A Review of Indocyanine Green Fluorescent Imaging in Surgery

The purpose of this paper is to give an overview of the recent surgical intraoperational applications of indocyanine green fluorescence imaging methods, the basics of the technology, and instrumentation used. Well over 200 papers describing this technique in clinical setting are reviewed. In addition to the surgical applications, other recent medical applications of ICG are briefly examined

Fluorescent-based nanosensors for selective detection of a wide range of biological macromolecules: A comprehensive review

Thanks to their unique attributes, such as good sensitivity, selectivity, high surface-to-volume ratio, and versatile optical and electronic properties, fluorescent-based bioprobes have been used to create highly sensitive nano -biosensors to detect various biological and chemical agents. These sensors are superior to other analytical instrumentation techniques like gas chromatography, high-performance liquid chromatography, and capillary electrophoresis for being biodegradable, eco-friendly, and more economical, operational, and cost-effective. Moreover, several reports have also highlighted their application in the early detection of biomarkers associ-ated with drug-induced organ damage such as liver, kidney, or lungs. In the present work, we comprehensively overviewed the electrochemical sensors that employ nanomaterials (nanoparticles/colloids or quantum dots, carbon dots, or nanoscaled metal-organic frameworks, etc.) to detect a variety of biological macromolecules based on fluorescent emission spectra. In addition, the most important mechanisms and methods to sense amino acids, protein, peptides, enzymes, carbohydrates, neurotransmitters, nucleic acids, vitamins, ions, metals, and electrolytes, blood gases, drugs (i.e., anti-inflammatory agents and antibiotics), toxins, alkaloids, antioxidants, cancer biomarkers, urinary metabolites (i.e., urea, uric acid, and creatinine), and pathogenic microorganisms were outlined and compared in terms of their selectivity and sensitivity. Altogether, the small dimensions and capability of these nanosensors for sensitive, label-free, real-time sensing of chemical, biological, and pharma-ceutical agents could be used in array-based screening and in-vitro or in-vivo diagnostics. Although fluorescent nanoprobes are widely applied in determining biological macromolecules, unfortunately, they present many challenges and limitations. Efforts must be made to minimize such limitations in utilizing such nanobiosensors with an emphasis on their commercial developments. We believe that the current review can foster the wider incorporation of nanomedicine and will be of particular interest to researchers working on fluorescence tech-nology, material chemistry, coordination polymers, and related research areas

Optical Diagnostics in Human Diseases

Optical technologies provide unique opportunities for the diagnosis of various pathological disorders. The range of biophotonics applications in clinical practice is considerably wide given that the optical properties of biological tissues are subject to significant changes during disease progression. Due to the small size of studied objects (from μm to mm) and despite some minimum restrictions (low-intensity light is used), these technologies have great diagnostic potential both as an additional tool and in cases of separate use, for example, to assess conditions affecting microcirculatory bed and tissue viability. This Special Issue presents topical articles by researchers engaged in the development of new methods and devices for optical non-invasive diagnostics in various fields of medicine. Several studies in this Special Issue demonstrate new information relevant to surgical procedures, especially in oncology and gynecology. Two articles are dedicated to the topical problem of breast cancer early detection, including during surgery. One of the articles is devoted to urology, namely to the problem of chronic or recurrent episodic urethral pain. Several works describe the studies in otolaryngology and dentistry. One of the studies is devoted to diagnosing liver diseases. A number of articles contribute to the studying of the alterations caused by diabetes mellitus and cardiovascular diseases. The results of all the presented articles reflect novel innovative research and emerging ideas in optical non-invasive diagnostics aimed at their wider translation into clinical practice

Multispectral image analysis in laparoscopy – A machine learning approach to live perfusion monitoring

Modern visceral surgery is often performed through small incisions. Compared to open surgery, these minimally invasive interventions result in smaller scars, fewer complications and a quicker recovery. While to the patients benefit, it has the drawback of limiting the physician’s perception largely to that of visual feedback through a camera mounted on a rod lens: the laparoscope. Conventional laparoscopes are limited by “imitating” the human eye. Multispectral cameras remove this arbitrary restriction of recording only red, green and blue colors. Instead, they capture many specific bands of light. Although these could help characterize important indications such as ischemia and early stage adenoma, the lack of powerful digital image processing prevents realizing the technique’s full potential. The primary objective of this thesis was to pioneer fluent functional multispectral imaging (MSI) in laparoscopy. The main technical obstacles were: (1) The lack of image analysis concepts that provide both high accuracy and speed. (2) Multispectral image recording is slow, typically ranging from seconds to minutes. (3) Obtaining a quantitative ground truth for the measurements is hard or even impossible. To overcome these hurdles and enable functional laparoscopy, for the first time in this field physical models are combined with powerful machine learning techniques. The physical model is employed to create highly accurate simulations, which in turn teach the algorithm to rapidly relate multispectral pixels to underlying functional changes. To reduce the domain shift introduced by learning from simulations, a novel transfer learning approach automatically adapts generic simulations to match almost arbitrary recordings of visceral tissue. In combination with the only available video-rate capable multispectral sensor, the method pioneers fluent perfusion monitoring with MSI. This system was carefully tested in a multistage process, involving in silico quantitative evaluations, tissue phantoms and a porcine study. Clinical applicability was ensured through in-patient recordings in the context of partial nephrectomy; in these, the novel system characterized ischemia live during the intervention. Verified against a fluorescence reference, the results indicate that fluent, non-invasive ischemia detection and monitoring is now possible. In conclusion, this thesis presents the first multispectral laparoscope capable of videorate functional analysis. The system was successfully evaluated in in-patient trials, and future work should be directed towards evaluation of the system in a larger study. Due to the broad applicability and the large potential clinical benefit of the presented functional estimation approach, I am confident the descendants of this system are an integral part of the next generation OR

National eHealth system – platform for preventive, predictive and personalized diabetes care

National eHealth System, covering all citizens and all healthcare levels in Republic of Macedonia, was introduced in July 2013, has been internationally recognized System for successful reduction of waiting times and instrumental in the management of national healthcare resources. For the first time, National Diabetes Committee, formed in February 2015 according to the Law on healthcare and being overall responsible for the diabetes care in the country, was able to derive exact figures on the national diabetes prevalence from the System, instead of extrapolations used before, serving as a basis for development of strategies for prediction and prevention of diabetic complications, as well as for personalized diabetes care. Number of diabetes cases identified through the National eHealth System in June 2015 was 84,568 (4.02 % of total population), 36,119 males (3.42 % of total male population) and 48,449 females (4.61% of total female population). Age stratified diabetes prevalence was as follows: less than 20 years – 549 cases (0.11 % of respective population), 20-39 years – 3,202 (0.49 %), 40-59 years – 26,561 (4.58 %), 60-79 years – 48,470 (14.57 %), 80 years or more – 5,786 (12.96 %). Addition of parameters for metabolic control and diabetic complications in the System is under way, further facilitating the modeling of diabetes treatment, metabolic control and the outcomes. Inclusion of pre-diabetes patients (IGT and IFG) is also planned, thus providing opportunity to also focus healthcare activities for prevention of progression into overt type 2 diabetes

Design and Analysis of Cloaked Fluorophores for Rapid Detection and Visualization of Cancer Cells Containing NAD(P)H:Quinone Oxidoreductase-1

The development of fluorogenic substrates for real-time tumor cell detection has led to a vastly expanding field for personal oncology. Fluorophores have been studied as appendages to larger scaffolds leading to accumulation of these dyes in tumor cells or their surrounding environment, taking advantage of tumor anatomy. A new class of fluorophores has been developed in which the dye is an active participant in the mechanism of cancer cell detection. These dyes have been conjugated such that their fluorescence has been eliminated or altered and will undergo a change to reveal their fluorescent signal upon activation by a mechanism that is unique to tumor cells. The research presented in this dissertation encompasses the design, synthesis, properties, and utilization of latent fluorophores that are specifically activated by an enzyme that is highly upregulated in tumor cells, NAD(P)H:quinone oxidoreductase-1 (NQO1). These dyes utilize the 2-electron reduction of quinones to hydroquinones, which NQO1 specifically catalyzes. A dye’s fluorescence can be quenched by conjugating a quinone directly to the fluorophore, only to have its signal uncloaked after activation by NQO1. The objectives in this research will be achieved by: (1) the characterization of properties (stability in biological environments, quantum yields) of the quinone, dyes, and their conjugated counterparts; (2) determination of kinetic parameters (Michaelis constant (Km), theoretical maximum velocity (Vmax), catalytic constant (kcat), enzyme efficiency (kcat/Km) of the substrates towards NQO1 and the way solvent affects such parameters during assay conditions; and (3) utilization of a latent fluorophore for in vivo NQO1 analysis (widefield imaging, confocal single-/two-photon microscopy, flow cytometry) and determining the fate of the released fluorophore. Integration of these studies led to the development of two different latent fluorophores that are readily activated by NQO1. Of these two fluorogenic cancer sensors, one was found to possess a highly novel quenching mechanism between the quinone and the dye