**3. Gliomatosis cerebri**

**2.3. MR spectroscopy**

168 Neurooncology - Newer Developments

Initial studies with MR spectroscopy showed promise for the diagnosis of brain lesions and grading; however, recent evidences are controversial. Several metabolites can be measured that correlate with various pathological alterations within lesions. NAA is the acetylated form of the amino acid, aspartate, which is found in increased concentrations in viable neurons. Given that non‐neuronal neoplasms destroy normal neurons there is a reduction in NAA signal. Choline is a marker of cell membrane and can be found elevated in tumors and inflammatory processes. Creatine is a measure of energy stores, whereas lactate increases in cases of ischemia, in which the cell switches to anaerobic glycolysis and lactates accumulates. Thus, lactate is more likely to be present in high‐grade than low‐grade gliomas. Lipids have been recognized as a marker of myelin breakdown. Several studies have evaluated both single‐ voxel and multi‐voxel spectroscopy. Multi‐voxel has the advantage of greater spatial resolu‐ tion and extent of coverage, thus permits the evaluation of different components of heterogeneous masses. Within tumor, some areas may be more metabolically active than others. In brain tumors, there is usually an increased signal of Cho, whereas NAA and Cr are reduced. Cho/Cr ratio tends to increase as glioma malignancy progresses. In a recent meta‐ analysis, Cho/NAA ratio showed a sensitivity of 80% and specificity of 76%, higher than Cho/ Cr ratio and NAA/Cr ratio for the differentiation of high‐grade from low‐grade gliomas [9]. However, both sensitivity and specificity do not enable an accurate diagnosis, thus addition‐ al imaging modalities may be needed. A CHO/NAA ratio >1, in voxels outside of the enhance‐ ment region, suggests tumor infiltration and is indicative of a high‐grade glioma (**Figure 2**).

**Figure 2.** MR proton spectrum of a grade II astrocytoma (A) and of a glioblastoma (B). Contrary to low‐grade glioma, glioblastoma exhibits depression of the NAA and creatine (Cr) peaks and elevation of the choline (Cho) peak.

Gliomatosis cerebri is a rare diffuse primary neoplastic process of glial origin with dismal prognosis. Based on WHO criteria, this diffusely infiltrating glial neoplasm involves at least three cerebral lobes. There is often bilateral involvement of the cerebral hemispheres and/or deep gray matter (**Figure 3**) [10]. Histopathologically, it is characterized by diffuse infiltra‐ tion of brain parenchyma by small, immature glial cells that resembles astrocytes, oligoden‐ droglia, or undifferentiated cells [10, 11]. The lesion can contain areas of WHO grades II or III tumors, and less frequent grade IV. Symptomatology is subtle and may involve changes in personality and mental status, headache, hemiparesis, ataxia, and seizures. Although it appears radiologically as extensive disease, clinical symptomatology may be silent. Diagno‐ sis requires brain biopsy and histopathological examination.

**Figure 3.** T2‐W axial images show diffuse hyperintense lesions with enlargement of the involved structures and little mass effect (arrows).

Two subtypes can be identified radiologically: type 1 with no discrete component and type II with a solid component and diffuse CNS involvement. *IDH1* mutations have been reported more frequent in type II GC [12]. MRI findings are essential for establishing the correct diagnosis. Hypointensity in T1‐weighted sequences and hyperintensity in T2‐weighted and FLAIR sequences are the classical findings. Another usual MRI finding consists of diffuse infiltration of the cortex with an enlargement of the cortical sulci and the absence of clear

delineation between white and gray. Contrast enhancement is absent [13]. In DWI, there is usually no restriction. Perfusion MR shows low or normal rCBV values correlating with the absence of vascular hyperplasia. MR spectroscopy reveals elevated Cho/NAA ratios and marked elevation of myoinositol [14] (**Figure 4**).

**Figure 4.** Short‐echo MR proton spectrum shows an elevated myoinositol (mI) peak (at 3.55 ppm) in a case of gliomato‐ sis cerebri.
