Development of Acute Edema Following Cerebral Hypoxia-Ischemia in Neonatal Compared with Juvenile Rats Using Magnetic Resonance Imaging

Abstract

We hypothesized that the evolution of cerebral edema accompanying cerebral hypoxia-ischemia is dependent on age and that such differences would be detectable using magnetic resonance imaging methods. Thus we examined in immature and juvenile rats the relationship between hypoxic-ischemic changes in T 1 and T 2 and the alterations in brain water content, as assessed by differences in tissue wet-dry weights. One-and 4-wk-old rats were anesthetized and subjected to unilateral carotid artery occlusion and subsequent exposure to hypoxia (8% oxygen). T 1 and T 2 maps were acquired at 9.4 T, and then brain water content was measured in sham controls or in hypoxic-ischemic animals before, during, and 1 or 24 h after hypoxia-ischemia. In sham controls, T 1 , T 2 , and proton density decreased with increasing age, corresponding to an ontogenic decrease in water content. In 1-wk-old rats, increases in T 1 and T 2 were observed during and at 1 and 24 h after hypoxia-ischemia, corresponding to elevations in water content. In 4-wk-old rats, T 1 and water content increased during and at 1 and 24 h after hypoxia-ischemia whereas T 2 was not increased until 24 h after hypoxia-ischemia. Regression analysis showed that T 1 correlated better with total water content than T 2 . In both immature and older brain, an increase in total brain water develops acutely and persists after an episode of cerebral hypoxia-ischemia, and T 1 imaging detects this change better than T 2 . Hypoxic-ischemic changes in T 2 are age dependent, reflecting other physicochemical changes of water in the tissue than water content alone. Cerebral ischemia produces a tissue edema consisting of a combination of intracellular and extracellular water accumulation within the tissue. The edema associated with ischemia has been assessed frequently using one or more noninvasive MR imaging techniques (1) in which the contrast has been based primarily on regional differences in proton density, spin-lattice (T 1 ), or spin-spin (T 2 ) proton relaxation times. Considering the fact that the majority of protons within the brain are found in water molecules, changes in intensity in T 1 -and T 2 -weighted images have often been interpreted to represent edema and have been used to monitor its progression under various pathologic states including cerebral ischemia and brain trauma (2). However, the actual changes in water content or the biophysical properties of the tissue that underlie many of the MR imaging changes remain poorly understood. Indeed, those studies measuring ontogenic or pathologic changes in tissue water content have reported a range of poor, mild, and good correlations between water content and MR variables such as T 2 and T 1 (3-12). The majority of such studies have not examined the correlation of the changes in MR relaxation variables with the evolution of the pathologic edema as a function of time, and even fewer have investigated directly the relationship between changes in MR variables and the edema resulting from a cerebral HI insult. Recently, we repor...

High‐resolution T1 mapping of the brain at 3T with driven equilibrium single pulse observation of T1 with high‐speed incorporation of RF field inhomogeneities (DESPOT1‐HIFI)

“…As such, use of the method has primarily been limited to lower field strengths, generally 1.5T and below, where patient-specific B1 variations are small. While DESPOT1 has been successfully applied at higher fields, such as at 9.4T (19), the FOV utilized in these applications have been small enough to justify the assumption of a spatially uniform B1 field. High field (3T and above) large-volume (ie, whole-brain) T1 mapping with DESPOT1, however, has remained challenging.…”

Mild Hypoxic-Ischemic Injury in the Neonatal Rat Brain: Longitudinal Evaluation of White Matter Using Diffusion Tensor MR Imaging

“…[1][2][3] Although severe injury is characterized by tissue loss and necrosis in both white matter (WM) and gray matter (GM), 3 mild injury leads predominantly to WM damage. 4 Such selective WM damage in mild hypoxia-ischemia may be due to apoptosis of immature oligodendrocyte progenitors and dysfunction of mature oligodendrocytes, which are susceptible to HI injury.…”

Characterization of White Matter Injury in a Hypoxic-Ischemic Neonatal Rat Model by Diffusion Tensor MRI

“…1 In mild neonatal HI, WM injury is diffuse and noncystic, whereas in severe neonatal HI focal cystic lesions in the WM often ensue. By varying the duration of hypoxia in the well established model of neonatal HI using a D7 rat, the severity of brain injury may be modified [2][3][4] leading to selective WM injury with relative sparing of gray matter (GM) 2 in the mild HI model and global necrosis and infarction in both WM and GM in the severe HI model. 4 The histological findings in the WM of mild HI injury include gliosis and reduced myelination, 5 and in severe HI injury, there is neuronal necrosis and infarction.…”

“…Previous animal studies 2,3,5,9,10 have demonstrated that conventional MRI sequences such as T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) measuring trace, could detect HI-induced brain damage. Diffusion tensor MR imaging (DTI) allows the measurement of the directional diffusivities of water and is more sensitive than conventional MRI sequences in detecting WM 1 injury.…”