Victor E. Yushmanov

Late Reversal of Cerebral Perfusion and Water Diffusion After Transient Focal Ischemia in Rats

Region-specific cerebral blood flow (CBF) and the apparent diffusion coefficient (ADC) of tissue water in the rat brain were quantified by high-field magnetic resonance imaging at 9.4 T in the rat suture occlusion model. Cerebral blood flow and ADC were compared during the short- (4.5 hours) and long-term (up to 6 days) reperfusion after 80 minutes of transient middle cerebral artery occlusion, and correlated with the histology analysis. On occlusion, average CBF fell from ∼100 to less than 50 mL 100 g−1 min−1 in the cortex, and to less than 20 mL 100 g−1 min−1 in the caudate putamen (CP). Corresponding ADC values decreased from (6.98 ± 0.82) × 10−4 to (5.49 ± 0.54) × 10−4 mm2/s in the cortex, and from (7.16 ± 0.58) × 10−4 to (4.86 ± 0.62) × 10−4 mm2/s in the CP. On average, CBF recovered to ∼50% of baseline in the first 24 hours of reperfusion. After 2 to 4 days, a strong hyperperfusion in the ipsilateral cortex and CP, up to ∼300 mL 100 g−1 min−1, was observed. The ADC ratio in the ipsilateral and contralateral CP was also inverted in the late reperfusion period. Histology revealed more severe tissue damage at the late stage of reperfusion than at 4.5 hours. Significant reversal of CBF and ADC during the late reperfusion period may reflect the impairment of autoregulation in the ischemic regions. Vascular factors may play an important role in the infarct development after 80-minute focal ischemia.

Sodium mapping in focal cerebral ischemia in the rat by quantitative 23Na MRI

To validate 23Na twisted projection magnetic resonance imaging (MRI) as a quantitative technique to assess local brain sodium concentration ([Na+]br) during rat focal ischemia every 5.3 minutes.

Inhomogeneous sodium accumulation in the ischemic core in rat focal cerebral ischemia by 23Na MRI

To test the hypotheses that (i) the regional heterogeneity of brain sodium concentration ([Na+]br) provides a parameter for ischemic progression not available from apparent diffusion coefficient (ADC) data, and (ii) [Na+]br increases more in ischemic cortex than in the caudate putamen (CP) with its lesser collateral circulation after middle cerebral artery occlusion in the rat.

NMR Studies of Drug Interaction with Membranes and Membrane-Associated Proteins

This review focuses on the recent developments in the study of drug interactions with biological membranes and membrane-associated proteins using nuclear magnetic resonance (NMR) spectroscopy and other spectroscopic techniques. Emphasis is placed on a class of low-affinity neurological agents as exemplified by volatile general anesthetics and structurally related compounds. The technical aspects are reviewed of how to prepare membrane-mimetic systems and of NMR approaches that are either in current use or opening new prospects. A brief literature survey covers studies ranging from drug distribution in simplified lipid matrix to specific drug interaction with neuronal receptors reconstituted in complicated synthetic membrane systems.

Monitoring of brain potassium with rubidium flame photometry and MRI

An animal model was developed to monitor [K+] in the brain using partial K+ replacement with Rb+ and 87Rb MRI. Fifty‐one rats were given 0–80 mM of RbCl in the drinking water for up to 90 days. Focal cerebral ischemia was produced in 15 of the animals. Na, K, and Rb content in precision‐guided submilligram samples of cortical brain were determined by emission flame photometry. Multinuclear 87Rb/23Na/1H MRI was performed on phantoms and rats at 3T using a twisted projection imaging (TPI) scheme for 87Rb/23Na, and custom‐built surface or parallel cosine transmit/receive coils. Brain [Rb+] was safely brought up to 17–25 mEq/kg within 2–3 weeks of feeding. The characteristic patterns of [K+] decrease (with a sharp drop at 3–4 hr of ischemia) and [Na+] increase (at a rate of 31%/hr) observed previously in animals without Rb/K substitution were reproduced in ischemic cortex. The Rb/(Rb+K) ratio increased over time in ischemic areas (R = 0.91, P < 0.001), suggesting an additional index of ischemia progression. Preliminary 87Rb MRI gave an estimate of 20–25 mEq Rb/kg brain weight (N = 2). In conclusion, brain Rb+ is detectable by 87Rb MRI and does not significantly interfere with ion dynamics in ischemic brain, which enables 87Rb MRI studies of K+ in ischemia. Magn Reson Med 57:494–500, 2007.

MAP2 immunostaining in thick sections for early ischemic stroke infarct volume in non-human primate brain

The delineation of early infarction in large gyrencephalic brain cannot be accomplished with triphenyl-tetrazolium chloride (TTC) due to its limitations in the early phase, nor can it be identified with microtubule-associated protein 2 (MAP2) immunohistochemistry, due to the fragility of large thin sections. We hypothesize that MAP2 immunostaining of thick brain sections can accurately identify early ischemia in the entire monkey brain. Using ischemic brains of one rat and three monkeys, a thick-section MAP2 immunostaining protocol was developed to outline the infarct region over the entire non-human primate brain. Comparison of adjacent thick and thin sections in a rat brain indicated complete correspondence between ischemic regions (100.4mm(3)+/-1.2%, n=7, p=0.44). Thick sections in monkey brain possessed the increased structural stability necessary for the extensive MAP2 immunostaining procedure permitting quantification of the ischemic region as a percent of total monkey brain, giving infarct volumes of 11.4, 16.3, and 19.0% of total brain. Stacked 2D images of the intact thick brain tissue sections provided a 3D representation for comparison to MRI images. The infarct volume of 16.1cm(3) from the MAP2 sections registered with MRI images agreed well with the volume calculated directly from the stained sections of 16.6 cm(3). Thick brain tissue section MAP2 immunostaining provides a new method for determining infarct volume over the entire brain at early time points in a non-human primate model of ischemic stroke.

ADC characterization of region-specific response to cerebral perfusion deficit in rats by MRI at 9.4 T.

Region‐specific cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) of water in the rat brain were quantified in vivo by high‐field MRI (9.4 T) for 6–7 h after middle cerebral artery occlusion (MCAO). Upon occlusion, average CBF fell from about 1.5–2 ml/g/min to below 0.5 ml/g/min in cortical areas and the amygdala, and below 0.2 ml/g/min in the caudate putamen. CBF in some of the homologous contralateral areas also decreased by 20–30%. Average ADC decreased from about 8 · 10−4 to 5 · 10−4 mm2/s in the caudate putamen and parietal cortex. Corresponding changes in ADC were lower in the frontal cortex and negligible in the piriform cortex, suggesting that the perfusion threshold for ADC decrease may be different for different brain regions in the same animal. The area of decreased ADC correlated well with the infarction area revealed by 2,3,5‐triphenyltetrazolium chloride (TTC) staining of brain slices in vitro. A better understanding of the mechanisms linking ADC and CBF changes to ischemic cell disorders may prove useful in characterizing the degree of tissue damage, and in developing and evaluating treatment strategies. Magn Reson Med 47:562–570, 2002.

K+ dynamics in ischemic rat brain in vivo by 87Rb MRI at 7 T

The aims of the present study were as follows: (i) to perform the first 87Rb MRI in live rats with focal ischemic stroke; and (ii) to test the hypothesis that K+ egress from the brain in this model is quantifiable in individual animals by high‐field (7‐T) K/Rb substitution MRI. Rats preloaded with dietary Rb+ (resulting in Rb/(K + Rb) replacement ratios of 0.1–0.2 in the brain) were subjected to permanent occlusion of the middle cerebral artery, and 87Rb MRI was implemented with 13‐min temporal resolution using a dedicated RF coil and a spiral ultrashort‐TE sequence (TR/TE = 3/0.07 ms). The ischemic core was localized by apparent diffusion coefficient mapping, by microtubule‐associated protein‐2 immunohistochemistry and by changes in surface reflectivity. [K], [Na] and [Rb] were determined independently in the micropunched samples by post‐mortem flame photometry. Both techniques were generally in agreement in the nonischemic cortex; however, the MRI‐assessed [K+ + Rb+] drop in ischemic brain was less pronounced (average efflux rate of 4.8 ± 0.2 nEq/mm3/h versus 10 ± 1 nEq/mm3/h by flame photometry; p < 0.0001). The use of higher field gradients for better spatial resolution, and hence more accurate quantification, is suggested. Copyright

Fast 3D rosette spectroscopic imaging of neocortical abnormalities at 3 T: Assessment of spectral quality

To use a fast 3D rosette spectroscopic imaging acquisition to quantitatively evaluate how spectral quality influences detection of the endogenous variation of gray and white matter metabolite differences in controls, and demonstrate how rosette spectroscopic imaging can detect metabolic dysfunction in patients with neocortical abnormalities.