Matching Items (41)

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Development of a Novel Smart Contrast Agent for Magnetic Resonance Imaging

Description

Smart contrast agents allow for noninvasive study of specific events or tissue conditions inside of a patient's body using Magnetic Resonance Imaging (MRI). This research aims to develop and characterize

Smart contrast agents allow for noninvasive study of specific events or tissue conditions inside of a patient's body using Magnetic Resonance Imaging (MRI). This research aims to develop and characterize novel smart contrast agents for MRI that respond to temperature changes in tissue microenvironments. Transmission Electron Microscopy, Nuclear Magnetic Resonance, and cell culture growth assays were used to characterize the physical, magnetic, and cytotoxic properties of candidate nanoprobes. The nanoprobes displayed thermosensitve MR properties with decreasing relaxivity with temperature. Future work will be focused on generating and characterizing photo-active analogues of the nanoprobes that could be used for both treatment of tissues and assessment of therapy.

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Created

Date Created
  • 2014-05

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Modeling and Characterization of Mass Transfer Kinetics in Tumor Tissue Using Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI)

Description

The objective of the research presented here was to validate the use of kinetic models for the analysis of the dynamic behavior of a contrast agent in tumor tissue and

The objective of the research presented here was to validate the use of kinetic models for the analysis of the dynamic behavior of a contrast agent in tumor tissue and evaluate the utility of such models in determining kinetic properties - in particular perfusion and molecular binding uptake associated with tissue hypoxia - of the imaged tissue, from concentration data acquired with dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) procedure. Data from two separate DCE-MRI experiments, performed in the past, using a standard contrast agent and a hypoxia-binding agent respectively, were analyzed. The results of the analysis demonstrated that the models used may provide novel characterization of the tumor tissue properties. Future research will work to further characterize the physical significance of the estimated parameters, particularly to provide quantitative oxygenation data for the imaged tissue.

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Created

Date Created
  • 2013-12

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Novel siloxane nanoprobes for molecular and cellular imagin

Description

Oxygen delivery is crucial for the development of healthy, functional tissue. Low tissue oxygenation, or hypoxia, is a characteristic that is common in many tumors. Hypoxia contributes to tumor malignancy

Oxygen delivery is crucial for the development of healthy, functional tissue. Low tissue oxygenation, or hypoxia, is a characteristic that is common in many tumors. Hypoxia contributes to tumor malignancy and can reduce the success of chemotherapy and radiation treatment. There is a current need to noninvasively measure tumor oxygenation or pO2 in patients to determine a personalized treatment method. This project focuses on creating and characterizing nanoemulsions using a pO2 reporter molecule hexamethyldisiloxane (HMDSO) and its longer chain variants as well as assessing their cytotoxicity. We also explored creating multi-modal (MRI/Fluorescence) nanoemulsions.

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Agent

Created

Date Created
  • 2013-05

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Direct nose-to-brain delivery of targeted polymeric nanoparticles

Description

There is growing interest in intranasal delivery of therapeutics because of direct nose-to-brain pathways which are able to bypass biological barriers, such as the blood-brain barrier (BBB), that have historically

There is growing interest in intranasal delivery of therapeutics because of direct nose-to-brain pathways which are able to bypass biological barriers, such as the blood-brain barrier (BBB), that have historically limited our ability to effectively deliver drugs to the central nervous system (CNS). Since these pathways were first discovered, there has been significant preclinical success in delivering a wide range of therapeutics to the CNS with additional growing efforts to further improve delivery through nanoparticle drug delivery systems. Here we sought to improve intranasal delivery of DiR, a lipophilic small molecule cyanine dye, to the CNS by surface modifying a poly (lactic-co-glycolic acid) (PLGA) nanoparticle with a short peptide derived from the rabies virus glycoprotein (RVG). The specific aims of this thesis were to evaluate administration route-dependent delivery of RVG nanoparticles to the CNS, and to identify anatomical transport pathways by which nanoparticles facilitate transport of small lipophilic molecules. Route-dependent delivery kinetics and distribution were studied by administering DiR loaded nanoparticles to healthy Balb/C mice. Specific tissues were homogenized and the fluorescent intensity of DiR was measured and compared to control tissue spiked with known amounts of dye. While bioavailability of DiR after intranasal administration was near 0% with minimal exposure to peripheral organs, quick and efficient delivery to the CNS was still observed. CNS delivery after intranasal administration was rapid with peak concentrations at 30 minutes post-administration followed by broad clearance by 2 hours. Regional differences of delivery of DiR to the CNS demonstrated engagement of direct nose-to-brain transport pathways with high delivery being observed to the olfactory bulb, brain stem, and trigeminal nerve. RVG modification however presented only modest targeting benefits. In conclusion, the biodistribution of DiR after intranasal administration of DiR loaded nanoparticles showed high potential for the direct nose-to-brain delivery while limiting peripheral exposure of lipophilic small molecule drugs.

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Agent

Created

Date Created
  • 2016-05

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Improving the Realism and Magnetic Resonance Imaging of Multicellular Tumor Spheroids

Description

Magnetic resonance imaging (MRI) of changes in metabolic activity in tumors and metabolic abnormalities can provide a window to understanding the complex behavior of malignant tumors. Both diagnostics and treatment

Magnetic resonance imaging (MRI) of changes in metabolic activity in tumors and metabolic abnormalities can provide a window to understanding the complex behavior of malignant tumors. Both diagnostics and treatment options can be improved through the further comprehension of the processes that contribute to tumor malignancy and growth. By detecting and disturbing this activity through personalized treatments, it is the hope to provide better diagnostics and care to patients. Experimenting with multicellular tumor spheroids (MCTS) allows for a rapid, inexpensive and convenient solution to studying multiple in vitro tumors. High quality magnetic resonance images of small samples, such as spheroid, however, are difficult to achieve with current radio frequency coils. In addition, in order for the information provided by these scans to accurately represent the interactions and metabolic activity in vivo, there is a need for a perfused vascular network. A perfused vascular network has the potential to improve metabolic realism and particle transport within a tumor spheroid. By creating a more life-like cancer model and allowing the progressive imaging of metabolic functions of such small samples, a better, more efficient mode of studying metabolic activity in cancer can be created and research efforts can expand. The progress described in this paper attempts to address both of these current shortcomings of metabolic cancer research and offers potential solutions, while acknowledging the potential of future work to improve cancer research with MCTS.

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Created

Date Created
  • 2016-12

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A Novel Temperature-Sensitive MR & Fluorescence Imaging Contrast Agent

Description

Contrast agents in medical imaging can help visualize structural details, distributions of particular cell types, or local environment characteristics. Multi-modal imaging techniques have become increasingly popular for their improved sensitivity,

Contrast agents in medical imaging can help visualize structural details, distributions of particular cell types, or local environment characteristics. Multi-modal imaging techniques have become increasingly popular for their improved sensitivity, resolution, and ability to correlate structural and functional information. This study addresses the development of dual-modality (magnetic resonance/fluorescence) and dual-functional (thermometry/detection) nanoprobes for enhanced tissue imaging.

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Agent

Created

Date Created
  • 2015-05

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A Novel Computing Platform for Accelerated Magnetic Resonance Spectroscopic Cancer Imaging

Description

Compressed sensing magnetic resonance spectroscopic imaging (MRSI) is a noninvasive and in vivo potential diagnostic technique for cancer imaging. This technique undersamples the distribution of specific cancer biomarkers within an

Compressed sensing magnetic resonance spectroscopic imaging (MRSI) is a noninvasive and in vivo potential diagnostic technique for cancer imaging. This technique undersamples the distribution of specific cancer biomarkers within an MR image as well as changes in the temporal dimension and subsequently reconstructs the missing data. This technique has been shown to retain a high level of fidelity even with an acceleration factor of 5. Currently there exist several different scanner types that each have their separate analytical methods in MATLAB. A graphical user interface (GUI) was created to facilitate a single computing platform for these different scanner types in order to improve the ease and efficiency with which researchers and clinicians interact with this technique. A GUI was successfully created for both prospective and retrospective MRSI data analysis. This GUI retained the original high fidelity of the reconstruction technique and gave the user the ability to load data, load reference images, display intensity maps, display spectra mosaics, generate a mask, display the mask, display kspace and save the corresponding spectra, reconstruction, and mask files. Parallelization of the reconstruction algorithm was explored but implementation was ultimately unsuccessful. Future work could consist of integrating this parallelization method, adding intensity overlay functionality and improving aesthetics.

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Agent

Created

Date Created
  • 2016-05

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Compressed Sensing to Accelerate Magnetic Resonance Spectroscopic Imaging: Evaluation and Application to Na-23-Imaging of Mouse Hearts

Description

Background: Magnetic Resonance Spectroscopic Imaging (MRSI) has wide applicability for non-invasive biochemical assessment in clinical and pre-clinical applications but suffers from long scan times. Compressed sensing (CS) has been successfully

Background: Magnetic Resonance Spectroscopic Imaging (MRSI) has wide applicability for non-invasive biochemical assessment in clinical and pre-clinical applications but suffers from long scan times. Compressed sensing (CS) has been successfully applied to clinical H-1 MRSI, however a detailed evaluation of CS for conventional chemical shift imaging is lacking. Here we evaluate the performance of CS accelerated MRSI, and specifically apply it to accelerate Na-23-MRSI on mouse hearts in vivo at 9.4 T.

Methods: Synthetic phantom data representing a simplified section across a mouse thorax were used to evaluate the fidelity of the CS reconstruction for varying levels of under-sampling, resolution and signal-to-noise ratios (SNR). The amplitude of signals arising from within a compartment, and signal contamination arising from outside the compartment relative to noise-free Fourier-transformed (FT) data were determined. Simulation results were subsequently verified experimentally in phantoms and in three mouse hearts in vivo.

Results: CS reconstructed MRSI data are scaled linearly relative to absolute signal intensities from the fully-sampled FT reconstructed case (R-2 > 0.8, p-value < 0.001). Higher acceleration factors resulted in a denoising of the reconstructed spectra, but also in an increased blurring of compartment boundaries, particularly at lower spatial resolutions. Increasing resolution and SNR decreased cross-compartment contamination and yielded signal amplitudes closer to the FT data. Proof-of-concept high-resolution, 3-fold accelerated Na-23-amplitude maps of murine myocardium could be obtained within similar to 23 mins.

Conclusions: Relative signal amplitudes (i.e. metabolite ratios) and absolute quantification of metabolite concentrations can be accurately determined with up to 5-fold under-sampled, CS-reconstructed MRSI. Although this work focused on murine cardiac Na-23-MRSI, the results are equally applicable to other nuclei and tissues (e.g. H-1 MRSI in brain). Significant reduction in MRSI scan time will reduce the burden on the subject, increase scanner throughput, and may open new avenues for (pre-) clinical metabolic studies.

Contributors

Created

Date Created
  • 2015-06-15

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Brain Volume of the Newly-Discovered Species Rhynchocyon Udzungwensis (Mammalia: Afrotheria: Macroscelidea): Implications for Encephalization in Sengis

Description

The Gray-faced Sengi (Rhynchocyon udzungwensis) is a newly-discovered species of sengi (elephant-shrew) and is the largest known extant representative of the order Macroscelidea. The discovery of R. udzungwensis provides an

The Gray-faced Sengi (Rhynchocyon udzungwensis) is a newly-discovered species of sengi (elephant-shrew) and is the largest known extant representative of the order Macroscelidea. The discovery of R. udzungwensis provides an opportunity to investigate the scaling relationship between brain size and body size within Macroscelidea, and to compare this allometry among insectivorous species of Afrotheria and other eutherian insectivores. We performed a spin-echo magnetic resonance imaging (MRI) scan on a preserved adult specimen of R. udzungwensis using a 7-Tesla high-field MR imaging system. The brain was manually segmented and its volume was compiled into a dataset containing previously-published allometric data on 56 other species of insectivore-grade mammals including representatives of Afrotheria, Soricomorpha and Erinaceomorpha. Results of log-linear regression indicate that R. udzungwensis exhibits a brain size that is consistent with the allometric trend described by other members of its order. Inter-specific comparisons indicate that macroscelideans as a group have relatively large brains when compared with similarly-sized terrestrial mammals that also share a similar diet. This high degree of encephalization within sengis remains robust whether sengis are compared with closely-related insectivorous afrotheres, or with more-distantly-related insectivorous laurasiatheres.

Contributors

Created

Date Created
  • 2013-03-13

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The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma

Description

Background
Malignant brain tumors affect people of all ages and are the second leading cause of cancer deaths in children. While current treatments are effective and improve survival, there remains

Background
Malignant brain tumors affect people of all ages and are the second leading cause of cancer deaths in children. While current treatments are effective and improve survival, there remains a substantial need for more efficacious therapeutic modalities. The ketogenic diet (KD) - a high-fat, low-carbohydrate treatment for medically refractory epilepsy - has been suggested as an alternative strategy to inhibit tumor growth by altering intrinsic metabolism, especially by inducing glycopenia.
Methods
Here, we examined the effects of an experimental KD on a mouse model of glioma, and compared patterns of gene expression in tumors vs. normal brain from animals fed either a KD or a standard diet.
Results
Animals received intracranial injections of bioluminescent GL261-luc cells and tumor growth was followed in vivo. KD treatment significantly reduced the rate of tumor growth and prolonged survival. Further, the KD reduced reactive oxygen species (ROS) production in tumor cells. Gene expression profiling demonstrated that the KD induces an overall reversion to expression patterns seen in non-tumor specimens. Notably, genes involved in modulating ROS levels and oxidative stress were altered, including those encoding cyclooxygenase 2, glutathione peroxidases 3 and 7, and periredoxin 4.
Conclusions
Our data demonstrate that the KD improves survivability in our mouse model of glioma, and suggests that the mechanisms accounting for this protective effect likely involve complex alterations in cellular metabolism beyond simply a reduction in glucose.

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Agent

Created

Date Created
  • 2010-09-10