Matching Items (59)

128661-Thumbnail Image.png

Simulation and Experimental Characterization of Microscopically Accessible Hydrodynamic Microvortices

Description

Single-cell studies of phenotypic heterogeneity reveal more information about pathogenic processes than conventional bulk-cell analysis methods. By enabling high-resolution structural and functional imaging, a single-cell three-dimensional (3D) imaging system can

Single-cell studies of phenotypic heterogeneity reveal more information about pathogenic processes than conventional bulk-cell analysis methods. By enabling high-resolution structural and functional imaging, a single-cell three-dimensional (3D) imaging system can be used to study basic biological processes and to diagnose diseases such as cancer at an early stage. One mechanism that such systems apply to accomplish 3D imaging is rotation of a single cell about a fixed axis. However, many cell rotation mechanisms require intricate and tedious microfabrication, or fail to provide a suitable environment for living cells. To address these and related challenges, we applied numerical simulation methods to design new microfluidic chambers capable of generating fluidic microvortices to rotate suspended cells. We then compared several microfluidic chip designs experimentally in terms of: (1) their ability to rotate biological cells in a stable and precise manner; and (2) their suitability, from a geometric standpoint, for microscopic cell imaging. We selected a design that incorporates a trapezoidal side chamber connected to a main flow channel because it provided well-controlled circulation and met imaging requirements. Micro particle-image velocimetry (micro-PIV) was used to provide a detailed characterization of flows in the new design. Simulated and experimental results demonstrate that a trapezoidal side chamber represents a viable option for accomplishing controlled single cell rotation. Further, agreement between experimental and simulated results confirms that numerical simulation is an effective method for chamber design.

Contributors

Agent

Created

Date Created
  • 2012-06-15

128818-Thumbnail Image.png

Multi-Parametric MRI and Texture Analysis to Visualize Spatial Histologic Heterogeneity and Tumor Extent in Glioblastoma

Description

Background
Genetic profiling represents the future of neuro-oncology but suffers from inadequate biopsies in heterogeneous tumors like Glioblastoma (GBM). Contrast-enhanced MRI (CE-MRI) targets enhancing core (ENH) but yields adequate tumor

Background
Genetic profiling represents the future of neuro-oncology but suffers from inadequate biopsies in heterogeneous tumors like Glioblastoma (GBM). Contrast-enhanced MRI (CE-MRI) targets enhancing core (ENH) but yields adequate tumor in only ~60% of cases. Further, CE-MRI poorly localizes infiltrative tumor within surrounding non-enhancing parenchyma, or brain-around-tumor (BAT), despite the importance of characterizing this tumor segment, which universally recurs. In this study, we use multiple texture analysis and machine learning (ML) algorithms to analyze multi-parametric MRI, and produce new images indicating tumor-rich targets in GBM.
Methods
We recruited primary GBM patients undergoing image-guided biopsies and acquired pre-operative MRI: CE-MRI, Dynamic-Susceptibility-weighted-Contrast-enhanced-MRI, and Diffusion Tensor Imaging. Following image coregistration and region of interest placement at biopsy locations, we compared MRI metrics and regional texture with histologic diagnoses of high- vs low-tumor content (≥80% vs <80% tumor nuclei) for corresponding samples. In a training set, we used three texture analysis algorithms and three ML methods to identify MRI-texture features that optimized model accuracy to distinguish tumor content. We confirmed model accuracy in a separate validation set.
Results
We collected 82 biopsies from 18 GBMs throughout ENH and BAT. The MRI-based model achieved 85% cross-validated accuracy to diagnose high- vs low-tumor in the training set (60 biopsies, 11 patients). The model achieved 81.8% accuracy in the validation set (22 biopsies, 7 patients).
Conclusion
Multi-parametric MRI and texture analysis can help characterize and visualize GBM’s spatial histologic heterogeneity to identify regional tumor-rich biopsy targets.

Contributors

Agent

Created

Date Created
  • 2015-11-24

128426-Thumbnail Image.png

Structural alterations of the brainstem in migraine

Description

Atypical brainstem modulation of pain might contribute to changes in sensory processing typical of migraine. The study objective was to investigate whether migraine is associated with brainstem structural alterations that

Atypical brainstem modulation of pain might contribute to changes in sensory processing typical of migraine. The study objective was to investigate whether migraine is associated with brainstem structural alterations that correlate with this altered pain processing.
MRI T1-weighted images of 55 migraine patients and 58 healthy controls were used to: (1) create deformable mesh models of the brainstem that allow for shape analyses; (2) calculate volumes of the midbrain, pons, medulla and the superior cerebellar peduncles; (3) interrogate correlations between regional brainstem volumes, cutaneous heat pain thresholds, and allodynia symptoms.
Migraineurs had smaller midbrain volumes (healthy controls = 61.28 mm[superscript 3], SD = 5.89; migraineurs = 58.80 mm[superscript 3], SD = 6.64; p = 0.038), and significant (p < 0.05) inward deformations in the ventral midbrain and pons, and outward deformations in the lateral medulla and dorsolateral pons relative to healthy controls. Migraineurs had a negative correlation between ASC-12 allodynia symptom severity with midbrain volume (r = − 0.32; p = 0.019) and a positive correlation between cutaneous heat pain thresholds with medulla (r = 0.337; p = 0.012) and cerebellar peduncle volumes (r = 0.435; p = 0.001).
Migraineurs with greater symptoms of allodynia have smaller midbrain volumes and migraineurs with lower heat pain thresholds have smaller medulla and cerebellar peduncles. The brainstem likely plays a role in altered sensory processing in migraine and brainstem structure might reflect severity of allodynia and hypersensitivity to pain in migraine.

Contributors

Agent

Created

Date Created
  • 2016-11-02

141463-Thumbnail Image.png

Mathematical Analysis of Glioma Growth in a Murine Model

Description

Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at

Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at five separate time points to characterize growth and development of the tumor. After 25 days, the final tumor volumes of the mice varied from 12 mm[superscript 3] to 62 mm[superscript 3], even though mice were inoculated from the same tumor cell line under carefully controlled conditions. We generated hypotheses to explore large variances in final tumor size and tested them with our simple reaction-diffusion model in both a 3-dimensional (3D) finite difference method and a 2-dimensional (2D) level set method. The parameters obtained from a best-fit procedure, designed to yield simulated tumors as close as possible to the observed ones, vary by an order of magnitude between the three mice analyzed in detail. These differences may reflect morphological and biological variability in tumor growth, as well as errors in the mathematical model, perhaps from an oversimplification of the tumor dynamics or nonidentifiability of parameters. Our results generate parameters that match other experimental in vitro and in vivo measurements. Additionally, we calculate wave speed, which matches with other rat and human measurements.

Contributors

Agent

Created

Date Created
  • 2017-05-31

134522-Thumbnail Image.png

Customized Endovascular Treatment Fixture Construction for Patient-Specific Cerebral Aneurysm Repair

Description

Cerebral aneurysms are pathological bulges in blood vessels of the brain that can rupture and cause brain damage or death. Treating aneurysms by isolating them from circulation can prevent aneurysm

Cerebral aneurysms are pathological bulges in blood vessels of the brain that can rupture and cause brain damage or death. Treating aneurysms by isolating them from circulation can prevent aneurysm rupture. Endovascular techniques for cerebral aneurysm treatment are preferred because they are minimally invasive and have a shorter recovery time, and endovascular coiling is considered the gold standard as a result. The coils used in endovascular treatment come in standard shapes and sizes, mass-manufactured by medical device companies. Clinicians select the coils for treatment based on the aneurysm volume. However, cerebral aneurysms have unique shapes and dimensions, and vary on a patient-specific basis. Therefore, customizing the coils to fit a unique aneurysm morphology by using shape memory alloys could potentially improve endovascular treatment outcomes. In order to shape set a shape memory alloy into a customized coil configuration a fixture based on the aneurysm morphology must first be developed. Digital surface models of aneurysm patient cases were collected from an online repository and isolated from surrounding vasculature. Anchors used to assist in winding coils around these models were then added to create a computational fixture model. These fixtures were 3D printed in stainless steel, and tested on their ability to maintain their shape after being exposed to high temperatures needed in shape setting processes. The study demonstrated that customized fixtures can be created from patient-specific images or models, and manufactured with high levels of accuracy without deformation at high temperatures. The results suggest that 3D printed stainless steel fixtures could be used to develop customized endovascular coils for cerebral aneurysm treatment.

Contributors

Agent

Created

Date Created
  • 2017-05

135354-Thumbnail Image.png

Developing a Virtual Heart Library for Use in Pediatric Heart Transplant Allograft Size Selection

Description

Introduction: There are 350 to 400 pediatric heart transplants annually according to the Pediatric Heart Transplant Database (Dipchand et al. 2014). Finding appropriate donors can be challenging especially

Introduction: There are 350 to 400 pediatric heart transplants annually according to the Pediatric Heart Transplant Database (Dipchand et al. 2014). Finding appropriate donors can be challenging especially for the pediatric population. The current standard of care is a donor-to-recipient weight ratio. This ratio is not necessarily a parameter directly indicative of the size of a heart, potentially leading to ill-fitting allografts (Tang et al. 2010). In this paper, a regression model is presented - developed by correlating total cardiac volume to non-invasive imaging parameters and patient characteristics – for use in determining ideal allograft fit with respect to total cardiac volume.
Methods: A virtual, 3D library of clinically-defined normal hearts was compiled from reconstructed CT and MR scans. Non-invasive imaging parameters and patient characteristics were collected and subjected to backward elimination linear regression to define a model relating patient parameters to the total cardiac volume. This regression model was then used to retrospectively accept or reject an ‘ideal’ donor graft from the library for 3 patients that had undergone heart transplantation. Oversized and undersized grafts were also transplanted to qualitatively analyze virtual transplantation specificity.
Results: The backward elimination approach of the data for the 20 patients rejected the factors of BMI, BSA, sex and both end-systolic and end-diastolic left ventricular measurements from echocardiography. Height and weight were included in the linear regression model yielding an adjusted R-squared of 82.5%. Height and weight showed statistical significance with p-values of 0.005 and 0.02 respectively. The final equation for the linear regression model was TCV = -169.320+ 2.874h + 3.578w ± 73 (h=height, w=weight, TCV= total cardiac volume).
Discussion: With the current regression model, height and weight significantly correlate to total cardiac volume. This regression model and virtual normal heart library provide for the possibility of virtual transplant and size-matching for transplantation. The study and regression model is, however, limited due to a small sample size. Additionally, the lack of volumetric resolution from the MR datasets is a potentially limiting factor. Despite these limitations the virtual library has the potential to be a critical tool for clinical care that will continue to grow as normal hearts are added to the virtual library.

Contributors

Agent

Created

Date Created
  • 2016-05

136943-Thumbnail Image.png

Hemodynamic Profiling of Endovascular Embolization Polymer Treatment of Cerebral Aneurysms

Description

Cerebral aneurysms, also known as intracranial aneurysms, are sac-like lesions in the arteries of the brain that can rupture to cause subarachnoid hemorrhaging, damaging and killing brain cells. Metal coil

Cerebral aneurysms, also known as intracranial aneurysms, are sac-like lesions in the arteries of the brain that can rupture to cause subarachnoid hemorrhaging, damaging and killing brain cells. Metal coil embolization has been traditionally used to occlude and treat cerebral aneurysms to limited success, but polymer embolization has been suggested, because it can provide a greater fraction of occlusion. One such polymer with low cytotoxicity is poly(propylene glycol)diacrylate (PPODA) crosslinked via Michael-type addition with pentaerythritol tetrakis(3-mercaptopropionate) (QT). This study was performed to examine the behavior of PPODA-QT gel in vitro under pulsatile flow emulating physiological conditions. An idealized cerebral aneurysm flow model was designed based on geometries associated with an increase in rupture risk. Pressure was monitored at the apex of the aneurysm dome for varied flow rates and polymer filling fractions of 32.4, 78.2, and 100%. The results indicate that the amount of PPODA-QT deployed into the aneurysm decreases the peak-to-peak oscillation in pressure at the aneurysm wall by an inverse proportion. The 32.4 and 78.2% treatments did not significantly decrease the mean pressure applied to the aneurysm dome, but the 100% treatment greatly reduced it by diverting flow. This study indicates that the maximum filling fraction after swelling of PPODA-QT polymer should be deployed into the aneurysmal sac for treatment.

Contributors

Created

Date Created
  • 2014-05

136778-Thumbnail Image.png

Designing and Troubleshooting a Signal Acquisition System for Vertically Aligned Piezoelectric Nanowire Sensors

Description

The Honors Thesis involved the use of vertically-aligned, piezoelectric nanowire sensor arrays configured by Dr. Henry A. Sodano and Dr. Aneesh Koka from the University of Florida, in order to

The Honors Thesis involved the use of vertically-aligned, piezoelectric nanowire sensor arrays configured by Dr. Henry A. Sodano and Dr. Aneesh Koka from the University of Florida, in order to acquire acceleration data. Originally, the project was focused on interfacing and calibrating the barium titanate (BaTio3) sensors to measure wall shear stress, a fluid dynamic characteristic. In order to gain an understanding of these novel piezoelectric sensors, the experiments performed by Sodano and Koka were to be investigated, replicated, and results reproduced. After initial trial phases, signals failed to be consistently measured from the sensors and the project's emphasis was re-defined. The outlined goals were 1) to re-design the initial system used for signal acquisition, 2) test the improved signal acquisition system, 3) successfully measure output signals from the BaTiO3 nanowire sensors, and 4) determine the cause for inconsistent signal measurements from the piezoelectric nanawire sensors. Following a detailed review of the previous experimental procedures and the initial signal acquisition system, an improved acquisition system was designed and its expected behavior was tested and verified. Despite the introduction of the improved acquisition system, voltage outputs were unable to be measured as a function of shaker table acceleration. It was impossible to verify the effect of the improved signal acquisition system on the measured BaTiO3 nanowire sensor output. Based on an analysis of data collected using a commercial 3-axis acceleromoeter, it is hypothesized that the BaTiO3 nanowire sensors were broken after the first experimental trial due to an excessively applied force from an external source (i.e. shaker table, improper handling during experimentation, and/or improper handling during transportation).

Contributors

Agent

Created

Date Created
  • 2014-05

Quantifying Effects of Stent Treatment on Cerebral Aneurysm Fluid Dynamics using Finite Element Modeling

Description

The purpose of this thesis was to explore how changes in the geometry of a bifurcating cerebral aneurysm will affect the hemodynamics in idealized models after stent treatment. This thesis

The purpose of this thesis was to explore how changes in the geometry of a bifurcating cerebral aneurysm will affect the hemodynamics in idealized models after stent treatment. This thesis explores the use of a computationally modeled Enterprise Vascular Reconstruction Device (Cordis, East Bridgewater, NJ), a high porosity and closed cell design. The models represent idealized cases of saccular aneurysms with dome sizes of either 4mm or 6mm and a dome to neck ratio of either 3:2 or 2:1. Two aneurysm contact angles are studied, one at 45 degrees and the other at 90 degrees. The stent was characterized and deployed with the use of Finite Element Analysis into each model. Computational Fluid Dynamic principles were applied in series of simulations on treated and untreated models. Data was gathered in the neck plane for the average velocity magnitude, root mean squared velocity, average flow vector angle of deflection, and the cross neck flow rate. Within the aneurysm, the average velocity magnitude, root mean squared velocity, and average pressure were calculated. Additionally, the mass flow rate at each outlet was recorded. The results of this study indicate that the Enterprise Stent was most effective in the sharper, 90 degree geometry of Model 3. Additionally, the stent had an adverse effect on the Models 1 and 4, which had the smallest neck sizes. Conclusions are that the Enterprise Stent, as a stand-alone treatment method is only reliable in situations that take advantage of its design.

Contributors

Agent

Created

Date Created
  • 2013-05

137749-Thumbnail Image.png

fMRI-Based Validation of Penfield Motor Homunculus

Description

In 1937 Canadian neurosurgeon Wilder Penfield made the first to attempt to map the sensorimotor cortex of the human brain in his paper entitled Somatic Motor and Sensory Representation in

In 1937 Canadian neurosurgeon Wilder Penfield made the first to attempt to map the sensorimotor cortex of the human brain in his paper entitled Somatic Motor and Sensory Representation in the Cerebral Cortex of Man as Studied by Electrical Stimulation. While analogous experimentation had been carried out previously using animal subjects, Penfield sought to understand the delicate and complex neuronal pathways that served as the hidden control mechanisms for human activity. The motor homunculus that followed from his findings has been widely accepted as the standard model for the relative spatial representation of the functionality of the motor cortex, and has been virtually unaltered since its inception. While Penfield took measures to collect cortical data in a manner as accurately as scientifically possible for the time period, his original model is deserving of further analysis using modern techniques. This study uses functional magnetic resonance imaging (fMRI) to quantitatively determine motor function volumes and spatial relationships for four motor tasks: toe, finger, eyebrow, and tongue. Although Penfield's general representation of the superior-to-inferior spatial distribution of the motor cortex was replicated with reasonable accuracy, relative mean task volumes seem to differ from Penfield's original model. The data was first analyzed in each individual patient's native anatomical space for task comparison within a single subject. The volumes of the motor cortex devoted to the eyebrow and toe tasks, which comprise only small portions of the Penfield homunculus, are shown to be relatively large in their fMRI representation compared to finger and tongue. However, these tasks have large deviation values, indicating a lack of consistency in task volume size among patients. Behaviorally, toe movement may include whole foot movement in some individuals, and eyebrows may include face movement, causing distributions that are more widespread. The data was then analyzed in the Montreal Neurological Institute (MNI) space, which is mathematically normalized for task comparison between different subjects. Tongue and finger tasks were the largest in volume, much like Penfield's model. However, they also had substantial deviation, again indicating task volume size inconsistencies. Since the Penfield model is only a qualitative spatial evaluation of motor function along the precentral gyrus, numerical deviation from the model cannot necessarily be quantified. Hence, the results of this study can be interpreted standalone without a current comparison. While future research will serve to further validate these distances and volumes, this quantitative model of the functionality of the motor cortex will be of great utility for future neurological research and during preoperative evaluations of neurosurgical patients.

Contributors

Agent

Created

Date Created
  • 2013-05