Small Vessel Disease, a Marker of Brain Health: What the Radiologist Needs to Know.

Small vessel disease, a disorder of cerebral microvessels, is an expanding epidemic and a common cause of stroke and dementia. Despite being almost ubiquitous in brain imaging, the clinicoradiologic association of small vessel disease is weak, and the underlying pathogenesis is poorly understood. The STandards for ReportIng Vascular changes on nEuroimaging (STRIVE) criteria have standardized the nomenclature. These include white matter hyperintensities of presumed vascular origin, recent small subcortical infarcts, lacunes of presumed vascular origin, prominent perivascular spaces, cerebral microbleeds, superficial siderosis, cortical microinfarcts, and brain atrophy. Recently, the rigid categories among cognitive impairment, vascular dementia, stroke, and small vessel disease have become outdated, with a greater emphasis on brain health. Conventional and advanced small vessel disease imaging markers allow a comprehensive assessment of global brain heath. In this review, we discuss the pathophysiology of small vessel disease neuroimaging nomenclature by means of the STRIVE criteria, clinical implications, the role of advanced imaging, and future directions.

The lichen transplant methodology in the source apportionment of metal deposition around a copper smelter in the former mining town of Karabash, Russia.

The lichen transplant monitoring methodology has been tested for source apportionment of metal deposition around the Cu smelter and former mining town of Karabash. Transplants of the lichen Hypogymnia physodes (L.) Nyl., collected from a 'control' site in July 2001, were set up at 10 stations along a 60 km NE-SW transect centred on Karabash. Samples were collected after 2 and 3 month monitoring periods and analysed using established wet-chemical techniques. The sources of particulate investigated were the smelter blast furnace and converter, floatation tailings, metallurgical slags, local road dusts, top soils and ambient airborne total suspended particulate. From multi-element least-squares modelling the blast furnace was the main source of particulate in transplants close to the smelter (<10 km). Particulate from the converter, with relatively high Pb and Zn, was found to be more widely dispersed, being finer-grained and so having a longer atmospheric residence time. Ambient airborne particulate, sampled in Karabash town using air-pump apparatus, was almost entirely derived from the converter, very different to the lichen transplants from the same area which mainly contained blast furnace particulate. It is proposed that lichens close to the smelter mainly trapped larger blast furnace-derived particulate as they have a low capture efficiency for smaller (converter) particles. The study demonstrates the utility of lichen transplants for monitoring atmospheric deposition and highlights the caution required in their use to assess ambient air quality in human health studies.

Biogeochemical signatures in the lichen Hypogymnia physodes in the mid Urals.

Multi-element content and uranium (U) isotopes were investigated in the lichen Hypogymnia physodes (native and transplants) sampled across a 60-km transect, centred on Karabash smelter town, from Turgoyak Lake (SW) to Kyshtym (NE) to investigate the origin of U. Kyshtym was the site of a major nuclear accident in 1957. (234)U/(238)U activity ratios in native thalli sampled during July 2001 were within the natural isotopic ratio in minerals. Uranium/thorium (U/Th) ratios were higher in native thalli towards the NE (average 0.73) than those in the SW (average 0.57). Element signatures in native thalli and transplants suggest U was derived from fossil fuel combustion from Karabash and sources lying further to the east. Systematic and significant U enrichment indicative of a nuclear fuel cycle source was not detected in any sample. Element signatures in epiphytic lichen transplants and native thalli provide a powerful method to evaluate U deposition.

Characterisation of airborne particulate pollution in the Cu smelter and former mining town of Karabash, South Ural Mountains of Russia.

Airborne total suspended particulates (TSP), dusts from smelter blast furnace and converter stacks, and filtrates of snow melt waters have been characterised in the Cu smelter and former mining town of Karabash, Russia. TSP was collected at sites up- and downwind of the smelter and large waste and tailings dumps (Oct. 2000 and July 2001). Methods for particle size, mineralogical and elemental determinations have been tested and described, and a new PSD-MicroSOURCE XRD technique developed for the mineralogical analysis of microsamples on filter substrates. TSP in downwind samples has a mean equivalent spherical diameter of 0.5 microm (s.d. = 0.2) and was found to be 100% respirable. The main element of human health/environmental concern, above Russian maximum permitted levels (1 microg m(-3), average over any time period), was Pb which was measured at 16-30 microg m(-3) in downwind samples. Individual particulates mainly consisted of complex mixtures of anglesite (PbSO4), Zn2SnO4 and poorly ordered Zn sulphates. From experimental and theoretical considerations, a high proportion of contained Pb, Zn, Cd and As in this material is considered to be in a readily bioavailable form. Chemical and mineralogical differences between the TSP, stack dusts and snow samples are discussed, as well as the implications for human and regional environmental health.

SEM-EDX analysis in the source apportionment of particulate matter on Hypogymnia physodes lichen transplants around the Cu smelter and former mining town of Karabash, South Urals, Russia.

Scanning electron microscopy with energy-dispersive X-ray analysis (SEM-EDX) of particulate matter on lichen transplant thalli (Hypogymnia physodes) was assessed as a complementary technique to wet chemical analysis for source apportionment of airborne contaminants. Transplants (2 month exposure) stationed in the Cu smelter and former mining town of Karabash were compared with those from a control site 30 km south. Particulate matter in Karabash samples (715 analyses) showed higher levels of S, Pb, Cu, Sn and Zn compared with the control (598 analyses). Complex element associations among the particles confounded detailed mineralogical identifications, and therefore a simplified particle classification scheme was devised for source apportionment. Karabash samples contained high levels of particles classified as mining-related (MRP), and these were also identified in control samples, indicating wide spatial dispersion from the smelter and highlighting the sensitivity of the method. It was noted that MRP <2.5-microm diameter were poorly represented on lichen surfaces suggesting this may limit the usefulness of Hypogymnia transplants as proxies when assessing human health impacts from airborne particulates. Analyses of the lichen thallus surface (away from surface particulates) revealed high levels of Cu, Zn, Fe and Pb associated with organics in the Karabash samples compared with the control, with a proportionate loss of K, interpreted as being due to a stress-related increase in cell membrane permeability. This type of analysis may provide a novel SEM-EDX-based method for assessing lichen vitality. The techniques developed are presented and further implications of the study are discussed.

Lead isotopes in lichen transplants around a Cu smelter in Russia determined by MC-ICP-MS reveal transient records of multiple sources.

Transplants of the lichen Hypogymnia physodes, which is relatively tolerant to SO2 and heavy metals, were deployed for 3 months over a 60 km long SW-NE transect centered on a highly polluting Cu smelter and its adjoining town of Karabash, southern Urals, Russia. The abundance of 206Pb, 207Pb, 208Pb, and 204Pb were determined by MC-ICP-MS. The measurement of 204Pb revealed critical features, which would otherwise remain concealed: (i) The precise isotope ratios referenced to 204Pb allowed several different sources to be resolved even within the small area covered: (a) the obvious pollutant source of the Karabash Cu smelter; (b) two dispersed sources, likely to include soil with lower and different contributions of thorogenic and uranogenic lead; and (c) one anthropogenic source with higher contribution of 235U derived Pb. (ii) In part of the transect, the Pb isotope composition changed while the Pb concentrations remained the same. This indicates that the Pb content of the transplantation material from the background site was largely replaced and that the transplants provide a transient record reflecting a continuous accumulation and loss of environmental Pb, probably mainly in the form of extracellular particles. Overall, the method of lichen transplantation coupled with Pb isotope ratio determinations proved effective in assessing the usefulness of lichens in biomonitoring and in resolving different sources of atmospheric deposition.

Bioaccumulation of lead by the lichen Acarospora smaragdula from smelter emissions.

Accumulation of lead in the crustose lichen Acarospora smaragdula sensu lato is reported in the vicinity of an ore- processing plant where it is subjected to acidification and metal particulate fallout. A combination of light microscopy, X-ray element mapping, field emission scanning electron microscopy (FESEM) and other analytical techniques identifies Pb accumulation within specific fungal tissues derived from smelter particles (PM10s). No Pb was detected within the photobiont layer. Our studies suggest that Pb is highly mobile under the prevailing acidic conditions, and is fixed within the lichen cortex and melanized apothecia. Lead is also accumulated within the medulla and at the rock-lichen interface where it may precipitate as amorphous botryoidal encrustations on medullary hyphae and iron-rich particles. Modern FESEMs and microprobes enable analysis of minute quantities of material, and are important tools in understanding the fate of metals within lichens necessary to develop their use as predictive and sensitive bioindicators of aerial particulate contaminants. We suggest that crustose lichens, hitherto largely ignored in metal pollution studies, may be useful bioindicators of aerial particulate contaminants in polluted areas where macrolichens are absent.

Absolute quinidine bioavailability.

The absolute bioavailability of quinidine was studied in 11 hospitalized patients. A 400-mg dose of quinidine gluconate was administered to each patient by intravenous infusion and as an oral solution. Drug treatments were separated by a 72-hr period. In 8 patients, peak plasma quinidine concentrations were reached in 65 min after the oral dose; in the remaining 3 subjects, peak concentrations were reached later. From the ratio of the total area under the plasma concentration-time curves (AUCoral/AUCir), the absolute bioavailability of quinidine ranged from 44% to 89% (mean, 72). In 8 patients, the ratio of the total amount of quinidine excreted in the urine in 48 hr (AUinfinity oral/AUinfinity ir) indicated that the extent of quinidine bioavailability varied form 47% to 96% (mean, 73). The predicted bioavailability of quindine due to first-pass effects was 76+/-11%. It is concluded that absorption after the oral solution was rapid and that the reduction of quinidine bioavailability was due to first-pass hepatic drug removal.

Disposition kinetics of dihydroquinidine following quinidine administration.

The disposition kinetics of dihydroquinidine, a known impurity in drug grade quinidine, was studied in 7 patients who were hospitalized for control of cardiac arrhythmias. Quinidine gluconate injection containing 5.4 to 6.2 percent dihydroquinidine was used. Following an overnite fast, dihydroquinidine doses of 0.16 to 0.31 mg/kg base were infused intravenously over 22 min. Plasma samples were collected at various times for 12 hr and analyzed for dihydroquinidine by a thin layer chromatography-fluorometric assay procedure. Postinfusion plasma dihydroquinidine concentration decline was described by a biexponential equation which suggested that the impurity distributes within the body in two kinetically distinguishable pools. The volume of the central pool (Vc) and steady-state volume of distribution (Vdss) were 0.67 +/- 0.15 L/kg and 2.76 +/- 0.63 L/kg, respectively. The halflife of the fast (t1/2alpha) and slow (t1/2beta) disposition processes were 4.71 +/- 0.26 min and 5.71 +/- 1.00 hr. Total plasma clearance was 4.17 +/- 0.68 ml/min/kg. Renal excretion of intact dihydroquinidine accounted for 16 percent of the administered dose. The corresponding value for renal dihydroquinidine clearance (Clr) was 0.61 +/- 0.08 ml/min/kg. The results of this study indicated that there were no significant differences in the distribution and elimination characteristics of dihydroquinidine and quinidine.

Disposition kinetics of quinidine.

The disposition kinetics of quinidine in 12 hospitalized patients in whom oral quinidine therapy was to be initiated is described. Quinidine in doses of 2.6 to 5.2 mg/kg base were infused intravenously over 22 min. Plasma samples were collected during the postinfusion for 24 hr and analyzed by a specific and sensitive assay procedure. In the 12 hr after administration, postinfusion plasma quinidine concentration decay was described by a biexponential equation. Attempts to include the 24-hr data point in the fitting procedures resulted in poorer agreements between the theoretical and experimental curves. A 2-compartment open model is proposed to describe the disposition of quinidine. The volume of the central pool (Vc) and steady-state volume of distribution (Vdss) were 0.91 +/- 0.11 L/kg and 3.03 +/- 0.25 L/kg, respectively, and indicate that quinidine distribution is predominantly extravascular. Quinidine distribution was quite rapid (t1/2alpha = 7.19 +/- 0.70 min), while the apparent elimination half-life (t1/2beta) was considerably longer, 6.333 +/- 0.47 hr. Total body plasma clearance ranged from 1.49 to 7.15 ml/min/kg (mean 4.70) and is primarily associated with nonrenal mechanisms of drug elimination. Urine specimens collected for 48 hr indicated that 17% of the dose is excreted intact and that urinary excretion was essentially complete within 24 hr. Renal clearance (Clr) was 0.80 +/- 0.18 ml/min/kg. The study demonstrated that there is substantial interpatient variability with respect to quinidine disposition.