Experimental Pulmonary Fat Embolism: Computed Tomography and Pathologic Findings of the Sequential Changes

This study was done to demonstrate the computed tomography (CT) and pathologic findings of the sequential changes for experimental pulmonary fat embolism (PFE), and to correlate the CT and pathologic findings of rabbit lung. PFE was induced by an intravenous injection of 0.2 mL linoleic acid in 24 rabbits. The rabbits were divided into 4 groups of 6 rabbits each. CT scans were obtained sequentially at 2 hr (n= 24), day 1 (n=18), day 3 (n=12) and day 7 (n=6) after fat embolization. The pathologic findings were analyzed and CT-pathologic correlation was done. CT scans showed bilateral ground-glass opacity (GGO), consolidation and nodule in all cases. The findings of PFE at 2 hr after fat embolization were areas of decreased attenuation, GGO, consolidation and nodule. These findings were aggravated on the follow- up CT after 1 day and 3 days. The follow-up CT revealed linear density in the subpleural lungs after 7 days. On CT-pathology correlation, wedge-shaped ischemic necrosis in the subpleural lungs correlated with nodule at 2 hr. GGO and consolidation at day 1 on CT correlated with congestion and edema, and these findings at day 3 were correlated with inflammation and hemorrhagic edema. The linear density in the subpleural lungs correlated with interstitial fibrosis and pleural contraction at day 7. In conclusion, PFE was caused by using linoleic acid which is kind of free fatty acid and this study served as one model of the occurrence of nontraumatic PFE. CT accurately depicted the natural evolution of PFE in the serial followup, and this correlated well with the pathologic findings.

Degradable Gelatin Microspheres as an Embolic Agent: an Experimental Study in a Rabbit Renal Model

OBJECTIVE: To investigate the basic characteristics of degradable gelatin microspheres (GMSs), including their embolic behavior and degradation periods when they are used as embolic materials in the renal arteries of rabbit models. MATERIALS AND METHODS: Based on the GMS particle size, 24 kidneys were divided into 3 groups of eight kidneys, and each group was embolized with a different GMS particle size (group 1: 35-100 micrometer, group 2: 100-200 micrometer, and group 3: 200-300 micrometer). From each group, two rabbits were sacrificed immediately after embolization (day 0), and a pair of rabbits from each group underwent an angiogram and were sacrificed on days 3, 7, and 14, respectively, after embolization. The level of arterial occlusion, the pathological changes in the renal parenchyma, and the degradation of the GMSs were evaluated angiographically and histologically. RESULTS: A follow-up angiogram on days 0, 3, 7, and 14 revealed the presence of wedge-shaped poorly-enhanced areas in the parenchymal phase as seen in all groups. The size of these areas tended to increase with the particle diameter, and persisted up to day 14. On days 3, 7, and 14, parenchymal infarctions were observed histologically in all cases, and this observation corresponded with the parenchyma being supplied by the embolized arteries. GMSs of group 1 mainly reached the interlobular arteries, while those of group 3 mainly reached the interlobar arteries. In all but two cases, the GMSs were identified histologically even on day 14, and sequential degradation was histologically identified in all GMS groups. CONCLUSION: GMSs can be used as degradable embolic materials which can control the level of embolization.

Experimental Model for Research on the Blood-Ocular Barrier

PURPOSE: The eyeball has 2 blood-ocular barriers, i.e., the blood-retinal and blood-aqueous barriers. The purpose of this study was to evaluate if triolein emulsion could disrupt the barriers, and we wanted to suggest as an experimental model for future blood-ocular barrier studies. MATERIALS AND METHODS: The triolein emulsion was made of 0.1 ml triolein and 20 ml normal saline, and this was infused into the carotid artery of ten cats (the experimental group). As a control group, only normal saline was infused in another ten cats. Precontrast and postcontrast T1-weighted MR images were obtained at 30 minutes and 3 hours after embolization in both groups. The signal intensities were evaluated qualitatively and quantitatively in the anterior and posterior chambers and also in the vitreus fluid. Statistical analysis was performed by employing the Kruskal Wallist test, Dunn's Multiple Comparison test and the Wilcoxon signed rank test. RESULTS: In the control group, no contrast enhancement was demonstrated in the anterior or posterior chamber or in the vitreus fluid of the ipsilateral or contralateral eyeball on the 30 minutes MR images. The anterior chambers of the ipsilateral and contralateral eyeballs revealed delayed contrast enhancement on the 3 hour MR images. In the experimental group, the 30 minute-postembolization MR images were not different from those of the control group. The 30 minute-postembolization MR images demonstrated delayed contrast enhancement in the anterior chamber of the ipsilateral and contralateral eyeballs and in the posterior chamber of the ipsilateral eyeball. The delayed contrast enhancement of the posterior chamber of the ipsilateral eyeball was statistically significant (p<0.05). CONCLUSION: The present study demonstrated significant contrast enhancement in the posterior chamber with infusion of the triolein emulsion, and this can serve as a model for blood-aqueous barrier studies.

The Effect of Micro-Particles of Linoleic Acid Emulsion on the Blood-Brain Barrier in Cats

PURPOSE: The purpose of this study was to investigate the permeability change of the blood-brain barrier and the reversibility of the embolized lesions induced with a fat-emulsion technique by using magnetic resonance imaging (MRI), and we also wished to evaluate the resultant histologic findings in cat brains. MATERIALS AND METHODS: MR imaging was scheduled serially at 1 hour, day 1, day 4 and day 7 after infusion of linoleic acid-emulsion (0.05 ml linoleic acid+20 ml saline) to the internal carotid artery in 12 cats. Abnormal signal intensity or contrast enhancement was evaluated on diffusion-weighted images (DWIs), the apparent diffusion coefficient (ADC) maps, and gadolinium-enhanced T1-weighted images (Gd-T1WIs) at the stated times. MR imaging was stopped if the lesion shows isointensity and no contrast enhancement was observed at the acquisition time, and then brain tissue was harvested and examined. Light microscopic (LM) and electron microscopic (EM) examinations were performed. RESULTS:The embolized lesions appeared as isointensities (n=7) or mild hyperintensities (n=5) on DWIs, as isointensities (n=12) on the ADC maps, and as contrast enhancements (n=12) on Gd-T1WIs at 1 hour. The lesions showed isointensity on DWIs and the ADC maps, and as no contrast enhancement for all cats at day 1. The LM findings revealed small (< 1 cm) focal necrosis and demyelination in three cats. EM examinations showed minimal findings of small (< 3 micrometer) fat globules within the endothelial wall (n=10) and mild swelling of the neuropils (< 5 micrometer). Widening of the interstitium or morphologic disruption of the endothelial wall was not seen. CONCLUSION: Cerebral fat embolism induced by linoleic acid emulsion revealed vasogenic edema and reversible changes as depicted on the MR images. These results might help us to understand the mechanisms of fat on the blood-brain barrier, and this technique could be used as a basic model for research of the effects of drugs on the disrupted blood-brain barrier, and also as a research model for the chemotherapeutic effects of drugs of the brain tumors.

Magnetic Resonance Imaging and Histologic Findings of Acute and Subacute Stage of Experimental Cerebral Fat Embolism in Cats

PURPOSE: To determine the magnetic resonance imaging (MRI) findings and natural history of cerebral fat embolism in a cat model, and to correlate the MRI and histologic findings. MATERIALS AND METHODS: Using the femoral arterial approach, the internel carotid artery of 11 cats was injected with 0.1 ml of triolein. T2-weighted (T2WI), T1-weighted (T1WI) and Gd-enhanced T1-weighted (Gd-T1WI) images were obtained serially at 2 hours, 1 and 4 days and 1, 2 and 3 weeks after embolization. Any abnormal signal intensity (SI) was evaluated. After MR imaging at 3 weeks, brain tissue was obtained for light microscopic (LM) examination using hematoxylin-eosin and Luxol fast blue staining, and for electron microscopic (EM) examination. The histologic and MRI findings were correlated. RESULTS: At 2 hours, lesions showed high SI at T2WI, iso- or low SI at T1WI, and strong enhancement at Gd-T1WI. The high SI seen at T2WI decreased thereafter, and most lesions became iso-intense. At week 3, however, small focal areas of high SI were seen in the grey matter of eight cats and in the white matter of three. The low SI noted at acute-stage T1W1 subsequcntly became normal, though in the areas in which T2W1 had depicted high SI, focal areas of low SI remained. Lesion enhancement demonstrated by Gd-T1WI decreased continuously from day 1, and at week 3, weak enhancement was seen at the margin of the remained hypointense lesions in the gray matter in five cats. At LM examination with hematoxylin-eosin staining revealed normal histologic findings in the greater park of an embolized lesion. Cystic change was observed in the gray matter of eight cats, and in the gray and white matter of three of the eight. At LM examination, Luxol fast blue, staining demonstrated demyelination around the cystic change occurring in the white matter, and EM examination of the embolized cortex revealed sporadic intracapillary fat vacuoles (n=11) and disruption of the blood-brain barrier (n=4). Most lesions were normal, however, and perivascular interstitial edema and cellular swelling were mild compared with the control side. CONCLUSION: Experimental cerebral fat embolism was clearly demonstrated by T2WI and Gd-T1WI images obtained at all time points. The greater part of an embolized lesion showed reversible findings at MR and histologic examination; irreversible focal necrosis was, however, observed in gray and white matter at week 3.

Experimentally Induced Cerebral Fat Embolism with Linoleic Acid: MR Imaging and Pathologic Correlation

PURPOSE: To investigate the correlation between the MRI findings of cerebral fat embolism induced by injecting linoleic acid into ten cats, and pathologic diagnosis. MATERIALS AND METHODS: Using a microcatheter, 30 microliter of linoleic acid was injected into the internal carotid artery of ten cats. MR T2-weighted (T2WI), diffusion-weighted (DWI), and Gd-enhanced T1-weighted images (Gd-enhanced T1WI) were obtained after 30 minutes and after 2 hours of embolization. We pathlogically examined endothelial cell damage, cellular change, perivascular abnormality and fat vacuoles, and then determined the correlation between MRI and the pathologic findings. RESULT: After 30 minutes of embolization, lesions of very high signal intensity were detected by T2WI in six cats, and of slightly high signal intensity in two; in the remaining two, signal intensity was normal. DWI showed lesions of very high intensity in nine animals and of slightly high intensity in one, while Gd-enhanced T1WI showed well-enhanced lesions in nine and a minimally enhanced lesion in one. After 2 hours of embolization, T2WI revealed lesions of very high signal intensity in nine cats, and of slightly high signal intensity in one, while DWI detected lesions of very high signal intensity in all cats. On Gd-enhanced T1WI, lesions in all cats were well enhanced. According to the findings of light microscopic examination, infarcted lesions mainly involved the gray matter, but also some white matter. In the lesions, neurophil matrix edema, neuronal degeneration, perivascular swelling, the widening of extracellular space, extravascular hemorrhage, and fat vacuoles were evident. CONCLUSION: During the initial two hours following injection, MR imaging of cerebral fat embolism induced by linoleic acid through the internal carotid artery in cats showed high signal intensity on T2WI and DWI, and clear enhancement on Gd-enhanced T1WI. In cases involving cellular edema, cerebrovascular injury and extracellular space widening, the pathologic evidence suggested the coexistence of cytotoxic and vasogenic edema.

Evaluation of the Embolic Effect of Polyvinyl Alcohol Foam particles According to Particle Size on the Cerebral Artery of a Cat, Focusing on T2 Weighted MR Images and Pathologic Study After 24 Hours

PURPOSE: This study was designed to determine the embolic effect of PVA particles of various sizes on the cerebral artery of a cat and to determine the appropriate particle size for embolization. MATERIALS AND METHODS: A total of 21 cats were divided into three groups according to the PVA particle size injected: group I(n=7), embolized with 45-150 micrometer PVA; group II(n=7), with 150-250 micrometer PVA; and group III(n=7), with 350-500 micrometer PVA. PVA particles were slowly injected into the left common carotid artery of each cat, and T2-weighted coronal MR images were obtained 24 hours after injection. During histologic examination of brain sections we analyzed the size, number of occluded vessels, and the ischemic changes caused by the particles. RESULTS: On T2 weighted images, areas of high signal intensity (infarction) were observed in four of the seven cats (57%) in group Iand in two of the seven (29%) in group II. High signal intensity was not found in group III. The mean percentage of areas of high signal intensity was 11.86 +/-1 . 37 % in group Iand 5.18 +/-1 . 77% in group II( P <0.05). During histologic examination, occlusion of the distal branches of the anterior cerebral (ACA) and/or the middle cerebral arteries(MCA) by PVA particles was observed in all seven cats (100%) in group I, and in four of the seven cats (57%) in group II. No group IIIcat showed occlusion of the distal branches of the ACA and/or MCA. The mean caliber of occluded vessels was 175 micrometer in Group Iand 258 micrometer in Group II. The mean number of occluded vessels seen on all slide sections was 14 in Group I and 5 in Group II. CONCLUSION: Small PVA particles had a greater cerebral embolic effect than did those which were medium or large. For the induction of embolic infarction in cat brain, PVA particles 45-150 micrometer in size are appropriate.

Evaluation of the Embolic Effect of Polyvinyl Alcohol Foam particles According to Particle Size on the Cerebral Artery of a Cat, Focusing on T2 Weighted MR Images and Pathologic Study After 24 Hours

PURPOSE: This study was designed to determine the embolic effect of PVA particles of various sizes on the cerebral artery of a cat and to determine the appropriate particle size for embolization. MATERIALS AND METHODS: A total of 21 cats were divided into three groups according to the PVA particle size injected: group I(n=7), embolized with 45-150 micrometer PVA; group II(n=7), with 150-250 micrometer PVA; and group III(n=7), with 350-500 micrometer PVA. PVA particles were slowly injected into the left common carotid artery of each cat, and T2-weighted coronal MR images were obtained 24 hours after injection. During histologic examination of brain sections we analyzed the size, number of occluded vessels, and the ischemic changes caused by the particles. RESULTS: On T2 weighted images, areas of high signal intensity (infarction) were observed in four of the seven cats (57%) in group Iand in two of the seven (29%) in group II. High signal intensity was not found in group III. The mean percentage of areas of high signal intensity was 11.86 +/-1 . 37 % in group Iand 5.18 +/-1 . 77% in group II( P <0.05). During histologic examination, occlusion of the distal branches of the anterior cerebral (ACA) and/or the middle cerebral arteries(MCA) by PVA particles was observed in all seven cats (100%) in group I, and in four of the seven cats (57%) in group II. No group IIIcat showed occlusion of the distal branches of the ACA and/or MCA. The mean caliber of occluded vessels was 175 micrometer in Group Iand 258 micrometer in Group II. The mean number of occluded vessels seen on all slide sections was 14 in Group I and 5 in Group II. CONCLUSION: Small PVA particles had a greater cerebral embolic effect than did those which were medium or large. For the induction of embolic infarction in cat brain, PVA particles 45-150 micrometer in size are appropriate.