Optical imaging in vivo with a focus on paediatric disease: technical progress, current preclinical and clinical applications and future perspectives

To obtain information on the occurrence and location of molecular events as well as to track target-specific probes such as antibodies or peptides, drugs or even cells non-invasively over time, optical imaging (OI) technologies are increasingly applied. Although OI strongly contributes to the advances made in preclinical research, it is so far, with the exception of optical coherence tomography (OCT), only very sparingly applied in clinical settings. Nevertheless, as OI technologies evolve and improve continuously and represent relatively inexpensive and harmful methods, their implementation as clinical tools for the assessment of children disease is increasing. This review focuses on the current preclinical and clinical applications as well as on the future potential of OI in the clinical routine. Herein, we summarize the development of different fluorescence and bioluminescence imaging techniques for microscopic and macroscopic visualization of microstructures and biological processes. In addition, we discuss advantages and limitations of optical probes with distinct mechanisms of target-detection as well as of different bioluminescent reporter systems. Particular attention has been given to the use of near-infrared (NIR) fluorescent probes enabling observation of molecular events in deeper tissue

Aqueous Humor Outflow Structure and Function Imaging At the Bench and Bedside: A Review.

Anterior segment glaucoma clinical care and research has recently gained new focus because of novel imaging modalities and the advent of angle-based surgical treatments. Traditional investigation drawn to the trabecular meshwork now emphasizes the entire conventional aqueous humor outflow (AHO) pathway from the anterior chamber to the episcleral vein. AHO investigation can be divided into structural and functional assessments using different methods. The historical basis for studying the anterior segment of the eye and AHO in glaucoma is discussed. Structural studies of AHO are reviewed and include traditional pathological approaches to modern tools such as multi-model two-photon microscopy and optical coherence tomography. Functional assessment focuses on visualizing AHO itself through a variety of non-real-time and real-time techniques such as aqueous angiography. Implications of distal outflow resistance and segmental AHO are discussed with an emphasis on melding bench-side research to viable clinical applications. Through the development of an improved structure: function relationship for AHO in the anterior segment of the normal and diseased eye, a better understanding of the eye with improved therapeutics may be developed

A Review on Advances in Intra-operative Imaging for Surgery and Therapy: Imagining the Operating Room of the Future

none4openZaffino, Paolo; Moccia, Sara; De Momi, Elena; Spadea, Maria FrancescaZaffino, Paolo; Moccia, Sara; De Momi, Elena; Spadea, Maria Francesc

Intraoperative hyperspectral label-free imaging: from system design to first-in-patient translation.

Despite advances in intraoperative surgical imaging, reliable discrimination of critical tissue during surgery remains challenging. As a result, decisions with potentially life-changing consequences for patients are still based on the surgeon's subjective visual assessment. Hyperspectral imaging (HSI) provides a promising solution for objective intraoperative tissue characterisation, with the advantages of being non-contact, non-ionising and non-invasive. However, while its potential to aid surgical decision-making has been investigated for a range of applications, to date no real-time intraoperative HSI (iHSI) system has been presented that follows critical design considerations to ensure a satisfactory integration into the surgical workflow. By establishing functional and technical requirements of an intraoperative system for surgery, we present an iHSI system design that allows for real-time wide-field HSI and responsive surgical guidance in a highly constrained operating theatre. Two systems exploiting state-of-the-art industrial HSI cameras, respectively using linescan and snapshot imaging technology, were designed and investigated by performing assessments against established design criteria and ex vivo tissue experiments. Finally, we report the use of our real-time iHSI system in a clinical feasibility case study as part of a spinal fusion surgery. Our results demonstrate seamless integration into existing surgical workflows

Clinical translation of laser speckle contrast imaging

Humankind is moving forward in an astonishing pace in every scientific specialty. It is therefore remarkable that the current standard-of-care for blood flow assessment has remained unchanged for decades. The desire to 'see' tissue perfusion (i.e. blood flow) intraoperatively has never been greater due to the increasing awareness that adequate perfusion is an essential part of organ function and wound healing and also plays a leading role in prevention of mortality and morbidity. Currently, intraoperative perfusion measurements are generally based on subjective clinical indicators of tissue vitality (e.g., tissue color, bleeding from resected edges, or pulsatile movement of tissue). This fuels the need for an objective imaging method capable of imaging the perfusion of organs and tissues in real time. The aim of this thesis was to develop and validate a laparoscopic tool to measure blood flow using laser speckle contrast imaging (LSCI) technology. In the first part of the thesis, a new LSCI method is described and validated on a pig kidney model. Next, setting up a scientifically sound imaging protocol for clinical optical imaging studies is described. The acquired knowledge about LSCI has been used in the development of a laparoscopic LSCI device. This device has been validated through two preclinical pig studies in which the blood flow in the large and small intestines was measured. The validated device has been used in two multicenter studies investigating the effect of the new imaging technique on clinical decision-making during colon resections

Pixel-level semantic understanding of ophthalmic images and beyond

Computer-assisted semantic image understanding constitutes the substrate of applications that range from biomarker detection to intraoperative guidance or street scene understanding for self-driving systems. This PhD thesis is on the development of deep learning-based, pixel-level, semantic segmentation methods for medical and natural images. For vessel segmentation in OCT-A, a method comprising iterative refinement of the extracted vessel maps and an auxiliary loss function that penalizes structural inaccuracies, is proposed and tested on data captured from real clinical conditions comprising various pathological cases. Ultimately, the presented method enables the extraction of a detailed vessel map of the retina with potential applications to diagnostics or intraoperative localization. Furthermore, for scene segmentation in cataract surgery, the major challenge of class imbalance is identified among several factors. Subsequently, a method addressing it is proposed, achieving state-of-the-art performance on a challenging public dataset. Accurate semantic segmentation in this domain can be used to monitor interactions between tools and anatomical parts for intraoperative guidance and safety. Finally, this thesis proposes a novel contrastive learning framework for supervised semantic segmentation, that aims to improve the discriminative power of features in deep neural networks. The proposed approach leverages contrastive loss function applied both at multiple model layers and across them. Importantly, the proposed framework is easy to combine with various model architectures and is experimentally shown to significantly improve performance on both natural and medical domain

Visual Perception and Cognition in Image-Guided Intervention

Surgical image visualization and interaction systems can dramatically affect the efficacy and efficiency of surgical training, planning, and interventions. This is even more profound in the case of minimally-invasive surgery where restricted access to the operative field in conjunction with limited field of view necessitate a visualization medium to provide patient-specific information at any given moment. Unfortunately, little research has been devoted to studying human factors associated with medical image displays and the need for a robust, intuitive visualization and interaction interfaces has remained largely unfulfilled to this day. Failure to engineer efficient medical solutions and design intuitive visualization interfaces is argued to be one of the major barriers to the meaningful transfer of innovative technology to the operating room. This thesis was, therefore, motivated by the need to study various cognitive and perceptual aspects of human factors in surgical image visualization systems, to increase the efficiency and effectiveness of medical interfaces, and ultimately to improve patient outcomes. To this end, we chose four different minimally-invasive interventions in the realm of surgical training, planning, training for planning, and navigation: The first chapter involves the use of stereoendoscopes to reduce morbidity in endoscopic third ventriculostomy. The results of this study suggest that, compared with conventional endoscopes, the detection of the basilar artery on the surface of the third ventricle can be facilitated with the use of stereoendoscopes, increasing the safety of targeting in third ventriculostomy procedures. In the second chapter, a contour enhancement technique is described to improve preoperative planning of arteriovenous malformation interventions. The proposed method, particularly when combined with stereopsis, is shown to increase the speed and accuracy of understanding the spatial relationship between vascular structures. In the third chapter, an augmented-reality system is proposed to facilitate the training of planning brain tumour resection. The results of our user study indicate that the proposed system improves subjects\u27 performance, particularly novices\u27, in formulating the optimal point of entry and surgical path independent of the sensorimotor tasks performed. In the last chapter, the role of fully-immersive simulation environments on the surgeons\u27 non-technical skills to perform vertebroplasty procedure is investigated. Our results suggest that while training surgeons may increase their technical skills, the introduction of crisis scenarios significantly disturbs the performance, emphasizing the need of realistic simulation environments as part of training curriculum

Multicenter study of pars plana vitrectomy for optic disc pit maculopathy: MACPIT study

Purpose To evaluate surgical intervention with pars plana vitrectomy (PPV) for correction of optic disc pit maculopathy (ODP-M). Patients and methods Retrospective chart review from 13 centres of 51 eyes of 50 patients with ODP-M who underwent PPV between 2002-2014. Anatomic and final best-corrected visual acuity (BCVA) outcomes were evaluated for all cases with different adjuvant techniques. Results There were 23 males and 27 females with median age 25.5 (6-68) years. Preoperative median foveal thickness was 694.5 (331-1384) mu m and improved to 252.5 (153-1405) mu m. Median BCVA improved from 20/200 (20/20000 to 20/40) to 20/40 (20/2000 to 20/20) with 20/40 or better in 31 eyes. Complete retinal reattachment was achieved in 44 eyes (86.3%) at 7.1 (5.9) months. The good surgical outcomes were achieved in different adjuvant groups. Median follow-up was 24 (6 to 120) months. Conclusions These results confirm the long-term effectiveness of PPV for ODP-M. Prospective studies are needed to determine the effectiveness of any adjuvant technique in improving the success of PPV for ODP-M