Experimental Cerebral Venous Thrombosis: Evaluation Using Magnetic Resonance Imaging

Abstract

Summary: Diffusion-weighted (DWI), dynamic contrast enhanced (perfusion imaging), and conventional spin-echo magnetic resonance imaging (MRI) were applied to character ize the pathophysiology of cerebral venous thrombosis (CVT) in the rat. We induced CVT by rostral and caudal ligation of the superior sagittal sinus (SSS) and injection of a thrombogenic cephalin suspension. The resulting pathology was monitored in an acute and long-term study group. Evans blue and hematoxy Iin-eosin staining was performed for comparison with MRI data. A subgroup of animals was treated with i.v. tissue plas minogen activator (t-PA). Successful thrombosis of the SSS was confirmed by macropathology or histopathology in all rats. Parenchymal lesions as shown by MRI, however, were present only in animals with additional involvement of cortical cerebral veins (II of 18 rats). The early pathology was clearly detected Cerebral venous thrombosis (CVT) is an underesti mated cause of stroke with an obscure pathophysiology that differs from other stroke mechanisms in the follow ing ways: (1) Increased pressure in the superior sagittal sinus (SSS) results in a reduced capillary perfusion pres sure (Wagner and Traystman, 1983) and increased cere bral blood volume (CBV) (Gotoh et aI., 1993); (2) ve nous flow obstruction leads to increased intracranial pressure and blood-brain barrier (BBB) disruption, re sulting in a decreased cerebral blood flow (CBF) (Kuro- 1353 with the DWI. The apparent diffusion coefficient declined to 56 ± 7% of control value at 0.5 h and slowly increased to 84 ± 8% by 48 h. Perfusion imaging showed parasagittal perfusion deficits. Treatment with t-PA partially resolved the hyperinten sity on DWI. Evidence of blood-brain-barrier disruption was observed 2 to 3 h after induction of CVT. In conclusion, ex perimental CVT is characterized by early cytotoxic edema closely followed by vasogenic edema. The t-PA treatment par tially reversed the DWI signal changes consistent with regional tissue recovery. as shown by histopathology. These results en courage the use of cytoprotective drugs in addition to antico agulant or thrombolytic therapy. Key Words: Sinus thrombo sis-Cerebral ischemia-Cerebral blood t1ow-Magnetic reso nance imaging-Rat-Tissue plasminogen activator. kawa et al.. 1990kawa et al.. : Fries et aI., 1992 Gotoh et aI., 1993; Ungersbock et aI., 1993; Nakase et aI., 1996); (3) the net capillary filtration increases leading to progressive cere bral edema; and (4) intracerebral and subarachnoid hem orrhage additionally compromise the brain tissue (Cer vos-Navarro and Diemer. 199 1;Garcia. 1990).-A model of cerebral sinus and venous thrombosis has been described in the rat that is believed to resemble the human condition (Deckert et aI., 1990). The combination of SSS ligation with the injection of thrombogenic cephalin suspension reliably induces SSS thrombosis. Damage to the underlying parenchyma is dependent on the additional involvement of cortical and bridging veins (Ungersbock et aI., 1993; Nakase et aI., 1996). P...

Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging in Deep Cerebral Venous Thrombosis

“…Pathological findings in CVT vary from blood-brain barrier disruption that results in vasogenic edema to obstructive hydrocephalus, perivascular hemorrhage, and ischemic venous infarction with reduced capillary perfusion pressure, which leads to irreversible cytotoxic edema. 5,6 In our case of deep CVT with rapidly declining state of consciousness, early diagnosis was established by CT, MRI, and MR angiography. The intraluminal thrombus was best visible in CT, whereas the hyperacute thrombus could not be detected on MRI because of susceptibility effects.…”

Compromise of Brain Tissue Caused by Cortical Venous Reflux of Intracranial Dural Arteriovenous Fistulas

“…10 Alternatively, previous experimental studies showed that retrograde venous pressure might counteract capillary perfusion pressure to decrease cerebral blood flow, and thus cause arterial ischemia resulting in cellular or cytotoxic edema. 12,21 Previous experimental and clinical diffusion-weight imaging studies of cerebral venous thrombosis have shown that ADC value was decreased, 12,22,23 normal, 23 increased, 24 or heterogeneous. 25,26 The ADC values decreased by 56% at 30 minutes after experimental cerebral venous thrombosis, and secondary increases in ADC subsequently developed in a rat model.…”

“…Experimental cerebral venous thrombosis in rats has suggested that the balance may depend on the severity as well as the duration of disturbed venous flow. 12 Increased 13,14 and decreased 15 ADC values have also been observed in the brain parenchyma of patients with DAVF, but the pathological conditions caused by disturbed venous flow from CVR associated with DAVFs remain unclear.…”

Post-ischemic Administration of Vascular Endothelial Growth Factor Inhibitor in a Rat Model of Cerebral Venous Infarction

“…Previous studies have found that cytotoxic and vasogenic brain edema is consistently associated with acute CVI. 23) This large low-flow area following CVI results not only in angiogenesis but also in increased VP, so edema formation is probably activated by the induction of VEGF expression. Therefore, we suggest that the present animal model was suitable for the evaluation of the relationship be-Neuroprotective Window for Anti-VEGF Therapy in Venous Infarction tween VEGF and brain edema.…”