[en] Identifying spontaneous CSF leaks can be difficult on CT myelography (CTM) in patients with suspected spontaneous intracranial hypotension (SIH). The current study compared renal collecting system (RCS) density during CTM in patients with suspected SIH relative to non-SIH controls and evaluated the overall utility as an indirect sign of spontaneous CSF leak in patients with SIH. All CTM performed over an 8-year period (n = 392) were retrospectively reviewed and included cases (n = 295) were divided into groups consisting of SIH patients with (n = 35) or without (n = 77) confirmed CSF leak on CTM and non-SIH controls (n = 183). Average and relative average (relative to systemic contrast density) RCS densities were compared with multivariate analysis adjusting for patient characteristics and CTM technical differences. Average RCS densities were greater for confirmed versus non-confirmed SIH groups and greater for both SIH groups relative to non-SIH controls. Correlations between RCS density and time from injection to CTM were higher within SIH patient groups compared to controls. Measured RCS density had a higher negative predictive value for excluding CSF leak both within the SIH patient groups as well as the overall cohort (84% and 96%, respectively), with optimized thresholds yielding 80% sensitivity and 70% specificity for the presence of leak in the overall cohort. Accounting for RCS density may provide reliable additional indirect diagnostic value about the suspicion of a CSF leak in patients undergoing CTM for evaluation of SIH symptoms.

[en] Introduction: Melanins are high-molecular-weight pigments that are ubiquitous in nature and can also be synthesized in the laboratory from a variety of precursors. Melanins possess numerous interesting physicochemical characteristics, including electromagnetic radiation absorption properties and ability to chelate metals. We have recently reported that melanin has remarkable ionizing-radiation-shielding properties, possibly because it can interact with photons via Compton scattering. We hypothesized that, if administered internally, melanin could play a beneficial role by scavenging various radionuclides, in addition to radiation shielding. Methods: Three melanins were synthesized from dopamine, 3,4-dihydroxyphenylalanine (L-Dopa) and a combination of L-cysteine and L-Dopa. For control, synthetic melanin made from tyrosine polymerization (Sigma) was used. Melanins were characterized by elemental analysis. The chemosorption of ¹¹¹In, ²²⁵Ac and ²¹³Bi by melanins was studied at 37 deg.C for up to 48 h. Results: The C-to-N molar ratios for dopamine, L-Dopa and tyrosine melanins were very close at 7.92, 8.39 and 8.48, respectively, while in mixed L-cysteine/L-Dopa melanin, that ratio was much lower at 3.63. This mixed melanin also contained 22.33% sulfur, thus confirming incorporation of S-containing motifs into its structure. Dopamine, L-Dopa and tyrosine melanins were very similar in their abilities to decrease the activity of ¹¹¹In, ²²⁵Ac and ²¹³Bi and their radioactive daughters in supernatants by >10-fold in comparison with the starting levels, while mixed L-cysteine/L-Dopa melanin was able to chemosorb only ¹¹¹In. Conclusions: We have demonstrated that synthetic melanins made of diverse precursors can chemosorb ¹¹¹In, ²¹³Bi and ²²⁵Ac, with dopamine, L-Dopa and tyrosine melanins being the most efficient towards all three of these radionuclides. Such properties of synthetic melanins can contribute to the development of the novel melanin-based radioprotective materials

[en] Posterior reversible encephalopathy syndrome (PRES) is a disorder of cerebrovascular autoregulation that can result in brain edema, hemorrhage, and infarction. We sought to investigate whether certain imaging characteristics in PRES are associated with clinically significant patient outcomes. We retrospectively reviewed all cases of PRES occurring between 2008 and 2014 at two major academic medical centers. Demographic, clinical, and radiographic data were collected. We analyzed imaging studies for vasogenic edema, hemorrhage, and diffusion restriction. We performed univariate analysis and stepwise logistic regression to assess the association between our radiologic findings of interest and clinical outcomes as defined by hospital discharge disposition and modified Rankin scale (mRS) at time of discharge. We identified 99 cases of PRES in 96 patients. The median age was 55 years (IQR 30-65) and 74% were women. In 99 cases, 60% of patients had active cancer, 19% had history of bone marrow or organ transplantation, 14% had autoimmune disease, and 8% were peripartum. Imaging at clinical presentation showed extensive vasogenic edema in 39%, hemorrhage in 36%, hemorrhage with mass effect in 7%, and restricted diffusion in 16%. In our final logistic regression models, the presence of extensive vasogenic edema, hemorrhage with mass effect, or diffusion restriction was associated with worse clinical outcome as defined by both discharge disposition (OR = 4.3; 95% CI: 1.4-36.3; p = 0.047) and mRS (OR = 3.6; 95% CI: 1.2-10.7; p = 0.019). Extensive vasogenic edema, hemorrhage, and restricted diffusion on initial imaging in PRES are associated with worse clinical outcomes. (orig.)

[en] Purpose: Protection of bone marrow against radiotoxicity during radioimmunotherapy and in some cases external beam radiation therapy such as hemi-body irradiation would permit administration of significantly higher doses to tumors, resulting in increased efficacy and safety of treatment. Melanin, a naturally occurring pigment, possesses radioprotective properties. We hypothesized that melanin, which is insoluble, could be delivered to the bone marrow by intravenously administrated melanin-covered nanoparticles (MNs) because of the human body's 'self-sieving' ability, protecting it against ionizing radiation. Methods and Materials: The synthesis of MNs was performed via enzymatic polymerization of 3,4-dihydroxyphenylalanine and/or 5-S-cysteinyl-3,4-dihydroxyphenylalanine on the surface of 20-nm plain silica nanoparticles. The biodistribution of radiolabeled MNs in mice was done at 3 and 24 h. Healthy CD-1 mice (Charles River Laboratories International, Inc., Wilmington, MA) or melanoma tumor-bearing nude mice were given MNs intravenously, 50 mg/kg of body weight, 3 h before either whole-body exposure to 125 cGy or treatment with 1 mCi of ¹⁸⁸Re-labeled 6D2 melanin-binding antibody. Results: Polymerization of melanin precursors on the surface of silica nanoparticles resulted in formation of a 15-nm-thick melanin layer as confirmed by light scattering, transmission electron microscopy, and immunofluorescence. The biodistribution after intravenous administration showed than MN uptake in bone marrow was 0.3% and 0.2% of injected dose per gram at 3 and 24 h, respectively, whereas pre-injection with pluronic acid increased the uptake to 6% and 3% of injected dose per gram, respectively. Systemic MN administration reduced hematologic toxicity in mice treated with external radiation or radioimmunotherapy, whereas no tumor protection by MNs was observed. Conclusions: MNs or similar structures provide a novel approach to protection of bone marrow from ionizing radiation based on prevention of free radical formation by melanin.