Analysis of normal-appearing white matter in multiple sclerosis: comparison of diffusion tensor MR imaging and magnetization transfer imaging.

BACKGROUND AND PURPOSE: Our purpose was to compare diffusion tensor MR and magnetization transfer imaging in assessing normal-appearing white matter (WM) regions in multiple sclerosis (MS). METHODS: Diffusion tensor, magnetization transfer, and conventional MR imaging were performed in 12 patients with MS. Fractional anisotropy, apparent diffusion coefficients (ADCs), and magnetization transfer ratios (MTRs) were measured in plaques, normal-appearing periplaque WM (PWM) regions, and normal-appearing WM regions remote from plaques. Mean fractional anisotropy, ADCs, and MTRs were calculated and compared in WM regions. RESULTS: Fractional anisotropy was lower in normal-appearing PWM regions than in remote WM regions (P <.001) but higher than in plaques (P <.001). MTRs were lower (not significantly, P =.19) in normal-appearing PWM regions than in remote regions. MTRs were higher in normal-appearing PWM regions than in plaques (P <.001). ADCs were higher in normal-appearing PWM regions than in remote regions (P =.008) but lower than in plaques (P =.001). Correlation between fractional anisotropy and MTRs of individual lesions was poor (r = 0.18) and between fractional anisotropy and ADC, modest (r = -0.39). CONCLUSION: In MS, diffusion tensor MR imaging can depict differences between WM regions that are not apparent on conventional MR images. Anisotropy measurements may be more sensitive than those of MTRs in detecting subtle abnormalities in PWM.

Cerebral abscesses: investigation using apparent diffusion coefficient maps.

The combination of high signal and reduced apparent diffusion coefficients (ADC) within abscesses on diffusion-weighted MRI (DWI) has been reported as characteristic of abscesses, and useful for distinguishing them from cystic or necrotic neoplasms. To assess whether these are consistent findings in abscesses, we used DWI-derived ADC to investigate changes in water diffusibility in cerebral abscesses. We reviewed the MRI studies and clinical records of five patients with brain abscesses, who underwent DWI. Regions of interest were drawn within the abscesses on ADC maps, to obtain the ADC. The center of all five abscesses gave signal higher than that of white matter on DWI. The three largest also appeared bright on ADC maps, i. e., showed ADC substantially lower than those of normal white matter, consistent with restricted diffusion. However, the two smaller abscesses were not visible on ADC maps because their ADC were essentially the same as that of white matter; they did not show restricted diffusion. The absence of restricted diffusion within small abscesses may be related to intrinsic differences in molecular microenvironment between small and large abscesses, or to greater influence of volume averaging with surrounding edema on the ADC in smaller abscesses.

Evaluation of white matter anisotropy in Krabbe disease with diffusion tensor MR imaging: initial experience.

PURPOSE: To compare diffusion tensor magnetic resonance imaging with conventional T2-weighted imaging for evaluation of white matter changes in patients with Krabbe disease. MATERIALS AND METHODS: In eight patients with Krabbe disease and eight age-matched control subjects, anisotropy maps were generated with diffusion tensor data by using echo-planar imaging with diffusion gradient encoding in six directions. Anisotropy maps and T2-weighted images were visually inspected. Relative anisotropy (RA) and normalized T2-weighted signal intensity in white matter tracts and gray matter nuclei were quantitatively compared between patients and controls (paired Student t test). RESULTS: Loss of diffusion anisotropy appeared on anisotropy maps as areas of decreased hyperintensity in patients with Krabbe disease. Differences in RA between Krabbe disease patients and control subjects were significant in eight of nine white matter structures studied (P =.001-.01) and in basal ganglia (P =.04). T2-weighted signal intensity was also significantly different in the same white matter structures (P =.006-.049) but not in basal ganglia. In the three patients imaged after stem cell transplantation, mean RA was between the RAs of untreated patients and control subjects. CONCLUSION: Diffusion tensor-derived anisotropy maps (a) provide a quantitative measure of abnormal white matter in patients with Krabbe disease, (b) are more sensitive than T2-weighted images for detecting white matter abnormality, and (c) may be a marker of treatment response.

Sodium-pump potentials and currents in guinea-pig ventricular muscles and myocytes.

When guinea-pig papillary muscles were depolarized to ca. -30 mV by superfusion with K+-free Tyrode's solution supplemented with Ba2+, Ni2+, and D600, addition of Cs+ transiently hyperpolarized the membrane in a reproducible manner. The size of the hyperpolarization (pump potential) depended on the duration of the preceding K+-free exposure; peak amplitudes (Epmax) elicited by 10 mM Cs+ after 5-, 10-, and 15-min K+-free exposures were 12.9, 17.7, and 23.2 mV, respectively. Pump potentials were unaffected by external Cl- but suppressed by cardiac glycosides, hyperosmotic conditions, and low-Na+ solution. Using Epmax as an indicator of Na+ pump activation, the half-maximal concentration for activation by Cs+ was 12-16.3 mM. At 6 mM, Cs+ was three times less potent than Rb+ or K+ and five times more potent than Li+. From these findings, and correlative voltage-clamp data from myocytes, we calculate that (i) a pump current of 7.8 nA/cm2 generates an Epmax of 1 mV and (ii) resting pump current in normally polarized muscle (approximately 0.16 microA/cm2) is five times smaller than previously estimated.

Potassium current and sodium pump involvement in the positive inotropy of cardiac muscle during hyperosmotic stress.

OBJECTIVE: To identify factors involved in the modification of cardiac electromechanical activity caused by hyperosmotic solution. DESIGN: Membrane potentials and contractions were recorded from isolated papillary muscles, and membrane ionic currents were measured in isolated ventricular myocytes by using the ruptured patch or perforated patch voltage clamp method. ANIMALS AND METHODS: Adult male guinea-pigs weighing 250 to 350 g were used. Normal Tyrode's solution for superfusing experimental preparations was replaced with hyperosmotic Tyrode's solution for observation periods of up to 10 mins. The hyperosmotic solution was normal Tyrode's solution supplemented with 50 or 150 mM sucrose (1.2 or 1.5 times normal osmolality). Sodium pump activity (hyperpolarization in muscles; outward current in myocytes) was activated by switching to pump-activating cation (cesium, potassium) solution from pump-inactivating potassium-free solution under conditions in which other ionic currents were suppressed. RESULTS: Hyperosmotic solution lengthened action potentials and enhanced developed tension in papillary muscles. Superfusion of myocytes with hyperosmotic solution inhibited inward L-type calcium current (ICa,L) by approximately 30% and the outward delayed rectifier potassium current (Ik) by approximately 50%. Hyperosmotic treatment also partially inhibited sodium pump-generated hyperpolarizations in papillary muscles. However, sodium pump current in myocytes was relatively small under isosmotic conditions and, therefore, unlikely to be a major factor in action potential lengthening. CONCLUSIONS: Inhibition of potassium current is a major factor in the lengthening of the action potential by hyperosmotic solution. It seems likely that the accompanying positive inotropy is due to an elevation of intracellular calcium caused by enhanced calcium influx related to action potential prolongation and sodium pump inhibition.

Protection by hypoxic preconditioning against hypoxia-reoxygenation injury in guinea-pig papillary muscles.

OBJECTIVE: Developed tension in guinea-pig papillary muscles is depressed by prolonged hypoxia; subsequent reoxygenation leads to a partial recovery that stabilizes after an early period of arrhythmia. We have investigated whether hypoxic preconditioning in these muscles (1) improves the recovery of developed tension, (2) protects against arrhythmia, and (3) causes other significant electromechanical changes. METHODS: Papillary muscles stimulated at 1 Hz were superfused with oxygenated Krebs solution for 60 min and either preconditioned (5 min of 3 Hz pacing substrate-free hypoxic conditions, 10 min of normoxic recovery) or equilibrated for an extra 15 min. Muscles were subsequently challenged with substrate-free hypoxia (1 Hz), and reoxygenated (1 Hz) for 60 min. Contractile performance, action potential parameters, and indicators of arrhythmic activity were measured in 10 preconditioned and 10 non-preconditioned muscles. RESULTS: Developed tension in preconditioned muscles declined to the same level (10-15% control) as in non-preconditioned muscles after 60 min hypoxia. A notable difference was that developed tension in the preconditioned muscles failed to rebound during mid-hypoxia, a hallmark feature in non-preconditioned muscles. The action potential duration and overshoot collapsed at a significantly faster rate in hypoxic preconditioned muscles. Action potential recovery during reoxygenation was similar in the two groups of muscles, but recovery of developed tension was significantly stronger in preconditioned (76.7 +/- 5.4%) than in non-preconditioned (42.9 +/- 1.7%) muscles (P < 0.001). Reoxygenation provoked arrhythmic activity in all muscles, but the summed average duration was shorter (5.5 +/- 1.0 vs. 9.4 +/- 1.5 min) (P < 0.05) in the preconditioned muscles. CONCLUSION: Hypoxic preconditioning can significantly enhance post-hypoxia recovery of developed tension, and significantly attenuate arrhythmic activity, in guinea-pig papillary muscles.

Comparison of effects of aprikalim and of hypoxic and ischaemic preconditioning on extracellular potassium accumulation, metabolism, and functional recovery of the globally ischaemic rat heart.

OBJECTIVE: The aim was to compare the effects of a potassium channel opener, aprikalim, and of hypoxic and ischaemic preconditioning on extracellular K+ concentration change, metabolism, and ventricular function in isolated globally ischaemic rat hearts. METHODS: Isovolumetric rat hearts (37 degrees C) were treated with 1 microM (apri 1) or 30 microM (apri 30) aprikalim, or preconditioned with either 10 min of hypoxia (N2PC) or 5 min of ischaemia followed by 5 min of perfusion (IPC5) or 10 min of ischaemia followed by 3 min of perfusion (IPC10). Control hearts received neither treatment nor preconditioning. All hearts received 30 min of sustained ischaemia followed by 25 min of reperfusion. Extracellular K+ concentration was measured with a potassium sensitive electrode inserted into the extracellular space of the left ventricular wall. RESULTS: Recovery of left ventricular developed pressure after 25 min of reperfusion was only 19.20(SEM 5.09)% of the preischaemic level in the control group. No recovery was obtained for the apri 1 group. In contrast, a very good recovery was obtained for the apri 30 group [96.69(10.92)%], the N2PC group [104.92(17.40)%], and the IPC10 group [84.96(9.86)%]. The IPC5 group, however, did not have improved recovery of left ventricular pressure [14.15(5.61)%]; this is likely to be related to differences in the stimulation of anaerobic glycolysis. The protection was also markedly attenuated by pretreatment with 50 microM glibenclamide in the apri 30, N2PC, and IPC10 groups [22.76(9.00), 66.06(6.09), and 46.18(7.06)%, respectively]. Hearts treated with aprikalim before inducing ischaemia showed a concentration dependent increase in [K+]e. Hypoxic (N2PC) and ischaemic preconditioning (IPC5 and IPC10) were also associated with an increase in [K+]e over the 5-10 min period preceding the 30 min of sustained ischaemia. During sustained ischaemia all groups showed a nearly triphasic pattern of extracellular K+ changes with an early rising phase, with the exception of the N2PC group for which the early [K+]e rise was barely detectable. CONCLUSIONS: An increase in [K+]e before sustained ischaemia is one of the mechanisms involved in the conditions affording protection. Although important, this is not sufficient, and further protection may be accomplished by decreased stimulation of anaerobic glycolysis during the sustained ischaemia.

Gender-related differences in regional cerebral glucose metabolism in normal volunteers.

Positron emission tomography studies have correlated changes in the cerebral metabolic rate of glucose utilization (CMRglu) with symptoms of depression, aggression, impulsivity, and hyperactivity. Psychiatric disorders in which these symptoms are manifested are disproportionately represented among the sexes. We evaluated gender differences in regional CMRglu in control subjects (21 men and 18 women) with particular interest in the global, orbital frontal, and left anterolateral prefrontal cortical (LAPFC) CMRglu. A trend was present for global CMRglu to be greater in women than in men. Regional CMRglu was lower in men than in women in the orbital frontal area. No differences were observed in the LAPFC region.

Skinned cardiac fibres of diabetic rats: contractile activation and effects of 2,3-butanedione monoxime (BDM) and caffeine.

OBJECTIVE: The aim was to examine contractile properties of skinned cardiac fibres from rats with streptozotocin induced diabetes and to compare the effects of two agents, caffeine and 2,3-butanedione monoxime (BDM), on myocardial contractile characteristics of normal and diabetic cardiac fibres. METHODS: Small fibre bundles dissected from papillary muscles of the left ventricle were chemically skinned by exposure to Triton X-100. The tension-pCa (pCa = -log10 [Ca2+]) relationships were determined under isometric conditions. RESULTS: In skinned fibres from diabetic rats maximum Ca2+ activated force was unchanged in comparison with normal rats, but a significant, though small, increase in the Ca2+ sensitivity [pCa for one half maximal activation (pCa50)] of contraction was shown. Caffeine (5-20 mM) increased Ca2+ sensitivity in a dose dependent manner and to the same extent in the two groups of preparations. Up to 10 mM caffeine, maximum force was not affected. On the other hand, BDM (2 and 5 mM) decreased Ca2+ sensitivity in both normal and diabetic fibres, but the rightward shift of the tension-pCa relationship induced by BDM was more pronounced in diabetic than in normal fibres: pCa50 was 5.55(SEM 0.02), 5.51(0.01), and 5.46(0.01) in normal fibres, and 5.62(0.01), 5.51(0.02), and 5.45(0.02) in diabetic fibres for 0, 2, and 5 mM BDM, respectively. Maximum tension was similarly decreased by BDM in the two groups of fibres. CONCLUSIONS: (1) No change is induced by diabetes in the site of action of caffeine; (2) some drugs that affect myofilament Ca2+ sensitivity, such as BDM, may act differently in diabetic and control myocardium.