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Biomedical subjects

D D Bigner

Publications and source records attributed to D D Bigner.

At least 217 records · Page 12Linked to original sources
PubMed1988

Melphalan transport, glutathione levels, and glutathione-S-transferase activity in human medulloblastoma.

Melphalan transport, glutathione levels, and glutathione-S-transferase activity were measured in two continuous human medulloblastoma cell lines and transplantable xenografts in athymic nude mice, TE-671 and Daoy. In vitro mean glutathione levels were 10.06 nmol/10(6) cells in TE-671 and 2.96 nmol/10(6) cells in Daoy. In vitro mean glutathione-S-transferase values were 91.52 nmol/min/mg protein in TE-671 and 50.31 nmol/min/mg protein in Daoy. Transport studies revealed kinetic parameters of Km = 108.3 microM, Vmax = 363.1 pmol/10(6) cells/min in TE-671 and Km = 111.7 microM, Vmax = 180.6 pmol/10(6) cells/min in Daoy. Melphalan transport was inhibited by both DL-alpha-2-aminobicyclo[2.2.1]heptane-2- carboxylic acid and sodium ion depletion in TE-671 and Daoy cells in vitro, indicating that both systems of amino acid transport are functional in these medulloblastoma lines. In vivo s.c. xenograft glutathione values were lower (7.79 nmol/mg protein) in TE-671 than in Daoy (13.68 nmol/mg protein). The mean plasma concentration in mice given a 10% lethal dose (71.3 mg/m2) of melphalan i.p. was 50.3 microM at 10 min, with the half-life of 29.9 min. At this dose, s.c. xenograft levels were 2- to 3-fold higher in TE-671 than in Daoy tumors for the 3-h period measured. These studies demonstrate transport parameters confirming facilitated transport of melphalan in human medulloblastoma, a mean murine plasma melphalan concentration (following treatment with melphalan) above the in vitro drug dose at which there is a 90% reduction in the number of colonies in comparison to controls for TE-671 and Daoy for 2 h, and glutathione and glutathione-S-transferase levels in the same range previously reported in other melphalan-sensitive and melphalan-resistant human tumors. Future work with spontaneous and acquired melphalan-resistant human medulloblastoma cell lines and xenografts will define the role of these mechanisms in mediating drug resistance.

Animals↗
PubMed1988

Experimental chemotherapy of human medulloblastoma cell lines and transplantable xenografts with bifunctional alkylating agents.

A series of bifunctional alkylators were tested against the genotypically and phenotypically heterogeneous continuous human medulloblastoma cell lines, TE-671, Daoy, and D283 Med in vitro and against TE-671 and Daoy growing as s.c. and intracranial xenografts in athymic mice. Drugs tested included melphalan, cyclophosphamide, iphosphamide, phenylketocyclophosphamide, thiotepa, 1,3-bis(2-chloroethyl)-1-nitrosourea (in vivo), and busulfan (in vivo). Melphalan and phenylketocyclophosphamide were the most active agents in vitro with drug doses at which there is a 90% reduction in the number of colonies in comparison to controls of 2.13, 5.29, and 4.72 microM for melphalan and 4.60, 5.01, and 4.34 microM for phenylketocyclophosphamide against TE-671, D283 Med, and Daoy, respectively. Melphalan, cyclophosphamide, iphosphamide, phenylketocyclophosphamide, and thiotepa produced significant growth delays against s.c. TE-671 and Daoy xenografts, while no activity could be demonstrated for 1,3-bis(2-chloroethyl)-1-nitrosourea or busulfan. Melphalan, cyclophosphamide, iphosphamide, and thiotepa also produced significant increases in median survival in mice bearing intracranial TE-671 and Daoy xenografts. These results extend our previous studies demonstrating the antitumor activity of nitrogen and phosphoramide mustard-based bifunctional alkylating agents in the treatment of human medulloblastoma continuous cell lines and transplantable xenografts, and support the continued use of these agents in clinical trials.

Alkylating Agents↗
PubMed1988

Treatment of intracranial human glioma xenografts with 131I-labeled anti-tenascin monoclonal antibody 81C6.

Lack of tumor specificity renders current modalities for treating malignant glioma ineffective. The administration of 131I-labeled monoclonal antibody (Mab) 81C6, which reacts with the glioma-associated extracellular matrix antigen, tenascin, to nude mice carrying s.c. human glioma xenografts has resulted in significant tumor growth delay and tumor regression. In this study, we evaluated the therapeutic efficacy of 131I-labeled 81C6 in athymic rats bearing intracranial human glioma xenografts, a more appropriate model for human gliomas. Mab 81C6, an IgG2b immunoglobulin, and an isotype-matched control Mab, 45.6, were labeled at 12.5-23.6 mCi/mg with chloramine-T. The Mabs were given i.v. at 1.25 and 2.5 mCi/animal for 131I-labeled 81C6, and 1.25 mCi for 131I-labeled 45.6 control. Therapeutic response was evaluated by survival prolongation using Wilcoxon rank sum analysis. Three experiments were done. No significant survival prolongation was found in the trial in which the average tumor size at the time of Mab administration was 60 +/- 14 mm3, two-thirds the size which causes animal death. In experiment 2, Mab was given at 16 +/- 14 mm3 average intracranial tumor volume. Statistically significant (P less than or equal to 0.005) survival prolongation was found for animals treated with 2.5 mCi 131I-labeled 81C6. In that experiment, male animals with intracranial xenografts had significantly shorter survival than females (P less than or equal to 0.005). When only female animals were used in the analysis, the 1.25-mCi 81C6 group also was found to have longer survival benefit (P less than or equal to 0.01). In the third experiment, only female animals were used and the tumor size at the initiation of treatment was 20 +/- 9 mm3. Highly significant survival prolongation again was found in both 1.25 (P = 0.001) and 2.5 mCi (P less than 0.001) 131I-labeled 81C6 groups. The estimated dose to intracranial tumors from 1.25 mCi of 131I-labeled Mab was 1585 rads for 81C6 and 168 rads for 45.6. Dose to other organs from 81C6 and 45.6 was similar, ranging between 31 rads to the brain and 734 rads to the bone marrow. However, normocellularity was observed in most marrow tissue examined microscopically. Three animals receiving the low dose (1.25 mCi 81C6) survived for more than 71 days with apparent cures. In conclusion, intracranial human glioma xenografts were treated successfully with 131I-labeled 81C6 but not control Mab.

Animals↗
PubMed1988

Enhanced melphalan cytotoxicity following buthionine sulfoximine-mediated glutathione depletion in a human medulloblastoma xenograft in athymic mice.

The effect and therapeutic consequences of buthionine-(SR)-sulfoximine (BSO)-mediated depletion of glutathione in the human medulloblastoma-derived cell line, TE-671, growing as s.c. xenografts in athymic nude mice were examined. The glutathione content of the s.c. xenografts was 1.11 +/- 0.15 mumol/g (7.79 +/- 1.61 nmol/mg of protein). Administration i.p. to tumor-bearing mice of D,L-BSO (two doses at 12-h intervals; 5 mmol/kg) depleted the glutathione content of the xenografts to 25.7% of control. Administration of a 30 mM solution of L-BSO in drinking water for 96 h depleted the glutathione content to 17.4% of control. Depletion of glutathione with these regimens resulted in a significant increase in the s.c. tumor growth delay over that produced by melphalan alone: 17.2 days versus 12.6 days for D,L-BSO (i.p.) plus melphalan versus melphalan and 22.9 days versus 16.6 days for L-BSO (p.o.) plus melphalan versus melphalan. These studies demonstrate the increased cytotoxicity of melphalan resulting from BSO-mediated depletion of glutathione in human medulloblastoma and support further efforts to modulate the chemosensitivity and radiosensitivity of this tumor by modulation of glutathione.

Animals↗
PubMed1988

Amplification and expression of the epidermal growth factor receptor gene in human glioma xenografts.

Xenografts from eight malignant human gliomas were established in athymic mice and were used to study amplification and expression of the epidermal growth factor receptor (EGFR) gene. Tissue identity between biopsy and xenografts was confirmed by karyotypic profiles, which showed that each glioma xenograft retained structural abnormalities, including double minute chromosomes, present in the parent glioma. EGFR gene amplification was found in six of the eight glioma biopsies and their corresponding xenografts. Expression of the EGFR gene was measured by Scatchard analysis, affinity reactions, immunoprecipitations, Western immunoblots, and immunocytochemistry; significant expression of the EGFR gene was only detectable in xenografts with EGFR gene amplification. Moreover, five of the six xenografts with EGFR gene amplification demonstrated structural alterations of the EGFR gene, which was associated with low-molecular-weight EGFR proteins. These xenografts represent an excellent tissue source and in vivo model system for characterizing the epidermal growth factor receptor in malignant human gliomas.

Animals↗
PubMed1988

Therapeutic efficacy of antiglioma mesenchymal extracellular matrix 131I-radiolabeled murine monoclonal antibody in a human glioma xenograft model.

The development of Mabs, particularly those reactive with primary brain tumors but not with normal brain, provides a potential means of delivering therapeutic agents selectively to human malignant gliomas. Mab 81C6, an IgG2b immunoglobulin, which defines an epitope of the glioma-associated extracellular matrix protein tenascin, has been shown to bind to human glioma cell lines, glioma xenografts in nude mice, and primary human gliomas, but not to normal adult or fetal brain. To test the therapeutic potential of this Mab for targeted delivery of isotopes, nude mice bearing progressively growing s.c. xenografts of D-54 MG, a human glioma cell line, were given injections via the tail vein of either buffer, unlabeled 81C6, 131I-labeled 81C6, or 131I-labeled 45.6, a nonspecific control Mab of the same isotype. Specific activities of the Mab range from 6.0 to 15.5 mCi/mg with protein doses from 7.6 to 167 micrograms. The doses given by injection per animal for labeled 81C6 were 50, 250, 500, and 1000 mu Ci and 500 and 1000 mu Ci for 45.6. Tumor response was measured by growth delay in reaching 1000 or 5000 mm3 tumor volumes using the Wilcoxon rank sum test, and by comparing the proportion of tumors that had regression in volume after treatment using the Fisher exact test. Statistically significant growth delays at 1000 mm3 were noted in 1 of 3 experiments with 500 mu Ci 81C6 (P less than 0.001) and 2 of 3 for 1000 mu Ci 81C6 (P = 0.001 and less than 0.001). At 5000 mm3, statistically significant growth delays were seen with radiolabeled 81C6 in 2 of 2 experiments at 250 mu Ci (P = 0.01 and 0.02), 4 of 4 at 500 mu Ci (P = 0.03-less than 0.001), and 2 of 2 at 1000 mu Ci (P = less than or equal to 0.001) and with radiolabeled 45.6 in 1 of 1 at 1000 mu Ci (P = 0.01). The percentage of animals with tumor regression progressively increased with increasing doses of isotope. For radiolabeled 45.6, there were 0 of 10 regressors at 500 and 1 of 10 at 1000 mu Ci. For radiolabeled 81C6, there were 0 of 6 regressors at 50 mu Ci, 1 of 16 (6%) at 250 mu Ci, 7 of 38 (18%) at 500, and 15 of 28 (54%) at 1000 mu Ci. Statistically significant tumor regression was seen only at doses of 500 and 1000 mu Ci of 131I-81C6.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Specific chromosomal abnormalities in malignant human gliomas.

Karyotypic analysis of 54 malignant human gliomas (5 anaplastic astrocytomas, 43 glioblastoma multiformes, 3 gliosarcomas, 2 giant cell glioblastomas, 1 anaplastic mixed glioma) has demonstrated that 12 tumors contained normal stemlines or only lacked one sex chromosome. The 42 tumors with abnormal karyotypes included 38 tumors which could be completely analyzed. Six of these 38 cases had near-triploid or near-tetraploid stemlines and 32 had near-diploid stemlines. Statistically significant numerical deviations in the near-diploid group were gains of chromosome 7 (26 of 32; P less than 0.001), and losses of chromosome 10 (19 of 32; P less than 0.001). Double minutes occurred in 18 of 32 near diploid tumors. The distribution of structural abnormalities was analyzed statistically by comparing the incidence of breakpoint in each chromosomal arm to the expected value based on chromosomal arm length. This analysis demonstrated that structural abnormalities of 9p and 19q were significant statistically (P less than 0.005 and P = 0.02, respectively). Although chromosome 1, 6p, the centromeric region of chromosome 11, 13q, and 15q were also frequently involved in structural abnormalities, the incidence of these breaks did not reach statistical significance. This demonstration of specific chromosomal abnormalities in near-diploid gliomas provides the basis for the investigation of genes which may be quantitatively or qualitatively altered in these neoplasms.

Adult↗
PubMed1988

Growth effects of epidermal growth factor (EGF) and a monoclonal antibody against the EGF receptor on four glioma cell lines.

Epidermal growth factor (EGF) has been shown to stimulate DNA synthesis and cell division in normal glia. At least half of malignant human gliomas (MHG) express high levels of the EGF receptor (EGFR), which are above those detected in normal brain. The demonstration that antibodies against the EGFR inhibit the growth of squamous cell carcinoma line A-431, with large numbers of EGFR, in vitro and in vivo raises the possibility that these agents could be used therapeutically against malignant human gliomas either alone or conjugated to other agents. We have measured the growth effects of EGF and an anti-EGFR monoclonal antibody, 528 (Ab-528), on four well-characterized human malignant glioma cell lines, D-263 MG, D-247 MG, U-343 MGa Cl 2:6, and D-37 MG, with 2.9 x 10(4), 1.5 x 10(5), 8.6 x 10(5) and 1.59 x 10(6) EGFRs per cell, respectively. EGF significantly increased cell number in D-263 MG and D-37 MG by 65% and 74%, respectively, had no effect on D-247 MG, and significantly decreased cell number in U-343 MGa Cl 2:6 by 39%. U-343 MGa Cl 2:6 growth was inhibited 19% by Ab-528, but Ab-528 had no effect on growth of the other MHG lines. Ab-528 significantly inhibited all EGF-mediated growth effects. These studies demonstrate that, although Ab-528 alone has little antiproliferative activity on MHG, it successfully competes with EGF to reduce the biological effects of EGF-EGFR binding. Therefore, this antibody could potentially be used to target radioisotopes to MHG via the EGFR for diagnosis and therapy.

Antibodies, Monoclonal↗
PubMed1988

Structural chromosomal abnormalities in human medulloblastoma.

Seven human medulloblastomas (four primary cerebellar, three recurrent or metastatic) were karyotyped in direct preparation and/or short-term or early culture. One tumor had a 46,XX stem line. Four of the six remaining tumors contained one or more i(17q), and three of these six tumors had deletions of extra copies of chromosome #1, resulting in trisomy of 1p, 1q, or both. Two tumors had near-centromeric breaks of chromosome #3, two tumors contained unbalanced translocations with breakpoints at 20q13, and two tumors contained double minutes. These findings suggest that the primary karyotypic deviations of human medulloblastomas are gains of whole chromosomes, which are then either deleted or involved in unbalanced translocations, resulting in partial trisomies.

Adolescent↗
PubMed1988

Gene amplification in malignant human gliomas: clinical and histopathologic aspects.

Gene amplification occurs in 45-50% of malignant human gliomas (MHG). In the present study, 64 genetically characterized gliomas were evaluated to determine if tumors with amplification of the epidermal growth factor receptor (EGFR), N-myc, c-myc, or gli genes had distinctive histopathologic features. There was no significant difference in age (p = 0.10) or gender (p = 0.78) between patients whose tumors contained amplified genes and those whose tumors did not exhibit this characteristic. Although the patients with amplified genes in their tumors survived slightly longer than patients whose tumors had no detectable gene amplification, these differences were not statistically significant (p = 0.21). The 28 tumors with amplification included 24/48 (50%) glioblastoma multiforme, 2/6 (33%) anaplastic astrocytomas and 2/5 (40%) gliosarcomas. No amplification was seen in one oligodendroglioma, three anaplastic mixed gliomas or one giant cell glioblastoma multiforme. Necrosis and endothelial proliferation were equally prevalent among tumors with and without amplification. Comparison of tumors with gene amplification and tumors without this characteristic revealed similar distributions of most morphologic cells types. Although prominent perivascular lymphocytic infiltrates were more frequent in tumors without amplification, this association was of borderline significance statistically. In situ hybridization of tumors with amplification using an EGFR mRNA probe showed intense labeling of different neoplastic cell types including fibrillary and protoplasmic astrocytes, gemistocytes, anaplastic cells, and multinucleated giant cells. Non-neoplastic cells such as hyperplastic endothelium within the tumors did not express detectable EGFR mRNA. These studies demonstrate that (a) cells with quite different morphology within the same tumor can contain the same genetic alteration; (b) tumors of identical histological appearance may have arisen and evolved by different molecular mechanisms; and (c) molecular analyses are necessary to evaluate gene amplification in MHG since this characteristic cannot be accurately predicted by the morphologic or clinical criteria used in this study.

Adult↗
PubMed1988

The localisation of radiolabelled murine monoclonal antibody 81C6 and its Fab fragment in human glioma xenografts in athymic mice.

The localisation of the radioiodinated Fab fragment of monoclonal antibody (Mab) 81C6, reactive with a glioma-associated extracellular matrix antigen, was studied in athymic mice bearing subcutaneous and intracranial xenografts of D-54 MG glioma cells. In vitro 81C6 Fab showed a marked loss of immunoreactivity and affinity for antigen compared to intact Mab 81C6. In vivo, the plasma half-life of 81C6 Fab was 7.0 hours compared to 2.1 days for 81C6. 81C6 Fab levels in tumours peaked at 2.6-3.8% injected dose/g in 2-6 h; Mab 81C6 reached 33.9% dose/g at 48 h. Localisation indices and tumour:tissue ratios were superior for Mab 81C6. Estimated radiation doses to tumour and normal tissues were lower for 131I-81C6 Fab than 131I-81C6. To realise the theoretical benefits of fragments as localising agents, Fab fragments of higher immunoreactivity and affinity, or bivalent F(ab')2 fragments are required.

Animals↗
PubMed1987

Regional localization of a glioma-associated antigen defined by monoclonal antibody 81C6 in vivo: kinetics and implications for diagnosis and therapy.

The pharmacokinetics and regional tissue distribution of two IgG2b immunoglobulins were studied in athymic mice with D54MG human glioma xenografts. Monoclonal antibody (Mab) 81C6, an antiglioma antibody, had a plasma half-life of 2.7 +/- 0.3 (SE) days; 45.6, a control immunoglobulin, had a plasma half-life of 3.3 +/- 0.4 days. The immunoreactive fraction of 81C6 in plasma fell slowly from 0.37 to 0.23 over 9 days. The blood-to-tissue transfer constant (K1) of Mab was 0.11 +/- 0.05 ml/g/h in brain xenografts and 0.07 +/- 0.02 ml/g/h in s.c. xenografts. In contrast, K1 in muscle (0.005 +/- 0.002) and brain (0.0004 +/- 0.0001 ml/g/h) was much lower. The equilibration half-time of Mab in extracellular space was 1.1 +/- 0.2 h in the brain xenografts, 3.6 +/- 1.4 h in s.c. xenografts, and 8.1 and 24 h in muscle and brain, respectively. Distribution and binding of 81C6 was heterogeneous in the xenografts. A binding potential of 5-14 was found centrally and a binding potential of 0.8-1.0 was found peripherally in the brain xenografts. In the s.c. xenografts, the binding potential was higher peripherally than centrally. The exposure of D54MG xenograft tissue to Mab 81C6 was not significantly limited by the permeability of the blood vessels or blood flow due to the long plasma half-life of the immunoglobulin. A comparison of Mab and alpha-aminoisobutyric acid influx constants suggests that Mab entry into intracerebral xenografts occurs through large pores without significant sieving or steric restriction. Under such conditions the differences in influx constants between immunoglobulin and smaller immunoglobulin fragments will be proportional to the differences in their aqueous diffusion constants.

Animals↗
PubMed1987

Identification of an amplified, highly expressed gene in a human glioma.

A gene, termed gli, was identified that is amplified more than 50-fold in a malignant glioma. The gene is expressed at high levels in the original tumor and its derived cell line and is located at chromosome 12 position (q13 to q14.3). The gli gene is a member of a select group of cellular genes that are genetically altered in primary human tumors.

Cell Line↗
PubMed1987

Comparison of monoclonal antibody delivery to intracranial glioma xenografts by intravenous and intracarotid administration.

Monoclonal antibody 81C6, which is directed against a human gliomamesenchymal extracellular matrix antigen, was used to evaluate the potential advantage of intracarotid (i.c.) administration versus i.v. delivery to D-54 MG human glioma intracranial xenografts in immunosuppressed rats. Two approaches were taken. In paired-label analysis, 125I-labeled 81C6 and 131I-labeled isotype control antibody were given to separate groups of animals by either the i.v. or i.c. route. Biodistribution measurements as a function of time were analyzed in terms of the percentage of injected dose/g of tissue and localization indices. No significant difference (P greater than 0.19 to P greater than 0.56) was demonstrated between the i.v. and i.c. routes. To control for the large localization variation inherent in the animal model used, an alternative experimental design, paired-injection analysis, was performed in which 125I- and 131I-labeled 81C6 were simultaneously administered by the i.c. and i.v. routes to the same animal. Significantly higher levels of percentage of dose/g of tissue and localization ratios (P less than 0.05 to P less than 0.005) were shown from Day 1 to Day 3 for 81C6 given i.c. Approximately 20% more antibody was delivered to the D-54 MG intracranial tumor by the i.c. route during the experimental period of 5 days. No difference in the levels of normal tissue exposure between the two routes of administration was seen. These data suggest an advantage exists for whole monoclonal antibody given i.c. and that, theoretically, a greater advantage may be present for smaller molecules such as Fab and F(ab')2 fragments.

Animals↗
PubMed1987

Simultaneous measurements of blood flow and blood-to-tissue transport in xenotransplanted medulloblastomas.

We used double-label quantitative autoradiography to study blood flow (with [131I]iodoantipyrine) and blood-to-tissue transport (with [14C]-alpha-aminoisobutyric acid) in 20 TE-671 medulloblastomas xenotransplanted into nude rats. Microscopically, two distinct patterns of tumor growth were observed: (a) a solid tumor mass; and (b) a tumor in which nearly all tumor cells were located perivascularly. These two tumor patterns differed markedly in values of blood flow (F) and the transfer constant (K) of alpha-aminoisobutyric acid. The solid tumors (N = 17) had averaged mean values of F = 36.8 +/- 5.3 (SE) and K = 8.0 +/- 0.7 ml/100 g/min. The perivascular tumors, which were fewer in number (N = 3), had averaged mean values of F = 83.8 +/- 9.8 and K = 0.4 +/- 0.06 ml/100 g/min. Calculated values of the net extraction fraction (En) of alpha-aminoisobutyric acid were 0.54 +/- 0.07 for the solid tumors and 0.009 +/- 0.001 for the perivascular tumors. K and En for the solid tumors are the highest for any brain tumor model reported to date. The high rates of blood-to-tissue transport may explain why intracranial TE-671 medulloblastomas in nude mice respond to treatment with water-soluble chemotherapeutic drugs, unlike most other brain tumor models.

Aminoisobutyric Acids↗
PubMed1987

Differential retention of rhodamine 123 by avian sarcoma virus-induced glioma and normal brain tissue of the rat in vivo.

The time course of uptake, retention and clearance of the cationic lipophilic dye, rhodamine 123 (Rh123), within the central nervous system was qualitatively evaluated in rats. Weanling rats were injected intracerebrally with avian sarcoma virus, which induced malignant gliomas in situ before injection of Rh123. Comparison was made of the amount of fluorescence of Rh123 within the normal cerebral cortex, myelinated tracts of the brain, meninges, choroid plexus, and neoplastic foci at 1, 4, 8, 12 and 24 hours after intravenous injection. Fluorescence microscopy was utilized to identify tissues containing the dye. Normal neuropil did not contain Rh123 at any of the time periods studied. Gliomas retained the dye at 1, 4, 8 and 12 hours, with increasing uniformity of distribution and decreasing intensity of fluorescence over this time period. Fluorescence was not detected at 24 hours within the neoplastic tissues, but was evident at all time periods studied within the choroid plexus. The specific retention of Rh123 by malignant glioma and by the choroid plexus in vivo suggests that Rh123 may be useful for photochemotherapeutic treatment of brain neoplasms and disorders of the choroid plexus.

Animals↗
PubMed1987

Correlation of neuropathologic findings, computerized tomographic and high-resolution ultrasound scans of canine avian sarcoma virus-induced brain tumors.

The location, size, geometry and neuropathological findings of anaplastic astrocytomas (AA), gliosarcomas and sarcomas induced by the avian sarcoma virus (ASV) in dogs were compared with images generated using computerized tomography (CT) and real time high-resolution ultrasound (HRUS). Seven AA showed a wide range of findings on CT. Pre-contrast CT scans showed that the tumors could be hyper, hypo, or isodense. Three of seven AA had no contrast enhancement; two of these tumors were also isodense which resulted in a false-negative CT exam. Partial enhancement was seen in one tumor. This resulted in a sensitivity of detection of 72%. Real time HRUS was able to define tumor location, size and geometry of the AA missed or incompletely imaged by CT. All tumors were hyperechoic. Inhomogeneity of the echo pattern was due to hemorrhage, cyst formation, and necrosis within the tumors. Such secondary tumor characteristics were more accurately defined by HRUS compared to CT. Vasogenic edema in the brain surrounding tumors was of low density on CT and hypoechoic or indistinguishable from normal brain on US. Similar findings were seen in six gliosarcomas, two of which were not visualized by either pre- or post-contrast enhanced CT scans (sensitivity of 66%). Sarcomas differed in that they were either hyper or isodense; none were hypodense. The area of increased density matched the tumor geometry and correlated with dense cellularity and reticulin deposition. All 13 sarcomas showed contrast enhancement (100% sensitivity), but in two tumors, contrast enhanced CT underestimated the size of the tumor. Because of the large size and multiplicity of the sarcomas, HRUS imaging was not able to resolve the entire tumor volume because of limited imaging access. Intravenously injected horseradish peroxidase (HRP) crossed the tumor blood-brain barrier (BBB) only in those tumors in which contrast enhancement was seen. These studies suggest that intraoperative HRUS imaging may be useful in detecting and delineating human AA incompletely visualized by CT.

Animals↗