Molecular Fluorescence Endoscopy:clinical development and validation within the lower gastrointestinal tract

Molecular Fluorescence Imaging is a new and evolving imaging technique. It uses exogenous fluorescent tracers that bind to specific proteins, thereby fluorescently highlighting the tissue of interest as a red-flag for the clinician. White-light endoscopy is the current gold standard for colorectal adenoma and cancer screening, where gastroenterologist evaluate aberrant tissue based on morphological aspects and architectural changes only. As adenoma miss rates in colonoscopy are unacceptably high, especially in high-risk populations, we describe in this thesis a clinical dose-escalation study towards the use of Molecular Fluorescence Endoscopy for colorectal adenoma detection. This technique showed to have the potential to improve the identification of colorectal adenomas. In the second part of this thesis, the added value of a restaging CT scan after neoadjuvant chemoradiotherapy is shown for patients with locally advanced rectal cancer, as it may detect newly developed metastases. In a clinical study, the potential of Molecular Fluorescence Endoscopy as tool to aid clinical response assessment is shown, in patients with locally advanced rectal cancer. When this technique is performed after neoadjuvant chemoradiotherapy, it can help identifying the presence of residual tumor and has potential to predict pathological compete response (pCR) and in this way help selecting patients suitable for organ-preserving strategies. Additionally, we show in a proof-of-concept study that molecular fluorescence imaging performed peri-operative can help the surgeon evaluating the circumferential resection margin at the surgical theatre, preventing under- and overtreatment of patients in the future

Reconstructing the somatotopic organization of the corticospinal tract remains a challenge for modern tractography methods

The corticospinal tract (CST) is a critically important white matter fiber tract in the human brain that enables control of voluntary movements of the body. Diffusion MRI tractography is the only method that enables the study of the anatomy and variability of the CST pathway in human health. In this work, we explored the performance of six widely used tractography methods for reconstructing the CST and its somatotopic organization. We perform experiments using diffusion MRI data from the Human Connectome Project. Four quantitative measurements including reconstruction rate, the WM-GM interface coverage, anatomical distribution of streamlines, and correlation with cortical volumes to assess the advantages and limitations of each method. Overall, we conclude that while current tractography methods have made progress toward the well-known challenge of improving the reconstruction of the lateral projections of the CST, the overall problem of performing a comprehensive CST reconstruction, including clinically important projections in the lateral (hand and face area) and medial portions (leg area), remains an important challenge for diffusion MRI tractography.Comment: 41 pages, 19 figure

Paper and Fiber-Based Bio-Diagnostic Platforms: Current Challenges and Future Needs

In this perspective article, some of the latest paper and fiber-based bio-analytical platforms are summarized, along with their fabrication strategies, the processing behind the product development, and the embedded systems in which paper or fiber materials were integrated. The article also reviews bio-recognition applications of paper/fiber-based devices, the detected analytes of interest, applied detection techniques, the related evaluation parameters, the type and duration of the assays, as well as the advantages and disadvantages of each technique. Moreover, some of the existing challenges of utilizing paper and/or fiber materials are discussed. These include control over the physical characteristics (porosity, permeability, wettability) and the chemical properties (surface functionality) of paper/fiber materials are discussed. Other aspects of the review focus on shelf life, the multi-functionality of the platforms, readout strategies, and other challenges that have to be addressed in order to obtain reliable detection outcomes. Keywords: paper-based bio-analytical devices; shelf life; equipment-free bio-recognition; flow rate; readout strategies; multi-functional platform

Recent advances in understanding and managing diverticulitis.

In the past few decades, the increasing socioeconomic burden of acute diverticulitis (AD) has become evident, and with the growth of the population age, this significant economic impact will likely continue to rise. Furthermore, recent evidence showed an increased rate of hospital admissions especially evident among women and younger individuals. The natural history and pathophysiology of this clinical condition is still to be fully defined, and efforts continue to be made in the identification of risk factors and the establishment of relative preventive strategies. The actual therapeutic strategies aimed to modulate gut microbiota, such as rifaximin or probiotics, or to reduce mucosal inflammation, such as mesalazine, present a relatively poor efficacy for both the prevention of the first AD episode (primary prevention) and its recurrence (secondary prevention). In the last few years, the main goal achieved has been in the management of AD in that uncomplicated AD can, to a larger extent, be managed in an outpatient setting with no or little supportive therapy, a strategy that will certainly impact on the health costs of this disease. The problem of AD recurrence remains a topic of debate. The aim of this review is to present updated evidence on AD epidemiology and relative open clinical questions and to analyze in detail predisposing and protective factors with an attempt to integrate their possible modes of action into the several pathogenic mechanisms that have been suggested to contribute to this multifactorial disease. A unifying hypothesis dealing with the colonic luminal and extra-luminal microenvironments separately is provided. Finally, evidence-based changes in therapeutic management will be summarized. Because of an ascertained multifactorial pathogenesis of uncomplicated and complicated AD, it is probable that a single ‘causa prima’ will not be identifiable, and a better stratification of patients could allow one to pursue tailored therapeutic algorithm strategies

Optical techniques for 3D surface reconstruction in computer-assisted laparoscopic surgery

One of the main challenges for computer-assisted surgery (CAS) is to determine the intra-opera- tive morphology and motion of soft-tissues. This information is prerequisite to the registration of multi-modal patient-specific data for enhancing the surgeon’s navigation capabilites by observ- ing beyond exposed tissue surfaces and for providing intelligent control of robotic-assisted in- struments. In minimally invasive surgery (MIS), optical techniques are an increasingly attractive approach for in vivo 3D reconstruction of the soft-tissue surface geometry. This paper reviews the state-of-the-art methods for optical intra-operative 3D reconstruction in laparoscopic surgery and discusses the technical challenges and future perspectives towards clinical translation. With the recent paradigm shift of surgical practice towards MIS and new developments in 3D opti- cal imaging, this is a timely discussion about technologies that could facilitate complex CAS procedures in dynamic and deformable anatomical regions

Practice parameters for the treatment of colonic diverticular disease: Italian Society of Colon and Rectal Surgery (SICCR) guidelines

The mission of the Italian Society of Colorectal Surgery (SICCR) is to optimize patient care. Providing evidence-based practice guidelines is therefore of key importance. About the present report it concernes the SICCR practice guidelines for the diagnosis and treatment of diverticular disease of the colon. The guidelines are not intended to define the sole standard of care but to provide evidence-based recommendations regarding the available therapeutic options

Multicolour interphase cytogenetics: 24 chromosome probes, 6 colours, 4 layers

From the late 1980s onwards, the use of DNA probes to visualise sequences on individual chromosomes (fluorescent in-situ hybridisation - FISH) revolutionised the study of cytogenetics. Following single colour experiments, more fluorochromes were added, culminating in a 24 colour assay that could distinguish all human chromosomes. Interphase cytogenetics (the detection of chromosome copy number in interphase nuclei) soon followed, however 24 colour experiments are hampered for this application as mixing fluorochromes to produce secondary colours produces images that are not easily distinguishable from overlapping signals. This study reports the development and use of a novel protocol, new fast hybridising FISH probes, and a bespoke image capture system for the assessment of chromosome copy number in interphase nuclei. The multicolour probe sets can be used individually or in sequential hybridisation layers to assess ploidy of all 24 human chromosomes in the same nucleus. Applications of this technique are in the investigation of chromosome copy number and the assessment of nuclear organisation for a range of different cell types including human sperm, cancer cells and preimplantation embryos