Neuroimaging clinics of North America
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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.
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Neuroimaging Clin. N. Am. · Nov 2002
ReviewAnti-angiogenic agents for the treatment of brain tumors.
It is accepted that novel therapeutic approaches are needed for the majority of patients with malignant brain tumors. The vascularity of many primary brain tumors and the encouraging preclinical studies suggest that antiangiogenic agents have the potential to become an important component of multimodality treatment of patients with brain tumors. The understanding of the biology of angiogenesis is improving rapidly, offering the hope for more specific vascular targeting of brain tumor neovasculature. Neuroimaging techniques evaluating the angiogenic process and the impact of antiangiogenic agents will be an important tool for the rapid development of these novel therapeutic agents.
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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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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
ReviewIntraoperative magnetic resonance imaging and magnetic resonance imaging-guided therapy for brain tumors.
Since their introduction into surgical practice in the mid 1990s, intraoperative MRI systems have evolved into essential, routinely used tools for the surgical treatment of brain tumors in many centers. Clear delineation of the lesion, "under-the-surface" vision, and the possibility of obtaining real-time feedback on the extent of resection and the position of residual tumor tissue (which may change during surgery due to "brain-shift") are the main strengths of this method. High-performance computing has further extended the capabilities of intraoperative MRI systems, opening the way for using multimodal information and 3D anatomical reconstructions, which can be updated in "near real time." MRI sensitivity to thermal changes has also opened the way for innovative, minimally invasive (LASER ablations) as well as noninvasive therapeutic approaches for brain tumors (focused ultrasound). Although we have not used intraoperative MRI in clinical applications sufficiently long to assess long-term outcomes, this method clearly enhances the ability of the neurosurgeon to navigate the surgical field with greater accuracy, to avoid critical anatomic structures with greater efficacy, and to reduce the overall invasiveness of the surgery itself.