Photoirradiation therapy of experimental malignant glioma with 5-aminolevulinic acid

2002 ◽  
Vol 97 (4) ◽  
pp. 970-976 ◽  
Author(s):  
Bernhard Olzowy ◽  
Cornelia S. Hundt ◽  
Susanne Stocker ◽  
Karl Bise ◽  
Hans Jürgen Reulen ◽  
...  
Keyword(s):  
Body Weight ◽  
Brain Tumors ◽  
Intravenous Administration ◽  
Aminolevulinic Acid ◽  
Cold Injury ◽  
Mr Images ◽  
Content Type ◽  
Experimental Brain Tumors ◽  
Photofrin Ii ◽  
Fine Print

Object. Accumulation of protoporphyrin IX (PPIX) in malignant gliomas is induced by 5-aminolevulinic acid (5-ALA). Because PPIX is a potent photosensitizer, the authors sought to discover whether its accumulation might be exploited for use in photoirradiation therapy of experimental brain tumors, without injuring normal or edematous brain. Methods. Thirty rats underwent craniotomy and were randomized to the following groups: 1) photoirradiation of cortex (200 J/cm2, 635-nm argon-dye laser); 2) photoirradiation of cortex (200 J/cm2) 6 hours after intravenous administration of 5-ALA (100 mg/kg body weight); 3) cortical cold injury for edema induction; 4) cortical cold injury with simultaneous administration of 5-ALA (100 mg/kg body weight) and photoirradiation of cortex (200 J/cm2) 6 hours later; or 5) irradiation of cortex (200 J/cm2) 6 hours after intravenous administration of Photofrin II (5 mg/kg body weight). Tumors were induced by cortical inoculation of C6 cells and 9 days later, magnetic resonance (MR) images were obtained. On Day 10, animals were given 5-ALA (100 mg/kg body weight) and their brains were irradiated (100 J/cm2) 3 or 6 hours later. Seventy-two hours after irradiation, the brains were removed for histological examination. Irradiation of brains after administration of 5-ALA resulted in superficial cortical damage, the effects of which were not different from those of the irradiation alone. Induction of cold injury in combination with 5-ALA and irradiation slightly increased the depth of damage. In the group that received irradiation after intravenous administration of Photofrin II the depth of damage inflicted was significantly greater. The extent of damage in response to 5-ALA and irradiation in brains harboring C6 tumors corresponded to the extent of tumor determined from pretreatment MR images. Conclusions. Photoirradiation therapy in combination with 5-ALA appears to damage experimental brain tumors selectively, with negligible damage to normal or perifocal edematous tissue.

Fluorescence-guided resection of glioblastoma multiforme utilizing 5-ALA-induced porphyrins: a prospective study in 52 consecutive patients

2000 ◽  
Vol 93 (6) ◽  
pp. 1003-1013 ◽  
Author(s):  
Walter Stummer ◽  
Alexander Novotny ◽  
Herbert Stepp ◽  
Claudia Goetz ◽  
Karl Bise ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Mr Imaging ◽  
Aminolevulinic Acid ◽  
Univariate Analysis ◽  
Tumor Resection ◽  
Mr Images ◽  
Content Type ◽  
Tissue Fluorescence ◽  
Solid Fluorescence ◽  
Fine Print

Object. It has been established that 5-aminolevulinic acid (5-ALA) induces the accumulation of fluorescent porphyrins in glioblastoma multiforme (GBM), a phenomenon potentially exploitable to guide tumor resection. In this study the authors analyze the influence of fluorescence-guided resection on postoperative magnetic resonance (MR) imaging and survival in a series of patients who underwent surgery in the authors' department.Methods. Fifty-two consecutive patients with GBM received oral doses of 5-ALA (20 mg/kg body weight) 3 hours before induction of anesthesia. Intraoperatively, tumor fluorescence was visualized using a modified operating microscope. Fluorescing tissue was removed whenever it was considered safely possible. Residual enhancement on early postoperative MR imaging was quantified and related to each patient's characteristics to determine which factors influenced resection. Survival was analyzed using the Kaplan—Meier method and multivariate analysis was performed in which the Karnofsky Performance Scale (KPS) score, residual fluorescence, patient age, and residual enhancement on MR images were considered.Intraoperatively, two fluorescence qualities were perceived: solid fluorescence generally reflected coalescent tumor, whereas vague fluorescence mostly corresponded to infiltrative tumor. Complete resection of contrast-enhancing tumor was accomplished in 33 patients (63%). Residual intraoperative tissue fluorescence left unresected for safety reasons predicted residual enhancement on MR images in 18 of the 19 remaining patients. Age, residual solid fluorescence, and absence of contrast enhancement in MR imaging were independent explanatory factors for survival, whereas the KPS score was significant only in univariate analysis. No perioperative deaths and one case of permanent morbidity were encountered.Conclusions. The observations in this study indicate the usefulness of 5-ALA—induced tumor fluorescence for guiding tumor resection. The completeness of resection, as determined intraoperatively from residual tissue fluorescence, was related to postoperative MR imaging findings and to survival in patients suffering from GBM.

Regional metabolism in experimental brain tumors in cats: relationship with acid/base, water, and electrolyte homeostasis

1992 ◽  
Vol 77 (6) ◽  
pp. 917-926 ◽  
Author(s):  
Yoshikazu Okada ◽  
Otmar Kloiber ◽  
Konstantin A. Hossmann
Keyword(s):  
Brain Tumors ◽  
Tumor Tissue ◽  
Atp Depletion ◽  
Resonance Spectroscopy ◽  
Peritumoral Edema ◽  
Metabolic Pattern ◽  
Tissue Ph ◽  
Content Type ◽  
Experimental Brain Tumors ◽  
Fine Print

✓ Experimental brain tumors were produced in cats by xenotransplantation of the rat glioma clone F98 into the white matter of the left hemisphere. One to 4 weeks after implantation, local adenosine triphosphate (ATP), glucose, lactate, and tissue pH were measured via imaging techniques in cryostat sections passing through the center of the tumor and correlated with changes in water and electrolyte content. The tumors exhibited a heterogeneous metabolic pattern, with a tendency for ATP to decrease and lactate to increase during tumor development. Tissue pH was above 7.5 in tumors with high ATP content but it sharply declined at low ATP levels. In peritumoral edema, ATP also decreased and lactate increased but, in contrast to tumor tissue, pH became more alkaline. Metabolic changes were associated with edema formation, as evidenced by the rise in water and sodium content. There was a distinct difference between tumor tissue and peritumoral edema: in tumor tissue, pH declined with increasing water content, whereas in peritumoral edema it increased. These observations are interpreted as follows: 1) in tumor tissue, “lactacidosis” and ATP depletion are attributed to disturbances in blood flow, resulting in metabolic failure and the intracellular “cytotoxic” accumulation of water; 2) in peritumoral edema, “lactalkalosis” is the result of an efflux of (alkaline) lactate salts from the tumor into the expanded extracellular compartment, and the decrease in ATP is the volumetric effect of extracellular “vasogenic” edema fluid and not the result of cellular energy failure. These findings are of importance for the interpretation of volume-selective magnetic resonance spectroscopy and may contribute to the establishment of spectroscopic criteria for the evaluation of therapeutical interventions.

Evaluation of gamma thalamotomy for parkinsonian and other tremors: survival of neurons adjacent to the thalamic lesion after gamma thalamotomy

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 120-127 ◽  
Author(s):  
Chihiro Ohye ◽  
Tohru Shibazaki ◽  
Junji Ishihara ◽  
Jie Zhang
Keyword(s):  
Tissue Reaction ◽  
Vascular Lesions ◽  
Thalamic Lesion ◽  
Mr Images ◽  
Unsatisfactory Result ◽  
Content Type ◽  
Rhythmic Discharge ◽  
Latent Interval ◽  
Fine Print

Object. The effects of gamma thalamotomy for parkinsonian and other kinds of tremor were evaluated. Methods. Thirty-six thalamotomies were performed in 31 patients by using a 4-mm collimator. The maximum dose was 150 Gy in the initial six cases, which was reduced to 130 Gy thereafter. The longest follow-up period was 6 years. The target was determined on T2-weighted and proton magnetic resonance (MR) images. The point chosen was in the lateral-most part of the thalamic ventralis intermedius nucleus. This is in keeping with open thalamotomy as practiced at the authors' institution. In 15 cases, gamma thalamotomy was the first surgical procedure. In other cases, previous therapeutic or vascular lesions were visible to facilitate targeting. Two types of tissue reaction were onserved on MR imaging: a simple oval shape and a complex irregular shape. Neither of these changes affected the clinical course. In the majority of cases, the tremor subsided after a latent interval of approximately 1 year after irradiation. The earliest response was demonstrated at 3 months. In five cases the tremor remained. In four of these cases, a second radiation session was administered. One of these four patients as well as another patient with an unsatisfactory result underwent open thalamotomy with microrecording. In both cases, depth recording adjacent to the necrotic area revealed normal neuronal activity, including the rhythmic discharge of tremor. Minor coagulation was performed and resulted in immediate and complete arrest of the remaining tremor. Conclusions. Gamma thalamotomy for Parkinson's disease seems to be an alternative useful method in selected cases.

The integration of metabolic imaging in stereotactic procedures including radiosurgery: a review

2002 ◽  
Vol 97 ◽  
pp. 542-550 ◽  
Author(s):  
Marc Levivier ◽  
David Wikler ◽  
Nicolas Massager ◽  
Philippe David ◽  
Daniel Devriendt ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Brain Tumors ◽  
Treatment Planning ◽  
Target Volume ◽  
Emission Tomography ◽  
Low Grade ◽  
Content Type ◽  
Positron Emission ◽  
Pet Scanning ◽  
Fine Print

Object. The authors review their experience with the clinical development and routine use of positron emission tomography (PET) during stereotactic procedures, including the use of PET-guided gamma knife radiosurgery (GKS). Methods. Techniques have been developed for the routine use of stereotactic PET, and accumulated experience using PET-guided stereotactic procedures over the past 10 years includes more than 150 stereotactic biopsies, 43 neuronavigation procedures, and 34 cases treated with GKS. Positron emission tomography—guided GKS was performed in 24 patients with primary brain tumors (four pilocytic astrocytomas, five low-grade astrocytomas or oligodendrogliomas, seven anaplastic astrocytomas or ependymomas, five glioblastomas, and three neurocytomas), five patients with metastases (single or multiple lesions), and five patients with pituitary adenomas. Conclusions. Data obtained with PET scanning can be integrated with GKS treatment planning, enabling access to metabolic information with high spatial accuracy. Positron emission tomography data can be successfully combined with magnetic resonance imaging data to provide specific information for defining the target volume for the radiosurgical treatment in patients with recurrent brain tumors, such as glioma, metastasis, and pituitary adenoma. This approach is particularly useful for optimizing target selection for infiltrating or ill-defined brain lesions. The use of PET scanning contributed data in 31 cases (93%) and information that was specifically utilized to adapt the target volume in 25 cases (74%). It would seem that the integration of PET data into GKS treatment planning may represent an important step toward further developments in radiosurgery: this approach provides additional information that may open new perspectives for the optimization of the treatment of brain tumors.

Gamma knife radiosurgery for metastatic brain tumors from lung cancer: a comparison between small cell and non—small cell carcinoma

2002 ◽  
Vol 97 ◽  
pp. 484-488 ◽  
Author(s):  
Toru Serizawa ◽  
Junichi Ono ◽  
Toshihiko Iichi ◽  
Shinji Matsuda ◽  
Makoto Sato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Tumors ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
Small Cell ◽  
Metastatic Brain Tumors ◽  
Cell Lung Carcinoma ◽  
Content Type ◽  
Significant Difference ◽  
Fine Print

Object. The purpose of this retrospective study was to evaluate the effectiveness of gamma knife radiosurgery (GKS) for the treatment of metastatic brain tumors from lung cancer, with particular reference to small cell lung carcinoma (SCLC) compared with non-SCLC (NSCLC). Methods. Two hundred forty-five consecutive patients meeting the following five criteria were evaluated in this study: 1) no prior brain tumor treatment; 2) 25 or fewer lesions; 3) a maximum of three tumors with a diameter of 20 mm or larger; 4) no surgically inaccessible tumor 30 mm or greater in diameter; and 5) more than 3 months of life expectancy. According to the same treatment protocol, large tumors (≥ 30 mm) were surgically removed and the other small lesions (< 30 mm) were treated with GKS. New lesions were treated with repeated GKS. Chemotherapy was administered, according to the primary physician's protocol, as aggressively as possible. Progression-free, overall, neurological, qualitative, and new lesion—free survival were calculated with the Kaplan—Meier method and were compared in the SCLC and NSCLC groups by using the log-rank test. The poor prognostic factors for each type of survival were also analyzed with the Cox proportional hazard model. Conclusions. Tumor control rate at 1 year was 94.5% in the SCLC group and 98% in the NSCLC group. The median survival time was 9.1 months in the SCLC group and 8.6 months in the NSCLC group. The 1-year survival rates in the SCLC group were 86.5% for neurological survival and 68.9% for qualitative survival; those in the NSCLC group were 87.9% for neurological and 78.9% for qualitative survival. The estimated median interval to emergence of a new lesion was 6.9 months in the SCLC group and 9.8 months in the NSCLC group. There was no significant difference between the two groups for any type of survival; this finding was verified by multivariate analysis. The results of this study suggest that GKS appears to be as effective in treating brain metastases from SCLC as for those from NSCLC.

Does gamma knife surgery stimulate cellular immune response to metastatic brain tumors? A histopathological and immunohistochemical study

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 180-184 ◽  
Author(s):  
György T. Szeifert ◽  
Isabelle Salmon ◽  
Sandrine Rorive ◽  
Nicolas Massager ◽  
Daniel Devriendt ◽  
...  
Keyword(s):  
Immune Response ◽  
Brain Tumors ◽  
Gamma Knife ◽  
Cellular Immune Response ◽  
Lymphocytic Infiltration ◽  
Gamma Knife Surgery ◽  
Metastatic Brain Tumors ◽  
Content Type ◽  
Cellular Immune ◽  
Fine Print

Object. The aim of this study was to analyze the cellular immune response and histopathological changes in secondary brain tumors after gamma knife surgery (GKS). Methods. Two hundred ten patients with cerebral metastases underwent GKS. Seven patients underwent subsequent craniotomy for tumor removal between 1 and 33 months after GKS. Four of these patients had one tumor, two patients had two tumors, and one patient had three. Histological and immunohistochemical investigations were performed. In addition to routine H & E and Mallory trichrome staining, immunohistochemical reactions were conducted to characterize the phenotypic nature of the cell population contributing to the tissue immune response to neoplastic deposits after radiosurgery. Light microscopy revealed an intensive lymphocytic infiltration in the parenchyma and stroma of tumor samples obtained in patients in whom surgery was performed over 6 months after GKS. Contrary to this, extensive areas of tissue necrosis with either an absent or scanty lymphoid population were observed in the poorly controlled neoplastic specimens obtained in cases in which surgery was undertaken in patients less than 6 months after GKS. Immunohistochemical characterization demonstrated the predominance of CD3-positive T cells in the lymphoid infiltration. Conclusions. Histopathological findings of the present study are consistent with a cellular immune response of natural killer cells against metastatic brain tumors, presumably stimulated by the ionizing energy of focused radiation.

Thymidine kinase-mediated killing of rat brain tumors

1993 ◽  
Vol 79 (5) ◽  
pp. 729-735 ◽  
Author(s):  
David Barba ◽  
Joseph Hardin ◽  
Jasodhara Ray ◽  
Fred H. Gage
Keyword(s):  
Gene Therapy ◽  
Brain Tumors ◽  
Tumor Cells ◽  
Wild Type ◽  
Cns Disorders ◽  
Content Type ◽  
Potential Applications ◽  
Ganciclovir Treatment ◽  
The Brain ◽  
Fine Print

✓ Gene therapy has many potential applications in central nervous system (CNS) disorders, including the selective killing of tumor cells in the brain. A rat brain tumor model was used to test the herpes simplex virus (HSV)-thymidine kinase (TK) gene for its ability to selectively kill C6 and 9L tumor cells in the brain following systemic administration of the nucleoside analog ganciclovir. The HSV-TK gene was introduced in vitro into tumor cells (C6-TK and 9L-TK), then these modified tumor cells were evaluated for their sensitivity to cell killing by ganciclovir. In a dose-response assay, both C6-TK and 9L-TK cells were 100 times more sensitive to killing by ganciclovir (median lethal dose: C6-TK, 0.1 µg ganciclovir/ml; C6, 5.0 µg ganciclovir/ml) than unmodified wild-type tumor cells or cultured fibroblasts. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to kill established brain tumors in rats as quantified by both stereological assessment of brain tumor volumes and studies of animal survival over 90 days. Rats with brain tumors established by intracerebral injection of wild-type or HSV-TK modified tumor cells or by a combination of wild-type and HSV-TK-modified cells were studied with and without ganciclovir treatments. Stereological methods determined that ganciclovir treatment eliminated tumors composed of HSV-TK-modified cells while control tumors grew as expected (p < 0.001). In survival studies, all 10 rats with 9L-TK tumors treated with ganciclovir survived 90 days while all untreated rats died within 25 days. Curiously, tumors composed of combinations of 9L and 9L-TK cells could be eliminated by ganciclovir treatments even when only one-half of the tumor cells carried the HSV-TK gene. While not completely understood, this additional tumor cell killing appears to be both tumor selective and local in nature. It is concluded that HSV-TK gene therapy with ganciclovir treatment does selectively kill tumor cells in the brain and has many potential applications in CNS disorders, including the treatment of cancer.

Early changes measured by magnetic resonance imaging in cerebral blood flow, blood volume, and blood-brain barrier permeability following dexamethasone treatment in patients with brain tumors

1999 ◽  
Vol 90 (2) ◽  
pp. 300-305 ◽  
Author(s):  
Leif Østergaard ◽  
Fred H. Hochberg ◽  
James D. Rabinov ◽  
A. Gregory Sorensen ◽  
Michael Lev ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Magnetic Resonance ◽  
Brain Tumors ◽  
Mr Imaging ◽  
Blood Volume ◽  
Cerebral Blood Volume ◽  
Clinical Effects ◽  
Content Type ◽  
Fine Print

Object. In this study the authors assessed the early changes in brain tumor physiology associated with glucocorticoid administration. Glucocorticoids have a dramatic effect on symptoms in patients with brain tumors over a time scale ranging from minutes to a few hours. Previous studies have indicated that glucocorticoids may act either by decreasing cerebral blood volume (CBV) or blood-tumor barrier (BTB) permeability and thereby the degree of vasogenic edema.Methods. Using magnetic resonance (MR) imaging, the authors examined the acute changes in CBV, cerebral blood flow (CBF), and BTB permeability to gadolinium-diethylenetriamine pentaacetic acid after administration of dexamethasone in six patients with brain tumors. In patients with acute decreases in BTB permeability after dexamethasone administration, changes in the degree of edema were assessed using the apparent diffusion coefficient of water.Conclusions. Dexamethasone was found to cause a dramatic decrease in BTB permeability and regional CBV but no significant changes in CBF or the degree of edema. The authors found that MR imaging provides a powerful tool for investigating the pathophysiological changes associated with the clinical effects of glucocorticoids.

The deposition of Hg203-chlormerodrin in experimental brain tumors

1971 ◽  
Vol 35 (3) ◽  
pp. 303-308 ◽  
Author(s):  
Tatsuya Kobayashi ◽  
Louis Bakay ◽  
Joseph C. Lee
Keyword(s):  
Brain Tumors ◽  
Tumor Cells ◽  
Normal Brain ◽  
Intracranial Tumors ◽  
Electron Microscopic ◽  
Electron Microscopic Autoradiography ◽  
Content Type ◽  
Meningeal Tumors ◽  
Vacuolar System ◽  
Fine Print

✓ The deposition of Hg203-chlormerodrin was studied in intracranial tumors in mice induced by implantation of 20-methyl cholanthrene by tissue assay, as well as light microscopic and electron microscopic autoradiography. The investigations were carried out in astrocytomas, glioblastomas, and meningeal tumors. The chlormerodrin content of the tumors exceeded that of normal brain with a significant tumor/brain ratio ranging from 5.8 to 22.5. It was found that the chlormerodrin molecule becomes rapidly incorporated in the tumor cells, with a preference for that portion of the cytoplasm associated with the vacuolar system.

Accelerated spondylotic changes adjacent to the fused segment following central cervical corpectomy: magnetic resonance imaging study evidence

2004 ◽  
Vol 100 (1) ◽  
pp. 2-6 ◽  
Author(s):  
Vaijayantee Kulkarni ◽  
Vedantam Rajshekhar ◽  
Lakshminarayan Raghuram
Keyword(s):  
Magnetic Resonance ◽  
Mr Imaging ◽  
Imaging Study ◽  
Degenerative Changes ◽  
Adjacent Segment ◽  
Mr Images ◽  
Short Term ◽  
Content Type ◽  
Fine Print

Object. The authors studied whether cervical spine motion segments adjacent to a fused segment exhibit accelerated degenerative changes on short-term follow-up magnetic resonance (MR) imaging. Methods. Preoperative and short-term follow-up (mean duration 17.5 months, range 10–48 months) cervical MR images obtained in 44 patients who had undergone one- or two-level corpectomy for cervical spondylotic myelopathy were evaluated qualitatively and quantitatively. The motion segment adjacent to the fused segment and a segment remote from the fused segment were evaluated for indentation of the thecal sac, disc height, and sagittal functional diameter of the spinal canal on midsagittal T2-weighted MR images. Thecal sac indentations were classifed as mild, moderate, and severe. New indentations of the thecal sac of varying severity (mild in 17 patients [38.6%], moderate in 10 [22.7%], and severe in six [13.6%]) had developed at the adjacent segments in 33 (75%) of 44 patients. The degenerative changes were seen at the superior level in 11 patients, inferior level in 10 patients, and at both levels in 12 patients and resulted from both anterior and posterior element degeneration in the majority (23 [69.6%]) of patients. The remote segments showed mild thecal sac indentations in seven patients and moderate indentations in two patients (nine [20.5%] of 44). Compared with the changes at the remote segment, the canal size was significantly decreased at the superior adjacent segment by 0.9 mm (p = 0.007). No patient sustained a new neurological deficit due to adjacent-segment changes. Conclusions. On short-term follow-up MR imaging, levels adjacent to the fused segment exhibited more pronounced degenerative changes (compared with remote levels) in 75% of patients who had undergone one- or two-level central corpectomy.

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