Neuroimaging clinics of North America
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Neuroimaging Clin. N. Am. · Nov 2002
ReviewCharacterization of untreated gliomas by magnetic resonance spectroscopic imaging.
Although there are trends in the morphologic, metabolic, hemodynamic, and structural properties of untreated gliomas that are reflected in MR measurements, there is considerable heterogeneity both within and between lesions of the same histologic grade. The spatial extent of the abnormality in ADC and RA images is similar to the T2 lesion, but there is no obvious difference in intensity between grades. The rCBV is significantly increased in the enhancing volume of grade 4 lesions but is similar or reduced in intensity for most grade 3 lesions. ⋯ The correlations between rCBV, Cho, and ADC suggest that cellularity, membrane turnover, and vascularity are linked in grade 4 lesions. It is not clear whether there is any relationship between these parameters regions in grade 2 or grade 3 gliomas. While further work is required to optimize the methodology associated with these MR parameters, it seems likely that combining the information from such measurements may be valuable for predicting outcome and tailoring therapy to individual patients.
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Neuroimaging Clin. N. Am. · Nov 2002
ReviewViral imaging in gene therapy noninvasive demonstration of gene delivery and expression.
Gene therapy is a rapidly developing modality of treatment, with applications in acquired and inherited disorders. Gene delivery vehicles ("vectors") are the main impediment in the evolution of gene therapy into a clinically acceptable mainstream therapy. Vectors based on viral particles are the most commonly used vehicles to carry genes to the organs and tissues of interest. ⋯ Recent progress in viral vector production and better understanding of molecular aspects of vector delivery and targeting issues has created the need for imaging techniques that would be useful in addressing the problems and opportunities inherent in viral gene therapy development. Two integral components of gene therapy monitoring, the imaging of gene delivery and the imaging of resultant exogenous gene expression, are recognized. These molecular imaging components provide a realistic means for assessment of safety and efficacy of preclinical and clinical development of gene therapy.
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As an immunization platform for brain tumors, dendritic cells supply an impressive host of advantages. On the simplest level, they provide the safety and tumor-specificity so wanted by current therapeutic options. ⋯ Directions to take now include the identification of new tumor-specific and tumor-associated antigens; the determination of the optimal dendritic cell subtype, generation, loading method, maturation state, dose, and route of delivery for immunizations; the further characterization of dendritic cells and their activities; and, potentially, the discovery of ways to pulse dendritic cells efficiently in vivo. Preclinical studies continue to play an important role in refining this form of active immunotherapy.
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Neuroimaging Clin. N. Am. · Nov 2002
ReviewMolecular abnormalities and correlations with tumor response and outcome in glioma patients.
Molecular analysis approaches hold promise to refine the management of patients with malignant gliomas. An important step in the application of these techniques to guide clinical decision-making involves transitioning these approaches from the research setting into the clinical diagnostic arena, using methods that can be performed rapidly and reliably on surgically obtained tumor specimens. ⋯ An associated challenge involves demonstrating that biological stratification can support therapeutic stratification that will influence, rather than merely predict, the outcome of patients with brain tumors. The realization of this long-range goal will require the identification of novel therapeutic strategies that hold promise for improving the outcome of molecularly defined subsets of high-grade gliomas, which as a group remain largely resistant to conventional therapies.
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Neuroimaging Clin. N. Am. · Nov 2002
ReviewImportance of hypoxia in the biology and treatment of brain tumors.
The resistance of gliomas to treatment with radiation and antineoplastic drugs may result in part from the effects of the extensive, severe hypoxia that is present in these tumors. It is clear that brain tumors contain extensive regions in which the tumor cells are subjected to unphysiological levels of hypoxia. Hypoxic cells are resistant to radiation. ⋯ During the past 50 years, many attempts have been made to circumvent the therapeutic resistance induced by hypoxia, by improving tumor oxygenation, by using oxygen-mimetic radiosensitizers, by adjuvant therapy with drugs that are preferentially toxic to hypoxic cells, by using hyperthermia, or by devising radiation sources and regimens that are less affected by hypoxia. Past clinical trials have provided tantalizing suggestions that the outcome of therapy can be improved by many of these approaches, but none has yet produced a significant, reproducible improvement in the therapeutic ratio, which would be needed for any of these approaches to become the standard therapy for these diseases. Several ongoing clinical trials are addressing other, hopefully better regimens; it will be interesting to see the results of these studies.