Mechanical & Flow Environment within Solid Tumors
Uneven drug coverage is a major problem encountered in chemotherapy since the clinical goal is to eliminate 100% of tumor cells. Our lab is developing theoretical mechanics models of solid tumors where leaky vessels and cell proliferation contribute to abnormal flow and tissue deformation patterns that adversely affect drug delivery. We use a new magnetic resonance imaging (MRI)-based approach for computational modeling (voxelized modeling method) that uniquely accounts for underlying vascular leakiness as determined by leakage of contrast agent as measured by MRI (dynamic-contrast enhanced MRI, DCE-MRI). This modeling approach accounts for heterogeneous deposition, elevated interstitial fluid pressures, and abnormal tissue flows and provides a major advance towards patient-specific tumor treatment. Currently, we are working with Henry Ford Hospital and Virginia Tech to develop DCE-MRI based models of soft glioma and surrounding brain tissue.
Flow and Drug Delivery in the Brain & Spinal Cord
Many promising therapeutic agents including tumor-targeting compounds, gene vectors, and nanoparticles are large molecules for which poor tissue penetration continues to be a major problem. Our lab has developed new computational models that uses flow channel information embedded in MR-based diffusion tensor and high resolution imaging data to account for paths of least resistance to flow. We then generate 3D MRI-based computational models to predict interstitial flow patterns in complex brain structures. These models are new tools that allow for personalized therapy of neurological diseases such as epilepsy, Parkinson’s disease and brain tumors. These studies are in collaboration with collaborators at UF, Henry Ford and Virginia Tech.
Perivascular spaces (PVS) are located throughout the brain. These fine features are thought to play an important role in brain clearance, e.g. glymphatic system, which is important for understanding disorders such as Alzheimer’s disease. We have been able to show PVS connections between ventricles and different parts of the brain suggesting a possible role for ventricles as a source or sink for solutes in the brain.
Flow and Drug Delivery in Plant Vasculature
Our group is also developing new MRI and 3D computational fluid dynamics (CFD) modeling tools for assessing plant vascular function non-invasively. These tools allow us to interrogate transient changes in vascular structure and flow with disease progression to provide a better understanding of processes that mediate antagonistic interactions between plants and bacterial or fungal loading. We have recently developed novel MRI sequences to measure slow-creeping fluid flows within compromised citrus stem and root structures, whereby we can uniquely assess changes in flow in vascular tissues. This method does not require chemical pre-treatments or the addition of tracking agents, e.g., nanoparticles, which can change flow within the phloem.
Mechanical Characterization of Soft Brain Tissue
Within very soft tissues, mechanical behavior is often dependent on the interplay of fluid and solid tissue constituents that include cells, extracellular matrix, and vasculature. Our lab has developed indentation methods for measuring very soft mechanical properties of live brain tissue slices in which fluid-filled extracellular spaces are maintained. These spaces are important to maintain since extracellular spaces disappear with swelling after cell death. We are also modeling the mechanical contributions of vasculature and/or axonal fibers as a fiber network in brain tissues.
Blast traumatic brain injury
Exposure to explosive blasts can produce complex brain pathology and debilitating functional outcomes collectively termed as blast-induced traumatic brain injury (bTBI). Our lab has studied the direct interaction of the blast wave within brain tissues, as well as, the formation and collapse of bubbles i.e. cavitation. Cavitation events can produce enormous localized strains and pressures which may have consequences for injury.
Contractility-induced Structural Changes
Tissue engineering and regenerative medicine hold the promise of rebuilding organs for transplants and reconstructing diseased tissues. These engineered tissues typically include millions of contracting cells that collectively generate residual stresses. We are using Raman spectroscopy in a novel application to monitor structural changes in scaffolds with the introduction of cells. Our lab is developing computational bio-composite models that quantify the contributions of cell contraction to the constitutive response of engineered tissues.
