Diss. (sammanfattning) Linköping : Linköpings universitet, 2008. / Härtill 4 uppsatser.

Plasmon resonance associated with nanoparticles of gold can enable photothermal ablation of tissues or controlled drug release with exquisite temporal and spatial control. These technologies may support many applications of precision medicine. However, clinical implementations of these technologies will require new methods of intraoperative imaging and guidance. Near-infrared laser surgery is a prime example that relies on improved image guidance. Here we set forth applications of augmented microscopy in guiding surgical procedures employing plasmon resonant gold-coated liposomes. Absorption of near-infrared laser light is the first step in activation of various diagnostic and therapeutic functions of these novel functional nanoparticles. Therefore, we demonstrate examples of near-infrared visualization of the laser beam and gold-coated liposomes. The augmented microscope proves to be a promisingimage guidance platform for a range of image-guided medical procedures.

This research was a collaborative effort between the Air Force Research Laboratory (AFRL) and the University of Texas to examine the laser-tissue interaction of thermal lensing induced by continuous-wave, CW, near-infrared, NIR, laser radiation in the eye and its influence on the formation of a retinal lesion from said radiation. CW NIR laser radiation can lead to a thermal lesion induced on the retina given sufficient power and exposure duration as related to three basic parameters; the percent of transmitted energy to, the optical absorption of, and the size of the laser-beam created at the retina. Thermal lensing is a well-known phenomenon arising from the optical absorption, and subsequent temperature rise, along the path of the propagating beam through a medium. Thermal lensing causes the laser-beam profile delivered to the retina to be time dependent. Analysis of a dual-beam, multidimensional, high-frame rate, confocal imaging system in an artificial eye determined the rate of thermal lensing in aqueous media exposed to 1110, 1130, 1150 and 1318-nm wavelengths was related to the power density created along the optical axis and linear absorption coefficient of the medium. An adaptive optics imaging system was used to record the aberrations induced by the thermal lens at the retina in an artificial eye during steady-state. Though the laser-beam profiles changed over the exposure time, the CW NIR retinal damage thresholds between 1110-1319-nm were determined to follow conventional fitting algorithms which neglected thermal lensing. A first-order mathematical model of thermal lensing was developed by conjoining an ABCD beam propagation method, Beer's law of attenuation, and a solution to the heat-equation with respect to radial diffusion. The model predicted that thermal lensing would be strongest for small (< 4-mm) 1/e² laser-beam diameters input at the corneal plane and weakly transmitted wavelengths where less than 5% of the energy is delivered to the retina. The model predicted thermal lensing would cause the retinal damage threshold for wavelengths above 1300-nm to increase with decreasing beam-diameters delivered to the corneal plane, a behavior which was opposite of equivalent conditions simulated without thermal lensing. / text

Hyperthermia is usually used at a sub-lethal level in cancer treatment to potentiate the effects of chemotherapy. The purpose of this study is to investigate the role of heating rate in achieving synergistic cell killing by chemotherapy and hyperthermia. For this purpose, in vitro cell culture experiments with a uterine cancer cell line (MES-SA) and its multidrug resistant (MDR) variant MES-SA/Dx5 were conducted. The cytotoxicitiy, mode of cell death, induction of thermal tolerance and P-gp mediated MDR following the two different modes of heating were studied. Doxorubicin (DOX) was used as the chemotherapy drug. Indocyanine green (ICG), which absorbs near infrared light at 808nm (ideal for tissue penetration), was chosen for achieving rapid rate hyperthermia. A slow rate hyperthermia was provided by a cell culture incubator. The results show that the potentiating effect of hyperthermia to chemotherapy can be maximized by increasing the rate of heating as evident by the results from the cytotoxicity assay. When delivered at the same thermal dose, a rapid increase in temperature from 37 °C to 43 °C caused more cell membrane damage than gradually heating the cells from 37 °C to 43 °C and thus allowed for more intracellular accumulation of the chemotherapeutic agents. Different modes of cell death are observed by the two hyperthermia delivery methods. The rapid rate laser-ICG hyperthermia @ 43 °C caused cell necrosis whereas the slow rate incubator hyperthermia @ 43 °C induced very mild apoptosis. At 43 °C a positive correlation between thermal tolerance and the length of hyperthermia exposure is identified. This study shows that by increasing the rate of heating, less thermal dose is needed in order to overcome P-gp mediated MDR.

abstract: Tissue approximation and repair have been performed with sutures and staples for centuries, but these means are inherently traumatic. Tissue repair using laser-responsive nanomaterials can lead to rapid tissue sealing and repair and is an attractive alternative to existing clinical methods. Laser tissue welding is a sutureless technique for sealing incised or wounded tissue, where chromophores convert laser light to heat to induce in tissue sealing. Introducing chromophores that absorb near-infrared light creates differential laser absorption and allows for laser wavelengths that minimizes tissue damage. In this work, plasmonic nanocomposites have been synthesized and used in laser tissue welding for ruptured porcine intestine ex vivo and incised murine skin in vivo. These laser-responsive nanocomposites improved tissue strength and healing, respectively. Additionally, a spatiotemporal model has been developed for laser tissue welding of porcine and mouse cadaver intestine sections using near-infrared laser irradiation. This mathematical model can be employed to identify optimal conditions for minimizing healthy cell death while still achieving a strong seal of the ruptured tissue using laser welding. Finally, in a model of surgical site infection, laser-responsive nanomaterials were shown to be efficacious in inhibiting bacterial growth. By incorporating an anti-microbial functionality to laser-responsive nanocomposites, these materials will serve as a treatment modality in sealing tissue, healing tissue, and protecting tissue in surgery. / Dissertation/Thesis / Doctoral Dissertation Chemical Engineering 2019