Cytotoxic edema associated with hemorrhage predicts poor outcome after traumatic brain injury

Magnetic resonance imaging (MRI) is rarely used in the acute evaluation of traumatic brain injury (TBI), but may identify findings of clinical importance not detected by computed tomography (CT). We aimed to characterize the association of cytotoxic edema and hemorrhage, including traumatic microbleeds, on MRI obtained within hours of acute head trauma and investigated the relationship to clinical outcomes. Patients prospectively enrolled in the Traumatic Head Injury Neuroimaging Classification study (NCT01132937) with evidence of diffusion-related findings or hemorrhage on neuroimaging were included. Blinded interpretation of MRI for diffusion-weighted imaging and hemorrhage was conducted, with subsequent quantification of apparent diffusion coefficient (ADC) values. Of 161 who met criteria, 82 patients had conspicuous hyperintense lesions on diffusion-weighted imaging (DWI) with corresponding regions of hypointense ADC in proximity to hemorrhage. Median time from injury to MRI was 21 (10-30) hours. Median ADC values per patient grouped by time from injury to MRI were lowest within 24 hours after injury. ADC values associated with hemorrhagic lesions are lowest early after injury, with an increase in diffusion during the subacute period, suggesting transformation from cytotoxic to vasogenic edema during the subacute post-injury period. Of 118 patients with outcome data, 60 had Glasgow Outcome Scale Extended <6 at 30/90 days post-injury. Cytotoxic edema on MRI (OR 2.91 [1.32-6.37], P=0.008) and TBI severity (OR 2.51 [1.32-4.74], P=0.005) were independent predictors of outcome. These findings suggest that in TBI patients with findings of hemorrhage on CT, patients with DWI/ADC lesions on MRI are more likely to do worse

Physicochemical characterization of ferumoxytol, heparin and protamine nanocomplexes for improved magnetic labeling of stem cells

Stem cell-based therapies have become a major focus in regenerative medicine and to treat diseases. A straightforward approach combining three drugs, heparin (H), protamine (P) with ferumoxytol (F) in the form of nanocomplexes (NCs) effectively labeled stem cells for cellular MRI. We report on the physicochemical characteristics for optimizing the H, P, and F components in different ratios, and mixing sequences, producing NCs that varied in hydrodynamic size. NC size depended on the order in which drugs were mixed in media. Electron microscopy of HPF or FHP showed that F was located on the surface of spheroidal shaped HP complexes. Human stem cells incubated with FHP NCs resulted in a significantly greater iron concentration per cell compared to that found in HPF NCs with the same concentration of F. These results indicate that FHP could be useful for labeling stem cells in translational studies in the clinic. Published by Elsevier Inc.Intramural Research Program of the Clinical Center at the National Institutes of HealthIntramural Research Program of the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of HealthCtr Clin, Lab Diagnost Radiol Res Radiol & Imaging Sci, Bethesda, MD USANIH, Frank Lab Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USANatl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD USANatl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USAUniv Fed Sao Paulo, Dept Biochem, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Biochem, Sao Paulo, BrazilWeb of Scienc