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Computational Methods For The Diagnosis of Rheumatoid Arthritis With Diffuse Optical Tomography
Diffuse optical tomography (DOT) is an imaging technique where near infrared (NIR) photons are used to probe biological tissue. DOT allows for the recovery of three-dimensional maps of tissue optical properties, such as tissue absorption and scattering coefficients. The application of DOT as a tool to aid in the diagnosis of rheumatoid arthritis (RA) is explored in this work. Algorithms for improving the image reconstruction process and for enhancing the clinical value of DOT images are presented in detail. The clinical data considered in this work consists of 99 fingers from subjects with RA and 120 fingers from healthy subjects. DOT scans of the proximal interphalangeal (PIP) joint of each finger is performed with modulation frequencies of 0, 300, and 600 MHz.
A computer-aided diagnosis (CAD) framework for extracting heuristic features from DOT images and a method for using these same features to classify each joint as affected or not affected by RA is presented. The framework is applied to the clinical data and results are discussed in detail. Then, an algorithm for recovering the optical properties of biological media using the simplified spherical harmonics (SPN) light propagation model is presented. The computational performance of the algorithm is analyzed and reported. Finally, the SPN reconstruction algorithm is applied to clinical data of subjects with RA and the resulting images are analyzed with the CAD framework.
As the first part of the CAD framework, heuristic image features are extracted from the absorption and the scattering coefficient images using multiple compression and dimensionality reduction techniques. Overall, 594 features are extracted from the images of each joint. Then, machine-learning techniques are used to evaluate the ability to discriminate between images of joints with RA and images of healthy joints. An evolution-strategy optimization algorithm is developed to evaluate the classification strength of each feature and to find the multidimensional feature combination that results in optimal classification accuracy. Classification is performed with k-nearest neighbors (KNN), linear (LDA) and quadratic discriminate analysis (QDA), self-organizing maps (SOM), or support vector machines (SVM). Classification accuracy is evaluated based on diagnostic sensitivity and specificity values.
Strong evidence is presented that suggest there are clear differences between the tissue optical parameters of joints with RA and joints without RA. It is first shown that data obtained at 600 MHz leads to better classification results than data obtained at 300 and 0 MHz. Analysis of each extracted feature shows that DOT images of subjects with RA are statistically different (p < 0.05) from images of subjects without RA for over 90% of the features. Evidence shows that subjects with RA that do not have detectable signs of erosion, effusion, or synovitis (i.e. asymptomatic subjects) in MRI and US images have optical profiles similar to subjects who do have signs of erosion, effusion, or synovitis; furthermore, both of these cohorts differ from healthy controls subjects. This shows that it may be possible to accurately identify asymptomatic subjects with DOT scans. In contrast, these subjects remain difficult to identify from MRI and US images. The implications of these results are profound, as they suggest it may be possible to identify RA with DOT at an earlier stage compared to standard imaging techniques.
Results from the feature-selection algorithm show that the SVM algorithm (with a third order polynomial kernel) achieves 100.0% sensitivity and 97.8% specificity. Lower bounds for these results (at 95.0% confidence level) are 96.4% and 93.8%, respectively. Image features most predictive of RA are from the spatial variation of optical properties and the absolute range in feature values. The optimal classifiers are low dimensional combinations (< 7 features). Robust cross- validation is performed to ensure the generalization of these classification results.
The SPN -based reconstruction algorithm uses a reduced-Hessian sequential quadratic programming (rSQP) PDE-constrained optimization approach to maximize computational efficiency. The complex-valued forward model, or frequency domain SPN equations (N = 1, 3), is discretized using the finite-volume method and solved on unstructured computational grids using the restarted GMRES algorithm. The image reconstruction algorithm is presented in detail and its performance benchmarked against the ERT algorithm. The algorithm is subsequently used to recover the absorption and scattering coefficient images of joints scanned in the RA clinical study.
While the SPN model is inherently less accurate than the ERT model, it is nevertheless shown that the images obtained with the SP3-based reconstruction algorithm are sufficiently accurate and allow for the diagnosis of RA at clinically relevant sensitivity [87.9% (78.1%, 100.0%)] and specificity [92.9% (84.6%, 100.0%)] values (the 95.0% confidence interval is specified in brackets). In contrast to results obtained with the SP3 model, the images generated with the SP1 algorithm yield significantly lower sensitivity [66.7% (46.6%, 100.0%)] and specificity [81.0% (64.8%, 100.0%)] values. While some numerical accuracy is sacrificed by selecting the SP3 model over the ERT model, the superior computational performance of the SP3 algorithm allows for computation of the absorption and the scattering coefficient images in under 15 minutes and requires less than 200 MB of RAM per finger (compared to the over 180 minutes and over 6 GB of RAM needed by the ERT-based algorithm).
Overall, results indicate that the SP3-based reconstruction algorithm provides computational advantages over the ERT-based algorithm without sacrificing significant classification accuracy. In contrast, the SP1 model provides computational advantages compared to the ERT at the expense of classification accuracy. This indicates that the frequency-domain SP3 model is an ideal light propagation model for use in DOT scanning of finger joints with RA.
Altogether, the results presented in this dissertation underscore the high potential for DOT to become a clinically useful diagnostic tool. The algorithms and framework developed as part of this dissertation can be directly used on future data to help further validate the hypotheses presented in this work and to further establish DOT imaging as a valuable diagnostic tool
Shortest Route at Dynamic Location with Node Combination-Dijkstra Algorithm
Abstract— Online transportation has become a basic
requirement of the general public in support of all activities to go
to work, school or vacation to the sights. Public transportation
services compete to provide the best service so that consumers
feel comfortable using the services offered, so that all activities
are noticed, one of them is the search for the shortest route in
picking the buyer or delivering to the destination. Node
Combination method can minimize memory usage and this
methode is more optimal when compared to A* and Ant Colony
in the shortest route search like Dijkstra algorithm, but can’t
store the history node that has been passed. Therefore, using
node combination algorithm is very good in searching the
shortest distance is not the shortest route. This paper is
structured to modify the node combination algorithm to solve the
problem of finding the shortest route at the dynamic location
obtained from the transport fleet by displaying the nodes that
have the shortest distance and will be implemented in the
geographic information system in the form of map to facilitate
the use of the system.
Keywords— Shortest Path, Algorithm Dijkstra, Node
Combination, Dynamic Location (key words
Removal of antagonistic spindle forces can rescue metaphase spindle length and reduce chromosome segregation defects
Regular Abstracts - Tuesday Poster Presentations: no. 1925Metaphase describes a phase of mitosis where chromosomes are attached and oriented on the bipolar spindle for subsequent segregation at anaphase. In diverse cell types, the metaphase spindle is maintained at a relatively constant length. Metaphase spindle length is proposed to be regulated by a balance of pushing and pulling forces generated by distinct sets of spindle microtubules and their interactions with motors and microtubule-associated proteins (MAPs). Spindle length appears important for chromosome segregation fidelity, as cells with shorter or longer than normal metaphase spindles, generated through deletion or inhibition of individual mitotic motors or MAPs, showed chromosome segregation defects. To test the force balance model of spindle length control and its effect on chromosome segregation, we applied fast microfluidic temperature-control with live-cell imaging to monitor the effect of switching off different combinations of antagonistic forces in the fission yeast metaphase spindle. We show that spindle midzone proteins kinesin-5 cut7p and microtubule bundler ase1p contribute to outward pushing forces, and spindle kinetochore proteins kinesin-8 klp5/6p and dam1p contribute to inward pulling forces. Removing these proteins individually led to aberrant metaphase spindle length and chromosome segregation defects. Removing these proteins in antagonistic combination rescued the defective spindle length and, in some combinations, also partially rescued chromosome segregation defects. Our results stress the importance of proper chromosome-to-microtubule attachment over spindle length regulation for proper chromosome segregation.postprin
Psr1p interacts with SUN/sad1p and EB1/mal3p to establish the bipolar spindle
Regular Abstracts - Sunday Poster Presentations: no. 382During mitosis, interpolar microtubules from two spindle pole bodies (SPBs) interdigitate to create an antiparallel microtubule array for accommodating numerous regulatory proteins. Among these proteins, the kinesin-5 cut7p/Eg5 is the key player responsible for sliding apart antiparallel microtubules and thus helps in establishing the bipolar spindle. At the onset of mitosis, two SPBs are adjacent to one another with most microtubules running nearly parallel toward the nuclear envelope, creating an unfavorable microtubule configuration for the kinesin-5 kinesins. Therefore, how the cell organizes the antiparallel microtubule array in the first place at mitotic onset remains enigmatic. Here, we show that a novel protein psrp1p localizes to the SPB and plays a key role in organizing the antiparallel microtubule array. The absence of psr1+ leads to a transient monopolar spindle and massive chromosome loss. Further functional characterization demonstrates that psr1p is recruited to the SPB through interaction with the conserved SUN protein sad1p and that psr1p physically interacts with the conserved microtubule plus tip protein mal3p/EB1. These results suggest a model that psr1p serves as a linking protein between sad1p/SUN and mal3p/EB1 to allow microtubule plus ends to be coupled to the SPBs for organization of an antiparallel microtubule array. Thus, we conclude that psr1p is involved in organizing the antiparallel microtubule array in the first place at mitosis onset by interaction with SUN/sad1p and EB1/mal3p, thereby establishing the bipolar spindle.postprin