**3. Neuroimaging**

**1. Introduction**

membranes (MAM) in astrocytomas is presented.

14 Glioma - Contemporary Diagnostic and Therapeutic Approaches

treatment modalities related to MN and MAM functions.

**2. Epidemiological and clinical aspects**

insidious onset and a long, protracted clinical course [11, 12].

astrocytomas [11, 12].

In the next lines, we do a brief journey through some aspects of gliomas, included epidemiological, clinical, neuroradiological, neuropathological, ultrastructural, therapeutics, and biologic behavior. An emphasis regarding the functional and therapeutics implications (metabolic therapy approach) of mitochondrial network (MN) and mitochondria-associated

The MN has been implicated in the process of carcinogenesis, which includes alterations of cellular metabolism and cell death pathways. Defects in mitochondrial function have been

Accumulating evidence indicates that MAMs are a subcellular "hot spot" for the intracellular signaling [2, 3]. Recent research has highlighted and broadened the functional roles of MAM in a variety of cellular processes from lipid synthesis/transport, Ca2+ signaling, and ER stress, to mitochondrial shape and autophagy/mitophagy and to inflammation and cell immunity [3, 4]. MAM dysfunction has been associated with several types of cancer [5]. Research from the past decade has identified the MAM as a potentially central regulator of tumor cell metabolism, as exemplified by the presence of critical tumor suppressors and oncoproteins on this structure [6]. The involvement of MAM in cancer has not been thoroughly investigated. Consequently, there is a huge open window for pathophysiological understanding and novel

Recently, we provide evidence showing MN and MAM ultrastructural aspects in a range of human astrocytomas, including pilocytic astrocytoma diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma [7–10]. Probably, this represents a contribution to the structural basis of functional roles of MN and MAM in astrocytic tumors as well as therapeutics implications.

Diffuse astrocytic tumors comprise approximately 60% of primary intracranial tumors. These tumors can arise at any age in children and the very elderly, although incidence increases substantially with advancing age. The median age is 30–40 for diffuse astrocytoma, 40–50 for anaplastic astrocytoma, and 50–60 years for glioblastoma. Older patients are also more likely to have higher grade gliomas, especially glioblastoma. The last one is the most frequent neoplasm in this category, accounting for approximately 80% of the diffusely infiltrative

The clinical presentation of the diffuse astrocytomas varies according to the sites of involvement and the rate of growth. The most common clinical symptoms are new-onset seizures, changes in behavior, motor deficits, and sing/symptoms of increased intracranial pressure (headache, nausea, vomiting, and papilledema). High-grade astrocytoma tend to have a short history with rapid progression, whereas low-grade astrocytoma are more indolent, often with

suspected to play an important role in the development and progression of cancer [1].

Astrocytomas are most commonly seen on magnetic resonance imaging MRI as ill-defined, deep-seated, or predominantly subcortical cerebral hemispheric masses. MRI sequences, where signal hyperintensity reflects vasogenic edema generated in response to diffuse infiltration by individual tumor cells. Secondary signs of mass effect include midline shift, ventricular compression, and sulcal effacement. Glioblastoma commonly show a rim-enhancing pattern with a central low-density region of necrosis surrounded by irregular, variable thickness rim of contrast enhancement. This rim-enhancing component is always surrounded by T2- or FLAIR signal hyperintensity that represents an associated diffusely infiltrating neoplasm [11, 12] (**Figure 1**).

**Figure 1.** Glioblastoma MRI. (A) Initial MRI from a 50-year-old male patient with seizures and a temporal lobe glioblastoma. (B) The same patient three months later. (C) A huge frontal lobe giant cell glioblastoma from a 65-years-old female patient with changes in behavior.
