Real-time 3D thermoacoustic imaging and thermometry using a self-calibration technique.

Thermoacoustic (TA) imaging is a modality where pulsed microwaves are used to generate ultrasound waves in tissue, which are highly correlated with temperature. This study uses a self-calibration approach to improve the estimation of temperature using 3D real-time TA thermometry in porcine tissue during localized heating. The self-calibration method estimated temperatures at eight embedded thermocouple locations with a normalized root-mean-square error of 3.25±2.08%. The results demonstrate that the method has the suitable accuracy and resolution to provide feedback control for breast cancer ablation therapy.

Computationally Optimizing the Compliance of Multilayered Biomimetic Tissue Engineered Vascular Grafts.

Coronary artery bypass grafts used to treat coronary artery disease (CAD) often fail due to compliance mismatch. In this study, we have developed an experimental/computational approach to fabricate an acellular biomimetic hybrid tissue engineered vascular graft (TEVG) composed of alternating layers of electrospun porcine gelatin/polycaprolactone (PCL) and human tropoelastin/PCL blends with the goal of compliance-matching to rat abdominal aorta, while maintaining specific geometrical constraints. Polymeric blends at three different gelatin:PCL (G:PCL) and tropoelastin:PCL (T:PCL) ratios (80:20, 50:50, and 20:80) were mechanically characterized. The stress-strain data were used to develop predictive models, which were used as part of an optimization scheme that was implemented to determine the ratios of G:PCL and T:PCL and the thickness of the individual layers within a TEVG that would compliance match a target compliance value. The hypocompliant, isocompliant, and hypercompliant grafts had target compliance values of 0.000256, 0.000568, and 0.000880 mmHg-1, respectively. Experimental validation of the optimization demonstrated that the hypercompliant and isocompliant grafts were not statistically significant from their respective target compliance values (p-value = 0.37 and 0.89, respectively). The experimental compliance values of the hypocompliant graft were statistically significant than their target compliance value (p-value = 0.047). We have successfully demonstrated a design optimization scheme that can be used to fabricate multilayered and biomimetic vascular grafts with targeted geometry and compliance.

Computationally Optimizing the Compliance of a Biopolymer Based Tissue Engineered Vascular Graft.

Coronary heart disease is a leading cause of death among Americans for which coronary artery bypass graft (CABG) surgery is a standard surgical treatment. The success of CABG surgery is impaired by a compliance mismatch between vascular grafts and native vessels. Tissue engineered vascular grafts (TEVGs) have the potential to be compliance matched and thereby reduce the risk of graft failure. Glutaraldehyde (GLUT) vapor-crosslinked gelatin/fibrinogen constructs were fabricated and mechanically tested in a previous study by our research group at 2, 8, and 24 hrs of GLUT vapor exposure. The current study details a computational method that was developed to predict the material properties of our constructs for crosslinking times between 2 and 24 hrs by interpolating the 2, 8, and 24 hrs crosslinking time data. matlab and abaqus were used to determine the optimal combination of fabrication parameters to produce a compliance matched construct. The validity of the method was tested by creating a 16-hr crosslinked construct of 130 µm thickness and comparing its compliance to that predicted by the optimization algorithm. The predicted compliance of the 16-hr construct was 0.00059 mm Hg-1 while the experimentally determined compliance was 0.00065 mm Hg-1, a relative difference of 9.2%. Prior data in our laboratory has shown the compliance of the left anterior descending porcine coronary (LADC) artery to be 0.00071 ± 0.0003 mm Hg-1. Our optimization algorithm predicts that a 258-µm-thick construct that is GLUT vapor crosslinked for 8.1 hrs would match LADC compliance. This result is consistent with our previous work demonstrating that an 8-hr GLUT vapor crosslinked construct produces a compliance that is not significantly different from a porcine coronary LADC.

Emerging photoacoustic and thermoacoustic imaging technologies for detecting primary and metastatic cancer and guiding therapy.

In recent years, there has been a progressive trend towards less invasive technologies for detecting metastatic cancer and guiding therapy with the goal of lower morbidity, better outcomes, and superior cosmetic appearance than traditional methods. This mini-review examines three emerging noninvasive hybrid technologies for detecting primary cancer, metastasis and guiding thermal therapy. Real-time thermoacoustic imaging and thermometry potentially provides valuable and critical feedback for guiding focused microwave ablation therapy. Label-free photoacoustic monitoring of cancer cells is a promising clinical diagnostic and theranostic tool for detecting metastatic disease and monitoring the response to therapy. Finally, immunologically targeted gold nanoparticles combined with photoacoustic imaging is able to detect lymph node micrometastasis in mouse models of breast cancer. These emerging techniques have the potential to improve the decision to biopsy, provide more accurate prognosis, and enhance the efficacy of therapy for early and late stage cancers.

A Subdomain Method for Mapping the Heterogeneous Mechanical Properties of the Human Posterior Sclera.

Although strongly correlated with elevated intraocular pressure, primary open-angle glaucoma (POAG) occurs in normotensive eyes. Mechanical properties of the sclera around the optic nerve head (ONH) may play a role in this disparity. The purpose of this study is to present an automated inverse mechanics based approach to determine the distribution of heterogeneous mechanical properties of the human sclera as derived from its surface deformations arising from pressure inflation experiments. The scleral shell of a 78 year old European Descent male donor eye was utilized to demonstrate the method; the sclera was coated with a speckle pattern on the outer surface and was subjected to inflation pressures of 5, 15, 30, and 45 mmHg. The speckle pattern was imaged at each pressure, and a displacement field was calculated for each pressure step using a previously described sequential digital image correlation (S-DIC) technique. The fiber splay and fiber orientation of the sclera collagen were determined experimentally, and the thickness across the scleral globe was determined using micro CT images. The displacement field from the inflation test was used to calculate the strain and also used as an input for inverse mechanics to determine the heterogeneity of material properties. The scleral geometry was divided into subdomains using the first principal strain. The Holzapfel anisotropic material parameters of matrix and fiber stiffness were estimated within each individual subdomain using an inverse mechanics approach by minimizing the sum of the square of the residuals between the computational and experimental displacement fields. The mean and maximum error in displacement across all subdomains were 8.9 ± 3.0 µm and 13.2 µm, respectively. The full pressure-inflation forward mechanics experiment was done using subdomain-specific mechanical properties on the entire scleral surface. The proposed approach is effective in determining the distribution of heterogeneous mechanical properties of the human sclera in a user-independent manner. Our research group is currently utilizing this approach to better elucidate how scleral stiffness influences those at high risk for POAG.

Racioethnic Differences in Human Posterior Scleral and Optic Nerve Stump Deformation.

Purpose: The purpose of this study was to quantify the biomechanical response of human posterior ocular tissues from donors of various racioethnic groups to better understand how differences in these properties may play a role in the racioethnic health disparities known to exist in glaucoma. Methods: Sequential digital image correlation (S-DIC) was used to measure the pressure-induced surface deformations of 23 normal human posterior poles from three racioethnic groups: African descent (AD), European descent (ED), and Hispanic ethnicity (HIS). Regional in-plane principal strains were compared across three zones: the optic nerve stump (ONS), the peripapillary (PP) sclera, and non-PP sclera. Results: The PP scleral tensile strains were found to be lower for ED eyes compared with AD and HIS eyes at 15 mm Hg (P = 0.024 and 0.039, respectively). The mean compressive strains were significantly higher for AD eyes compared with ED eyes at 15 mm Hg (P = 0.018). We also found that the relationship between tensile strain and pressure was significant for those of ED and HIS eyes (P < 0.001 and P = 0.004, respectively), whereas it was not significant for those of AD (P = 0.392). Conclusions: Our results suggest that, assuming glaucomatous nerve loss is caused by mechanical strains in the vicinity of the optic nerve head, the mechanism of increased glaucoma prevalence may be different in those of AD versus HIS. Our ONS strain analysis also suggested that it may be important to account for ONS geometry and material properties in future scleral biomechanical analysis.

TGFß2 differentially modulates smooth muscle cell proliferation and migration in electrospun gelatin-fibrinogen constructs.

A main goal of tissue engineering is the development of scaffolds that replace, restore and improve injured tissue. These scaffolds have to mimic natural tissue, constituted by an extracellular matrix (ECM) support, cells attached to the ECM, and signaling molecules such as growth factors that regulate cell function. In this study we created electrospun flat sheet scaffolds using different compositions of gelatin and fibrinogen. Smooth muscle cells (SMCs) were seeded on the scaffolds, and proliferation and infiltration were evaluated. Additionally, different concentrations of Transforming Growth Factor-beta2 (TGFß2) were added to the medium with the aim of elucidating its effect on cell proliferation, migration and collagen production. Our results demonstrated that a scaffold with a composition of 80% gelatin-20% fibrinogen is suitable for tissue engineering applications since it promotes cell growth and migration. The addition of TGFß2 at low concentrations (≤ 1 ng/ml) to the culture medium resulted in an increase in SMC proliferation and scaffold infiltration, and in the reduction of collagen production. In contrast, TGFß2 at concentrations >1 ng/ml inhibited cell proliferation and migration while stimulating collagen production. According to our results TGFß2 concentration has a differential effect on SMC function and thus can be used as a biochemical modulator that can be beneficial for tissue engineering applications.