3D Deep Learning on Medical Images: A Review

The rapid advancements in machine learning, graphics processing technologies and availability of medical imaging data has led to a rapid increase in use of deep learning models in the medical domain. This was exacerbated by the rapid advancements in convolutional neural network (CNN) based architectures, which were adopted by the medical imaging community to assist clinicians in disease diagnosis. Since the grand success of AlexNet in 2012, CNNs have been increasingly used in medical image analysis to improve the efficiency of human clinicians. In recent years, three-dimensional (3D) CNNs have been employed for analysis of medical images. In this paper, we trace the history of how the 3D CNN was developed from its machine learning roots, give a brief mathematical description of 3D CNN and the preprocessing steps required for medical images before feeding them to 3D CNNs. We review the significant research in the field of 3D medical imaging analysis using 3D CNNs (and its variants) in different medical areas such as classification, segmentation, detection, and localization. We conclude by discussing the challenges associated with the use of 3D CNNs in the medical imaging domain (and the use of deep learning models, in general) and possible future trends in the field.Comment: 13 pages, 4 figures, 2 table

Cellular crosstalk mechanism of Toll-like receptors in gingival overgrowth (review)

Gingival overgrowth is an undesirable outcome of systemic medication and is evidenced by the accretion of collagenous components in gingival connective tissues along with diverse degrees of inflammation. Phenytoin therapy has been found to induce the most fibrotic lesions in gingiva, cyclosporine caused the least fibrotic lesions, and nifedipine induced intermediate fibrosis in drug induced gingival overgrowth. In drug induced gingival overgrowth, efficient oral hygiene is compromised and has negative consequences for the systemic health of the patients. Toll like receptors (TLRs) are involved in the effective recognition of microbial agents and play a vital role in innate immunity and inflammatory signaling responses. TLRs stimulate fibrosis and tissue repairs in several settings, although with evident differences between organs. In particular, TLRs exert a distinct effect on fibrosis in organs with greater exposure to TLR ligands, such as the gingiva. Cumulative evidence from diverse sources suggested that TLRs can affect gingival overgrowth in several ways. Numerous studies have demonstrated the expression of TLRs in gingival tissues and suggested its potential role in gingival inflammation, cell proliferation and synthesis of the extracellular matrix which is crucial to the development of gingival overgrowth. In the present review, we assessed the role of TLRs on individual cell populations in gingival tissues that contribute to the progression of gingival inflammation, and the involvement of TLRs in the development of gingival overgrowth. These observations suggest that TLRs provide new insight into the connection among infection, inflammation, drugs and gingival fibrosis, and are therefore efficient therapeutic target molecules. We hypothesize that TLRs are critical for the development and progression of gingival overgrowth, and thus blocking TLR expression may serve as a novel target for antifibrotic therapy

Direct myosin-2 inhibition enhances cerebral perfusion resulting in functional improvement after ischemic stroke

Acute ischemic stroke treatment faces an unresolved obstacle as capillary reperfusion remains insufficient after thrombolysis and thrombectomy causing neuronal damage and poor prognosis. Hypoxia-induced capillary constriction is mediated by actomyosin contraction in precapillary smooth muscle cells (SMCs) therefore smooth muscle myosin-2 could be an ideal target with potentially high impact on reperfusion of capillaries. Methods: The myosin-2 inhibitor para-aminoblebbistatin (AmBleb) was tested on isolated human and rat arterioles to assess the effect of AmBleb on vasodilatation. Transient middle cerebral artery occlusion (MCAO) was performed on 38 male Wistar rats followed by local administration of AmBleb into the ischemic brain area. Development of brain edema and changes in cerebrovascular blood flow were assessed using MRI and SPECT. We also tested the neurological deficit scores and locomotor asymmetry of the animals for 3 weeks after the MCAO operation. Results: Our results demonstrate that AmBleb could achieve full relaxation of isolated cerebral arterioles. In living animals AmBleb recovered cerebral blood flow in 32 out of the 65 affected functional brain areas in MCAO operated rats, whereas only 8 out of the 67 affected areas were recovered in the control animals. Animals treated with AmBleb also showed significantly improved general and focal deficit scores in neurological functional tests and showed significantly ameliorated locomotor asymmetry. Conclusion: Direct inhibition of smooth muscle myosin by AmBleb in pre-capillary SMCs significantly contribute to the improvement of cerebral blood reperfusion and brain functions suggesting that smooth muscle myosin inhibition may have promising potential in stroke therapies as a follow-up treatment of physical or chemical removal of the occluding thrombus.Published versio

Fluorescent, Prussian Blue-Based Biocompatible Nanoparticle System for Multimodal Imaging Contrast

(1) Background. The main goal of this work was to develop a fluorescent dye-labelling technique for our previously described nanosized platform, citrate-coated Prussian blue (PB) nanoparticles (PBNPs). In addition, characteristics and stability of the PB nanoparticles labelled with fluorescent dyes were determined. (2) Methods. We adsorbed the fluorescent dyes Eosin Y and Rhodamine B and methylene blue (MB) to PB-nanoparticle systems. The physicochemical properties of these fluorescent dye-labeled PBNPs (iron(II);iron(III);octadecacyanide) were determined using atomic force microscopy, dynamic light scattering, zeta potential measurements, scanning- and transmission electron microscopy, X-ray diffraction, and Fourier-transformation infrared spectroscopy. A methylene-blue (MB) labelled, polyethylene-glycol stabilized PBNP platform was selected for further assessment of in vivo distribution and fluorescent imaging after intravenous administration in mice. (3) Results. The MB-labelled particles emitted a strong fluorescent signal at 662 nm. We found that the fluorescent light emission and steric stabilization made this PBNP-MB particle platform applicable for in vivo optical imaging. (4) Conclusion. We successfully produced a fluorescent and stable, Prussian blue-based nanosystem. The particles can be used as a platform for imaging contrast enhancement. In vivo stability and biodistribution studies revealed new aspects of the use of PBNPs

Synthesis and Preclinical Application of a Prussian Blue-Based Dual Fluorescent and Magnetic Contrast Agent (CA)

The aim of this study was to develop and characterize a Prussian Blue based biocompatible and chemically stable T1 magnetic resonance imaging (MRI) contrast agent with near infrared (NIR) optical contrast for preclinical application. The physical properties of the Prussian blue nanoparticles (PBNPs) (iron (II); iron (III);octadecacyanide) were characterized with dynamic light scattering (DLS), zeta potential measurement, atomic force microscopy (AFM), and transmission electron microscopy (TEM). In vitro contrast enhancement properties of PBNPs were determined by MRI. In vivo T1-weighted contrast of the prepared PBNPs was investigated by MRI and optical imaging modality after intravenous administration into NMRI-Foxn1 nu/nu mice. The biodistribution studies showed the presence of PBNPs predominantly in the cardiovascular system. Briefly, in this paper we show a novel approach for the synthesis of PBNPs with enhanced iron content for T1 MRI contrast. This newly synthetized PBNP platform could lead to a new diagnostic agent, replacing the currently used Gadolinium based substances

Multifunctional iron oxide nanoparticles for diagnostics, therapy and macromolecule delivery

In recent years, multifunctional nanoparticles (NPs) consisting of either metal (e.g. Au), or magnetic NP (e.g. iron oxide) with other fluorescent components such as quantum dots (QDs) or organic dyes have been emerging as versatile candidate systems for cancer diagnosis, therapy, and macromolecule delivery such as micro ribonucleic acid (microRNA). This review intends to highlight the recent advances in the synthesis and application of multifunctional NPs (mainly iron oxide) in theranostics, an area used to combine therapeutics and diagnostics. The recent applications of NPs in miRNA delivery are also reviewed.ASTAR (Agency for Sci., Tech. and Research, S’pore)Published versio

Neurophysiological Correlates of Cognition as Revealed by Virtual Reality: Delving the Brain with a Synergistic Approach

The synergy of perceptual psychology, technology, and neuroscience can be used to comprehend how virtual reality affects cognition of human brain. Numerous studies have used neuroimaging modalities to assess the cognitive state and response of the brain with various external stimulations. The virtual reality-based devices are well known to incur visual, auditory, and haptic induced perceptions. Neurophysiological recordings together with virtual stimulations can assist in correlating humans’ physiological perception with response in the environment designed virtually. The effective combination of these two has been utilized to study human behavior, spatial navigation performance, and spatial presence, to name a few. Moreover, virtual reality-based devices can be evaluated for the neurophysiological correlates of cognition through neurophysiological recordings. Challenges exist in the integration of real-time neuronal signals with virtual reality-based devices, and enhancing the experience together with real-time feedback and control through neuronal signals. This article provides an overview of neurophysiological correlates of cognition as revealed by virtual reality experience, together with a description of perception and virtual reality-based neuromodulation, various applications, and existing challenges in this field of research

Neurophysiological correlates of cognition as revealed by virtual reality : delving the brain with a synergistic approach

The synergy of perceptual psychology, technology, and neuroscience can be used to comprehend how virtual reality affects cognition of human brain. Numerous studies have used neuroimaging modalities to assess the cognitive state and response of the brain with various external stimulations. The virtual reality-based devices are well known to incur visual, auditory, and haptic induced perceptions. Neurophysiological recordings together with virtual stimulations can assist in correlating humans' physiological perception with response in the environment designed virtually. The effective combination of these two has been utilized to study human behavior, spatial navigation performance, and spatial presence, to name a few. Moreover, virtual reality-based devices can be evaluated for the neurophysiological correlates of cognition through neurophysiological recordings. Challenges exist in the integration of real-time neuronal signals with virtual reality-based devices, and enhancing the experience together with real-time feedback and control through neuronal signals. This article provides an overview of neurophysiological correlates of cognition as revealed by virtual reality experience, together with a description of perception and virtual reality-based neuromodulation, various applications, and existing challenges in this field of research.Nanyang Technological UniversityPublished versionS.M., P.P., and B.G. acknowledge the support from Lee Kong Chian School of Medicine and Data Science and AI Research (DSAIR) Centre of NTU (Project Number ADH-11/2017-DSAIR, and the support from the Cognitive Neuroimaging Centre (CONIC) at Nanyang Technological University, Singapore

Effect of mutation on aggregation propensity in homology model structures of syntaxin-3 from <i style="mso-bidi-font-style:normal">Homo sapiens</i>

335-342Perception of molecular mechanism would provide potent additional knowledge on mammalian membrane proteins involved in causing diseases. In human, syntaxin-3 (STX3) is a significant apical targeting protein in the epithelial membrane and in exocytosis process; it also acts as a vesicle transporter by cellular receptor in neutrophils, which is crucial for protein trafficking event. Structurally, syntaxin-3 has hydrophobic domain at carboxyl terminus that directs itself to intra-cellular compartments. In addition, the experimental structure of STX3 is not available and no mutational study has been carried out with natural variants of proteins. Moreover, there is no evidence so far for the natural variant Val286 of STX3 causing any diseases. Hence, in the present study, analyses of residue-based properties of the homology model STX3 were carried out along with mutations at carboxyl terminus of STX3 by implementing protein engineering and in silico approaches. The model structure of STX3 was constructed adopting Modeller v9.11 and the aggregation propensity was analyzed with BioLuminate tool. The results showed that there was reduction in aggregation propensity with point mutation at Val286, instead of Ile, resulting into increasing the structural stability of STX3. In conclusion, the Ccap exposed residue would be a suitable position for further mutational studies, particularly with Val286 of STX3 in human. This approach could gainfully be applied to STX3 for efficient drug designing which would be a valuable target in the cancer treatment. </span