It is characterized by blood-brain barrier breakdown, neuroinflammation, and demyelinating plaques. However, the exact pathogenesis of MS is still unknown and there is currently no known cure. Recently, a new hypothesis implicating chronic cerebral venous insufficiency, coined chronic cerebrospinal venous insufficiency, as the cause of MS has gained widespread attention and interest from patients and physicians. There is an increasing number of studies linking cerebral venous insufficiency to various neurologic diseases such as transient global amnesia and MS. The idea of MS having a vascular etiology was first introduced over a century ago by Charcot who found thickening of small blood vessels in MS patients, but other hypotheses are more commonly invoked as possible causes. It has been proposed that CCSVI may lead to increased iron deposition in the brain, leading to an inflammatory or immune reaction and the formation of MS lesions. Percutaneous transluminal angioplasty and stenting have emerged as potential Clinafloxacin treatment options for MS patients as a result of this new hypothesis. However, the invasive nature of the procedure can lead to serious complications, including stent migration, cerebral hemorrhage, jugular vein thrombosis, and even death. Since the original study on CCSVI and its reported strong association to MS, several other studies have not been able to show a definitive confirmation of the CCSVI hypothesis for MS. Given that there is no cure for MS and the current disease modifying immunomodulatory therapies only help to slow the disease progression, treatment of CCSVI could represent a breakthrough for MS patients if CCSVI is indeed the cause of MS. Conversely, MS patients may be at risk from unnecessary endovenous interventions if the validity of the CCSVI hypothesis is ultimately disproven. To date, there has been no animal model of CCSVI reported in the literature that investigates the relationship between venous congestion arising from extracranial stenosis and the development of demyelination. Thus, we aimed to investigate this hypothesis in a controlled animal model by creating chronic cerebral venous insufficiency in mice. We hypothesized that these animals could exhibit the hallmarks of demyelinating diseases such as MS, including clinical signs, blood-brain barrier breakdown, neuroinflammation, and demyelination. To evaluate whether our model causes cerebral inflammation, we performed MPO-Gd molecular imaging to assess in vivo MPO activity. MPO is a highly oxidizing enzyme secreted in abundance by activated neutrophils, macrophages, and microglia in inflammation, and MPO-Gd is an activatable MR imaging agent that can Lomefloxacin hydrochloride report MPO activity in vivo with high specificity and sensitivity. The MRI T1 gadolinium enhanced images were performed to assess contrast agent extravasation as a marker for blood-brain barrier breakdown. Images were quantified by manually segmenting out an ROI of normal brain and an area outside the boundaries of the mouse for noise. An automatic segmentation algorithm was used to segment out the brain in utilizing Matlab, which finds the largest connected region in the head. Contrast-tonoise ratios of the post-Gd images was found by taking the mean value over the whole brain minus the mean normal brain background and dividing by the standard deviation of the noise.