Sodium magnetic resonance imaging in the management of human high-grade brain tumors

The treatment of high-grade brain tumors involves surgical resection followed by targeted fractionated radiation therapy with concomitant chemotherapy and then follow-up chemotherapy. Conventional proton magnetic resonance (MR) imaging plays a role in the initial detection and anatomical and physiological characterization of the mass, preoperative functional mapping of eloquent cortex for neurosurgical planning, and postoperative imaging for radiation planning usually combined with computed tomography (CT). Subsequent surveillance follow-up MR imaging, usually every 3-4 months beginning after radiation, is used to detect recurrence. These follow-up studies ideally include perfusion and permeability MR imaging techniques to detect increases in tissue vascularity that herald local recurrence of high-grade tumors. Early changes, termed pseudo-progression, induced by the combination of radiation and low-dose chemotherapy with temozolomide (Temodar), occur within weeks to a few months of completing radiation treatment and mimic recurrence, but resolve without further intervention. Later changes of radiation necrosis can also result in a false-positive indication of recurrence, usually beginning many months or even years after completing radiation treatment. Unfortunately, some chemotherapeutic interventions, such as bevacizumab (Avastin), may actually disguise vascular indicators of recurrence (pseudo-response), thereby further delaying the detection of recurrence. Unlike most tumors outside the central nervous system, the failure of treatment for brain tumors results from local recurrence rather than metastatic disease. This behavior of local recurrence along with the poor prognosis suggests that the current standard of medical care for high-grade tumors requires improvement. Despite the multimodality approach to treatment, the assessment of response is currently done retrospectively by the absence of recurrence in follow-up imaging studies rather than prospectively by measuring the response during treatment. Prospective monitoring has been the goal for investigating if tumor response can be measured sensitively in a timely fashion during treatment. Such a detection method would open the possibility for adaptive therapy based on local responses measured in real time or, in the absence of a response, consideration of alternative treatments. Such a detection method should detect cell kill across the tumor volume during treatment. Such a parameter can be measured directly by quantitative sodium MR imaging based on a simple model of sodium ion homeostasis. This chapter describes this investigational methodology in detail and presents preliminary results through individual clinical cases. Other approaches to this measurement such as by water diffusion MR imaging may also indirectly reflect this process, but may be more of a surrogate qualitative marker rather than a direct quantitative parameter.