The Study of Cerebral Hemodynamics in the Hyperacute Stage of Fat Embolism Induced by Triolein Emulsion

Animal Models and Experimental Design of Fat Embolism

All animal experiments were conducted in accordance with our institutional guidelines. Adult domestic cats used in this study weighed 2.7–3.8 kg; they were anesthetized by an intramuscular injection of ketamine HCl (2.5 mg/kg; Korea United Pharm Inc., Seoul, Korea) and xylazine (0.125 mg/kg; Bayer Korea, Seoul, Korea). The cats were allowed to breathe ambient air spontaneously during the procedure. An 18-gauge intravenous catheter (Angiocath; Becton Dickinson, Sandy, Utah) was placed in the right femoral vein for the purpose of contrast injection. The right femoral artery was isolated and its distal portion was ligated with 4.0 silk. Then a second 18-gauge intravenous catheter was inserted into the artery. A 3.0F microcatheter (MicroFerret-18 Infusion Catheter; William Cook Europe, Bjaeverskov, Denmark) with a microguidewire was passed through the intravenous catheter into the lumen of the artery. Either the right or the left internal carotid artery was selected. The tip of the microcatheter was positioned just proximal to the entrance of the intracranial portion of the carotid artery.

A 1-mL syringe containing 0.05 mL of neutral triglyceride triolein (1,2,3-tri [cis-9-octadecenoyl]glycerol, 99% purity, d = 0.91 g/mL; Sigma, St. Louis, Mo) and a 25-mL syringe containing 20 mL of saline were connected to a 3-way stopcock. The fat emulsion was made by mixing triolein and saline via the stopcock with a vigorous to-and-fro movement of the syringes for 2 minutes. The fat globules in the emulsion ranged from 1 μm to 30 μm. The emulsified fat was infused manually into the selected carotid artery at a rate of 4 mL/min for 5 minutes followed by injection of 3 mL of saline.

MR Imaging

Serial MR imaging was performed at 30 minutes and 2, 4, and 6 hours after infusion. Each cat was placed in a prone position within a pediatric MR infant restrainer, and a flexible surface coil was placed around its head. All studies were performed on a 1.5T MR Sonata scanner (Siemens, Erlangen, Germany). All images were acquired in the coronal plane. With each animal, T2-weighted (T2WI), diffusion-weighted (DWI), perfusion-weighted (PWI), and gadolinium-enhanced T1-weighted (Gd-T1WI) coronal images were obtained.

For spin-echo imaging, the following scan parameters were used: repetition time (TR) = 3000 milliseconds; echo time (TE) = 96 milliseconds for T2-weighted; section thickness = 4 mm with a 0.1-mm gap; field of view = 70–75 mm; 2 excitations; and acquisition matrix = 210 × 256. Diffusion-weighted imaging was performed by using an echo-planar sequence. The imaging parameters were as follows: field of view = 130 mm; phase-encoding steps = 128; section thickness = 4 mm with a 0.1-mm gap; and acquisition matrix = 96 × 160. The diffusion sensitizing gradients were oriented in the 3 axes with b values of 0 and 1000 s/mm². The apparent diffusion coefficient (ADC) map was obtained simultaneously by using standard software. PWIs were obtained by using a single-shot gradient echo-planar sequence with a bolus injection of 0.2 mmol/kg Gd-DTPA. The imaging parameters were as follows: TR = 1200 milliseconds; TE = 33 milliseconds; section thickness = 4 mm; flip angle = 90°; acquisition matrix = 104 × 128; and field of view = 123 mm. Forty-four images were obtained with a 1-second repetition time for 44 seconds in 4 sections. Sequential imaging was initiated, and a bolus contrast agent was injected through a femoral vein catheter between acquisition of the fourth and fifth images and was followed by injection of 10 mL of saline. Gd-T1WIs were then obtained with TR/TE = 320/20 milliseconds; the other parameters were the same as T2WI.

Analysis of MR Images

Qualitative Analyses

The lesions occurred diffusely in the superficial cortex of the ipsilateral cerebral hemisphere. On T2WIs, the lesions were hyperintense at 30 minutes. The hyperintensity showed a tendency to increase for 4 hours and to decrease thereafter.

The lesions were remarkably enhanced in all cases, and the lesion contrast was more conspicuous on Gd-T1WIs than on T2WIs or DWIs. At 30 minutes, all cats showed leptomeningeal and adjacent parenchymal enhancement which tended to increase markedly for 2 hours and to decrease thereafter.

On DWIs, the lesions were isointense at 30 minutes and subtly hyperintense thereafter. On the ADC map images, however, the lesions were isointense at all acquisition times in all cats (Fig 1).

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Fig 1.

Sequential T2-weighted (A), Gd-enhanced T1-weighted (B), diffusion-weighted (C), and ADC map (D) images at 30 minutes (first column), 2 hours (second column), 4 hours (third column), and 6 hours (fourth column) after triolein emulsion infusion in cat 320. T2 hyperintensity (A) is shown at 30 minutes, extends into the subcortical white matter at 2 hours, is maximal in size and intensity at 4 hours, and decreases thereafter. Lesion enhancement on Gd-enhanced T1-weighted imaging (B) is revealed from 30 minutes, increases at 2 hours, and decreases thereafter. Diffusion-weighted images (C) show mild hyperintensity at 2, 4, and 6 hours. ADC map images (D) all reveal isointensity over time.

Quantitative Analyses

The SIRs on T2WIs significantly increased for 4 hours (P < .05) but decreased thereafter (Table 1).

On the Gd-T1WIs, the SIRs at 2, 4, and 6 hours increased significantly compared with those at 30 minutes (P < .05). The SIRs peaked at 2 hours (Table 2).

The SIRs on the DWIs increased for 2 hours but not to a statistically significant degree (P = .16). On ADC map images, the SIRs significantly increased for 2 hours (P < .05) but decreased thereafter (Table 3).

On PWIs, there were no significant differences in the rCBVs, rCBF, and MTT in the lesions or in the contralateral normal side at each acquisition time (P = .09, 0.30, and 0.13, respectively). The rCBV, rCBF, and MTT ratios of 2, 4, and 6 hours showed no significant change compared with those at 30 minutes (P = .17, 0.31, 0.66, respectively) (Table 4).