Developing Motorized Spectroscopy System for Tissue Scanning
The aim of the presented study was to develop a newly motorized spectroscopy system. Our system is composed of probe and motor parts. The probe part consists of bioimpedance and fiber optic components that include two platinum wires (each 25 micrometer in diameter) and two fiber cables (each 50 micrometers in diameter) respectively. Probe was examined on tissue phantom (polystyrene microspheres with different diameters). In the bioimpedance part of the probe current was transferred to the phantom and conductivity information was obtained. Adjacent two fiber cables were used in the fiber optic part of the system. Light was transferred to the phantom by fiber that was connected to the light source and backscattered light was collected with the other adjacent fiber for analysis. It is known that the nucleus expands and the nucleus-cytoplasm ratio increases during the cancer progression in the cell and this situation is one of the most important criteria for evaluating the tissue for pathologists. The sensitivity of the probe to particle (nucleus) size in phantom was tested during the study. Spectroscopic data obtained from our system on phantom was evaluated by multivariate statistical analysis. Thus the information about the particle size in the phantom was obtained. Bioimpedance and fiber optic experiments results which were obtained from polystyrene microspheres showed that the impedance value and the oscillation amplitude were increasing while the size of particle was enlarging. These results were compatible with the previous studies. In order to motorize the system within the motor part, three driver electronic circuits were designed primarily. In this part, supply capacitors were placed symmetrically near to the supply inputs which were used for balancing the oscillation. Female capacitors were connected to the control pin. Optic and mechanic switches were made. Drivers were structurally designed as they could command highly calibrated motors. It was considered important to keep the drivers’ dimension as small as we could (4.4x4.4x1.4 cm). Then three miniature step motors were connected to each other along with three drivers. Since spectroscopic techniques are quantitative methods, they yield more objective results than traditional ones. In the future part of this study, it is planning to get spectroscopic data that have optic and impedance information from the cell culture which is normal, low metastatic and high metastatic breast cancer. In case of getting high sensitivity in differentiated cells, it might be possible to scan large surface tissue areas in a short time with small steps. By means of motorize feature of the system, any region of the tissue will not be missed, in this manner we are going to be able to diagnose cancerous parts of the tissue meticulously. This work is supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) through 3001 project (115E662).
Classification of Multiple Cancer Types with Deep Convolutional Neural Network
Thousands of patients with metastatic tumors were diagnosed with cancers of unknown primary sites each year. The inability to identify the primary cancer site may lead to inappropriate treatment and unexpected prognosis. Nowadays, a large amount of genomics and transcriptomics cancer data has been generated by next-generation sequencing (NGS) technologies, and The Cancer Genome Atlas (TCGA) database has accrued thousands of human cancer tumors and healthy controls, which provides an abundance of resource to differentiate cancer types. Meanwhile, deep convolutional neural networks (CNNs) have shown high accuracy on classification among a large number of image object categories. Here, we utilize 25 cancer primary tumors and 3 normal tissues from TCGA and convert their RNA-Seq gene expression profiling to color images; train, validate and test a CNN classifier directly from these images. The performance result shows that our CNN classifier can archive >80% test accuracy on most of the tumors and normal tissues. Since the gene expression pattern of distant metastases is similar to their primary tumors, the CNN classifier may provide a potential computational strategy on identifying the unknown primary origin of metastatic cancer in order to plan appropriate treatment for patients.
Analysis of Wall Deformation of the Arterial Plaque Models: Effects of Viscoelasticity
Viscoelastic wall properties of the arterial plaques change as the disease progresses, and estimation of wall viscoelasticity can provide a valuable assessment tool for plaque rupture prediction. Cross section of the stenotic coronary artery was modeled based on the IVUS image, and the finite element analysis was performed to get wall deformation under pulsatile pressure. The effects of viscoelastic parameters of the plaque on luminal diameter variations were explored. The result showed that decrease of viscous effect reduced the phase angle between the pressure and displacement waveforms, and phase angle was dependent on the viscoelastic properties of the wall. Because the viscous effect of tissue components could be identified using the phase angle difference, wall deformation waveform analysis may be applied to predict plaque wall composition change and vascular wall disease progression.
Quantification of Ciliary Movement Using Optical Coherence Tomography: An in vivo Rabbit Study
Motile cilia are responsible for maintaining the proper physiologic functions of multiples processes in the body. In the upper airway particularly, ciliated epithelial cells populate up to 80% of the surface area, and beat at a rhythmic pattern to propel mucus that traps pathogens, allergens, and pollutants. Thus, maintaining mucociliary clearance in the upper airway is of critical importance with respect to respiratory health. One common method to describe the overall function of ciliated epithelial cells is to measure the ciliary beat frequency (CBF). The present standard of CBF measurement is via ex vivo (i.e., swab or biopsy) phase-contrast microscopy with the aid of high-speed video analysis. While some groups have developed algorithms to objectively quantify CBF ex vivo, most clinicians still rely on subjective measurements, and direct, in vivo determination of CBF has thus far not been technically feasible. Optical coherence tomography (OCT) is minimally invasive tomographic imaging technology that can provide cross sectional images with micrometer-depth resolution in vivo. A brief description of the OCT setup employed in this study is as follows: a swept-source laser with center wavelength of 1310 nm and scan rate of 50 kHz is utilized as the light source. The OCT system is comprised of a 90-10 fiber coupler that splits the output laser light into the sample arm and the reference arm, respectively. An acousto-optic modulator is incorporated into the reference arm to generate a carrier frequency of 150 MHz for the OCT signal. The scanning rigid endoscope probe is comprised of one gold-plated galvanometer scanning mirror allowing for 2-dimentional scanning of the sample beam, and a gradient index lens (127 mm in length and 2.70 mm in diameter) that is fitted into a stainless steel housing (3.18 mm in diameter). The OCT probe and system have a working distance of ~8.5 mm, field of view of ~1.2 mm, lateral resolution of ~5.4 μm, and axial resolution of ~10 μm. Ethical approval for this study was obtained from the University of California Institutional Animal Care and Use Committee. New Zealand White rabbits (Oryctolagus cuniculus) weighing ~4.5 kg were used as the animal model. After direct visualization and exposure of the maxillary sinuses, OCT of the control and drug administered sinus mucosa were taken. For the experimental cases, a drug with known effect to cilia (lidocaine and epinephrine) was applied topically at a given concentration, and 2D OCT data was acquired. Software stabilization was employed to reduce motion artifices induced by the rabbit’s heartbeat and breathing. To quantify ciliary motion, Fourier analysis was performed on the ciliary layer (i.e., the top layer of the tissue with high speckle variation), and the difference between pre- and post-administration of the drug was recorded. In conclusion, while the OCT system does not have the ability to resolve individual cilium, it does have the ability to correlate ciliary induced movement in vivo. Direct in vivo quantification of CBF is made possible, and our future work will focus on bringing this technology to the clinic.
Maackiain Attenuates Alpha-Synuclein Accumulation and Improves 6-OHDA-Induced Dopaminergic Neuron Degeneration in Parkinson's Disease Animal Model
Parkinson’s disease (PD) is a degenerative disorder of the central nervous system that is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta and motor impairment. Aggregation of α-synuclein in neuronal cells plays a key role in this disease. At present, therapeutics for PD provides moderate symptomatic benefit but is not able to delay the development of this disease. Current efforts for the treatment of PD are to identify new drugs that show slow or arrest progressive course of PD by interfering with a disease-specific pathogenetic process in PD patients. Maackiain is a bioactive compound isolated from the roots of the Chinese herb Sophora flavescens. The purpose of the present study was to assess the potential for maackiain to ameliorate PD in Caenorhabditis elegans models. Our data reveal that maackiain prevents α-synuclein accumulation in the transgenic Caenorhabditis elegans model and also improves dopaminergic neuron degeneration, food-sensing behavior, and life-span in 6-hydroxydopamine-induced Caenorhabditis elegans model, thus indicating its potential as a candidate antiparkinsonian drug.
Compartmental Model Approach for Dosimetric Calculations of ¹⁷⁷Lu-DOTATOC in Adenocarcinoma Breast Cancer Based on Animal Data
Dosimetry is an indispensable and precious factor in patient treatment planning; to minimize the absorbed dose in vital tissues. In this study, In accordance with the proper characteristics of DOTATOC and ¹⁷⁷Lu, after preparing ¹⁷⁷Lu-DOTATOC at the optimal conditions for the first time in Iran, radionuclidic and radiochemical purity of the solution was investigated using an HPGe spectrometer and ITLC method, respectively. The biodistribution of the compound was assayed for treatment of adenocarcinoma breast cancer in bearing BALB/c mice. The results have demonstrated that ¹⁷⁷Lu-DOTATOC is a profitable selection for therapy of the tumors. Because of the vital role of internal dosimetry before and during therapy, the effort to improve the accuracy and rapidity of dosimetric calculations is necessary. For this reason, a new method was accomplished to calculate the absorbed dose through mixing between compartmental model, animal dosimetry and extrapolated data from animal to human and using MIRD method. Despite utilization of compartmental model based on the experimental data, it seems this approach may increase the accuracy of dosimetric data, confidently.
SIPTOX: Spider Toxin Database Information Repository System of Protein Toxins from Spiders by Using MySQL Method
Spider produces a special kind of substance. This special kind of substance is called a toxin. The toxin is composed of many types of protein, which differs from species to species. Spider toxin consists of several proteins and non-proteins that include various categories of toxins like myotoxin, neurotoxin, cardiotoxin, dendrotoxin, haemorrhagins, and fibrinolytic enzyme. Protein Sequence information with references of toxins was derived from literature and public databases. From the previous findings, the Spider toxin would be the best choice to treat different types of tumors and cancer. There are many therapeutic regimes, which causes more side effects than treatment hence a different approach must be adopted for the treatment of cancer. The combinations of drugs are being encouraged, and dramatic outcomes are reported. Spider toxin is one of the natural cytotoxic compounds. Hence, it is being used to treat different types of tumors; especially its positive effect on breast cancer is being reported during the last few decades. The efficacy of this database is that it can provide a user-friendly interface for users to retrieve the information about Spiders, toxin and toxin protein of different Spiders species. SPIDTOXD provides a single source information about spider toxins, which will be useful for pharmacologists, neuroscientists, toxicologists, medicinal chemists. The well-ordered and accessible web interface allows users to explore the detail information of Spider and toxin proteins. It includes common name, scientific name, entry id, entry name, protein name and length of the protein sequence. The utility of this database is that it can provide a user-friendly interface for users to retrieve the information about Spider, toxin and toxin protein of different Spider species. The database interfaces will satisfy the demands of the scientific community by providing in-depth knowledge about Spider and its toxin. We have adopted the methodology by using A MySQL and PHP and for designing, we used the Smart Draw. The users can thus navigate from one section to another, depending on the field of interest of the user. This database contains a wealth of information on species, toxins, and clinical data, etc. This database will be useful for the scientific community, basic researchers and those interested in potential pharmaceutical Industry.
Region of Interest Compression of Medical Images in Wavelet Domain Using Space Frequency Quantization
This paper presents a new Region-of-Interest (ROI) based compression scheme for medical images using joint optimization of spatial quantization mode and subband adaptive uniform scalar quantizer in the minimum description length (MDL) framework. It has been analyzed that the statistics of wavelet coefficients in the medical image can be better approximated by the Gamma distribution for the positive data and generalized Student t-distribution for negative data. By combining these statistics with the operational rate-distortion (RD) criterion, a space-frequency quantizer (SFQ) called the ROI SFQ coder is designed, which uses an efficient zero-tree quantization technique for zeroing out the tree-structured sets of wavelet coefficients and an adaptive scalar quantizer to quantize the non-zero coefficients. For this we have taken the ROI of a medical image and apply the space frequency quantization (SFQ) over both ROI and background (i.e., remaining part of the image) and compare the results with some existing compression techniques (SPIHT and MDL-SFQ) based on peak signal to noise ratio (PSNR).
MONDO Neutron Tracker Characterisation by Means of Proton Therapeutical Beams and MonteCarlo Simulation Studies
The MONDO (MOnitor for Neutron Dose in hadrOntherapy) project aims a precise characterisation of the secondary fast and ultrafast neutrons produced in particle therapy treatments. The detector is composed of a matrix of scintillating fibres (250 um) readout by CMOS Digital-SPAD based sensors. Recoil protons from n-p elastic scattering are detected and used to track neutrons. A prototype was tested with proton beams (Trento Proton Therapy Centre): efficiency, light yield, and track-reconstruction capability were studied. The results of a MonteCarlo FLUKA simulation used to evaluated double scattering efficiency and expected backgrounds will be presented.
Secondary Charged Fragments Tracking for On-Line Beam Range Monitoring in Particle Therapy
, G. Battistoni
, F. Collamati
, E. De Lucia
, R. Faccini
, C. Mancini-Terracciano
, M. Marafini
, S. Muraro
, A. Sarti
, A. Sciubba
, E. Solfaroli Camillocci
, M. Toppi
, S. M. Valle
, C. Voena
, V. Patera
In Particle Therapy (PT) treatments a large amount of secondary particles, whose emission point is correlated to the dose released in the crossed tissues, is produced. The measurement of the secondary charged fragments component could represent a valid technique to monitor the beam range during the PT treatments, that is a still missing item in the clinical practice. A sub-millimetrical precision on the beam range measurement is required to significantly optimise the technique and to improve the treatment quality. In this contribution, a detector, named Dose Profiler (DP), is presented. It is specifically planned to monitor on-line the beam range exploiting the secondary charged particles produced in PT Carbon ions treatment. In particular, the DP is designed to track the secondary fragments emitted at large angles with respect to the beam direction (mainly protons), with the aim to reconstruct the spatial coordinates of the fragment emission point extrapolating the measured track toward the beam axis. The DP is currently under development within of the INSIDE collaboration (Innovative Solutions for In-beam Dosimetry in hadrontherapy). The tracker is made by six layers (20 × 20 cm²) of BCF-12 square scintillating fibres (500 μm) coupled to Silicon Photo-Multipliers, followed by two plastic scintillator layers of 6 mm thickness. A system of front-end boards based on FPGAs arranged around the detector provides the data acquisition. The detector characterization with cosmic rays is currently undergoing, and a data taking campaign with protons will take place in May 2017. The DP design and the performances measured with using MIPs and protons beam will be reviewed.
Performance Evaluation of Joint Filtering and
Histogram Equalization Techniques for Retinal
Fundus Image Enhancement
Fundus retinal images often suffer from non-uniform illumination, poor contrast, and noise, this demands implementation of suitable pre-processing techniques for enhancing the image quality. Pre-processing technique includes methods of noise removal as well as contrast enhancement. Fundus images are often corrupted by salt and pepper noise (or impulse noise). At the same time, quality of retinal fundus image suffers due to non-uniform illumination and low contrast due to anatomy of eye fundus. This paper presents the performance evaluation of joint noise filtering and histogram equalization techniques for the overall quality enhancement of retinal fundus image. In the first stage of the work, two emerging noise filtering methods namely, noise adaptive fuzzy switching median (NAFSM) filter and block-matching and 3D filtering (BM3D) techniques are implemented for de-noising. In second stage, histogram equalization (HE), adaptive histogram equalization (ADHE), contrast limited adaptive histogram equalization (CLAHE), exposure based sub-image histogram equalization (ESIHE) techniques are investigated one by one for obtaining the best suited combination of the filtering and histogram equalization techniques for the enhancement of retinal fundus images. Performance evaluation of these techniques has been carried out by determining the performance parameters such as histogram, SNR, entropy, absolute mean brightness error and peak signal-to-noise ratio (PSNR) of processed retinal fundus images.
Biosurfactant Production on Crude Glycerol Medium
The biodiesel production is continuously growing and huge amounts of crude glycerol, a by-product from this process, is more and more available. Crude glycerol contains impurities making it unsuitable for markets which require refined material. In this study was investigated the kinetic of crude biosurfactant production by Bacillus subitilis ATCC 6633 in a low-cost medium using crude glycerol as carbon source. B. subtilis ATCC 6633 was cultivated in erlenmeyer flasks containing 50 mL of Bushnell-Haas broth and 5% (v/v) of crude glycerol. Erlenmeyer flasks were maintained in an oscillatory shaker at 180 rpm 35ºC during 96 hours. Every 24 hours of incubation, three flasks were collected, and the following parameters were determined: biomass (dry weight), substrate consumption, the concentration of crude biosurfactant and the emulsifying activity. The highest concentration of biosurfactant was 0.34 g/l at 48 h. The residual glycerol concentration was 21 g/l after 96 hours. The crude biosurfactant solution at 1mg/ml showed the emulsifying activity of 28 % (±5) against diesel fuel. Results indicated that biosurfactant production correlated well with exponential cell growth. However, after 96 h of incubation, the biosurfactant concentration decreased to 0.19 g/l. The glycerol was a carbon source that allowed the biosurfactant production. However, the effects of metabolites produced in the glycerol medium must be identified to optimize the biosurfactant production on large scale. The low-cost substrate and the efficient downstream processing of biosurfactant can contribute to the environmental application.
The Backlift Technique among South African Cricket Players
This study primarily aimed to investigate the batting backlift technique (BBT) among semi-professional, professional and current international cricket players. A key question was to investigate if the lateral batting backlift technique (LBBT) is more common at the highest levels of the game. The participants in this study sample (n = 130) were South African semi-professional players (SP) (n = 69) and professional players (P) (n = 49) and South African international professional players (SAI) (n = 12). Biomechanical and video analysis were performed on all participant groups. Classifiers were utilised to identify the batting backlift technique type (BBTT) employed by all batsmen. All statistics and wagon wheels (scoring areas of the batsmen on a cricket field) were sourced online. This study found that a LBBT is more common at the highest levels of cricket batsmanship with batsmen at the various levels of cricket having percentages of the LBBT as follows: SP = 37.7%; P = 38.8%; SAI = 75%; p = 0.001. This study also found that SAI batsmen who used the LBBT were more proficient at scoring runs in various areas around the cricket field (according to the wagon wheel analysis). This study found that a LBBT is more common at the highest levels of cricket batsmanship. Cricket coaches should also pay attention to the direction of the backlift with players, especially when correlating the backlift to various scoring areas on the cricket field. Further in-depth research is required to fully investigate the change in batting backlift techniques among cricket players over a long-term period.
Understanding Nanocarrier Efficacy in Drug Delivery Systems Using Molecular Dynamic
Introduction: The intensive labor and high cost of developing new vehicles for controlled drug delivery highlights the need for a change in their discovery process. Computational models can be used to accelerate experimental steps and control the high cost of experiments. Methods: In this work, to better understand the interaction of anti-cancer drug and the nanocarrier with the cell membrane, we have done molecular dynamics simulation using NAMD. We have chosen paclitaxel for the drug molecule and dipalmitoylphosphatidylcholine (DPPC) as a natural phospholipid nanocarrier. Results: Next, center of mass (COM) between molecules and the van der Waals interaction energy close to the cell membrane has been analyzed. Furthermore, the simulation results of the paclitaxel interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane have been compared. Discussion: Analysis by molecular dynamics (MD) showed that not only the energy between the nanocarrier and the cell membrane is low, but also the center of mass amount decreases in the nanocarrier and the cell membrane system during the interaction; therefore they show significantly better interaction in comparison to the individual drug with the cell membrane.
First Experimental Evidence on Feasibility of Molecular Magnetic Particle Imaging of Tumor Marker Alpha-1-Fetoprotein Using Antibody Conjugated Nanoparticles
Purpose: The purpose of this work is to examine possibilities for noninvasive imaging and identification of tumor markers for cancer diagnosis. The proposed method uses antibody conjugated iron oxide nanoparticles and multicolor Magnetic Particle Imaging (mMPI). The method has the potential for radiation exposure free real-time estimation of local tumor marker concentrations in vivo. In this study, the method is applied to human Alpha-1-Fetoprotein. Materials and Methods: As tracer material AFP antibody-conjugated Dendrimer-Fe3O4 nanoparticles were used. The nanoparticle bioconjugates were then incubated with bovine serum albumin (BSA) to block any possible nonspecific binding sites. Parts of the resulting solution were then incubated with AFP antigen. MPI measurements were done using the preclinical MPI scanner (Bruker Biospin MRI GmbH) and the multicolor method was used for image reconstruction. Results: In multicolor MPI images the nanoparticles incubated only with BSA were clearly distinguished from nanoparticles incubated with BSA and AFP antigens. Conclusion: Tomographic imaging of human tumor marker Alpha-1-Fetoprotein is possible using AFP antibody conjugated iron oxide nanoparticles in presence of BSA. This opens interesting perspectives for cancer diagnosis.
Comparison of Breast Surface Doses for Full-Field Digital Mammography and Digital Breast Tomosynthesis Using Breast Phantoms
Background: Full field digital mammography (FFDM) is widely used in diagnosis of breast cancer. Digital breast tomosynthesis (DBT) has recently been introduced into the clinic and is being used for screening for breast cancer in the general population. Hence, the radiation dose delivered to the patients involved in an imaging protocol is of utmost concern. Aim: To compare the surface radiation dose (ESD) of digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) by using breast phantoms. Method: We analyzed the average entrance surface dose (ESD) of FFDM and DBT by using breast phantoms. Optically Stimulated luminescent Dosimeters (OSLD) were placed in a tissue-equivalent Breast phantom at difference sites of interest. Absorbed dose measurements were obtained after digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) exposures.
Results: An automatic exposure control (AEC) is proposed for surface dose measurement during DBT and FFDM. The mean ESD values for DBT and FFDM were 6.37 mGy and 3.51mGy, respectively. Using of OSLD measured for surface dose during DBT and FFDM. There were 19.87 mGy and 11.36 mGy, respectively. The surface exposure dose of DBT could possibly be increased by two times with FFDM. Conclusion: The radiation dose from DBT was higher than that of FFDM and the difference in dose between AEC and OSLD measurements at phantom surface.
Flexible and Color Tunable Inorganic Light Emitting Diode Array for High Resolution Optogenetic Devices
Light emitting diode (LED) array is an ideal optical stimulation tool for optogenetics, which controls inhibition and excitation of specific neurons with light-sensitive ion channels or pumps. Although a ﬁber-optic cable with an external light source, either a laser or LED mechanically connected to the end of the ﬁber-optic cable has widely been used for illumination on neural tissue, a new approach to use micro LEDs (µLEDs) has recently been demonstrated. The LEDs can be placed directly either on the cortical surface or within the deep brain using a penetrating depth probe. Accordingly, this method would not need a permanent opening in the skull if the LEDs are integrated with miniature electrical power source and wireless communication. In addition, multiple color generation from single µLED cell would enable to excite and/or inhibit neurons in localized regions. Here, we demonstrate flexible and color tunable µLEDs for the optogenetic device applications. The flexible and color tunable LEDs was fabricated using multifaceted gallium nitride (GaN) nanorod arrays with GaN nanorods grown on InxGa1−xN/GaN single quantum well structures (SQW) anisotropically formed on the nanorod tips and sidewalls. For various electroluminescence (EL) colors, current injection paths were controlled through a continuous p-GaN layer depending on the applied bias voltage. The electric current was injected through different thickness and composition, thus changing the color of light from red to blue that the LED emits. We believe that the flexible and color tunable µLEDs enable us to control activities of the neuron by emitting various colors from the single µLED cell.
Evaluation of Random Forest and SVM Classification Performance for the Prediction of Early Multiple Sclerosis from Resting State FMRI Connectivity Data
The work aim was to evaluate how well Random Forest (RF) and Support Vector Machine (SVM) algorithms could support the early diagnosis of Multiple Sclerosis (MS) from resting-state functional connectivity data. In particular, we wanted to explore the ability in distinguishing between controls and patients of mean signals extracted from ICA components corresponding to 15 well-known networks. Eighteen patients with early-MS (mean-age 37.42±8.11, 9 females) were recruited according to McDonald and Polman, and matched for demographic variables with 19 healthy controls (mean-age 37.55±14.76, 10 females). MRI were acquired by a 3T scanner with 8-channel head coil: (a)whole-brain T1-weighted; (b)conventional T2-weighted; (c)resting-state functional MRI (rsFMRI), 200 volumes. Estimated total lesion load (ml) and number of lesions were calculated using LST-toolbox from the corrected T1 and FLAIR. All rsFMRI were pre-processed using tools from the FMRIB's Software Library as follows: (1)discarding of the first 5 volumes to remove T1 equilibrium effects, (2)skull-stripping of images, (3)motion and slice-time correction, (4)denoising with high-pass temporal filter (128s), (5)spatial smoothing with a Gaussian kernel of FWHM 8mm. No statistical significant differences (t-test, p < 0.05) were found between the two groups in the mean Euclidian distance and the mean Euler angle. WM and CSF signal together with 6 motion parameters were regressed out from the time series. We applied an independent component analysis (ICA) with the GIFT-toolbox using the Infomax approach with number of components=21. Fifteen mean components were visually identified by two experts. The resulting z-score maps were thresholded and binarized to extract the mean signal of the 15 networks for each subject. Statistical and machine learning analysis were then conducted on this dataset composed of 37 rows (subjects) and 15 features (mean signal in the network) with R language. The dataset was randomly splitted into training (75%) and test sets and two different classifiers were trained: RF and RBF-SVM. We used the intrinsic feature selection of RF, based on the Gini index, and recursive feature elimination (rfe) for the SVM, to obtain a rank of the most predictive variables. Thus, we built two new classifiers only on the most important features and we evaluated the accuracies (with and without feature selection) on test-set. The classifiers, trained on all the features, showed very poor accuracies on training (RF:58.62%, SVM:65.52%) and test sets (RF:62.5%, SVM:50%). Interestingly, when feature selection by RF and rfe-SVM were performed, the most important variable was the sensori-motor network I in both cases. Indeed, with only this network, RF and SVM classifiers reached an accuracy of 87.5% on test-set. More interestingly, the only misclassified patient resulted to have the lowest value of lesion volume. We showed that, with two different classification algorithms and feature selection approaches, the best discriminant network between controls and early MS, was the sensori-motor I. Similar importance values were obtained for the sensori-motor II, cerebellum and working memory networks. These findings, in according to the early manifestation of motor/sensorial deficits in MS, could represent an encouraging step toward the translation to the clinical diagnosis and prognosis.
Improving the Optoacoustic Signal by Monitoring the Changes of Coupling Medium
In this report, we discussed the coupling medium in the optoacoustic imaging. The coupling medium is placed between the scanned object and the ultrasound transducers. Water with varying temperature was used as the coupling medium. The water temperature is gradually varied between 25 to 40 degrees. This heating process is taken with care in order to avoid the bubble formation. Rise in the photoacoustic signal is noted through an unfocused transducer with frequency of 2.25MHz as the temperature increases. The temperature rise is monitored using a NTC thermistor and the values in degrees are calculated using an embedded evaluation kit. Also the temperature is transmitted to PC through a serial communication. All these process are synchronized using a trigger signal from the laser source.
[Keynote Speech]: Simulation Studies of Pulsed Voltage Effects on Cells
In order to predict or explain a complicated biological process, it is important first to construct mathematical models that can be used to yield analytical solutions. Through numerical simulation, mathematical model results can be used to test scenarios that might not be easily attained in a laboratory experiment, or to predict parameters or phenomena. High-intensity, nanosecond pulse electroporation has been a recent development in bioelectrics. The dynamic pore model can be achieved by including a dynamic aspect and a dependence on the pore population density into pore formation energy equation to analyze and predict such electroporation effects. For greater accuracy, with inclusion of atomistic details, molecular dynamics (MD) simulations were also carried out during this study. Besides inducing pores in cells, external voltages could also be used in principle to modulate action potential generation in nerves. This could have an application in electrically controlled ‘pain management’. Also a simple model-based rate equation treatment of the various cellular bio-chemical processes has been used to predict the pulse number dependent cell survival trends.
Retina Registration for Biometrics Based on Characterization of Retinal Feature Points
The unique structure of the blood vessels in the retina has been used for biometric identification. The retina blood vessel pattern is a unique pattern in each individual and it is almost impossible to forge that pattern in a false individual. The retina biometrics’ advantages include high distinctiveness, universality, and stability overtime of the blood vessel pattern. Once the creases have been extracted from the images, a registration stage is necessary, since the position of the retinal vessel structure could change between acquisitions due to the movements of the eye. Image registration consists of following steps: Feature detection, feature matching, transform model estimation and image resembling and transformation. In this paper, we present an algorithm of registration; it is based on the characterization of retinal feature points. For experiments, retinal images from the DRIVE database have been tested. The proposed methodology achieves good results for registration in general.
Radio-Guided Surgery with β− Radiation: Test on Ex-Vivo Specimens
Elena Solfaroli Camillocci
, Riccardo Faccini
, Silvio Morganti
, Carlo Mancini Terracciano
, Francesco Collamati
, Andrea Russomando
, Valerio Bocci
, Luigi Recchia
, Chiara Maria Grana
, Marco Schiariti
, P. Ferroli
, Marta Cremonesi
, M. E. Ferrari
, F. Ghielmetti
, Michela Marafini
, G. Pedroli
, Giacomo Traini
, Marco Toppi
, A. Carollo
, M. Colandrea
, M. Patane
, B. Pollo
A Radio-Guided Surgery technique exploiting β− emitting radio-tracers has been suggested to overcome the impact of the large penetration of γ radiation. The detection of electrons in low radiation background provides a clearer delineation of the margins of lesioned tissues. As a start, the clinical cases were selected between the tumors known to express receptors to a β− emitting radio-tracer: 90Y-labelled DOTATOC. The results of tests on ex-vivo specimens of meningioma brain tumor and abdominal neuroendocrine tumors are presented. Voluntary patients were enrolled according to the standard uptake value (SUV > 2 g/ml) and the expected tumor-to-non-tumor ratios (TNR∼10) estimated from PET images after administration of 68Ga-DOTATOC. All these tests validated this technique yielding a significant signal on the bulk tumor and a negligible background from the nearby healthy tissue. Even injecting as low as 1.4 MBq/kg of radiotracer, tumor remnants of 0.1 ml would be detectable. The negligible medical staff exposure was confirmed and among the biological wastes only urine had a significant activity.
Assessment of the High-Speed Ice Friction of Bob Skeleton Runners
Bob skeleton is a Winter Olympic sport, in which an athlete slides head first down an icy track reaching speeds of up to 40 m/s. The race times of the top five athletes in international competitions often vary by less than one second after four descents. The two steel cylindrical cross section runners are the only part of the sled in contact with the ice. The runners are manufactured from a specific grade of steel, supplied and monitored by the International Bobsleigh and Skeleton Federation. There are a variety of runner designs available on the market, and their selection will depend on environmental conditions and the ability of the athlete. The friction between the runners and ice corresponds to around 40% of the total energy loss during a descent. A small modification to the runner design or its setup may have a significant effect on the performance of the athlete. There is only limited experimental data regarding the friction of bob skeleton runners or indeed steel on ice at high sliding speeds ( > 20 m/s). The aim of the work presented is to assess the possible runner friction testing methods and to compare and contrast results available from published sources, field testing, pin-on-disk and a novel linear ice tribometer developed for testing skis. We will consider the physics of the ice-steel interaction, and the methods of assessing the runner setup and measuring the friction of bob skeleton runners on ice are compared. The effects of sliding speed and load on the coefficient of friction are presented and likely errors and repeatability discussed.
Sensing of Cancer DNA Using Resonance Frequency
Lung cancer is one of the most common severe diseases driving to the death of a human. Lung cancer can be divided into two cases of small-cell lung cancer (SCLC) and non-SCLC (NSCLC), and about 80% of lung cancers belong to the case of NSCLC. From several studies, the correlation between epidermal growth factor receptor (EGFR) and NSCLCs has been investigated. Therefore, EGFR inhibitor drugs such as gefitinib and erlotinib have been used as lung cancer treatments. However, the treatments result showed low response (10~20%) in clinical trials due to EGFR mutations that cause the drug resistance. Patients with resistance to EGFR inhibitor drugs usually are positive to KRAS mutation. Therefore, assessment of EGFR and KRAS mutation is essential for target therapies of NSCLC patient. In order to overcome the limitation of conventional therapies, overall EGFR and KRAS mutations have to be monitored. In this work, the only detection of EGFR will be presented. A variety of techniques has been presented for the detection of EGFR mutations. The standard detection method of EGFR mutation in ctDNA relies on real-time polymerase chain reaction (PCR). Real-time PCR method provides high sensitive detection performance. However, as the amplification step increases cost effect and complexity increase as well. Other types of technology such as BEAMing, next generation sequencing (NGS), an electrochemical sensor and silicon nanowire field-effect transistor have been presented. However, those technologies have limitations of low sensitivity, high cost and complexity of data analyzation. In this report, we propose a label-free and high-sensitive detection method of lung cancer using quartz crystal microbalance based platform. The proposed platform is able to sense lung cancer mutant DNA with a limit of detection of 1nM.
An Inverse Heat Transfer Algorithm for Predicting the Thermal Properties of Tumors during Cryosurgery
This study aimed at developing an inverse heat transfer approach for predicting the time-varying freezing front and the temperature distribution of tumors during cryosurgery. Using a temperature probe pressed against the layer of tumor, the inverse approach is able to predict simultaneously the metabolic heat generation and the blood perfusion rate of the tumor. Once these parameters are predicted, the temperature-field and time-varying freezing fronts are determined with the direct model. The direct model rests on 1D Pennes bioheat equation. The phase change problem is handled with the enthalpy method. The Levenberg-Marquardt Method (LMM) combined to the Broyden Method (BM) is used to solve the inverse model. The effect (a) of the thermal properties of the diseased tissues; (b) of the initial guesses for the unknown thermal properties; (c) of the data capture frequency; and (d) of the noise on the recorded temperatures is examined. It is shown that the proposed inverse approach remains accurate for all the cases investigated.
Electromyography Analysis during Walking and Seated Stepping in the Elderly
The number of the elderly in the world population and the rate of falls in this increasing numbers of older people are increasing. Decreasing muscle strength and an increasing risk of falling are associated with the ageing process. Because the effects of seated stepping training on the walking performance in the elderly remain unclear, the main purpose of the proposed study is to perform electromyography analysis during walking and seated stepping in the elderly. Four surface EMG electrodes were sticked on the surface of lower limbs muscles, including vastus lateralis (VL), and gastrocnemius (GT) of both sides. Before test, maximal voluntary contraction (MVC) of the respective muscle was obtained using manual muscle testing. The analog raw data of EMG signals were digitized with a sampling frequency of 2000 Hz. The signals were fully rectified and the linear envelope were calculated. Stepping motion cycle was separated into two phases by stepping timing (ST) and pedal return timing (PRT). ST refer to the time when the pedal marker reached the highest height, representing the contra-lateral leg was going to release the pedal. PRT refer to the time when the pedal marker reached the lowest height, representing the contra-lateral leg was going to step the pedal. We assumed that ST acted the same role in initial contact during walking, and PRT for toe-off. The period from ST to next PRT was called pushing phase (PP), during which the leg would start to step with resistance, and we compare this phase with the stance phase in level walking. The period from PRT to next ST was called returning phase (RP), during which leg would not have any resistance in this phase, and we compare this phase with the swing phase in level walking. VL and Gastro muscular activation had similar patterns in both side. The ability may transfer to those needed during loading response, mid-stance and terminal swing phase. User needed to make more effort in stepping compared with walking with similar timing; thus the strengthening of the VL and Gastro may be helpful to improve the walking endurance and efficiency for the elderly.
The Monitor for Neutron Dose in Hadrontherapy Project: Secondary Neutron Measurement in Particle Therapy
The particle therapy (PT) is a very modern technique of non invasive radiotherapy mainly devoted to the treatment of tumours untreatable with surgery or conventional radiotherapy, because localised closely to organ at risk (OaR). Nowadays, PT is available in about 55 centres in the word and only the 20\% of them are able to treat with carbon ion beam. However, the efficiency of the ion-beam treatments is so impressive that many new centres are in construction. The interest in this powerful technology lies to the main characteristic of PT: the high irradiation precision and conformity of the dose released to the tumour with the simultaneous preservation of the adjacent healthy tissue. However, the beam interactions with the patient produce a large component of secondary particles whose additional dose has to be taken into account during the definition of the treatment planning. Despite, the largest fraction of the dose is released to the tumour volume, a non-negligible amount is deposed in other body regions, mainly due to the scattering and nuclear interactions of the neutrons within the patient body. One of the main concerns in PT treatments is the possible occurrence of secondary malignant neoplasm (SMN). While SMNs can be developed up to decades after the treatments, their incidence impacts directly life quality of the cancer survivors, in particular in pediatric patients. Dedicated Treatment Planning Systems (TPS) are used to predict the normal tissue toxicity including the risk of late complications induced by the additional dose released by secondary neutrons. However, no precise measurement of secondary neutrons flux is available, as well as their energy and angular distributions: an accurate characterization is needed in order to improve TPS and reduce safety margins. The project MONDO (MOnitor for Neutron Dose in hadrOntherapy) is devoted to the construction of a secondary neutron tracker tailored to the characterization of that secondary neutron component. The detector, based on the tracking of the recoil protons produced in double-elastic scattering interactions, is a matrix of thin scintillating fibres, arranged in layer x-y oriented. The final size of the object is 10 x 10 x 20 cm3 (squared 250µm scint. fibres, double cladding). The readout of the fibres is carried out with a dedicated SPAD Array Sensor (SBAM) realised in CMOS technology by FBK (Fondazione Bruno Kessler). The detector is under development as well as the SBAM sensor and it is expected to be fully constructed for the end of the year. MONDO will make data tacking campaigns at the TIFPA Proton Therapy Center of Trento, at the CNAO (Pavia) and at HIT (Heidelberg) with carbon ion in order to characterize the neutron component and predict the additional dose delivered on the patients with much more precision and to drastically reduce the actual safety margins. Preliminary measurements with charged particles beams and MonteCarlo FLUKA simulation will be presented.
Dose Profiler: A Tracking Device for Online Range Monitoring in Particle Therapy
, F. Collamati
, E. De Lucia
, R. Faccini
, C. Mancini-Terracciano
, M. Marafini
, I. Mattei
, S. Muraro
, V. Patera
, A. Sarti
, A. Sciubba
, E. Solfaroli Camillocci
, M. Toppi
, G. Traini
, S. M. Valle
, C. Voena
Accelerated charged particles, mainly protons and carbon ions, are presently used in Particle Therapy (PT) to treat solid tumors. The precision of PT exploiting the charged particle high localized dose deposition in tissues and biological effectiveness in killing cancer cells demands for an online dose monitoring technique, crucial to improve the quality assurance of treatments: possible patient mis-positionings and biological changes with respect to the CT scan could negatively affect the therapy outcome. In PT the beam range confined in the irradiated target can be monitored thanks to the secondary radiation produced by the interaction of the projectiles with the patient tissue. The Dose Profiler (DP) is a novel device designed to track charged secondary particles and reconstruct their longitudinal emission distribution, correlated to the Bragg peak position. The feasibility of this approach has been demonstrated by dedicated experimental measurements. The DP has been developed in the framework of the INSIDE project, MIUR, INFN and Centro Fermi, Museo Storico della Fisica e Centro Studi e Ricerche 'E. Fermi', Roma, Italy and will be tested at the Proton Therapy center of Trento (Italy) within the end of 2017. The DP combines a tracker, made of six layers of two-view scintillating fibers with square cross section (0.5 x 0.5 mm2) with two layers of two-view scintillating bars (section 12.0 x 0.6 mm2). The electronic readout is performed by silicon photomultipliers. The sensitive area of the tracking planes is 20 x 20 cm2. To optimize the detector layout, a Monte Carlo (MC) simulation based on the FLUKA code has been developed. The complete DP geometry and the track reconstruction code have been fully implemented in the MC. In this contribution, the DP hardware will be described. The expected detector performance computed using a dedicated simulation of a 220 MeV/u carbon ion beam impinging on a PMMA target will be presented, and the result will be discussed in the standard clinical application framework. A possible procedure for real-time beam range monitoring is proposed, following the expectations in actual clinical operation.
Influence of Coenzyme as a Corrosion Barrier for Biodegradable Magnesium
Magnesium is an essential element in human body and has unique characteristics such as bioabsorbable and biodegradable properties. Therefore, there has been much attention on studies on the implants based on magnesium to avoid subsequent surgery. However, high amount of hydrogen gas is generated by relatively severe corrosion of magnesium especially in aqueous condition with chloride ions. And it contributes to the causes of swelling of skin and causes consequent inflammation of soft tissue where is directly in contact with implants. Therefore, there is still concern about the safety of the using biodegradable magnesium alloys, which is limited to various applications. In this study, we analyzed the influence of coenzyme on corrosion behavior of magnesium. The analysis of corrosion rate was held by using Hanks’ balanced salt solution (HBSS) as a body stimulated fluid and in condition of 37°C. Thus, with deferring the concentration of the coenzyme used in this study, corrosion rates from 0.0654ml/ cm² to 0.0438ml/cm² were observed in immersion tests. Also, comparable results were obtained in electrochemical tests. Results showed that hydrogen gas produced from corrosion of magnesium can be controlled.
Probing Mechanical Mechanism of Three-Hinge Formation on a Growing Brain: A Numerical and Experimental Study
Cortical folding, characterized by convex gyri and concave sulci, has an intrinsic relationship to the brain’s functional organization. Understanding the mechanism of the brain’s convoluted patterns can provide useful clues into normal and pathological brain function. During the development, the cerebral cortex experiences a noticeable expansion in volume and surface area accompanied by tremendous tissue folding which may be attributed to many possible factors. Despite decades of endeavors, the fundamental mechanism and key regulators of this crucial process remain incompletely understood. Therefore, to taking even a small role in unraveling of brain folding mystery, we present a mechanical model to find mechanism of 3-hinges formation in a growing brain that it has not been addressed before. A 3-hinge is defined as a gyral region where three gyral crests (hinge-lines) join. The reasons that how and why brain prefers to develop 3-hinges have not been answered very well. Therefore, we offer a theoretical and computational explanation to mechanism of 3-hinges formation in a growing brain and validate it by experimental observations. In theoretical approach, the dynamic behavior of brain tissue is examined and described with the aid of a large strain and nonlinear constitutive model. Derived constitute model is used in the computational model to define material behavior. Since the theoretical approach cannot predict the evolution of cortical complex convolution after instability, non-linear finite element models are employed to study the 3-hinges formation and secondary morphological folds of the developing brain. Three-dimensional (3D) finite element analyses on a multi-layer soft tissue model which mimics a small piece of the brain are performed to investigate the fundamental mechanism of consistent hinge formation in the cortical folding. Results show that after certain amount growth of cortex, mechanical model starts to be unstable and then by formation of creases enters to a new configuration with lower strain energy. By further growth of the model, formed shallow creases start to form convoluted patterns and then develop 3-hinge patterns. Simulation results related to 3-hinges in models show good agreement with experimental observations from macaque, chimpanzee and human brain images. These results have great potential to reveal fundamental principles of brain architecture and to produce a unified theoretical framework that convincingly explains the intrinsic relationship between cortical folding and 3-hinges formation. This achieved fundamental understanding of the intrinsic relationship between cortical folding and 3-hinges formation would potentially shed new insights into the diagnosis of many brain disorders such as schizophrenia, autism, lissencephaly and polymicrogyria.