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The deployment of hyperthermia as a routine adjuvant to radiation or chemotherapy is limited largely by the inability to devise treatment plans which can be monitored through temperature distribution feedback during therapy. A non-invasive microwave tomographic thermal imaging system is currently being developed which has previously exhibited excellent correlation between the recovered electrical conductivity of a heated zone and its actual temperature change during phantom studies. To extend the validation of this approach in vivo, the imaging system has been re-configured for small animal experiments to operate within the bore of a CT scanner for anatomical and thermometry registration. A series of 5–7 day old pigs have been imaged during hyperthermia with a monopole antenna array submerged in a saline tank where a small plastic tube surgically inserted the length of the abdomen has been used to create a zone of heated saline at pre-selected temperatures. Tomographic microwave data over the frequency range of 300–1000MHz of the pig abdomen in the plane perpendicular to the torso is collected at regular intervals after the tube saline temperatures have settled to the desired settings. Images are reconstructed over a range of operating frequencies. The tube location is clearly visible and the recovered saline conductivity varies linearly with the controlled temperature values. Difference images utilizing the baseline state prior to heating reinforces the linear relationship between temperature and imaged saline conductivity. Demonstration of in vivo temperature recovery and correlation with an independent monitoring device is an important milestone prior to clinical integration of this non-invasive imaging system with a thermal therapy device. [ABSTRACT FROM AUTHOR]

Stress-induced release of IL-1alpha and fibroblast growth factor-1 is dependent on intracellular copper and is a major driver of neointimal hyperplasia. Therefore, we assessed the effect of tetrathiomolybdate (TTM), a clinically proven copper chelator, on in-stent restenosis. Nine pigs were treated with TTM (5 mg/kg po) twice daily for 2 wk before stent implantation and for 4 wk thereafter, and nine pigs served as controls. In-stent restenosis was assessed by quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), and histomorphometry. Serum ceruloplasmin activity was used as a surrogate marker of copper bioavailability. In TTM-treated animals, ceruloplasmin dropped 70 +/- 10% below baseline levels. Baseline characteristics were comparable in TTM-treated and control animals. At 4-wk follow-up, all parameters relevant to in-stent restenosis were significantly reduced in TTM-treated animals: minimal lumen diameter by QCA was 2.03 +/- 0.57 and 1.47 +/- 0.45 mm in TTM-treated and control animals, respectively (P < 0.05), percent stenosis diameter was 39% less in TTM-treated animals (27.1 +/- 16.6% vs. 44.5 +/- 16.1%, P < 0.05), minimal lumen area by IVUS was 60% larger in TTM-treated animals (4.27 +/- 1.56 vs. 2.67 +/- 1.19 mm(2), P < 0.05), and neointimal volume by histomorphometry was 37% less in TTM-treated animals (34.9 +/- 11.5 vs. 55.2 +/- 19.6 mm(3), P < 0.05). We conclude that systemic copper chelation with a clinically approved chelator significantly inhibits in-stent restenosis.

The deployment of hyperthermia as a routine adjuvant to radiation or chemotherapy is limited largely by the inability to devise treatment plans which can be monitored through temperature distribution feedback during therapy. A non-invasive microwave tomographic thermal imaging system is currently being developed which has previously exhibited excellent correlation between the recovered electrical conductivity of a heated zone and its actual temperature change during phantom studies. To extend the validation of this approach in vivo, the imaging system has been re-configured for small animal experiments to operate within the bore of a CT scanner for anatomical and thermometry registration. A series of 5-7 day old pigs have been imaged during hyperthermia with a monopole antenna array submerged in a saline tank where a small plastic tube surgically inserted the length of the abdomen has been used to create a zone of heated saline at pre-selected temperatures. Tomographic microwave data over the frequency range of 300-1000 MHz of the pig abdomen in the plane perpendicular to the torso is collected at regular intervals after the tube saline temperatures have settled to the desired settings. Images are reconstructed over a range of operating frequencies. The tube location is clearly visible and the recovered saline conductivity varies linearly with the controlled temperature values. Difference images utilizing the baseline state prior to heating reinforces the linear relationship between temperature and imaged saline conductivity. Demonstration of in vivo temperature recovery and correlation with an independent monitoring device is an important milestone prior to clinical integration of this non-invasive imaging system with a thermal therapy device.

Purpose: Microwave thermal keratoplasty applies microwave energy to elevate the temperature of the paracentral stroma of the cornea to its thermal shrinkage temperature of about 60 degrees C. A suitable pattern of shrinkage in the paracentral cornea can flatten the central cornea. A surface cooling system preserves the epithelium during the procedure., Methods: Fourteen enucleated porcine eyes were treated with a prototype microwave thermal keratoplasty applicator that heated in a ring pattern with inner diameter of 3.2 mm and width of 0.7 mm. The change in corneal power was quantified by a videokeratoscope. Slit-lamp microscope examinations and histological assessments were made., Results: The 3-mm simulated keratometry reading showed an average of 6.60+/-6.00 D (standard deviation) of flattening. The region of opacity associated with shrinkage extended to 62% (+/-26%) of the corneal thickness. The epithelium was intact in all eyes., Conclusions: Microwave thermal keratoplasty applied in the paracentral cornea may flatten the central cornea.

A noninvasive in situ fluorescence-based method for the quantification of the photosensitizer chloroaluminum disulfonated phthalocyanine was compared to the highly accurate but nonreal time ex vivo spectrofluorometry method. Our in vivo fluorescence technique is designed to allow real-time assessment of photosensitizer in tumor and normal tissues and therefore temporally optimal light delivery. Laser-induced fluorescence was used to measure photosensitizer concentration from multiple microscopic regions of tissue. Ex vivo chemical extraction was used to quantify photosensitizer concentration in the same volume of tissue. The amount of photosensitizer in the vascular and/or parenchymal compartments of skeletal muscle and liver was determined by quantifying fluorescent signal in vivo, ex vivo and after blood removal. Confocal microscopy was used to spatially document photosensitizer localization 30 min and 24 h after delivery. While a linear correlation can exist between the fluorescence intensity measured by our fiber-optic bundle system and actual tissue concentration, temporal changes to this calibration line exist as the photosensitizer changes its partitioning fraction between the blood (vasculature) and the tissue parenchyma. In situ photosensitizer fluorescence microsampling (dosimetry) systems can be performed in real time and linearly correlated to actual tissue concentration with minimal intertissue variance. Tissue-specific differences may require temporal alterations in the calibration.