Telescope

In this thesis the use of widefield imaging techniques and VLBI observations with a limited number of antennas are explored. I present techniques to efficiently and accurately image extremely large UV datasets. Very large VLBI datasets must be reduced into multiple, smaller datasets if today’s imaging algorithms are to be used to image them. I present a procedure for accurately shifting the phase centre of a visibility dataset. This procedure has been thoroughly tested and found to be almost two orders of magnitude more accurate than existing techniques. Errors have been found at the level of one part in 1.1 million. These are unlikely to be measurable except in the very largest UV datasets. Results of a four-station VLBI observation of a field containing multiple sources are presented. A 13 gigapixel image was constructed to search for sources across the entire primary beam of the array by generating over 700 smaller UV datasets. The source 1320+299A was detected and its astrometric position with respect to the calibrator J1329+3154 is presented. Various techniques for phase calibration and imaging across this field are explored including using the detected source as an in-beam calibrator and peeling of distant confusing sources from VLBI visibility datasets. A range of issues pertaining to wide-field VLBI have been explored including; parameterising the wide-field performance of VLBI arrays; estimating the sensitivity across the primary beam both for homogeneous and heterogeneous arrays; applying techniques such as mosaicing and primary beam correction to VLBI observations; quantifying the effects of time-average and bandwidth smearing; and calibration and imaging of wide-field VLBI datasets. The performance of a computer cluster at the Istituto di Radioastronomia in Bologna has been characterised with regard to its ability to correlate using the DiFX software correlator. Using existing software it was possible to characterise the network speed particularly for MPI applications. The capabilities of the DiFX software correlator, running on this cluster, were measured for a range of observation parameters and were shown to be commensurate with the generic performance parameters measured. The feasibility of an Italian VLBI array has been explored, with discussion of the infrastructure required, the performance of such an array, possible collaborations, and science which could be achieved. Results from a 22 GHz calibrator survey are also presented. 21 out of 33 sources were detected on a single baseline between two Italian antennas (Medicina to Noto). The results and discussions presented in this thesis suggest that wide-field VLBI is a technique whose time has finally come. Prospects for exciting new science are discussed in the final chapter.

In vivo evaluation of the translations of the gleno-humeral joint using Magnetic resonance imaging

Gleno-humeral joint (GHJ) is the most mobile joint of the human body. This is related to theincongr uence between the large humeral head articulating with the much smaller glenoid (ratio 3:1). The GHJ laxity is the ability of the humeral head to be passively translated on the glenoid fossa and, when physiological, it guarantees the normal range of motion of the joint. Three-dimensional GHJ linear displacements have been measured, both in vivo and in vitro by means of different instrumental techniques. In vivo gleno-humeral displacements have been assessed by means of stereophotogrammetry, electromagnetic tracking sensors, and bio-imaging techniques. Both stereophotogrammetric systems and electromagnetic tracking devices, due to the deformation of the soft tissues surrounding the bones, are not capable to accurately assess small displacements, such as gleno-humeral joint translations. The bio-imaging techniques can ensure for an accurate joint kinematic (linear and angular displacement) description, but, due to the radiation exposure, most of these techniques, such as computer tomography or fluoroscopy, are invasive for patients. Among the bioimaging techniques, an alternative which could provide an acceptable level of accuracy and that is innocuous for patients is represented by magnetic resonance imaging (MRI). Unfortunately, only few studies have been conducted for three-dimensional analysis and very limited data is available in situations where preset loads are being applied. The general aim of this doctoral thesis is to develop a non-invasive methodology based on open-MRI for in-vivo evaluation of the gleno-humeral translation components in healthy subjects under the application of external loads.

Diffusion-weighted magnetic resonance imaging detects local recurrence after radical prostatectomy: initial experience

Current conventional cross-sectional imaging techniques, such as contrast-enhanced computed tomography and magnetic resonance imaging (MRI), are largely inaccurate in detecting local recurrence after radical prostatectomy. We report on five patients with biochemical recurrence after radical retropubic prostatectomy and pelvic lymph node dissection for whom local recurrence could only be detected with diffusion-weighted (DW) MRI. Prior to DW-MRI, all patients had negative digital rectal examinations, negative or equivocal conventional cross-sectional imaging, and negative bone scans. All suspicious lesions on DW-MRI imaging were histologically proved to be local recurrences of prostate cancer after either transrectal ultrasound-guided or transurethral biopsy. These results should encourage other centres to test our findings.

Importance of 3D-CT imaging in single-bullet cranioencephalic gunshot wounds

PURPOSE: The aim of this paper is to demonstrate that computed tomography (CT) and three-dimensional (3D) CT imaging techniques can be useful tools for evaluating gunshot wounds of the skull in forensic medicine. Three purposes can be achieved: (1) identifying and recognising the bullet entrance wound - and exit wound, if present; (2) recognising the bullet's intracranial course by studying damage to bone and brain tissue; (3) suggesting hypotheses as to the dynamics of the event. MATERIALS AND METHODS: Ten cadavers of people who died of a fatal head injury caused by a single gunshot were imaged with total-body CT prior to conventional autoptic examination. Three-dimensional-CT reconstructions were obtained with the volume-rendering technique, and data were analysed by two independent observers and compared with autopsy results. RESULTS: In our experience, CT analysis and volumetric reconstruction techniques allowed the identification of the bullet entrance and exit wounds and intracranial trajectory, as well as helping to formulate a hypothesis on the extracranial trajectory to corroborate circumstantial evidence. CONCLUSIONS: CT imaging techniques are excellent tools for addressing the most important questions of forensic medicine in the case of gunshot wounds of the skull, with results as good as (or sometimes better than) traditional autoptic methods.

A global ”imaging” view on systems approaches in immunology

The immune system exhibits an enormous complexity. High throughput methods such as the "-omic'' technologies generate vast amounts of data that facilitate dissection of immunological processes at ever finer resolution. Using high-resolution data-driven systems analysis, causal relationships between complex molecular processes and particular immunological phenotypes can be constructed. However, processes in tissues, organs, and the organism itself (so-called higher level processes) also control and regulate the molecular (lower level) processes. Reverse systems engineering approaches, which focus on the examination of the structure, dynamics and control of the immune system, can help to understand the construction principles of the immune system. Such integrative mechanistic models can properly describe, explain, and predict the behavior of the immune system in health and disease by combining both higher and lower level processes. Moving from molecular and cellular levels to a multiscale systems understanding requires the development of methodologies that integrate data from different biological levels into multiscale mechanistic models. In particular, 3D imaging techniques and 4D modeling of the spatiotemporal dynamics of immune processes within lymphoid tissues are central for such integrative approaches. Both dynamic and global organ imaging technologies will be instrumental in facilitating comprehensive multiscale systems immunology analyses as discussed in this review.

VIRTOPSY: minimally invasive, imaging-guided virtual autopsy

Invasive "body-opening" autopsy represents the traditional means of postmortem investigation in humans. However, modern cross-sectional imaging techniques can supplement and may even partially replace traditional autopsy. Computed tomography (CT) is the imaging modality of choice for two- and three-dimensional documentation and analysis of autopsy findings including fracture systems, pathologic gas collections (eg, air embolism, subcutaneous emphysema after trauma, hyperbaric trauma, decomposition effects), and gross tissue injury. Various postprocessing techniques can provide strong forensic evidence for use in legal proceedings. Magnetic resonance (MR) imaging has had a greater impact in demonstrating soft-tissue injury, organ trauma, and nontraumatic conditions. However, the differences in morphologic features and signal intensity characteristics seen at antemortem versus postmortem MR imaging have not yet been studied systematically. The documentation and analysis of postmortem findings with CT and MR imaging and postprocessing techniques ("virtopsy") is investigator independent, objective, and noninvasive and will lead to qualitative improvements in forensic pathologic investigation. Future applications of this approach include the assessment of morbidity and mortality in the general population and, perhaps, routine screening of bodies prior to burial.