Navegando por Autor "Silva, Afonso C."
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Artigo Arterial Spin Labeling Measurements of Cerebral Perfusion Territories in Experimental Ischemic Stroke(2011) Leoni, Renata F.; Paiva, Fernando F.; Kang, Byeong-Teck; Henning, Erica C.; Nascimento, George Carlos; Tannús, Alberto; Araújo, Dráulio Barros de; Silva, Afonso C.Collateral circulation, defined as the supplementary vascular network that maintains cerebral blood flow (CBF) when the main vessels fail, constitutes one important defense mechanism of the brain against ischemic stroke. In the present study, continuous arterial spin labeling (CASL) was used to quantify CBF and obtain perfusion territory maps of the major cerebral arteries in spontaneously hypertensive rats (SHRs) and their normotensive Wistar-Kyoto (WKY) controls. Results show that both WKY and SHR have complementary, yet significantly asymmetric perfusion territories. Right or left dominances were observed in territories of the anterior (ACA), middle and posterior cerebral arteries, and the thalamic artery. Magnetic resonance angiography showed that some of the asymmetries were correlated with variations of the ACA. The leptomeningeal circulation perfusing the outer layers of the cortex was observed as well. Significant and permanent changes in perfusion territories were obtained after temporary occlusion of the right middle cerebral artery in both SHR and WKY, regardless of their particular dominance. However, animals with right dominance presented a larger volume change of the left perfusion territory (23±9%) than animals with left dominance (7±5%, P<0.002). The data suggest that animals with contralesional dominance primarily safeguard local CBF values with small changes in contralesional perfusion territory, while animals with ipsilesional dominance show a reversal of dominance and a substantial increase in contralesional perfusion territory. These findings show the usefulness of CASL to probe the collateral circulation.Artigo Assessing Cerebrovascular Reactivity in Carotid Steno-Occlusive Disease UsingMRI BOLD and ASL Techniques(2012-04-17) Leoni, Renata F.; Mazzetto-Betti, Kelley C.; Silva, Afonso C.; Santos, Antonio C. dos; Araújo, Dráulio Barros de; Leite, João P.; Pontes-Neto, Octavio M.Impaired cerebrovascular reactivity (CVR), a predictive factor of imminent stroke, has been shown to be associated with carotid steno-occlusive disease. Magnetic resonance imaging (MRI) techniques, such as blood oxygenation level-dependent (BOLD) and arterial spin labeling (ASL), have emerged as promising noninvasive tools to evaluate altered CVR with whole-brain coverage, when combined with a vasoactive stimulus, such as respiratory task or injection of acetazolamide. Under normal cerebrovascular conditions, CVR has been shown to be globally and homogenously distributed between hemispheres, but with differences among cerebral regions. Such differences can be explained by anatomical specificities and different biochemical mechanisms responsible for vascular regulation. In patients with carotid steno-occlusive disease, studies have shown that MRI techniques can detect impaired CVR in brain tissue supplied by the affected artery. Moreover, resulting CVR estimations have been well correlated to those obtained with more established techniques, indicating that BOLD and ASL are robust and reliable methods to assess CVR in patients with cerebrovascular diseases. Therefore, the present paper aims to review recent studies which use BOLD and ASL to evaluate CVR, in healthy individuals and in patients with carotid steno-occlusive disease, providing a source of information regarding the obtained results and the methodological difficulties.Artigo Cerebrospinal fluid to brain transport of manganese in a non-human primate revealed by MRI(Elsevier, 2008-03-10) Bock, Nicholas A.; Paiva, Fernando F.; Nascimento, George Carlos do; Newman, John D.; Silva, Afonso C.Manganese overexposure in non-human primates and humans causes a neurodegenerative disorder called manganism thought to be related to an accumulation of the metal in the basal ganglia. Here, we assess changes in the concentration of manganese in regions of the brain of a non-human primate (the common marmoset, Callithrix jacchus) following four systemic injections of 30 mg/kg MnCl2 H2O in the tail vein using T1-weighted magnetic resonance imaging (MRI) and compare these to changes in the rat following the same exposure route and dose. The doses were spaced 48 h apart and we imaged the animals 48 h after the final dose. We find that marmosets have significantly larger T1-weighted image enhancements in regions of the brain compared to rats, notably in the basal ganglia and the visual cortex. To confirm this difference across species reflects actual differences in manganese concentrations and not variations in the MRI properties of manganese, we measured the longitudinal relaxivity of manganese (χ1) in the in vivo brain and found no significant species' difference. The high manganese uptake in the marmoset basal ganglia and visual cortex can be explained by CSF-brain transport from the large lateral ventricles and we confirm this route of uptake with time-course MRI during a tail-vein infusion of manganese. There is also high uptake in the substructures of the hippocampus that are adjacent to the ventricles. The large manganese accumulation in these structures on overexposure may be common to all primates, including humansArtigo fMRI in the awake marmoset: somatosensory-evoked responses, functional connectivity, and comparison with propofol anesthesia(Elsevier, 2013-09) Liu, Junjie V.; Hirano, Yoshiyuki; Nascimento, George Carlos; Stefanovic, Bojana; Leopold, David A.; Silva, Afonso C.Functional neuroimaging in animal models is essential for understanding the principles of neurovascular coupling and the physiological basis of fMRI signals that are widely used to study sensory and cognitive processing in the human brain. While hemodynamic responses to sensory stimuli have been characterized in humans, animal studies are able to combine very high resolution imaging with invasive measurements and pharmacological manipulation. To date, most high-resolution studies of neurovascular coupling in small animals have been carried out in anesthetized rodents. Here we report fMRI experiments in conscious, awake common marmosets (Callithrix jacchus), and compare responses to animals anesthetized with propofol. In conscious marmosets, robust BOLD fMRI responses to somatosensory stimulation of the forearm were found in contralateral and ipsilateral regions of the thalamus, primary (SI) and secondary (SII) somatosensory cortex, and the caudate nucleus. These responses were markedly stronger than those in anesthetized marmosets and showed a monotonic increase in the amplitude of the BOLD response with stimulus frequency. On the other hand, anesthesia significantly attenuated responses in thalamus, SI and SII, and abolished responses in caudate and ipsilateral SI. Moreover, anesthesia influenced several other aspects of the fMRI responses, including the shape of the hemodynamic response function and the interareal (SI–SII) spontaneous functional connectivity. Together, these findings demonstrate the value of the conscious, awake marmoset model for studying physiological responses in the somatosensory pathway, in the absence of anesthesia, so that the data can be compared most directly to fMRI in conscious humansArtigo Investigation of the BOLD and CBV fMRI responses to somatosensory stimulation in awake marmosets (Callithrix jacchus)(Wiley, 2017-12-29) Hirano, Yoshiyuki; Yen, Cecil C.; Liu, Junjie V.; Mackel, Julie B.; Merkle, Hellmut; Nascimento, George Carlos do; Stefanovic, Bojana; Silva, Afonso C.Understanding the spatiotemporal features of the hemodynamic response function (HRF) to brain stimulation is essential for the correct application of neuroimaging methods to study brain function. Here, we investigated the spatiotemporal evolution of the blood oxygen level‐dependent (BOLD) and cerebral blood volume (CBV) HRF in conscious, awake marmosets (Callithrix jacchus ), a New World non‐human primate with a lissencephalic brain and with growing use in biomedical research. The marmosets were acclimatized to head fixation and placed in a 7‐T magnetic resonance imaging (MRI) scanner. Somatosensory stimulation (333‐μs pulses; amplitude, 2 mA; 64 Hz) was delivered bilaterally via pairs of contact electrodes. A block design paradigm was used in which the stimulus duration increased in pseudo‐random order from a single pulse up to 256 electrical pulses (4 s). For CBV measurements, 30 mg/kg of ultrasmall superparamagnetic ironoxide particles (USPIO) injected intravenously, were used. Robust BOLD and CBV HRFs were obtained in the primary somatosensory cortex (S1), secondary somatosensory cortex (S2) and caudate at all stimulus conditions. In particular, BOLD and CBV responses to a single 333‐μs‐long stimulus were reliably measured, and the CBV HRF presented shorter onset time and time to peak than the BOLD HRF. Both the size of the regions of activation and the peak amplitude of the HRFs grew quickly with increasing stimulus duration, and saturated for stimulus durations greater than 1 s. Onset times in S1 and S2 were faster than in caudate. Finally, the fine spatiotemporal features of the HRF in awake marmosets were similar to those obtained in humans, indicating that the continued refinement of awake non‐human primate models is essential to maximize the applicability of animal functional MRI studies to the investigation of human brain functionArtigo Magnetic resonance imaging quantification of regional cerebral blood flow and cerebrovascular reactivity to carbon dioxide in normotensive and hypertensive rats(2011-06-25) Leoni, Renata F.; Paiva, Fernando F.; Henning, Erica C.; Nascimento, George Carlos do; Tannús, Alberto; Araújo, Dráulio Barros de; Silva, Afonso C.Hypertension afflicts 25% of the general population and over 50% of the elderly. In the presentwork, arterial spin labeling MRI was used to non-invasively quantify regional cerebral blood flow (CBF), cerebrovascular resistance and CO2 reactivity in spontaneously hypertensive rats (SHR) and in normotensive Wistar Kyoto rats (WKY), at two different ages (3 months and 10months) and under the effects of two anesthetics, α-chloralose and 2% isoflurane (1.5 MAC). Repeated CBF measurements were highly consistent, differing by less than 10% and 18% within and across animals, respectively. Under α-chloralose, whole brain CBF at normocapnia did not differ between groups (young WKY: 61±3 ml/100 g/min; adult WKY: 62±4 ml/100 g/min; young SHR: 70± 9 ml/100 g/min; adult SHR: 69±8 ml/100 g/min), indicating normal cerebral autoregulation in SHR. At hypercapnia, CBF values increased significantly, and a linear relationship between CBF and PaCO2 levels was observed. In contrast, 2% isoflurane impaired cerebral autoregulation. Whole brain CBF in SHR was significantly higher than inWKYrats at normocapnia (young SHR: 139±25 ml/100 g/min; adult SHR: 104±23 ml/100 g/min; young WKY: 55±9ml/100 g/min; adult WKY: 71±19 ml/100 g/min). CBF values increased significantly with increasing CO2; however, there was a clear saturation of CBF at PaCO2 levels greater than 70 mm Hg in both young and adult rats, regardless of absolute CBF values, suggesting that isoflurane interferes with the vasodilatory mechanisms of CO2. This behavior was observed for both cortical and subcortical structures. Under either anesthetic, CO2 reactivity values in adult SHRwere decreased, confirming that hypertension, when combined with age, increases cerebrovascular resistance and reduces cerebrovascular compliance.Artigo Quantification of BOLD fMRI Parameters to Infer Cerebrovascular Reactivity of the Middle Cerebral Artery(2013) Mazzetto-Betti, Kelley C.; Leoni, Renata F.; Pontes-Neto, Octavio M.; Sturzbecher, Marcio J.; Santos, Antonio C.; Leite, Joao P.; Silva, Afonso C.; Araújo, Dráulio Barros dePurpose: To quantify the amplitude and temporal aspects of the blood oxygenation level-dependent (BOLD) response to an auditory stimulus during normocapnia and hypercapnia in healthy subjects in order to establish which BOLD parameters are best suited to infer the cerebrovascular reactivity (CVR) in the middle cerebral artery (MCA) territory. Materials and Methods: Twenty healthy volunteers (mean age: 23.6 6 3.7 years, 11 women) were subjected to a functional paradigm composed of five epochs of auditory stimulus (3 sec) intercalated by six intervals of rest (21 sec). Two levels of hypercapnia were achieved by a combination of air and CO2 while the end-tidal CO2 (ETCO2) was continually measured. An autoregressive method was applied to analyze four parameters of the BOLD signal: onset-time, time-to-peak, full-width-at-halfmaximum (FWHM), and amplitude. Results: BOLD onset time (P < 0.001) and full-width at half-maximum (FWHM) (P < 0.05) increased linearly, while BOLD amplitude decreased (P < 0.001) linearly with increasing levels of hypercapnia. Test–retest for reproducibility in five subjects revealed excellent concordance for onset time and amplitude. Conclusion: The robust linear dependence of BOLD onset time, FWHM, and amplitude to hypercapnia suggest future application of this protocol in clinical studies aimed at evaluating CVR of the MCA territory.