Radiation therapy and hyperthermia improve the oxygenation of human soft tissue sarcomas.

The adverse prognostic impact of tumor hypoxia has been demonstrated in human malignancy. We report the effects of radiotherapy and hyperthermia (HT) on soft tissue sarcoma oxygenation and the relationship between treatment-induced changes in oxygenation and clinical treatment outcome. Patients receiving preoperative radiotherapy and HT underwent tumor oxygenation measurement pretreatment after the start of radiation/pre-HT and one day after the first HT treatment. The magnitude of improvement in tumor oxygenation after the first HT fraction relative to pretreatment baseline was positively correlated with the amount of necrosis seen in the resection specimen. Patients with <90% resection specimen necrosis experienced longer disease-free survival than those with > or = 90% necrosis. Increasing levels of tumor hypoxia were also correlated with diminished metabolic status as measured by P-31 magnetic resonance spectroscopy.

Metastatic head and neck malignancy treated using MRI guided interstitial laser phototherapy: an initial case report.

Interstitial laser phototherapy (ILP) guided by magnetic resonance imaging (MRI) may become an attractive adjunctive modality for the treatment of deep and surgically inaccessible tumors of the head and neck when accurate methods of laser dosimetry and "real-time" monitoring techniques with the MRI are introduced. We recently demonstrated in ex vivo and in vivo models, a linear relationship between levels of laser energies, thermal profiles, MR signal intensity changes, and histopathological tissue damage. Results of treatment in a patient with an unresectable large right jugulodigastric metastatic squamous carcinoma using new approach of MRI guided ILP are now reported. The patient complained of significant right-sided neck pain and headaches secondary to a rapidly growing metastatic lymphadenopathy which recurred after previous surgery, radiation, and chemotherapy. Two treatment sessions were used at an interval of 2 weeks. Each treatment was performed in the MRI suite under heavy sedation. Using a 600-microns bare fiber of the Nd:YAG laser implanted interstitially under MR guidance, the metastatic node was treated at three sites. T1- and T2-weighted images were performed prior to, immediately after, 24 and 48 hours, and 4, 5, 7, 9, 16, and 25 days post-treatment. Successful relief of pain and growth arrest of this node was observed after the second treatment and at the 3-month follow-up. These results demonstrate that this technique of ILP guided by MRI may be feasible in humans, and will become clinically practical when appropriate methods of dosimetry and instrumentation are developed.

MR imaging-guided interstitial Nd:YAG laser phototherapy: dosimetry study of acute tissue damage in an in vivo model.

A dosimetry study of acute tissue damage induced by interstitial application of the neodymium-yttrium-aluminum-garnet (Nd:YAG) laser was performed with magnetic resonance (MR) imaging. The MR appearance of the lesion was correlated with gross and histopathologic findings. Seventy-six lesions were induced in rabbit muscle with laser power outputs of 5-20 W and exposure times of 20-600 seconds. MR imaging was performed immediately after laser exposure. T2-weighted spin-echo images clearly showed the acute thermal injuries caused by laser energy deposition and correlated best with histopathologic findings. These images showed three distinct layers, corresponding to central ablation, coagulative necrosis, and interstitial edema, respectively, in the pathologic findings. Lesion diameters measured on MR images showed a linear correlation with those in gross sections. Lesion volume increased not only with increasing total energy delivered but with increasing power output for a fixed total energy delivered. MR imaging is an accurate modality for dosimetry studies of laser-induced acute lesions.

Nd: YAG interstitial laser phototherapy guided by magnetic resonance imaging in an ex vivo model: dosimetry of laser-MR-tissue interaction.

Interstitial laser phototherapy (ILP) is a promising technique in which laser energy is delivered percutaneously to various depths of tumors. This technique will become clinically useful only when efficient, sensitive, and noninvasive monitoring systems are developed. In this study, the spatial distribution of ILP in bovine liver tissue, induced by a Nd: YAG laser with an interstitial sapphire-frosted contact probe, was evaluated by magnetic resonance imaging (MRI). Tissue was exposed to three energy densities of the Nd:YAG laser by a reproducible method of dosimetry. Thermal profiles were measured with a probe inserted 5 mm from the laser tip. T1-weighted magnetic resonance images were taken after the laser exposure. Tissue specimens were then evaluated for standard quantification of laser-induced damages. A linear correlation between the level of laser energy, induced temperature change, lesion size on T1 magnetic resonance image, and volume of histological damage was observed. Further improvement of this technique of dosimetry in an in vivo model should allow the development of software for MRI which will correlate the above parameters and render this technique of ILP clinically useful.

Photodynamic therapy using rhodamine-123 as a new laser dye: biodistribution, metabolism and histology in New Zealand rabbits.

Rhodamine-123 (Rh-123) has been tested recently as a new laser dye for photodynamic therapy of human tumors in vitro and in vivo. Prior to initiation of clinical studies of this technique, we evaluated the biodistribution, metabolism, and pathological changes of Rh-123 in rabbits after systemic, repetitive injections of the dye in escalating doses. At doses between 0.1 to 1 mg/kg of Rh-123 injected intramuscularly (IM) daily for 5 days, no local or systemic toxicity was observed during the 4 weeks of follow-up. The peak concentrations of Rh-123 in micrograms/g of tissue was distributed as follows: kidney (3.24) greater than heart (2.24) greater than spleen (1.77) greater than lung (0.61) greater than liver (0.38) greater than skin (0.30) greater than skeletal muscle (0.17) greater than genitals (0.13) greater than brain (0.04). The elimination of Rh-123 was very rapid, with the dye falling to 2.7% of peak concentration at 72 hours in the kidneys, and to undetectable levels at 240 hours postinjection in all organs, except the skin, which retained 3% of the peak level at 240 hours. The low toxicity and rapid metabolism of Rh-123 in this preclinical model suggests that the dye and Argon laser may represent an effective combination for treatment of superficial malignancies.

Interstitial laser phototherapy assisted by magnetic resonance imaging: a new technique for monitoring laser-tissue interaction.

The rapid technological advances of magnetic resonance imaging, laser fiberoptics, and compatible probes may allow treatment of deep and sometimes surgically unreachable tumors of the head and neck with minimal morbidity through interstitial laser phototherapy. In this study, a new application of magnetic resonance imaging was developed to monitor and quantify laser-induced tissue damages. Pig skin was exposed to increased levels of argon laser (514.5 nm) at energy densities between 62.5 and 375 J/cm2 as determined by an accurate and reproducible method of dosimetry. Thermal profiles were recorded using an infrared sensor and T1- and T2-weighted magnetic resonance images were taken; afterward, biopsies were performed to quantitate the level of tissue damage. Our results demonstrate that above a certain threshold of laser energy, the magnetic resonance imaging findings are temperature dependent. Appropriate development of a scale matching laser energies, temperature profiles, T1- and T2-weighted magnetic resonance images, and histological quantitation of tissue destruction will allow us to optimize the three-dimensional control and monitoring of laser-tissue interactions.