Quantitative sodium MR imaging and sodium bioscales for the management of brain tumors.

The standard of care for the comprehensive treatment of high-grade primary brain tumors includes surgery, radiation treatment and chemotherapy. Magnetic resonance (MR) imaging is involved in the initial diagnosis for detection and characterization of the lesion, focusing on size, location and its effect on surrounding brain and then on the heterogeneity of the signal characteristics, the presence of hemorrhage, MR perfusion characteristics and integrity of the blood-brain-barrier. These imaging properties have been correlated with tumor grade that has prognostic significance. Functional MRI can be used for presurgical planning and for image guidance of the surgical procedures (biopsy, resection) to minimize disruption of eloquent cortex. The surgical debulking is not considered curative for high-grade tumors but a preliminary step towards improving response to the subsequent treatments. After a short recovery period to allow some degree of healing of the surgical site, radiation planning and treatment begins. The radiation planning uses the X-ray attenuation coefficients from computed tomography (CT) to design the distribution of the radiation used in the treatment plan. Advantage is taken of the better display of tumors on MRI by fusing the MR and CT images. The course of radiation involves fractionated targeted radiation projected along multiple beams at many angles to achieve high dose over the tumor volume and margins while minimizing the dose to surrounding normal brain. The radiation is fractionated, usually administered for 5 days per week over about 6 weeks to a total dose of about 55 Gy. Imaging is not routinely performed during radiation treatment. Symptoms of brain swelling are controlled by use of oral steroids. Chemotherapy at low dose may be delivered during radiation treatment. Full dose, single agent chemotherapy then follows after the completion of radiation and is administered over multiple cycles to maintain tumor control. Follow-up MR imaging studies begin after radiation treatment is completed and are then performed every few months or more frequently depending on the clinical status of the patient. Although this protocol has been developed based on experience from large numbers of patients in multi-center trials, the prognosis has not changed in three decades (20% survival at 2 yrs, [1]). This extremely poor success rate for a not insignificant neoplasm, despite such this comprehensive protocol after decades of experience, suggests that there is a fundamental oversight in the current treatment of this disease. This material provides an imaging perspective of how regional responses of primary brain tumors may be examined during treatment to guide a flexible treatment plan to the response of each patient’s tumor, rather than using a fixed rigid protocol based on population studies. Sodium imaging provides a direct measurement of cell density that can be used to measure regional cell kill during treatment. These bioscales of regionally and temporally sensitive biological-based parameters may be helpful to measure tumor responsiveness that the oncologists can use to guide treatment for each patient. The suggestions are speculative and still being examined experimentally but are presented to challenge the medical community to be receptive to changes in the standard of care when that standard continues to fail.