Several forms of edema have been identified under the larger rubric of “brain edema.” These generally fall into the cellular or extracellular forms. Cellular edema denotes cytotoxic edema (CE). Extracellular edema refers to vasogenic edema (VE) and “special” forms of osmotic edema and hyperemic edema.^1,​2 The pathophysiology of these forms of brain edema were characterized and defined more than 50 years ago.¹

This chapter defines the two most common forms of brain edema (VE and CE), discusses their imaging characteristics, and presents representative disease processes that can be readily investigated using diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI). The text incorporates causes of excitotoxic brain injury (EBI), which ultimately leads to cytotoxic edema. VE and CE can present separately or in combination. This chapter demonstrates a wide variety of representative and commonly seen adult-specific conditions that have DWI and DTI findings, spanning multiple categories of diseases, including vascular, infectious, inflammatory, neoplastic, and demyelinating diseases. Subsequent chapters provide in-depth discussions of additional diseases and their DWI and DTI findings.

2.2 Pathophysiology

2.2.1 Vasogenic Edema

VE results from leakage of fluid through a disrupted blood–brain barrier (BBB). Although extracellular protein breakdown has been shown to attenuate fluid clearance, no evidence to date suggests that the protein breakdown products result in fluid exiting the vascular space.³ Through a combination of bulk flow and diffusion of water, fluid accumulates preferentially in the usually tightly bundled white matter. If the BBB is reconstituted early in the process, the VE can be reversed.⁴

2.2.2 Cytotoxic Edema and Excitotoxic Brain Injury

Excitotoxic Brain Injury

EBI includes temporary or permanent dysfunction of excitatory amino acid homeostasis. Among the excitatory amino acids glutamate, aspartate, and glycine, glutamate is the most important. It is involved in numerous functions, such as cognition, memory, movement, and sensation.⁵ Abnormal levels of glutamate can cause neuronal injury and demise related to activation of the N-methyl-d-aspartate (NMDA) receptor subtype of the glutamate receptor.⁶

In the acute phase, three mechanisms are known to cause excessive extracellular glutamate: (1) glutamate leakage from disrupted axonal membranes, (2) abnormal neuronal membrane depolarization causing further glutamate release, and (3) dysfunctional reuptake of extracellular glutamate. These mechanisms can self-propagate in a transaxonal or transynaptic manner along white matter tracts.^5,​6,​7

Cytotoxic Edema

Abnormal increases in intracellular water content cause CE. On the molecular level, the sodium–potassium (Na+-K+) adenosine triphosphatase (ATPase) and calcium ion pumps become dysfunctional, resulting in net diffusion of water into the cell. The BBB remains intact initially, yielding stable extracellular water content. Continuous insults cause BBB breakdown and subsequent VE. Apoptotic pathways are activated as well.⁷

The discovery of various subtypes of aquaporin (AQP) channel proteins has shed light on another mechanism of CE.⁸ Specifically, AQP-4 channels are found in the brain and allow massive free water transport across the astroglial endfeet membranes.⁹ These findings are supported by numerous mouse model studies^10,​11; however, the relationship between these water channels and cerebral edema in humans remains to be demonstrated.

2.3 Diseases Associated With Cerebral Edema

2.3.1 Vasogenic Edema

On magnetic resonance imaging (MRI), VE is T1 hypointense and T2 hyperintense, predominantly within the white matter. VE is bright on both DWI and ADC maps. Decreased fractional anisotropy (FA) is seen on DTI sequences.⁴

Neoplasm-Related Vasogenic Edema

Both benign and malignant neoplasms can cause VE due to tumor angiogenesis and BBB breakdown and show increased diffusivity on DWI and ADC maps. Type-1 peritumoral VE is associated with low-grade (▶ Fig. 2.1) and nonglial tumors, such as metastases and meningiomas. Parenchymal compression causes ischemia and necrosis, which can persist after the tumor is removed.

Type-2 peritumoral edema is associated with high-grade glial neoplasms, which show highly infiltrative behavior and significant destruction of the BBB. VE extension beyond the vicinity of enhancing tumor is characteristic and represents tumor microinvasion (▶ Fig. 2.2). Partial to complete resolution of VE can occur after removal of the tumor. Relative to type-1 VE, type-2 edema shows more increased ADC signal and further diminishment of FA on DTI, likely related to greater tissue destruction by malignant neoplasms.

2.3.2 Cytotoxic Edema/Excitotoxic Brain Injury

Computed tomography shows a loss of gray–white matter differentiation early in CE/EBI. In subacute phases, BBB breakdown can show white matter hypoattenuation of VE, presenting a mixed edema picture. MRI reveals swelling of the gray matter and loss of gray–white matter differentiation. ADC dark and DWI bright areas are present in CE/EBI; FA is decreased on DTI.⁴

Arterial Infarction

Hypoxia caused by acute arterial infarction leads to rapid depletion of adenosine triphosphate (ATP) and resultant CE.⁴ Excitotoxicity causes sodium–potassium pump failure and rapid influx of water into the cell. Intracellular calcium increases causing release of lipase and protease, ultimately leading to cell death.⁵ Experimental studies on NMDA-type glutamate receptor antagonists (MK-801) have shown a reduced volume of ischemic injury after occlusion of the middle cerebral artery (MCA).¹² Accordingly, excitotoxic injury related to glutamate is associated with the pathophysiological findings of ischemic penumbra.^5,​12

Within 30 minutes CE develops, often peaking between 24 and 72 hours, and can persist for up to 24 hours after reperfusion. Detection of hyperacute infarction (< 30 min from onset of neurological deficit) is most sensitive on DWI⁴ (▶ Fig. 2.3a–c). As the infarction evolves, the CE (DWI bright, ADC dark) will be surrounded by VE (DWI bright, ADC bright) and associated mass effect. ADC can show pseudonormalization between 10 and 15 days, with persistent DWI hyperintensity due to T2 shine-through of VE¹³ (▶ Fig. 2.3d–f). Chronic infarction shows ADC bright signal due to encephalomalacia and gliosis.¹⁴

Cerebral Venous Infarction

Venous infarction is caused by thrombus in the dural venous sinuses, cortical veins, or deep cerebral veins. The area of infarction does not correspond to an arterial distribution and has a propensity to undergo hemorrhagic transformation. Risk factors include chronic inflammation, infection, thrombophilic states (e.g., dehydration, hypercoagulation disorders, cancer), and cranial surgery.¹⁵ CE surrounded by VE and mass effect is typically seen (▶ Fig. 2.4). CT or magnetic resonance venography can identify thrombus.

Multiple Sclerosis

CE in multiple sclerosis (MS) plaques is rarely captured on MRI. As seen in the early (hyperacute and acute) phases of MS, these lesions are profoundly hypointense on ADC maps and bright on DWI⁵ (▶ Fig. 2.5).

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