Quantitative Sodium MR Imaging and Sodium Bioscales for the Management of Brain Tumors




Treatment of high-grade primary brain tumors is based on experience from multicenter trials. However, the prognosis has changed little in 3 decades. This suggests that there is a fundamental oversight in treatment. This article provides an imaging perspective of how regional responses of primary brain tumors may be examined to guide a flexible treatment plan. Sodium imaging provides a measurement of cell density that can be used to measure regional cell kill. Such a bioscales of regionally and temporally sensitive biologic-based parameters may be helpful to guide tumor treatment. These suggestions are speculative and still being examined, but are presented to challenge the medical community to be receptive to changes in the standard of care when that standard continues to fail.


The standard of care for the comprehensive treatment of high-grade primary brain tumors includes surgery, radiation treatment, and chemotherapy. 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, magnetic resonance (MR) perfusion characteristics, and integrity of the blood-brain barrier. These imaging properties have been correlated with tumor grade that has prognostic significance. Functional MR imaging 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 toward improving response to the subsequent treatments. After a short recovery period to allow some degree of healing of the surgical site, radiation treatment planning begins. The radiation planning uses the radiography attenuation coefficients from CT scans to design the distribution of the radiation used in the treatment plan. Advantage is taken of the better display of tumors on MR imaging by fusing the MR and CT scan 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 follows 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 multicenter trials, the prognosis has not changed in 3 decades (20% survival at 2 years). This extremely poor success rate for a significant neoplasm, despite this, comprehensive protocol after decades of experience, suggests that there is a fundamental oversight in the current treatment of this disease. This article 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 biologic-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.


The conventional imaging workup for a brain tumor is a proton MR imaging examination with and without gadolinium contrast enhancement. The standard T1- and T2-weighted images define the location and dimensions of the mass. Diffusion-weighted imaging defines the extent of vasogenic edema while excluding cytotoxic edema. Perfusion imaging defines the regions of tumor with high vascularity on the relative cerebral blood volume map consistent with high-grade tumor ( Fig. 1 ). The role of perfusion imaging in tumor grading is discussed in another article elsewhere in this issue.




Fig. 1


Representative MR images from the 3.0 Tesla clinical examination of a patient with a large right hemispheric high-grade glioneuroma before treatment. Images are from the following acquisition sequences. Top left: non–contrast-enhanced T1-weighted 3-dimensional (D) inversion recovery gradient echo. Top middle: contrast-enhanced T1-weighted 3D inversion recovery gradient echo. Top right: magnetic susceptibility-sensitive 2D gradient echo. Bottom left: 3D quantitative 3D sodium image at a nominal resolution of 5 x 5 × 5 mm 3 acquired in under 10 minutes. Bottom middle: relative cerebral blood volume map from a dynamic susceptibility contrast MR perfusion study. Bottom right: 2D T2-weighted FLAIR propeller. The interpretation is a large, heterogeneous mass with cystic and hemorrhagic components and markedly increased ( red ) relative cerebral blood volume centered in the right parietotemporal region. The lesion has been biopsied. Surgical resection was not considered as an option.


These anatomic characteristics are important in defining the proximity of eloquent cortex that should be mapped with functional MR (fMR) imaging before biopsy and surgical resection. The fMR imaging study is best done with fiducial markers in place over the head so that accurate anatomic registration of the patient’s head with the images can be achieved on the neurosurgical workstation to guide the location and size of the craniotomy ( Fig. 2 ). The functional maps are best registered over the contrast-enhanced images to aid in distinguishing tumor margins from eloquent cortex. Functional mapping for presurgical planning is also discussed in more detail in another article elsewhere in this issue.




Fig. 2


Functional MR imaging performed for presurgical planning of a contrast-enhancing abnormality appearing in the surgical bed years after treatment for a brain tumor in the left frontal lobe. The activation map from the fMR imaging using the reading language comprehension paradigm is presented superimposed over the contrast-enhanced 3D T1-weighted inversion recovery gradient echo images (3D SPGR +C, top row ) and over the T2-weighted spin-echo, echo-planar images (AX SE EPI, bottom row ) in the axial ( left column ), coronal ( middle column ) and sagittal ( right column ) planes. The planes are cross-referenced with colored lines ( blue, axial; green , coronal; yellow , sagittal). The Broca area is cross-referenced (intersection of planes) and is anterior and inferior to the lesion, but in close proximity to it so that the surgeon was aware of the potential of producing an aphasia. This location of function was confirmed by intraoperative cortical mapping. The lesion was primarily radiation necrosis as predicted by the low relative cerebral blood volume.


Once surgical resection is accomplished, a few weeks are allowed for healing and anatomic stabilization before beginning radiation planning. The radiation treatment uses a CT scan for establishing radiation attenuation coefficients but requires a new MR imaging study to be merged with the CT scan to delineate the margins of the surgical bed and residual tumor and regions of normal brain. Radiation exposure to normal brain should be minimized while dose to the tumor bed should be maximized ( Fig. 3 ). The functional maps could also be used in this setting, but this is rarely done.




Fig. 3


The radiation treatment planning fuses the CT scans and MR imaging studies ( left ), especially the perfusion study for high-grade tumors, to generate a radiation distribution ( middle ) that covers the tumor while minimizing the dose to normal brain. The contour of the head is drawn as the blue outline. The base dose ( middle left ) is supplemented by an additional boost to the tumor ( middle right ). The radiation plan ( red ) can then be superimposed over the contrast-enhanced MR image. The large enhancing tumor in the right temporal lobe is well covered but there is still considerable exposure to the rest of the brain despite targeted treatment.


Once radiation treatment commences, a CT scan is used to ensure that the alignment of the radiation distribution is accurately maintained. MR imaging is rarely done during radiation treatment unless there is a dramatic clinical change that requires specific evaluation. After radiation treatment is completed, there is a baseline MR imaging study to which all subsequent imaging is referred. The full-dose chemotherapy begins after radiation is completed and is used across multiple cycles. All follow-up MR examinations should include perfusion imaging (as discussed elsewhere in this issue), but this is still not done universally. The issue of pseudoprogression ( Fig. 4 , consequence of combined radiation and chemotherapy) with worsening gadolinium contrast enhancement but reduced cerebral blood volume in the few weeks to months after radiation with subsequent resolution is also discussed elsewhere in this issue.


Mar 28, 2017 | Posted by in NEUROLOGICAL IMAGING | Comments Off on Quantitative Sodium MR Imaging and Sodium Bioscales for the Management of Brain Tumors
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